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Furthermore, T2DM increases susceptibility to TB and vice versa, worsening disease outcomes. This comorbidity is, however, not well described nor understood, despite its rising prevalence globally.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This investigation aimed to better characterize the urinary metabolic profiles of patients with the TB and T2DM comorbidity in a South African cohort, to better understand its metabolic basis and associated clinical implications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using untargeted GCxGC-TOFMS metabolomics, urine samples from 17 patients with TB and T2DM and 34 healthy controls were analyzed and statistically compared to identify significantly altered urinary metabolites.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      TB-T2DM comorbid patients were characterized by altered metabolism of: (1) tryptophan and kynurenine (reduced kynurenic acid, anthranilic acid, picolinic acid) associated with changes to NAD\n                      <jats:sup>+<\/jats:sup>\n                      synthesis and a redox imbalance, (2) nucleotides (reduced 3-aminoisobutyric acid, orotic acid, thymine, \u03b2-alanine, adenine, hypoxanthine), (3) tyrosine (reduced 3,4-dihydroxyphenylglycol, 4-hydroxy-3-methoxyphenylglycol, hydroxyphenylpyruvate), (4) lipids (reduced dec-2-enedioate, adipic acid, methylmalonic acid), (5) reduced concentrations of various glycine conjugates associated with glycine depletion, and (6) reduced urinary concentrations of various gut microbial metabolites indicative of microbial dysbiosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These results indicate several metabolic disruptions to amino acids, nucleotides, lipids, NAD\u207a homeostasis and the host microbiome, in TB-T2DM patients, mainly driven by inflammation and oxidative stress. Overall, the findings indicate synergistic amplification of metabolic stress, associated with immune suppression and TB-T2DM disease progression, and subsequently suggests how TB increases T2DM susceptibility and vice versa, as foundation for further investigations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11306-025-02389-y","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T12:28:48Z","timestamp":1768825728000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Characterizing the tuberculosis and type 2 diabetes mellitus comorbidity in a South African cohort using untargeted GCxGC-TOFMS metabolomics"],"prefix":"10.1007","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4849-3500","authenticated-orcid":false,"given":"Karla","family":"Reinecke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1635-253X","authenticated-orcid":false,"given":"L\u00e9anie","family":"Kleynhans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2487-125X","authenticated-orcid":false,"given":"Katharina","family":"Ronacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0339-6237","authenticated-orcid":false,"given":"Du Toit","family":"Loots","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,19]]},"reference":[{"key":"2389_CR1","doi-asserted-by":"publisher","first-page":"4065","DOI":"10.1007\/s11033-020-05413-7","volume":"47","author":"B Acharya","year":"2020","unstructured":"Acharya, B., Acharya, A., Gautam, S., Ghimire, S. 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