Serum nutritional-metabolic recovery during tuberculosis treatment across BMI-defined undernutrition strata: A longitudinal proteomic reanalysis
13 affiliations
- 1Department of Microbiology and Parasitology, Faculty of Medicine, St. Francis University College of Health and Allied Sciences, Ifakara, Tanzania.
- 2Kibong'oto Infectious Diseases Hospital, Siha, Kilimanjaro, Tanzania.
- 3Department of Medicine, Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, VA, USA.
- 4Kilimanjaro Clinical Research Institute, Kilimanjaro Christian Medical Center, Moshi, Tanzania.
- 5Department of Medical Biochemistry and Molecular Biology, KCMC University, Moshi, Tanzania.
- 6Department of Clinical Pharmacy and Pharmacology, School of Pharmacy, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
- 7Kilimanjaro Clinical Research Institute, Moshi, Tanzania.
- 8Environmental Molecular Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
- 9Center for Tuberculosis, Institute for Global Health Sciences, University of California, San Francisco, San Francisco, California 94143, United States of America.
- 10Center for Data Science, Division of Infectious Diseases, Rutgers University, New Jersey Medical School, Newark, NJ, USA.
- 11Section of Infectious Diseases, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
- 12Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.
- 13Duke Clinical Research Institute, Duke University, Durham, NC, USA.
Abstract
Background Tuberculosis remains the leading cause of death from a single infectious agent, and undernutrition is a major modifiable risk factor. Serum proteomics can capture systemic host recovery during therapy, but whether baseline BMI-defined undernutrition alters this trajectory is unclear. Methods We reanalysed processed longitudinal tandem-mass-tag serum proteomics from 30 adults with pulmonary tuberculosis and durable cure sampled at baseline and weeks 8, 17, 26 and 52. Thirteen participants had baseline BMI <18.5 kg/m2 and 17 had BMI >=18.5 kg/m2. Protein-level analyses evaluated baseline differences and week-specific within-participant change; module and recovery-axis models evaluated BMI-by-time interactions, with random-intercept mixed models added as a repeated-measures sensitivity analysis. Three complementary treatment-responsive modules were integrated into an exploratory, nonredundant 36-protein nutritional-metabolic summary axis. Results The reconstructed dataset contained 1,923 quantified features across 150 participant-visits. Inflammatory/acute-phase and metal-handling/nutritional-immunity module scores declined during follow-up, whereas lipid/apolipoprotein-transport, nutritional-carrier and endocrine-immunometabolic scores increased. In the primary week-specific paired-change analyses, no protein-level between-BMI difference in longitudinal change survived false-discovery-rate correction; no curated-module BMI-by-time interaction survived correction. The 36-protein summary axis increased in both BMI strata from week 17 onward. In a random-intercept model without interaction, the BMI <18.5 kg/m2 stratum had a lower average axis score across visits than the BMI >=18.5 kg/m2 comparison stratum, although the confidence interval included zero (difference -1.34, 95% CI -2.76 to 0.08; p = .064). Categorical and continuous BMI-by-time interaction tests did not detect differential axis trajectories. Conclusions Tuberculosis treatment was accompanied by broad longitudinal remodelling of circulating inflammatory and nutritional-metabolic protein systems. An exploratory 36-protein summary axis increased in both baseline BMI strata, while formal interaction tests did not detect BMI-dependent trajectories and remained too imprecise to establish equivalence. BMI should be regarded as an anthropometric proxy rather than a comprehensive measure of nutritional state. The defined axis provides a framework for prospective validation alongside direct measures of body composition, micronutrients, treatment exposure and clinical outcomes.
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BibTeX
@misc{maghembe2026serum,
title = {{Serum nutritional-metabolic recovery during tuberculosis treatment across BMI-defined undernutrition strata: A longitudinal proteomic reanalysis}},
author = {Reuben S. Maghembe and Vesla I. Kullaya and Ritah Francis Mutagonda and Megan Null and Peter M. Mbelele and Kennedy M. Ngowi and Jon M. Jacobs and Payam Nahid and W. Evan Johnson and Pranay Sinha and Syed Sana and Stellah George Mpagama and Scott K. Heysell},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.26.761896},
url = {https://www.biorxiv.org/content/10.64898/2026.10.26.761896v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Serum nutritional-metabolic recovery during tuberculosis treatment across BMI-defined undernutrition strata: A longitudinal proteomic reanalysis
AU - Reuben S. Maghembe
AU - Vesla I. Kullaya
AU - Ritah Francis Mutagonda
AU - Megan Null
AU - Peter M. Mbelele
AU - Kennedy M. Ngowi
AU - Jon M. Jacobs
AU - Payam Nahid
AU - W. Evan Johnson
AU - Pranay Sinha
AU - Syed Sana
AU - Stellah George Mpagama
AU - Scott K. Heysell
PY - 2026
DA - 2026/10/26
PB - bioRxiv
DO - 10.64898/2026.10.26.761896
UR - https://www.biorxiv.org/content/10.64898/2026.10.26.761896v1
AB - Background Tuberculosis remains the leading cause of death from a single infectious agent, and undernutrition is a major modifiable risk factor. Serum proteomics can capture systemic host recovery during therapy, but whether baseline BMI-defined undernutrition alters this trajectory is unclear. Methods We reanalysed processed longitudinal tandem-mass-tag serum proteomics from 30 adults with pulmonary tuberculosis and durable cure sampled at baseline and weeks 8, 17, 26 and 52. Thirteen participants had baseline BMI <18.5 kg/m2 and 17 had BMI >=18.5 kg/m2. Protein-level analyses evaluated baseline differences and week-specific within-participant change; module and recovery-axis models evaluated BMI-by-time interactions, with random-intercept mixed models added as a repeated-measures sensitivity analysis. Three complementary treatment-responsive modules were integrated into an exploratory, nonredundant 36-protein nutritional-metabolic summary axis. Results The reconstructed dataset contained 1,923 quantified features across 150 participant-visits. Inflammatory/acute-phase and metal-handling/nutritional-immunity module scores declined during follow-up, whereas lipid/apolipoprotein-transport, nutritional-carrier and endocrine-immunometabolic scores increased. In the primary week-specific paired-change analyses, no protein-level between-BMI difference in longitudinal change survived false-discovery-rate correction; no curated-module BMI-by-time interaction survived correction. The 36-protein summary axis increased in both BMI strata from week 17 onward. In a random-intercept model without interaction, the BMI <18.5 kg/m2 stratum had a lower average axis score across visits than the BMI >=18.5 kg/m2 comparison stratum, although the confidence interval included zero (difference -1.34, 95% CI -2.76 to 0.08; p = .064). Categorical and continuous BMI-by-time interaction tests did not detect differential axis trajectories. Conclusions Tuberculosis treatment was accompanied by broad longitudinal remodelling of circulating inflammatory and nutritional-metabolic protein systems. An exploratory 36-protein summary axis increased in both baseline BMI strata, while formal interaction tests did not detect BMI-dependent trajectories and remained too imprecise to establish equivalence. BMI should be regarded as an anthropometric proxy rather than a comprehensive measure of nutritional state. The defined axis provides a framework for prospective validation alongside direct measures of body composition, micronutrients, treatment exposure and clinical outcomes.
SN - 2692-8205
ER -