Gut microbiota characteristics and its biological function analysis in patients with tuberculosis and diabetes mellitus co-morbidity.

Tuberculosis and diabetes mellitus co-morbidity (TB_DM) poses harmful for human health and not conducive to early control. The gut microbiota has been proven to play an important role in a variety of diseases. In this study, we investigated the characteristics of the intestinal flora according to 16s rRNA sequencing results in their fecal samples in TB_DM, screened out independent bacterial genera to determine their diagnostic alone and in combination and explore their biological functions. A total 128 patients of 40 patients with diabetes mellitus (DM group), 40 patients with tuberculosis (TB group), 48 patients with TB_DM who met inclusion and exclusion criteria and 40 healthy persons as control group (HC group). We found that the sparse curves of the four groups were stable. The OTU analysis showed the most genus classification in the HC group and the least ones in the TB_DM group. Compared with the HC group, the α and β diversity were significantly decreased in the DM, TB and TB_DM group, particularly in TB_DM group. In the screening of independent genera, top 14 differential genera were found between the DM and the TB_DM group and top 18 ones between the TB and the TB_DM group.The top 3 bacterial genera Enterococcus, Flavonifractor and Romboutsia between DM and TB_DM groups were identified for analyzing diagnostic efficacy. The AUC, 95%CI, sensitivity and specificity were 0.742, 0.638 ~ 0.846, 64.58% and 80.00% in Enterococcus; 0.663, 0.547 ~ 0.779, 75.00% and 60.00% in Flavonifractor; 0.646, 0.530 ~ 0.762, 54.17% and 77.50% in Romboutsia and 0.835, 0.752 ~ 0.918, 79.17% and 75.00% in combined them, respectively. Also, the top 3 different genera Paeniclostridium, Dialister, and Lachnospira were found between TB and TB_DM groups for evaluating above diagnostic efficacy. The AUC, 95%CI, sensitivity and specificity were 0.716, 0.607 ~ 0.824, 81.25% and 57.50% in Paeniclostridium; 0.689, 0.575 ~ 0.803, 87.50% and 50.00% in Dialister; 0.672, 0.557–0.786, 83.33% and 55.00% in Lachnospira; and 0.914, 0.853 ~ 0.975, 85.42% and 85.00% in combined them, respectively. PICRUSt2 analysis indicated that differentially expressed genes (DEGs) predominantly influenced porphyrin and chlorophyll metabolism, pantothenate and CoA biosynthesis, as well as D-alanine metabolism between the DM and TB_DM groups. Furthermore, the DEGs were primarily associated with porphyrin and chlorophyll metabolism, Alzheimer’s disease and carotenoid biosynthesis when comparing the TB group to the TB_DM group. Our results provide key insights into the intestinal flora diversity, function and its independent genus in distinguishing TB_DM, TB and DM patients.