Connecting the Dots Between Inflammatory Bowel Disease and Metabolic Syndrome: A Focus on Gut-Derived Metabolites

Andrea Verdugo-Meza, Jiayu Ye, Hansika Dadlani, Sanjoy Ghosh, Deanna L Gibson, Andrea Verdugo-Meza, Jiayu Ye, Hansika Dadlani, Sanjoy Ghosh, Deanna L Gibson

Abstract

The role of the microbiome in health and disease has gained considerable attention and shed light on the etiology of complex diseases like inflammatory bowel disease (IBD) and metabolic syndrome (MetS). Since the microorganisms inhabiting the gut can confer either protective or harmful signals, understanding the functional network between the gut microbes and the host provides a comprehensive picture of health and disease status. In IBD, disruption of the gut barrier enhances microbe infiltration into the submucosae, which enhances the probability that gut-derived metabolites are translocated from the gut to the liver and pancreas. Considering inflammation and the gut microbiome can trigger intestinal barrier dysfunction, risk factors of metabolic diseases such as insulin resistance may have common roots with IBD. In this review, we focus on the overlap between IBD and MetS, and we explore the role of common metabolites in each disease in an attempt to connect a common origin, the gut microbiome and derived metabolites that affect the gut, liver and pancreas.

Keywords: gut microbiome; immunometabolism; inflammatory bowel disease; insulin resistance; metabolism; microbiomics.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The host–microbial metabolites interplay in health and chronic inflammatory disorders. Gut microbes produce metabolites that act either at local tissue or remotely in the liver and pancreas (A). In inflammatory bowel disease (IBD), damage to intestinal permeability is associated with changes in microbiota composition (dysbiosis). Consequently, this disrupts the homeostasis of microbial-derived metabolites, leading to increased inflammatory potential locally and systematically (B). Ultimately, protective metabolites (SCFA, SBA and indoles) are decreased, whereas pre-disorder metabolites such as BCAA are increased. This further disrupts the energy metabolism by impairing the insulin signaling pathway and accumulating fat droplets in the liver, as a result of developing hepatic (NAFLD) and pancreatic disorders (AP, T1D and T2D). The production of two energy regulating hormones, GLP-1 and PYY, is triggered by the secretion of SCFA (butyrate). With decreased SCFA in disease state, production of GLP-1 and PYY is also limited, therefore worsening the disrupted energy metabolism. AP: acute pancreatitis; BA: bile acid; BCAA: branched-chain amino acid; GLP-1: glucagon-like peptide 1; NAFLD: non-alcoholic fatty liver disease; ROS: reactive oxygen species; PYY: peptide YY; SBA: secondary bile acid; SCFA: short-chain fatty acids; T1D: type 1 diabetes; T2D: type 2 diabetes.

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