Gut Microbial Populations Research Articles

Free Fatty Acids Profiles Are Related to Gut Microbiota Signatures and Short-Chain Fatty Acids.

A growing body of evidence highlights the relevance of free fatty acids (FFA) for human health, and their role in the cross talk between the metabolic status and immune system. Altered serum FFA profiles are related to several metabolic conditions, although the underlying mechanisms remain unclear. Recent studies have highlighted the link between gut microbiota and host metabolism. However, although most of the studies have focused on different clinical conditions, evidence on the role of these mediators in healthy populations is lacking. Therefore, we have addressed the analysis of the relationship among gut microbial populations, short-chain fatty acid (SCFA) production, FFA levels, and immune mediators (IFNγ, IL-6, and MCP-1) in 101 human adults from the general Spanish population. Levels of selected microbial groups, representing the major phylogenetic types present in the human intestinal microbiota, were determined by quantitative PCR. Our results showed that the intestinal abundance of Akkermansia was the main predictor of total FFA serum levels, displaying a negative association with total FFA and the pro-inflammatory cytokine IL-6. Similarly, an altered FFA profile, identified by cluster analysis, was related to imbalanced levels of Akkermansia and Lactobacillus as well as increased fecal SCFA, enhanced IL-6 serum levels, and higher prevalence of subclinical metabolic alterations. Although no differences in nutritional intakes were observed, divergent patterns in the associations between nutrient intakes with intestinal microbial populations and SCFA were denoted. Overall, these findings provide new insights on the gut microbiota–host lipid metabolism axis and its potential relevance for human health, where FFA and SCFA seem to play an important role.

Using probiotics to improve swine gut health and nutrient utilization.

To maintain a healthy gut is definitely key for a pig to digest and absorb dietary nutrients efficiently. A balanced microbiota (i.e., a healthy micro-ecosystem) is an indispensable constituent of a healthy gut. Probiotics, the live microorganisms which, when administered in adequate amounts, confer good health benefits onto the host, are a category of feed additives that can be used to replenish the gut microbial population while recuperating the host immune system. Besides their antitoxin and diarrhea reduction effects, dietary supplementation of probiotics can improve gut health, nutrient digestibilities and, therefore, benefit nutrient utilization and growth performance of pigs. Current knowledge in the literature pertinent to the beneficial effects of utilizing various probiotics for swine production has been comprehensively reviewed, and the safety and the risk issues related to probiotic usage have also been discussed in this paper. Considering that the foremost cost in a swine operation is feed cost, feed efficiency holds a very special, if not the paramount, significance in commercial swine production. Globally, the swine industry along with other animal industries is moving towards restricting and eventually a total ban on the usage of antibiotic growth promoters. Therefore, selection of an ideal alternative to the in-feed antibiotics to compensate for the lost benefits due to the ban on the antibiotic usage is urgently needed to support the industry for profitable and sustainable swine production. As is understood, a decision on this selection is not easy to make. Thus, this review paper aims to provide some much needed up-to-date knowledge and comprehensive references for swine nutritionists and producers to refer to before making prudent decisions and for scientists and researchers to develop better commercial products.

Analysis of the gut bacterial communities in beef cattle and their association with feed intake, growth, and efficiency.

The impetus behind the global food security challenge is direct, with the necessity to feed almost 10 billion people by 2050. Developing a food-secure world, where people have access to a safe and sustainable food supply, is the principal goal of this challenge. To achieve this end, beef production enterprises must develop methods to produce more pounds of animal protein with less. Selection for feed-efficient beef cattle using genetic improvement technologies has helped to understand and improve the stayability and longevity of such traits within the herd. Yet genetic contributions to feed efficiency have been difficult to identify, and differing genetics, feed regimens, and environments among studies contribute to great variation and interpretation of results. With increasing evidence that hosts and their microbiomes interact in complex associations and networks, examining the gut microbial population variation in feed efficiency may lead to partially clarifying the considerable variation in the efficiency of feed utilization. The use of metagenomics and high-throughput sequencing has greatly impacted the study of the ruminant gut. The ability to interrogate these systems at great depth has permitted a greater understanding of the microbiological and molecular mechanisms involved in ruminant nutrition and health. Although the microbial communities of the reticulorumen have been well documented to date, our understanding of the populations within the gastrointestinal tract as a whole is limited. The composition and phylogenetic diversity of the gut microbial community are critical to the overall well-being of the host and must be determined to fully understand the relationship between the microbiomes within segments of the cattle gastrointestinal tract and feed efficiency, ADG, and ADFI. This review addresses recent research regarding the bacterial communities along the gastrointestinal tract of beef cattle; their association with ADG, ADFI, and feed efficiency; and the potential implications for beef production.

Stability of the microbial population in the gut of omnivorous wireworms (Coleoptera, Elateridae)

The variability of the microbial population structure of the gut of omnivorous wireworms Agriotes obscurus (L) and Selatosomus aeneus (L) was studied. The limits of intra- and interspecific and intersite variation were determined. The stability of the microbial composition of the gut allows us to reveal the list of obligate saprotrophs (with 95% probability) using only five replications. In the case of S. aeneus, the influence of starvation and diet change was studied. Starvation changed the microbial population structure, while the diet did not. The results confirm that omnivorous wireworms have a stable gut microbial population, which suggests an advanced mutualistic relationship between wireworms and their gut bacteria, possibly assisting in digestion and providing for ecological flexibility of wireworms.

Review of Pro- and/or Prebiotics in Extensively Hydrolyzed or Amino Acid-Based Infant Formula for Food Allergy

Background:The incidence of food allergy is a growing health concern in the United States. Research suggests that there is a link between the gut microbiota and the development of allergy. As a result, researchers propose that gut microbial populations could affect the development and management of immunological disease.Objectives:The purpose of this review is to present current evidence of the advantages and disadvantages of probiotic and/or prebiotic addition to extensively hydrolyzed protein (EHF) and amino acid-based infant formulas (AAF) for the management of food allergy.Method:Only randomized controlled trials were included for review. The randomized controlled trials were limited to human subjects less than 12 years of age with a confirmed case of food allergy who were consuming EHF or AAF supplemented with probiotics and/or prebiotics.Results:Eleven studies were included for review. Probiotic and synbiotic addition was associated with an improvement in SCORAD index in EHF and AAF, and EHF significantly moderated immunologic and/or inflammatory responses. Probiotic addition to EHF benefited patients exhibiting hematochezia, and synbiotic addition resulted in softer stool, higher stool frequency, and decreased incidence of infection in some studies.Conclusion:Although few studies report statistically significant effects upon feeding prebiotics or probiotics with EHF and AAF on food allergy, this review sheds light on evidence that such inclusion may have positive impacts on SCORAD index, stool quality, immunologic and inflammatory factors, and incidence of infection.

Effects of Dietary Non-Fiber Carbohydrates on Composition and Function of Gut Microbiome in Monogastrics: A Review.

Non-fiber carbohydrates (NFC) have a crucial function on the gut health of monogastrics. This paper aims to review the relevant published materials on the influence of NFCs on the gut's microbial population and composition in monogastrics, and points out the areas of the required research. Total bacteria count and Lactobacillus sp. were decreased with an increase in composition of dietary NFC intake, as well as accompanied by a decrease in the short-chain fatty acids (SCFAs) levels. Consequently, some metabolites were affected by the accumulation of the bile acids, including molecules which control different gene expression levels, as regulators involved in glucose (FXR and TGR5) and fat metabolism (cholesterol). Cell proliferation rate of both gastrointestinal epithelium and microbiome cells was negatively correlated with the dietary NFC levels in many species of monogastric animals. Low levels of NFC diet are negatively associated with digestibility, total gut weight, and gastrointestinal secretions. High levels of dietary NFC have negative effects on the digestion and absorption of macronutrients, with an increase of the contact time of the carcinogens in the intestinal lumen. The data obtained from different animals' studies did not give the same results. In conclusion, dietary NFC should be adjusted to the optimal consumption levels as the human and the monogastric animals are anatomically and physiologically different. Digestion, metabolism, host wellbeing, and host behavior were negatively affected by the administration of high NFC levels. The relations between sulphate-reducing bacteria and some metabolic diseases such as diabetes mellitus and obesity need further exploration.

Can gut microbes play a role in mental disorders and their treatment?

The gut microbes, collectively called microbiota, are linked to the brain through a bidirectional system that involves the vagus nerve, the immune system, and various neurotransmitters. Stress response, memory functions, social behavior, and mood are modulated by microbiota. Furthermore, microbiota play a role in the development of the central nervous system. These features, established largely in rodent studies, have informed hypotheses about the role of microbiota in human psychiatric disorders. Microbiota affect phenomena that are known to be parts of the depression phenotype, such as exaggerated response to stress and inflammatory features. Furthermore, the role of microbiota in neurodevelopment and in the modulation of social behavior suggests the possibility of its role in autism spectrum disorder and in schizophrenia. If altered, microbiota play a role in psychiatric disorders, then efforts to normalize the gut microbial population by the ingestion of probiotics (live bacteria) could have antidepresssant or antipsychotic effects. Testing such hypotheses in translational human studies is a matter of future research.

Of the milk sugars, galactose, but not prebiotic galacto-oligosaccharide, improves insulin sensitivity in male Sprague-Dawley rats.

BackgroundConsumption of dairy products reduces risk of type 2 diabetes. Milk proteins and fats exhibit anti-diabetic properties but milk sugars have been studied little in this context. Galactose from milk lactose is readily converted to glycogen in the liver but its effects on insulin sensitivity have not been assessed. Prebiotic oligosaccharides from milk alter gut microbiota and can thereby influence host metabolism. Our objective was to assess the effect on insulin sensitivity of dietary galactose compared to glucose and fructose, and fermentable galacto-oligosaccharides compared to non-fermentable methylcellulose.MethodsDiets containing 15% of dry matter from glucose, fructose, galactose, galacto-oligosaccharides, or methylcellulose were fed to 36 rats per diet for 9 weeks. Hyperinsulinemic-euglycemic clamps with [3-3H]glucose infusion and a steady-state 2-[1-14C]deoxyglucose bolus injection were used to assess insulin sensitivity and glucose uptake indices. Tissue was collected in fed, fasted and fasted, insulin-stimulated states.ResultsGalactose increased glucose infusion rate during the clamp by 53% and decreased endogenous glucose production by 57% compared to glucose and fructose. Fed-state hepatic glycogen content was greater with galactose compared to glucose and fructose, consistent with a potentiation of the insulin effect on glycogen synthase by dephosphorylation. Galactose decreased the fecal Firmicutes:Bacteroidetes ratio while galacto-oligosaccharides increased abundance of fecal Bifidobacterium spp. 481-fold compared to methylcellulose, and also increased abundance of Lactobacillus spp. and Bacteroidetes. Galacto-oligosaccharides did not affect glucose infusion rate or endogenous glucose production during basal or clamp periods compared to methylcellulose.ConclusionsGalactose at 15% of daily intake improved hepatic insulin sensitivity in rats compared to glucose and fructose. Galactose caused an increase in fed-state hepatic glycogen content and a favourable shift in gut microbial populations. Intake of galacto-oligosaccharides improved the gut microbial profile but did not improve insulin sensitivity.

Vertical sleeve gastrectomy reduces blood pressure and hypothalamic endoplasmic reticulum stress in mice.

ABSTRACTBariatric surgery, such as vertical sleeve gastrectomy (VSG), causes remarkable improvements in cardiometabolic health, including hypertension remission. However, the mechanisms responsible remain undefined and poorly studied. Therefore, we developed and validated the first murine model of VSG that recapitulates the blood pressure-lowering effect of VSG using gold-standard radiotelemetry technology. We used this model to investigate several potential mechanisms, including body mass, brain endoplasmic reticulum (ER) stress signaling and brain inflammatory signaling, which are all critical contributors to the pathogenesis of obesity-associated hypertension. Mice fed on a high-fat diet underwent sham or VSG surgery and radiotelemeter implantation. Sham mice were fed ad libitum or were food restricted to match their body mass to VSG-operated mice to determine the role of body mass in the ability of VSG to lower blood pressure. Blood pressure was then measured in freely moving unstressed mice by radiotelemetry. VSG decreased energy intake, body mass and fat mass. Mean arterial blood pressure (MAP) was reduced in VSG-operated mice compared with both sham-operated groups. VSG-induced reductions in MAP were accompanied by a body mass-independent decrease in hypothalamic ER stress, hypothalamic inflammation and sympathetic nervous system tone. Assessment of gut microbial populations revealed VSG-induced increases in the relative abundance of Gammaproteobacteria and Enterococcus, and decreases in Adlercreutzia. These results suggest that VSG reduces blood pressure, but this is only partly due to the reduction in body weight. VSG-induced reductions in blood pressure may be driven by a decrease in hypothalamic ER stress and inflammatory signaling, and shifts in gut microbial populations.

In vitro fermentation of B-GOS: impact on faecal bacterial populations and metabolic activity in autistic and non-autistic children.

Children with autism spectrum disorders (ASD) often suffer gastrointestinal problems consistent with imbalances in the gut microbial population. Treatment with antibiotics or pro/prebiotics has been postulated to regulate microbiota and improve gut symptoms, but there is a lack of evidence for such approaches, especially for prebiotics. This study assessed the influence of a prebiotic galactooligosaccharide (B-GOS) on gut microbial ecology and metabolic function using faecal samples from autistic and non-autistic children in an in vitro gut model system. Bacteriology was analysed using flow cytometry combined with fluorescence in situ hybridization and metabolic activity by HPLC and 1H-NMR. Consistent with previous studies, the microbiota of children with ASD contained a higher number of Clostridium spp. and a lower number of bifidobacteria compared with non-autistic children. B-GOS administration significantly increased bifidobacterial populations in each compartment of the models, both with autistic and non-autistic-derived samples, and lactobacilli in the final vessel of non-autistic models. In addition, changes in other bacterial population have been seen in particular for Clostridium, Rosburia, Bacteroides, Atopobium, Faecalibacterium prausnitzii, Sutterella spp. and Veillonellaceae. Furthermore, the addition of B-GOS to the models significantly altered short-chain fatty acid production in both groups, and increased ethanol and lactate in autistic children.

Hyperosmolality regulates UT-A6 urea transporter expression in the Caco-2 cell line.

Gastrointestinal facilitative urea transporters play a significant role in the urea nitrogen salvaging process, which supports the symbiotic relationship between mammals and their gut microbial populations. UT‐A6 urea transporters have been previously reported in the human gastrointestinal tract, specifically in the colon. As renal UT‐A transporters can be regulated by external osmolality, this study investigated whether UT‐A6 expression could also be regulated in this manner. Initial end‐point RT‐PCR experiments confirmed UT‐A6 expression along the human gastrointestinal tract (colon > small intestine ≫ stomach) and also in the Caco‐2 intestinal cell line. Using Caco‐2 cells exposed for 24 hours to changed external osmotic conditions (from 350 to 250, 500, or 600 mOsm), end‐point PCR suggested UT‐A6 expression increased in hyperosmotic conditions. Using quantitative PCR, it was confirmed that 24 h exposure to 600 mOsm stimulated a significant ~15‐fold increase in UT‐A6 expression (P < 0.001, N = 5, ANOVA). Finally, inhibitory experiments suggested that protein kinase C and calcium were involved in this hyperosmotic‐stimulated regulatory pathway. In conclusion, these data demonstrated UT‐A6 expression was indeed regulated by external osmolality. The physiological significance of this regulatory process upon gastrointestinal urea transport has yet to be determined.

Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls

Multiple sclerosis (MS) is an immune-mediated disease, the etiology of which involves both genetic and environmental factors. The exact nature of the environmental factors responsible for predisposition to MS remains elusive; however, it’s hypothesized that gastrointestinal microbiota might play an important role in pathogenesis of MS. Therefore, this study was designed to investigate whether gut microbiota are altered in MS by comparing the fecal microbiota in relapsing remitting MS (RRMS) (n = 31) patients to that of age- and gender-matched healthy controls (n = 36). Phylotype profiles of the gut microbial populations were generated using hypervariable tag sequencing of the V3–V5 region of the 16S ribosomal RNA gene. Detailed fecal microbiome analyses revealed that MS patients had distinct microbial community profile compared to healthy controls. We observed an increased abundance of Psuedomonas, Mycoplana, Haemophilus, Blautia, and Dorea genera in MS patients, whereas control group showed increased abundance of Parabacteroides, Adlercreutzia and Prevotella genera. Thus our study is consistent with the hypothesis that MS patients have gut microbial dysbiosis and further study is needed to better understand their role in the etiopathogenesis of MS.

Gut Bacteria Metabolism Impacts Immune Recovery in HIV-infected Individuals

While changes in gut microbial populations have been described in human immuno-deficiency virus (HIV)-infected patients undergoing antiretroviral therapy (ART), the mechanisms underlying the contributions of gut bacteria and their molecular agents (metabolites and proteins) to immune recovery remain unexplored. To study this, we examined the active fraction of the gut microbiome, through examining protein synthesis and accumulation of metabolites inside gut bacteria and in the bloodstream, in 8 healthy controls and 29 HIV-infected individuals (6 being longitudinally studied). We found that HIV infection is associated to dramatic changes in the active set of gut bacteria simultaneously altering the metabolic outcomes. Effects were accentuated among immunological ART responders, regardless diet, subject characteristics, clinical variables other than immune recovery, the duration and type of ART and sexual preferences. The effect was found at quantitative levels of several molecular agents and active bacteria which were herein identified and whose abundance correlated with HIV immune pathogenesis markers. Although, we cannot rule out the possibility that some changes are partially a random consequence of the disease status, our data suggest that most likely reduced inflammation and immune recovery is a joint solution orchestrated by both the active fraction of the gut microbiota and the host.

Influence of Phenol-Enriched Olive Oils on Human Intestinal Immune Function.

Olive oil (OO) phenolic compounds (PC) are able to influence gut microbial populations and metabolic output. Our aim was to investigate whether these compounds and changes affect the mucosal immune system. In a randomized, controlled, double blind cross-over human trial, for three weeks, preceded by two-week washout periods, 10 hypercholesterolemic participants ingested 25 mL/day of three raw virgin OO differing in their PC concentration and origin: (1) an OO containing 80 mg PC/kg (VOO); (2) a PC-enriched OO containing 500 mg PC/kg from OO (FVOO); and (3) a PC-enriched OO containing a mixture of 500 mg PC/kg from OO and thyme (1:1, FVOOT). Intestinal immunity (fecal immunoglobulin A (IgA) and IgA-coated bacteria) and inflammation markers (C-reactive protein (CRP) and fecal interleukin 6 (IL-6), tumor necrosis factor α (TNFα) and calprotectin) was analyzed. The ingestion of high amounts of OO PC, as contained in FVOO, tended to increase the proportions of IgA-coated bacteria and increased plasma levels of CRP. However, lower amounts of OO PC (VOO) and the combination of two PC sources (FVOOT) did not show significant effects on the variables investigated. Results indicate a potential stimulation of the immune system with very high doses of OO PC, which should be further investigated.

Soy Protein Compared with Milk Protein in a Western Diet Increases Gut Microbial Diversity and Reduces Serum Lipids in Golden Syrian Hamsters

Background: Diet is a major factor influencing the composition and metabolic activity of the gut microbiota.Objective: This study investigated the effect of soy compared with dairy protein on the gut microbiota of hamsters to determine whether changes in microbiota could account for soy protein's lipid lowering properties.Methods: Thirty-two 6- to 8-wk-old, male Golden Syrian hamsters were fed a Western diet containing 22% (%wt) milk protein isolate (MPI) as the single protein source for 3 wk followed by 6 wk of one of 4 diets containing either [22% protein (%wt)]: MPI, soy protein concentrate (SPC), partially hydrolyzed soy protein isolate (SPI1), or intact soy protein isolate. Serum lipids, hepatic gene expression, and gut microbial populations were evaluated.Results: Serum total and LDL-cholesterol concentrations were lower in the SPC-fed group (183 ± 9.0 and 50 ± 4.2 mg/dL, respectively) than in the MPI group (238 ± 8.7 and 72 ± 3.9 mg/dL, respectively) (P < 0.05). Triglyceride (TG) concentrations were lower (P < 0.05) in the SPI1-fed group (140 ± 20.8 mg/dL) than in the MPI-fed group (223 ± 14.2 mg/dL). VLDL and non-HDL-cholesterol concentrations were lower (by 40–49% and 17–33%, respectively) in all soy-fed groups than in the MPI-fed group (P < 0.05). Sequencing of the 16S ribosomal RNA gene revealed greater microbial diversity in each soy-fed group than in the MPI-fed group (P < 0.05). The cholesterol- and TG-lowering effect of soy protein was associated with higher expression of 3-hydroxy-3-methylglutaryl-CoA reductase (Hmgcr), lanosterol synthase (Lss), and farnesyl-diphosphosphate farnesyl-transferase 1 (Fdft1) (1.6–2.5-fold higher), and lower steroyl-CoA desaturase-1 (Scd1) expression (37–46% lower) in all soy-fed groups (P < 0.05) compared with the MPI-fed group. Gut microbes that showed significant diet differences were significantly correlated (ρ = −0.68 to 0.65, P < 0.05) with plasma lipids and hepatic gene expression.Conclusion: Dietary protein sources in male Golden Syrian hamsters fed a Western diet affect the gut microbiota, and soy protein may reduce lipogenesis through alterations of the gut microbial community.

The effects of Blood Rumen Content Mixture (BRCM) meal supplemented with yeast on the performance and gut microbial populations of broiler chickens

One hundred and twenty (120) arbor acre strain day old broiler chicks were used to investigate the effects of blood rumen content mixture (BRCM) meal supplemented with Levucel SB yeast on the performance and gut microbial populations of broiler chickens. Four diets were formulated both at the starter and finisher stages of the experiment. Diet 1 had neither blood rumen content mixture (BRCM) nor yeast supplementation. However diets 2, 3 and 4 contained 3.5, 7.0 and 10.5% BRCM respectively all supplemented with 2.5g/kg diet Levucel SB yeast. Dietary treatments were replicated three times using a completely randomized design. Each replicate treatment had 10 chicks. The experiment lasted for eight weeks. Results showed a significant increase (p 0.05). Ileal and caecal microbial populations were significantly increased both at 10-2 and 10-3 serial dilutions (P<0.05). All dietary treatments had Bacillus species of bacteria in their isolates. Only dietary treatments containing BRCM supplemented with Levucel SB yeast had Streptococcus and Staphylococcus species of bacteria in the isolates from the ileum and ceacum portions of the small intestine. It was concluded that when supplemented with yeast, BRCM meal up to 10.5% in broiler feed had no detrimental effect on broiler performance. It also enhanced the development of beneficial gut microbes. Keywords: Broilers, Blood Rumen Content, Performance, gut microbes, Levucel SB yeast

Effects of HIV, Immune Deficiency, and Confounding on the Distal Gut Microbiota

Human immunodeficiency virus (HIV) infection progressively destroys CD4 + mononuclear cells leading to profound cellular immune deficiency that manifests as life threatening opportunistic infections and malignancies, i.e., the acquired immune deficiency syndrome (AIDS). The gut mucosa-associated lymphoid tissue (MALT, e.g., Peyer's patches) is a major locus of CD4 + cells. HIV's asymptomatic and insidious destruction of these cells compromises the integrity of the gut mucosa, allowing translocation (leakage) of microbes and other luminal contents into the circulation (Brenchley et al., 2004). Microbial translocation induces subtle but sustained and widespread immune activation, which is a major contributor to HIV's pathogenesis (Brenchley et al., 2006).

Effect of Dietary Inclusion of Ginger (Zingiber officinale) Dried with Different Methods on Performance and Gut Microbial Population of Broiler Chicks

Effect of Dietary Inclusion of Ginger (Zingiber officinale) Dried with Different Methods on Performance and Gut Microbial Population of Broiler Chicks

Le microbiote intestinal : description, rôle et implication physiopathologique

The human gut contains 1014 bacteria and many other micro-organisms such as Archaea, viruses and fungi. Studying the gut microbiota showed how this entity participates to gut physiology and beyond this to human health, as a real “hidden organ”. In this review, we aimed to bring information about gut microbiota, its structure, its roles and its implication in human pathology. After bacterial colonization in infant, intestinal microbial composition is unique for each individual although more than 95% can be assigned to four major phyla. The use of culture independent methods and more recently the development of high throughput sequencing allowed to depict precisely gut microbiota structure and diversity as well as its alteration in diseases. Gut microbiota is implicated in the maturation of the host immune system and in many fundamental metabolic pathways including sugars and proteins fermentation and metabolism of bile acids and xenobiotics. Imbalance of gut microbial populations or dysbiosis has important functional consequences and is implicated in many digestive diseases (inflammatory bowel diseases, colorectal cancer, etc.) but also in obesity and autism. These observations have led to a surge of studies exploring therapeutics which aims to restore gut microbiota equilibrium such as probiotics or fecal microbiota transplantation. But recent research also investigates biological activity of microbial products which could lead to interesting therapeutics leads.

Microbiota and bile acid profiles in retinoic acid-primed mice that exhibit accelerated liver regeneration.

All-trans Retinoic acid (RA) regulates hepatic lipid and bile acid homeostasis. Similar to bile acid (BA), RA accelerates partial hepatectomy (PHx)-induced liver regeneration. Because there is a bidirectional regulatory relationship between gut microbiota and BA synthesis, we examined the effect of RA in altering the gut microbial population and BA composition and established their relationship with hepatic biological processes during the active phases of liver regeneration. C57BL/6 mice were treated with RA orally followed by 2/3 PHx. The roles of RA in shifting gut microbiota and BA profiles as well as hepatocyte metabolism and proliferation were studied. RA-primed mice exhibited accelerated hepatocyte proliferation revealed by higher numbers of Ki67-positive cells compared to untreated mice. Firmicutes and Bacteroidetes phyla dominated the gut microbial community (>85%) in both control and RA-primed mice after PHx. RA reduced the ratio of Firmicutes to Bacteroidetes, which was associated with a lean phenotype. Consistently, RA-primed mice lacked transient lipid accumulation normally found in regenerating livers. In addition, RA altered BA homeostasis and shifted BA profiles by increasing the ratio of hydrophilic to hydrophobic BAs in regenerating livers. Accordingly, metabolic regulators fibroblast growth factor 21, Sirtuin1, and their downstream targets AMPK and ERK1/2 were more robustly activated in RA-primed than unprimed regenerating livers. Priming mice with RA resulted in a lean microbiota composition and hydrophilic BA profiles, which were associated with facilitated metabolism and enhanced cell proliferation.