Call It a Gut Feeling

Call It a Gut Feeling

By: Cassidy Myhre

Autoimmune diseases are characterized by irregular autoantibody production, causing abnormal generation of autoantibody-producing B cells and autoreactive T cells, due to both genetic predisposition and environmental factors. It has been hypothesized that the increasing incidence of autoimmune diseases, including type 1 diabetes (T1D), is due to imbalances in the gut microbiota among other multifactorial reasons.

The association between gut microbiota imbalance and autoimmune diseases may be due to several mechanisms possibly impacting the human immune system and function, such as:

  • The modulation of the host immune response and activation of antigen-presenting cells (APCs), including dendritic cells (DCs), which may evoke antigen presentation and cytokine production, subsequently affecting T cell differentiation and function. 
  • The disruption of the homeostasis between T helper 17 (Th17) cells and T regulatory cells (Tregs). 
  • The similarities between foreign antigens and self-antigens that activate pathogen-derived autoreactive T and B cells, thus promoting autoimmunity.

In the past decade, growing evidence has suggested that gut dysbiosis may be a major contributor to T1D development. Based on a systematic review using 16S rRNA gene sequencing on the intestinal microflora profile in patients with T1D compared to healthy subjects, research showed that:

  • The altered intestinal microbiota impacts T1D pathogenesis by increasing gut permeability, facilitating intestinal inflammation and disturbing immunological maturation.
  • T1D patients show reduced microbiota richness and diversity when compared with that of healthy controls.
  • There is a notable reduction in the ratio of Firmicutes/Bacteroidetes (F/B) in T1D patients compared with healthy controls.
  • Levels of inflammatory interleukin-6 (IL-6) were significantly higher in the plasma of T1D patients than in that of controls.  

Gut dysbiosis has also been presumed to lead to alterations in circulating Mucosal-associated invariant T (MAIT) cells, which have previously been reported in patients with T1D. Analysis of MAIT cell alterations in individuals at different stages of T1D progression found:

  • The frequency of MAIT cells was decreased in AAb+ at-risk children who later progressed to T1D and in adult patients with a short duration of T1D. 
  • Decreased expression of CD27 and production of IFN-γ have also been reported by others in patients with T1D. 
  • The decrease in the expression of the homing receptors CCR5 and β7 integrin could be due to increased trafficking to inflamed tissues in children with T1D, causing a proportional decrease in MAIT cells expressing these markers in the circulation. 

The discovery of the causative relationship between the gut microbiota and T1D, as well as the linking of gut microbiota dysbiosis with autoimmune mechanisms, will provide significant clinical assistance in identifying future effective approaches in the  prevention of autoimmune diseases.

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