Dataset Information

Preventive Role of Salsalate in Diabetes Is Associated With Reducing Intestinal Inflammation Through Improvement of Gut Dysbiosis in ZDF Rats.

ABSTRACT: A safe and effective approach is needed to prevent and reduce the incidence of diabetes worldwide. The hypoglycemic efficacy of salicylic acid (salsalate, SAL), which has anti-inflammatory properties, has been empirically demonstrated in studies conducted at the Joslin Diabetes Center and elsewhere. Here, we investigated the potential role of SAL in preventing the onset of diabetes in Zucker diabetic fatty (ZDF) rats and attempted to elucidate its underlying mechanisms. ZDF and Zucker lean (ZL) rats were administered a high-fat diet with or without SAL intervention, and their relative rates of diabetes were compared. Our results showed that all rats in the placebo group developed diabetes, whereas only 10% of the SAL-treated rats presented with impaired glucose tolerance (IGT). None of the latter progressed to diabetes. Relative to the untreated rats, SAL lowered plasma glucagon and insulin while improving insulin sensitivity and ?-cell function. SAL may protect against hyperglycemia by increasing the microbial diversity, ameliorating gut dysbiosis, restoring intestinal epithelial cell connections, inhibiting endotoxin influx into the blood, and attenuating inflammation. Together, these findings suggest that SAL may be a candidate prophylactic therapy against diabetes. The protective role of SAL may be attributed to its ability to reduce intestinal inflammation and improve gut dysbiosis.

SUBMITTER: Zhang X

PROVIDER: S-EPMC7096544 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Preventive Role of Salsalate in Diabetes Is Associated With Reducing Intestinal Inflammation Through Improvement of Gut Dysbiosis in ZDF Rats.

Zhang Xinrong X Cui Xiao X Jin Xiaofang X Han Fei F Wang Jingyu J Yang Xiaoyun X Xu Jie J Shan Chunyan C Gao Zhongai Z Li Xiaochen X Zuo Minxia M Yang Juhong J Chang Baocheng B

Frontiers in pharmacology 20200319

A safe and effective approach is needed to prevent and reduce the incidence of diabetes worldwide. The hypoglycemic efficacy of salicylic acid (salsalate, SAL), which has anti-inflammatory properties, has been empirically demonstrated in studies conducted at the Joslin Diabetes Center and elsewhere. Here, we investigated the potential role of SAL in preventing the onset of diabetes in Zucker diabetic fatty (ZDF) rats and attempted to elucidate its underlying mechanisms. ZDF and Zucker lean (ZL) ...[more]

PMID: 32265702

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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.

Project description:Lung inflammation induced by Mycoplasma hyorhinis infection accounts for significant economic losses in the swine industry. Increasing evidence suggests that there is cross talk between the lungs and the gut, but little is known about the effect of the lung inflammation caused by M. hyorhinis infection on gut microbiota and intestinal barrier function. Here, we investigated changes in the fecal microbiotas of pigs with M. hyorhinis infection and the microbial regulatory role of such infection in intestinal barrier function. We infected pigs with M. hyorhinis and performed 16S rRNA gene sequencing analyses of fecal samples, data-independent acquisition (DIA) quantitative proteomic analyses of intestinal mucosa, and analyses of barrier dysfunction indicators in serum. We found that pigs with M. hyorhinis infection exhibit lung and systemic inflammation, as reflected by the histopathological changes and activation of the TLR4/MyD88/NF-κB p65 signaling pathway in lung tissue, as well as the increased concentrations of serum inflammatory cytokines. Gut microbiotas tended to become disturbed, as evidenced by the enrichment of opportunistic pathogens. The increased diamine oxidase activities and d-lactate concentrations in serum and the decreased relative mRNA expression of Occludin, ZO-1, and Mucin2 indicated the impairment of intestinal barrier function. Quantitative proteomic analyses showed a variety of altered proteins involved in immunomodulatory and inflammatory functions. There was a positive correlation between the abundance of opportunistic pathogens and inflammatory-cytokine concentrations, as well as intestinal immunomodulatory proteins. Our results suggest that lung inflammation induced by M. hyorhinis infection can contribute to the dysbiosis of gut microbiota and intestinal barrier dysfunction, and dysbiosis of gut microbiota was associated with systemic inflammation and intestinal immune status. IMPORTANCE Cumulative evidence suggests that bacterial pneumonia may contribute to the dysbiosis of the gut microbiota and other gastrointestinal symptoms. Our experiment has demonstrated that lung inflammation induced by M. hyorhinis infection was associated with gut microbiota dysbiosis and intestinal barrier dysfunction, which may provide a theoretical basis for exploring the gut-lung axis based on M. hyorhinis infection.

Dataset Information

Preventive Role of Salsalate in Diabetes Is Associated With Reducing Intestinal Inflammation Through Improvement of Gut Dysbiosis in ZDF Rats.

Publications

Preventive Role of Salsalate in Diabetes Is Associated With Reducing Intestinal Inflammation Through Improvement of Gut Dysbiosis in ZDF Rats.

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