An Integrative Multi-Omics Approach to Characterize Interactions between Tuberculosis and Diabetes Mellitus

Abstract

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/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.

Note:
Funding Information: This work was supported by the Departamento de Ciência e Tecnologia (DECIT) - Secretaria de Ciência e Tecnologia (SCTIE) – Ministério da Saúde (MS), Brazil [25029.000507/2013-07 to VR], the National Institutes of Allergy and Infectious Diseases [U01-AI069923] at NIH, and by The Civilian Research and Development Foundation (CRDF) Global #DAA3-17-63144. The study was partially supported by the Intramural Research Program of the Fundaçaão Oswaldo Cruz and the Intramural Research Program of the Fundação José Silveira.

Declaration of Interests: The authors declare that there is no conflict of interest.

Ethics Approval Statement: The study was conducted according to the Declaration of Helsinki. Data and specimens were obtained from the RePORT-Brazil observational cohort study. The study was approved by the Institutional Review Boards of the Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Brazil (CAAE: 25102412.3.1001.5262). Written informed consents were obtained from all voluntary participants.

Keywords: Tuberculosis, Diabetes, Inflammation, Multi-omics