CHANGES IN HUMAN GUT MICROBIOTA INDUCES BY DOTS TREATMENT IN TB PATIENTS OF INDIAN COHORT

Abstract

Objective: Dysbiosis of the gut microbiota can lead to many prolonged maladies such as inflammatory bowel disease, obesity, cancer and autism. It is now also known that antibiotic usage exert strong effects on metabolism of intestinal microbes and thus the human health. But, there is not much systematic characterization of microbiota associated with the Tuberculosis (TB) patients and DOTS. Accordingly, a comparative metagenomics analysis of human gut microbiota of fecal samples taken at several time points from TB patients subjected to DOTS (Direct Observed Treatment, Short-course) was conducted. Methods: Fecal DNA of 6 different TB patients were collected at three different time points viz. at the time of diagnosis, after 1 week and after 1 month of DOTS and from their healthy family member, was sequenced using Illuminia HiSeq 2000 sequencer at BGI, China. Metagenomics approach was adopted to investigate the taxonomic diversity and functional profile from the data thus obtained, for associated variations in the human gut microbiome of TB patients before, during and after 1 month of DOTS. Further results were compared with the taxonomic diversity and functional profile of healthy human gut microbiota. Results: We apparently observed oscillatory population dynamics in all the samples. Prevotella copri was the most abundant species in all samples except “T” and “U” controls. Also, striking difference in relative abundance of Prevotella copri in ‘Y’ sample was observed where controls displayed its high prevalence in the gut but it remained only a minority in ‘YTB’. An inverse relationship was observed between members of phylum Bacteroidetes and phylum Firmicutes. Many pathways were found to be enriched in TB (0th day) samples. We may conclude that short-term surveillance of TB patients under DOTS pointed towards it minimal effect on the gut microbiota. Also, no fixed trends were observed in case of both taxonomic diversity and functional composition of the gut. Conclusions: The present study envisioned inter-relationships between taxonomic diversity and functional profile of human gut microbiome and Tuberculosis. The study provides report of human gut microbiota variations to follow-up DOTS. However insights obtained until the midway of this study, suggests that further metagenomic investigations on larger population of TB patients are required to accurately describe the association of the human gut microbiome with TB and DOTS.