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Crosstalk between Microbiota-Derived Short-Chain Fatty Acids and Intestinal Epithelial HIF Augments Tissue Barrier Function.

ABSTRACT: Interactions between the microbiota and distal gut are fundamental determinants of human health. Such interactions are concentrated at the colonic mucosa and provide energy for the host epithelium through the production of the short-chain fatty acid butyrate. We sought to determine the role of epithelial butyrate metabolism in establishing the austere oxygenation profile of the distal gut. Bacteria-derived butyrate affects epithelial O2 consumption and results in stabilization of hypoxia-inducible factor (HIF), a transcription factor coordinating barrier protection. Antibiotic-mediated depletion of the microbiota reduces colonic butyrate and HIF expression, both of which are restored by butyrate supplementation. Additionally, germ-free mice exhibit diminished retention of O2-sensitive dyes and decreased stabilized HIF. Furthermore, the influences of butyrate are lost in cells lacking HIF, thus linking butyrate metabolism to stabilized HIF and barrier function. This work highlights a mechanism where host-microbe interactions augment barrier function in the distal gut.

SUBMITTER: Kelly CJ

PROVIDER: S-EPMC4433427 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Project description:The gut microbiota play an important role in the growth and intestinal health of broilers. The present study was to investigate the gut microbiota, short-chain fatty acids, and intestinal morphology of broilers at different ages. A total of 320 one-day-old male broilers were raised in 8 replicates and fed the same corn-soybean diets for 42 D. The duodenal, jejunal, and ileal segments and their and cecal microbiota were collected on day 1, 7, 14, 21, and 42, respectively. The villous height (VH), crypt depth (CD), and their ratio of VH:CD in the duodenum, jejunum, and ileum all increased (P < 0.05) with age. Caecal acetate, propionate, butyrate, valerate, and isovalerate increased (P < 0.01), but isobutyrate decreased (P < 0.001) with age. The cecum had the greatest (P < 0.001) alpha diversity of bacterial community in broilers at different ages. Beta diversities showed distinct differences in gut microbial compositions among different ages (R = 0.55, P < 0.002) and different intestinal segments (R = 0.53, P < 0.002). Lactobacillus was the most abundant genus in the duodenum (36∼97%), jejunum (39∼72%), and ileum (24∼96%) at all ages, and in the ileum, it was positively correlated with VH (R = 0.559, P < 0.03), VH:CD (R = 0.55, P < 0.03), and acetate contents (R = 0.541, P < 0.04) but negatively correlated (R = -0.50, P < 0.05) with isobutyrate contents. Escherichia-Shigella and Salmonella dominated in the cecum of newly hatched broilers, and then the Bacteroides dominated in the cecum on day 42. In the cecum, Escherichia-Shigella was positively correlated (R = 0.577∼0.662, P < 0.05) with isobutyrate contents and Salmonella negatively correlated (R = -0.539∼-0.843, P < 0.05) with isovalerate, butyrate, and acetate contents. These aforementioned results indicated that the most abundant Lactobacillus from the small intestine and the most diversity of microflora community and short-chain fatty acids in the cecum might contribute to the development of intestinal structure in the whole growing period of broilers.

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Crosstalk between Microbiota-Derived Short-Chain Fatty Acids and Intestinal Epithelial HIF Augments Tissue Barrier Function.

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