# Sex-based associations between neighborhood disadvantage and brain–gut alterations in individuals with irritable bowel syndrome

## TL;DR

Living in disadvantaged neighborhoods affects brain structure and gut microbes in IBS patients differently in males and females, influencing symptoms and stress.

## Contribution

This study reveals sex-specific brain and gut microbiome changes linked to neighborhood disadvantage in IBS patients.

## Key findings

- Neighborhood disadvantage is associated with increased symptom severity in males with IBS.
- Females with IBS show increased stress and Prevotella abundance in disadvantaged neighborhoods.
- Brain regions related to emotion and pain are more affected in females than males.

## Abstract

Irritable bowel syndrome (IBS) is a stress-sensitive disorder that exhibits sex differences in brain–gut–microbiome interactions. Neighborhood disadvantage is a chronic stressor that may influence brain–gut–microbiome health in patients with IBS, potentially contributing to clinical profiles in a sex-specific manner. This study evaluated sex-based associations between neighborhood disadvantage and clinical characteristics, cortical morphology, and Prevotella relative abundance (a sex-specific microbial marker in IBS) in individuals with IBS compared to healthy controls (HCs).

Brain magnetic resonance imaging scans were obtained in 182 individuals with IBS (age, 31.0 ± 0.8 years; 128 females) and 161 HCs (age, 32.7 ± 1.0 years; 94 females). Fecal microbiome data was available in 113 IBS participants (80 females) and 127 HCs (74 females). Current neighborhood disadvantage was assessed as the Area Deprivation Index (ADI), with ADI⩾5 defined as high ADI. Group differences in the associations of high ADI with symptoms, Prevotella, and cortical morphology were evaluated using partial least squares.

Diagnosis Differences: High ADI was associated with greater lateral intraparietal surface area in IBS vs HCs. Sex Differences: There were greater negative associations between high ADI and surface area in frontal operculum and thickness in frontopolar and primary somatosensory regions in females vs males. Diagnosis*Sex Differences: There were greater negative associations between high ADI and surface area in superior parietal and sensorimotor regions in IBS females vs males, and greater negative associations between high ADI and surface area and thickness in dorsolateral prefrontal and parietal regions, respectively, in IBS males vs females. High ADI was associated with greater symptom severity in IBS males, greater perceived stress in both IBS and HC females, and Prevotella relative abundance in IBS females (all p’s < 0.01).

Neighborhood disadvantage is associated with greater symptom severity in IBS males and both higher perceived stress (exacerbates symptoms) and Prevotella abundance (protective) in IBS females. It generally has a greater negative impact on emotion/pain-related cortical morphology in females vs males. However, there are more prominent somatosensory reductions in IBS females, and prefrontal reductions in IBS males. These findings highlight the interplay between social and biological factors in IBS and underscore the need for targeted, sex-specific interventions.

Irritable bowel syndrome (IBS) is a stress-sensitive disorder that is more common in females than in males and has been linked to changes in the brain–gut microbiome system. Living in a disadvantaged neighborhood is a type of chronic stressor that could contribute to changes in the brain–gut microbiome system and symptoms in IBS. Here, we investigated whether the area deprivation index, a measure of neighborhood disadvantage (based on neighborhood rates of poverty, unemployment, etc.), is associated with differences in symptoms, stress, brain structure, and the level of Prevotella in the gut in males and females with IBS and healthy individuals. Based on our results, neighborhood disadvantage negatively affects the structure of brain regions involved in emotion and pain processing to a greater extent in females than in males; this may contribute to a greater risk of IBS in females, but additional research is needed. Neighborhood disadvantage is associated with additional changes in somatosensory brain regions (involved in pain processing) in females with IBS and cognitive control brain regions (involved in pain modulation) in males with IBS. We also found that high neighborhood disadvantage is associated with worse symptom severity in males with IBS, and with greater stress and Prevotella in females with IBS. As stress is positively associated with symptoms while Prevotella is negatively associated with symptoms in females with IBS, both risk (stress) and protective factors (Prevotella) may be present in disadvantaged neighborhoods. Understanding how these factors affect individuals with IBS can aid in improving treatment effectiveness.

Neighborhood disadvantage is associated with increased symptom severity in males with IBS.Neighborhood disadvantage is associated with increased stress and Prevotella relative abundance in females with IBS, which have opposing relationships with symptom severity, suggesting that sex-specific risk (stress) and protective factors (Prevotella) exist in disadvantaged neighborhoods.Neighborhood disadvantage negatively affects the morphology of brain regions involved in emotion and pain processing to a greater extent in females than in males.Neighborhood disadvantage shows additional sex-specific associations in IBS, with more prominent somatosensory alterations in females with IBS and cognitive control alterations in males with IBS.

Neighborhood disadvantage is associated with increased symptom severity in males with IBS.

Neighborhood disadvantage is associated with increased stress and Prevotella relative abundance in females with IBS, which have opposing relationships with symptom severity, suggesting that sex-specific risk (stress) and protective factors (Prevotella) exist in disadvantaged neighborhoods.

Neighborhood disadvantage negatively affects the morphology of brain regions involved in emotion and pain processing to a greater extent in females than in males.

Neighborhood disadvantage shows additional sex-specific associations in IBS, with more prominent somatosensory alterations in females with IBS and cognitive control alterations in males with IBS.