Host and gut microbial tryptophan metabolism and type 2 diabetes: an integrative analysis of host genetics, diet, gut microbiome and circulating metabolites in cohort studies.

Summary

This integrative analysis of five diverse racial/ethnic cohorts (9,180 participants) examined how host genetics, diet, and gut microbiota influence tryptophan metabolism and type 2 diabetes risk. Higher dietary fibre intake—but not protein or tryptophan intake—was most strongly associated with a favourable tryptophan metabolite profile, with effects partly mediated through fibre-utilising Firmicutes bacteria producing indolepropionate. A novel gene–diet interaction was identified whereby lactase non-persistent individuals who consumed more milk showed higher Bifidobacterium abundance and serum indolepropionate, a protective metabolite.

Regional applicability

The study included diverse racial/ethnic backgrounds across five cohorts, though specific geographic locations are not detailed in the abstract. Findings on fibre intake and gut bacteria associations with tryptophan metabolism and T2D prevention are applicable to United Kingdom populations; the lactase persistence genotype interaction may have particular relevance in UK populations with varying ancestry. UK dietary guidelines on fibre intake align with the protective associations identified.

Key measures

Circulating levels of 11 tryptophan metabolites; incident type 2 diabetes; host genome-wide variants; dietary intake (fibre, protein, tryptophan); gut microbiome composition and abundance; lactase persistence genotype

Outcomes reported

The study examined associations between circulating tryptophan metabolites and incident type 2 diabetes, and identified host genetic variants, dietary factors and gut bacteria associated with these metabolites. Several tryptophan metabolites were positively associated with T2D risk (tryptophan, kynurenine, kynurenate, xanthurenate, quinolinate, indolelactate) whilst indolepropionate was inversely associated with T2D risk.

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