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. 2017 Nov 17:8:822.
doi: 10.3389/fphys.2017.00822. eCollection 2017.

Alternation of Gut Microbiota in Patients with Pulmonary Tuberculosis

Mei Luo  1   2 , Yong Liu  2 , Pengfei Wu  1 , Dong-Xia Luo  2 , Qun Sun  1 , Han Zheng  1 , Richard Hu  3 , Stephen J Pandol  4 , Qing-Feng Li  2 , Yuan-Ping Han  1 , Yilan Zeng  2
Affiliations

Alternation of Gut Microbiota in Patients with Pulmonary Tuberculosis

Mei Luo et al. Front Physiol. .

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.

Keywords: Mycobacterium tuberculosis; gut microbiota; microbial diversity; new tuberculosis; pulmonary tuberculosis; recurrent tuberculosis.

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Figures

Figure 1
Figure 1
Altered biodiversity of gut microbiota in the new and recurrent tuberculosis patients in comparison with healthy control. (A,B) The new TB patients (NTB, n = 19), recurrent TB group (NTB, n = 18), and healthy human subjects, control (CG) are described in the Methods and Materials. The alpha-diversity, richness of gut microbes, was determined by ACE index and Chao1 index. (C,D) The ecological diversity of gut microbiota in the three groups of human subjects was measured by Simpson index and Shannon index. The p-values were calculated using Wilcox test. Statistical significance is displayed as *p < 0.05.
Figure 2
Figure 2
The beta-diversity of the microbial communities in the new and recurrent tuberculosis patients and the healthy control. (A) Principal Coordinates Analysis (PCoA) plot based on unweighted UniFrac distance. Each dot represents one sample from each group. (B) Beta-diversity index difference based on unweighted UniFrac. (C) Beta-diversity index difference based on weighted UniFrac. The p-values were calculated using Wilcox test. Statistical significance is displayed as **p < 0.01.
Figure 3
Figure 3
The major gut bacterial phyla and genus in new and recurrent tuberculosis patients as well as the healthy control. (A) Bacterial phylum levels of new and recurrent tuberculosis groups, NTB and RTB respectively. (B) Bacterial genus levels. (C) Comparison of gut microbiota of relative abundance at the bacterial phylum levels. (D) Comparison of gut microbiota of relative abundance at genus levels. The p-values were calculated using T-test, and significance was compared against the CG. *P < 0.05. **P < 0.01.
Figure 4
Figure 4
Different species as biomarkers in relative abundance identified by LEfSe analysis between the two groups of tuberculosis patients and the healthy control. (A) The length of the column represents the influence of significantly different species in relative abundance (LDA scores > 4). (B) The significantly different species are shown in the clado-gram. Each circle represents phylogenetic level from phylum to genus inside to outside. Each circle's diameter is proportional to the taxon's abundance and biomarker is consistent with the group marked with color. Red in CG, green in NTB, and blue in RTB.
Figure 5
Figure 5
Correlation between the relative abundance of Prevotella, Lachnospira, Streptococcus, Veillonella, Escherichia with blood CD4+ T cell counts. Taxa of bacteria at the genus level were further analyzed at each of patient group. (A,C) The new tuberculosis group. (B,D) The recurrent tuberculosis group. X axis denotes the CD4+ T cell counts/μl. The assessment was done with Spearman's rank order correlation. Black dots indicate data.
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