A comprehensive review of probiotics and human health-current prospective and applications

✅ 全文

益生菌与人类健康的全面综述——当前前景与应用

作者 Bhutada Sarita; Dahikar Samadhan; Md Zakir Hassan; Elena G. Kovaleva 期刊 Frontiers in Microbiology 发表日期 2025 ISSN 1664-302X DOI 10.3389/fmicb.2024.1487641 类型 原创研究 (Original Research)

📄 英文摘要 English Abstract

EN

The beneficial properties of probiotics have always been a point of interest. Probiotics play a major role in maintaining the health of Gastrointestinal Tract (GIT), a healthy digestive system is responsible for modulating all other functions of the body. The effectiveness of probiotics can be enhanced by formulating them with prebiotics the formulation thus formed is referred to as synbiotics. It not only improves the viability and stability of probiotic cells, but also inhibits the growth of pathogenic strains. Lactobacillus and Bifidobacterium spp. are most commonly used as probiotics. The other microbial spp. that can be used as probiotics are Bacillus, Streptococcus , Enterococcus , and Saccharomyces . Probiotics can be used for the treatment of diabetes, obesity, inflammatory, cardiovascular, respiratory, Central nervous system disease (CNS) and digestive disorders. It is also essential to encapsulate live microorganisms that promote intestinal health. Encapsulation of probiotics safeguards them against risks during production, storage, and gastrointestinal transit. Heat, pressure, and oxidation eradicate probiotics and their protective qualities. Encapsulation of probiotics prolongs their viability, facilitates regulated release, reduces processing losses, and enables application in functional food products. Probiotics as microspheres produced through spray drying or coacervation. This technique regulates the release of gut probiotics and provides stress resistance. Natural encapsulating materials including sodium alginate, calcium chloride, gel beads and polysaccharide promoting safeguards in probiotics during the digestive process. However, several methods including, spray drying where liquid is atomized within a heated air chamber to evaporate moisture and produce dry particles that improves the efficacy and stability of probiotics. Additionally, encapsulating probiotics with prebiotics or vitamins enhance their efficacy. Probiotics enhance immune system efficacy by augmenting the generation of antibodies and immunological cells. It combats illnesses and enhances immunity. Recent studies indicate that probiotics may assist in the regulation of weight and blood glucose levels and influence metabolism and insulin sensitivity. Emerging research indicates that the “gut-brain axis” connects mental and gastrointestinal health. Probiotics may alleviate anxiety and depression via influencing neurotransmitter synthesis and inflammation. Investigations are underway about the dermatological advantages of probiotics that forecasting the onsite delivery of probiotics, encapsulation is an effective technique and requires more consideration from researchers. This review focuses on the applications of probiotics, prebiotics and synbiotics in the prevention and treatment of human health.

📄 中文摘要 Chinese Abstract

中文
益生菌在维持胃肠道(GIT)健康方面发挥着重要作用,健康的消化系统负责调节机体的所有其他功能。益生菌的功效可以通过与益生元配伍来增强,由此形成的制剂被称为合生元。合生元不仅能提高益生菌细胞的活力和稳定性,还能抑制病原菌株的生长。乳杆菌属和双歧杆菌属是最常用的益生菌。其他可用作益生菌的微生物种类包括芽孢杆菌属、链球菌属、肠球菌属和酵母菌属。益生菌可用于治疗糖尿病、肥胖症、炎症性疾病、心血管疾病、呼吸系统疾病、中枢神经系统疾病(CNS)及消化系统疾病。对促进肠道健康的活微生物进行包埋也至关重要。益生菌的包埋可保护其在生产、储存和胃肠道转运过程中免受损害。高温、高压和氧化作用会破坏益生菌及其保护特性。益生菌的包埋可延长其存活时间、促进受控释放、减少加工损失,并使其能够应用于功能性食品产品中。本综述重点介绍了益生菌、益生元和合生元在预防和治疗人类健康疾病方面的应用。

📋 英文结构化总结 English Structured Summary

全文整理

EN

Background:

Probiotics play a major role in maintaining the health of Gastrointestinal Tract (GIT), a healthy digestive system is responsible for modulating all other functions of the body. The effectiveness of probiotics can be enhanced by formulating them with prebiotics the formulation thus formed is referred to as synbiotics. It not only improves the viability and stability of probiotic cells, but also inhibits the growth of pathogenic strains. Lactobacillus and Bifidobacterium spp. are most commonly used as probiotics. The other microbial spp. that can be used as probiotics are Bacillus, Streptococcus, Enterococcus, and Saccharomyces. Probiotics can be used for the treatment of diabetes, obesity, inflammatory, cardiovascular, respiratory, Central nervous system disease (CNS) and digestive disorders. It is also essential to encapsulate live microorganisms that promote intestinal health. Encapsulation of probiotics safeguards them against risks during production, storage, and gastrointestinal transit. Heat, pressure, and oxidation eradicate probiotics and their protective qualities. Encapsulation of probiotics prolongs their viability, facilitates regulated release, reduces processing losses, and enables application in functional food products. This review focuses on the applications of probiotics, prebiotics and synbiotics in the prevention and treatment of human health.

Methods:

N/A - Review article. This is a comprehensive review that focuses on the applications of probiotics, prebiotics and synbiotics in the prevention and treatment of human health; no specific systematic methodology is described.

Results:

Probiotics improve the microbial balance of the GI tract. They exert their effects via enhancing the epithelial barrier, promoting microbial adherence to the intestinal mucosa while suppressing pathogen adhesion, modulating the immune system, and creating biochemicals that can suppress the growth of pathogenic microorganisms. These antimicrobial compounds are known as bacteriocins; they have active protein moiety. These bacteria also produce short chain fatty acids (SCFAs), hydrogen peroxide (H2O2) and diacetyl, these biochemicals modify the intestinal microflora leading to positive health benefits. Almost all strains of Bifidobacteria and Lactobacilli are capable of producing these bacteriocins. Probiotics enhance immune system efficacy by augmenting the generation of antibodies and immunological cells. It combats illnesses and enhances immunity. Recent studies indicate that probiotics may assist in the regulation of weight and blood glucose levels and influence metabolism and insulin sensitivity. Emerging research indicates that the “gut-brain axis” connects mental and gastrointestinal health. Probiotics may alleviate anxiety and depression via influencing neurotransmitter synthesis and inflammation.

Data Summary:

The review does not provide specific quantitative data or key statistics. It highlights general findings, such as that almost all strains of Bifidobacteria and Lactobacilli are capable of producing bacteriocins, and that heat, pressure, and oxidation eradicate probiotics and their protective qualities.

Conclusions:

Probiotics enhance immune system efficacy by augmenting the generation of antibodies and immunological cells. It combats illnesses and enhances immunity. Recent studies indicate that probiotics may assist in the regulation of weight and blood glucose levels and influence metabolism and insulin sensitivity. Emerging research indicates that the “gut-brain axis” connects mental and gastrointestinal health. Probiotics may alleviate anxiety and depression via influencing neurotransmitter synthesis and inflammation. Investigations are underway about the dermatological advantages of probiotics that forecasting the onsite delivery of probiotics, encapsulation is an effective technique and requires more consideration from researchers.

Practical Significance:

Probiotics can be used for the treatment of diabetes, obesity, inflammatory, cardiovascular, respiratory, Central nervous system disease (CNS) and digestive disorders. Encapsulation of probiotics enables application in functional food products. Probiotics may assist in the regulation of weight and blood glucose levels, and investigations are underway about dermatological advantages. The use of synbiotics (probiotics formulated with prebiotics) improves viability and stability of probiotic cells while inhibiting pathogenic strains, offering real-world applications in human health management.

📋 中文结构化总结 Chinese Structured Summary

中文

背景:

益生菌在维持胃肠道(GIT)健康方面发挥着重要作用,健康的消化系统负责调节机体的所有其他功能。益生菌的功效可以通过与益生元配伍来增强,由此形成的制剂被称为合生元。合生元不仅能提高益生菌细胞的活力和稳定性,还能抑制病原菌株的生长。乳杆菌属和双歧杆菌属是最常用的益生菌。其他可用作益生菌的微生物种类包括芽孢杆菌属、链球菌属、肠球菌属和酵母菌属。益生菌可用于治疗糖尿病、肥胖症、炎症性疾病、心血管疾病、呼吸系统疾病、中枢神经系统疾病(CNS)及消化系统疾病。对促进肠道健康的活微生物进行包埋也至关重要。益生菌的包埋可保护其在生产、储存和胃肠道转运过程中免受损害。高温、高压和氧化作用会破坏益生菌及其保护特性。益生菌的包埋可延长其存活时间、促进受控释放、减少加工损失,并使其能够应用于功能性食品产品中。本综述重点介绍了益生菌、益生元和合生元在预防和治疗人类健康疾病方面的应用。

方法:

不适用——综述文章。本文为一篇综合性综述,重点介绍益生菌、益生元和合生元在预防和治疗人类健康疾病方面的应用;未描述具体的系统性方法。

结果:

益生菌可改善胃肠道微生物平衡。其作用机制包括增强上皮屏障功能、促进微生物在肠道黏膜上的黏附同时抑制病原体黏附、调节免疫系统以及产生可抑制病原微生物生长的生化物质。这些抗菌化合物被称为细菌素,具有活性蛋白组分。这些细菌还可产生短链脂肪酸(SCFAs)、过氧化氢(H2O2)和二乙酰,这些生化物质可改变肠道微菌群,从而带来积极的健康益处。几乎所有双歧杆菌和乳杆菌菌株均能产生这些细菌素。益生菌通过增加抗体和免疫细胞的生成来增强免疫系统效能,对抗疾病并增强免疫力。近期研究表明,益生菌可能有助于调节体重和血糖水平,并影响代谢和胰岛素敏感性。新兴研究表明,"肠-脑轴"将心理健康与胃肠道健康联系起来。益生菌可能通过影响神经递质合成和炎症反应来缓解焦虑和抑郁。

数据总结:

本综述未提供具体的定量数据或关键统计数据。综述强调了一般性发现,例如几乎所有双歧杆菌和乳杆菌菌株均能产生细菌素,以及高温、高压和氧化作用会破坏益生菌及其保护特性。

结论:

益生菌通过增加抗体和免疫细胞的生成来增强免疫系统效能,对抗疾病并增强免疫力。近期研究表明,益生菌可能有助于调节体重和血糖水平,并影响代谢和胰岛素敏感性。新兴研究表明,"肠-脑轴"将心理健康与胃肠道健康联系起来。益生菌可能通过影响神经递质合成和炎症反应来缓解焦虑和抑郁。目前关于益生菌皮肤学益处的研究正在进行中,鉴于益生菌的定点递送需求,包埋是一种有效的技术,需要研究者给予更多关注。

实际意义:

益生菌可用于治疗糖尿病、肥胖症、炎症性疾病、心血管疾病、呼吸系统疾病、中枢神经系统疾病(CNS)及消化系统疾病。益生菌的包埋使其能够应用于功能性食品产品中。益生菌可能有助于调节体重和血糖水平,目前关于其皮肤学益处的研究也在进行中。合生元(益生菌与益生元配伍制剂)的使用可提高益生菌细胞的活力和稳定性,同时抑制病原菌株,在人类健康管理中具有实际应用价值。

📖 英文全文 English Full Text

EN

TYPE Review PUBLISHED 06 January 2025 DOI 10.3389/fmicb.2024.1487641 OPEN ACCESS EDITED BY K. B. Arun, Christ University, India REVIEWED BY

Anjani Devi Chintagunta, Vignan’s Foundation for Science, Technology and Research, India Iftikhar Younis Mallhi, Minhaj University Lahore, Pakistan *CORRESPONDENCE Bhutada Sarita sabhutada13@gmail.com RECEIVED 28 August 2024

A comprehensive review of probiotics and human health-current prospective and applications Bhutada Sarita 1*, Dahikar Samadhan 1, Md Zakir Hassan 2,3 and Elena G. Kovaleva 2 Department of Microbiology, Sanjivani Arts, Commerce and Science College, Kopargaon, India, Department of Technologies for Organic Synthesis, Institute of Chemical Technology, Ural Federal University named after the First President of Russia B. N. Yeltsin, Yekaterinburg, Russia, 3 Bangladesh Livestock Research Institute, Savar, Bangladesh 1

ACCEPTED 16 December 2024 PUBLISHED 06 January 2025 CITATION

Sarita B, Samadhan D, Hassan MZ and Kovaleva EG (2025) A comprehensive review of probiotics and human health-current prospective and applications. Front. Microbiol. 15:1487641. doi: 10.3389/fmicb.2024.1487641 COPYRIGHT

© 2025 Sarita, Samadhan, Hassan and Kovaleva. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

The beneficial properties of probiotics have always been a point of interest. Probiotics play a major role in maintaining the health of Gastrointestinal Tract (GIT), a healthy digestive system is responsible for modulating all other functions of the body. The effectiveness of probiotics can be enhanced by formulating them with prebiotics the formulation thus formed is referred to as synbiotics. It not only improves the viability and stability of probiotic cells, but also inhibits the growth of pathogenic strains. Lactobacillus and Bifidobacterium spp. are most commonly used as probiotics. The other microbial spp. that can be used as probiotics are Bacillus, Streptococcus, Enterococcus, and Saccharomyces. Probiotics can be used for the treatment of diabetes, obesity, inflammatory, cardiovascular, respiratory, Central nervous system disease (CNS) and digestive disorders. It is also essential to encapsulate live microorganisms that promote intestinal health. Encapsulation of probiotics safeguards them against risks during production, storage, and gastrointestinal transit. Heat, pressure, and oxidation eradicate probiotics and their protective qualities. Encapsulation of probiotics prolongs their viability, facilitates regulated release, reduces processing losses, and enables application in functional food products. Probiotics as microspheres produced through spray drying or coacervation. This technique regulates the release of gut probiotics and provides stress resistance. Natural encapsulating materials including sodium alginate, calcium chloride, gel beads and polysaccharide promoting safeguards in probiotics during the digestive process. However, several methods including, spray drying where liquid is atomized within a heated air chamber to evaporate moisture and produce dry particles that improves the efficacy and stability of probiotics. Additionally, encapsulating probiotics with prebiotics or vitamins enhance their efficacy. Probiotics enhance immune system efficacy by augmenting the generation of antibodies and immunological cells. It combats illnesses and enhances immunity. Recent studies indicate that probiotics may assist in the regulation of weight and blood glucose levels and influence metabolism and insulin sensitivity. Emerging research indicates that the “gut-brain axis” connects mental and gastrointestinal health. Probiotics may alleviate anxiety and depression via influencing neurotransmitter synthesis and inflammation. Investigations are underway about the dermatological advantages of probiotics that forecasting the onsite delivery of probiotics, encapsulation is an effective technique and requires more consideration from researchers. This review focuses on the applications of probiotics, prebiotics and synbiotics in the prevention and treatment of human health. KEYWORDS

probiotics, human health, synbiotics, intestinal disorders and encapsulation, prebiotics Frontiers in Microbiology 01 frontiersin.org Sarita et al. 10.3389/fmicb.2024.1487641 1 Introduction

promotes the growth and development of beneficial bacteria like Bifidobacterium (Lacerda et al., 2020). Survival of probiotics is sometimes difficult in the GIT, to curb the survival difficulties synbiotics were created. The viability and efficiency of probiotics are dependent on several factors including oxygen, moisture, stress, pH, etc. (Mazziotta et al., 2023). Synbiotics are a combination of prebiotics and probiotics formulated in a way that not only improves the chances of survival of beneficial microbes, but also stimulates the growth and proliferation of the native bacterial population in the GI tract. Prebiotics improve the tolerance of probiotics to environmental factors like temperature, oxygenation and pH inside the GIT. But when prebiotics and probiotics are combined, efficiency of microbes and their tolerance to limiting factors get drastically improved causing a beneficial effect on the host’s body (Manigandan et al., 2012). Synbiotics not only inhibit the growth of harmful pathogens, but also maintains intestinal biostructure and reduce the undesired metabolite concentration. Synbiotics are quite efficient in reducing blood fat and glucose levels, immune system modulation, osteoporosis prevention and in the treatment of neuro disorders arising from abnormal hepatic functions. Lactobacilli, B. coagulans, Bifidobacteria sp., S. boulardi, etc. are the most commonly used probiotic strains in synbiotic formulations along with oligosaccharide-based prebiotics (Pandey et al., 2015). Synbiotics amalgamate probiotics (viable advantageous bacteria) with prebiotics (agents that facilitate their proliferation) to enhance health. Multiple factors influence synbiotic formulation. Choosing Probiotics and Prebiotics the selection of probiotic and prebiotic strains is essential. Probiotics must be selected for their health benefits and capacity to last in the gastrointestinal tract, whereas prebiotics should enhance their proliferation. The chosen strains and substrates must collaborate to attain health benefits (Chan and Liu, 2022). Sustainability ensuring probiotic viability during manufacturing, storage, and distribution poses significant challenges. The survival of probiotics in yogurt is influenced by pH, moisture, and oxygen concentrations. Consequently, probiotics are frequently encapsulated to shield them from environmental stressors and maintain their stability until they arrive in the stomach. The matrix formulation of probiotics and prebiotics influences the release and effectiveness of synbiotic products. The formulation must deliver probiotics at the appropriate time and location inside the gastrointestinal tract to optimize health benefits (Chan et al., 2021; Chan and Liu, 2022). Synbiotics may be classified into several categories, such as dietary supplements and functional foods, complicating regulation. The diversity may influence the approval and market introduction of synbiotic products. Synbiotics are increasing in popularity; yet, consumers are still acquiring knowledge regarding their advantages and distinctions from probiotics and prebiotics. The market applications of synbiotics are expanding as consumers become increasingly informed about gut health, probiotics, and prebiotics. Primary applications encompass Synbiotics are commonly used into yogurts, smoothies, and dietary supplements (Rashidinejad et al., 2022). These products provide convenient solutions for intestinal health. Moreover, Synbiotics may address dysbiosis-related conditions such as gastrointestinal disorders, obesity, and metabolic syndrome. Additionally, microbiome research may provide tailored synbiotic formulations to address specific health requirements and microbiome characteristics. This could enhance the effectiveness of synbiotics for particular health outcomes (Chaturvedi and Chakraborty, 2021) (Figure 1).

1.1 Probiotics-a brief introduction Probiotic is a Greek word meaning “for life,” coined by Lilley and Stillwell. Probiotics refer to microbes of non-pathogenic nature that are beneficial to their hosts (Soccol et al., 2014). Probiotics have been in use for quite a long time as Romans and Greeks, the ancient civilizations developed fermented milk and used it as probiotics, even the bible mentions this sour milk so the concept of probiotics is not entirely new (Hosono, 1992). Probiotics improve the microbial balance of the GI tract. World Health Organization (WHO) defines probiotics as “Live microbes which confer a health benefit to their host when administered in adequate amounts” (Chen and Sears, 2015). Lactobacillus, Bifidobacterium, Enterococcus, Lactococcus, and Streptococcus are most commonly used as probiotics (de Sequeira et al., 2022). Safety and functionality criteria must be cleared before using any microbial strain as a probiotic. These criteria include genetic stability, tolerance to acid and bile, ability to adhere to the gut lining, anti-genotoxic properties, non-pathogenic nature, production of lactic acid, tolerance to harsh processing conditions, and shorter generation time (de Melo Pereira et al., 2018). Probiotics exert their effects via enhancing the epithelial barrier, promoting microbial adherence to the intestinal mucosa while suppressing pathogen adhesion, modulating the immune system, and creating biochemicals that can suppress the growth of pathogenic microorganisms (Bermudez-Brito et al., 2012). These antimicrobial compounds are known as bacteriocins; they have active protein moiety. These bacteria also produce short chain fatty acids (SCFAs,) hydrogen peroxide (H2O2) and diacetyl, these biochemicals modify the intestinal microflora leading to positive health benefits (Hawrelak and BNat, 2013). Almost all strains of Bifidobacteria and Lactobacilli are capable of producing these bacteriocins.

1.2 Prebiotics and synbiotics Prebiotics can be defined as indigestible food components that provide health benefits by restoring the growth of beneficial microbes in the gastrointestinal tract (GI)T. Prebiotics are known majorly for stimulating the activity and growth of good bacteria in the GIT. They stimulate the growth of bacteria present in the colon. Unlike other food components, they are hardly affected by hydrolyzing enzymes or acids which are present in our GIT, but are prone to fermentation by beneficial bacteria (Kuo, 2013). Jerusalem artichoke, chicory roots, berries, tomatoes, unrefined wheat, onions, asparagus, garlic, soybeans, undigestible carbohydrates, etc. are all sources of prebiotics (Pokusaeva et al., 2011). There are certain prebiotics that exhibits several health benefits apart from modulating the growth of beneficial microbes. They act as anti-inflammatory, anti-diarrheal and lower the risk of colon cancer (Peña, 2007). Alginate and agar that have been derived from seaweed. In addition to being abundant in the polysaccharide known as Ulvan, Gelidium is also a unique prebiotic for the bacteria known as Faecalibacterium prausnitzii (Saulnier et al., 2009). The by-products of their fermentation are short-chain chain fatty acids (SCFAs) namely acetic or propionic acids, these acids reduce the intestinal pH, but certain bacteria like Bifidobacterium are tolerant to SCFAs. This inhibits the growth of harmful bacteria and

Sources and applications of probiotics, prebiotics and synbiotics. 1.2.1 Safety criteria of probiotics, potential risks and safety concerns for specific populations

maintaining the potency, stability, and shelf life of probiotic products while adhering to superior manufacturing practices. Adverse Events—Post-marketing surveillance is essential to monitor probiotic side effects (Bodke and Jogdand, 2022). This ongoing examination highlights potential safety concerns that may arise post-release of items. At-risk populations, including individuals with compromised immune systems or other health conditions, should be prioritized to mitigate risks. The safety of probiotics is crucial as they are consumed by diverse populations, including infants, the elderly, and immunocompromised individuals (Sharifi-Rad et al., 2020). The subsequent safety criteria are typically evaluated. Probiotic strains must be accurately characterized to ensure identification, purity, and viability. This entails verifying the strain’s viability and characterizing its genetic and phenotypic attributes. Consumer safety necessitates well delineated strains with established safety attributes. Probiotics must undergo testing for pathogenicity. We evaluate if strains can induce diseases or generate toxic substances. Animal models are utilized to investigate safety hazards such as endocarditis in vulnerable populations. Probiotic products must undergo testing for harmful bacteria, mycotoxins, and heavy metals. The final product must be free of hazardous contaminants to ensure customer safety. Clinical Safety—Clinical trials must establish the safety of probiotics within the target population. This entails overseeing trial adverse effects and confirming the safety of probiotic strains. Regulatory compliance: Standards for probiotic products vary by region. This entails

The safety of probiotics is crucial due to their consumption by diverse populations, including infants, the elderly, and immunocompromised individuals. The subsequent safety criteria are typically evaluated. Incorporating with Probiotic strains must be accurately characterized to ensure identification, purity, and viability (Mazziotta et al., 2023). This encompasses verifying the strain’s viability and determining its genetic and phenotypic characteristics. Consumer safety necessitates clearly defined strains with established safety attributes. Probiotics must undergo evaluation for pathogenicity (Damián et al., 2022). Therefore, evaluation of strains can induce diseases or generate toxic substances. Animal models are employed to investigate safety hazards such as endocarditis in vulnerable populations. Probiotic products must undergo testing for harmful bacteria, mycotoxins, and heavy metals. The final product must be free from hazardous contaminants to ensure customer safety. Clinical Safety—Probiotics must demonstrate safety in the target population as evidenced by clinical research. This entails overseeing trial adverse effects and confirming the safety of probiotic strains. Regulations differ by region, although probiotic products must comply. This entails adhering to the safety and efficacy requirements for probiotics established by health authorities for food and supplements (Tegegne and Kebede, 2022). Quality Control—Manufacturers must rigorously oversee quality during the whole production process. This entails

TABLE 1 Bacterial strains that are commonly used as probiotics. adhering to the safety and efficacy requirements for probiotics established by health authorities for food and supplements (Victoria Obayomi et al., 2024). Manufacturers must rigorously enforce quality control measures during production. This include maintaining the potency, stability, and shelf life of probiotic products while adhering to superior manufacturing practices. Adverse Events—Post-marketing surveillance is essential for monitoring probiotic side effects. This ongoing examination detects safety concerns that may arise postrelease of items. Priority should be given to vulnerable groups, including individuals with compromised immune systems or other health conditions. In the United States, probiotics are regulated by the Food and Drug Administration (FDA) as dietary supplements or food products (Al-Rashidi et al., 2022). The 1994 Dietary Supplement Health and Education Act (DSHEA) is applicable; however, pre-market approval is not mandated. Manufacturers are required to label and guarantee product safety. Opportunistic infections, particularly in immunocompromised individuals, afflict probiotics. Probiotic strains and other benign bacteria can induce illness when the immune system is compromised. Users of central venous catheters and those with severe diseases have experienced Saccharomyces fungemia (Palacios et al., 2023). Some individuals may encounter bloating, flatulence, or diarrhea after initiating probiotic use. The symptoms are often mild and temporary; however, consumers express concern. Probiotics may influence the efficacy of immunosuppressive medications. This combination may elevate the risk of infection or diminish treatment efficacy. Probiotics can be detrimental to people undergoing chemotherapy, organ transplants, and those with HIV/ AIDS. Individuals with diminished infection resistance require an assessment of probiotic strain safety prior to utilization. Administer probiotics wisely to avert gastrointestinal complications in neonates and early children (Ashaolu, 2020).

acidophilus rhamnosus fermentum johnsonii lactis reuteri Bifidobacterium spp. breve infantis longum bifidum lactis thermophilum Bacillus spp. coagulans Streptococcus spp. thermophilus Enterococcus spp.

faecium Saccharomyces spp. cerevisae tropical fruits of Indochina. It is quite resistant to acid and temperature stress, thus can be easily used as a probiotic (Bhukya et al., 2019). Probiotics refer to living microorganisms that provide a range of health benefits when ingested or administered for optimal levels within the body. Table 1 provides information on the prevalent probiotic bacteria present in yogurt, fermented meals, dietary supplements, and beauty items (Elhossiny et al., 2023).

2.1 Lactobacillus acidophilus Lactobacillus acidophilus is a strain of probiotic bacteria that has been widely utilized due to its potential health advantages. This strain possesses the capacity to cling to diverse intestinal cells, exhibits tolerance to bile, and demonstrates resistance to acid, which are essential attributes for a probiotic strain. Nevertheless, previous research conducted in laboratory settings has demonstrated that certain strains of Lactobacillus acidophilus had the ability to decrease cholesterol levels by over 50%. This finding underscores their potential significance in enhancing cardiovascular well-being, particularly when used in conjunction with other probiotic strains. Moreover, it has demonstrated efficacy in the prevention of gastrointestinal illnesses among adults and the mitigation of symptoms associated with the common cold in children. The strains of Lactobacillus acidophilus that are commercially accessible include LA-1, LA-5, NCFM, DDS-1, and SBT-2026 (Elhossiny et al., 2023).

2 Probiotics classification At present, there are a variety of microbes that are being used as probiotics (Hawrelak and BNat, 2013). Table 1 represents bacterial strains that are commonly used as probiotics. Bacteria belonging to the Lactobacillus genus are gram-positive bacilli that are capable of producing lactic acid in the GIT and GUT (Genitourinary tract), they are anaerobes that can improve uptake and bioavailability of minerals and reduce intestinal permeability. In fact, some strains of this genus exhibit anti-cancer and hypolipidemic activity (Cichonska and Ziarno, 2022). Bifidobacterium is pleomorphic, anaerobic, gram-positive bacilli which produce acetic acid and lactic acid as metabolic by-products. It can reduce the effects of Helicobacter pylori infection if used in combination with either Saccharomyces cerevisiae and Lactobacilli (Chen et al., 2019). Bacillus coagulans are known for producing lactic acid and are sometimes commercialized as Lactobacillus sporogenes, but it is not a part of normal intestinal flora, unlike Lactobacillus. But it is quite helpful in inhibiting colonization by pathogens and restoring normal intestinal microbiota and they are highly prone to acidic environments and high temperatures (Cao et al., 2020). Saccharomyces cerevisiae or S. boulardii is commonly used for the treatment of diarrhea, in natural forms, it is isolated from skin of

2.2 Lactobacillus rhamnosus The strain Lactobacillus rhamnosus has developed distinctive adaptations that enable its survival in the acidic and basic environments present in the human body. The capacity of L. rhamnosus to attach and colonize the intestinal walls enables it to potentially provide extended advantages. Consequently, it is frequently used into yogurts, cheeses, milk, and other dairy products to augment probiotic levels. Additionally, L. rhamnosus plays a pivotal part in the

04 frontiersin.org Sarita et al. 10.3389/fmicb.2024.1487641 process of cheese ripening, so boosting the overall flavor. Moreover, some strains of L. rhamnosus have demonstrated advantageous effects on both adults and children, specifically in the treatment of irritable bowel syndrome (IBS), eczema, allergies, and immune system support (Gao et al., 2022).

the production of inflammatory factors triggered by lipopolysaccharides (LPS). Certain strains of Lactobacillus lactis have been linked to enhancing the immune system and avoiding infections in the gastrointestinal and upper respiratory tract (Zanjani et al., 2017; Nazia et al., 2014).

2.3 Lactobacillus fermentum 2.6 Lactobacillus reuteri

Lactobacillus fermentum is a probiotic bacterium that exhibits abilities in adhesion and anti-infective properties. It is commonly found in cheese ripening and is classified as a non-starter lactic acid bacteria (NSLAB) within specific cheese varieties. These characteristics suggest that Lactobacillus fermentum has the potential to effectively combat infections and promote health in the urinary-reproductive tract. In addition, it has been observed that Lactobacillus fermentum strain JDFM216 has the potential to enhance cognitive and physiological functioning, while also demonstrating immunomodulatory properties. This particular strain has been linked to heightened phagocytic activity of macrophages, elevated synthesis of IgA, and heightened activation of immune cells. The probiotic strain Lactobacillus fermentum has been recognized for its antibacterial and antioxidative capabilities, ability to metabolize cholesterol, and possible contribution to cardiovascular health. These attributes make it a distinctive strain with prospects for boosting health. Furthermore, it has been observed that Lactobacillus fermentum strains exhibit a notable capacity for auto-aggregation, a crucial factor in their ability to cling to epithelial cells and facilitate the production of biofilms within the gastrointestinal tract (Anjum et al., 2014).

Lactobacillus reuteri has been linked to a wide range of health advantages, encompassing the prevention and management of urogenital disorders and bacterial vaginosis in females, atopic disorders, food hypersensitivity, and the prevention of dental caries. Furthermore, it has been examined for its capacity to prevent colitis and decrease contacts between P-selectin-associated leukocytes and platelets with endothelial cells, emphasizing its significance in intestinal illnesses. Extensive research has been conducted on its capacity to inhibit the growth of harmful bacteria, yeasts, and other microorganisms, so demonstrating its potential as a helpful probiotic for the treatment of gastrointestinal and urogenital ailments, including infantile colic (Assimos, 2020).

One of the initial cultures suggested as a probiotic dairy supplement is Lactobacillus johnsonii strain LA-1. This strain is utilized in Nestlé’s LC-1 yogurt products and possesses the capacity to augment immune responses, withstand diverse conditions such as bile salts and antibiotics, combat antimicrobial multidrug resistance microorganisms, and maintain a high level of probiotic viability in food items. Moreover, Lactobacillus johnsonii has demonstrated the ability to decrease the adhesion and activity of pathogenic strains, impede the growth of gut pathogens, and shorten the duration of diarrhea and enterocolitis (Tavasoli et al., 2022).

The bacterial species Bifidobacterium breve, belonging to the genus Bifidobacterium, is renowned for its probiotic characteristics. This bacterium is a symbiotic organism that resides in the human intestines and has been employed for the treatment of several ailments, such as constipation, diarrhea, irritable bowel syndrome, and even the common cold and flu. Scientific research has substantiated several applications, showcasing the potential physiological advantages of B. breve. This rod-shaped bacterium is gram-positive, anaerobic, and non-motile. It creates branches with its neighboring organisms. Bifidobacterium breve strains have been extensively employed in the field of pediatrics and are recognized as the prevailing species in the gastrointestinal tract of infants who are breastfed. Furthermore, they have been extracted from human milk, emphasizing their inherent existence in the gastrointestinal tract of infants. The strains of B. breve have undergone successful trials in pediatric populations and have demonstrated efficacy in addressing various health issues, hence establishing their significance as a probiotic strain for enhancing digestion and general well-being (Zanjani et al., 2017).

The lactic acid bacterium species known as Lactobacillus lactis has been the subject of substantial research due to its potential probiotic capabilities in enhancing immune system function and alleviating inflammatory bowel illness. This analysis presents a comprehensive examination of the probiotic properties and potential health advantages associated with Lactobacillus lactis, which is commonly employed as a probiotic. The evaluation is based on specific criteria including bile tolerance, acid resistance, cholesterol assimilation activity, and adhesion to intestinal cells. The anti-inflammatory capabilities of some strains of Lactobacillus lactis, such as L. lactis ML-2018, have been recognized, particularly in their ability to inhibit

Bifidobacterium infantis, scientifically referred to as Bifidobacterium longum subsp. infantis, is a benign bacterial strain that naturally inhabits the mouth and digestive system. It belongs to the same group as Lactobacillus and is a type of lactic acid bacteria that is essential for keeping a healthy digestive system. Bifidobacterium infantis 35,624 has been extensively studied and has been specifically examined for its potential in treating irritable bowel syndrome (IBS). Its efficacy in alleviating symptoms such as bloating, bowel issues, pain, and gut dysbiosis in infants has been demonstrated. Moreover, it has been linked to enhanced management of gastrointestinal distress and enhancement of the overall well-being of pediatric patients

diagnosed with irritable bowel syndrome (IBS) (Azad et al., 2018; Sanders et al., 2018). efficient in mitigating gastrointestinal distress and various other medical conditions. Additionally, it has the ability to control the host’s symbiotic microbiota and hinder the proliferation of harmful bacteria, so promoting general gastrointestinal well-being and providing support to the digestive and immune systems. In natural food sources, such as fermented foods like sauerkraut, kimchi, and yogurt, Bacillus coagulans can be found. Furthermore, it finds utility in several probiotic food additives, showcasing its suitability for industrial implementation in the food sector (Ma et al., 2021).

2.9 Bifidobacterium longum Bifidobacterium longum is a commensal bacteria that resides in the gastrointestinal system and is widely acknowledged as a prominent constituent of the human gut microbiota. It is particularly prevalent in the baby gut, where it is the most numerous species. It demonstrates a multitude of advantageous health benefits, encompassing the synthesis of bioactive compounds and the interaction between bifidobacterial surface-associated molecules and the host organism. Extensive study has been conducted on Bifidobacterium longum, revealing its effectiveness in managing the symptoms associated with irritable bowel syndrome (IBS), such as bloating, diarrhea, abdominal pain, and distress. Furthermore, it has been examined for its capacity to prevent antibiotic-associated diarrhea in children and irritable bowel syndrome (IBS). Additionally, it has been explored for its effectiveness in promoting remission in active ulcerative colitis and its ability to degrade the mucin layers in the host gut, thereby preserving the microbial community. Moreover, much research has been conducted on the phytochemical bio-catalytic properties of this substance, its capacity to adhere to cells, its potential to inhibit carcinogenesis in cell lines, its ability to modulate immune cells, and its potential to reduce allergic reactions in mice models and treat inflammatory bowel disease (Azad et al., 2018).

2.13 Streptococcus thermophilus The bacterium Streptococcus thermophilus is frequently employed in the manufacturing of many dairy commodities, such as cheeses and yogurt. It aids in the hydrolysis of lactose in milk, leading to the distinctive flavor and consistency of yogurt. Furthermore, this substance is acknowledged for its capacity to decrease the fat content in specific types of cheeses, such as Swiss cheese, by means of generating natural polymer extracts. This particular strain of probiotics has been linked to a range of health advantages, such as bolstering the immune system and mitigating inflammation in the gastrointestinal and urogenital systems. Additionally, it has demonstrated potential in combating viral, fungal, and parasitic infections. The coexistence of Bifidobacterium bifidum and Streptococcus thermophilus in babies has been associated with a reduced incidence of rotavirus diarrhea. This combination has been found to potentially mitigate inflammation-induced harm resulting from sepsis, hence underscoring its potential as a dietary supplement (Qu et al., 2023).

2.10 Bifidobacterium lactis In vitro testing has extensively established the strain characteristics and processes of Bifidobacterium lactis, demonstrating its great stability in meals and freeze-dried powders. Clinical evidence has demonstrated that Bifidobacterium lactis HN019 promotes gut health, digestion, and immunological function (Sanders et al., 2019).

2.14 Enterococcus faecium There is no evidence to suggest that probiotic strains of Enterococcus faecium possess the capacity to induce antibiotic resistance. In order to guarantee the safe consumption of probiotic products containing Enterococcus faecium, stringent safety standards have been established to exclusively employ microbial strains that are deemed suitable for use in food or food supplements. It possesses a distinct advantage in enduring the process of digestion and thriving in the gastrointestinal tract, fostering a harmonious gut milieu by engaging in competition with detrimental species for nutrients and adhesion sites. Moreover, strains of Enterococcus faecium exhibit promising therapeutic properties, including the ability to prevent and treat diarrhea in domesticated animals, as well as block the proliferation of pathogenic Listeria spp. (Tilwani et al., 2022).

2.11 Bifidobacterium thermophilum Bifidobacterium thermophilum is acknowledged as an aerotolerant bacteria, possessing the ability to endure and flourish in oxygendepleted settings, rendering it a promising contender for probiotic application. Bifidobacterium thermophilum demonstrates bacteriocinlike antimicrobial properties against various pathogens, including Listeria spp., Salmonella spp., Campylobacter jejuni in broiler and rota virus infection. This makes it a highly promising candidate for incorporation into probiotic formulations and functional foods due to its aerotolerance and antimicrobial activity (Sanders et al., 2019).

2.15 Saccharomyces cerevisiae Saccharomyces cerevisiae, specifically the variant S. boulardii, is widely acknowledged for its probiotic capabilities and has undergone extensive investigation for its advantageous impacts on gastrointestinal well-being in both human and animal populations. It is commonly employed as an adjunctive measure against gastrointestinal tract disorders, including inflammatory bowel disease, and for the management of diverse forms of diarrhea. The defensive mechanisms of this entity are manifested through the binding and neutralization

2.12 Bacillus coagulans Bacillus coagulans is a spore-forming probiotic bacteria renowned for its exceptional resilience to adverse settings and its multitude of probiotic traits, enabling it to remain inactive under harsh conditions, such as elevated gastric acidity. The inherent durability of this substance allows it to endure harsh conditions, rendering it highly

Frontiers in Microbiology 06 frontiersin.org Sarita et al. 10.3389/fmicb.2024.1487641 of enteric pathogens or their toxins, the reduction of inflammation, and the stimulation of IgA secretion. These strains possess the potential to be employed in functional food applications and exhibit the capability to safeguard DNA from harm. The possible probiotic features of Saccharomyces cerevisiae yeast include its tendency to autoaggregate, co-aggregation with pathogens, hydrophobicity, ability to survive in simulated gastrointestinal tract settings, and its ability to adhere to Caco-2 cells. These aforementioned attributes render them viable contenders for therapeutic implementations (FernandezPacheco et al., 2018).

vegetables are substrates for probiotic bacteria because they contain nutrients they can easily absorb. Microbial populations can also be hosted and delivered via plant-based matrices due to their high nutritional, fiber, vitamin, mineral, and bioactive phytochemical content. In novel vegetable probiotic products, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus plantarum, Lactobacillus rhamnosus, and Bifidobacterium lactis are commonly used. Vegetables include probiotic microorganisms that stimulate the immune system, prevent gastrointestinal illnesses, and regulate fat storage. They also regulate gut microbial composition and metabolism (Palanisamy et al., 2024). Vegetables contain probiotic bacteria, a natural source. Fermented foods, particularly raw and fermented vegetables, contain Lactobacillus acidophilus, a gut bacteria. Fresh produce like fruits and vegetables contains a variety of germs, some of which may be healthy. The average apple contains 100 million microorganisms, many of which are harmless or useful. Fruits, vegetables, and cereals may carry probiotics. Fruit and vegetable juices and raw and fermented vegetables have been employed as probiotic bacteria substrates due to their nutrient content. Lactobacillus plantarum, a vegetable-fermented lactic acid bacterium, has been studied for its probiotic qualities. This strain was immunomodulating and antibacterial against pathogenic bacteria, suggesting it could be a probiotic and food additive (Gagnière et al., 2016). White peas, green peas, chickpeas and dragon fruit have lactic acid bacteria. Lactic acid bacteria (LAB) including Lactobacillus, Enterococcus, and Bifidobacterium are present in vegetable substrates (Jha et al., 2022). When added to vegetable substrates through lactic fermentation, these probiotic bacteria regulate the gut flora and improve health. However, using vegetable substrates to transport probiotic lactic acid bacteria (LAB) in food matrices. Micronutrients, antioxidants, and fiber make vegetable substrates ideal for bioprocess development (Sharma et al., 2021). Fruits, vegetables, legumes, and cereals have been studied as probiotic vehicles, demonstrating their gut health benefits. Fruits and vegetables can feed probiotic microorganisms in lactic fermentation. Among them are mango, apple, banana, passion fruit, carrot, orange, and soybeans. Probiotic bacteria can grow and thrive on these veggies’ various nutritional profiles and bioactive substances. Probiotic bacteria are found in kimchi and sauerkraut. Kimchi contains Leuconostoc, Weissella, and Lactobacillus, while sauerkraut contains Leuconostoc mesenteroides, Lactobacillus plantarum, Pediococcus pentosaceus, and others (Junnarkar et al., 2019). These microorganisms may aid digestion. The best thing for gut health is eating a range of natural meals, particularly fresh produce. Fruits and vegetables contain more microbial species than probiotic pills. Thus, eating a variety of fresh fruits and vegetables supports gut microbiota health and general wellness. Fermented fruits and vegetables contain Lactobacillus, Streptococcus, Leuconostoc, and other LAB. These bacteria dominate fermented foods and may be probiotic. LAB, along with other bacteria, yeast, and fungi, ferment these foods and generate live microorganisms, making them good carriers for probiotic bacteria (Bernal-Castro et al., 2024). Probiotic bacteria are found in kimchi and sauerkraut. Kimchi contains Lactobacillus kimchii and other lactic acid bacteria, which may aid digestion (Acevedo-Martínez et al., 2018). Leuconostoc mesenteroides, Lactobacillus plantarum, Pediococcus pentosaceus, and others in sauerkraut may enhance gut health. Fruits include vitamins, minerals, carbohydrates, fibers, and antioxidants, making them good probiotic substrates. Fruit surfaces’ microarchitecture protects probiotic bacteria from stomach acid, enhancing their survival and health benefits. Fruit

3 Substrates for probiotics 3.1 Cereals as a substrate for probiotics In Asia and Africa, lactic fermentation of grains is a processing method to produce various products such as drinks, porridge and amaj. During fermentation, acidity increases due to microbial activity and the accumulation of lactic acid and other organic acids. On the other hand, in western countries, grains such as wheat and rye are used to produce sour dough. Lactobacillus and Bifidobacteria have different nutritional requirements, including the need for carbohydrates, amino acids, peptides, fatty esters, salt, and acid derivatives (Setta et al., 2020). It is nucleic and vitamin. The composition of the main carbohydrates of cereals includes starch, dietary fiber soluble and insoluble in water, several Sugar includes glucose, glycerol, stachyose, xylose, fructose, maltose, sucrose and arabinose. Compared to milk, cereals contain It is higher than some essential vitamins, dietary fiber and minerals, especially phosphorus. In a study of microbial species with human source includes Lactobacillus plantarum, Lactobacillus acidophilus, Lactobacillus rotoi, and Lactobacillus fermentum. It was isolated and grown in the culture medium containing grains such as malt, barley and wheat (Behera et al., 2018).

3.2 Dietary fiber obtained from cereals and its prebiotic effect Edible fiber or carbohydrate of plants is a dietary fiber that is resistant to hydrolysis by digestive enzymes and is divided into two categories soluble and insoluble fiber is divided. Soluble fiber includes non-starch polysaccharides, which, due to the creation of a viscous environment, It delays the emptying time of the stomach and reduces the absorption of glucose and sterol by the small intestine. Insoluble fiber included Lignin, cellulose and hemicellulose. The amount of dietary fibers in cereals decreases from the external pericarp side to the endosperm; Except Arabinoxylan, which is the main component of the endosperm cell wall, and conventional milling methods have been developed for the separation and purification of dietary fiber (Seyedain-Ardabili et al., 2016; Brasil et al., 2011).

3.3 Vegetables and fruits as substrates for probiotics Using probiotic microorganisms in vegetable-based substrates has been shown to provide numerous health benefits. Raw and fermented Frontiers in Microbiology

07 frontiersin.org Sarita et al. 10.3389/fmicb.2024.1487641 juices, especially citrus, are promising probiotic carriers. Fruit juices are ideal for probiotic bacteria growth because lactic acid bacteria can ferment mildly acidic plant and vegetable substrates. The research utilized fruits as raw materials for the growth of Lactobacillus acidophilus and Lactobacillus plantarum, two probiotic bacteria often found in fruit substrates (Xia, 2020). These fruits were ideal substrates for non-dairy probiotic products because they offered the essential conditions for probiotic bacteria growth and lowered pH and enhanced vitality after cold storage at 4°C. Lactobacillus acidophilus and Lactobacillus plantarum are common probiotic bacteria in fruits and non-dairy probiotic beverages. These lactic acid bacteria strains survive on fruit substrates because they tolerate acidity. Probiotic microorganisms utilized in apple, banana, carrot, and tomato juices to make non-dairy probiotic drinks. Dairy products are a good source of probiotics, which promote health. However, lactose intolerance and high cholesterol in dairy products have increased demand for non-dairy probiotics (Bernal-Castro et al., 2024).

numerous nanocarriers are available which can be conveniently used as carriers for delivering probiotics (Kumari et al., 2014). Encapsulation can be defined as continuously coating any active agent to protect it from the external environment. A number of materials are being used for the encapsulation of drugs but probiotics are living cells so the choice of encapsulating material has to be specific as the polymer used must be biocompatible and biodegradable. The material used for encapsulation must allow bi-directional transport of nutrients in order for probiotic cells to survive (Gurruchaga et al., 2015). The effectiveness of encapsulation is dependent on the matrix that is utilized, which can be made up of either substances that are synthetic or substances that are natural. Materials such as alginate, carrageenan, whey protein, gelatin, chitosan, cellulose acetate phthalate, and locust bean gum are utilized widely in the process of microencapsulation. Within the temperature range of 60–80°C and alginate maintains its stability and has the potential to maintain cell viability in acidic environments (Bollinger et al., 2024). Encapsulation techniques are crucial for safeguarding probiotics and augmenting their viability (Puscaselu et al., 2020). This document presents a comparison of frequently employed techniques. The spray drying method is an efficient and widely employed process in the food industry, particularly for improving the biofortification of fruit juice. Conversely, the elevated temperatures associated with spray drying may harm the probiotics. Co-encapsulation technology refers to the simultaneous encapsulation of many components. It is favored over encapsulating individual components because it is more convenient and cost-effective (Ansari et al., 2023). Furthermore, it has been ascertained that co-encapsulation enhances long-term preservation efficacy, resulting in its extensive application within the pharmaceutical industry. The extrusion method is a mild approach for encapsulating probiotics, characterized by its simplicity and cost-effectiveness, while minimizing cellular damage. A considerable quantity of probiotics remains encapsulated via extrusion and alginate techniques. Emulsion methodologies, often known as two-phase system approaches, are a fundamental strategy for encapsulating probiotic microorganisms (Zhang et al., 2023). The specifics of the methodology may vary, but it generally involves formulating an emulsion of the probiotic substance inside a suitable carrier material for the intended application. Probiotic encapsulation technology, referred to as PET, has shown promising results in both preclinical and clinical studies, resulting in the incorporation of probiotics into various products. Nonetheless, despite encapsulation, ensuring the sustained viability of cells for prolonged durations remains challenging. Pharmaceuticals and nutraceuticals available in European pharmacies and supermarkets frequently use probiotic components (Cui et al., 2021). However, encapsulated probiotics are utilized in numerous nutritional supplements. This is implemented to guarantee that the bacteria can endure the manufacturing process, subsequent storage, and transit through the digestive system. Encapsulated probiotics are employed in several food and beverages items, including yogurts, cheeses, and fermented beverages, among others. The encapsulation enhances the product’s shelf life and safeguards the probiotics from harsh manufacturing conditions. Pharmaceuticals that incorporate probiotics through the management of specific health conditions, such as gastrointestinal disorders, can be achieved by the use of encapsulated probiotics in particular pharmaceutical formulations. The encapsulation enables probiotics to reach specific regions of the body (Palacios et al., 2023). Carrageenan apart from being used as a

4 Oligosaccharides compounds and application in prebiotic and probiotic Biological processing of cereals using enzymatic reactions or through fermentation causes the production of a high amount of oligosaccharides with potential properties. It becomes a prebiotic. These oligosaccharides are isolated from plant materials or they are made enzymatically. Oligosaccharides such as lactose, fructooligosaccharides and transgalacto-oligosaccharides stimulate the growth of probiotics. In the food industry, these compounds are added as supplements to some baby products, which have properties similar to Oligosaccharides of human milk. Resistant starch is usually produced through partial hydrolysis with acid, heat treatment, extrusion cooking, chemical modification and Polymerization takes place again. As a useful fiber, resistant starch has an important role in the physiology of digestion and the like Oligosaccharides are indigestible. This combination provides fermentable carbohydrates for river bacteria. Including the beneficial properties of resistant starch include the production of desirable metabolites in the intestine, including short-chain fatty acids, and as a prebiotic, it reduces the risk of gastrointestinal diseases. In addition to therapeutic effects, this type of starch improves appearance, texture, and feel compared to other conventional fibers (Hosseinvand et al., 2022).

5 Encapsulation method for onsite delivery of probiotics Complete efficiency of any probiotic can be achieved only if the number of viable organisms is either higher or is equal to 107 CFU/mL (Serna-Cock and Vallejo-Castillo, 2013). There are several other factors that affect the survival of microbe that is being used as probiotics. These factors include H2O2 production, pH, temperature, presence of bile salts and acids, etc. All these factors determine the efficiency and viability of probiotics. Providing a shield against these factors is quite an interesting approach these days. This approach enables delivery at the exact site of action which not only improves the viability of organisms used in formulation but also enhances their stability (Alvarez et al., 2021). With advancements in nanotechnology, Frontiers in Microbiology

feed additive can also be used as potential material for encapsulation. Since it is approved both by FDA and joint (Food Agricultural Organization) FAO/WHO. It forms a gel that can be used for encapsulation of cells, this gel however hardens at room temperature. This also enhances the stability of probiotics (Chakraborty, 2017). Whey proteins are amphoteric in nature; this enables their mixing with carrageenan and pectin. Their net charge becomes positive when pH drops below isoelectric point as a result of which they can interact with negatively charged polysaccharides. Thus, they can be effectively used as immobilization material (Vonasek et al., 2014). Deacetylation of chitin yields a positively charged polysaccharide chitosan. When pH is higher than 5.4 it becomes insoluble in the media, this is one of its major limitations as in case of high pH the contents are not fully released in the gut this limits the effectiveness of probiotics. On the contrary CAP (Cellulose Acetate Phthalate) is insoluble if pH is below 5, but it does not form beads like Chitosan, it can however be used as a coating material to further improve the stability of material used in encapsulation (Rokka and Rantamäki, 2010). At present either extrusion or emulsification technique is used for the encapsulation of microbial cells. The former one is a quite simple technique as it can be automated, it involves retention of a large number of cells and it yields beads which are basically gelled droplets. Emulsification technique yields capsules that are either oily or aqueous droplets (Frakolaki et al., 2021). Microencapsulation is a protective method of compounds to avoid deterioration due to environmental factors such as oxygen, temperature, moisture, enzymes, and acids; it also allows the delivery of encapsulated compounds in a specific site. Various biopolymers are used as wall materials for bioactive components incorporated into foods (Altamirano-Fortoul et al., 2012). In recent years, various microencapsulation techniques using cereal components have been used to improve the viability of probiotic strains in Extra-beneficial products are used. The possibility of using corn starch granules containing high amylose as a system delivery was investigated for probiotic bacteria (Hosseinvand et al., 2022). In this review, Bifidobacterium strains isolated from humans starch granules were glued. Laboratory studies showed an increase in the survival of probiotic breeds in these conditions. The use of calcium alginate for microencapsulation of probiotic bacteria in yogurt was done by researchers. The binding of corn starch (prebiotic) with alginate also improved the microcovering of living bacteria. Methods such as spray drying for production the microbial microbeads that are uniformly coated and contain live bacteria are the focus of many researchers (Krasaekoopt et al., 2004).

investigation for their potential in treating obesity, metabolic syndrome, respiratory infections, and COVID-19. Probiotics and prebiotics are projected to reach approximately $50 billion in sales and manufacturing within a few years (Bodke and Jogdand, 2022). This increase signifies consumer knowledge of gastrointestinal health and its impact on overall well-being. As the microbiome is comprehended more thoroughly, these products may enhance neurological and cancer preventive results. Recent studies on probiotics and prebiotics are uncovering their potential roles in neurobiology and cancer prevention. The search results do not address probiotics and prebiotics in neurobiology; nonetheless, the gut-brain axis is receiving increased attention in research. This study indicates that gut microbiota may influence brain function and behavior, potentially impacting depression, anxiety, and neurodegenerative diseases. Probiotics and prebiotics influence gut microbiota, perhaps benefiting neurological health. Investigations into probiotics and prebiotics for cancer prophylaxis appear encouraging (The Lancet Global Health, 2020). Numerous illnesses, including cancer, are associated with gut microbial dysbiosis. Prebiotics and probiotics may restore equilibrium and enhance immune surveillance, potentially exhibiting oncostatic properties. Numerous epidemiological and experimental studies have enhanced our understanding of probiotics and microbial therapy as anticarcinogenic agents (Cui et al., 2021). Certain human studies indicate that probiotics and prebiotics are beneficial. Certain clinical probiotic strains may decrease postoperative inflammation in cancer patients. Oral probiotics alleviated diarrhea associated with chemotherapy or radiotherapy. Probiotic aerosol therapy is an innovative treatment for preventing lung metastases in high-risk melanoma patients. Altered gut microbiota influences cancer progression and the efficacy of anticancer therapies. In vivo and molecular studies on probiotics and cancer prevention have demonstrated encouraging outcomes (Ezeji et al., 2021).

6.1 Probiotics in cancer treatment Cancer is undoubtedly one of the leading causes of death around the globe. Nearly 755 cancer patients die as a result of diet and lifestyle-associated factors and the diet-related factors alone account for 50% of deaths. Numerous in-vitro and animal studies indicate the role of intestinal and gut microbiota in reducing the risk of death from diet-related factors. Probiotics play an important role in reducing the risk of colon and bladder cancer. Helicobacter, Pseudomonas and Acinetobacter are responsible for tumor formation in the colon which ultimately leads to colon cancer. They proliferate easily in absence of beneficial bacteria. Probiotics can play a major role in modulating the intestinal and gut microbiome. Lactobacillus acidophilus and L. casei shirota are the most commonly used strains (Dasari et al., 2017; Maleki et al., 2016). Probiotics have the potential to inhibit the proliferation and growth of colorectal cancer (CRC) through a variety of methods, including the normalization of intestinal flora and the enhancement of the gastrointestinal barrier of the gastrointestinal tract. Short chain fatty acids (SCFAs), which are essential metabolites of probiotics, serve as a source of energy for the colonic mucosa, strengthen the intestinal protective barrier, regenerate the colonic epithelium, regulate the pH of the intestinal lumen, inhibit the proliferation of cancer cells, and encourage the death of cancer cells through the process of apoptosis (Wong and Yu, 2019). In addition,

6 Role of probiotics in promoting human health Probiotics are used for the management of an array of disorders and unusual physiological conditions. There is enough evidence indicating the potential of various probiotic strains in the treatment of a number of health issues including gastrointestinal issues, tumors, respiratory issues, etc. The swift advancement of microbiome science has resulted in various applications of probiotics and prebiotics. Synbiotics, a combination of probiotics and prebiotics, are being formulated to enhance their efficacy. Probiotics are now under

short-chain fatty acids (SCFAs) perform the function of signaling molecules through the use of G-protein coupled receptors (GPCRs), thereby reducing the production of pro-inflammatory cytokines and increasing the number of transgenic cells in the colon. There is still a lack of understanding regarding the mechanism of action of probiotics in the prevention and treatment of colorectal cancer (CRC) (Cristofori et al., 2021). As a result of the numerous forms of probiotics, which each have their own unique features and modes of action, the effects of these probiotics are complex and varied. It is required to do additional clinical research in order to examine the regulatory mechanisms of probiotics on colorectal cancer (CRC), understand each process, and then go on to use it as an adjuvant therapy for the prevention and treatment of CRC (Torres-Maravilla et al., 2021). Suitable probiotic-related treatments may be utilized for the purpose of preventing colorectal cancer (CRC) prior to the development of the disease (Ezeji et al., 2021). These interventions may include the direct oral delivery of probiotics and the fermentation byproducts of probiotics, in conjunction with probiotics or anticancer medicines. It is possible to use probiotics in conjunction with intensive cancer treatments such as surgery, chemotherapy, and immunotherapy in order to reduce the risk of complications during surgical and chemotherapeutic procedures, improve the effectiveness of chemotherapy, and enhance the quality of life of patients. Probiotics that are considered traditional are currently being used as an adjuvant therapy in the treatment and care of colorectal cancer (CRC), primarily for the purpose of mitigating surgical complications and alleviating the adverse effects of chemotherapy (Zhao et al., 2023).

been found in the vaginal swab of many women are quite effective in lowering the pH. For treating UTI there are over 50 probiotics that can effectively treat UTI, all these are based on Lactobacillus spp. i.e. Lactobacillus brevis, L. reuteri, L. vaginalis, L. rhamnosus (Figure 2; Van et al., 2023).

6.5 Probiotics for obesity Genetic variability, energy intake and expenditure imbalance are the major reasons for obesity which is a growing issue in these times. Adiponectin and leptin are present in adipocyte tissues and these are majorly responsible for obesity, Lactobacillus gasseri BNR17 inhibits their growth. Probiotics stimulate the adrenergic nervous system which generates a thermogenic response, this facilitates weight loss. Certain probiotics like Lactobacillus acidophilus, L. casei, Bifidobacterium longum exhibit hypocholesterolemic activity, they reduce the level of triglycerides, Low Density Lipids (LDL) and High Density Lipids (HDL) (George et al., 2018).

6.6 Probiotics for CNS and neurobiology If Lactobacillus plantanum is administered to children with autism, it shows a promising effect. There are certain strains of Lactobacillus like L. helveticus, L. casei, L. rhamnosus which are known to reduce psychological distress, anxiety symptoms, autism-associated symptoms, respectively. In fact, some neuroactive compounds are being synthesized by some bacteria that resemble that of the host (Park et al., 2018). Probiotics and prebiotics affect the gut-brain axis, which bolsters the central nervous system and mitigates or regulates mental disorders such as depression, anxiety, autism, schizophrenia, and Alzheimer’s disease. This review presents intricate relationships among microbiota, the stomach, and the brain, along with recent research findings on the impact of probiotics and prebiotics on mental disorders. Probiotics and prebiotics may enhance central nervous system function and mitigate certain neurological illnesses. The relationship between the brain and the gastrointestinal tract is well-established (Victoria Obayomi et al., 2024). Mutual effects are ascribed to direct neural signals and indirect hormonal and enzymatic connections. A novel, natural therapy for mental disorders utilizing prebiotics, probiotics, and synbiotics to regulate the central nervous system with minimal side effects has been suggested. This review identified positive effects of prebiotics, probiotics, and synbiotics on anxiety, depression, stress, sleep, and Alzheimer’s disease (Centurion et al., 2022). Although research indicates the beneficial effects of pre-, pro-, and synbiotics on many mental disorders such as schizophrenia and autism spectrum disorder, the evidence is inadequate to justify their application for these conditions. It is essential to conduct meticulously organized clinical trials utilizing various prebiotics, probiotics, and synbiotics in clearly defined and sizable populations to obtain more precise and dependable results. Recent research is sufficiently persuasive to develop prebiotic, probiotic, and synbiotic formulations for mental disorders (Cryan et al., 2019). This may encompass the evaluation of pharmaceutical protocols alongside conventional treatments and the use of prebiotics, probiotics, or synbiotics (Ansari et al., 2023). Alterations in gut microbiota can influence mood, indicating that the microbiota–gut–brain (MGB) axis plays a role in depression. Numerous processes intersect with the role of

6.2 Probiotics for treatment of GI tract issues Probiotics can be effectively used for the treatment of lactose intolerance, gastrointestinal and urogenital infections, ulcerative colitis, gastrointestinal tumors and Chrohn’s disease. Probiotics compete with pathogens for the binding site at epithelial tissue and some synthesize biochemicals that inhibit the growth of pathogens. Lactobacillus plantanum effectively prevents bloating and abdominal pain, S. boulardii is used for the treatment of diarrhea and for improving overall gut functioning (Iannitti and Palmieri, 2010).

6.3 Probiotics for diabetes Probiotics can effectively modulate gut hormones, the hormones are known for controlling homeostasis, their modification neutralizes the resistance to insulin which is the major cause of type 2 diabetes. There are some probiotics that can reduce the growth of adipocytes which aids in the prevention of a range of metabolic disorders (Westfall et al., 2018).

6.4 Probiotics for UTI Urinary Tract Infections (UTI) result from an imbalance in vaginal microbiota. It is quite common in both elder and young women. It can be both upper UTI and lower UTI. It is recurrent problem and prophylactic antibiotics can sometimes be beneficial but there is a risk of resistance development. Lactic acid bacteria have

Frontiers in Microbiology 10 frontiersin.org Sarita et al. 10.3389/fmicb.2024.1487641 FIGURE 2 Probiotics in treatment of diseases. 6.8 Probiotics for respiratory diseases

gut bacteria in the development of metabolic disorders and obesity. In rats, prebiotics and probiotics modify the makeup and function of gut microbiota (Yuan et al., 2022). Probiotics and germ-free rodent models have demonstrated a causal relationship between microorganisms, microbial metabolites, and neurochemical signaling and inflammatory pathways in the brain. Further therapeutically pertinent research is required; nonetheless, probiotic supplementation has demonstrated modest antidepressant effects in individuals with depression (Franzosa et al., 2018). However, preclinical and clinical findings to critically assess the function of the MGB axis in the pathophysiology of depression and the putative communication pathways between the microbiota-gut interface and the brain. A comprehensive evaluation of methodologies in depression microbiome research is presented. Future MGB axis research must incorporate stringent placebo-controlled trials and a comprehensive molecular and biochemical understanding of prebiotic and probiotic mechanisms to translate preclinical successes into novel medicines (Radford-Smith and Anthony, 1880).

Bronchitis, sinusitis, pharyngitis, rhinosinusitis, otitis is some of the most common respiratory disorders. Probiotics exhibit both antiinflammatory and anti-microbial properties owing to which they can be used for the prevention of a number of respiratory disorders. For example: for controlling episodes of pneumonia in patients with cystic fibrosis, Lactobacillus rhamnosus can be administered. Lactobacillus fermentum, L. casei, and Bifidobacterium longum are some of the common probiotics used for the treatment of respiratory issues (Soccol et al., 2014).

6.9 Probiotics for cardiovascular diseases Angiotensin-Converting Enzyme (ACE) is a key enzyme behind hypertension. Lactobacillus helvetics and Saccharomyces cerevisiae are known to synthesize peptides that can inhibit the activity of ACE (Mayta-Tovalino et al., 2023).

6.7 Probiotics for angiogenesis 6.10 Probiotics for inflammatory diseases

New vessels are regenerated from old vessels via angiogenesis, it aids in faster wound healing. If not done in a proper way, it may lead to cancer and diabetic retinopathy. S. boulardii is known for protecting the host body against inflammation and injury by decreasing visceral hypersensitivity and modifying inflammatory cytokine profile (Xu et al., 2024).

Frontiers in Microbiology

Probiotics can be used for the treatment of Ulcerative colitis and Chrohn’s disease. They result in inflammation of GIT, both aerobic and anaerobic bacteria are responsible. These two diseases in combination are known as inflammatory bowel disease. Lactobacillus, 11

frontiersin.org Sarita et al. 10.3389/fmicb.2024.1487641 Enterobacter, and Bifidobacillus are used for the treatment of inflammation (Roy et al., 2023).

delivery via various methods with minimal negative effects. Many probiotics have been approved for sale in large quantities to alleviate symptoms of diseases. The use of probiotics for the treatment of bowel disorders such as infectious diarrhea, antibiotic-induced diarrhea, lactose intolerance and allergies has been documented. The use of probiotics is not just limited to GIT disorders but has also expanded in the treatment of other disorders like obesity, respiratory, cardiovascular and CNS disorders. The delivery of probiotics to the site of action is another challenging task but there are various techniques available to overcome this limitation as well like the encapsulation of probiotic cells in a suitable carrier medium that is resistant to acids, bile salts and temperature so that the effect of probiotic can be maximized. Another approach to improve the effectiveness of probiotics is to administer them with antibiotics so that side effects can be reduced and the eradication of microbes can be enhanced without the development of antibiotic resistance.

7 Other recent approaches Antimicrobials are quite effective but they do have limitations namely high cost, potential side effects and development of antimicrobial resistance with continued use (Vitor and Vale, 2011). In order to overcome this limitation antimicrobial drugs are being administered with probiotics, this not only improves the healing but also reduces the dose that is required to be administered, it ultimately leads to improved eradication of microbes from the site of infection and also reduces the potential side effects associated with full dosage (Kosgey et al., 2019). For the treatment of Helicobacter pylori-induced stomach ulcers antimicrobial are usually prescribed, they not only have potential side effects but they also develop antibiotic resistance in the causative organism. The eradication rate for an antibiotic is about 71% but when antibiotics are administered with probiotics this rate rises up to 81%. There is a significant reduction in side effects as well. In 2018, Russo et al. studied the synergism of oral probiotic formulation and tropical clotrimazole for the treatment of vulvovaginal candidiasis. Lactobacillus acidophilus and Lactobacillus rhamnosus were used along with Lactoferrin glycoprotein. The combination of probiotics with clotrimazole effectively reduced the symptoms and it also affected the recurrence of infection (Shenoy and Gottlieb, 2019). Probiotics along with anti-fungal ointments are highly effective against Candida spp. they not only reduce the symptoms but also help in the restoration of normal vaginal microbiota (Mastubara et al., 2016). Chronic periodontitis results from inflammation in tissues that support teeth, this leads to loss of periodontal ligament. It is a multifactorial disease; antibiotics are mostly used to reduce the bacterial load present. Probiotics can be used as adjuvant treatment along with conventional antibiotics. L. reuteri is especially used as it forms reuterin, it reduces oxidative stress and competes with pathogenic strains for adhesion sites, it also reduces the expression of MMP-8 by controlling the production of TNF-α, IL-17 which are pro-inflammatory cytokines (Soler and Kutsner, 2020).

Author contributions BS: Supervision, Writing – original draft, Writing – review & editing. DS: Supervision, Writing – original draft, Writing – review & editing. MH: Supervision, Writing – original draft, Writing – review & editing. EK: Investigation, Writing – original draft, Writing – review & editing.

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# 益生菌与人类健康——当前展望及应用综述

**类型** 综述 **发表日期** 2025年1月6日 **DOI** 10.3389/fmicb.2024.1487641 **开放获取** **编辑** K. B. Arun,印度基督大学 **审稿人**

Anjani Devi Chintagunta,印度Vignan科学与技术研究基金会 Iftikhar Younis Mallhi,巴基斯坦Minhaj大学拉合尔分校 **通讯作者** Bhutada Sarita sabhutada13@gmail.com **收稿日期** 2024年8月28日

**益生菌与人类健康——当前展望及应用综述**

Bhutada Sarita 1*,Dahikar Samadhan 1,Md Zakir Hassan 2,3,Elena G. Kovaleva 2

1 印度Kopargaon Sanjivani文理学院微生物学系 2 俄罗斯叶卡捷琳堡乌拉尔联邦大学(以俄罗斯第一任总统B. N. 叶利钦命名)有机合成技术研究所 3 孟加拉国萨瓦尔孟加拉国畜牧研究所

**录用日期** 2024年12月16日 **发表日期** 2025年1月6日

**引用格式**

Sarita B, Samadhan D, Hassan MZ and Kovaleva EG (2025) A comprehensive review of probiotics and human health-current prospective and applications. Front. Microbiol. 15:1487641. doi: 10.3389/fmicb.2024.1487641

**版权声明**

© 2025 Sarita, Samadhan, Hassan and Kovaleva. 本文为开放获取文章,依据知识共享署名许可协议(CC BY)条款分发。在其他论坛使用、分发或复制本文须注明原作者和版权所有者,并引用本期刊的原始发表信息,符合公认的学术规范。任何不符合上述条款的使用、分发或复制行为均不被允许。

益生菌的有益特性一直是研究关注的重点。益生菌在维持胃肠道(GIT)健康方面发挥着重要作用,健康的消化系统负责调节机体的所有其他功能。通过与益生元配方可增强益生菌的功效,由此形成的配方被称为合生元。合生元不仅提高了益生菌细胞的活力和稳定性,还能抑制病原菌株的生长。乳杆菌属(Lactobacillus)和双歧杆菌属(Bifidobacterium)是最常用的益生菌。其他可用作益生菌的微生物种类包括芽孢杆菌属(Bacillus)、链球菌属(Streptococcus)、肠球菌属(Enterococcus)和酵母菌属(Saccharomyces)。益生菌可用于治疗糖尿病、肥胖症、炎症性疾病、心血管疾病、呼吸系统疾病、中枢神经系统疾病(CNS)及消化系统疾病。对促进肠道健康的活微生物进行包埋也至关重要。益生菌的包埋可保护其在生产、储存及胃肠道转运过程中免受风险。高温、高压和氧化作用会破坏益生菌及其保护特性。益生菌的包埋可延长其存活时间、促进受控释放、减少加工损失,并使其能够应用于功能性食品产品中。通过喷雾干燥或凝聚法制备的微球形式益生菌可调节肠道益生菌的释放并提供抗逆性。海藻酸钠、氯化钙、凝胶珠及多糖等天然包埋材料可在消化过程中为益生菌的保护提供保障。此外,多种方法(如喷雾干燥法——液体在加热空气室中雾化以蒸发水分并产生干燥颗粒)可提高益生菌的功效和稳定性。另外,用益生元或维生素包埋益生菌也可增强其功效。益生菌通过增加抗体和免疫细胞的生成来提高免疫系统效能,对抗疾病并增强免疫力。近期研究表明,益生菌可能有助于调节体重和血糖水平,并影响代谢和胰岛素敏感性。新兴研究表明,"肠-脑轴"将心理健康与胃肠道健康联系起来。益生菌可能通过影响神经递质合成和炎症反应来缓解焦虑和抑郁。益生菌在皮肤健康方面的优势研究也在进行中,预测益生菌的原位递送中,包埋是一种有效的技术,需要研究者给予更多关注。本综述重点探讨了益生菌、益生元和合生元在预防和治疗人类健康疾病中的应用。

**关键词**

益生菌,人类健康,合生元,肠道疾病与包埋,益生元

# 前言

促进双歧杆菌(Bifidobacterium)等有益菌的生长和发育(Lacerda et al., 2020)。

益生菌在胃肠道(GIT)中的存活有时较为困难,为解决存活难题,合生元应运而生。益生菌的活力和功效取决于多种因素,包括氧气、水分、应激、pH值等(Mazziotta et al., 2023)。合生元是益生元与益生菌的组合配方,其配制方式不仅提高了有益微生物的存活几率,还能刺激胃肠道内原生菌群的生长和增殖。益生元可提高益生菌对环境因素(如温度、氧气和胃肠道内pH值)的耐受性。然而,当益生元与益生菌结合时,微生物的效能及其对限制性因素的耐受性将显著改善,从而对宿主机体产生有益影响(Manigandan et al., 2012)。合生元不仅能抑制有害病原体的生长,还能维持肠道生物结构并降低不良代谢产物的浓度。合生元在降低血脂和血糖水平、免疫调节、骨质疏松预防以及由肝功能异常引起的神经障碍治疗方面具有显著功效。乳杆菌、凝结芽孢杆菌(B. coagulans)、双歧杆菌、布拉氏酵母菌(S. boulardii)等是合生元配方中最常用的益生菌菌株,通常与低聚糖类益生元配合使用(Pandey et al., 2015)。合生元将益生菌(有活力的有益细菌)与益生元(促进其增殖的制剂)相结合以增强健康。多种因素影响合生元的配方设计。益生菌和益生元的选择至关重要——益生菌必须基于其健康益处和在胃肠道中持续存活的能力进行选择,而益生元则应促进其增殖。所选菌株和底物必须协同作用以实现健康效益(Chan and Liu, 2022)。确保益生菌在制造、储存和分销过程中的活力面临重大挑战。酸奶中益生菌的存活受pH值、水分和氧气浓度的影响。因此,益生菌常被包埋以保护其免受环境应激因素的影响,并保持其稳定性直至到达胃部。益生菌和益生元的基质配方影响合生元产品的释放和功效。该配方必须在胃肠道内的适当时间和位置释放益生菌以优化健康效益(Chan et al., 2021; Chan and Liu, 2022)。合生元可分为多种类别,如膳食补充剂和功能性食品,这使其监管变得复杂。这种多样性可能影响合生元的审批和市场推广。尽管合生元日益受到欢迎,但消费者仍在逐步了解其优势及与益生菌和益生元的区别。随着消费者对肠道健康、益生菌和益生元认知的不断提高,合生元的市场应用正在扩展。主要应用包括将合生元添加到酸奶、冰沙和膳食补充剂中(Rashidinejad et al., 2022)。这些产品为肠道健康提供了便捷的解决方案。此外,合生元还可用于治疗与菌群失调相关的疾病,如胃肠道疾病、肥胖症和代谢综合征。此外,微生物组研究可能提供针对特定健康需求和微生物组特征的定制化合生元配方,从而提高合生元对特定健康结局的有效性(Chaturvedi and Chakraborty, 2021)(图1)。

## 1.1 益生菌简介

"Probiotic"一词源自希腊语,意为"为了生命",由Lilley和Stillwell提出。益生菌是指对宿主有益的非致病性微生物(Soccol et al., 2014)。益生菌的使用历史悠久,古罗马和古希腊等古代文明就已开发发酵乳并将其用作益生菌,甚至圣经中也提到了这种酸乳,因此益生菌的概念并非全新(Hosono, 1992)。益生菌可改善胃肠道的微生物平衡。世界卫生组织(WHO)将益生菌定义为"当以足量施用时,能够对宿主健康产生益处的活微生物"(Chen and Sears, 2015)。乳杆菌属、双歧杆菌属、肠球菌属、乳球菌属和链球菌属是最常用的益生菌(de Sequeira et al., 2022)。任何微生物菌株在用作益生菌之前必须满足安全性和功能性标准。这些标准包括遗传稳定性、耐酸耐胆盐能力、肠道黏附能力、抗基因毒性、非致病性、产乳酸能力、耐严苛加工条件以及较短的世代时间(de Melo Pereira et al., 2018)。益生菌通过增强上皮屏障、促进微生物在肠道黏膜上的定殖同时抑制病原体黏附、调节免疫系统以及产生可抑制病原微生物生长的生化物质来发挥作用(Bermudez-Brito et al., 2012)。这些抗菌化合物被称为细菌素,具有活性蛋白组分。这些细菌还产生短链脂肪酸(SCFAs)、过氧化氢(H2O2)和二乙酰,这些生化物质可改变肠道微生物区系,从而带来积极的健康益处(Hawrelak and BNat, 2013)。几乎所有双歧杆菌和乳杆菌菌株都能产生这些细菌素。

## 1.2 益生元与合生元

益生元可定义为不可消化的食物成分,通过恢复胃肠道(GIT)中有益微生物的生长来提供健康益处。益生元主要以刺激胃肠道中有益细菌的活性和生长而闻名。它们能刺激结肠中细菌的生长。与其他食物成分不同,它们几乎不受胃肠道中水解酶或酸的影响,但易被有益细菌发酵(Kuo, 2013)。菊芋、菊苣根、浆果、番茄、未精制小麦、洋葱、芦笋、大蒜、大豆、不可消化碳水化合物等都是益生元的来源(Pokusaeva et al., 2011)。某些益生元除调节有益微生物的生长外,还具有多种健康益处,如抗炎、抗腹泻及降低结肠癌风险(Peña, 2007)。从海藻中提取的海藻酸盐和琼脂,以及石花菜(Gelidium)中富含的多糖——石花菜多糖(Ulvan),也是粪杆菌(Faecalibacterium prausnitzii)的独特益生元(Saulnier et al., 2009)。其发酵副产物为短链脂肪酸(SCFAs),即乙酸或丙酸,这些酸可降低肠道pH值,但某些细菌(如双歧杆菌)对短链脂肪酸具有耐受性。这抑制了有害细菌的生长并

**益生菌、益生元与合生元的来源及应用。**

### 1.2.1 益生菌的安全性标准、潜在风险及特定人群的安全隐患

在保持益生菌产品效价、稳定性和货架期的同时遵循优良制造规范。不良事件——上市后监测对于监控益生菌副作用至关重要(Bodke and Jogdand, 2022)。这种持续审查突出了产品上市后可能出现的安全隐患。应优先考虑高危人群,包括免疫功能低下者或其他健康状况不佳者,以降低风险。益生菌的安全性至关重要,因为其消费人群多样,包括婴幼儿、老年人和免疫功能低下者(Sharifi-Rad et al., 2020)。通常需评估以下安全性标准。益生菌菌株必须经过准确鉴定以确保识别、纯度和活力。这包括验证菌株的活力并表征其遗传和表型特征。消费者安全性要求具有明确安全属性的清晰界定菌株。益生菌必须经过致病性测试。我们评估菌株是否会诱发疾病或产生有毒物质。动物模型被用于研究易感人群中的安全隐患,如心内膜炎。益生菌产品必须经过有害真菌、霉菌毒素和重金属的检测。最终产品必须不含有害污染物以确保消费者安全。临床安全性——临床试验必须确立益生菌在目标人群中的安全性。这包括监督试验中的不良反应并确认益生菌菌株的安全性。法规合规性:各地区益生菌产品的标准各不相同。这包括

益生菌的安全性至关重要,因为其消费人群多样,包括婴幼儿、老年人和免疫功能低下者。通常需评估以下安全性标准。益生菌菌株必须经过准确鉴定以确保识别、纯度和活力(Mazziotta et al., 2023)。这包括验证菌株的活力并确定其遗传和表型特征。消费者安全性要求具有明确安全属性的清晰界定菌株。益生菌必须经过致病性评估(Damián et al., 2022)。因此,需评估菌株是否会诱发疾病或产生有毒物质。动物模型被用于研究易感人群中的安全隐患,如心内膜炎。益生菌产品必须经过有害细菌、霉菌毒素和重金属的检测。最终产品必须不含有害污染物以确保消费者安全。临床安全性——益生菌必须在目标人群中通过临床研究证明其安全性。这包括监督试验中的不良反应并确认益生菌菌株的安全性。各地区法规有所不同,但益生菌产品必须遵守相关规定。这包括遵守卫生主管部门为食品和补充剂制定的益生菌安全性和功效要求(Tegegne and Kebede, 2022)。

质量控制——制造商必须在整个生产过程中严格监督质量。这包括

**表1 常用作益生菌的细菌菌株**

遵守卫生主管部门为食品和补充剂制定的益生菌安全性和功效要求(Victoria Obayomi et al., 2024)。

制造商必须在生产过程中严格执行质量控制措施。这包括保持益生菌产品的效价、稳定性和货架期,同时遵循优良制造规范。不良事件——上市后监测对于监控益生菌副作用至关重要。这种持续审查可发现产品上市后可能出现的安全隐患。应优先考虑弱势群体,包括免疫功能低下者或其他健康状况不佳者。在美国,益生菌由美国食品药品监督管理局(FDA)作为膳食补充剂或食品进行监管(Al-Rashidi et al., 2022)。1994年《膳食补充剂健康与教育法》(DSHEA)适用,但不要求上市前审批。制造商必须标注产品并保证产品安全性。机会性感染,尤其是免疫功能低下者的机会性感染,困扰着益生菌。益生菌菌株和其他良性细菌在免疫系统受损时可诱发疾病。中心静脉导管使用者和重症患者曾发生酵母菌血症(Palacios et al., 2023)。部分人在开始使用益生菌后可能出现腹胀、胀气或腹泻。这些症状通常轻微且为暂时性,但消费者仍表示担忧。益生菌可能影响免疫抑制药物的疗效。这种联合使用可能增加感染风险或降低治疗效果。益生菌可能对正在接受化疗、器官移植及HIV/AIDS患者有害。感染抵抗力降低的人在使用前需评估益生菌菌株的安全性。明智地使用益生菌以预防新生儿和幼儿的胃肠道并发症(Ashaolu, 2020)。

嗜酸乳杆菌(Lactobacillus acidophilus) 鼠李糖乳杆菌(Lactobacillus rhamnosus) 发酵乳杆菌(Lactobacillus fermentum) 约氏乳杆菌(Lactobacillus johnsonii) 乳酸乳球菌(Lactobacillus lactis) 罗伊氏乳杆菌(Lactobacillus reuteri) 双歧杆菌属(Bifidobacterium spp.) 短双歧杆菌(Bifidobacterium breve) 婴儿双歧杆菌(Bifidobacterium infantis) 长双歧杆菌(Bifidobacterium longum) 两歧双歧杆菌(Bifidobacterium bifidum) 乳双歧杆菌(Bifidobacterium lactis) 嗜热双歧杆菌(Bifidobacterium thermophilum) 芽孢杆菌属(Bacillus spp.) 凝结芽孢杆菌(Bacillus coagulans) 链球菌属(Streptococcus spp.) 嗜热链球菌(Streptococcus thermophilus) 肠球菌属(Enterococcus spp.) 粪肠球菌(Enterococcus faecium) 酵母菌属(Saccharomyces spp.) 酿酒酵母(Saccharomyces cerevisiae)

印度支那的热带水果。它对酸和温度胁迫具有很强的抵抗力,因此可轻松用作益生菌(Bhukya et al., 2019)。益生菌是指当摄入或施用以在体内达到最佳水平时能提供多种健康益处的活微生物。表1提供了酸奶、发酵食品、膳食补充剂和美容产品中常见益生菌的信息(Elhossiny et al., 2023)。

## 2 益生菌分类

目前,有多种微生物被用作益生菌(Hawrelak and BNat, 2013)。表1列出了常用作益生菌的细菌菌株。乳杆菌属的细菌为革兰氏阳性杆菌,能够在胃肠道(GIT)和泌尿生殖道(GUT)中产生乳酸,它们是厌氧菌,可提高矿物质的吸收和生物利用度并降低肠道通透性。事实上,该属某些菌株表现出抗癌和降血脂活性(Cichonska and Ziarno, 2022)。

双歧杆菌为多形性、厌氧、革兰氏阳性杆菌,其代谢副产物为乙酸和乳酸。与酿酒酵母和乳杆菌联合使用时,可减轻幽门螺杆菌感染的影响(Chen et al., 2019)。

凝结芽孢杆菌以产生乳酸而闻名,有时被商品化为产孢乳杆菌(Lactobacillus sporogenes),但它与乳杆菌不同,不属于正常肠道菌群。但它在抑制病原体定植和恢复正常肠道菌群方面非常有帮助,且对酸性环境和高温度具有高度耐受性(Cao et al., 2020)。

酿酒酵母(Saccharomyces cerevisiae)或布拉氏酵母菌(S. boulardii)常用于治疗腹泻,其自然形式从

### 2.1 嗜酸乳杆菌

嗜酸乳杆菌是一种已被广泛应用的益生菌菌株,因其潜在的健康益处而备受关注。该菌株具有黏附多种肠道细胞的能力,表现出耐胆盐性和耐酸性,这些都是益生菌菌株的重要特性。然而,此前的实验室研究表明,某些嗜酸乳杆菌菌株能够将胆固醇水平降低50%以上。这一发现凸显了它们在增强心血管健康方面的潜在重要性,尤其是与其他益生菌菌株联合使用时。此外,它已被证明在预防成人胃肠道疾病和减轻儿童普通感冒症状方面具有功效。商业化的嗜酸乳杆菌菌株包括LA-1、LA-5、NCFM、DDS-1和SBT-2026(Elhossiny et al., 2023)。

### 2.2 鼠李糖乳杆菌

鼠李糖乳杆菌菌株已发展出独特的适应性,使其能够在人体内酸性环境中存活。鼠李糖乳杆菌黏附和定殖于肠壁的能力使其可能提供持久的益处。因此,它常被添加到酸奶、奶酪、牛奶和其他乳制品中以增加益生菌水平。此外,鼠李糖乳杆菌在奶酪成熟过程中发挥着关键作用,从而提升整体风味。此外,某些鼠李糖乳杆菌菌株已被证明对成人和儿童具有有益效果,特别是在治疗肠易激综合征(IBS)、湿疹、过敏和免疫系统支持方面(Gao et al., 2022)。

### 2.3 发酵乳杆菌

发酵乳杆菌是一种具有黏附和抗感染特性的益生菌细菌。它常见于奶酪成熟过程中,在某些奶酪品种中被归类为非发酵剂乳酸菌(NSLAB)。这些特性表明发酵乳杆菌在对抗感染和促进泌尿生殖道健康方面具有潜力。此外,已观察到发酵乳杆菌菌株JDFM216具有增强认知和生理功能的潜力,同时表现出免疫调节特性。该特定菌株与巨噬细胞吞噬活性增强、IgA合成增加及免疫细胞活化增强相关。益生菌菌株发酵乳杆菌因其抗菌和抗氧化能力、代谢胆固醇的能力以及对心血管健康的潜在贡献而受到认可。这些特性使其成为具有促进健康前景的独特菌株。此外,已观察到发酵乳杆菌菌株具有显著的自身聚集能力,这是其黏附上皮细胞和促进胃肠道内生物膜产生的关键因素(Anjum et al., 2014)。

### 2.6 罗伊氏乳杆菌

罗伊氏乳杆菌与广泛的健康益处相关,包括预防和管理女性泌尿生殖系统疾病和细菌性阴道病、特应性疾病、食物过敏以及预防龋齿。此外,其预防结肠炎和减少P-选择素相关白细胞与血小板与内皮细胞之间相互作用的能力已被研究,凸显了其在肠道疾病中的重要性。对其抑制有害细菌、酵母菌和其他微生物生长的能力进行了广泛研究,从而证明其作为治疗胃肠道和泌尿生殖系统疾病(包括婴儿肠绞痛)的有益益生菌的潜力(Assimos, 2020)。

### 2.4 约氏乳杆菌

约氏乳杆菌菌株LA-1是最早被提议作为益生菌乳制品补充剂的培养物之一。该菌株用于雀巢LC-1酸奶产品中,具有增强免疫反应、耐受胆盐和抗生素等多种条件、对抗抗菌素耐药微生物以及在食品中保持高益生菌活力的能力。此外,约氏乳杆菌已被证明能够降低病原体菌株的黏附和活性、抑制肠道病原体的生长并缩短腹泻和肠小肠结肠炎的持续时间(Tavasoli et al., 2022)。

### 2.5 短双歧杆菌

短双歧杆菌属于双歧杆菌属,以其益生菌特性而闻名。该细菌是一种共生生物,栖息于人类肠道中,已被用于治疗多种疾病,如便秘、腹泻、肠易激综合征,甚至普通感冒和流感。科学研究已证实多种应用,展示了短双歧杆菌潜在的生理益处。这种杆状细菌为革兰氏阳性、厌氧、非运动性。它与邻近生物形成分支。短双歧杆菌菌株在儿科领域得到了广泛应用,并被认为是母乳喂养婴儿胃肠道中的主要物种。此外,它们已从人乳中提取,强调了其在婴儿胃肠道中的天然存在。短双歧杆菌菌株已在儿科人群中成功进行了试验,并证明在治疗各种健康问题方面具有功效,从而确立了其作为增强消化和整体健康的益生菌菌株的重要性(Zanjani et al., 2017)。

### 2.7 乳酸乳球菌

乳酸乳球菌作为一种乳酸菌,因其在增强免疫功能和缓解炎症性肠病方面的潜在益生菌能力而受到大量研究。本分析全面考察了乳酸乳球菌的益生菌特性和潜在健康益处,乳酸乳球菌通常被用作益生菌。评估基于特定标准,包括耐胆盐性、耐酸性、胆固醇同化活性和对肠道细胞的黏附能力。某些乳酸乳球菌菌株(如乳酸乳球菌ML-2018)的抗炎能力已被认可,特别是在抑制脂多糖(LPS)触发的炎性因子产生方面。某些乳酸乳球菌菌株已被证明与增强免疫系统和预防胃肠道及上呼吸道感染相关(Zanjani et al., 2017; Nazia et al., 2014)。

### 2.8 婴儿双歧杆菌

婴儿双歧杆菌,科学上称为长双歧杆菌婴儿亚种(Bifidobacterium longum subsp. infantis),是一种天然栖息于口腔和消化系统的良性细菌菌株。它与乳杆菌同属一类,是一种乳酸菌,对维持健康的消化系统至关重要。婴儿双歧杆菌35,624已被广泛研究,并专门考察了其治疗肠易激综合征(IBS)的潜力。其在缓解婴儿腹胀、排便问题、疼痛和肠道菌群失调等症状方面的功效已被证实。此外,它已被证明与改善胃肠不适的管理和增强肠易激综合征(IBS)患儿的整体健康相关(Azad et al., 2018; Sanders et al., 2018)。在缓解胃肠不适和其他医疗状况方面具有高效性。此外,它能够控制宿主的共生微生物群并抑制有害细菌的增殖,从而促进整体胃肠道健康并为消化系统和免疫系统提供支持。在天然食品来源中,如酸菜、泡菜和酸奶等发酵食品中可发现凝结芽孢杆菌。此外,它在多种益生菌食品添加剂中有所应用,展示了其在食品工业中工业化实施的适用性(Ma et al., 2021)。

### 2.9 长双歧杆菌

长双歧杆菌是一种栖息于胃肠系统的共生菌,被广泛认可为人类肠道菌群的重要组成成分。它在婴儿肠道中尤为普遍,是数量最多的物种。它展现出多种有益健康益处,包括生物活性化合物的合成以及双歧杆菌表面相关分子与宿主之间的相互作用。对长双歧杆菌进行了广泛研究,揭示了其在管理肠易激综合征(IBS)相关症状方面的有效性,如腹胀、腹泻、腹部疼痛和不适。此外,其预防儿童抗生素相关性腹泻和肠易激综合征(IBS)的能力已被研究。此外,其在促进活动性溃疡性结肠炎缓解和降解宿主肠道黏液层以维持微生物群落方面的有效性已被探索。此外,对其植物化学生物催化特性、黏附细胞的能力、在细胞系中抑制致癌作用的能力、调节免疫细胞的能力以及在小鼠模型中减轻过敏反应和治疗炎症性肠病的能力进行了大量研究(Azad et al., 2018)。

### 2.10 乳双歧杆菌

体外测试已广泛确立了乳双歧杆菌的菌株特征和过程,证明了其在食品和冷冻干燥粉末中的高度稳定性。临床证据表明,乳双歧杆菌HN019可促进肠道健康、消化和免疫功能(Sanders et al., 2019)。

### 2.11 嗜热双歧杆菌

嗜热双歧杆菌被认为是一种耐氧细菌,具有在缺氧环境中存活和繁殖的能力,使其成为益生菌应用的有前景候选者。嗜热双歧杆菌对多种病原体(包括李斯特菌属、沙门菌属、肉鸡中的空肠弯曲菌和轮状病毒感染)表现出细菌素样抗菌特性。这使其因其耐氧性和抗菌活性而成为纳入合生元和功能性食品的高度有前景候选者(Sanders et al., 2019)。

### 2.12 凝结芽孢杆菌

凝结芽孢杆菌是一种产孢益生菌细菌,以其对恶劣环境的卓越抗逆性和多种益生菌特性而闻名,使其能够在严苛条件下(如高胃酸度)保持非活性状态。该物质的固有耐久性使其能够承受恶劣条件,使其具有高度

### 2.13 嗜热链球菌

嗜热链球菌常用于多种乳制品(如奶酪和酸奶)的生产。它有助于牛奶中乳糖的水解,从而形成酸奶独特的风味和质地。此外,其通过产生天然聚合物提取物降低某些类型奶酪(如瑞士奶酪)脂肪含量的能力已得到认可。该益生菌菌株与多种健康益处相关,如增强免疫系统及减轻胃肠道和泌尿生殖系统的炎症。此外,其在对抗病毒、真菌和寄生虫感染方面已显示出潜力。婴儿中两歧双歧杆菌与嗜热链球菌的共存与轮状病毒腹泻发病率降低相关。已发现该组合可能减轻脓毒症引起的炎症损伤,从而凸显其作为膳食补充剂的潜力(Qu et al., 2023)。

### 2.14 粪肠球菌

没有证据表明粪肠球菌的益生菌菌株具有诱导抗生素耐药性的能力。为确保含有粪肠球菌的益生菌产品的安全消费,已制定严格的安全标准,仅使用被认为适合用于食品或食品补充剂的微生物菌株。它在消化过程中存活和在胃肠道中繁殖方面具有独特优势,通过与有害物种竞争营养和黏附位点来促进和谐的肠道环境。此外,粪肠球菌菌株表现出有前景的治疗特性,包括预防和治疗家畜腹泻以及抑制致病性李斯特菌属的增殖(Tilwani et al., 2022)。

### 2.15 酿酒酵母

酿酒酵母,特别是布拉氏酵母(S. boulardii)变种,因其益生菌能力而受到广泛认可,并已在人类和动物群体中对其对胃肠道健康的有益影响进行了广泛研究。它通常用作胃肠道疾病(包括炎症性肠病)的辅助治疗措施,并用于管理各种形式的腹泻。该实体的防御机制表现为结合和中和肠道病原体或其毒素、减少炎症以及刺激IgA分泌。这些菌株具有应用于功能性食品的潜力,并表现出保护DNA免受损伤的能力。酿酒酵母的可能益生菌特征包括自身聚集倾向、与病原体的共聚集、疏水性、在模拟胃肠道环境中存活的能力以及对Caco-2细胞的黏附能力。上述属性使其成为治疗应用的可行候选者(Fernandez-Pacheco et al., 2018)。

蔬菜是益生菌的底物,因为它们含有易于被益生菌吸收的营养物质。植物基质因其丰富的营养、膳食纤维、维生素、矿物质和生物活性植物化学成分,也可作为微生物种群的宿主和递送载体。在新型蔬菜益生菌产品中,常用的菌种包括嗜酸乳杆菌(Lactobacillus acidophilus)、干酪乳杆菌(Lactobacillus casei)、植物乳杆菌(Lactobacillus plantarum)、鼠李糖乳杆菌(Lactobacillus rhamnosus)和乳双歧杆菌(Bifidobacterium lactis)。蔬菜中含有能刺激免疫系统、预防胃肠道疾病并调节脂肪储存的益生菌微生物。它们还能调节肠道微生物的组成与代谢(Palanisamy et al., 2024)。蔬菜是益生菌的天然来源。发酵食品,尤其是生鲜和发酵蔬菜,含有嗜酸乳杆菌——一种肠道细菌。水果和蔬菜等新鲜农产品含有多种微生物,其中一些可能对人体有益。一个普通苹果含有约1亿个微生物,其中许多是无害或有益的。水果、蔬菜和谷物均可作为益生菌的载体。由于其营养成分,果蔬汁以及生鲜和发酵蔬菜已被用作益生菌的底物。植物乳杆菌是一种在蔬菜发酵过程中产生的乳酸菌,已被研究其益生特性。该菌株具有免疫调节作用,并能抑制致病菌生长,表明其可作为益生菌和食品添加剂使用(Gagnière et al., 2016)。白豌豆、青豌豆、鹰嘴豆和火龙果中均含有乳酸菌。蔬菜底物中存在包括乳杆菌属(Lactobacillus)、肠球菌属(Enterococcus)和双歧杆菌属(Bifidobacterium)在内的乳酸菌(LAB)(Jha et al., 2022)。通过乳酸发酵将这些益生菌添加至蔬菜底物中,可调节肠道菌群并改善健康状况。然而,利用蔬菜底物在食品基质中递送益生菌乳酸菌(LAB)仍具挑战性。微量营养素、抗氧化剂和膳食纤维使蔬菜底物成为生物工艺开发的理想选择(Sharma et al., 2021)。水果、蔬菜、豆类和谷物已被研究作为益生菌的载体,证明其对肠道健康有益。水果和蔬菜可在乳酸发酵过程中为益生菌微生物提供营养,其中包括芒果、苹果、香蕉、百香果、胡萝卜、橙子和大豆。益生菌可利用这些蔬菜中多样的营养成分和生物活性物质生长繁殖。泡菜和酸菜中也含有益生菌。泡菜中含有明串珠菌属(Leuconostoc)、魏斯氏菌属(Weissella)和乳杆菌属(Lactobacillus),而酸菜则含有肠膜明串珠菌(Leuconostoc mesenteroides)、植物乳杆菌(Lactobacillus plantarum)、戊糖片球菌(Pediococcus pentosaceus)等(Junnarkar et al., 2019)。这些微生物可能有助于消化。对肠道健康最有益的是摄入多种天然食物,尤其是新鲜农产品。水果和蔬菜所含的微生物种类远超益生菌补充剂。因此,食用多种新鲜果蔬有助于维护肠道微生物群健康及整体健康。发酵水果和蔬菜中含有乳杆菌属(Lactobacillus)、链球菌属(Streptococcus)、明串珠菌属(Leuconostoc)及其他乳酸菌。这些细菌在发酵食品中占主导地位,可能具有益生特性。乳酸菌与其他细菌、酵母和真菌共同发酵这些食品,产生活的微生物,使其成为益生菌的良好载体(Bernal-Castro et al., 2024)。泡菜和酸菜中也含有益生菌。泡菜含有嗜酸乳杆菌(Lactobacillus kimchii)及其他乳酸菌,可能有助于消化(Acevedo-Martínez et al., 2018)。酸菜中的肠膜明串珠菌、植物乳杆菌、戊糖片球菌等可促进肠道健康。水果富含维生素、矿物质、碳水化合物、膳食纤维和抗氧化剂,是良好的益生菌底物。水果表面的微结构可保护益生菌免受胃酸侵害,从而提高其存活率及健康效益。水果

3 益生菌底物 3.1 谷物作为益生菌底物 在亚洲和非洲,谷物的乳酸发酵是一种加工方法,用于生产饮料、粥和amaj等产品。发酵过程中,由于微生物活动及乳酸等有机酸的积累,酸度升高。而在西方国家,小麦和黑麦等谷物被用于生产酸面团。乳杆菌和双歧杆菌具有不同的营养需求,包括对碳水化合物、氨基酸、肽、脂肪酸酯、盐和酸衍生物的需求(Setta et al., 2020),以及核酸和维生素。谷物的主要碳水化合物成分包括淀粉、水溶性及不溶性膳食纤维,以及多种糖类,如葡萄糖、甘油、水苏糖、木糖、果糖、麦芽糖、蔗糖和阿拉伯糖。与牛奶相比,谷物含有更高的某些必需维生素、膳食纤维和矿物质,尤其是磷。一项关于人体来源微生物物种的研究表明,植物乳杆菌(Lactobacillus plantarum)、嗜酸乳杆菌(Lactobacillus acidophilus)、罗伊氏乳杆菌(Lactobacillus rotoi)和发酵乳杆菌(Lactobacillus fermentum)可在含麦芽、大麦和小麦等谷物的培养基中分离并培养(Behera et al., 2018)。

3.2 谷物来源的膳食纤维及其益生元作用 植物可食用纤维或碳水化合物是抵抗消化酶水解的膳食纤维,分为可溶性和不溶性两类。可溶性纤维包括非淀粉多糖,因其形成黏性环境,可延缓胃排空时间,减少小肠对葡萄糖和固醇的吸收。不溶性纤维包括木质素、纤维素和半纤维素。谷物中膳食纤维含量从外果皮向胚乳递减;但阿拉伯木聚糖是胚乳细胞壁的主要成分。常规碾磨方法已被开发用于膳食纤维的分离与纯化(Seyedain-Ardabili et al., 2016; Brasil et al., 2011)。

3.3 蔬菜和水果作为益生菌底物 在植物性底物中使用益生菌微生物已被证明具有多种健康益处。生鲜和发酵果汁,尤其是柑橘类果汁,是有前景的益生菌载体。果汁适合益生菌生长,因为乳酸菌可发酵弱酸性的植物和蔬菜底物。研究利用水果作为嗜酸乳杆菌和植物乳杆菌这两种常见于水果底物的益生菌的原料(Xia, 2020)。这些水果是非乳制品益生菌产品的理想底物,因其提供了益生菌生长所需的基本条件,并在4°C冷藏后降低pH值并增强活力。嗜酸乳杆菌和植物乳杆菌是水果和非乳制品益生菌饮料中常见的益生菌。这些乳酸菌菌株因耐酸性而在水果底物上存活。益生菌微生物已被用于苹果、香蕉、胡萝卜和番茄汁中,以制备非乳制品益生菌饮品。乳制品是益生菌的良好来源,有助于健康。然而,乳糖不耐受和乳制品中高胆固醇问题增加了对非乳制品益生菌的需求(Bernal-Castro et al., 2024)。

多种纳米载体可作为益生菌递送的便捷载体(Kumari et al., 2014)。封装可定义为持续包覆任何活性剂以保护其免受外部环境影响。多种材料已被用于药物封装,但益生菌是活细胞,因此封装材料的选择必须具有特异性,所用聚合物必须具有生物相容性和生物降解性。封装材料必须允许营养物质的双向运输,以确保益生菌细胞存活(Gurruchaga et al., 2015)。封装效果取决于所用基质,该基质可由天然或合成物质构成。海藻酸盐、卡拉胶、乳清蛋白、明胶、壳聚糖、醋酸纤维素酞酸酯和刺槐豆胶等材料被广泛应用于微胶囊化过程。在60–80°C温度范围内,海藻酸盐保持稳定,并能在酸性环境中维持细胞活力(Bollinger et al., 2024)。封装技术对保护益生菌并提高其活力至关重要(Puscaselu et al., 2020)。本文对常用技术进行了比较。喷雾干燥法是食品工业中高效且广泛应用的工艺,尤其用于改善果汁的生物强化。然而,喷雾干燥的高温可能损害益生菌。共封装技术指同时封装多种成分。与单独封装相比,因其更便捷且成本更低而受到青睐(Ansari et al., 2023)。此外,已证实共封装可提高长期保存效果,因此在制药行业广泛应用。挤出法是一种温和的益生菌封装方法,具有简单、经济且细胞损伤小的特点。大量益生菌可通过挤出和海藻酸盐技术实现封装。乳化法,又称两相系统法,是封装益生菌微生物的基本策略(Zhang et al., 2023)。具体方法可能有所不同,但通常涉及将益生菌物质在适合目标应用的载体材料中形成乳液。益生菌封装技术(PET)在临床前和临床试验中均显示出良好效果,促使益生菌被纳入多种产品中。然而,尽管有封装技术,确保细胞在长时间内持续存活仍具挑战性。欧洲药房和超市中的药品和营养保健品常含有益生菌成分(Cui et al., 2021)。然而,封装益生菌被用于多种营养补充剂中,以确保细菌能耐受生产过程、后续储存及消化系统运输。封装益生菌被用于多种食品和饮料中,包括酸奶、奶酪和发酵饮料等。封装可延长产品保质期,并保护益生菌免受严苛生产条件的影响。通过特定药物制剂使用封装益生菌,可用于治疗特定健康状况,如胃肠道疾病。封装使益生菌能到达身体特定部位(Palacios et al., 2023)。卡拉胶除作为

4 低聚糖化合物及其在益生元和益生菌中的应用 谷物通过酶促反应或发酵进行生物处理,可产生大量具有潜在特性的低聚糖,成为益生元。这些低聚糖可从植物材料中分离或通过酶法合成。乳糖、果寡糖和反式半乳寡糖等低聚糖可刺激益生菌生长。在食品工业中,这些化合物作为添加剂加入某些婴儿产品中,其特性类似于人乳低聚糖。抗性淀粉通常通过酸部分水解、热处理、挤压蒸煮、化学改化和再聚合生成。作为一种功能性纤维,抗性淀粉在消化生理中发挥重要作用,类似于低聚糖,难以被消化。该组合为肠道细菌提供可发酵碳水化合物。抗性淀粉的有益特性包括产生理想代谢物(如短链脂肪酸),并作为益生元降低胃肠道疾病风险。此外,这种淀粉在外观、质地和口感方面优于其他常规纤维(Hosseinvand et al., 2022)。

5 益生菌现场递送封装方法 任何益生菌的完整功效仅当活菌数达到或高于107 CFU/mL时才能实现(Serna-Cock and Vallejo-Castillo, 2013)。影响益生菌存活的其他因素包括H2O2产生、pH、温度、胆汁盐和酸的存在等。这些因素共同决定益生菌的效率和活力。目前,为益生菌提供屏蔽以抵御这些因素是一种有趣的方法。该方法可实现精准递送,不仅提高制剂中微生物的活力,还增强其稳定性(Alvarez et al., 2021)。随着纳米技术的进步,Frontiers in Microbiology

饲料添加剂也可用作封装的潜在材料。因其已获得FDA和联合国粮农组织/世界卫生组织(FAO/WHO)批准。其形成的凝胶可用于细胞封装,但该凝胶在室温下会变硬,从而增强益生菌的稳定性(Chakraborty, 2017)。乳清蛋白具有两性性质,使其能与卡拉胶和果胶混合。当pH降至等电点以下时,其净电荷变为正,从而可与带负电的多糖相互作用。因此,它们可有效用作固定化材料(Vonasek et al., 2014)。

甲壳素脱乙酰化得到带正电的多糖——壳聚糖。当pH高于5.4时,其在介质中不溶,这是其主要局限性之一,因为在肠道高pH环境下内容物无法完全释放,限制了益生菌的有效性。相反,醋酸纤维素酞酸酯(CAP)在pH低于5时不溶,但不像壳聚糖那样形成微球,可作为涂层材料进一步提高封装材料的稳定性(Rokka and Rantamäki, 2010)。

目前,微生物细胞的封装采用挤出或乳化技术。前者是一种简单且可自动化的高效技术,可截留大量细胞,产生凝胶化微滴。乳化技术则产生油相或水相微胶囊(Frakolaki et al., 2021)。

微胶囊化是一种保护性方法,可防止化合物因氧气、温度、水分、酶和酸等环境因素而劣化,并允许封装化合物在特定部位释放。多种生物聚合物被用作食品中活性成分的壁材(Altamirano-Fortoul et al., 2012)。

近年来,利用谷物成分的各种微胶囊化技术被用于提高益生菌菌株在额外有益产品中的活力。研究探讨了使用含高直链玉米淀粉颗粒作为益生菌细菌递送系统的可能性(Hosseinvand et al., 2022)。本综述中,从人体分离的双歧杆菌菌株被黏附于淀粉颗粒上。实验室研究表明,在此条件下益生菌的存活率提高。研究人员使用海藻酸钙对酸奶中的益生菌进行微胶囊化。玉米淀粉(益生元)与海藻酸的结合也改善了活细菌的包埋效果。喷雾干燥等方法被许多研究者关注,用于生产均匀包埋且含有活细菌的微生物微球(Krasaekoopt et al., 2004)。

益生菌和益生元在治疗肥胖、代谢综合征、呼吸道感染和COVID-19方面的潜力正在被研究。预计几年内益生菌和益生元的销售额和产量将达到约500亿美元(Bodke and Jogdand, 2022)。这一增长反映了消费者对胃肠道健康及其对整体健康影响的认识。随着对微生物组的深入理解,这些产品可能增强神经学和癌症预防效果。近期关于益生菌和益生元的研究揭示了其在神经生物学和癌症预防中的潜在作用。搜索结果未涉及益生菌和益生元在神经生物学中的应用,但肠-脑轴正受到越来越多的研究关注。本研究表明,肠道微生物群可能影响大脑功能和行为,潜在影响抑郁症、焦虑症和神经退行性疾病。益生菌和益生元可调节肠道微生物群,可能有益于神经健康。益生菌和益生元在癌症预防方面的研究前景广阔(The Lancet Global Health, 2020)。

许多疾病,包括癌症,与肠道微生物群失调有关。益生元和益生菌可能恢复平衡并增强免疫监视,潜在表现出抑癌特性。大量流行病学和实验研究增进了我们对益生菌和微生物疗法作为抗癌剂的理解(Cui et al., 2021)。某些人体研究表明益生菌和益生元具有益处。某些临床益生菌菌株可减少癌症患者术后炎症。口服益生菌可缓解化疗或放疗引起的腹泻。益生菌雾化疗法是一种创新疗法,用于预防高风险黑色素瘤患者的肺转移。肠道微生物群的改变影响癌症进展和抗癌疗法的疗效。益生菌和癌症预防的体内和分子研究已显示出令人鼓舞的结果(Ezeji et al., 2021)。

6 益生菌在促进人类健康中的作用 益生菌用于管理多种疾病和异常生理状态。有充分证据表明,多种益生菌株在治疗包括胃肠道问题、肿瘤、呼吸系统问题等多种健康问题方面具有潜力。微生物组科学的快速发展导致益生菌和益生元的多种应用。合生元(益生菌与益生元的组合)正被配制以提高其效力。益生菌目前正在

6.1 益生菌在癌症治疗中的作用 癌症无疑是全球主要死因之一。近755名癌症患者的死亡与饮食和生活方式相关因素有关,仅饮食相关因素就占死亡人数的50%。大量体外和动物研究表明,肠道和肠道微生物群在降低饮食相关因素导致的死亡风险中发挥作用。益生菌在降低结肠癌和膀胱癌风险中发挥重要作用。幽门螺杆菌、假单胞菌和不动杆菌是导致结肠肿瘤形成并最终引发结肠癌的元凶。它们在缺乏有益菌的情况下容易增殖。益生菌在调节肠道和肠道微生物组中发挥重要作用。嗜酸乳杆菌和干酪乳杆菌代田株是最常用的菌株(Dasari et al., 2017; Maleki et al., 2016)。益生菌通过多种方法抑制结直肠癌(CRC)的增殖和生长,包括正常化肠道菌群和增强胃肠道屏障。短链脂肪酸(SCFAs)是益生菌的关键代谢物,作为结肠黏膜的能量来源,增强肠道保护屏障,再生结肠上皮,调节肠腔pH值,抑制癌细胞增殖,并通过凋亡过程促进癌细胞死亡(Wong and Yu, 2019)。此外,

短链脂肪酸(SCFAs)通过G蛋白偶联受体(GPCRs)发挥信号分子功能,从而减少促炎细胞因子的产生并增加结肠中转基因细胞的数量。目前对益生菌在预防和治疗结直肠癌(CRC)中的作用机制仍缺乏充分理解(Cristofori et al., 2021)。由于益生菌种类繁多,各具独特特性和作用模式,其效果复杂多样。需要进一步临床研究以探讨益生菌对结直肠癌(CRC)的调控机制,理解各过程,进而将其作为预防和治疗CRC的辅助疗法(Torres-Maravilla et al., 2021)。在疾病发展前,可采用合适的益生菌相关疗法预防结直肠癌(CRC)(Ezeji et al., 2021)。这些干预措施包括直接口服益生菌、益生菌发酵产物,以及与益生菌或抗癌药物联合使用。益生菌可与手术、化疗和免疫疗法等强化癌症治疗联合使用,以降低手术和化疗过程中的并发症风险,提高化疗效果,并改善患者生活质量。传统益生菌目前正作为结直肠癌(CRC)治疗和护理的辅助疗法,主要用于减轻手术并发症和缓解化疗不良反应(Zhao et al., 2023)。

从许多女性阴道拭子中发现的乳酸菌在降低pH值方面非常有效。治疗尿路感染(UTI)有超过50种有效的益生菌,均基于乳杆菌属(Lactobacillus spp.),即短乳杆菌(Lactobacillus brevis)、罗伊氏乳杆菌(L. reuteri)、阴道乳杆菌(L. vaginalis)、鼠李糖乳杆菌(L. rhamnosus)(图2;Van et al., 2023)。

6.5 益生菌与肥胖 遗传变异、能量摄入与消耗失衡是当今日益严重的肥胖问题的主要原因。脂肪细胞组织中含有脂联素和瘦素,它们是导致肥胖的主要因素。加氏乳杆菌BNR17(Lactobacillus gasseri BNR17)可抑制其生长。益生菌刺激肾上腺素能神经系统,产生产热反应,从而促进体重减轻。某些益生菌如嗜酸乳杆菌、干酪乳杆菌和长双歧杆菌具有降胆固醇活性,可降低甘油三酯、低密度脂蛋白(LDL)和高密度脂蛋白(HDL)水平(George et al., 2018)。

6.6 益生菌与中枢神经系统和神经生物学 给自闭症儿童服用植物乳杆菌(Lactobacillus plantarum)显示出良好效果。某些乳杆菌菌株如瑞士乳杆菌(L. helveticus)、干酪乳杆菌(L. casei)、鼠李糖乳杆菌(L. rhamnosus)分别可减轻心理困扰、焦虑症状和自闭症相关症状。事实上,某些细菌合成的神经活性化合物与宿主相似(Park et al., 2018)。益生菌和益生元影响肠-脑轴,增强中枢神经系统功能,并缓解或调节抑郁症、焦虑症、自闭症、精神分裂症和阿尔茨海默病等精神障碍。本综述阐述了微生物群、胃与脑之间复杂关系,以及益生菌和益生元对精神障碍影响的最新研究发现。益生菌和益生元可能增强中枢神经系统功能并缓解某些神经系统疾病。大脑与胃肠道之间的关系已确立(Victoria Obayomi et al., 2024)。其相互作用归因于直接神经信号和间接激素与酶连接。一种利用益生元、益生菌和合生元调节中枢神经系统、副作用小的新型自然疗法已被提出。本综述发现益生元、益生菌和合生元对焦虑、抑郁、压力、睡眠和阿尔茨海默病具有积极影响(Centurion et al., 2022)。尽管研究表明益生元、益生菌和合生元对精神分裂症和自闭症谱系障碍等多种精神障碍有益,但证据不足以支持其应用于这些疾病。必须使用多种益生元、益生菌和合生元在明确界定且规模较大的人群中开展精心组织的临床试验,以获得更精确可靠的结果。近期研究足以开发用于精神障碍的益生元、益生菌和合生元制剂(Cryan et al., 2019)。这可能包括评估与传统治疗联合使用的药物方案,以及益生元、益生菌或合生元的使用(Ansari et al., 2023)。肠道微生物群的变化可影响情绪,表明微生物群-肠-脑(MGB)轴在抑郁症中发挥作用。多种过程与

肠道细菌在代谢性疾病和肥胖发展中的作用有关。在大鼠中,益生元和益生菌可改变肠道微生物群的组成和功能(Yuan et al., 2022)。益生菌和无菌啮齿动物模型已证明微生物、微生物代谢物与大脑中神经化学信号和炎症通路之间的因果关系。需要更多治疗相关研究;然而,益生菌补充剂已在抑郁症患者中显示出轻微的抗抑郁作用(Franzosa et al., 2018)。然而,临床前和临床结果需批判性评估MGB轴在抑郁症病理生理学中的作用,以及微生物群-肠界面与脑之间的潜在沟通途径。本文对抑郁症微生物组研究方法进行了全面评估。未来MGB轴研究必须纳入严格的安慰剂对照试验,并对益生元和益生菌机制进行全面分子和生化理解,以将临床前成功转化为新型药物(Radford-Smith and Anthony, 1880)。

支气管炎、鼻窦炎、咽炎、鼻窦炎、中耳炎是一些最常见的呼吸系统疾病。益生菌具有抗炎和抗菌特性,因此可用于预防多种呼吸系统疾病。例如:鼠李糖乳杆菌可用于控制囊性纤维化患者的肺炎发作。发酵乳杆菌、干酪乳杆菌和长双歧杆菌是治疗呼吸系统问题的常用益生菌(Soccol et al., 2014)。

6.9 益生菌与心血管疾病 血管紧张素转换酶(ACE)是高血压的关键酶。瑞士乳杆菌和酿酒酵母可合成抑制ACE活性的肽(Mayta-Tovalino et al., 2023)。

6.7 益生菌与血管生成 血管生成是从旧血管再生新血管的过程,有助于伤口愈合。若过程异常,可能导致癌症和糖尿病视网膜病变。布拉氏酵母菌(S. boulardii)通过降低内脏敏感性和调节炎症细胞因子谱,保护宿主免受炎症和损伤(Xu et al., 2024)。

Frontiers in Microbiology

益生菌可用于治疗溃疡性结肠炎和克罗恩病。它们导致胃肠道炎症,需氧和厌氧菌均参与其中。这两种疾病合称为炎症性肠病。乳杆菌属(Lactobacillus)、肠杆菌属(Enterobacter)和双歧杆菌属(Bifidobacillus)用于治疗炎症(Roy et al., 2023)。

通过多种方法实现递送,副作用小。许多益生菌已被批准大量销售以缓解疾病症状。益生菌用于治疗感染性腹泻、抗生素诱发腹泻、乳糖不耐受和过敏等肠道疾病已有记录。益生菌的应用不仅限于胃肠道疾病,已扩展至肥胖、呼吸系统、心血管和中枢神经系统疾病等其他疾病的治疗。将益生菌递送至作用部位是另一项挑战,但有多种技术可克服此限制,例如将益生菌细胞封装在耐酸、耐胆盐、耐温的合适载体介质中,以最大化益生菌效果。另一种提高益生菌效果的方法是与抗生素联合使用,以减少副作用并增强微生物清除效果,同时避免抗生素耐药性产生。

7 其他最新方法 抗菌药物非常有效,但也存在局限性,即成本高、潜在副作用以及长期使用导致抗菌药物耐药性产生(Vitor and Vale, 2011)。为克服此限制,抗菌药物正与益生菌联合使用,不仅改善愈合,还减少所需剂量,最终提高感染部位微生物清除率,并减少全剂量相关的潜在副作用(Kosgey et al., 2019)。治疗幽门螺杆菌引起的胃溃疡通常使用抗菌药物,但它们不仅有潜在副作用,还导致病原体产生抗生素耐药性。单用抗菌药物的根除率约为71%,而与益生菌联合使用时,该比率上升至81%。副作用也显著减少。

2018年,Russo等人研究了口服益生菌制剂与局部克霉唑联合治疗外阴阴道念珠菌病的协同作用。嗜酸乳杆菌和鼠李糖乳杆菌与乳铁蛋白糖蛋白联合使用。益生菌与克霉唑联合有效减轻症状,并影响感染复发(Shenoy and Gottlieb, 2019)。益生菌与抗真菌药膏联合对念珠菌属(Candida spp.)高度有效,不仅减轻症状,还有助于恢复正常阴道微生物群(Mastubara et al., 2016)。

慢性牙周炎由支持牙齿的组织炎症引起,导致牙周韧带丧失。这是一种多因素疾病,通常使用抗生素减少细菌负荷。益生菌可作为常规抗生素的辅助治疗。特别是罗伊氏乳杆菌(L. reuteri),因其产生reuterin,减少氧化应激,与病原菌株竞争黏附位点,并通过控制TNF-α和IL-17等促炎细胞因子的产生来减少MMP-8的表达(Soler and Kutsner, 2020)。

作者贡献 BS:监督、撰写初稿、审阅与编辑。DS:监督、撰写初稿、审阅与编辑。MH:监督、撰写初稿、审阅与编辑。EK:调查、撰写初稿、审阅与编辑。