Diet, gut microbiota and histidine metabolism toward imidazole propionate production in relation to type 2 diabetes

OBJECTIVE: To examine associations of serum imidazole propionate (ImP), histidine and their ratio with incident type 2 diabetes (T2D) and related dietary and gut microbial factors in US Hispanics/Latinos.

RESEARCH DESIGN AND METHODS: In the Hispanic Community Health Study/Study of Latinos, we evaluated serum ImP, histidine and ImP-to-histidine ratio at baseline (2008-2011) and their cross-sectional associations with dietary intake and prospective associations with incident T2D over ~12 years (n=4632). In a subsample with gut microbiota data during a follow-up visit (2016-2018), we examined gut microbial species associated with serum ImP and their potential interactions with dietary intake.

RESULTS: Serum ImP and ImP-to-histidine ratio were positively associated with incident T2D (Hazard ratio=1.17 [95% CI:1.00-1.36] and 1.33 [1.14-1.55], respectively, comparing highest to lowest tertile), while histidine was inversely associated with incident T2D (Hazard ratio=0.75 [0.64-0.86]). Higher fiber intake was associated with lower serum ImP and ImP-to-histidine ratio, while histidine intake was not associated with serum ImP in overall sample. Fifty-three bacterial species, including 19 putative ImP-producers, were associated with serum ImP. Histidine intake was positively associated with serum ImP and ImP-to-histidine ratio only in participants with a high ImP-associated gut microbiota score (Pinteraction=0.03 and 0.02, respectively). The associations of fiber intake with serum ImP and ImP-to-histidine ratio were partly mediated by ImP-associated gut microbiota (proportion mediated=31.4% and 19.8%, respectively).

CONCLUSIONS: This study suggested an unfavorable relationship between histidine metabolism toward ImP production, potentially regulated by dietary intake and gut microbiota, and risk of T2D in US Hispanics/Latinos.