The gut and lung microbiota in pulmonary tuberculosis: susceptibility, function, and new insights into treatment

Figures & data

Figure 1. (A) Prevotella and peripheral CD4+ cells were positively correlated in new-onset TB patients, whereas showed a negative correlation in relapsed TB patients. (B) Bacteroides fragilis upregulated the lncRNA-CGB, which then contacts EZH2 of histone methyltransferase PRC2, negatively controlling the epigenetic regulation of H3K27Me3, leading to increased expression of IFN-γ and a robust capacity to against Mtb. (C) miRNA-21 was predicted to interact with IFN-γ during the dysbiosis of the gut microbiota after constructing a “loss-of-function” model. Then the IFN-γ expression was decreased, which in turn leads to a weakened anti-TB immune function. (D) Anaerostipes may actively engage with “interferon signalling”, “Nur77 signalling” and “inflammasome” pathways, all of which are aimplicated in the pro-inflammatory responses to TB, and therefore it may predict pro-inflammatory responses. (E) The colonization of Helicobacter in mice promoted changes in the gut microbiota, outbreak of inflammation,reduced innate immunity and accumulation of activated T cells, all of which resulted in a loss of the immunity to suppress Mtb infection.

Table 1. Impact of antibiotic therapy on the gut-lung microbiota in TB patients.

Table1			Paticipants				Race	Specimen	Diversity of microbiota in TB	Significant alteration	Ref.
Location	Method	region	TB	Therapy state 1	Therapy state 2	TC
GUT	16s rRNA gene sequencing	V4	28	13(TB-1 week)	10(TB-2 week)	10	Chinese	Fecal	decrease	genus Clostridium Firmicutes decrease while genus Bacteroides increase	[28]
	16s rRNA gene sequencing	V3-V4	29	29(TB2MT)	19(TB6MT)	/	Chinese	Fecal	decrease	genus Bacteroides and Bifidobacterium increase	[55]
LUNG	Metagenome sequencing		12	15(≥2 weeks)	/	11	Chinese	BAL/Throat swab	increase	Staphylococcus aureus and Pasteurella multocida decrease	[48]
	16s rRNA gene sequencing	V3-V4	12	/	/	12	Chinese	BAL	increase	Rothia increase and Serratia decrease	[56]

Table 2. Dysbiosis of gut and lung microbiota in TB.

Table2			Paticipants				Race	Specimen	Diversity of microbiota in TB	Significant alteration	Ref.
Location	Method	region	TB	LTBI	IP	HC
GUT	16s rRNA gene sequencing	V4	28	10	/	13	Chinese	Fecal	α diversity decrease	Genus Bacteroides decreases in TB	[28]
	16s rRNA gene sequencing	V3-V4	83	/	/	52	Chinese	Fecal	α diversity decrease	Genus Bacteroides and Paracoides etc. increase while Blautia, Roseburia etc. decrease	[41]
	16s rRNA gene sequencing	/	56	36	/	50	Chinese	Fecal	α diversity decrease	Genus Bifidobacterium and Bacteroides increase, while Roseburia and Faecalibacterium decrease in TB	[39]
	16s rRNA gene sequencing	/	18	/	/	18	Chinese	Fecal	decrease	Genus Enterococcus and Prevotella increase while Faecalibacterium, Bacteroides and Dorea decrease	[43]
	16s rRNA gene sequencing	V4	37(18NTB +19RTB)	/	/	20	Chinese	Fecal	/	Genus Prevotella and Lachnospira decrease in both new and recurrent TB patients	[44]
LUNG	Realtime-PCR	Mashhad/TB = 10; Control = 5	10	/	/	6	Mashhad	BAL	/	Genus Streptococcus increases	[23]
	Metagenome sequencing		12	15(≥2 weeks)	/	11	Chinese	BAL/Throat swab	increase	Staphylococcus aureus and Neisseria gonorrhoeae were enriched in untreated PTB group	[48]
	16s rRNA gene sequencing	V6-V7	25	/	/	16	Indian	Sputum	increase	Genus Streptococcus, Neisseria and Veillonella are dominant genera.	[49]
	16s rRNA gene sequencing	V3-V4	11	19	/	18	Chinese	Nasopharyngeal swab samples	no difference	Compared with LTBI group, Proteobacteria and Gammaproteobacteria increase in TB. Compared with HC group, Pseudomonadales and Moraxellaceae increase, while Bacillales and Lachnospiraceae decrease in TB.	[50]

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Data availability statement

The datasets generated or analyzed during this study are available in PubMed.