Effects of regulating gut microbiota on the serotonin metabolism in the chronic unpredictable mild stress rat model.
ABSTRACT: OBJECTIVE:This study was to inspect the antidepressant-like effect of prebiotics and probiotics, and to explore the effect of modulating gut microbiota on the serotonin (5-HT) metabolism. METHODS:Fifty rats were separated into control and other four groups randomly. The four groups underwent the chronic unpredictable mild stress (CUMS) intervention with or without prebiotics and probiotics (Bifidobacterium longum, L. rhamnosus) treatment. After weighted, the animals underwent a series of behavioral tests comprising the sucrose preference test (SPT) and the forced swimming test (FST). Central and colonic serotonin levels and relative metabolism factors were measured and analyzed. Microbiota was examined by 16S rRNA gene pyrosequencing. RESULTS:CUMS intervention caused a decrease in body weight, an increase in FST, and a decrease in SPT. Prebiotics and probiotics all ameliorated the CUMS-induced loss of weight and depressive-like behaviors to a certain extent, especially L. rhamnosus. Compared with the group of CUMS intervention, the rats of probiotics and probiotics treatment had a tendency to reduce colonic 5-HT and increase 5-HT in frontal cortex and hippocampus. However, there was no significant difference in peripheral blood 5-HT among these groups. Furthermore, CUMS caused noteworthy gut microbiota variations at the phylum and other levels in rats. Remarkably, there were considerable relations of perturbed gut microbiota with the changed metabolism of 5-HT. CONCLUSION:In conclusion, these findings implied that prebiotics and probiotics have antidepressive effects, and a considerable effect on the regulation of 5-HT metabolism, especially L. rhamnosus.
Project description: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.
Project description:Glycosaminoglycans (GAGs) (e.g. heparin, chondroitin sulfate, and hyaluronan) show various significant physiological functions as a major component of extracellular matrix in animals. Some bacteria target GAGs for adhesion and/or infection to host cells, although no probiotics have been known to degrade GAGs. Here, we show GAG degradation by probiotics from human gut microbiota and their adhesion to human intestinal cells through a GAG. GAG-degrading bacteria were isolated from human faeces and identified as Enterococcus faecium, and some typical probiotics such as Lactobacillus casei, Lactobacillus rhamnosus and Enterococcus faecalis were also found to degrade heparin. GAG-degrading lactobacilli and enterococci including the isolated E. faecium possessed a genetic cluster encoding GAG-degrading/metabolising enzymes in the bacterial genome. KduI and KduD enzymes encoded in the GAG cluster of L. rhamnosus functioned as 4-deoxy-l-threo-5-hexosulose-uronate ketol-isomerase and 2-keto-3-deoxy-d-gluconate dehydrogenase, respectively, both of which were crucial for GAG metabolism. GAG-degrading L. rhamnosus and E. faecium attached to human intestinal Caco-2 cells via heparin. Some species of Bacteroides, considered to be the next generation probiotics, degraded chondroitin sulfate C and hyaluronan, and genes coding for the Bacteroides GAG-degrading enzyme were frequently detected from human gut microbiota. This is the first report on GAG-degrading probiotics in human gut microbiota.
Project description:Background: Chronic constipation, including functional constipation and constipation-type irritable bowel syndrome, is a prevalent, multifactorial gastrointestinal disorder, and its etiology and pathophysiology remain poorly understood. Recently studies using 16S rRNA-based microbiota profiling have demonstrated dysbiosis of gut microbiota in chronic constipation. Aims: To provide an overview of recent studies for microbiota in chronic constipation and treatments for chronic constipation using probiotics, prebiotics, synbiotics, antibiotics and fecal microbiota transplantation (FMT). Methods: PubMed searches were performed up to 1 August 2018 using keywords: "IBS," "IBS-C," "irritable bowel syndrome," "irritable bowel syndrome with constipation," "functional constipation," "chronic constipation" in combination with "gut microbiota," "dysbiosis," "gut microflora" for microbiota in chronic constipation, and in combination with "probiotics," "prebiotics," "synbiotics," "antibiotics," and "fecal microbiota transplantation." Results: The findings of gut microbiota in functional constipation are inconsistent, and currently no consensus exists. Although no clear consensus exists, compared with healthy subjects, IBS-C patients have a lower level of Actinobacteria, including Bifidobacteria, in their fecal samples and a higher level of Bacteroidetes in their mucosa. In most randomized controlled and parallel-group trials, probiotics, prebiotics, synbiotics, antibiotics, and FMT therapy for chronic constipation were effective with few side effects. However, there are many studies in a small number and the types of probiotics are different, it is difficult to evaluate the effect. Conclusions: Evidence indicates that dysbiosis of gut microbiota may contribute to functional constipation and constipation-type irritable bowel syndrome. Targeting treatments for the dysbiosis of constipation by probiotics, prebiotics, synbiotics, antibiotics, and FMT may be a new option, especially for refractory constipation to conventional therapies.
Project description:The aging process leads to a potential decline in immune function and adversely affects the gut microbiota. To date, many in vitro and in vivo studies focused on the application of synbiotics (prebiotics combined with probiotics) as a promising dietary approach to affect gut microbiota composition and improved functioning of the immune system. However, studies using synbiotic preparations often have the limitation that it remains unclear whether any effect observed is a result of the prebiotic or probiotic or a synergistic effect of the combined supplement.We investigated the effects of a probiotic Lactobacillus rhamnosus GG and pilus-deficient L. rhamnosus GG-PB12 combined with Promitor™ Soluble Corn Fiber (SCF, a candidate prebiotic) on fecal microbiota, metabolism, immunity, and blood lipids in healthy elderly persons. A prospective, double-blind, placebo controlled, randomized, single-centered, crossover study in 40 healthy elderly subjects (aged 60-80?years) was carried out. Volunteers were randomized to consume either probiotic and prebiotic as synbiotic, prebiotic or placebo (maltodextrin) during 3?weeks. Three-week washout periods separated all the treatments. We assessed effects upon blood lipids, glucose, cytokines, natural killer (NK) cell activity, phenotype, and intestinal microbiota composition. SCF decreased IL-6, which was not observed with the synbiotics.Consumption of L. rhamnosus GG combined with SCF increased NK cell activity compared to baseline in females and the older group. In the fecal microbiota analyses, the strongest community shifts were due to L. rhamnosus GG combined with SCF and SCF treatments. L. rhamnosus GG combined with SCF and L. rhamnosus GG-PB12 combined with SCF significantly increased the genus Parabacteroides. L. rhamnosus GG combined with SCF and SCF increased concentrations of Ruminococcaceae Incertae Sedis. Oscillospira and Desulfovibrio slightly decreased in the L. rhamnosus GG combined with SCF group, whereas Desulfovibrio decreased also in the L. rhamnosus GG-PB12 combined with SCF group. L. rhamnosus GG combined with SCF reduced total cholesterol and LDL-cholesterol in volunteers with initially elevated concentrations. C-reactive protein significantly decreased during L. rhamnosus GG-PB12 combined with SCF intervention compared to baseline.In conclusion, the synbiotic combination of L. rhamnosus GG with SCF showed a tendency to promote innate immunity by increasing NK cell activity in elderly women and in 70 to 80-year-old volunteers and decreased TC and LDL-c in hypercholesterolemic patients. In addition, L. rhamnosus GG-PB12 combined with SCF demonstrated an increase in NK cell activity compared to SCF alone in older volunteers. We also found significant positive effects on the immune response, evidenced by a decrease of the pro-inflammatory cytokine IL-6. Therefore, dietary intervention with L. rhamnosus GG combined with SCF could be of importance in elderly as an attractive option for enhancement of both the microbial and immune systems.
Project description:BACKGROUND: Growing evidence indicates that intestinal microbiota regulate our metabolism. Probiotics confer health benefits that may depend on their ability to affect the gut microbiota. The objective of this study was to examine the effect of supplementation with the probiotic strain, Lactobacillus rhamnosus hsryfm 1301, on the gut microbiota in a hyperlipidemic rat model, and to explore the associations between the gut microbiota and the serum lipids. METHODS: The hyperlipidemic rat model was established by feeding rats a high-fat diet for 28 d. The rats' gut microbiota were analyzed using high-throughput sequencing before and after L. rhamnosus hsryfm 1301 supplementation or its fermented milk for 28 d. The serum lipids level was also tested. RESULTS: The rats' primary gut microbiota were composed of Bacteroidetes, Firmicutes, Proteobacteria, Spirochaetes and Verrucomicrobia. The abundance and diversity of the gut microbiota generally decreased after feeding with a high-fat diet, with a significant decrease in the relative abundance of Bacteroidetes, but with an increase in that of Firmicutes (P < 0.05). Administration of L. rhamnosus hsryfm 1301 or its fermented milk for 28 d, could recover the Bacteroidetes and Verrucomicrobia abundance and could decrease the Firmicutes abundance, which was associated with a significant reduction in the serum lipids' level in the hyperlipidemic rats with high-fat diet induced. The abundance of 22 genera of gut bacteria was changed significantly after probiotic intervention for 28 d (P < 0.05). A positive correlation was observed between Ruminococcus spp. and serum triglycerides, Dorea spp. and serum cholesterol (TC) and low-density lipoprotein (LDL-C), and Enterococcus spp. and high-density lipoprotein. The Butyrivibrio spp. negatively correlated with TC and LDL-C. CONCLUSIONS: Our results suggest that the lipid metabolism of hyperlipidemic rats was improved by regulating the gut microbiota with supplementation of L.rhamnosus hsryfm 1301 or its fermented milk for 28 d.
Project description:Accumulating evidence indicates that the intestinal microbiota regulates our physiology and metabolism. Bacteria marketed as probiotics confer health benefits that may arise from their ability to affect the microbiota. Here high-throughput screening of the intestinal microbiota was carried out and integrated with serum lipidomic profiling data to study the impact of probiotic intervention on the intestinal ecosystem, and to explore the associations between the intestinal bacteria and serum lipids. We performed a comprehensive intestinal microbiota analysis using a phylogenetic microarray before and after Lactobacillus rhamnosus GG intervention. While a specific increase in the L. rhamnosus-related bacteria was observed during the intervention, no other changes in the composition or stability of the microbiota were detected. After the intervention, lactobacilli returned to their initial levels. As previously reported, also the serum lipid profiles remained unaltered during the intervention. Based on a high-resolution microbiota analysis, intake of L. rhamnosus GG did not modify the composition of the intestinal ecosystem in healthy adults, indicating that probiotics confer their health effects by other mechanisms. The most prevailing association between the gut microbiota and lipid profiles was a strong positive correlation between uncultured phylotypes of Ruminococcus gnavus-group and polyunsaturated serum triglycerides of dietary origin. Moreover, a positive correlation was detected between serum cholesterol and Collinsella (Coriobacteriaceae). These associations identified with the spectrometric lipidome profiling were corroborated by enzymatically determined cholesterol and triglyceride levels. Actinomycetaceae correlated negatively with triglycerides of highly unsaturated fatty acids while a set of Proteobacteria showed negative correlation with ether phosphatidylcholines. Our results suggest that several members of the Firmicutes, Actinobacteria and Proteobacteria may be involved in the metabolism of dietary and endogenous lipids, and provide a scientific rationale for further human studies to explore the role of intestinal microbes in host lipid metabolism.
Project description:Severe, repeated or chronic stress produces negative health outcomes including disruptions of the sleep/wake cycle and gut microbial dysbiosis. Diets rich in prebiotics and glycoproteins impact the gut microbiota and may increase gut microbial species that reduce the impact of stress. This experiment tested the hypothesis that consumption of dietary prebiotics, lactoferrin (Lf) and milk fat globule membrane (MFGM) will reduce the negative physiological impacts of stress. Male F344 rats, postnatal day (PND) 24, received a diet with prebiotics, Lf and MFGM (test) or a calorically matched control diet. Fecal samples were collected on PND 35/70/91 for 16S rRNA sequencing to examine microbial composition and, in a subset of rats; Lactobacillus rhamnosus was measured using selective culture. On PND 59, biotelemetry devices were implanted to record sleep/wake electroencephalographic (EEG). Rats were exposed to an acute stressor (100, 1.5 mA, tail shocks) on PND 87 and recordings continued until PND 94. Test diet, compared to control diet, increased fecal Lactobacillus rhamnosus colony forming units (CFU), facilitated non-rapid eye movement (NREM) sleep consolidation (PND 71/72) and enhanced rapid eye movement (REM) sleep rebound after stressor exposure (PND 87). Rats fed control diet had stress-induced reductions in alpha diversity and diurnal amplitude of temperature, which were attenuated by the test diet (PND 91). Stepwise multiple regression analysis revealed a significant linear relationship between early-life Deferribacteres (PND 35) and longer NREM sleep episodes (PND 71/72). A diet containing prebiotics, Lf and MFGM enhanced sleep quality, which was related to changes in gut bacteria and modulated the impact of stress on sleep, diurnal rhythms and the gut microbiota.
Project description:Increasing researches have confirmed the relationship between slow-transit constipation and gut microbiota dysbiosis. Many population and animal experiments have identified probiotics as effectors for the relief of constipation symptoms, but the specific mechanism remains unclear. In this intervention study, Lactobacillus rhamnosus strains isolated from five different sources were administered to mice with loperamide-induced constipation, and the impacts of these strains on constipation-related indicators were evaluated. All five strains of L. rhamnosus were found to improve constipation to various degrees. However, contrary to previous studies, the abilities of L. rhamnosus strains to improve constipation symptoms were not associated with the levels of short-chain fatty acids (SCFAs) in the colon. The effects of different strains of L. rhamnosus on constipation relief were associated with different aspects of the GI tract, including gastrointestinal regulatory peptides, neurotransmitters, neurotrophic factors, and gut microbiota. The findings of this study demonstrate that L. rhamnosus strains can alleviate constipation-related symptoms via different pathways independent of SCFAs regulation. This study yields a new perspective for clinical use of probiotics to better improve constipation symptoms, by combining strains with different mechanisms for alleviation of constipation.
Project description:The link between gut microbiota and the development of colorectal cancer has been investigated. An imbalance in the gut microbiota promotes the progress of colorectal carcinogenesis via multiple mechanisms, including inflammation, activation of carcinogens, and tumorigenic pathways as well as damaging host DNA. Several therapeutic methods are available with which to alter the composition and the activity of gut microbiota, such as administration of prebiotics, probiotics, and synbiotics; these can confer various benefits for colorectal cancer patients. Nowadays, fecal microbiota transplantation is the most modern way of modulating the gut microbiota. Even though data regarding fecal microbiota transplantation in colorectal cancer patients are still rather limited, it has been approved as a clinical method of treatment-recurrent Clostridium difficile infection, which may also occur in these patients. The major benefits of fecal microbiota transplantation include modulation of immunotherapy efficacy, amelioration of bile acid metabolism, and restoration of intestinal microbial diversity. Nonetheless, more studies are needed to assess the long-term effects of fecal microbiota transplantation. In this review, the impact of gut microbiota on the efficiency of anti-cancer therapy and colorectal cancer patients' overall survival is also discussed.
Project description:Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent metabolic disorder with steadily increasing incidence rates worldwide, especially in the West. There are no drugs available at present to treat NAFLD, and the primary therapeutic options include weight loss and the combination of healthy diet and exercise. Therefore, novel interventions are required that can target the underlying risk factors. Gut microbiota is an “invisible organ” of the human body and vital for normal metabolism and immuno-modulation. The number and diversity of microbes differ across the gastrointestinal tract from the mouth to the anus, and is most abundant in the intestine. Since dysregulated gut microbiota is an underlying pathological factor of NAFLD, it is a viable therapeutic target that can be modulated by antibiotics, probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and microbial metabolites. In this review, we summarize the most recent advances in gut microbiota-targeted therapies against NAFLD in clinical and experimental studies, and critically evaluate novel targets and strategies for treating NAFLD.