Introduction
Individuals with disorders of brain gut interaction (DBGI) such as irritable bowel syndrome (IBS) and functional dyspepsia (FD) have symptoms that generally originate either first in the GI tract (e.g. fullness, pain: gut to brain) or brain (e.g. anxiety: brain- to –gut). It is unclear however what risk factors may moderate the order of incidence of either a DBGI or psychological diagnosis.
Aims & Methods
This study aimed to determine the proportion of individuals in general practice with a diagnosis of a DBGI (IBS and/or FD, IBS only, FD only, overlap IBS/FD) prior to a mood or anxiety disorder (gut to brain), and vice versa (brain to gut) and whether specific factors moderate the order of incidence of the diagnosis. Data was collected from a retrospective study of 152,674 patients diagnosed with a DBGI (excluding inflammatory bowel disease, coeliac disease, peptic ulcer disease, colorectal and gastric cancer) and psychological disorder (mood or anxiety disorder) at general practices in the United Kingdom over an average period of 16 years (SD=7 years). Information on which diagnosis appeared first was recorded (January 1994 to end 2022, inclusive). Multiple logistic regression was performed to compare a diagnosis of a DBGI (IBS and/or FD) first versus psychological diagnosis first on a range of sociodemographic factors (age, gender), medical conditions (allergy, eczema, Helicobacter pylori, Type 1 and Type 2 diabetes, autoimmune disease, rheumatoid arthritis, lupus, scleroderma, alcohol related diseases and prior gastrointestinal infection) and medication usage (antibiotics, proton pump inhibitors (PPI) and non-steroidal anti-inflammatory drugs (NSAIDs)) ever and prior to a diagnosis of either a DBGI or psychological disorder. Only individual moderators that reached the criterion of p<0.01 are included in the multivariate model.
Results
Of the 152,674 eligible individuals in the UK GP data set, just over half (56.2% n=85843) were diagnosed with a mood or anxiety disorder first compared with (42.9%, n=64739, 55.43%) a DBGI first. In a multivariate model being female, prior GI infection and prior PPI, antibiotic and NSAID use significantly increased the odds of being diagnosed with a DBGI first, whereas alcohol related diseases, asthma and ever having PPI and NSAID use significantly reduced the odds of having a DBGI diagnosis first (Table 1). Of clinical relevance people diagnosed with a DBGI first were twice as likely to have had prior PPI use compared with those with a psychological diagnosis first (OR=2.0, 95%CI 1.94, 2.06; P=0.000). These results were similar for IBS only, FD only and overlap DBGI.
Table 1. Multivariate model of predictors of a DBGI prior to a mood or anxiety disorder
Variable
| OR (95%CI)
| P Value
|
Female Gender
| 1.21 (1.18,1.23)
| 0.0000
|
Alcohol related diseases
| 0.66 (0.61,0.71)
| 0.0000
|
Asthma
| 0.92 (0.90,0.95)
| 0.0000
|
Prior GI infection
| 1.23 (1.16,1.31)
| 0.0000
|
Ever PPI use
| 0.66 (0.64,0.67)
| 0.0000
|
Ever NSAID use
| 0.89 (0.86,0.91)
| 0.0000
|
Prior PPI use
| 2.0 (1.94,2.06)
| 0.0000
|
Prior NSAID use
| 1.06 (1.04,1.09)
| 0.0000
|
Prior antibiotic use
| 1.19 (1.16,1.22)
| 0.0000
|
Conclusion
In a large sample of primary care patients, prior PPI use was associated with an increased probability of a gut to brain pathway. While PPI use may indicate the presence of a upper gut DGBI, the data may equally point towards the possibility that PPI use may cause changes in the gut microbiome including reduced bacterial richness.