Impact of Diabetes on the Gut and Salivary IgA Microbiomes

Abstract

Mucosal surfaces like those present in the lung, gut, and mouth interface with distinct external environments. These mucosal gateways are not only portals of entry for potential pathogens but homes to microbial communities that impact host health. Secretory immunoglobulin A (SIgA) is the single most abundant acquired immune component secreted into mucosal surfaces and via the process of immune exclusion, shapes the architecture of these microbiomes. Not all microorganisms at mucosal surfaces are targeted by SIgA, therefore a better understanding of the SIgA-coated fraction may identify the microbial constituents that stimulate host immune responses in the context of health and disease. Chronic diseases like type 2 diabetes are associated with altered microbial communities (dysbiosis) that in turn affect immune-mediated homeostasis. 16S rDNA sequencing of SIgA-coated/uncoated bacteria (IgA-Biome) was conducted on stool and saliva samples of normoglycemic participants and individuals with prediabetes or diabetes (n=8/group). These analyses demonstrated shifts in relative abundance in the IgA-Biome profiles between normoglycemic, prediabetic, or diabetic samples distinct from that of the overall microbiome. Differences in IgA-Biome alpha diversity were apparent for both stool and saliva, while overarching bacterial community differences (beta diversity) were also observed in saliva. These data suggest that IgA-Biome analyses can be used to identify novel microbial signatures associated with diabetes and support the need for further studies exploring these communities. Ultimately, an understanding of the IgA-Biome may promote development of novel strategies to restructure the microbiome as a means of preventing or treating diseases associated with dysbiosis at mucosal surfaces.

Microbiome in Blood Samples From the General Population Recruited in the MARK-AGE Project: A Pilot Study

“…Increased insulin, a marker for insulin resistance, has been implicated in gut permeability, and impaired fasting glucose subjects show higher markers of gut permeability than controls ( Carnevale et al, 2017 ; Mkumbuzi et al, 2020 ). On the other hand, gut and oral microbiota dysbiosis has been found in type 2 diabetes (DM2) subjects and different microbiome compartmentalization has been observed in DM2 ( Brown et al, 2020 ; Shi et al, 2020 ). Therefore, increased circulating DNA in healthy subjects could also represent a predictor of pre-diabetes or diabetes conditions.…”

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

“…This study was approved by the Institutional Review Board Committee for the Protection of Human Subjects of the University of Texas Health Science Center (HSC-SPH-06-0225), and informed written consent was obtained from each participant. Stool, saliva, and buffy coat samples were collected upon enrollment from an age matched subset of 24 participants, 8 with normal glycemia, 8 with prediabetes, and 8 with diabetes [ 13 ]. Characterization of the gut and salivary IgA-Biomes and demographics of the study participants and were previously published by our group [ 13 ].…”

“…Stool, saliva, and buffy coat samples were collected upon enrollment from an age matched subset of 24 participants, 8 with normal glycemia, 8 with prediabetes, and 8 with diabetes [ 13 ]. Characterization of the gut and salivary IgA-Biomes and demographics of the study participants and were previously published by our group [ 13 ]. Briefly, 16.67% (4/24) of subjects were male and the mean age of participants was 47.75 years (standard deviation (SD) = 5.96).…”

“…We recently conducted a preliminary study of the IgA-Biome, 16Sv4 rDNA profiling of the microbiota based on their SIgA coating, by diabetes status in a group of Mexican American adults [ 13 ]. We observed relative shifts in the SIgA + and SIgA - bacterial communities distinct from that of the overall microbiome [ 13 ], highlighting the unique perspective of IgA-Biome sequencing to identify novel relationships between the gut and salivary microbiota and the immune system in dysglycemia (those with prediabetes and diabetes).…”

“…We recently conducted a preliminary study of the IgA-Biome, 16Sv4 rDNA profiling of the microbiota based on their SIgA coating, by diabetes status in a group of Mexican American adults [ 13 ]. We observed relative shifts in the SIgA + and SIgA - bacterial communities distinct from that of the overall microbiome [ 13 ], highlighting the unique perspective of IgA-Biome sequencing to identify novel relationships between the gut and salivary microbiota and the immune system in dysglycemia (those with prediabetes and diabetes). To better understand the complex dynamic between T-helper cell profiles and SIgA in the gut and saliva in the context of diabetes, we used qPCR to epigenetically quantify T-cell ratios to examine associations between the Th17:Treg axis and the gut/salivary IgA-Biomes across the glycemic spectrum [ 40 , 58 – 61 ].…”