# Evidence for Brain‐To‐Gut and Gut‐To‐Brain Pathways in Primary Care Patients With Disorders of Gut‐Brain Interaction, Inflammatory Bowel Disease and Gastroesophageal Reflux Disease

## TL;DR

This study shows that gut and brain disorders often overlap, with some conditions starting in the gut and others in the brain, influenced by factors like medications and infections.

## Contribution

The study provides evidence for bidirectional gut-brain pathways in common GI disorders and identifies factors influencing the order of diagnosis.

## Key findings

- Psychological diagnoses often precede GERD and DGBI, but not Crohn's disease.
- Medications like PPIs and NSAIDs, and prior gastroenteritis, predict earlier GI diagnoses.
- Gut-brain interactions vary by disorder, with brain-to-gut pathways more common in IBS and FD.

## Abstract

Apart from disorders of gut‐brain interaction (DGBI), little data exist on the magnitude of the brain‐to‐gut pathway in other chronic gastrointestinal conditions such as gastroesophageal reflux disease (GERD) or inflammatory bowel disease (IBD) and what factors modify order of diagnosis. We aimed to determine the proportion of patients who received a diagnosis of a DGBI, GERD, or IBD prior to a new psychological diagnosis (gut‐to‐brain), and vice versa (brain‐to‐gut), and whether specific factors moderate the order of diagnosis.

Data was collected from a retrospective study of 1,129,104 patients attending general practices in the United Kingdom. Patients diagnosed with DGBI, GERD, or IBD and a psychological disorder (anxiety and/or depression) were included (excluding those with other organic GI disease). Information on which diagnosis appeared first was recorded. Multiple logistic regression was performed to compare a diagnosis of a DGBI, GERD, or IBD first versus a psychological diagnosis first on sociodemographic factors, medical conditions, and medication usage.

Just over half of patients were diagnosed with a psychological condition first versus after for IBS (53.9%) and ulcerative colitis (55.6%). This proportion was higher for FD (61.5%) and GERD (64.2%) but lower for Crohn's disease (45.7%). In a multivariate model, being female (OR = 1.37, 95% CI 1.25, 1.49), prior PPI (OR = 9.17, 95% CI 8.4, 10.0), antibiotic (OR = 2.54, 95% CI 2.29, 2.81) and NSAID use (OR = 1.29, 95% CI 1.18, 1.42), and prior gastroenteritis (OR = 2.19, 95% CI, 1.79, 2.67) were significant predictors for being diagnosed with GERD first. Similar results were found for DGBI.

Prior medication usage and gastroenteritis may play a role in generating gut‐to‐brain pathway disturbances.

Gut–brain pathways are bidirectional, but one pathway may predominate in certain disorders. The brain‐to‐gut pathway predominates in IBS, FD, and GERD, while a gut‐to‐brain disturbance dominates in overlap IBS/FD. Prior medications and gastroenteritis may indicate gut‐brain disturbances and may lead first to DGBI or GERD and later psychological disturbance.