Distinct gut metagenomics and metaproteomics signatures in prediabetics and treatment-naïve type 2 diabetics

Abstract

BackgroundThe gut microbiota plays important roles in modulating host metabolism. Previous studies have demonstrated differences in the gut microbiome of T2D and prediabetic individuals compared to healthy individuals, with distinct disease-related microbial profiles being reported in groups of different age and ethnicity. However, confounding factors such as anti-diabetic medication hamper identification of the gut microbial changes in disease development.MethodWe used a combination of in-depth metagenomics and metaproteomics analyses of faecal samples from treatment-naïve type 2 diabetic (TN-T2D, n=77), pre-diabetic (Pre-DM, n=80), and normal glucose tolerant (NGT, n=97) individuals to investigate compositional and functional changes of the gut microbiota and the faecal content of microbial and host proteins in Pre-DM and treatment-naïve T2D individuals to elucidate possible host-microbial interplays characterising different disease stages.FindingsWe observed distinct differences characterizing the gut microbiota of these three groups and validated several key features in an independent TN-T2D cohort. We also demonstrated that the content of several human antimicrobial peptides and pancreatic enzymes differed in faecal samples between three groups, such as reduced faecal level of antimicrobial peptides and pancreatic enzymes in TN-T2D.InterpretationOur findings suggest a complex, disease stage-dependent interplay between the gut microbiota and the host and emphasize the value of metaproteomics to gain further insight into interplays between the gut microbiota and the host.FundingNational Key Research and Development Program of China, No. 2017YFC0909703, Shenzhen Municipal Government of China, No. JCYJ20170817145809215, and National Natural Science Foundation of China, No. 31601073.

Geographic differences in gut microbiota composition impact susceptibility to enteric infection

“…Overall, this study highlights the need to expand microbiome studies to account for the greater diversity in microbiome compositions globally not only in cohort-based studies (Mejía-Leó n et al, 2014;Monaco et al, 2016;Subramanian et al, 2014;Zhong et al, 2019) but also in gnotobiotic animal experiments, which serve as a predominant tool for examining causal linkages between the microbiome and disease. On one hand, these studies may reveal population-level differences that can contribute to our understanding of the mechanisms by which the microbiome affects immunity and disease and which may contribute to geographic differences in incidence.…”

“…However, these studies have primarily involved human subjects from high-income and upper-middleincome nations across North America, Europe, and Asia (Almeida et al, 2019;Brewster et al, 2019;Gupta et al, 2017;Magne et al, 2016;Nayfach et al, 2019;Olesen et al, 2020;Pasolli et al, 2019;Porras and Brito, 2019). In spite of the growing appreciation for the large-scale differences in the composition of microbiomes throughout the world (Almeida et al, 2019;Brito et al, 2016;De Filippo et al, 2010;He et al, 2018;Lin et al, 2013;Martínez et al, 2015;Nayfach et al, 2019;Pasolli et al, 2019;Yatsunenko et al, 2012;Zhong et al, 2019), studies causally linking the microbiome to health and disease outcomes have not broadly considered the global diversity of human gut microbiomes. This unexplored diversity in the composition of the gut microbiome can have important consequences for immunological function in the host (Sonnenburg and Sonnenburg, 2019).…”