Psychosocial adversity experienced in utero and early life is associated with variation in gut microbiota: a prospective case-control study

Abstract

Social disadvantage (SD) and psychological stressors (PS) trap some populations in poverty, resulting in health inequities. How these two factors become biologically embedded and the pathways leading to adverse health outcomes is unclear, especially in infants exposed to psychosocial adversity in utero and during early life. Variation in gut microbiome structure and functions, and systemic elevations in circulating cytokines levels as indices of inflammation, offer two possible causative pathways. Here, we interrogate the gut microbiome of mother-child dyads and maternal inflammatory markers, and compare high-SD/high-PS dyads to pairs with low-SD/Low-PS, and demonstrate that the GM of high-SD and high-PS mothers may already be compromised, resulting in the lowest observed inter-individual similarity in that group. The strong predictors of maternal high-SD and high-PS based on mothers and children microbiomes were phylogenetically very distinct bacteria indicating different GM pathways associated with SD versus PS. We identified sets of SD- and PS-discriminatory metabolic pathways in the mothers and in the children, however their predictive power was lower compared to the discriminatory bacterial species. Prediction accuracy was consistently greater for IL-6 than for the other inflammatory markers, supporting an association between systemic inflammation and psychosocial adversity. The gut microbiome of the infants can be used to predict the psychosocial adversity of mothers, and are embedded in the gut microbiota of 4-month-old infants.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This study was funded by the Washington University in St. Louis GTAC@MGI for library construction and sequencing, NIMH grant RO1 MH113883, March of Dimes (SKE), Childrens Discovery Institute II MD-II-2015-489 (BBW, IMN), Biobank Core P30DK052574 (PIT).

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Human Research Protection Office of Washington University in St. Louis gave ethical approval for this work. Informed consent was obtained from the mother for each dyad. The study was performed in accordance with Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

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I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.

Yes

Data Availability

All data produced in the present work are contained in the manuscript.

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