Differential peripheral immune signatures elicited by vegan versus ketogenic diets in humans.

"microbiome sequencing data are available through bioproject accession prjna981159 . the study protocol was approved by the institutional review board of the national institute of diabetes and digestive and kidney diseases ( nct03878108 ) and is available on the open science framework website ( https://osf io/fjykq/ )."

"enrichment was assessed with a gene-set list that included msigdb's hallmark collection ( https://www gsea-msigdb org/gsea/msigdb/human/collections jsp ) and btms ( https://github com/shuzhao-li/btm )."

"Competing interests The authors declare no competing interests."

"We thank all study participants who volunteered to participate in this demanding study protocol, as well as the nursing and nutrition staff at the NIH MCRU for their assistance. We thank A. Mukherjee for sample processing. We thank P. Loke, N. Collins, M. Enamorado and A. Wells for comments and discussions. Parts of Figs. 1a, 3b and 6d were created with BioRender.com. This research was supported in part by the Intramural Research Program of NIAID and federal funds from NIAID under BCBB Support Services Contract HHSN316201300006W/75N93022F00001 to Guidehouse, Inc."

"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."