Perturbation of the human gastrointestinal tract microbial ecosystem by oral drugs to treat chronic disease results in a spectrum of individual specific patterns of extinction and persistence of dominant microbial strains.

Abstract

BackgroundOral drugs can have side effects such as diarrhea that indicate the perturbation of the gut microbial community. To further understand the dynamics of perturbation, we have assessed the strain relatedness of samples from previously published data sets from pre and post bowel evacuation, episodes of diarrhea, and administration of oral drugs to treat diabetes and rheumatoid arthritis.MethodsWe analyzed a total of published five data sets using our strain-tracking tool called Window-based Single Nucleotide Variant (SNV) Similarity (WSS) to identify related strains from the same individual.ResultsStrain-tracking analysis using the first data set from 8 individuals pre and 21-50 days post iso-osmotic bowel wash revealed almost all microbial strains were related in an individual between pre and post samples. Similarly, in a second study, strain-tracking analysis of 4 individuals pre and post sporadic diarrhea revealed the majority of strains were related over time (up to 44 weeks). In contrast, the analysis of a third data set from 22 individuals pre and post 3-day exposure of oral metformin revealed that no individuals had a related strain. In a fourth study, the data set taken at 2 and 4 months from 38 individuals on placebo or metformin revealed individual specific sharing of pre and post strains. Finally, the data set from 18 individuals with rheumatoid arthritis given disease-modifying antirheumatic drugs methotrexate or glycosides of the traditional Chinese medicinal component Tripterygium wilfordii showed individual specific sharing of pre and post strains up to 16 months.ConclusionOral drugs used to treat chronic disease can result in individual specific microbial strain change for the majority of species. Since the gut community provides essential functions for the host, our study supports personalized monitoring to assess the status of the dominant microbial strains after initiation of oral drugs to treat chronic disease.