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Dietary bioactives increase gut microbiome diversity and alter host and microbial metabolite profiles

Duncan, A.; Bernuzzi, F.; Ahn-Jarvis, J.; Zhang, L.; Segovia-Lizano, D.; Petrou, M.; Bedarf, J. R.; Ng, D.; Savva, G. M.; Stanstrup, J.; Dragsted, L. O.; Traka, M.; Hildebrand, F.

2025-10-17 nutrition
10.1101/2025.10.16.25338140 medRxiv
Show abstract

ObjectiveDietary bioactives have been associated with positive health effects such as cardiovascular health, or having anti-diabetic properties. Many bioactive compounds survive digestion arriving in the colon, where the gut microbiome can further metabolise them to forms more available to the host. Previous work has shown diets such as the Mediterranean diet, enriched in plant bioactives, affecting the composition and diversity of the gut microbiome. However, it is unclear which factors in such whole diet interventions underlie these changes, such as the bioactives themselves, the percentage of dietary fibres or macronutrient composition. In the Dietary BIoactives and Microbiome DivErsity (DIME) study we investigated the impact of a diet rich in a wide range of plant bioactives compared to a low bioactive diet with matched total fibre intake. DesignWe conducted a randomised crossover intervention trial to assess alterations to the gut microbiome, urinary and faecal metabolites in 20 healthy subjects receiving two-week high- or low-bioactive diets, separated by a 4-week washout period. Macronutrient and total fibre content was carefully matched between diets. ResultsAlpha diversity of both microbial taxa and function increased in the high bioactive diet. Microbiome compositions between participants appear more similar after the high bioactive diet than low, suggesting that the high bioactive diet selected for bacteria with a similar functional spectrum. Both faecal and urinary metabolites were strongly impacted by the diet intervention, including o-coumaric acid, theobromine, and secondary bile acids. Metabolite profiles were more strongly associated to the dietary intervention arms than microbiome profiles, suggesting that a diet high in bioactives may change the activity of the existing community despite only small shifts in community composition. ConclusionHigh intake of dietary bioactives leads to significant changes in both microbial and host metabolite profiles. However, the shift in microbiome composition was substantially less pronounced, highlighting the need of future studies to investigate metabolic activities instead of taxonomic compositions.

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