Research Papers

Summary:

Nutrition has powerfully widespread effects on physiological processes, yet its influence on human immunity remains largely elusive. This study investigated the effects of dietary interventions on both immunity and the microbiota through an analysis of clinical trials involving 20 participants who followed vegan or ketogenic diets for 2 weeks. The authors evaluated the impact of each diet on host immunity and the microbiota. Our findings revealed that a ketogenic diet significantly upregulated pathways and enriched cells associated with the adaptive immune system, while a vegan diet notably impacted the innate immune system, particularly enhancing pathways related to anti-viral immunity. Both diets also distinctly affected the microbiome, with the ketogenic diet notably reducing microbial functions and pathways compared to baseline and the vegan diet. Overall, the study underscores the significant and divergent impact of short-term dietary interventions on host immunity, highlighting the potential for precision nutritional interventions.

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Abstract:

Nutrition has broad impacts on all physiological processes. However, how nutrition affects human immunity remains largely unknown. Here we explored the impact of a dietary intervention on both immunity and the microbiota by performing a post hoc analysis of a clinical trial in which each of the 20 participants sequentially consumed vegan or ketogenic diets for 2 weeks (NCT03878108). Using a multiomics approach including multidimensional flow cytometry, transcriptomic, proteomic, metabolomic and metagenomic datasets, we assessed the impact of each diet, and dietary switch, on host immunity and the microbiota. Our data revealed that overall, a ketogenic diet was associated with a significant upregulation of pathways and enrichment in cells associated with the adaptive immune system. In contrast, a vegan diet had a significant impact on the innate immune system, including upregulation of pathways associated with antiviral immunity. Both diets significantly and differentially impacted the microbiome and host-associated amino acid metabolism, with a strong downregulation of most microbial pathways following ketogenic diet compared with baseline and vegan diet. Despite the diversity of participants, we also observed a tightly connected network between datasets driven by compounds associated with amino acids, lipids and the immune system. Collectively, this work demonstrates that in diverse participants 2 weeks of controlled dietary intervention is sufficient to significantly and divergently impact host immunity, which could have implications for precision nutritional interventions. ClinicalTrials.gov registration: NCT03878108.

Article Publication Date: 30/01/2024
DOI: 10.1038/s41591-023-02761-2