Systemic Regulation of Host Energy and Oogenesis by Microbiome-Derived Mitochondrial Coenzymes.
Adenosine Triphosphate
/ metabolism
Animals
Coenzymes
/ metabolism
Drosophila melanogaster
/ genetics
Female
Fertility
Flavin Mononucleotide
/ metabolism
Flavin-Adenine Dinucleotide
/ metabolism
Gastrointestinal Microbiome
Gene Expression Regulation
Germ-Free Life
Host Microbial Interactions
Metabolome
Mitochondria
/ genetics
Mitochondrial Proteins
/ metabolism
Oogenesis
Ovarian Follicle
/ metabolism
Ovary
/ metabolism
Drosophila
metabolomics
microbiome
mitochondria
oogenesis
riboflavin
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
05 01 2021
05 01 2021
Historique:
received:
23
07
2019
revised:
02
10
2020
accepted:
10
12
2020
entrez:
6
1
2021
pubmed:
7
1
2021
medline:
15
12
2021
Statut:
ppublish
Résumé
Gut microbiota have been shown to promote oogenesis and fecundity, but the mechanistic basis of remote influence on oogenesis remained unknown. Here, we report a systemic mechanism of influence mediated by bacterial-derived supply of mitochondrial coenzymes. Removal of microbiota decreased mitochondrial activity and ATP levels in the whole-body and ovary, resulting in repressed oogenesis. Similar repression was caused by RNA-based knockdown of mitochondrial function in ovarian follicle cells. Reduced mitochondrial function in germ-free (GF) females was reversed by bacterial recolonization or supplementation of riboflavin, a precursor of FAD and FMN. Metabolomics analysis of GF females revealed a decrease in oxidative phosphorylation and FAD levels and an increase in metabolites that are degraded by FAD-dependent enzymes (e.g., amino and fatty acids). Riboflavin supplementation opposed this effect, elevating mitochondrial function, ATP, and oogenesis. These findings uncover a bacterial-mitochondrial axis of influence, linking gut bacteria with systemic regulation of host energy and reproduction.
Identifiants
pubmed: 33406416
pii: S2211-1247(20)31572-2
doi: 10.1016/j.celrep.2020.108583
pii:
doi:
Substances chimiques
Coenzymes
0
Mitochondrial Proteins
0
Flavin-Adenine Dinucleotide
146-14-5
Flavin Mononucleotide
7N464URE7E
Adenosine Triphosphate
8L70Q75FXE
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
108583Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.