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Scope: This study aims to identify the gut enterotypes that explain differential responses to intervention with whole grain rye by proposing an “enterotype - metabolic” model.

Methods and results: A 12-week randomized controlled trial is conducted in Chinese adults, with 79 subjects consuming whole grain products with fermented rye bran (FRB) and 77 consuming refined wheat products in this exploratory post-hoc analysis. Responders or non-responders are identified according to whether blood glucose decreased by more than 10% after rye intervention. Compared to non-responders, responders in FRB have higher baseline Bacteroides (p < 0.001), associated with reduced blood glucose (p < 0.001), increased Faecalibacterium (p = 0.020) and Erysipelotrichaceae_UCG.003 (p = 0.022), as well as deceased 7β-hydroxysteroid dehydrogenase (p = 0.033) after intervention. The differentiated gut microbiota and metabolites between responders and non-responders after intervention are enriched in aminoacyl-tRNA biosynthesis.

Conclusion: The work confirms the previously suggested importance of microbial enterotypes in differential responses to whole grain interventions and supports taking enterotypes into consideration for improved efficacy of whole grain intervention for preventing type 2 diabetes. Altered short-chain fatty acids and bile acid metabolism might be a potential mediator for the beneficial effects of whole grain rye on glucose metabolism.