The influence of non-steroidal anti-inflammatory drugs on the gut microbiome

Abstract

The composition of the gut microbiome with the use of non-steroidal anti-inflammatory drugs (NSAIDs) has not been fully characterized. Drug use within the past 30 days was ascertained in 155 adults, and stool specimens were submitted for analysis. Area under the receiver operating characteristic curve (AUC) was calculated in logit models to distinguish the relative abundance of operational taxonomic units (OTUs) by medication class. The type of medication had a greater influence on the gut microbiome than the number of medications. NSAIDs were particularly associated with distinct microbial populations. Four OTUs (Prevotella species, Bacteroides species, family Ruminococcaceae, and Barnesiella species) discriminated aspirin users from those using no medication (AUC = 0.96; 95% CI 0.84-1.00). The microbiome profile of celecoxib users was similar to that of ibuprofen users, with both showing enrichment of Acidaminococcaceae and Enterobacteriaceae. Bacteria from families Propionibacteriaceae, Pseudomonadaceae, Puniceicoccaceae and Rikenellaceae were more abundant in ibuprofen users than in controls or naproxen users. Bacteroides species and Erysipelotrichaceae species discriminated individuals using NSAIDs plus proton-pump inhibitors from those using NSAIDs alone (AUC = 0.96; 95% CI 0.87-1.00). Bacteroides species and a bacterium of family Ruminococcaceae discriminated individuals using NSAIDs in combination with antidepressants and laxatives from those using NSAIDs alone (AUC = 0.98; 95% CI 0.93-1.00). In conclusion, bacteria in the gastrointestinal tract reflect the combinations of medications that people ingest. The bacterial composition of the gut varied with the type of NSAID ingested.

Keywords: Bacteria; drug; gastrointestinal tract; microbiota; non-steroidal anti-inflammatory drugs.

FIGURE 1

Gut Bacterial Operational Taxonomic Units (OTUs) for Subjects using only one Medication versus Subjects using no Medication

FIGURE 2

Prevalence of Gut Bacterial Families for Subjects using only NSAIDs versus Subjects not using Medications

FIGURE 3

ROC Curves for Individuals Taking (A) NSAIDs or (B) Naproxen showing Discrimination by Age, Gender and Microbiome Data

FIGURE 4

Heat Map for Bacterial Families showing differences in Relative Abundance by Medication Use

FIGURE 5

Principal Component Analysis Biplot of Bacteria to distinguish Ibuprofen Users from Naproxen Users

FIGURE 6

Relative Abundance of Bacterial Operational Taxonomic Units (OTUs) by Medication Type