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The antibiotic resistance crisis underlies globally increasing failures in treating deadly bacterial infections, largely due to the selection of antibiotic resistance genes (ARG) collection, known as the resistome, in human gut microbiota. So far, little is known about the relationship between gut antibiotic resistome and host metabolic disorders such as type 2 diabetes (T2D). Here, metagenomic landscape of gut antibiotic resistome is profiled in a large multiomics human cohort (n = 1210). There is a significant overall shift in gut antibiotic resistome structure among healthy, prediabetes, and T2D groups. It is found that larger ARG diversity is associated with a higher risk of T2D. The novel diabetes ARG score is positively associated with glycemic traits. Longitudinal validation analysis confirms that the ARG score is associated with T2D progression, characterized by the change of insulin resistance. Collectively, the data describe the profiles of gut antibiotic resistome and support its close relationship with T2D progression. [ABSTRACT FROM AUTHOR]

Objective: To identify the core gut microbial features associated with type 2 diabetes risk and potential demographic, adiposity, and dietary factors associated with these features.Research Design and Methods: We used an interpretable machine learning framework to identify the type 2 diabetes-related gut microbiome features in the cross-sectional analyses of three Chinese cohorts: one discovery cohort (n = 1,832, 270 cases of type 2 diabetes) and two validation cohorts (cohort 1: n = 203, 48 cases; cohort 2: n = 7,009, 608 cases). We constructed a microbiome risk score (MRS) with the identified features. We examined the prospective association of the MRS with glucose increment in 249 participants without type 2 diabetes and assessed the correlation between the MRS and host blood metabolites (n = 1,016). We transferred human fecal samples with different MRS levels to germ-free mice to confirm the MRS-type 2 diabetes relationship. We then examined the prospective association of demographic, adiposity, and dietary factors with the MRS (n = 1,832).Results: The MRS (including 14 microbial features) consistently associated with type 2 diabetes, with risk ratio for per 1-unit change in MRS 1.28 (95% CI 1.23-1.33), 1.23 (1.13-1.34), and 1.12 (1.06-1.18) across three cohorts. The MRS was positively associated with future glucose increment (P < 0.05) and was correlated with a variety of gut microbiota-derived blood metabolites. Animal study further confirmed the MRS-type 2 diabetes relationship. Body fat distribution was found to be a key factor modulating the gut microbiome-type 2 diabetes relationship.Conclusions: Our results reveal a core set of gut microbiome features associated with type 2 diabetes risk and future glucose increment. [ABSTRACT FROM AUTHOR]

Objective: To examine the association of erythrocyte n-6 polyunsaturated fatty acid (PUFA) biomarkers with incident type 2 diabetes and explore the potential role of gut microbiota in the association.Research Design and Methods: We evaluated 2,731 participants without type 2 diabetes recruited between 2008 and 2013 in the Guangzhou Nutrition and Health Study (Guangzhou, China). Case subjects with type 2 diabetes were identified with clinical and biochemical information collected at follow-up visits. Using stool samples collected during the follow-up in the subset (n = 1,591), 16S rRNA profiling was conducted. Using multivariable-adjusted Poisson or linear regression, we examined associations of erythrocyte n-6 PUFA biomarkers with incident type 2 diabetes and diversity and composition of gut microbiota.Results: Over 6.2 years of follow-up, 276 case subjects with type 2 diabetes were identified (risk 0.10). Higher levels of erythrocyte γ-linolenic acid (GLA), but not linoleic or arachidonic acid, were associated with higher type 2 diabetes incidence. Comparing the top to the bottom quartile groups of GLA levels, relative risk was 1.72 (95% CI 1.21, 2.44) adjusted for potential confounders. Baseline GLA was inversely associated with gut microbial richness and diversity (α-diversity, both P < 0.05) during follow-up and significantly associated with microbiota β-diversity (P = 0.002). α-Diversity acted as a potential mediator in the association between GLA and type 2 diabetes (P < 0.05). Seven genera (Butyrivibrio, Blautia, Oscillospira, Odoribacter, S24-7 other, Rikenellaceae other, and Clostridiales other) were enriched in quartile 1 of GLA and in participants without type 2 diabetes.Conclusions: Relative concentrations of erythrocyte GLA were positively associated with incident type 2 diabetes in a Chinese population and also with gut microbial profiles. These results highlight that gut microbiota may play an important role linking n-6 PUFA metabolism and type 2 diabetes etiology. [ABSTRACT FROM AUTHOR]