Ketogenic Diets Alter the Gut Microbiome Resulting in Decreased Intestinal Th17 Cells

Study information

Edit History Delete Add a new Experiment

incomplete

study design

Citation

PMID PubMed identifier for scientific articles.

32437658

DOI Digital object identifier for electronic documents.

10.1016/j.cell.2020.04.027

URI

Authors

Ang QY, Alexander M, Newman JC, Tian Y, Cai J, Upadhyay V, Turnbaugh JA, Verdin E, Hall KD, Leibel RL, Ravussin E, Rosenbaum M, Patterson AD, Turnbaugh PJ

Journal

Cell

Year

2020

Keywords:

Th17 cells, adipose tissue, bifidobacteria, intestinal immunity, ketogenic diet, ketone bodies, ketone ester, microbiome, β-hydroxybutyrate

Very low-carbohydrate, high-fat ketogenic diets (KDs) induce a pronounced shift in metabolic fuel utilization that elevates circulating ketone bodies; however, the consequences of these compounds for host-microbiome interactions remain unknown. Here, we show that KDs alter the human and mouse gut microbiota in a manner distinct from high-fat diets (HFDs). Metagenomic and metabolomic analyses of stool samples from an 8-week inpatient study revealed marked shifts in gut microbial community structure and function during the KD. Gradient diet experiments in mice confirmed the unique impact of KDs relative to HFDs with a reproducible depletion of bifidobacteria. In vitro and in vivo experiments showed that ketone bodies selectively inhibited bifidobacterial growth. Finally, mono-colonizations and human microbiome transplantations into germ-free mice revealed that the KD-associated gut microbiota reduces the levels of intestinal pro-inflammatory Th17 cells. Together, these results highlight the importance of trans-kingdom chemical dialogs for mediating the host response to dietary interventions.

Experiment 1

Edit History Delete Duplicate this Experiment Add a new Signature

incomplete

Curated date: 2022/11/21

Curator: Fatima

Revision editor(s): Fatima, Lwaldron

Subjects

Location of subjects: United Kingdom

Host species Species from which microbiome was sampled (if applicable): Homo sapiens

Group 0 name Corresponds to the control (unexposed) group for case-control studies: 0
Group 1 name Corresponds to the case (exposed) group for case-control studies: 1
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: test
Group 0 sample size Number of subjects in the control (unexposed) group: 1
Group 1 sample size Number of subjects in the case (exposed) group: 1
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): test

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V2-V2

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Human Intestinal Tract Chip

Statistical Analysis

Statistical test: T-Test

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: Yes
Matched on Factors on which subjects have been matched on in a case-control study: sex, body mass index
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment: demographics, body mass index