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

Study information

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study design

randomized controlled trial

Citation

PMID PubMed identifier for scientific articles.

38291301

DOI Digital object identifier for electronic documents.

10.1038/s41591-023-02761-2

URI

https://pubmed.ncbi.nlm.nih.gov/38291301/

Authors

Link VM, Subramanian P, Cheung F, Han KL, Stacy A, Chi L, Sellers BA, Koroleva G, Courville AB, Mistry S, Burns A, Apps R, Hall KD, Belkaid Y

Journal

Nature medicine

Year

2024

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 .

Experiment 1

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Reviewed Marked as Reviewed by Svetlana up on 2024-7-30

Curated date: 2024/03/10

Curator: Johnpaul

Revision editor(s): Johnpaul, Aleru Divine, WikiWorks

Subjects

Location of subjects: United States of America

Host species Species from which microbiome was sampled. Contact us to have more species added.: Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Diet Dietary,Diets,Diet,diet

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Participants on vegan diet

Group 1 name Corresponds to the case (exposed) group for case-control studies: Participants on ketogenic diet

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: To determine the impact of dietary intervention on human immunity and microbiota, this group of participants were placed on a ketogenic diet, and would later be switched to a vegan diet.

Group 0 sample size Number of subjects in the control (unexposed) group: 10

Group 1 sample size Number of subjects in the case (exposed) group: 10

Lab analysis

Sequencing type: WMS

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: Not specified

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: centered log-ratio

Statistical test: MaAsLin2

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: Yes

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: unchanged

Chao1 Abundance-based estimator of species richness: unchanged

Signature 1

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Curator: Johnpaul

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Source: Fig. 4e

Description: Differentially abundant species between ketogenic and vegan diets for all significant taxa, showing the impact of a ketogenic diet on participants compared to a vegan diet.

Abundance in Group 1: increased abundance in Participants on ketogenic diet

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Bilophila wadsworthia
Butyricimonas faecihominis
Butyricimonas virosa
Dielma fastidiosa
Enterocloster bolteae
Enterocloster citroniae
Eubacterium ramulus
Lactococcus lactis
Neobittarella massiliensis (ex Bilen et al. 2018)
Odoribacter splanchnicus
Phascolarctobacterium faecium
Phocaeicola sartorii
Phocaeicola vulgatus
[Eubacterium] sulci

Revision editor(s): WikiWorks, Scholastica, Aleru Divine, Johnpaul

Signature 2

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Curated date: 2024/03/10

Curator: Johnpaul

Revision editor(s): WikiWorks, Scholastica, Aleru Divine, Johnpaul

Source: Fig. 4e

Description: Differentially abundant species between ketogenic and vegan diets for all significant taxa, showing the impact of a ketogenic diet on participants compared to a vegan diet.

Abundance in Group 1: decreased abundance in Participants on ketogenic diet

NCBI	Quality Control	Links
Agathobacter rectalis
Agathobaculum butyriciproducens
Anaerofustis stercorihominis
Anaerostipes hadrus
Bacillota bacterium
Bifidobacterium breve
Bifidobacterium catenulatum
Bifidobacterium longum
Bifidobacterium pseudocatenulatum
Blautia massiliensis (ex Durand et al. 2017)
Butyricicoccus sp.
Eubacterium sp.
Eubacterium ventriosum
Fusicatenibacter saccharivorans
Intestinibacter bartlettii
Lachnospiraceae bacterium
Roseburia faecis
Ruminococcus bromii
Ruminococcus sp.
Subdoligranulum sp.
Catonella morbi
Blautia sp.

Revision editor(s): WikiWorks, Scholastica, Aleru Divine, Johnpaul