Probiotics function mechanistically as delivery vehicles for neuroactive compounds: Microbial endocrinology in the design and use of probiotics

I hypothesize here that the ability of probiotics to synthesize neuroactive compounds provides a unifying microbial endocrinology-based mechanism to explain the hitherto incompletely understood action of commensal microbiota that affect the host's gastrointestinal and psychological health. Once ingested, probiotics enter an interactive environment encompassing microbiological, immunological, and neurophysiological components. By utilizing a trans-disciplinary framework known as microbial endocrinology, mechanisms that would otherwise not be considered become apparent since any candidate would need to be shared among all three components. The range of neurochemicals produced by probiotics includes neurochemicals for which receptor-based targets on immune and neuronal elements (intestinal and extra-intestinal) have been well characterized. Production of neurochemicals by probiotics therefore allows for their consideration as delivery vehicles for neuroactive compounds. This unifying microbial endocrinology-based hypothesis, which may facilitate the selection and design of probiotics for clinical use, also highlights the largely unrecognized role of neuroscience in understanding how microbes may influence health.     

益生菌调控幼龄畜禽消化道微生物研究进展

益生菌是一类对宿主(人类或动物)有益的活性微生物,包括细菌、真菌(如酵母)等,具有促进动物生长、提高免疫力的作用,是潜在的抗生素替代品。益生菌可能通过与动物消化道微生物互作来发挥益生作用,但具体机制仍不明确。综述了基于高通量测序技术研究益生菌调控幼龄畜禽(仔猪、雏鸡、反刍动物)消化道微生物群落组成的最新进展,并提出了未来研究方向,包括益生菌如何通过与消化道微生物互作影响其功能,益生菌对于幼龄畜禽不同健康状态下肠道微生物的影响,以及宿主因素如何影响益生菌对于幼龄畜禽消化道微生物的作用效果。     

Methods to Assess the Antioxidative Properties of Probiotics

Probiotics prove useful in correcting and preventing numerous health conditions, including those having severe impact on society, e.g., obesity and cancer. Notably, these capabilities of probiotics appear to be associated with their antioxidant properties. The mechanisms of antioxidant action of probiotics range from immediate biochemical scavenging of reactive substances to induction of signaling events leading to increased capacity of the host’s cytoprotective systems. Since the antioxidant effects of probiotics significantly vary in types and details, a broad selection of methods of assessment of these properties is required in order to identify, characterize, and develop novel probiotics for medical purposes, as well as to explain the mechanisms of action of probiotics already in use in healthcare. This review revises the versatile toolbox, which can be used to assess the antioxidant properties of probiotics.     

Probiotics: Potent Immunomodulatory Tool Against Allergy

Probiotics are defined as live microbial food ingredients that produce several beneficial effects to human health. Probiotic bacteria have been mostly investigated in the prevention of and treatment for different gastrointestinal diseases and allergies. It is not fully clear how probiotics exert their beneficial effects on health, but one of the most probable mechanisms of action is the modulation of immune responses via the mucosal immune system of the gut. Commensal bacteria in the gastrointestinal tract play an integral role in both innate and humoral immunity. It is well established that this protective role can be maintained or modulated by the ingestion of probiotics. More recently, it has been shown that specific probiotic strains can influence the secretion of cytokines to help direct naïve T-helper cells toward either a Th1-dominant, cell-mediated immune response or toward a Th2-dominant, humoral immune response. This paper will review current knowledge of the Th1/Th2 model of humoral immunity as well as introduce how strain-specific probiotics can be used therapeutically to help balance this immune response and therefore help prevent allergy.     

Using a Mathematical Model to Analyze the Role of Probiotics and Inflammation in Necrotizing Enterocolitis

Background

Necrotizing enterocolitis (NEC) is a severe disease of the gastrointestinal tract of pre-term babies and is thought to be related to the physiological immaturity of the intestine and altered levels of normal flora in the gut. Understanding the factors that contribute to the pathology of NEC may lead to the development of treatment strategies aimed at re-establishing the integrity of the epithelial wall and preventing the propagation of inflammation in NEC. Several studies have shown a reduced incidence and severity of NEC in neonates treated with probiotics (beneficial bacteria species).

Methodology/Principal Findings

The objective of this study is to use a mathematical model to predict the conditions under which probiotics may be successful in promoting the health of infants suffering from NEC. An ordinary differential equation model is developed that tracks the populations of pathogenic and probiotic bacteria in the intestinal lumen and in the blood/tissue region. The permeability of the intestinal epithelial layer is treated as a variable, and the role of the inflammatory response is included. The model predicts that in the presence of probiotics health is restored in many cases that would have been otherwise pathogenic. The timing of probiotic administration is also shown to determine whether or not health is restored. Finally, the model predicts that probiotics may be harmful to the NEC patient under very specific conditions, perhaps explaining the detrimental effects of probiotics observed in some clinical studies.

Conclusions/Significance

The reduced, experimentally motivated mathematical model that we have developed suggests how a certain general set of characteristics of probiotics can lead to beneficial or detrimental outcomes for infants suffering from NEC, depending on the influences of probiotics on defined features of the inflammatory response.     

Rhizosphere pseudomonads as probiotics improving plant health

Many root‐colonizing microbes are multifaceted in traits that improve plant health. Although isolates designated as biological control agents directly reduce pathogen growth, many exert additional beneficial features that parallel changes induced in animal and other hosts by health‐promoting microbes termed probiotics. Both animal and plant probiotics cause direct antagonism of pathogens and induce systemic immunity in the host to pathogens and other stresses. They also alter host development and improve host nutrition. The probiotic root‐colonizing pseudomonads are generalists in terms of plant hosts, soil habitats and the array of stress responses that are ameliorated in the plant. This article illustrates how the probiotic pseudomonads, nurtured by the carbon (C) and nitrogen (N) sources released by the plant in root exudates, form protective biofilms on the root surface and produce the metabolites or enzymes to boost plant health. The findings reveal the multifunctional nature of many of the microbial metabolites in the plant–probiotic interplay. The beneficial effects of probiotics on plant function can contribute to sustainable yield and quality in agricultural production.     

Evidence-based review of probiotics for antibiotic-associated diarrhea and Clostridium difficile infections

Probiotics are living microbes taken to confer a health benefit on the host. Although probiotics have a long history of use in Europe and Asia and have been on the U.S. market for over 14 years, there is still confusion about how to effectively use them. The use of probiotics for the prevention of antibiotic-associated diarrhea (AAD) and the treatment of Clostridium difficile infections (CDI) has been tested in randomized controlled clinical trials.This paper will review the evidence supporting probiotic therapy for these two diseases and also review the advantages and disadvantages of probiotics. The advantages of probiotic therapy include multiple mechanisms of action against pathogens, the ability to interact with the host's natural defense systems, survival to the target organ and a good risk to benefit ratio. Disadvantages of probiotics include lack of standardization for clinical trial designs, variations in regulatory standards, poor quality control for some products and infrequent serious adverse reactions. Overall, probiotics offer a promising strategy for the prevention and treatment for AAD and CDI     

益生菌的安全性

益生菌是一类重要的微生物调节剂,对人类的营养和健康具有重大的意义。目前,益生菌具有医疗和保健作用毋庸质疑,但是对于益生菌的安全性还存在争议。本文对益生菌的安全性和不安全性研究进行综述,以利于临床正确认识、了解和使用益生菌制剂,对进一步开发利用益生菌也有积极意义。 更多还原     

功能性益生乳酸菌的研究进展

益生菌的效果已被认识和探究了超过一个世纪,有关益生菌的功效以及它们与宿主之间的相互关系已逐渐为世人所知,越来越多的益生机制得到了验证。虽然现在有足够的临床证据支持益生菌的某些健康宣称,然而,我们还需要进行大量的工作来证实其功能性作用,如提供必需营养因子,保护肠道和心血管健康,甚至预防神经系统退行性衰老。本文综述了几种典型的益生菌功能特性,为更好的将益生菌应用于人体提供理论参考。     

The oral biome in the aetiology and management of dental disease: Current concepts and ethical considerations

Our understanding of the complexity of the oral biome and of the role of the various constituent bacteria in the aetiology of dental disease is growing. Probiotics and their relationship with prebiotics, as well as other microbiome‐based interventions, could be useful in preventing and treating dental disease and in promoting oral health. However, given the promise and early stage of this treatment approach, there are also a number of ethical, social and regulatory issues associated with innovative probiotic therapy. In this article, a brief update is given on contemporary theories of the aetiology and management of the two commonest dental diseases, and on the roles of pre‐ and probiotics and oral biome transplant in the management of these diseases. The focus is primarily on four core issues: informed consent, risk–benefit assessment, how to determine suitable healthy donors, and commercialization and regulation. We discuss the safety and benefits of oral probiotics, not only concerning the products and quality control during their manufacture, but also regarding the depth of public knowledge about this topic. We point out that the requirement of listing ingredients honestly might be insufficient, and that the prevalent rhetoric of ‘natural’ and ‘organic’ as well as some health claims in the translational, innovative probiotic industry and markets are themselves misleading and should be carefully scrutinized. Finally, we suggest an ethical imperative to find a balance between scientific research and industry, and public health in the regulation of probiotics.     

The mucus binding of Bifidobacterium lactis Bb12 is enhanced in the presence of Lactobacillus GG and Lact. delbrueckii subsp. bulgaricus

The ability to adhere to mucosal surfaces is related to many probiotic health effects. In the presence of Lactobacillus GG or Lact. bulgaricus, the adhesion of Bifidobacterium lactis Bb12 to a mucus model was more than doubled. Other tested lactobacilli did not affect the adhesion, nor was the adhesion of the lactobacilli influenced by the bifidobacteria. Co-aggregation between Bif. lactis Bb12 and the tested lactobacilli was insignificant and does not explain the observed effect. The results suggest that combinations of probiotics strains may have synergistic adhesion effects. Such specific strain combinations should also be assessed in clinical studies.     

Probiotics: time for a dose of realism

There is already a long research and retail history of probiotics, but progress in the scientific and medical validation of these products has been extremely slow. Even now, adequate information by which the consumer and health professional can judge the efficacy and safety of retailed probiotics is lacking. Probiotic products have not been subjected to large scale trials of efficacy that are used in the pharmaceutical industry. Without these trials and subsequent approval by fastidious regulatory agencies such as the FDA (USA), probiotics continue to languish in the self-care health market. Optimistically, a new generation of probiotics may be developed that have medical validity with respect to the prevention or treatment of atopic and inflammatory bowel diseases. These new products, however, will need to be targeted at the alleviation of specific medical conditions, and the mechanistic basis of their effectiveness will need to be provided.     

Comparative genomics of in vitro and in vivo evolution of probiotics reveals energy restriction not the main evolution driving force in short term

Probiotics have attracted much attention because of their health-promoting effects, but little is known about the in vivo evolution of probiotics. This study analyzed the genome adaptation of the probiotic Lactiplantibacillus plantarum P-8 strain cultivated in ordinary and glucose restrictive growth media. Then, this study re-analyzed genomes of P-8 isolates recovered from the gut contents of subjects in two feeding trials (in rat and human). The sampling time points were similar to that of the in vitro evolution experiment, which might give parallel comparison of the in vitro and in vivo evolution processes. Our results showed that intra-individual specific microbial genomic variants of the original strain were detected in all human and some rat subjects. The divergent patterns of evolution within the host gastrointestinal tract suggested intra-individual-specific environmental adaptation. Based on comprehensive analysis of adapted-isolates recovered from these experiments, our results showed that the energy restriction was not the main driving force for evolution of probiotics. The individual-specific adaptation of probiotics might partially explain the varying extent of health effects seen between different individuals after probiotic consumption. In addition, the results suggest that probiotics should not only adapt to the environment of the birth canal, but also adapt to other species in the gut, revealing the Red Queen hypothesis in the process of intestinal flora.     

Towards understanding molecular modes of probiotic action

The possibility that certain microorganisms might be beneficial to human health is highlighted by the numerous consumer products containing probiotic bacteria. Probiotics are typically administered in food that, following entry into the gastro-intestinal tract, results in measurable health-promoting effects. Although there is a growing list of health benefits provided by the consumption of probiotics, their precise mechanisms of action remain largely unknown. Recent molecular- and genomics-based studies are starting to provide insight into the ways probiotic bacteria sense and adapt to the gastro-intestinal tract environment. Complementary approaches using host cell in vitro systems together with animal models and human volunteers are revealing specific intestinal cell responses to probiotics. These studies should ultimately disclose the molecular mechanisms and pinpoint the bacterial and host effector molecules and pathways by which probiotics are able to modulate human health.     

益生菌的应用现状和发展前景

益生菌是一类严格选择的，如果给予足够的量，能够为宿主带来健康益处的活性微生物。常见的具有益生功能的微生物，包括传统益生菌乳酸菌(lactic acid bacteria)和酵母菌(Saccharomyces)等，以及下一代益生菌普拉梭菌(Faecalibacterium prausnitzii)、脆弱拟杆菌(Bacteroides fragilis)、嗜黏蛋白阿克曼菌(Akkermansia muciniphila)和普雷沃氏菌(Prevotella copri)等。益生菌与人体健康之间存在密切的关系，这些微生物可通过肠道刺激胃肠道反应或直接作用于口腔、阴道、皮肤等其他部位以调节宿主健康。因此，它们在食品、种植业、畜牧业以及医疗领域中得到广泛应用，成为改善宿主健康的有力工具。本文对乳酸菌等传统益生菌以及嗜黏蛋白阿克曼菌等下一代益生菌的功能的开发与应用进行了综述，总结了这几种益生菌在食品生产、疾病治疗以及农业生产等方面的应用潜力，展望了益生菌资源研究与应用的发展趋势，以期为研究新老益生菌功能的开发与应用提供参考。     

Combined analysis of chromosomal instabilities and gene expression for colon cancer progression inference

Background

The human body plays host to a vast array of bacteria, found in oral cavities, skin, gastrointestinal tract and the vagina. Some bacteria are harmful while others are beneficial to the host. Despite the availability of many methods to identify bacteria, most of them are only applicable to specific and cultivable bacteria and are also tedious. Based on high throughput sequencing technology, this work derives 16S rRNA sequences of bacteria and analyzes probiotics and pathogens species.

Results

We constructed a database that recorded the species of probiotics and pathogens from literature, along with a modified Smith-Waterman algorithm for assigning the taxonomy of the sequenced 16S rRNA sequences. We also constructed a bacteria disease risk model for seven diseases based on 98 samples. Applicability of the proposed platform is demonstrated by collecting the microbiome in human gut of 13 samples.

Conclusions

The proposed platform provides a relatively easy means of identifying a certain amount of bacteria and their species (including uncultivable pathogens) for clinical microbiology applications. That is, detecting how probiotics and pathogens inhabit humans and how affect their health can significantly contribute to develop a diagnosis and treatment method.     

Probiotics in human health and disease: from nutribiotics to pharmabiotics

Probiotics are the most useful tools for balancing the gut microbiota and thereby influencing human health and disease. Probiotics have a range of effects, from those on nutritional status to medical conditions throughout the body from the gut to non-intestinal body sites such as the brain and skin. Research interest in probiotics with nutritive claims (categorized as nutribiotics) has evolved into interest in therapeutic and pharmacological probiotics with health claims (pharmabiotics). The concept of pharmabiotics emerged only two decades ago, and the new categorization of probiotics to nutribiotics and pharmabiotics was recently suggested, which are under the different regulation depending on that they are food or drug. Information of the gut microbiome has been continuously accumulating, which will make possible the gut microbiome-based healthcare in the future, when nutribiotics show potential for maintaining health while pharmabiotics are effective therapeutic tools for human diseases. This review describes the current understanding in the conceptualization and classification of probiotics. Here, we reviewed probiotics as nutribiotics with nutritional functions and pharmabiotics with pharmaceutic functions in different diseases.     

益生菌与肠道健康

肠道菌群与人体肠道健康密切相关.益生菌在防治感染、调节机体菌群平衡,提高机体免疫力和儿童生长发育等发挥关键作用.本文主要介绍了益生菌与肠道健康的主要作用机制及益生菌在消化道疾病的应用.     

益生菌冷冻干燥高活性保护机制研究进展

摄取足量益生菌有助于维持肠道微生物群落的稳态,对维持人体肠道健康具有重要意义。然而,在工业化应用中,益生菌抗逆能力较弱且对储存条件要求高,导致益生菌产品对运输和活性维持条件要求较高,这些产业需求对高活力益生菌的制备工艺提出了挑战。干燥处理常应用于保持益生菌活性和稳定性,其中冷冻干燥技术应用最广泛,但冻干过程中益生菌会受到各类环境压力的刺激,引起细胞损伤甚至死亡。因此,可以显著提高益生菌存活率的冻干保护剂成为目前益生菌工业应用的研究热点。本文从益生菌常用及新发现的冻干保护剂种类及其作用机制进行了系统归纳,对菌株冻干后细胞存活率的影响因素进行全面综述,并对冻干保护剂研究方向进行了展望,旨在为高活力益生菌冻干菌粉的研制提供理论支持。     

分子水平上益生菌研究进展

益生菌是指能在生物体内存活 ,对生物体的健康有益的一类微生物。目前已经对益生菌的作用机理进行了深入和广泛的研究 ,获得了许多使用益生菌的经验。近些年来 ,分子生物学特别是基因工程技术的发展将益生菌的理论和应用研究推向了一个新的高度。从益生菌菌株的鉴定、菌株的遗传学修饰、益生菌功能基因组学和安全性等几个方面 ,综述了近年来国际上在分子水平上研究益生菌的技术方法、获得的主要研究成果和面临的挑战 ,并提出了益生菌研究的发展方向。