iScience (Mar 2024)
An integrative multi-omics approach to characterize interactions between tuberculosis and diabetes mellitus
- Caian L. Vinhaes,
- Eduardo R. Fukutani,
- Gabriel C. Santana,
- María B. Arriaga,
- Beatriz Barreto-Duarte,
- Mariana Araújo-Pereira,
- Mateus Maggiti-Bezerril,
- Alice M.S. Andrade,
- Marina C. Figueiredo,
- Ginger L. Milne,
- Valeria C. Rolla,
- Afrânio L. Kristki,
- Marcelo Cordeiro-Santos,
- Timothy R. Sterling,
- Bruno B. Andrade,
- Artur T.L. Queiroz
Affiliations
- Caian L. Vinhaes
- Laboratório de Pesquisa Clínica e Translacional, Instituto Gonçalo Moniz, FUndação Oswaldo Cruz, Salvador 40296-710, Brazil; Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador 41810-710, Brazil; Programa de Pós-Graduação em Medicina e Saúde Humana, Escola Bahiana de Medicina e Saúde Pública (EBMSP), Salvador 40290-150, Brazil; Departamento de Infectologia, Hospital Português da Bahia, Salvador 40140-901, Brazil; Instituto de Pesquisa Clínica e Translacional, Faculdade de Tecnologia e Ciências, Salvador 41741-590, Brazil
- Eduardo R. Fukutani
- Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador 41810-710, Brazil; Instituto de Pesquisa Clínica e Translacional, Faculdade de Tecnologia e Ciências, Salvador 41741-590, Brazil; Centro de Integração de Dados e Conhecimentos para Saúde, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil
- Gabriel C. Santana
- Laboratório de Pesquisa Clínica e Translacional, Instituto Gonçalo Moniz, FUndação Oswaldo Cruz, Salvador 40296-710, Brazil; Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador 41810-710, Brazil; Curso de Medicina, Universidade Salvador, Salvador, Brazil
- María B. Arriaga
- Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- Beatriz Barreto-Duarte
- Laboratório de Pesquisa Clínica e Translacional, Instituto Gonçalo Moniz, FUndação Oswaldo Cruz, Salvador 40296-710, Brazil; Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador 41810-710, Brazil; Instituto de Pesquisa Clínica e Translacional, Faculdade de Tecnologia e Ciências, Salvador 41741-590, Brazil; Curso de Medicina, Universidade Salvador, Salvador, Brazil; Programa Acadêmico de Tuberculose. Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
- Mariana Araújo-Pereira
- Laboratório de Pesquisa Clínica e Translacional, Instituto Gonçalo Moniz, FUndação Oswaldo Cruz, Salvador 40296-710, Brazil; Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador 41810-710, Brazil; Instituto de Pesquisa Clínica e Translacional, Faculdade de Tecnologia e Ciências, Salvador 41741-590, Brazil; Faculdade de Medicina, Univerdidade Federal da Bahia, Salvador, Brazil
- Mateus Maggiti-Bezerril
- Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador 41810-710, Brazil; Instituto de Pesquisa Clínica e Translacional, Faculdade de Tecnologia e Ciências, Salvador 41741-590, Brazil
- Alice M.S. Andrade
- Laboratório de Pesquisa Clínica e Translacional, Instituto Gonçalo Moniz, FUndação Oswaldo Cruz, Salvador 40296-710, Brazil; Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador 41810-710, Brazil; Instituto de Pesquisa Clínica e Translacional, Faculdade de Tecnologia e Ciências, Salvador 41741-590, Brazil
- Marina C. Figueiredo
- Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- Ginger L. Milne
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA
- Valeria C. Rolla
- Instituto Nacional de Infectologia Evandro Chagas, Fiocruz, Rio de Janeiro, Brazil
- Afrânio L. Kristki
- Programa Acadêmico de Tuberculose. Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
- Marcelo Cordeiro-Santos
- Fundação Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, Brazil; Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas, Manaus, Brazil; Universidade Nilton Lins, Manaus, Brazil
- Timothy R. Sterling
- Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- Bruno B. Andrade
- Laboratório de Pesquisa Clínica e Translacional, Instituto Gonçalo Moniz, FUndação Oswaldo Cruz, Salvador 40296-710, Brazil; Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador 41810-710, Brazil; Programa de Pós-Graduação em Medicina e Saúde Humana, Escola Bahiana de Medicina e Saúde Pública (EBMSP), Salvador 40290-150, Brazil; Instituto de Pesquisa Clínica e Translacional, Faculdade de Tecnologia e Ciências, Salvador 41741-590, Brazil; Curso de Medicina, Universidade Salvador, Salvador, Brazil; Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Faculdade de Medicina, Univerdidade Federal da Bahia, Salvador, Brazil; Corresponding author
- Artur T.L. Queiroz
- Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador 41810-710, Brazil; Instituto de Pesquisa Clínica e Translacional, Faculdade de Tecnologia e Ciências, Salvador 41741-590, Brazil; Centro de Integração de Dados e Conhecimentos para Saúde, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil
- Journal volume & issue
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Vol. 27,
no. 3
p. 109135
Abstract
Summary: Tuberculosis-diabetes mellitus (TB-DM) is linked to a distinct inflammatory profile, which can be assessed using multi-omics analyses. Here, a machine learning algorithm was applied to multi-platform data, including cytokines and gene expression in peripheral blood and eicosanoids in urine, in a Brazilian multi-center TB cohort. There were four clinical groups: TB-DM(n = 24), TB only(n = 28), DM(HbA1c ≥ 6.5%) only(n = 11), and a control group of close TB contacts who did not have TB or DM(n = 13). After cross-validation, baseline expression or abundance of MMP-28, LTE-4, 11-dTxB2, PGDM, FBXO6, SECTM1, and LINCO2009 differentiated the four patient groups. A distinct multi-omic-derived, dimensionally reduced, signature was associated with TB, regardless of glycemic status. SECTM1 and FBXO6 mRNA levels were positively correlated with sputum acid-fast bacilli grade in TB-DM. Values of the biomarkers decreased during the course of anti-TB therapy. Our study identified several markers associated with the pathophysiology of TB-DM that could be evaluated in future mechanistic investigations.
