Early-Life gut inflammation drives sex-dependent shifts in the microbiome-endocrine-brain axis.

Autor: Sullivan O; Graduate Program in Neuroscience, University of British Columbia, Vancouver, Canada; Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada., Sie C; Department of Microbiology & Immunology, University of British Columbia, Vancouver, Canada., Ng KM; Department of Microbiology & Immunology, University of British Columbia, Vancouver, Canada., Cotton S; Department of Microbiology & Immunology, University of British Columbia, Vancouver, Canada., Rosete C; Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada., Hamden JE; Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, Canada., Singh AP; Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA., Lee K; Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, Canada., Choudhary J; Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada., Kim J; Graduate Program in Neuroscience, University of British Columbia, Vancouver, Canada; Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada., Yu H; Department of Chemistry, University of British Columbia, Vancouver, Canada., Clayton CA; Department of Microbiology & Immunology, University of British Columbia, Vancouver, Canada., Carranza Garcia NA; Department of Microbiology & Immunology, University of British Columbia, Vancouver, Canada., Voznyuk K; Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada., Deng BD; Department of Microbiology & Immunology, University of British Columbia, Vancouver, Canada., Plett N; Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada., Arora S; Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada., Ghezzi H; Department of Bioinformatics, University of British Columbia, Vancouver, Canada., Huan T; Department of Chemistry, University of British Columbia, Vancouver, Canada., Soma KK; Graduate Program in Neuroscience, University of British Columbia, Vancouver, Canada; Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada; Department of Psychology, University of British Columbia, Vancouver Canada., Yu JJ; Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA., Tropini C; Department of Microbiology & Immunology, University of British Columbia, Vancouver, Canada; School of Biomedical Engineering, University of British Columbia, Vancouver, Canada; Humans and the Microbiome Program, Canadian Institute for Advanced Research (CIFAR), Toronto, Canada. Electronic address: carolina.tropini@ubc.ca., Ciernia AV; Graduate Program in Neuroscience, University of British Columbia, Vancouver, Canada; Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, Canada. Electronic address: annie.ciernia@ubc.ca.
Jazyk: angličtina
Zdroj: Brain, behavior, and immunity [Brain Behav Immun] 2024 Dec 12. Date of Electronic Publication: 2024 Dec 12.
DOI: 10.1016/j.bbi.2024.12.003
Abstrakt: Despite recent advances in understanding the connection between the gut microbiota and the adult brain, there remains a wide knowledge gap in how gut inflammation impacts brain development. We hypothesized that intestinal inflammation in early life would negatively affect neurodevelopment through dysregulation of microbiota communication to the brain. We therefore developed a novel pediatric chemical model of inflammatory bowel disease (IBD), an incurable condition affecting millions of people worldwide. IBD is characterized by chronic intestinal inflammation, and has comorbid symptoms of anxiety, depression and cognitive impairment. Significantly, 25% of patients with IBD are diagnosed during childhood, and the effect of chronic inflammation during this critical period of development is largely unknown. This study investigated the effects of early-life gut inflammation induced by DSS (dextran sulfate sodium) on a range of microbiota, endocrine, and behavioral outcomes, focusing on sex-specific impacts. DSS-treated mice exhibited increased intestinal inflammation, altered microbiota membership, and changes in microbiota-mediated circulating metabolites. The majority of behavioral measures were unaffected, with the exception of impaired mate-seeking behaviors in DSS-treated males. DSS-treated males also showed significantly smaller seminal vesicles, lower circulating androgens, and decreased intestinal hormone-activating enzyme activity. In the brain, microglia morphology was chronically altered with DSS treatment in a sex-specific manner. The results suggest that early-life gut inflammation causes changes in gut microbiota composition, affecting short-chain fatty acid (SCFA) producers and glucuronidase (GUS) activity, correlating with altered SCFA and androgen levels. The findings emphasize the developmental sensitivity to inflammation-induced changes in endocrine signalling and underscore long-lasting physiological and microbiome changes associated with juvenile IBD.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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