Alterations in gut microbiota characteristics along a type 2 diabetes risk gradient linked with family history.

Type 2 diabetes (T2D) is a major global health issue, with growing evidence linking it to gut microbiome changes. However, whether these alterations precede T2D onset and act as predictors, risk factors, or contributors remains unclear. This study analyzed the gut microbiota of 192 individuals from the French NutriNet-Santé cohort, divided into four groups: non-T2D adults with no (n = 47), one (n = 48), or two (n = 51) T2D-affected parents, and T2D-affected adults (n = 46). A progressive microbiota shift was observed in non-T2D groups based on parental history, converging toward the T2D profile. Changes included altered enterotype distribution, increased oral-associated species, disrupted ecological networks, and a shift in Gram-positive-to-negative ratios. Notably, Prevotella copri abundance increased, alongside bacteria potentially enhancing branched-chain amino acid (BCAA), lipopolysaccharide (LPS), and acetate production. Diet also influenced microbiota patterns, with sweet product intake, vitamin levels, and copper/zinc ratios playing roles. A gradual microbiome transition from non-diabetic to T2D participants underscores its association with family history-based risk. While these shifts may reflect or drive T2D progression, further studies are needed to confirm these findings and explore their potential for preventive strategies.