Gut bacterial nutrient preferences quantified in vivo

Xianfeng Zeng; Xi Xing; Meera Gupta; Felix C Keber; Jaime G Lopez; Ying-Chiang J Lee; Asael Roichman; Lin Wang; Michael D Neinast; Mohamed S Donia; Martin Wühr; Cholsoon Jang; Joshua D Rabinowitz

doi:10.1016/j.cell.2022.07.020

Gut bacterial nutrient preferences quantified in vivo

Cell. 2022 Sep 1;185(18):3441-3456.e19. doi: 10.1016/j.cell.2022.07.020.

Authors

Affiliations

¹ Department of Chemistry, Princeton University, Princeton, NJ 08544, USA; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
² Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA; Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
³ Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
⁴ Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
⁵ Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
⁶ Department of Chemistry, Princeton University, Princeton, NJ 08544, USA; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA; Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 5 Dong Dan San Tiao, Dongcheng District, Beijing 100005, China.
⁷ Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA. Electronic address: wuhr@princeton.edu.
⁸ Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA. Electronic address: choljang@uci.edu.
⁹ Department of Chemistry, Princeton University, Princeton, NJ 08544, USA; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA; Ludwig Institute for Cancer Research, Princeton Branch, Princeton University, Princeton, NJ 08544, USA. Electronic address: joshr@princeton.edu.

Abstract

Great progress has been made in understanding gut microbiomes' products and their effects on health and disease. Less attention, however, has been given to the inputs that gut bacteria consume. Here, we quantitatively examine inputs and outputs of the mouse gut microbiome, using isotope tracing. The main input to microbial carbohydrate fermentation is dietary fiber and to branched-chain fatty acids and aromatic metabolites is dietary protein. In addition, circulating host lactate, 3-hydroxybutyrate, and urea (but not glucose or amino acids) feed the gut microbiome. To determine the nutrient preferences across bacteria, we traced into genus-specific bacterial protein sequences. We found systematic differences in nutrient use: most genera in the phylum Firmicutes prefer dietary protein, Bacteroides dietary fiber, and Akkermansia circulating host lactate. Such preferences correlate with microbiome composition changes in response to dietary modifications. Thus, diet shapes the microbiome by promoting the growth of bacteria that preferentially use the ingested nutrients.

Keywords: diet; host-microbiome interactions; isotope tracing; metabolism; metabolomics; methodology; mice; microbiome; nutrient; proteomics.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bacteria
Diet
Dietary Fiber / metabolism
Dietary Proteins / metabolism
Gastrointestinal Microbiome*
Lactates / metabolism
Mice
Nutrients

Substances

Dietary Fiber
Dietary Proteins
Lactates

Abstract

Publication types

MeSH terms

Substances

Grants and funding