How Discrimination Gets Under the Skin: Biological Determinants of Discrimination Associated With Dysregulation of the Brain-Gut Microbiome System and Psychological Symptoms

Tien S Dong; Gilbert C Gee; Hiram Beltran-Sanchez; May Wang; Vadim Osadchiy; Lisa A Kilpatrick; Zixi Chen; Vishvak Subramanyam; Yurui Zhang; Yinming Guo; Jennifer S Labus; Bruce Naliboff; Steve Cole; Xiaobei Zhang; Emeran A Mayer; Arpana Gupta

doi:10.1016/j.biopsych.2022.10.011

How Discrimination Gets Under the Skin: Biological Determinants of Discrimination Associated With Dysregulation of the Brain-Gut Microbiome System and Psychological Symptoms

Biol Psychiatry. 2023 Aug 1;94(3):203-214. doi: 10.1016/j.biopsych.2022.10.011. Epub 2022 Oct 28.

Authors

Tien S Dong¹, Gilbert C Gee², Hiram Beltran-Sanchez², May Wang³, Vadim Osadchiy⁴, Lisa A Kilpatrick⁵, Zixi Chen⁶, Vishvak Subramanyam⁶, Yurui Zhang⁶, Yinming Guo⁶, Jennifer S Labus⁷, Bruce Naliboff⁷, Steve Cole⁸, Xiaobei Zhang⁵, Emeran A Mayer⁷, Arpana Gupta⁹

Affiliations

¹ Vatche and Tamar Manoukian Division of Digestive Diseases, University of California, Los Angeles, Los Angeles, California; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; UCLA Microbiome Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; G. Oppenheimer Center for Neurobiology of Stress and Resilience, University of California, Los Angeles, Los Angeles, California; Division of Gastroenterology, Hepatology and Parenteral Nutrition, VA Greater Los Angeles Healthcare System, Los Angeles, California. Electronic address: TSDong@mednet.ucla.edu.
² Department of Community Health Sciences Fielding School of Public Health, Los Angeles, California; California Center for Population Research, University of California, Los Angeles, Los Angeles, California.
³ Department of Community Health Sciences Fielding School of Public Health, Los Angeles, California.
⁴ Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
⁵ Vatche and Tamar Manoukian Division of Digestive Diseases, University of California, Los Angeles, Los Angeles, California; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; G. Oppenheimer Center for Neurobiology of Stress and Resilience, University of California, Los Angeles, Los Angeles, California.
⁶ Vatche and Tamar Manoukian Division of Digestive Diseases, University of California, Los Angeles, Los Angeles, California.
⁷ Vatche and Tamar Manoukian Division of Digestive Diseases, University of California, Los Angeles, Los Angeles, California; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; UCLA Microbiome Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; G. Oppenheimer Center for Neurobiology of Stress and Resilience, University of California, Los Angeles, Los Angeles, California.
⁸ David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; Department of Psychiatry & Biobehavioral Sciences and Medicine, University of California, Los Angeles, Los Angeles, California.
⁹ Vatche and Tamar Manoukian Division of Digestive Diseases, University of California, Los Angeles, Los Angeles, California; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; UCLA Microbiome Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; G. Oppenheimer Center for Neurobiology of Stress and Resilience, University of California, Los Angeles, Los Angeles, California. Electronic address: AGupta@mednet.ucla.edu.

Abstract

Background: Discrimination is associated with negative health outcomes as mediated in part by chronic stress, but a full understanding of the biological pathways is lacking. Here we investigate the effects of discrimination involved in dysregulating the brain-gut microbiome (BGM) system.

Methods: A total of 154 participants underwent brain magnetic resonance imaging to measure functional connectivity. Fecal samples were obtained for 16S ribosomal RNA profiling and fecal metabolites and serum for inflammatory markers, along with questionnaires. The Everyday Discrimination Scale was administered to measure chronic and routine experiences of unfair treatment. A sparse partial least squares-discriminant analysis was conducted to predict BGM alterations as a function of discrimination, controlling for sex, age, body mass index, and diet. Associations between discrimination-related BGM alterations and psychological variables were assessed using a tripartite analysis.

Results: Discrimination was associated with anxiety, depression, and visceral sensitivity. Discrimination was associated with alterations of brain networks related to emotion, cognition and self-perception, and structural and functional changes in the gut microbiome. BGM discrimination-related associations varied by race/ethnicity. Among Black and Hispanic individuals, discrimination led to brain network changes consistent with psychological coping and increased systemic inflammation. For White individuals, discrimination was related to anxiety but not inflammation, while for Asian individuals, the patterns suggest possible somatization and behavioral (e.g., dietary) responses to discrimination.

Conclusions: Discrimination is attributed to changes in the BGM system more skewed toward inflammation, threat response, emotional arousal, and psychological symptoms. By integrating diverse lines of research, our results demonstrate evidence that may explain how discrimination contributes to health inequalities.

Keywords: Brain resting state; Discrimination; Gut microbiome; Inflammation; Psychological symptoms; Systems biology.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Anxiety
Brain / diagnostic imaging
Brain / metabolism
Cognition / physiology
Gastrointestinal Microbiome* / genetics
Humans
Inflammation / metabolism

Abstract

Publication types

MeSH terms

Grants and funding