The role of the gut microbiota in the pathology and prevention of liver disease

Several microorganisms belonging to the intestinal microbiota act in an ecosystem responsible for maintaining the homeostasis and vital functions of human beings. From birth to old age the diversity of the intestinal microbiota may change due to environmental factors such as nutrition, immunity, diseases or the use of antibiotics leading to dysbiosis. Improvement in microbiota diversity can be achieved by modifying related risk factors through changes in lifestyle and a healthy diet. Besides, the addition of probiotics, prebiotics or the combination of both (symbiotics), can result in the improvement of the intestinal permeability, inflammatory pathways and the immune system. Also, the use of probiotics prevents harmful bacteria and their derived products (e.g., bacteriocins, endotoxins, hydrogen sulfide, etc.) to leak through the intestinal wall to the circulation that results in the activation of signaling pathways that may be implicated in liver disease. The liver receives a constant flow of noxious entities that promote inflammation and oxidative stress. The use of probiotics with clinical evidence in liver disease, represent a novel therapeutic alternative, inducing positive changes in the balance of the intestinal microbiota which lead to improvement in liver function tests (AST and ALT), decreasing tumor necrosis factor-α (TNF-α), andblood cholesterol, among other risk factors. In this review, we discuss the main elements that play a leading role in the development of steatosis as well as the benefits of using probiotics and the impact in the quality of life of patients that develop cirrhosis.     

Use of a vaginal probiotic suppository and antibiotics to influence the composition of the endometrial microbiota

The aim of the present study was to determine the status of the endometrial microbiota in patients with repeated implantation failure (RIF) and to assess treatment strategies for nondominant Lactobacillus (NLD) cases. A total of 392 patients with RIF were enrolled in this prospective cohort study (UMIN-CTR 000038582) and underwent endometrial microbiota analysis. Patients diagnosed with NLD were treated with a combination of oral and vaginal probiotics or oral prebiotics and antibiotics. The outcome was evaluated through re-analysis of the endometrial microbiota following treatment, and the results are presented as cure rates. NLD represented 44.9 % of the total endometrial microbiota in patients with RIF. The most commonly detected bacterium was Gardnerella vaginalis. The cure rates in the oral probiotics + oral prebiotics, antibiotics, oral probiotics + oral prebiotics + antibiotics, vaginal probiotic suppository, and vaginal probiotic suppository + antibiotics groups were 29.5, 33.33, 33.33, 43.6, and 78.6 %, respectively. Significant improvements were noted in the vaginal probiotic suppository + antibiotics group. Moreover, we revealed that approximately half of patients with RIF had NLD. Thus, the combination of a vaginal probiotic suppository and antibiotics may represent an effective treatment for NLD cases.     

肠道菌群及其代谢产物对心肌纤维化影响与治疗的研究进展

心肌纤维化是多种心血管疾病,如冠心病、心肌梗死和心力衰竭等的终末期表现和主要致病因素。研究发现,免疫和炎症过程在心肌纤维化的发病机制中起决定性作用。近年来,人们发现肠道微生物在心肌纤维化的发病机制和发展中起着至关重要的作用。肠道菌群的失调可导致微生物的代谢产物转移到血液循环中,如短链脂肪酸、脂多糖和氧化三甲胺等。这些代谢物直接或间接地诱导组织损伤免疫和激活全身炎症反应,进而影响心肌纤维化。如何改变肠道菌群来改善心肌纤维化已成为当前的研究重点,包括饮食干预、使用抗生素、补充益生菌和益生元,以及粪便微生物群移植等。本综述旨在回顾肠道菌群及其代谢产物与心肌纤维化的相互作用,介绍通过干预肠道菌群改善心肌纤维化的研究进展,为心肌纤维化的治疗提供新思路。     

益生菌以及益生元在肥胖及其代谢综合征中的潜在作用

肥胖以及相关的代谢综合征已经成为全球性的公共健康问题。大量的研究表明,肥胖形成以及减肥过程均与肠道菌群密切相关且相互影响。肠道菌群以及弱炎症反应成为肥胖以及相关代谢综合征的两大重要影响因素。本文综述了近几年来,肠道菌群失调对宿主能量储存以及新陈代谢的影响,以及弱炎症反应对肥胖引起的代谢综合征的影响。大量的研究证明,益生元有助于益生菌的生长,而益生菌可以调节肠道菌群以及改善肠道内弱炎症反应,借助于益生菌以及益生元的方法也许能为由肠道菌群失调以及弱炎症反应引起的肥胖及其代谢综合征提供一种新的治疗方法。     

The development of gut immune responses and gut microbiota: effects of probiotics in prevention and treatment of allergic disease

The infant's immature intestinal immune system develops as it comes into contact with dietary and microbial antigens in the gut. The evolving indigenous intestinal microbiota have a significant impact on the developing immune system and there is accumulating evidence indicating that an intimate interaction between gut microbiota and host defence mechanisms is mandatory for the development and maintenance of a balance between tolerance to innocuous antigens and capability of mounting an inflammatory response towards potential pathogens. Disturbances in the mucosal immune system are reflected in the composition of the gut microbiota and vice versa. Distinctive alterations in the composition of the gut microbiota appear to precede the manifestation of atopic disease, which suggests a role for the interaction between the intestinal immune system and specific strains of the microbiota in the pathogenesis of allergic disorders. The administration of probiotics, strains of bacteria from the healthy human gut microbiota, have been shown to stimulate antiinflammatory, tolerogenic immune responses, the lack of which has been implied in the development of atopic disorders. Thus probiotics may prove beneficial in the prevention and alleviation of allergic disease.     

Top‐down systems biology integration of conditional prebiotic modulated transgenomic interactions in a humanized microbiome mouse model

Gut microbiome–host metabolic interactions affect human health and can be modified by probiotic and prebiotic supplementation. Here, we have assessed the effects of consumption of a combination of probiotics (Lactobacillus paracasei or L. rhamnosus) and two galactosyl‐oligosaccharide prebiotics on the symbiotic microbiome–mammalian supersystem using integrative metabolic profiling and modeling of multiple compartments in germ‐free mice inoculated with a model of human baby microbiota. We have shown specific impacts of two prebiotics on the microbial populations of HBM mice when co‐administered with two probiotics. We observed an increase in the populations of Bifidobacterium longum and B. breve, and a reduction in Clostridium perfringens, which were more marked when combining prebiotics with L. rhamnosus. In turn, these microbial effects were associated with modulation of a range of host metabolic pathways observed via changes in lipid profiles, gluconeogenesis, and amino‐acid and methylamine metabolism associated to fermentation of carbohydrates by different bacterial strains. These results provide evidence for the potential use of prebiotics for beneficially modifying the gut microbial balance as well as host energy and lipid homeostasis.     

In vitro effects of selected synbiotics on the human faecal microbiota composition

Synbiotics are recognized means of modulating gut microbiota composition and activities. However, whether synbiotics are superior to prebiotics and probiotics alone in moderating the gut microbiota towards a purportedly healthy composition has not been determined. Eight selected synbiotics (short-chain fructooligosaccharides or fructooligosaccharides, each combined with one of four probiotics, Lactobacillus fermentum ME-3, Lactobacillus plantarum WCFS1, Lactobacillus paracasei 8700:2 or Bifidobacterium longum 46) were added to 24-h pH-controlled anaerobic faecal batch cultures. The prebiotic and probiotic components were also tested alone to determine their respective role within the synbiotic for modulation of the faecal microbiota. Effects upon major groups of the microbiota were evaluated using FISH. Rifampicin variant probiotic strains were used to assess probiotic levels. Synbiotic and prebiotics increased bifidobacteria and the Eubacterium rectale-Clostridium coccoides group. Lower levels of Escherichia coli were retrieved with these combinations after 5 and 10 h of fermentation. Probiotics alone had little effect upon the groups, however. Multivariate analysis revealed that the effect of synbiotics differed from the prebiotics as higher levels of Lactobacillus-Enterococcus were observed when the probiotic was stimulated by the prebiotic component. Here, the synbiotic approach was more effective than prebiotic or probiotic alone to modulate the gut microbiota.     

Gastrointestinal microflora,food components and colon cancer prevention

Evidence that the intestinal microbiota is intrinsically linked with overall health, including cancer risk, is emerging. Moreover, its composition is not fixed but can be influenced by several dietary components. Dietary modifiers, including the consumption of live bacteria (probiotics) and indigestible or limited digestible food constituents such as oligosaccharides (prebiotics) and polyphenols or both (synbiotics), are recognized modifiers of the numbers and types of microbes and have been reported to reduce colon cancer risk experimentally. Microorganisms also have the ability to generate bioactive compounds from food components. Examples include equol from isoflavones, enterodiol and enterolactone from lignans and urolithins from ellagic acid, which have also been demonstrated to retard experimentally induced cancers. The gastrointestinal microbiota can also influence both sides of the energy balance equation, namely, as a factor influencing energy utilization from the diet and as a factor that influences host genes that regulate energy expenditure and storage. Because of the link between obesity and cancer incidence and mortality, this complex complexion deserves greater attention. Overall, a dynamic interrelationship exists between the intestinal microbiota and colon cancer risk, which can be modified by dietary components and eating behaviors.     

Beneficial modulation of the gut microbiota

The human gut microbiota comprises approximately 100 trillion microbial cells and has a significant effect on many aspects of human physiology including metabolism, nutrient absorption and immune function. Disruption of this population has been implicated in many conditions and diseases, including examples such as obesity, inflammatory bowel disease and colorectal cancer that are highlighted in this review. A logical extension of these observations suggests that the manipulation of the gut microbiota can be employed to prevent or treat these conditions. Thus, here we highlight a variety of options, including the use of changes in diet (including the use of prebiotics), antimicrobial-based intervention, probiotics and faecal microbiota transplantation, and discuss their relative merits with respect to modulating the intestinal community in a beneficial way.     

Updating the importance of lactic acid bacteria in fish farming: natural occurrence and probiotic treatments

Many recent papers have deepened the state of knowledge about lactic acid bacteria (LAB) in fish gut. In spite of high variability in fish microbiota, LAB are sometimes abundant in the intestine, notably in freshwater fish. Several strains of Streptococcus are pathogenic to fish. Streptococcus iniae and Lactococcus garvieae are major fish pathogens, against which commercial vaccines are available. Fortunately, most LAB are harmless, and some strains have been reported for beneficial effects on fish health. A major step forward in recent years was the converging evidence that LAB can stimulate the immune system in fish. An open question is whether viability can affect immunostimulation. The issue is crucial to commercialize live probiotics rather than inactivated preparations or extracts. There has been a regain of interest in allochthonous strains used as probiotics for terrestrial animals or humans, due to economical and regulatory constraints, but the short survival in sea water may limit application to marine fish. If viability is required, alternative treatments may include the incorporation of prebiotics in feed, and other dietary manipulations that could promote intestinal LAB. Antagonism to pathogens is the other main feature of candidate probiotics, and there are many reports concerning mainly carnobacteria and Enterococcus. Some bacteriocins were characterized which may be of interest not only for aquaculture, but also for food preservation.     

Review: The development of the gastrointestinal tract microbiota and intervention in neonatal ruminants

The complex microbiome colonizing the gastrointestinal tract (GIT) of ruminants plays an important role in the development of the immune system, nutrient absorption and metabolism. Hence, understanding GIT microbiota colonization in neonatal ruminants has positive impacts on host health and productivity. Microbes rapidly colonize the GIT after birth and gradually develop into a complex microbial community, which allows the possibility of GIT microbiome manipulation to enhance newborn health and growth and perhaps induce lasting effects in adult ruminants. This paper reviews recent advances in understanding how host-microbiome interactions affect the GIT development and health of neonatal ruminants. Following initial GIT microbiome colonization, continuous exposure to host-specific microorganisms is necessary for GIT development and immune system maturation. Furthermore, the early GIT microbial community structure is significantly affected by early life events, such as maternal microbiota exposure, dietary changes, age and the addition of prebiotics, probiotics and synbiotics, supporting the idea of microbial programming in early life. However, the time window in which interventions can optimally improve production and reduce gastrointestinal disease as well as the role of key host-specific microbiota constituents and host immune regulation requires further study.     

Immunomodulation by food: impact on gut immunity and immune cell function

Abstract

Recent studies have revealed that various food components affect the immune response. These components act on various immune cells, and their effects are mediated through the intestinal immune system and, in some cases, the intestinal microbiota. In this review, we describe the immunomodulating effects of various food components, including probiotics, prebiotics, polysaccharides, vitamins, minerals, fatty acids, peptides, amino acids and polyphenols. Some of these components enhance immune responses, leading to host defense against infection, whereas others inhibit immune responses, thus suppressing allergy and inflammation.     

Bio-therapeutics from human milk: prospects and perspectives

Human milk is elixir for neonates and is a rich source of nutrients and beneficial microbiota required for infant growth and development. Its benefits prompted research into probing the milk components and their use as prophylactic or therapeutic agents. Culture-independent estimation of milk microbiome and high-resolution identification of milk components provide information, but a holistic purview of these research domains is lacking. Here, we review the current research on bio-therapeutic components of milk and simplified future directions for its efficient usage. Publicly available databases such as PubMed and Google scholar were searched for keywords such as probiotics and prebiotics related to human milk, microbiome and milk oligosaccharides. This was further manually curated for inclusion and exclusion criteria relevant to human milk and clinical efficacy. The literature was classified into subgroups and then discussed in detail to facilitate understanding. Although milk research is still in infancy, it is clear that human milk has many functions including protection of infants by passive immunization through secreted antibodies, and transfer of immune regulators, cytokines and bioactive peptides. Unbiased estimates show that the human milk carries a complex community of microbiota which serves as the initial inoculum for establishment of infant gut. Our search effectively screened for evidence that shows that milk also harbours many types of prebiotics such as human milk oligosaccharides which encourage growth of beneficial probiotics. The milk also trains the naive immune system of the infant by supplying immune cells and stimulatory factors, thereby strengthening mucosal and systemic immune system. Our systematic review would improve understanding of human milk and the inherent complexity and diversity of human milk. The interrelated functional role of human milk components especially the oligosaccharides and microbiome has been discussed which plays important role in human health.     

Differences in faecal bacterial communities in coeliac and healthy children as detected by PCR and denaturing gradient gel electrophoresis

Coeliac disease (CD) is a chronic inflammatory disorder of the small intestinal mucosa. Scientific evidence supports a role of the gut microbiota in chronic inflammatory disorders; yet information is not specifically available for CD. In this study, a comparative denaturing gradient gel electrophoresis analysis of faecal samples from coeliac children and age-matched controls was carried out. The diversity of the faecal microbiota was significantly higher in coeliac children than in healthy controls. The presence of the species Lactobacillus curvatus, Leuconostoc mesenteroides and Leuconostoc carnosum was characteristic of coeliac patients, while that of the Lactobacillus casei group was characteristic of healthy controls. The Bifidobacterium population showed a significantly higher species diversity in healthy children than in coeliacs. In healthy children, this population was characterized by the presence of Bifidobacterium adolescentis. Overall, the results highlighted the need for further characterization of the microbiota in coeliac patients, and suggested a potential role of probiotics and/or prebiotics in restoring their gut microbial balance.     

Intestinal bacteria and ageing

Advancements in science and medicine, as well as improved living standards, have led to a steady increase in life expectancy, and subsequently a rise in the elderly population. The intestinal microbiota is important for maintenance of host health, providing energy, nutrients and protection against invading organisms. Although the colonic microbiota is relatively stable throughout adult life, age-related changes in the gastrointestinal (GI) tract, as well as changes in diet and host immune system reactivity, inevitably affect population composition. Recent studies indicate shifts in the composition of the intestinal microbiota, which may lead to detrimental effects for the elderly host. Increased numbers of facultative anaerobes, in conjunction with a decrease in beneficial organisms such as the anaerobic lactobacilli and bifidobacteria, amongst other anaerobes, have been reported. These changes, along with a general reduction in species diversity in most bacterial groups, and changes to diet and digestive physiology such as intestinal transit time, may result in increased putrefaction in the colon and a greater susceptibility to disease. Therapeutic strategies to counteract these changes have been suggested in ageing people. These include dietary supplements containing prebiotics, probiotics and a combination of both of these, synbiotics. Limited feeding trials show promising results with these supplements, although further longer-term investigations are required to substantiate their use in elderly healthcare fields.     

The role of IL-10 in microbiome-associated immune modulation and disease tolerance

Current research on the microbiome of humans and other species is revealing a fundamental role for the interaction between the microbiota and the immune system in determining the health status of the host. In these studies, the cytokine interleukin-10 (IL-10) is emerging as an important player. We present here an overview of the developments in the field emphasizing how the microbiota composition and its interplay with immune cells affect the health of the host through changes in IL-10 production. In addition, we explore the function that IL-10-producing immune cells may have on the qualitative and quantitative changes in the microbiota and thus influence the balance between microbial commensalism and pathogenicity. In the last section of this review, we present a summary of the strategies that target IL-10 for therapeutic purposes using probiotics, purified proteins or biologicals.     

In vitro fermentation of rice bran combined with Lactobacillus acidophilus 14 150B or Bifidobacterium longum 05 by the canine faecal microbiota

The fermentability of rice bran (RB), alone or in combination with one of two probiotics, by canine faecal microbiota was evaluated in stirred, pH-controlled, anaerobic batch cultures. RB enhanced the levels of bacteria detected by probes Bif164 (bifidobacteria) and Lab158 (lactic acid bacteria); however, addition of the probiotics did not have a significant effect on the predominant microbial counts compared with RB alone. RB sustained levels of Bifidobacterium longum 05 throughout the fermentation; in contrast, Lactobacillus acidophilus 14 150B levels decreased significantly after 5-h fermentation. RB fermentation induced changes in the short-chain fatty acid (SCFA) profile. However, RB combined with probiotics did not alter the SCFA levels compared with RB alone. Denaturing gradient gel electrophoresis analysis of samples obtained at 24 h showed a treatment effect with RB, which was not observed in the RB plus probiotic systems. Overall, the negative controls displayed lower species richness than the treatment systems and their banding profiles were distinct. This study illustrates the ability of a common ingredient found in pet food to modulate the canine faecal microbiota and highlights that RB may be an economical alternative to prebiotics for use in dog food.     

Probiotic Lactobacillus rhamnosus GG Enhanced Th1 Cellular Immunity but Did Not Affect Antibody Responses in a Human Gut Microbiota Transplanted Neonatal Gnotobiotic Pig Model

This study aims to establish a human gut microbiota (HGM) transplanted gnotobiotic (Gn) pig model of human rotavirus (HRV) infection and diarrhea, and to verify the dose-effects of probiotics on HRV vaccine-induced immune responses. Our previous studies using the Gn pig model found that probiotics dose-dependently regulated both T cell and B cell immune responses induced by rotavirus vaccines. We generated the HGM transplanted neonatal Gn pigs through daily feeding of neonatal human fecal suspension to germ-free pigs for 3 days starting at 12 hours after birth. We found that attenuated HRV (AttHRV) vaccination conferred similar overall protection against rotavirus diarrhea and virus shedding in Gn pigs and HGM transplanted Gn pigs. HGM promoted the development of the neonatal immune system, as evidenced by the significantly enhanced IFN-γ producing T cell responses and reduction of regulatory T cells and their cytokine production in the AttHRV-vaccinated pigs. The higher dose Lactobacillus rhamnosus GG (LGG) feeding (14 doses, up to 10⁹ colony-forming-unit [CFU]/dose) effectively increased the LGG counts in the HGM Gn pig intestinal contents and significantly enhanced HRV-specific IFN-γ producing T cell responses to the AttHRV vaccine. Lower dose LGG (9 doses, up to 10⁶ CFU/dose) was ineffective. Neither doses of LGG significantly improved the protection rate, HRV-specific IgA and IgG antibody titers in serum, or IgA antibody titers in intestinal contents compared to the AttHRV vaccine alone, suggesting that an even higher dose of LGG is needed to overcome the influence of the microbiota to achieve the immunostimulatory effect in the HGM pigs. This study demonstrated that HGM Gn pig is an applicable animal model for studying immune responses to rotavirus vaccines and can be used for studying interventions (i.e., probiotics and prebiotics) that may enhance the immunogenicity and protective efficacy of vaccines through improving the gut microbiota.     

Prebiotics and other microbial substrates for gut functionality

The intestinal microbiota is of great importance to our health and wellbeing. Modulation of the intestinal microbiota by exogenous and endogenous substrates can be expected to improve various physiological functions of our body, not just those in the intestine. Recently, new targets such as immune function and areas outside the colon have been considered to be influenced by the intestinal microbiota. Novel approaches might include the application of prebiotics in different combinations or the provision of nutrients to different bacterial groups and to different parts of the intestine.     

A review on prebiotics and probiotics for the control of dysbiosis: present status and future perspectives

Dysbiosis or dysbacteriosis is defined as a shift in the intestinal microbiota composition resulting in an imbalance between beneficial and harmful bacteria. Since the ban on the use of growth-promoting antibiotics in animal feed in the EU, dysbiosis has emerged as a major problem in intensive animal production. Prebiotics and probiotics are currently under investigation as possible alternatives to growth-promoting antibiotics, as their mode of action is thought to be based largely on a modulation of the composition and function of the intestinal microbiota. In this review, we analyse the currently available data from both animal and human nutrition that document the potential and limitations of prebiotics and probiotics for the control of dysbiosis. An impressive number of empirical feeding trials have been carried out in healthy animals, yielding sometimes contradictory results. More in-depth studies have revealed the complexity of the interactions taking place in the lower intestinal tract, thus illustrating that pre- and probiotics cannot be a simple replacement for growth-promoting antibiotics. Although there are indications that the strategic use of pre- and probiotics can provide major benefits, there is still a lack of basic knowledge on the delicate interactions between the microbiota, the host and the feed components, which hampers the widespread use of these valuable feed additives.