Microbial indoles: key regulators of organ growth and metabolic function
File(s)
Author(s)
Type
Journal Article
Abstract
Gut microbes supporting body growth are known but the mechanisms are less well documented. Using the microbial tryptophan metabolite indole, known to regulate prokaryotic cell division and metabolic stress conditions, we mono-colonized germ-free (GF) mice with indole-producing wild-type Escherichia coli (E. coli) or tryptophanase-encoding tnaA knockout mutant indole-non-producing E. coli. Indole mutant E. coli mice showed multiorgan growth retardation and lower levels of glycogen, cholesterol, triglycerides, and glucose, resulting in an energy deficiency despite increased food intake. Detailed analysis revealed a malfunctioning intestine, enlarged cecum, and reduced numbers of enterochromaffin cells, correlating with a metabolic phenotype consisting of impaired gut motility, diminished digestion, and lower energy harvest. Furthermore, indole mutant mice displayed reduction in serum levels of tricarboxylic acid (TCA) cycle intermediates and lipids. In stark contrast, a massive increase in serum melatonin was observed—frequently associated with accelerated oxidative stress and mitochondrial dysfunction. This observational report discloses functional roles of microbe-derived indoles regulating multiple organ functions and extends our previous report of indole-linked regulation of adult neurogenesis. Since indoles decline by age, these results imply a correlation with age-linked organ decline and levels of indoles. Interestingly, increased levels of indole-3-acetic acid, a known indole metabolite, have been shown to correlate with younger biological age, further supporting a link between biological age and levels of microbe-derived indole metabolites. The results presented in this resource paper will be useful for the future design of food intervention studies to reduce accelerated age-linked organ decline.
Date Issued
2024-04-02
Date Acceptance
2024-03-29
Citation
Microorganisms, 2024, 12 (4)
ISSN
2076-2607
Publisher
MDPI AG
Journal / Book Title
Microorganisms
Volume
12
Issue
4
Copyright Statement
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/38674663
PII: microorganisms12040719
Subjects
BACTERIA
germ-free
gut microbiota
GUT MICROBIOTA
HEALTH
host metabolism
indoles
INHIBITION
Life Sciences & Biomedicine
MELATONIN
Microbiology
organ function decline
oxidative stress
PUBERTY
Science & Technology
SEROTONIN
SERUM
TRYPTOPHAN-METABOLITES
Publication Status
Published
Coverage Spatial
Switzerland
Article Number
ARTN 719
Date Publish Online
2024-04-02