Gut Mycobiota Dysbiosis in Pulmonary Tuberculosis Patients Undergoing Anti-Tuberculosis Treatment

Abstract

ABSTRACT Patients with pulmonary tuberculosis (TB) undergoing anti-tuberculosis (anti-TB) treatment were previously reported to present gut bacterial microbiota dysbiosis, but the role of the mycobiota has not been reported. Here, we conducted a follow-up study of 29 naive TB patients who received first-line anti-TB drug treatment; we collected their fecal samples at different time points, as well as 22 fecal samples from healthy subjects. Fungal ITS2 and bacterial 16S rRNA amplicon sequencing were used to analyze the effects of active TB and anti-TB treatment on the gut microbiota. We found that naive TB patients had bacterial and fungal dysbiosis with altered community composition and a decreased density of the transkingdom correlation network. Anti-TB drug treatment significantly decreased the diversity of bacteria and fungi with altered composition. Notably, we observed that the abundance of Purpureocillium lilacinum tended to decrease and Nakaseomyces spp. tended to increase in the anti-TB treatment, and all of them had increased proportions in the three TB groups compared with healthy subjects. We found that the fungal-bacterial transkingdom network was severely altered in TB patients after 2 months of treatment, and new fungal-enriched connections that were not observed in other groups after 6 months of treatment. This study provides the first detailed analysis of dysbiosis of the gut mycobiota due to active TB and anti-TB treatment. The results suggest that fungi play an important role in the balance of the gut microbiota and may be associated with the progression of TB, influencing the microbiota and immunity homeostasis in those receiving anti-TB treatment. IMPORTANCE Numerous studies have shown that the gut bacterial microbiota is altered in active TB patients and that anti-TB drugs have profound and long-term impacts. However, as an integral part of the microbiota, fungi have rarely been studied. The need to investigate both the bacterial and fungal microbiota, as well as the relationship between them is apparent. The significance of our study is in our examination of the changes in the bacterial and fungal microbiota simultaneously in both active TB and patients receiving anti-TB treatment. We found that fungi play an important role in the bacterial-fungal transkingdom network, especially during the anti-TB therapy. These findings underscore the importance of fungi in gut microbiota dysbiosis during active TB and anti-TB treatment processes. In addition, our findings suggest it is meaningful to research potential adjunctive therapies that reduce fungal expansion and increase commensal bacterial abundance after anti-TB treatment, which would help the recovery of TB patients.

Keywords

• gut mycobiota
• anti-tuberculosis treatment
• pulmonary tuberculosis