{ "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.", "abstract_shown": true, "affiliations": [ "Department of Microbiology and Parasitology, Faculty of Medicine, St. Francis University College of Health and Allied Sciences, Ifakara, Tanzania.", "Kibong'oto Infectious Diseases Hospital, Siha, Kilimanjaro, Tanzania.", "Department of Medicine, Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, VA, USA.", "Kilimanjaro Clinical Research Institute, Kilimanjaro Christian Medical Center, Moshi, Tanzania.", "Department of Medical Biochemistry and Molecular Biology, KCMC University, Moshi, Tanzania.", "Department of Clinical Pharmacy and Pharmacology, School of Pharmacy, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.", "Kilimanjaro Clinical Research Institute, Moshi, Tanzania.", "Environmental Molecular Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.", "Center for Tuberculosis, Institute for Global Health Sciences, University of California, San Francisco, San Francisco, California 94143, United States of America.", "Center for Data Science, Division of Infectious Diseases, Rutgers University, New Jersey Medical School, Newark, NJ, USA.", "Section of Infectious Diseases, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.", "Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.", "Duke Clinical Research Institute, Duke University, Durham, NC, USA." ], "article_type": "New results", "arxiv": null, "author_total": 13, "authors": [ { "affs": [ 0, 1, 2 ], "name": "Reuben S. Maghembe", "orcid": "0000-0003-2453-5993" }, { "affs": [ 3, 4 ], "name": "Vesla I. Kullaya" }, { "affs": [ 5 ], "name": "Ritah Francis Mutagonda" }, { "affs": [ 2 ], "name": "Megan Null" }, { "affs": [ 1 ], "name": "Peter M. Mbelele" }, { "affs": [ 6 ], "name": "Kennedy M. Ngowi" }, { "affs": [ 7 ], "name": "Jon M. Jacobs" }, { "affs": [ 8 ], "name": "Payam Nahid" }, { "affs": [ 9 ], "name": "W. Evan Johnson" }, { "affs": [ 10 ], "name": "Pranay Sinha" }, { "affs": [ 11, 12 ], "name": "Syed Sana" }, { "affs": [ 1 ], "name": "Stellah George Mpagama" }, { "affs": [ 2 ], "name": "Scott K. Heysell" } ], "bibtex": "https://research.draconitic.com/paper/dd2y7px25j9t8.bib", "cited_by": 0, "doi": "10.64898/2026.10.26.761896", "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.26.761896v1.full", "id": "dd2y7px25j9t8", "issns": [ "2692-8205" ], "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.26.761896v1", "language": "en", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "biorxiv", "bioinformatics" ], [ "heading", "Article" ] ], "openalex": null, "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.26.761896v1.full.pdf", "pmcid": "PMC13733846", "pmid": "42990259", "published": "2026-10-26", "publisher": "Cold Spring Harbor Laboratory Preprints", "ris": "https://research.draconitic.com/paper/dd2y7px25j9t8.ris", "sources": [ { "first_seen": "2026-10-31T12:21:10Z", "native_id": "10.64898/2026.10.26.761896", "source": "biorxiv", "url": "https://www.biorxiv.org/content/10.64898/2026.10.26.761896v1" }, { "first_seen": "2026-11-08T12:23:32Z", "native_id": "PMC13733846", "source": "pmc", "url": "https://doi.org/10.64898/2026.10.26.761896" } ], "subjects": [ { "field": "biology", "origin": "biorxiv:bioinformatics", "subfield": "bioinformatics" } ], "title": "Serum nutritional-metabolic recovery during tuberculosis treatment across BMI-defined undernutrition strata: A longitudinal proteomic reanalysis", "title_text": "Serum nutritional-metabolic recovery during tuberculosis treatment across BMI-defined undernutrition strata: A longitudinal proteomic reanalysis", "type": "preprint", "updated_at": "2026-11-08T12:23:32Z", "url": "https://research.draconitic.com/paper/dd2y7px25j9t8", "venue": "bioRxiv", "versions": [] }