Abstract
Mycobacterium tuberculosis causes pulmonary tuberculosis, a deadly infection of which the clinical expression and prognosis are not fully understood at the individual level, apart from genetic susceptibility traits. We investigated whether individual gut microbiota may correlate with pulmonary tuberculosis status. Culturomics investigations of gut microbiota in two pulmonary tuberculosis patients and two controls in Burkina Faso found 60 different bacterial species in patients and 97 in controls, including 45 in common. Further analysis of the results at the individual level indicated seven bacteria, including Enterococcus mundtii and Enterococcus casseliflavus, which were exclusively cultured in controls. Blind quantitative PCR-based exploration of faeces samples in two cohorts in Burkina Faso and in France confirmed a nonsignificant association of E. mundtii and E. casseliflavus with controls. Further in vitro explorations found four E. mundtii and E. casseliflavus strains inhibiting the growth of M. tuberculosis strains representative of four different lineages as well as Mycobacterium africanum, Mycobacterium canettii, and Mycobacterium bovis, in an inoculum-dependent manner. Heat-killed E. mundtii or E. casseliflavus were ineffective. These unprecedented observations of direct interactions between gut E. mundtii and E. casseliflavus with M. tuberculosis complex mycobacteria suggest that gut microbiota may modulate the expression of pulmonary tuberculosis.
Highlights
Tuberculosis is a deadly bacterial infection due to mycobacteria forming the Mycobacterium tuberculosis complex (MTBC), and is responsible for a high burden of morbidity and mortality in the most countries worldwide [1]
We investigated faeces samples collected from two TB-positive and two TB-negative patients in Burkina Faso
A total of 60 bacterial species scattered across 28 genera were identified in the stools collected from two TB-positive patients and 97 species scattered across 43 genera were identified in the stools collected in two TB-negative patients
Summary
Tuberculosis is a deadly bacterial infection due to mycobacteria forming the Mycobacterium tuberculosis complex (MTBC), and is responsible for a high burden of morbidity and mortality in the most countries worldwide [1]. The interplay between host and pathogen determining the clinical expression and prognosis of tuberculosis is not fully understood at the individual level. The M. tuberculosis inoculum, genotype and antibiotic susceptibility profile may play in part the clinical expression and prognosis of pulmonary tuberculosis [3,4]. Host traits mostly related to genetic alterations of the interferon gamma pathway have been elucidated in highly susceptible tuberculosis individuals and families [5]. Such genetic traits have been significantly associated with certain clinical expressions of tuberculosis, such as onset in the early years of life [6,7]. At the population level, discrete co-evolution of certain M. tuberculosis genotypes with certain populations has been clearly established in some geographic areas [3,7,8,9]
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