The contribution of gut bacterial metabolites in the human immune signaling pathway of non-communicable diseases.

ABSTRACT

The interaction disorder between gut microbiota and its host has been documented in different non-communicable diseases (NCDs) such as metabolic syndrome, neurodegenerative disease, and autoimmune disease. The majority of these altered interactions arise through metabolic cross-talk between gut microbiota and host immune system, inducing a low-grade chronic inflammation that characterizes all NCDs. In this review, we discuss the contribution of bacterial metabolites to immune signaling pathways involved in NCDs. We then review recent advances that aid to rationally design microbial therapeutics. A deeper understanding of these intersections between host and gut microbiota metabolism using metabolomics-based system biology platform promises to reveal the fundamental mechanisms that drive metabolic predispositions to disease and suggest new avenues to use microbial therapeutic opportunities for NCDs treatment and prevention. Abbreviations NCDs non-communicable disease, IBD inflammatory bowel disease, IL interleukin, T2D type 2 diabetes, SCFAs short-chain fatty acids, HDAC histone deacetylases, GPCR G-protein coupled receptors, 5-HT 5-hydroxytryptamine receptor signaling, DCs dendritic cells, IECs intestinal epithelial cells, T-reg T regulatory cell, NF-κB nuclear factor κB, TNF-α tumor necrosis factor alpha, Th T helper cell, CNS central nervous system, ECs enterochromaffin cells, NSAIDs non-steroidal anti-inflammatory drugs, AhR aryl hydrocarbon receptor, IDO indoleamine 2,3-dioxygenase, QUIN quinolinic acid, PC phosphatidylcholine, TMA trimethylamine, TMAO trimethylamine N-oxide, CVD cardiovascular disease, NASH nonalcoholic steatohepatitis, BAs bile acids, FXR farnesoid X receptor, CDCA chenodeoxycholic acid, DCA deoxycholic acid, LCA lithocholic acid, UDCA ursodeoxycholic acid, CB cannabinoid receptor, COBRA constraint-based reconstruction and analysis.