Novel fecal microbiota associations with common diseases and medications revealed in the TwinsUK cohort

While changes in the human gut microbiome’s composition and function have been related to several diseases and types of medication, variability between studies limits the comparing of findings. Another factor that limits our understanding of how disease-medication interactions have an impact on gut microbiota is the fact that the gut microbiome has been studied in relation to single diseases without considering the concomitant presence of multiple conditions usually shown by patients in clinical practice.

A new cross-sectional study, led by Dr. Claire Steves from King’s College London (UK), has identified new fecal microbiota associations with 17 diseases and 19 prescription drugs, together with shared associations between them.

The researchers looked at fecal microbiota composition associations with 38 self-reported common diseases and 51 common prescription medications in 2737 individuals from the TwinsUK cohort, of whom 89% female with mean age of 60 and mean body mass index (BMI) of 26 kg/m². What makes this population unique is its well characterized phenotype, as this group of older British twins have shared their health story and many biological samples for over 25 years.

Fecal microbiota composition was studied using 16S ribosomal ribonucleic acid gene sequencing and 68 gut microbiome taxa and diversity measures were used in analyses. Associations were adjusted for age, BMI and technical confounders.

Common diseases reported in the cohort included hypercholesterolemia, respiratory allergies, anxiety, osteoarthritis, hypertension, celiac disease, epilepsy and inflammatory bowel disease (IBD). Among the 38 common diseases that were self-reported, diversity measures showed that 17 had significant associations with gut microbiota markers.

New associations not previously reported include negative associations between Prevotellaceae and food allergy, Mollicutes and cholelithiasis, Odoribacteraceae and urinary incontinence, Deltaproteobacteria and acne, and Lentisphaeria and osteoarthritis. IBD, type 2 diabetes, constipation, recurrent urinary tract infections, food allergies and celiac disease showed the greatest association with the gut microbiota.

On the other hand, almost all the 68 microbiota markers studied showed associations with at least two diseases and were classified into two groups depending on a lower or higher abundance with disease states. These results are in agreement with previous findings that have reported gut microbiota differences across multiple diseases and which are likely to be part of a non-specific shared response to health and disease.

In a recent article in The Independent, Claire Steves highlighted how the researchers were surprised by how specific gut microbes such as Enterobacteriaceae increased across a range of diseases—gut microbiome composition was fairly similar across multiple diseases. These bacteria have adapted in order to survive in higher oxygen environments than the normal colon and usually harbor antibiotic-resistant genes. In contrast, specific commensal gut microbes with known health benefits were reduced in all 38 diseases studied.

According to Steves: “The most striking finding from our analysis was that the microbes weren’t specific to individual diseases, but rather to the state of general health. From a biological perspective, this makes sense. The environment that each bug likes is quite specific; anything that alters it, even slightly, means some sensitive bugs won’t survive.”

Significant fecal microbiota associations with 19 common medications were also found. Novel associations included paracetamol and opioids with a higher abundance of Streptococcaceae, a negative association between selective serotonin reuptake inhibitors (SSRIs) and Turicibacteraceae abundance, and a negative association between inhaled anticholinergic medication and Ruminococcaceae and Peptococcaceae abundance and alpha diversity. Proton pump inhibitors, antibiotics, anticholinergic inhalers, paracetamol, SSRIs and opioids showed the greatest association with the gut microbiota.

Some medications shared similar associations across several microbiota markers. These results can be explained by the impact of common diseases on the gut microbiome composition and also by the drug’s own mechanism of action.

Finally, overlap of disease and treatment associations in the gut microbiota were also found, which made separating the effect of the disease and that of the medication difficult in most cases.

This is the latest large-cohort gut microbiota association study to find microbiota associations with 17 diseases and 19 prescription drugs, with some novel drug associations including paracetamol, opioids, SSRIs and anticholinergic inhalers. Based on these findings, future studies of the gut microbiome should include disease and medication interactions when analyzing and interpreting the results.

Reference:

Jackson MA, Verdi S, Maxan ME, et al. Gut microbiota associations with common diseases and prescription medications in a population-based cohort. Nat Commun. 2018; 9(1):2655. doi: 10.1038/s41467-018-05184-7.