Progressive shifts in the gut microbiome reflect prediabetes and diabetes development in a treatment-naive Mexican cohort

Type 2 diabetes (T2D) is global epidemic that affects more than 8% of the world’s population and is a leading cause of death in Mexico. T2D onset is driven by diet and lifestyle which has led to the question whether the gut microbiome may play a role in disease progression. However, associations between microbiome composition and diabetes are often confounded by secondary effects such as medication, obesity, and diet. Here we present a study on the gut microbiomes of a treatment-naive Mexican cohort of 405 individuals across varying stages of T2D severity. Association tests between the bacterial abundances obtained by 16S amplicon sequencing and more than 200 clinical variables identified a defined set of bacterial genera that were consistent markers of T2D prevalence and risk. These changes in microbial composition were gradual across disease progression, increasing blood glucose levels, beta cell dysfunction, and accumulation of risk factors. Comparison with a previously treated cohort of 25 individuals showed that T2D treatment returned all of the identified bacterial genera to levels of normoglycemic individuals. Our deep clinical characterization allowed us to broadly control for confounding variables, indicating that these microbiome patterns were independent of common T2D comorbidities like obesity or cardiovascular disease. Our characterization of the gut microbiota in a Mexican cohort reaffirms a link between the gut microbiome and type 2 diabetes and gives a first look at this relationship in a critically high-risk population.