Center for Infectious Disease, Division of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas Health Science Center, Houston, TX, United States of America.
Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, United States of America.
PLoS One. 2021 Oct 20;16(10):e0258812. doi: 10.1371/journal.pone.0258812. eCollection 2021.
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.
分泌型免疫球蛋白 A（SIgA）被释放到黏膜表面，其功能不仅局限于宿主防御，还包括通过调节特定微生物的排除/纳入和调节细菌基因表达来塑造常驻微生物群落。在这种情况下，SIgA 充当了宿主免疫和微生物组健康平衡的支点。我们最近完成了对墨西哥裔美国成年人肠道和唾液 IgA 生物群（SIgA 包被/未包被细菌的 16S rDNA 测序）的分析，该分析确定了整个血糖谱中 IgA 生物群的差异。由于 Th17:Treg 比值失衡与肠道微生物群失调和慢性炎症性疾病（如 2 型糖尿病）有关，本研究通过检查 Th17:Treg 比值（促炎：抗炎 T 细胞比值）和 SIgA 反应（Th17:Treg-SIgA 轴）对微生物群落的影响，扩展了我们之前的工作。检查 Th17:Treg 比值（通过表观遗传 qPCR 淋巴细胞亚群定量确定）对糖尿病表型中 IgA 生物群的影响，确定了 Th17:Treg 比值与粪便 IgA 生物群中多样性的比例关系，在血糖谱中，粪便和唾液微生物群的群落组成发生了显著变化，并且根据 T 细胞炎症表型优先丰富了某些属。这是第一项将表观遗传定量的 Th17:Treg 比值与更大的和 SIgA 分离的微生物组相关联的研究，在慢性炎症性疾病的背景下评估这些关联，并提供了一个通过宿主反应和炎症来评估黏膜微生物组的新框架。
