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

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.