An ongoing US prospective cohort study suggests that lactase (LCT) genotype may modify the relationship between milk intake and risk of type 2 diabetes (T2D), with higher milk intake associated with lower risk of T2D only in lactase non-persistent (LNP) individuals but not in lactase persistence (LP) individuals. The study included 16,415 Hispanic/Latino adults of diverse backgrounds. In both sexes, higher milk intake is associated with lower risk of T2D in LNP individuals (determined by a variant of the LCT gene, single nucleotide polymorphism rs4988235) but not in LP individuals. The finding is validated in a larger UK cohort. Further analyses reveal a potential mechanism among LNP individuals, higher milk intake is associated with alterations in gut microbiota (for example, enriched Bifidobacterium and reduced Prevotella) and circulating metabolites (for example, increased indolepropionate and reduced branched-chain amino acid metabolites). Many of these metabolites are related to the identified milk-associated bacteria and partially mediate the association between milk intake and T2D in LNP individuals. The findings may help explain the previously observed population difference in the relationship between milk intake and risk of T2D. The Hispanic/Latino population has relatively balanced distribution of LNP and LP individuals, while other populations either have the predominance of LP individuals (European ancestry) or LNP individuals (East Asians). Source: https://www.nature.com/