Logo image
Back
Microbial indoles: key regulators of organ growth and metabolic function
Journal article   Open access   Peer reviewed

Microbial indoles: key regulators of organ growth and metabolic function

Peter Yuli Xing, Ruchi Agrawal, Anusha Jayaraman, Katherine Ann Martin, George Wei Zhang, Ee Ling Ngu, Llanto Elma Faylon, Staffan Kjelleberg, Scott A Rice, Yulan Wang, …
Microorganisms (Basel), Vol.12(4), 719
2024
DOI: https://doi.org/10.3390/microorganisms12040719
PMID: 38674663
pdf
Published 4.72 MBDownloadView
Published (Version of Record)CC BY V4.0,  Open Access

Abstract

germ-free indoles host metabolism organ function decline gut microbiota oxidative stress
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.

Details

Metrics

24 File views/ downloads
98 Record Views
Logo image