Alternation of Gut Microbiota in Patients with Pulmonary Tuberculosis

Abstract

One-third of the world's population has been infected with Mycobacterium tuberculosis (M. tuberculosis), a primary pathogen of the mammalian respiratory system, while about 10% of latent infections progress to active tuberculosis (TB), indicating that host and environmental factors may determine the outcomes such as infection clearance/persistence and treatment prognosis. The gut microbiota is essential for development of host immunity, defense, nutrition and metabolic homeostasis. Thus, the pattern of gut microbiota may contribute to M. tuberculosis infection and prognosis. In current study we characterized the differences in gut bacterial communities in new tuberculosis patients (NTB), recurrent tuberculosis patients (RTB), and healthy control. The abundance-based coverage estimator (ACE) showed the diversity index of the gut microbiota in the patients with recurrent tuberculosis was increased significantly compared with healthy controls (p < 0.05). At the phyla level, Actinobacteria and Proteobacteria, which contain many pathogenic species, were significantly enriched in the feces RTB patients. Conversely, phylum Bacteroidetes, containing a variety of beneficial commensal organisms, was reduced in the patients with the recurrent tuberculosis compared to healthy controls. The Gram-negative genus Prevotella of oral origin from phylum of Bacteroidetes and genus Lachnospira from phylum of Firmicutes were significantly decreased in both the new and recurrent TB patient groups, compared with the healthy control group (p < 0.05). We also found that there was a positive correlation between the gut microbiota and peripheral CD4+ T cell counts in the patients. This study, for the first time, showed associations between gut microbiota with tuberculosis and its clinical outcomes. Maintaining eubiosis, namely homeostasis of gut microbiota, may be beneficial for host recovery and prevention of recurrence of M. tuberculosis infection.

The role of the lung microbiota and the gut-lung axis in respiratory infectious diseases

“…These studies revealed that bacterial diversity in the gut of TB patients is altered and this may correlate with the progress of the disease (Luo et al, 2017;Maji et al, 2018). These studies revealed that bacterial diversity in the gut of TB patients is altered and this may correlate with the progress of the disease (Luo et al, 2017;Maji et al, 2018).…”

“…Gut microbiota has been analysed during the course of TB infections and also during anti-TB treatment in humans. These studies revealed that bacterial diversity in the gut of TB patients is altered and this may correlate with the progress of the disease (Luo et al, 2017;Maji et al, 2018). Anti-TB therapy includes antibiotics, such as rifampicin, that target bacteria other than mycobacteria, and one study showed that prolonged anti-TB treatment broadly alters the gut microbiota of TB patients and that the resulting dysbiotic state persists following cessation of therapy (Wipperman et al, 2017).…”

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

“…The findings above, nevertheless, differed from three studies conducted in China (Table 1). 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).…”

“…(Table 1). 6,14 Nevertheless, HRZE exposure reduced genera belonging to Clostridiales, such as Ruminococcus spp., Ruminococcus gnavus, and Faecalibacterium spp., while Bacteroidetes members, such as Bacteroides spp. (B. fragilis, B. plebeius, B. caccae, and B. coprophilus), and Parabacteroides distasonis, were significantly enriched.…”

“…Furthermore, as Mtb can revert to dormancy/latency within the host and later revived into active disease, some investigators question whether there are different effects of latent and recurrent TB on lung-gut microbiome dynamics. 4,6,14 Given the intracellular nature of Mtb, it remains to be seen if it can directly cause dysbiosis. It is also not clear if Mtb can indirectly cause dysbiosis through immune dysregulation, particularly given that a strong association between the microbiota and immune system has been already established.…”