Early life adversity predicts brain-gut alterations associated with increased stress and mood

Elena J.L. Coley; Emeran A. Mayer; Vadim Osadchiy; Zixi Chen; Vishvak Subramanyam; Yurui Zhang; Elaine Y. Hsiao; Kan Gao; Ravi Bhatt; Tien Dong; Priten Vora; Bruce Naliboff; Jonathan P. Jacobs; Arpana Gupta

Neurobiology of Stress (Nov 2021)

Early life adversity predicts brain-gut alterations associated with increased stress and mood

Elena J.L. Coley,
Emeran A. Mayer,
Vadim Osadchiy,
Zixi Chen,
Vishvak Subramanyam,
Yurui Zhang,
Elaine Y. Hsiao,
Kan Gao,
Ravi Bhatt,
Tien Dong,
Priten Vora,
Bruce Naliboff,
Jonathan P. Jacobs,
Arpana Gupta

Affiliations

Elena J.L. Coley: Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, USA
Emeran A. Mayer: G. Oppenheimer Center for Neurobiology of Stress and Resilience, University of California, Los Angeles, USA; David Geffen School of Medicine, University of California, Los Angeles, USA; Vatche and Tamar Manoukian Division of Digestive Diseases, Los Angeles, CA, USA; UCLA Microbiome Center, Los Angeles, CA, USA
Vadim Osadchiy: G. Oppenheimer Center for Neurobiology of Stress and Resilience, University of California, Los Angeles, USA; David Geffen School of Medicine, University of California, Los Angeles, USA; Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
Zixi Chen: G. Oppenheimer Center for Neurobiology of Stress and Resilience, University of California, Los Angeles, USA
Vishvak Subramanyam: G. Oppenheimer Center for Neurobiology of Stress and Resilience, University of California, Los Angeles, USA
Yurui Zhang: G. Oppenheimer Center for Neurobiology of Stress and Resilience, University of California, Los Angeles, USA
Elaine Y. Hsiao: David Geffen School of Medicine, University of California, Los Angeles, USA; UCLA Microbiome Center, Los Angeles, CA, USA; Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, USA
Kan Gao: Laboratory of Gastrointestinal Microbiology, Nanjing Agricultural University, PR China
Ravi Bhatt: G. Oppenheimer Center for Neurobiology of Stress and Resilience, University of California, Los Angeles, USA; Imaging Genetics Center, Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles, CA, USA
Tien Dong: G. Oppenheimer Center for Neurobiology of Stress and Resilience, University of California, Los Angeles, USA; David Geffen School of Medicine, University of California, Los Angeles, USA; Vatche and Tamar Manoukian Division of Digestive Diseases, Los Angeles, CA, USA; UCLA Microbiome Center, Los Angeles, CA, USA; Division of Gastroenterology, Hepatology and Parenteral Nutrition, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA
Priten Vora: G. Oppenheimer Center for Neurobiology of Stress and Resilience, University of California, Los Angeles, USA
Bruce Naliboff: G. Oppenheimer Center for Neurobiology of Stress and Resilience, University of California, Los Angeles, USA; David Geffen School of Medicine, University of California, Los Angeles, USA; Vatche and Tamar Manoukian Division of Digestive Diseases, Los Angeles, CA, USA
Jonathan P. Jacobs: David Geffen School of Medicine, University of California, Los Angeles, USA; Vatche and Tamar Manoukian Division of Digestive Diseases, Los Angeles, CA, USA; UCLA Microbiome Center, Los Angeles, CA, USA; Division of Gastroenterology, Hepatology and Parenteral Nutrition, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA
Arpana Gupta: G. Oppenheimer Center for Neurobiology of Stress and Resilience, University of California, Los Angeles, USA; David Geffen School of Medicine, University of California, Los Angeles, USA; Vatche and Tamar Manoukian Division of Digestive Diseases, Los Angeles, CA, USA; UCLA Microbiome Center, Los Angeles, CA, USA; Corresponding author. Oppenheimer Family Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA CHS, 42-210 MC737818 10833 Le Conte Avenue, USA.

Journal volume & issue: Vol. 15
p. 100348

Abstract

Read online

Alterations in the brain-gut system have been implicated in various disease states, but little is known about how early-life adversity (ELA) impacts development and adult health as mediated by brain-gut interactions. We hypothesize that ELA disrupts components of the brain-gut system, thereby increasing susceptibility to disordered mood. In a sample of 128 healthy adult participants, a history of ELA and current stress, depression, and anxiety were assessed using validated questionnaires. Fecal metabolites were measured using liquid chromatography tandem mass spectrometry-based untargeted metabolomic profiling. Functional brain connectivity was evaluated by magnetic resonance imaging. Sparse partial least squares-discriminant analysis, controlling for sex, body mass index, age, and diet was used to predict brain-gut alterations as a function of ELA. ELA was correlated with four gut-regulated metabolites within the glutamate pathway (5-oxoproline, malate, urate, and glutamate gamma methyl ester) and alterations in functional brain connectivity within primarily sensorimotor, salience, and central executive networks. Integrated analyses revealed significant associations between these metabolites, functional brain connectivity, and scores for perceived stress, anxiety, and depression. This study reveals a novel association between a history of ELA, alterations in the brain-gut axis, and increased vulnerability to negative mood and stress. Results from the study raise the hypothesis that select gut-regulated metabolites may contribute to the adverse effects of critical period stress on neural development via pathways related to glutamatergic excitotoxicity and oxidative stress.

Published in Neurobiology of Stress

ISSN: 2352-2895 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry: Neurology. Diseases of the nervous system; Science: Physiology: Neurophysiology and neuropsychology
Website: http://www.journals.elsevier.com/neurobiology-of-stress/

About the journal

Abstract

Keywords