Progressive Shifts in the Gut Microbiome Reflect Prediabetes and Diabetes Development in a Treatment-Naive Mexican Cohort

By Katie E. Golden, MD

Type 2 Diabetes (T2D) is an increasingly common disease in the US and world-wide, and we are still trying to better understand the risk factors and contributors to the development of this multifactorial condition. It is a significant contributor to morbidity and mortality of more than 8% of the world’s population, and is placing a heavy burden on the respective healthcare systems trying to provide for these complicated patients. Scientists and physicians alike have placed increasing emphasis on the role of the microbiome in T2D development, as research across multiple different populations (European, American, and Chinese) has demonstrated an association between the disease and particular microbiome compositions. These studies, however, have  been limited by confounding factors among the study populations, as well as the unknown effect of first-line treatment regimens on intestinal microbes (such as the oral hypoglycemic metformin, as well as lifestyle and dietary changes). In a recently published article,¹ researchers address these limitations by studying a treatment naive cohort in Mexico, and specifically identify four bacterial genera that correlate with clinical markers of T2D pathophysiology after controlling for confounding variables.

The Mexican population has proven a particularly vulnerable population to T2D, and the researchers in this study chose a tightly controlled cohort from a specific region of the country to eliminate some of the varied phenotypes that have limited prior investigations. Their cohort consisted of 405, treatment-naive individuals without prior T2D diagnosis (along with a control group with a previously established diagnosis). The cohort then underwent oral glucose testing and was stratified into 5 metabolic groups, from normal glucose tolerance, to pre-diabetes, to T2D. Each individual was exhaustively analyzed across 226 clinical variables, and their stool samples were subsequently analyzed with genetic sequencing.

The associations between microbiome characteristics (both bacterial genera and relative abundance) and clinical variables of disease were identified through a robust testing strategy of all combinations. Researchers ultimately identified four specific bacterial genera that closely correlated with T2D risk and progression. These bacterial populations, more specifically, correlated with increasing blood glucose levels, beta cell dysfunction, the accumulation of T2D risk factors. When they performed similar stool analysis on their control group, they found that these genera returned to near-normal levels after treatment with metformin. Importantly, these correlations remained strong after tightly controlling for common T2D comorbidities (such as obesity and cardiovascular disease). While there still remain many unanswered questions about the direct causation of microbiome changes and disease development, this study is the first to convincingly establish the relationship between specific bacterial genera and the clinical progression of T2D.

1. Diener C, et al. Progressive shifts in the gut microbiome reflect prediabetes and diabetes development in a treatment-naive Mexican cohort. BioRxiv 710152; doi:  https://doi.org/10.1101/710152