Metabolic and Immune Consequences of Antibiotic Related Microbiome Alterations during first-line Tuberculosis Treatment in Bamako, Mali

Abstract

Abstract Background Tuberculosis (TB) infection is known to lead to the unbalance of the gut microbiota and act synergistically on the decline of the host immune response, when untreated. Moreover, previous work has found a correlation between dysbiosis in the gut microbiota composition and the use of antibiotics. However, there is a need for an in-depth understanding of the metabolic and immune consequences of antibiotic-related microbiome alterations during first-line TB treatment. Methods In a longitudinal cohort study, which included TB-infected cohorts and healthy individuals (control group), we studied the anti-TB-related changes in the gut microbiota composition and related functional consequences. Sputum, whole blood and stool samples were collected from participants at four time-points including before (Month-0), during (Month-2), at the end of drug treatment (Month-6) and 9 months after treatment (Month-15). Controls were sampled at inclusion and Month-6. We analyzed the microbiota composition and microbial functional pathways with shotgun metagenomics, analyzed the blood metabolomics using high-performance liquid chromatography (HPLC), and measured the levels of metabolites and cytokines with cytometric bead array. Results We found that the gut microbiota of patients infected with TB was different from that of the healthy controls. The gut microbiota became similar to healthy controls after treatment but was still significantly different after 6 months treatment and at the follow up 9 months after treatment. Our data also showed disturbance in the plasma metabolites such as tryptophan and tricarboxylic acids components of patients during TB treatment. Levels of IL-4, IL-6, IL-10, and IFN-γ decreased during treatment and levels were maintained after treatment completion, while IL-17A known to have a strong link with the gut microbiota was highly expressed during treatment period and longer than the 9-month post treatment completion. We found that some fatty acids were negatively correlated with the abundance of taxa. For example, Roseburia, Megasphaera, and alpha proteobacterium HIMB5 species were negatively correlated (rho = -0.6) with the quinolinate production. Conclusion Changes in the composition and function of gut microbiota was observed in TB patients before and after treatment compared to healthy controls. The differences persisted at nine months after treatment completion. Alterations in some bacterial taxa were correlated to the changes in metabolite levels in peripheral blood, thus the altered microbial community might lead to changes in immune status that influence the disease outcome and future resistance to infections.