Project description:Background & Aims: Non-alcoholic fatty liver disease (NALFLD)-associated changes in gut microbiota are important drivers of disease progression toward fibrosis. Therefore, reversing microbiota alterations could ameliorate NAFLD progression. Oat beta-glucan, a non-digestible polysaccharides, has shown promising therapeutic effects on hyperlipidemia associated with NAFLD, but its impact on gut microbiota and most importantly NAFLD fibrosis remains unknown. Methods: We performed detailed metabolic phenotyping including body composition, glucose tolerance, and lipid metabolism as well as comprehensive characterization of the gut-liver axis in a western-style diet (WSD)-induced model of NAFLD and assessed the effect of a beta-glucan intervention on early and advanced liver disease. Gut microbiota was modulated using broad-spectrum antibiotic (Abx) treatment. Results: Oat beta-glucan supplementation did not affect WSD-induced body weight gain, glucose intolerance, and the metabolic phenotype remained largely unaffected. Interestingly, oat beta-glucan dampened NAFLD inflammation, associated with significantly reduced monocyte-derived macrophages (MoMFs) infiltration, fibroinflammatory gene expression, and strongly reduced fibrosis development. Mechanistically, this protective effect was not mediated by changes in bile acid composition or signaling, but was dependent on gut microbiota and was lost upon Abx treatment. Specifically, oat beta-glucan partially reversed unfavorable changes in gut microbiota, resulting in an expansion of protective taxa, including Ruminococcus, and Lactobacillus followed by reduced translocation of TLR ligands. Conclusions: Our findings identify oat beta-glucan as a highly efficacious food supplement that dampens inflammation and fibrosis development in diet-induced NAFLD. These results, along with its favorable dietary profile, suggest that it may be a cost-effective and well-tolerated approach to preventing NAFLD progression and should be assessed in clinical studies.
Project description:We established a bacteria infective intestinal inflammation in turbot (Scophthalmus maximus). And found that β-glucan could significantly alleviate the phenotype of turbot intestinal inflammation. We performed single cell transcriptome analysis to study bacteria infective intestinal inflammation and the effects of β-glucan. Furthermore, we revealed that β-glucan through activates Th17 cells to alleviate intestinal inflammation in turbot.
Project description:To evaluate the DC genome-wide gene expression in response to beta-glucan and its regulation by IL-1 receptor antagonist (IL-1RA) we used a whole genome microarray. The gene expression profiling was performed in DC left untreated or exposed to beta-glucan for 4 and 12 h, in absence or presence of IL-1RA. This strategy allowed the identification of early/immediate and late/secondary genes regulated by beta-glucan in an IL-1-dependent and -independent manner. Human monocyte-derived DC were obtained by a 6/7-d cultures of freshly isolated monocytes with recombinant human IL-4 (10 ng/ml) and GM-CSF (50 ng/ml). Beta-glucan-associated gene expression and its regulation by IL-1RA in human DC was measured in cells left untreated or at 4 and 12 h after exposure to 10 ug/ml of particulate beta-glucan in absence or presence of 2.5 ug/ml of IL-1RA. Five different conditions (Untreated 0h, beta-glucan 4h, IL-1RA + beta-glucan 4h, beta-glucan 12h, and IL-1RA + beta-glucan 12h) were tested using DC from three different donors.
Project description:Irritable Bowel Syndrome (IBS) is a disorder of the gut-brain axis, characterized by altered gut function and frequent psychiatric co-morbidity. Although altered intestinal microbiome profiles have been documented, their relevance to the clinical expression of IBS is unknown. To evaluate a functional role of the microbiota, we colonized germ-free mice with fecal microbiota from healthy controls or IBS patients with accompanying anxiety, and monitored gut function and behavior. Mouse microbiota profiles clustered according to their human donors. Despite having taxonomically similar composition as controls, mice with IBS microbiota had distinct serum metabolomic profiles related to neuro- and immunomodulation. Mice with IBS, but not control microbiota, exhibited faster gastrointestinal transit, intestinal barrier dysfunction, innate immune activation and anxiety-like behavior. These results support the notion that the microbiota contributes to both intestinal and behavioral manifestations of IBS and rationalize the use of microbiota-directed therapies in ameliorating IBS.
Project description:A clone encoding carboxymethylcellulase activity was isolated during functional screening of a human gut metagenomic library using Lactococcus lactis MG1363 as heterologous host. The insert sequence revealed a glycoside hydrolase family 9 (GH9) catalytic domain with sequence similarity to a gene from Coprococcus sp. ART55/1, which is closely related to Coprocococcus eutactus. Surveys of available genomes indicated a limited distribution of GH9 domains among dominant human colonic anaerobes. Genomes of two Coprococcus-related strains showed the presence of two GH9-encoding and four GH5-encoding genes, however, the strains did not appear to be able to degrade cellulose. Instead, they grew well on beta-glucans and one of the strains also showed growth on galactomannan, galactan and glucomannan. Gene expression and proteomic analysis of Coprococcus sp. ART55/1 grown on cellobiose, beta-glucan and lichenan led to a similar change in expression in comparison to glucose. On beta-glucan and lichenan only, one of the four GH5 genes was strongly upregulated. Growth on glucomannan lead to a transcriptional response of many genes, in particular a strong upregulation of glycoside hydrolases involved in mannan degradation. Thus, beta-glucans are a major growth substrate for species related to Coprococcus eutactus, with glucomannan and galactans alternative substrates for some strains.
Project description:The gut bacterium Coprococcus sp. ART55/1 has been found to encode two genes containing glycoside hydrolase family 9 (GH9) catalytic domains. These genes are hypothesised to impact upon the ability of this bacteria to utilise different carbon sources. To further investigate the role of these genes, as well as the wider transcriptome, Coprococcus sp. ART55/1 was grown on five different carbon sources - beta-glucan, lichenan, cellobiose, glucose and glucomannan - and the transcriptional response was investigated using RNA sequencing.
Project description:The increased consumption of various beverages has been paralleled by an epidemic of several intestinal diseases around the world, such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and colorectal cancer. Mounting evidence have shown that excessive consumption of beverages increases the risk of IBD and IBS. In addition, sugar-sweeter, food additives and food ingredients were identified to play important roles in these conditions. Consuming cold beverage is common among some people, especially in the youngsters. However, whether the cold stress contribute directly to host metabolism, gut barrier and gut-brain axis is unclear. In an intestinal function disorder model induced by cold water in mice, we investigated changes in gut transit, anxiety and depression like behavior. To evaluate the effect of cold water on gut barrier, we investigate the tight junctions in the colon. In addition, we employed RNA sequencing transcriptomic analysis to identify genes potentially driving the gut injury, and in parallel, examine the gut microbiota and metabolites in the feces.In an intestinal function disorder model induced by cold water in mice, we investigated changes in gut transit, anxiety and depression like behavior. To evaluate the effect of cold water on gut barrier, we investigate the tight junctions in the colon. In addition, we employed RNA sequencing transcriptomic analysis to identify genes potentially driving the gut injury, and in parallel, examine the gut microbiota and metabolites in the feces.
Project description:Chronic acid suppression by proton pump inhibitor (PPI) has been hypothesized to alter the gut microbiota via a change in intestinal pH. To evaluate the changes in gut microbiota composition by long-term PPI treatment. Twenty-four week old F344 rats were fed with (n = 5) or without (n = 6) lansoprazole (PPI) for 50 weeks. Then, profiles of luminal microbiota in the terminal ileum were analyzed. Pyrosequencing for 16S rRNA gene was performed by genome sequencer FLX (454 Life Sciences/Roche) and analyzed by metagenomic bioinformatics.