The Gut Microbiome Signatures Discriminate Healthy From Pulmonary Tuberculosis Patients

Abstract

Cross talk occurs between the human gut and the lung through a gut-lung axis involving the gut microbiota. However, the signatures of the human gut microbiota after active Mycobacterium tuberculosis infection have not been fully understood. Here, we investigated changes in the gut microbiota in tuberculosis (TB) patients by shotgun sequencing the gut microbiomes of 31 healthy controls and 46 patients. We observed a dramatic changes in gut microbiota in tuberculosis patients as reflected by significant decreases in species number and microbial diversity. The gut microbiota of TB patients were mostly featured by the striking decrease of short-chain fatty acids (SCFAs)-producingbacteria as well as associated metabolic pathways. A classification model based on the abundance of three species, Haemophilus parainfluenzae, Roseburia inulinivorans , and Roseburia hominis , performed well for discriminating between healthy and diseased patients. Additionally, the healthy and diseased states can be distinguished by SNPs in the species of B. vulgatus . We present a comprehensive profile of changes in the microbiota in clinical TB patients. Our findings will shed light on the design of future diagnoses and treatments for M. tuberculosis infections.

Mycobacterium tuberculosis, antimicrobials, immunity, and lung–gut microbiota crosstalk: current updates and emerging advances

“…Thus, factors affecting microbiome stability indirectly influence susceptibility to Mtb, such that a restoration of eubiosis reverses Mtb pathogenesis, granulomas, and dissemination. 12,13,30 Therefore, the microbiome-immunity-Mtb interactions are discussed under seven main sections, according to the dysbiotic factors: (1) antimicrobials; (2) immunity; (3) pathogens; (4) Mtb; (5) smoking; (6) diet; and (7) current challenges and future perspectives.…”

“…6,14,30 In particular, the studies in China observed changes in species diversity and abundance between healthy and TB patients. Unfortunately, the antimicrobials used by the cohorts in China, except for one study that used HRZE, 30 were not delineated, as was the case in Haiti (Table 1). Hence, it remains to be seen if the observations made were the result of Mtb infection or of the antimicrobials taken by the patients.…”

“…35 Nevertheless, Hu et al, in two separate studies, have tried to identify distinct microbiome signatures using species composition and single-nucleotide polymorphisms (SNPs) in specific genes involved in carbohydrate metabolism. 6,30 These signatures, which were identified using only patients from China, have been suggested as a TB diagnostic index. Notably, Enterobacter cloacae, Phascolarctobacterium succinatutens, Methanobrevibacter smithii, Bilophila spp., and Parabacteroides spp.…”

“…were distinct in cured patients, while Haemophilus parainfluenzae, Roseburia inulinivorans, and Roseburia hominis were abundant in TB patients. 6,30 SNPs in carbohydrate biosynthesis genes were also suggested as distinct biomarkers. 30 Furthermore, Vorkas et al observed a strong correlation between certain gut microbiota species and immune phenotypes in TB contacts.…”

“…6,30 SNPs in carbohydrate biosynthesis genes were also suggested as distinct biomarkers. 30 Furthermore, Vorkas et al observed a strong correlation between certain gut microbiota species and immune phenotypes in TB contacts. For example, the depletion of some species directly correlated with reduced granzyme B inducibility of mucosal-associated invariant T (MAIT) cells, while CD4 + MAIT cells increased in TB contacts.…”