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. 2025 Aug 11;16(1):61.
doi: 10.1186/s13293-025-00739-y.

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

Lisa A Kilpatrick  1   2   3   4   5 , Lin Chang  6   7   8   9   10 , Jennifer S Labus  6   7   8   9   10   11 , Andrea S Shin  6   7   8   9   10 , Michelle Choy  6   7   8   9   10 , Tien S Dong  6   7   8   9   10 , Bruce Naliboff  6   7   8   9   10 , Emeran A Mayer  6   7   8   9   10 , Arpana Church  6   7   8   9   10
Affiliations

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

Lisa A Kilpatrick et al. Biol Sex Differ. .

Abstract

Background: 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).

Methods: 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.

Results: 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).

Conclusions: 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.

Keywords: Prevotella; Area deprivation index; Brain–gut–microbiome interactions; Irritable bowel syndrome; Sex-differences.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study was approved by the Institutional Review Board at the University of California, Los Angeles’s Office of Protection for Research Subjects (Nos. 20-000540, 20-000515, 20-0540, 20-0515). Consent for publication: All participants provided written informed consent. No individual data is reported, all data is anonymized and reported at the group level. Competing interests: A.C. is a research consultant for YAMAHA. E.A.M. is a member of the scientific advisory boards of Danone, Axial Therapeutics, Amare, Mahana Therapeutics, Pendulum, Bloom Biosciences, and APC Microbiome Ireland. L.C. serves as an advisory board member or consultant for Ardelyx, Arena Pharmaceuticals, Bausch Health, Immunic, Ironwood Pharmaceuticals, Inc., Mauna Kea Technologies, and Trellus; and receives grant support from AnX Robotica, Arena Pharmaceuticals, and Ironwood Pharmaceuticals. All other authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Graphical abstract. This study investigated associations between the area deprivation index, a measure of neighborhood disadvantage, and symptoms, stress, brain morphology, and Prevotella relative abundance in males and females with IBS and healthy individuals. We found that neighborhood disadvantage is associated with increased symptom severity in males with IBS, and both perceived stress and Prevotella relative abundance in females with IBS, which have positive and negative relationships with symptom severity, respectively. Additionally, neighborhood disadvantage mainly has a negative impact on cortical morphology, with greater reductions in emotion/pain-related regions in females vs males, somatosensory regions in IBS females vs IBS males, and cognitive control regions in IBS males vs IBS females
Fig. 2
Fig. 2
Distribution of National and California ADI in the present sample. The National ranking is provided in percentiles (range, 1–100), while the California state-wide ranking is provided in deciles (range, 1–10). The cutoff for low/high ADI is shown according to both National and California ranking. It is important to note that although the cutoff results in comparisons between participants living in the lowest ~ 30% to the highest ~ 70% of neighborhoods in terms of the California ADI, the low ADI group represents extremely low ADI at the National level. This is due to the relatively low ADI estimates in southern California compared to those in other area of the nation. ADI area deprivation index
Fig. 3
Fig. 3
Relationships between high ADI and brain morphology parameters (surface area and cortical thickness). Relationships between ADI and brain alterations are presented according to (1) diagnosis (2) sex, and (3) sex*diagnosis. Red and Blue indicate positive and negative associations, respectively, that are greater in one group vs another group (as indicated in headings). Abbreviations for brain regions are provided in Tables 2 and 3. ADI area deprivation index. CT cortical thickness, IBS irritable bowel syndrome, SA surface area
Fig. 4
Fig. 4
Relationships between high ADI and symptom/microbial parameters. High ADI is significantly associated with increased stress in HC and IBS females, symptom severity in IBS males, and Prevotella relative abundance in IBS females. ADI area deprivation index, IBS irritable bowel syndrome, HC healthy control
Fig. 5
Fig. 5
Summary of relationships between ADI-related morphological and clinical/microbial findings in IBS. High ADI is associated with increased cortical thickness in right area 10 pp in IBS males, which are also associated with increased symptom severity. In contrast, high ADI is significantly associated with decreased surface area in 7Am, which shows opposing relationships with stress and Prevotella relative abundance, in IBS females. High ADI is not associated with symptom severity in IBS females because high ADI is associated with increased stress and Prevotella relative abundance, which show opposing relationships with symptom severity. Significant associations are indicated with solid lines, trends are indicated with dashed lines. ADI area deprivation index, IBS irritable bowel syndrome, PBelt parabelt complex, 10 pp area 10 polar-polar, 7Am antero-medial area 7
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