Disorders of gut microbiota and fecal–serum metabolic patterns are associated with pulmonary tuberculosis and pulmonary tuberculosis comorbid type 2 diabetes mellitus

ABSTRACT Pulmonary tuberculosis (PTB) and diabetes mellitus (DM) are prevalent chronic diseases with substantial implications for human health. DM patients are more susceptible to PTB, which exacerbates diabetes-related complications. However, the complex molecular mechanisms underlying the enhanced susceptibility of DM patients to PTB infection remain poorly understood. In this study, α- and β-diversity of gut microbiota was significantly reduced in PTB patients and PTB–DM patients. The abundances of families Lachnospiraceae and Ruminococcaceae in the the Firmicutes phylum were reduced in PTB patients and further diminished in PTB–DM patients. On the other hand, untargeted metabolomics in frozen serum and stool samples indicated that phenylalanine, tyrosine, and tryptophan biosynthesis, metabolites of arginine, proline, tryptophan, and histidine were consistently altered in PTB patients and PTB–DM patients, with significant upregulation of most metabolites. Amino acids like serine, proline, and histidine were both remarkably elevated in PTB and PTB–DM patients. The correlation network analysis reveals the relationships between the shared microbial biomarkers and the shared metabolic pathways. This research contributes to the exploration of pivotal diagnostic biomarkers for both patients with PTB and PTB accompanied by diabetes. Specifically, shared reductions were identified in the genera g-Roseburia , g-Ruminococcaceae_UCG.013 , g-Ruminococcaceae_NK4A214 , g-Lachnospiraceae _ unclassified , and g-Firmicutes _ unclassified in addition to notable regulation of amino acids, like glycine, serine, and histidine in patients with PTB and PTB–DM. Our study expands the comprehension of the intricate connections linking gut microbiota, fecal metabolites, and serum metabolites in PTB and PTB–DM patients. IMPORTANCE This study expands the understanding of the complex links between gut microbiota, fecal metabolites, and serum metabolites in patients with PTB and PTB-DM through multi-omics techniques. It is helpful for us to understand the complex molecular mechanism of increased susceptibility to PTB infection in diabetic patients.