Sleeve gastrectomy decreases high-fat diet induced colonic pro-inflammatory status through the gut microbiota alterations

Abstract

BackgroundHigh-fat diet (HFD) induced obesity is characterized with chronic low-grade inflammation in various tissues and organs among which colon is the first to display pro-inflammatory features associated with alterations of the gut microbiota. Sleeve gastrectomy (SG) is currently one of the most effective treatments for obesity. Although studies reveal that SG results in decreased levels of inflammation in multiple tissues such as liver and adipose tissues, the effects of surgery on obesity related pro-inflammatory status in the colon and its relation to the microbial changes remain unknown.MethodsTo determine the effects of SG on the colonic pro-inflammatory condition and the gut microbiota, SG was performed on HFD-induced obese mice. To probe the causal relationship between alterations of the gut microbiota and improvements of pro-inflammatory status in the colon following SG, we applied broad-spectrum antibiotics cocktails on mice that received SG to disturb the gut microbial changes. The pro-inflammatory shifts in the colon were assessed based on morphology, macrophage infiltration and expressions of a variety of cytokine genes and tight junction protein genes. The gut microbiota alterations were analyzed using 16s rRNA sequencing. RNA sequencing of colon was conducted to further explore the role of the gut microbiota in amelioration of colonic pro-inflammation following SG at a transcriptional level.ResultsAlthough SG did not lead to pronounced changes of colonic morphology and macrophage infiltration in the colon, there were significant decreases in the expressions of several pro-inflammatory cytokines including interleukin-1β (IL-1β), IL-6, IL-18, and IL-23 as well as increased expressions of some tight junction proteins in the colon following SG, suggesting an improvement of pro-inflammatory status. This was accompanied by changing populations of the gut microbiota such as increased richness of Lactobacillus subspecies following SG. Importantly, oral administrations of broad-spectrum antibiotics to delete most intestinal bacteria abrogated surgical effects to relieve colonic pro-inflammation. This was further confirmed by transcriptional analysis of colon indicating that SG regulated inflammation related pathways in a manner that was gut microbiota relevant.ConclusionThese results support that SG decreases obesity related colonic pro-inflammatory status through the gut microbial alterations.

The relationship between AGR2 levels and intestinal barrier function in high-fat diet animal models

“…The characteristic of HFD-induced obesity is the chronic micro-inflammatory state of various tissues and organs. The colon is the first tissue organ to exhibit pro-inflammatory characteristics associated with changes in the gut microbiota (7). Therefore, the degree of damage to the colonic IBF is one of the indicators that clinical at-tention must be paid.…”

Whey Protein Hydrolysate Exerts Anti-Inflammatory Effects to Alleviate Dextran Sodium Sulfate (DSS)-Induced Colitis via Microbiome Restoration

“…This is consistent with the results of the present study in which the Model group of mice suffered from the most severe colitis and had the highest expression levels of pro-inflammatory factors. The overexpression of pro-inflammatory factors can damage the intestinal epithelial barrier, leading to increased intestinal permeability, which in turn causes the transfer of some intestinal bacteria and intestinal dysfunction [27]. Thus, we hypothesized that WPH intervention could protect the intestinal barrier by inhibiting the elevated levels of pro-inflammatory factors, which could play a role in maintaining the balance of the gut microbiome.…”