# Multi-omics analysis reveal clinical-gut-brain interactions in female ibs patients with adverse childhood experiences

## TL;DR

This study shows how early life stress affects the brain and gut microbiome in women with IBS, leading to worse symptoms and altered brain function.

## Contribution

The study identifies a multi-omic signature linking adverse childhood experiences to IBS in women through brain, gut, and clinical features.

## Key findings

- Women with IBS and high ACE scores show greater anxiety, stress, and somatic symptoms compared to healthy controls.
- High ACE IBS patients have reduced beneficial gut bacteria like Akkermansia and Bifidobacterium linked to symptom severity.
- Machine learning models accurately distinguished IBS patients with high ACE from others with 78% accuracy and an AUC of 0.87.

## Abstract

The brain-gut system, which involves bidirectional communication between the central nervous system and the gut, plays a central role in stress responses. Its dysregulation is implicated in irritable bowel syndrome (IBS), a stress-sensitive, female-predominant disorder characterized by abdominal pain and altered bowel habits. Adverse childhood experiences (ACE) increase the risk and severity of IBS, likely by amplifying stress responsiveness and gut-brain dysfunction in females. However, the mechanisms involved are unknown.

This study aimed to identify a multi-omic signature linking ACE exposure to IBS females via clinical, neuroimaging, and gut microbiome features as compared to healthy control (HC) females.

Data was analyzed from participants with Rome positive IBS and HCs. Four subgroups were created based on IBS diagnosis and ACE score with high ACE defined as ≥2 and low as ACE 0-1. Validated questionnaires assessed clinical variables. Biological markers included multimodal brain MRI, and gut microbial function using metagenomics. eXtreme gradient boosting (XGBoost) identified key differentiating features between the groups. Connectograms visualized relationships across mutli-omics data within each group.

Among 188 female participants, the four groups included IBS with high ACE (n=37), IBS with low ACE (n=55), HCs with high ACE (n=19), and HCs with low ACE (n=77). Key findings include: 1. High ACE participants with IBS versus their HC counterparts showed increased depression and anxiety symptoms, GI-symptom related anxiety, perceived stress, somatic symptom severity, and poorer physical and mental health scores. 2. High ACE participants with IBS had negative associations between key bacteria such as Akkermansia (a beneficial bacteria) and somatic symptom severity, and between Bifidobacterium and ACE parental divorce/separation and alterations in the salience and central autonomic networks. 3. The ensemble model accurately distinguished IBS patients with high ACE (AUC of 0.87), demonstrating strong predictive performance with an overall model accuracy of 78%.

Our findings highlight the unique microbiota and brain networks contributing to a complex interplay of chronic stress as measured by early life adversity, the brain-gut-microbiome system, and IBS pathophysiology which can inform therapeutic targets aimed at mitigating the long-term impacts of early life stress in female IBS patients.

Irritable Bowel Syndrome (IBS) is a common, female-predominant disorder of gut brain interactions, often linked to stress and early life adversity. This study explores how adverse childhood experiences (ACE) impact IBS symptoms, brain structure and function, and gut microbiome composition in women. We studied 188 premenopausal women, dividing them into groups based on IBS diagnosis and early life adversity history. Using a machine-learning approach, we identified key biological signatures associated with IBS and ACE. Our findings show that women with IBS and high ACE scores have unique brain connectivity patterns, altered gut bacteria, and greater somatic symptom severity compared to those with low ACE scores or healthy controls. Specifically, differences in brain regions related to stress and pain processing, along with changes in gut bacteria linked to inflammation and digestion, highlight the complex interactions within the brain-gut-microbiome system. These results reinforce the concept that IBS is a complex disorder influenced by multiple biological systems. This study highlights the importance of understanding how early-life stress shapes the brain-gut microbiome system and identifies potential targets for improving IBS management and overall patient well-being.

Adverse childhood experiences are strongly linked to IBS, affect brain structure and function, gut microbiome, and symptom severity.

IBS is also more common in women, potentially due to the influence of adverse childhood experiences on the brain-gut microbiome system.

Our study analyzed 188 premenopausal women with IBS or healthy controls using clinical assessments, gut microbiome sequencing, and brain imaging.

Machine-learning models identified unique IBS brain-gut signatures, highlighting increased somatic symptom severity, gut bacterial changes, and brain connectivity alterations in women with IBS and high ACE.

Key microbiome changes included reduced beneficial bacteria.

Neuroimaging findings showed alterations in stress and pain processing brain regions, particularly in women with high ACE.

Adverse childhood experiences are strongly linked to IBS, affect brain structure and function, gut microbiome, and symptom severity.

IBS is also more common in women, potentially due to the influence of adverse childhood experiences on the brain-gut microbiome system.

Our study analyzed 188 premenopausal women with IBS or healthy controls using clinical assessments, gut microbiome sequencing, and brain imaging.

Machine-learning models identified unique IBS brain-gut signatures, highlighting increased somatic symptom severity, gut bacterial changes, and brain connectivity alterations in women with IBS and high ACE.

Key microbiome changes included reduced beneficial bacteria.

Neuroimaging findings showed alterations in stress and pain processing brain regions, particularly in women with high ACE.