Table 1.

Summary of recent studies on gut microbiome and tuberculosis

Authors	Study location	Study type	Study description	Main differences in microbiota between groups	Immune correlates/effect	Ref
Hu et al. (2019)	China	Human	A total of 46 TB cases and 61 controls. Patients were newly diagnosed with pulmonary TB and anti-TB drug naïve.	1. SCFA producers enriched in control cohorts compared to TB cases 2. Three microbiota signatures comprising Roseburia hominis, Roseburia inulinivorans and Hemophilus parainfluenzae discriminated active TB cases from healthy controls with AUC of 84.4%		[13]
Khan et al. (2019)	Canada	Animal	Experimental animals were pretreated with INH/PYZ or RIF followed by H37Rv infection. Control animals were antibiotics untreated but infected with H37Rv. 4-5 mice per group	1. Significant difference in Clostridia IV and XIV following INH/PYZ treatment. 2. RIF depleted Firmicutes population and increased Verrucomicrobia and Bacteroidetes abundance	INH/PYZ treatment dampened alveolar macrophage spare respiratory capacity, basal respiration and ATP production. Reduced IL-1β, TNF-α and MHCII. Increased macrophage permissiveness and mouse susceptibility to M.tb which was reversed by FT	[3]
Hu et al. (2019)	China	Human	A total of 61 TB cases, 10 LTBI and 13 healthy controls. TB cases were divided into 28 active TB, 13 and 10 TB patients on 1- and 2-weeks anti-TB therapy, respectively, and 10 cured TB patients	1. Minor changes during M.tb infection mainly within the genus Bacteroides 2. Decreased Ruminococcus and Fecaelibacterium belonging to Clostridiales and increased Bacteroides during anti-TB drug treatment.		[5]
Dumas et al. (2018)	France	Animal	Treatment of mice with broad-spectrum antibiotics, infection with M.tb followed by FT	Bacteroidetes and Firmicutes depleted, Proteobacteria enriched in antibiotics-treated animals	No change in neutrophils, macrophages, dendritic cells, IFN-γ, TNF-α and IL-1β in antibiotics-treated animals. Decrease in MAIT cells and IL17A in treated animals and increased M.tb susceptibility. FT improved immunity	[2]
Luo et al. (2017)	China	Human	37 TB patients and 20 healthy controls. TB patients were divided into NTB (new diagnose with TB and less than I week anti-TB treatment) and RTB (previously treated and cured prior to becoming culture-positive)	1. Bacteroidetes decreased while Actinobacteria and Proteobacteria increased in RTB 2. Depleted Lachnospira and Prevotella genus in NTB and RTB	Both Prevotella and Lachnospira positively and negatively correlated with CD4 T cell count in NTB and RTB, respectively.	[8]
Wipperman et al. (2017)	Haiti	Human	Cohorts of 19 TB patients on treatment, 19 patients treated and cured of TB and 75 controls. 3 TB patients were on treatment for more than 6 months. Controls were divided into 50 IGRA positive and 25 IGRA negative (LTBI)	1. Clostridium, Fusobacterium and Prevotella enriched whereas, Lactobacillus, Coprococcus, Ruminococcus and Bifidobacterium depleted in treatment cases 2. Bacteroides depleted, while Ruminococcus, Faecalibacterium and Eubacterium were enriched in cured patients		[6]

Authors	Study location	Study type	Study description	Key microbiota differences between groups	Immune correlates/effect	Ref
Huang et al. (2019)	Taiwan	Human	Cohorts consisting of 25 active TB, 32 LTBI and 23 healthy controls	Differences in Firmicutes/Bacteroidetes ratio between groups	Number of neutrophils correlated with abundance of Bacteroidetes in latent and active TB, Coriobacteriales abundance positively correlated to IFN-γ production in latent TB cases	[39]
Namasivayam et al. (2017)	USA	Animal	Infection of mice with M.tb followed by treatment with anti-TB drugs for up to 4 months	Anti-TB antibiotics-treated depleted Ruminococcus, Butyricicoccus, Acetivibrio, Alkaliphilus and Peptococcus genera while Erysipelatoclostridium was increased		[7]
Khan et al. (2016)	India	Animal	Treatment of mice with broad-spectrum antibiotics, infection with M.tb followed by FT	Decline in Bifidobacterium, Lactobacillus Campylobacter and Bacteroides. Increase in Enterococcus in treated animals	Increased Tregs, decreased IFN-γ and TNF-α- producing Th1 cells. Increased M.tb burden in lung and spleen in antibiotics-treated animals. FT improved mouse immunity	[38]
Maji et al. (2018)	India	Human	6 TB patients and 6 healthy household contacts as control. Stool collected from TB patients before the start of treatment, 1 week and 1 month into treatment.	1. Butyrate and propionate producing bacteria, e.g., Eubacterium rectale, Faecalibacterium prausnitzii, and Roseburia inulinivorans abundance increased in TB cases. Prevotella and Bifidobacterium were enriched in controls 2. Biosynthesis of amino acids and vitamin metabolism declined in TB patients		[23]

SCFA Short chain fatty acid, FT faecal transplant, INH Isoniazid, RIF Rifampicin, PYZ pyrazinamide, LTBI Latent tuberculosis infection, IGRA interferon gamma release assay, IFN-γ interferon gamma, TNF-α tumor necrosis factor-alpha, Th T helper, IL  interleukin, MAIT mucosal associated invariant T, MHCII Major histocompatibility complex II, AUC Area under curve