Changes in gut microbiome following anti-tuberculosis treatment: a prospective cohort from eastern China.

Abstract

Background: The treatment of people with tuberculosis necessitates the administration of both broad-spectrum and narrow-spectrum antibiotics for a minimum duration of six months. Prolonged antibiotic therapy may result in dysregulation of the gut microbiota, potentially influencing the onset and progression of tuberculosis. There is a paucity of studies focus on the characteristics of gut microbiota changes at various time points during tuberculosis treatment. This study aims to elucidate the relationship between the composition of gut microbiota and their stage within anti-tuberculosis therapy.

Methods: A multi-center, observational prospective cohort study was conducted at four designated hospitals in Jiangsu Province in eastern China. The Gastrointestinal Symptom Rating Scale was employed to evaluate the gastrointestinal discomfort experienced during anti-tuberculosis treatment. Fecal samples were collected at baseline before initiating anti-tuberculosis therapy and at the end of 2 months and 6 months during treatment. Total microbial genomic DNA was extracted and sequenced. Rarefaction curves and alpha diversity indices including observed operational taxonomic units, Chao1 richness and Shannon index were calculated.

Results: From October 2020 to December 2022, a total of 204 people with tuberculosis were diagnosed. Among these, 85 people with tuberculosis provided baseline, 2-month, and 6-month fecal samples. The average age was 41.8 ± 15.193 years, with a gender ratio of 77 males to 8 females. Only 28.2% of the cohort reported being free of gastrointestinal symptoms during anti-tuberculosis treatment. Anti-tuberculosis treatment significantly reduced gut microbiota diversity, with a transient decrease in alpha diversity indices observed after two months. A higher alpha diversity in baseline (Shannon index with mean ± standard deviation (SD) 2.92 ± 0.93 vs. 2.50 ± 0.84, P = 0.0014, inverse Simpson's index with 11.9 ± 8.66 vs. 7.87 ± 6.42, P = 0.0012), compared with people with tuberculosis after 2 months of treatment. No significant differences were identified between 2 months of treatment and at the end of treatment microbiota diversity (Shannon index 2.50 ± 0.84 vs 2.58 ± 0.81, P = 0.55, inverse Simpson's index 7.87 ± 6.42 vs 11.90 ± 8.66, P = 0.43).

Conclusions: Findings from our study show that anti-tuberculosis treatment has profound effects on people with tuberculosis gastrointestinal function and the gut microbiota, particularly during the intensive phase of therapy. After the intensive treatment phase, the gut microbiota has partially recovered, but it is an extremely slow process.