Project description:The study will target a population at high risk for colorectal cancer, overweight and obese participants with a history of a colon polyp in the past 3 years to test whether a high-legume, high-fiber diet will simultaneously increase weight loss and suppress intestinal biomarkers of cancer risk compared to a control diet (healthy American). In addition, it will explore potential mechanisms through which the high-legume intervention diet facilitates weight loss and intestinal health.
Project description:Despite accepted health benefits of dietary fiber, little is known about the mechanisms by which fiber deprivation impacts the gut microbiota and alters disease risk. Using a gnotobiotic model, in which mice were colonized with a synthetic human gut microbiota, we elucidated the functional interactions between dietary fiber, the gut microbiota and the colonic mucus barrier, which serves as a primary defence against pathogens. We show that during chronic or intermittent dietary fiber deficiency, the gut microbiota resorts to host-secreted mucus glycoproteins as a nutrient source, leading to erosion of the colonic mucus barrier. Dietary fiber deprivation promoted greater epithelial access and lethal colitis by the mucosal pathogen, Citrobacter rodentium, but only in the presence of a fiber-deprived microbiota that is pushed to degrade the mucus layer. Our work reveals intricate pathways linking diet, gut microbiome and intestinal barrier dysfunction, which could be exploited to improve health using dietary therapeutics. Germ-free mice (Swiss Webster) were colonized with synthetic human gut microbiota comprising of 14 species belonging to five different phyla (names of bacterial species: Bacteroides thetaiotaomicron, Bacteroides ovatus, Bacteroides caccae, Bacteroides uniformis, Barnesiella intestinihominis, Eubacterium rectale, Marvinbryantia formatexigens, Collinsella aerofaciens, Escherichia coli HS, Clostridium symbiosum, Desulfovibrio piger, Akkermansia muciniphila, Faecalibacterium prausnitzii and Roseburia intestinalis). These mice were fed either a fiber-rich diet or a fiber-free diet for about 6 weeks. The mice were then sacrificed and their cecal tissues were immediately flash frozen for RNA extraction. The extracted RNA was subjected to microarray analysis based on Mouse Gene ST 2.1 strips using the Affy Plus kit. Expression values for each gene were calculated using robust multi-array average (RMA) method.
Project description:A diet rich in dietary fiber and polyphenols supports the normal intestinal barrier function crucial for intestinal and overall health. Birch wood-derived fiber containing glucuronoxylans (GX)- and polyphenols have the potential in multiple food technological applications and have favorable effects on gut microbiota and colonic metabolism. However, their impact on intestinal barrier function is unknown. To elucidate their potential as new intestinal health-supporting food ingredients, we investigated the effect of GX- and polyphenol-rich extract (GXpoly ) and highly purified GX-rich extract (pureGX) on the gene expression of the colon mucosa.
Project description:Abstract: Our intake of ultra-processed foods has dramatically increased over the past few decades in line with the prevalence of obesity and diabetes, key risk factors for microvascular diseases such as chronic kidney disease (CKD). The extent to which long-term intake of highly processed food influences CKD outcome is unclear. Here, we show in rodent models that a highly processed diet drives intestinal barrier permeability and an increased risk of CKD. Inhibition of the advanced glycation pathway, which generates Maillard reaction products within foods upon thermal processing, reversed kidney injury. Consequently, a highly processed diet leads to innate immune complement activation and local kidney inflammation via the potent proinflammatory effector molecule complement 5a (C5a). C5a receptor inhibition ameliorated albuminuria. In a mouse model of diabetes, a high resistant starch fiber diet led to a redistribution of the gut commensal consortium, prevented impaired gut barrier function and decreased the severity of kidney injury via suppression of complement. These results provide mechanistic insight into the role of highly processed foods on inflammation and chronic disease risk. One Sentence Summary: Ultra-processed diets promote chronic kidney disease
Project description:Here we have shown that diet-mediated alterations of the gut microbiota composition cause an erosion of the colonic mucus barrier. A compensatory increase in cellular mucus production by the host is not sufficient to re-establish the barrier, possibly due to a lacking increase in mucus secretion. While microbial transplant from mice fed a fiber-rich diet can prevent the mucus defects, the mechanism seems to be independent of general fiber fermentation and rather depend on distinct bacterial species and/or their metabolites.
Project description:This clinical trial tests whether daily fiber supplementation will change the mucosal microbiome of the colon. The microbiome are microorganisms that live in the human gut. They serve a vital role in maintaining health. Certain microbial strains are associated with the growth of colon polyps, which eventually could go on to form colon cancer. Giving dietary fiber supplements may help prevent precancerous polyps from ever developing.