Project description:Short-chain fatty acids (SCFAs) are metabolic products produced during the microbial fermentation of non-digestible fibers and play an important role in metabolic homeostasis and overall gut health. In this study, we investigated the effects of supplementation with multispecies probiotics (MSPs) containing Bacillus amyloliquefaciens, Limosilactobacillus reuteri, and Levilactobacillus brevis on the gut microbiota, and fecal SCFAs and lactate levels of weaned pigs. A total of 38 pigs weaned at 4 weeks of age were fed either a basal diet or a diet supplemented with MSPs for 6 weeks. MSP administration significantly increased the fecal concentrations of lactate (2.3-fold; p < 0.01), acetate (1.8-fold; p < 0.05), and formate (1.4-fold; p < 0.05). Moreover, MSP supplementation altered the gut microbiota of the pigs by significantly increasing the population of potentially beneficial bacteria such as Olsenella, Catonella, Catenibacterium, Acidaminococcus, and Ruminococcaceae. MSP supplementation also decreased the abundance of pathogenic bacteria such as Escherichia and Chlamydia. The modulation of the gut microbiota was observed to be strongly correlated with the changes in fecal SCFAs and lactate levels. Furthermore, we found changes in the functional pathways present within the gut, which supports our findings that MSP modulates the gut microbiota and SCFAs levels in pigs. The results support the potential use of MSPs to improve the gut health of animals by modulating SCFAs production.
Project description:Following birth, the neonatal intestine is exposed to maternal and environmental bacteria that successively form a dense and highly dynamic intestinal microbiota. Whereas the effect of exogenous factors has been extensively investigated, endogenous, host-mediated mechanisms have remained largely unexplored. Concomitantly with microbial colonization, the liver undergoes functional transition from a hematopoietic organ to a central organ of metabolic regulation and immune surveillance. The aim of the present study was to analyze the influence of the developing hepatic function and liver metabolism on the early intestinal microbiota. Here, we report on the characterization of the colonization dynamics and liver metabolism in the murine gastrointestinal tract (n = 6-10 per age group) using metabolomic and microbial profiling in combination with multivariate analysis. We observed major age-dependent microbial and metabolic changes and identified bile acids as potent drivers of the early intestinal microbiota maturation. Consistently, oral administration of tauro-cholic acid or β-tauro-murocholic acid to newborn mice (n = 7-14 per group) accelerated postnatal microbiota maturation.
Project description:Accumulating evidence suggests that the bile acid regulates type 2 diabetes mellitus (T2DM) through gut microbiota-host interactions. However, the mechanisms underlying such interactions have been unclear. Here, we found that glycoursodeoxycholic acid (GUDCA) positively regulates gut microbiota by altering bile acid metabolism. GUDCA in mice resulted in higher taurolithocholic acid (TLCA) level and Bacteroides vulgatus abundance. Together, these changes resulted in the activation of the adipose G-protein-coupled bile acid receptor, GPBAR1 (TGR5) and upregulated expression of uncoupling protein UCP-1, resulting in elevation of white adipose tissue thermogenesis. The anti-T2DM effects of GUDCA are linked with the regulation of the bile acid and gut microbiota composition. This study suggests that altering bile acid metabolism, modifying the gut microbiota may be of value for the treatment of T2DM.
Project description:ObjectiveTo examine the role of hepatocyte myeloid differentiation primary-response gene 88 (MyD88) on glucose and lipid metabolism.DesignTo study the impact of the innate immune system at the level of the hepatocyte and metabolism, we generated mice harbouring hepatocyte-specific deletion of MyD88. We investigated the impact of the deletion on metabolism by feeding mice with a normal control diet or a high-fat diet for 8 weeks. We evaluated body weight, fat mass gain (using time-domain nuclear magnetic resonance), glucose metabolism and energy homeostasis (using metabolic chambers). We performed microarrays and quantitative PCRs in the liver. In addition, we investigated the gut microbiota composition, bile acid profile and both liver and plasma metabolome. We analysed the expression pattern of genes in the liver of obese humans developing non-alcoholic steatohepatitis (NASH).ResultsHepatocyte-specific deletion of MyD88 predisposes to glucose intolerance, inflammation and hepatic insulin resistance independently of body weight and adiposity. These phenotypic differences were partially attributed to differences in gene expression, transcriptional factor activity (ie, peroxisome proliferator activator receptor-α, farnesoid X receptor (FXR), liver X receptors and STAT3) and bile acid profiles involved in glucose, lipid metabolism and inflammation. In addition to these alterations, the genetic deletion of MyD88 in hepatocytes changes the gut microbiota composition and their metabolomes, resembling those observed during diet-induced obesity. Finally, obese humans with NASH displayed a decreased expression of different cytochromes P450 involved in bioactive lipid synthesis.ConclusionsOur study identifies a new link between innate immunity and hepatic synthesis of bile acids and bioactive lipids. This dialogue appears to be involved in the susceptibility to alterations associated with obesity such as type 2 diabetes and NASH, both in mice and humans.
Project description:Bariatric surgery is the only procedure to obtain and maintain weight loss in the long term, although the mechanisms driving these benefits are not completely understood. In the last years, gut microbiota has emerged as one of the drivers through its metabolites, especially secondary bile acids. In the current study, we have compared the gut microbiota and the bile acid pool, as well as anthropometric and biochemical parameters, of patient with morbid obesity who underwent bariatric surgery by two different techniques, namely Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). Gut microbiota populations differed after the respective procedures, particularly with respect to the Enterobacteriaceae family. Both techniques resulted in changes in the bile acids pool, but RYGB was the procedure which suffered the greatest changes, with a reduction in most of their levels. Blautia and Veillonella were the two genera that more relationships showed with secondary bile acids, indicating a possible role in their formation and inhibition, respectively. Correlations with the anthropometric and biochemical variables showed that secondary bile acids could have a role in the amelioration of the glucose and HDL-cholesterol levels. Thus, we have observed a possible relationship between the interaction of the bile acids pool metabolized by the gut microbiota in the metabolic improvements obtained by bariatric surgery in the frame of morbid obesity, deserving further investigation in greater cohorts to decipher the role of each bile acid in the homeostasis of the host for their possible use in the development of microbiota-based therapeutics, such as new drugs, postbiotics or probiotics.
Project description:Comprehensive thermal proteomic analyses was conducted to unravel and comprehend the protein targets affected by microbiota-derived bile acids in AD.
Project description:Bile acids are critical for lipid absorption, however, their new roles in maintaining or regulating systemic metabolism are irreplaceable. The negative impacts of heat stress (HS) on growth performance, lipid metabolism, and antioxidant status have been reported, but it remains unknown whether the bile acids (BA) composition of broiler chickens can be affected by HS. Therefore, this study aimed to investigate the modulating effects of the environment (HS) and whether dietary BA supplementation can benefit heat-stressed broiler chickens. A total of 216 Arbor Acres broilers were selected with a bodyweight approach average and treated with thermal neutral (TN), HS (32°C), or HS-BA (200 mg/kg BA supplementation) from 21 to 42 days. The results showed that an increase in average daily gain (P < 0.05) while GSH-Px activities (P < 0.05) in both serum and liver were restored to the normal range were observed in the HS-BA group. HS caused a drop in the primary BA (P = 0.084, 38.46%) and Tauro-conjugated BA (33.49%) in the ileum, meanwhile, the secondary BA in the liver and cecum were lower by 36.88 and 39.45% respectively. Notably, results were consistent that SBA levels were significantly increased in the serum (3-fold, P = 0.0003) and the ileum (24.89-fold, P < 0.0001). Among them, TUDCA levels (P < 0.01) were included. Besides, BA supplementation indeed increased significantly TUDCA (P = 0.0154) and THDCA (P = 0.0003) levels in the liver, while ileal TDCA (P = 0.0307), TLCA (P = 0.0453), HDCA (P = 0.0018), and THDCA (P = 0.0002) levels were also increased. Intestinal morphology of ileum was observed by hematoxylin and eosin (H&E) staining, birds fed with BA supplementation reduced (P = 0.0431) crypt depth, and the ratio of villous height to crypt depth trended higher (P = 0.0539) under the heat exposure. Quantitative RT-PCR showed that dietary supplementation with BA resulted in upregulation of FXR (P = 0.0369), ASBT (P = 0.0154), and Keap-1 (P = 0.0104) while downregulation of iNOS (P = 0.0399) expression in ileum. Moreover, 16S rRNA gene sequencing analysis and relevance networks revealed that HS-derived changes in gut microbiota and BA metabolites of broilers may affect their resistance to HS. Thus, BA supplementation can benefit broiler chickens during high ambient temperatures, serving as a new nutritional strategy against heat stress.
Project description:BackgroundAs the gut microbiota contributes to metabolic health, it is important to determine specific diet-microbiota interactions that influence host metabolism. Bile acids and dietary fat source can alter phenotypes of diet-induced obesity, but the interplay with intestinal microorganisms is unclear. Here, we investigated metabolic consequences of diets enriched in primary bile acids with or without addition of lard or palm oil, and studied gut microbiota structure and functions in mice.ResultsIn combination with bile acids, dietary lard fed to male C57BL/6N mice for a period of 8 weeks enhanced fat mass accumulation in colonized, but not in germ-free mice when compared to palm oil. This was associated with impaired glucose tolerance, lower fasting insulin levels, lower counts of enteroendocrine cells, fatty liver, and elevated amounts of hepatic triglycerides, cholesteryl esters, and monounsaturated fatty acids. Lard- and bile acid-fed mice were characterized by shifts in dominant gut bacterial communities, including decreased relative abundances of Lachnospiraceae and increased occurrence of Desulfovibrionaceae and the species Clostridium lactatifermentans and Flintibacter butyricus. Metatranscriptomic analysis revealed shifts in microbial functions, including lipid and amino acid metabolism.ConclusionsCaution is required when interpreting data from diet-induced obesity models due to varying effects of dietary fat source. Detrimental metabolic consequences of a diet enriched with lard and primary bile acids were dependent on microbial colonization of the host and were linked to hepatic lipid rearrangements and to alterations of dominant bacterial communities in the cecum.
Project description:Bacteria from the Turicibacter genus are prominent members of the mammalian gut microbiota and correlate with alterations in dietary fat and body weight, but the specific connections between these symbionts and host physiology are poorly understood. To address this knowledge gap, we characterize a diverse set of mouse- and human-derived Turicibacter isolates, and find they group into clades that differ in their transformations of specific bile acids. We identify Turicibacter bile salt hydrolases that confer strain-specific differences in bile deconjugation. Using male and female gnotobiotic mice, we find colonization with individual Turicibacter strains leads to changes in host bile acid profiles, generally aligning with those produced in vitro. Further, colonizing mice with another bacterium exogenously expressing bile-modifying genes from Turicibacter strains decreases serum cholesterol, triglycerides, and adipose tissue mass. This identifies genes that enable Turicibacter strains to modify host bile acids and lipid metabolism, and positions Turicibacter bacteria as modulators of host fat biology.
Project description:Inflammatory bowel disease (IBD) and colorectal cancer (CRC) are heterogeneous intestinal diseases that threaten the health of an increasing number of individuals as their lifestyles become westernized. New insights have been discovered with the development of various omics techniques, revealing that gut-microbiota-derived metabolites play important roles in maintaining intestinal homeostasis and modulating the progression of intestinal diseases from both metabolic and immunological perspectives. Clinical metagenomic and metabolomic studies have revealed links between microbial bile acid (BA) metabolism and IBD and CRC progression. Several BA-derived metabolites were recently been demonstrated to play a role in intestinal immunity, providing fresh insights into how BAs affect the course of IBD and CRC. In this review, we discuss recent studies on the involvement of gut microbiota-derived BAs in intestinal immunity, inflammation, and tumorigenesis along with human omics data to provide prospective insights into future prevention and treatment of IBD and CRC.