(OR24-04-26) The Gut Microbiome Mediates the Association Between Processed Red Meat Consumption and Risk of Type 2 Diabetes: Evidence From a Swedish Prospective Cohort Study

Objectives: Meat intake has been suggested to influence gut microbiome composition and type 2 diabetes (T2D) risk. We aimed to identify gut microbiome features associated with meat intake and to evaluate their potential mediating role in the prospective association between meat intake and incident T2D.

Methods: We analysed shotgun metagenomic sequencing data from 4,169 individuals (mean age 73.9 years; 50.7% women) in a clinical subsample of the Swedish SIMPLER cohort. Intake of white meat, unprocessed red meat, and processed red meat was assessed using a food frequency questionnaire. Multivariable linear regression identified meat-associated microbiome features, which were then tested as mediators of incident T2D using causal mediation analyses within a counterfactual framework (Cox model for outcome; linear regression for mediator). Mediators were further characterised by their associations with clinical metabolic biomarkers. All models were adjusted for demographic, anthropometric, lifestyle, and dietary factors.

Results: Processed red meat was associated with lower α diversity and white meat with higher α diversity. Only processed red meat was associated with 41 microbial species (false discovery rate [FDR] p< 0.05). Four species mediated the association between processed meat intake and incident T2D, reflecting two patterns: two harmful mediators enriched by processed meat and associated with higher T2D risk (R. gnavus, M. glycyrrhizinilyticus), and two protective mediators, including one enriched by processed meat but associated with lower T2D risk (Clostridia unclassified SGB14844) and one depleted by processed meat (GGB3478 SGB4643). Harmful mediators were positively associated with triglycerides levels, whereas protective mediators were inversely associated with glucose levels.

Conclusions: Specific gut microbiome alterations associated with processed red meat intake may partially mediate increased risk of T2D risk. These mediating species and their associations with metabolic biomarkers support the biological link between processed meat consumption, gut microbiome composition, and T2D-related metabolic dysfunction.

Funding Sources: The authors acknowledge financial support from the European Union and the Swiss State Secretariat for Education, Research and Innovation (SERI).