Acute stress triggers sex-dependent rapid alterations in the human small intestine microbiota composition

Abstract

Irritable bowel syndrome; Small intestine microbiota; Stress

Síndrome del intestino irritable; Microbiota del intestino delgado; Estrés

Síndrome de l'intestí irritable; Microbiota de l'intestí prim; Estrès

Background/aims: Digestive disorders of gut-brain interaction (DGBI) are very common, predominant in females, and usually associated with intestinal barrier dysfunction, dysbiosis, and stress. We previously found that females have increased susceptibility to intestinal barrier dysfunction in response to acute stress. However, whether this is associated with changes in the small bowel microbiota remains unknown. We have evaluated changes in the small intestinal microbiota in response to acute stress to better understand stress-induced intestinal barrier dysfunction. Methods: Jejunal biopsies were obtained at baseline and 90 min after cold pain or sham stress. Autonomic (blood pressure and heart rate), hormonal (plasma cortisol and adrenocorticotropic hormone) and psychological (Subjective Stress Rating Scale) responses to cold pain and sham stress were monitored. Microbial DNA from the biopsies was analyzed using a 16S metabarcoding approach before and after cold pain stress and sham stress. Differences in diversity and relative abundance of microbial taxa were examined. Results: Cold pain stress was associated with a significant decrease in alpha diversity (P = 0.015), which was more pronounced in females, along with significant sex differences in the abundance of specific taxa and the overall microbiota composition. Microbiota alterations significantly correlated with changes in psychological responses, hormones, and gene expression in the intestinal mucosal. Cold pain stress was also associated with activation of autonomic, hormonal and psychological response, with no differences between sexes. Conclusions: Acute stress elicits rapid alterations in bacterial composition in the jejunum of healthy subjects and these changes are more pronounced in females. Our results may contribute to the understanding of female predominance in DGBI.

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by Fondo Europeo de Desarrollo Regional (FEDER), Fondo de Investigación Sanitaria and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), y de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Subdirección General de Investigación Sanitaria, Ministerio de Economía y Competitividad y Ministerio de Ciencia e Innovación: EII2011-0035, CD15/00010 and MV17-00043 (BR-J); CM10/00155 (MP); FI12/00254 (ES-R); FI20/00256 (MA-B); CP18/00116 (CM); PI19/01643 (BL); PI16/00583, PI19/01643 and CPII16/00031 (MV); PI17/0190 (JS); INB Grant PT17/0009/0023 (TG); PI15/00301 (CA-C); CIBEREHD CB06/04/0021 (AG-C, DG, BL, MV, JS, CA-C); CIBERINFEC CB21/13/00061 (TG). Vall d'Hebron Institut de Recerca, Programa de becas predoctorales Amics de Vall d'Hebron: PRED-VHIR-2014-018 (MF), PRED-VHIR-2016-53 (CP-C). Ajuts per a la contractació de personal investigador FI, Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR), Generalitat de Catalunya: 2020FI_B1 00127 & 2019FI_B 00817 (MA-B), SGR423 (TG). Formación de profesorado universitario (FPU) program from the Spanish Ministerio de Universidades: FPU2020-02907 (OK-L). European Union's Horizon 2020 research and innovation program: ERC-2016-724173 (TG). Gordon and Betty Moore Foundation: GBMF9742 (TG).