The impact of the Th17:Treg axis on the IgA-Biome across the glycemic spectrum

Abstract

Secretory IgA (SIgA) is released into mucosal surfaces where its function extends beyond that of host defense to include the shaping of resident microbial communities by mediating exclusion/inclusion of respective microbes and regulating bacterial gene expression. In this capacity, SIgA acts as the fulcrum on which host immunity and the health of the microbiota are balanced. We recently completed an analysis of the gut and salivary IgA-Biomes (16S rDNA sequencing of SIgA-coated/uncoated bacteria) in Mexican-American adults that identified IgA-Biome differences across the glycemic spectrum. As Th17:Treg ratio imbalances are associated with gut microbiome dysbiosis and chronic inflammatory conditions such as type 2 diabetes, the present study extends our prior work by examining the impact of Th17:Treg ratios (pro-inflammatory:anti-inflammatory T-cell ratios) and the SIgA response (Th17:Treg-SIgA axis) in shaping microbial communities. Examining the impact of Th17:Treg ratios (determined by epigenetic qPCR lymphocyte subset quantification) on the IgA-Biome across diabetes phenotypes identified a proportional relationship between Th17:Treg ratios and alpha diversity in the stool IgA-Biome of those with dysglycemia, significant changes in community composition of the stool and salivary microbiomes across glycemic profiles, and genera preferentially abundant by T-cell inflammatory phenotype. This is the first study to associate epigenetically quantified Th17:Treg ratios with both the larger and SIgA-fractionated microbiome, assess these associations in the context of a chronic inflammatory disease, and offers a novel frame through which to evaluate mucosal microbiomes in the context of host responses and inflammation.

Unveiling contrasts in microbiota response: A1c control improves dysbiosis in low-A1c T2DM, but fails in high-A1c cases—a key to metabolic memory?

“…However, this perspective is currently undergoing scrutiny, primarily because diversity does not necessarily equate to quality: a more diverse pathobiont-based microbiota does not inherently indicate better health. 10 Such observation could explain other groups data showing higher MB richness in patients with higher A1c. 9 …”

“…Given that dysglycemia substantially shifts the MB balance, highlighted by the Th17:Treg response compared with patients with normal blood sugar levels, 10 and considering the continuous MB spectrum correlated with A1c levels, 9 we hypothesized that intensive glucose-lowering treatment might help reverse the MB’s dysglycemia-influenced immune selection.…”

IgA-Biome Profiles Correlate with Clinical Parkinson’s Disease Subtypes

“…To identify bacterial taxa that discriminate the IgA coated versus uncoated sorting fractions, we used the biomarker discovery tool Linear Discriminant Analysis Effect Size (LEfSe) [23,36,37] (Fig. 7).…”

The gut microbiota pathway mechanisms of diabetes

“…For pregnant women with T1D in the third trimester, lipopolysaccharides producing bacteria are enhanced against short-chain fatty acids producing bacteria (Roth-Schulze et al 2021 ). T2DM patients have an imbalance Th17: Treg ratio, which is correlated with their gut microbiota dysbiosis (Essigmann et al 2021 ). A stable coronary artery disease (SCAD) -type 2 diabetes (SCAD + T2DM) patients have been seen with an increased carbohydrates and aromatic amino acids.…”