Spatial bacterial subpopulations of a human lung lobe and their potential impact on the progression of pulmonary tuberculosis

Better understanding the spatial variation in resident pulmonary bacteria can help to link the disease severity of pulmonary tuberculosis (TB) with lung bacteriomes. This study aimed to investigate bacterial compositions in subniches of a lung lobe from pulmonary TB patient with two separate visible lesions. There were no significant differences between the bacterial compositions in normal tissue and TB lesions, but the bacterial compositions of the two TB lesions differed significantly (P = 0.009). Interestingly, 52 OTUs (relative abundance >1%) that specifically inhabiting certain lung niches were observed and they were affiliated with five phyla. Specific OTUs affiliated with Firmicutes mainly inhabited normal tissues. The dominant phylum in the lung subniches was Proteobacteria, with a relative abundance between 67.03% and 99.99%. Ralstonia, Achromobacter, and Pseudomonas were the most abundant genera, collectively accounting for 34.02% of total bacterial species. A total of 667 of the 700 bacterial connections in a co-correlation network of 145 OTUs (Operational Taxonomic Unit) were positive, indicating a cooperative relationship between bacterial members. Using PICRUSt tool, we do predict bacterial MetaCyc functions responsible for lipid synthesis and heme biosynthesis across the lung lobe that are essential for generation of caseous necrosis and TB disease pathology. MetaCyc pathways responsible for the degradation of aromatic biogenic amines, sulfur oxidation, and denitrification were all related to M.tb growth status, and they were significantly enriched in the lesion with necrosis than that with inflammation. These results open a new insight for us to comprehend the spatial profile of bacteriomes in a pulmonary TB human lung lobe, and shed light on the design of future diagnosis and treatment for pulmonary TB disease.