Impact of a 7-day homogeneous diet on interpersonal variation in human gut microbiomes and metabolomes

Leah Guthrie; Sean Paul Spencer; Dalia Perelman; Will Van Treuren; Shuo Han; Feiqiao Brian Yu; Erica D Sonnenburg; Michael A Fischbach; Timothy W Meyer; Justin L Sonnenburg

doi:10.1016/j.chom.2022.05.003

Impact of a 7-day homogeneous diet on interpersonal variation in human gut microbiomes and metabolomes

Cell Host Microbe. 2022 Jun 8;30(6):863-874.e4. doi: 10.1016/j.chom.2022.05.003. Epub 2022 May 27.

Authors

Affiliations

¹ Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
² Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
³ Stanford Prevention Research Center, Department of Medicine, Stanford School of Medicine, Stanford, CA 94305, USA.
⁴ Chan-Zuckerburg Biohub, San Francisco, CA 94158, USA.
⁵ Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; ChEM-H, Stanford University, Stanford, CA 94305, USA; Chan-Zuckerburg Biohub, San Francisco, CA 94158, USA; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
⁶ Department of Medicine, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.
⁷ Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Chan-Zuckerburg Biohub, San Francisco, CA 94158, USA; Center for Human Microbiome Studies, Stanford, CA 94305, USA. Electronic address: jsonnenburg@stanford.edu.

Abstract

Gut microbiota metabolism of dietary compounds generates a vast array of microbiome-dependent metabolites (MDMs), which are highly variable between individuals. The uremic MDMs (uMDMs) phenylacetylglutamine (PAG), p-cresol sulfate (PCS), and indoxyl sulfate (IS) accumulate during renal failure and are associated with poor outcomes. Targeted dietary interventions may reduce toxic MDM generation; however, it is unclear if inter-individual differences in diet or gut microbiome dominantly contribute to MDM variance. Here, we use a 7-day homogeneous average American diet to standardize dietary precursor availability in 21 healthy individuals. During dietary homogeneity, the coefficient of variation in PAG, PCS, and IS (primary outcome) did not decrease, nor did inter-individual variation in most identified metabolites; other microbiome metrics showed no or modest responses to the intervention. Host identity and age are dominant contributors to variability in MDMs. These results highlight the potential need to pair dietary modification with microbial therapies to control MDM profiles.

Keywords: dietary intervention; microbiome; microbiome-dependent metabolites; precision medicine; uremic solutes.

MeSH terms

Diet
Gastrointestinal Microbiome*
Humans
Indican
Metabolome
Microbiota*

Substances

Indican

Abstract

MeSH terms

Substances

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