Diabetes Mellitus and Increased Tuberculosis Susceptibility: The Role of Short-Chain Fatty Acids

Abstract

Type 2 diabetes mellitus confers a threefold increased risk for tuberculosis, but the underlying immunological mechanisms are still largely unknown. Possible mediators of this increased susceptibility are short-chain fatty acids, levels of which have been shown to be altered in individuals with diabetes. We examined the influence of physiological concentrations of butyrate on cytokine responses to Mycobacterium tuberculosis (Mtb) in human peripheral blood mononuclear cells (PBMCs). Butyrate decreased Mtb-induced proinflammatory cytokine responses, while it increased production of IL-10. This anti-inflammatory effect was independent of butyrate's well-characterised inhibition of HDAC activity and was not accompanied by changes in Toll-like receptor signalling pathways, the eicosanoid pathway, or cellular metabolism. In contrast blocking IL-10 activity reversed the effects of butyrate on Mtb-induced inflammation. Alteration of the gut microbiota, thereby increasing butyrate concentrations, can reduce insulin resistance and obesity, but further studies are needed to determine how this affects susceptibility to tuberculosis.

The role of the lung microbiota and the gut-lung axis in respiratory infectious diseases

“…Two recent studies have shown that the short chain fatty acid (SCFA) butyrate modulates the production of M. tuberculosis-induced pro-and anti-inflammatory cytokines in the lungs, associated with an increased susceptibility to M. tuberculosis (Lachmandas et al, 2016;Segal et al, 2017). Two recent studies have shown that the short chain fatty acid (SCFA) butyrate modulates the production of M. tuberculosis-induced pro-and anti-inflammatory cytokines in the lungs, associated with an increased susceptibility to M. tuberculosis (Lachmandas et al, 2016;Segal et al, 2017).…”

Diabetes Mellitus as Hub for Tuberculosis Infection: A Snapshot

“…Gliptins, a new agent for the treatment of type 2 DM also known as DPP-4 inhibitors (inhibitors of dipeptidyl peptidase 4), control the glucagon release and stimulate the release of insulin which lowers the blood glucose level [45]. Therefore, the dose of insulin should be modified while prescribing these drugs to patients [46]. Furthermore, till now how to standardize the control of glucose level in people who are suffering from both TB and DM is not clear.…”

Diabetes and tuberculosis: An important relationship

“…The unique characteristics of diabetes, with overnutrition leading to insulin resistance and inflammation, coupled with the unique mechanism of M. tuberculosis infection involving abnormality of macrophage function may suggest novel approaches to TB treatment. Aspects of the dysmetabolism of diabetes increasing susceptibility to TB may be important, and efforts to better characterize relationships between TB and glycemia, dyslipidemia, hypercoagulability, inflammation, and insulin resistance could be fruitful. The recent suggestion that metformin may be beneficial for TB control by reducing deleterious inflammation and enhancing antimycobacterial activity of immune cells is of interest .…”