Dataset Information

Obesity-Linked Gut Microbiome Dysbiosis Associated with Derangements in Gut Permeability and Intestinal Cellular Homeostasis Independent of Diet.

ABSTRACT: This study aimed to determine the association between non-high-fat diet-induced obesity- (non-DIO-) associated gut microbiome dysbiosis with gut abnormalities like cellular turnover of intestinal cells, tight junctions, and mucin formation that can impact gut permeability. We used leptin-deficient (Lepob/ob) mice in comparison to C57BL/6J control mice, which are fed on identical diets, and performed comparative and correlative analyses of gut microbiome composition, gut permeability, intestinal structural changes, tight junction-mucin formation, cellular turnover, and stemness genes. We found that obesity impacted cellular turnover of the intestine with increased cell death and cell survival/proliferation gene expression with enhanced stemness, which are associated with increased intestinal permeability, changes in villi/crypt length, and decreased expression of tight junctions and mucus synthesis genes along with dysbiotic gut microbiome signature. Obesity-induced gut microbiome dysbiosis is also associated with abnormal intestinal organoid formation characterized with decreased budding and higher stemness. Results suggest that non-DIO-associated gut microbiome dysbiosis is associated with changes in the intestinal cell death versus cell proliferation homeostasis and functions to control tight junctions and mucous synthesis-regulating gut permeability.

SUBMITTER: Nagpal R

PROVIDER: S-EPMC6140100 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Obesity-Linked Gut Microbiome Dysbiosis Associated with Derangements in Gut Permeability and Intestinal Cellular Homeostasis Independent of Diet.

Nagpal Ravinder R Newman Tiffany M TM Wang Shaohua S Jain Shalini S Lovato James F JF Yadav Hariom H

Journal of diabetes research 20180903

This study aimed to determine the association between non-high-fat diet-induced obesity- (non-DIO-) associated gut microbiome dysbiosis with gut abnormalities like cellular turnover of intestinal cells, tight junctions, and mucin formation that can impact gut permeability. We used leptin-deficient (Lep<sup>ob/ob</sup>) mice in comparison to C57BL/6J control mice, which are fed on identical diets, and performed comparative and correlative analyses of gut microbiome composition, gut permeability, ...[more]

PMID: 30250849

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Project description:A causal correlation between the metabolic disorders associated with sugar intake and disruption of the gastrointestinal (GI) homeostasis has been suggested, but the underlying mechanisms remain unclear. To unravel these mechanisms, we investigated the effect of physiological amounts of fructose and glucose on barrier functions and inflammatory status in various regions of the GI tract and on the cecal microbiota composition. C57BL/6 mice were fed chow diet and given 15% glucose or 15% fructose in drinking water for 9 weeks. We monitored caloric intake, body weight, glucose intolerance, and adiposity. The intestinal paracellular permeability, cytokine, and tight junction protein expression were assessed in the jejunum, cecum, and colon. In the cecum, the microbiota composition was determined. Glucose-fed mice developed a marked increase in total adiposity, glucose intolerance, and paracellular permeability in the jejunum and cecum while fructose absorption did not affect any of these parameters. Fructose-fed mice displayed increased circulation levels of IL6. In the cecum, both glucose and fructose intake were associated with an increase in Il13, Ifnγ, and Tnfα mRNA and MLCK protein levels. To clarify the relationships between monosaccharides and barrier function, we measured the permeability of Caco-2 cell monolayers in response to IFNγ+TNFα in the presence of glucose or fructose. In vitro, IFNγ+TNFα-induced intestinal permeability increase was less pronounced in response to fructose than glucose. Mice treated with glucose showed an enrichment of Lachnospiracae and Desulfovibrionaceae while the fructose increased relative abundance of Lactobacillaceae. Correlations between pro-inflammatory cytokine gene expression and bacterial abundance highlighted the potential role of members of Desulfovibrio and Lachnospiraceae NK4A136 group genera in the inflammation observed in response to glucose intake. The increase in intestinal inflammation and circulating levels of IL6 in response to fructose was observed in the absence of intestinal permeability modification, suggesting that the intestinal permeability alteration does not precede the onset of metabolic outcome (low-grade inflammation, hyperglycemia) associated with chronic fructose consumption. The data also highlight the deleterious effects of glucose on gut barrier function along the GI tract and suggest that Desulfovibrionaceae and Lachnospiraceae play a key role in the onset of GI inflammation in response to glucose.

Dataset Information

Obesity-Linked Gut Microbiome Dysbiosis Associated with Derangements in Gut Permeability and Intestinal Cellular Homeostasis Independent of Diet.

Publications

Obesity-Linked Gut Microbiome Dysbiosis Associated with Derangements in Gut Permeability and Intestinal Cellular Homeostasis Independent of Diet.

Similar Datasets

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