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

Qi Yan Ang, Margaret Alexander, John C. Newman, Yuan Tian, Jingwei Cai, Vaibhav Upadhyay, Jessie A. Turnbaugh, Eric Verdin, Kevin D. Hall, Rudolph L. Leibel, Eric Ravussin, Michael Rosenbaum, Andrew D. Patterson, Peter J. Turnbaugh

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1263-1275.e16
JournalCell
Volume181
Issue number6
DOIs
StatePublished - Jun 11 2020

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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    Ang, Q. Y., Alexander, M., Newman, J. C., Tian, Y., Cai, J., Upadhyay, V., Turnbaugh, J. A., Verdin, E., Hall, K. D., Leibel, R. L., Ravussin, E., Rosenbaum, M., Patterson, A. D., & Turnbaugh, P. J. (2020). Ketogenic Diets Alter the Gut Microbiome Resulting in Decreased Intestinal Th17 Cells. Cell, 181(6), 1263-1275.e16. https://doi.org/10.1016/j.cell.2020.04.027