Longitudinal Multi-omics Reveals Persistent Gut Microbial and Metabolic Dysbiosis Following Anti-Tuberculosis Therapy
- 1BRIC-National Institute of Immunology
Abstract
Pulmonary tuberculosis (TB) is associated with systemic alterations extending beyond the lungs, yet the longitudinal impact of anti-tuberculosis therapy (ATT) on gut ecosystem recovery remains poorly understood. Here, we performed a longitudinal multi-omics analysis of gut microbial and metabolic dynamics in pulmonary TB patients (n=8) followed at baseline, 1, 6, and 8 months of ATT, compared with healthy household contacts (HHCs; n=8). Shotgun metagenomics, functional profiling, untargeted fecal metabolomics, resistome, plasmidome, virome, and microbiome-metabolome integration analyses were performed to characterize disease-associated alterations and treatment-associated recovery. Active, treatment-naive TB was characterized by reduced microbial diversity, altered community structure, depletion of beneficial commensals, and disruption of microbial functional pathways and metabolic profiles. During ATT, microbial diversity and functional/metabolic features progressively recovered; however, post-treatment profiles remained distinct from HHCs, indicating incomplete ecological restoration after microbiological cure. Microbiome-metabolome analysis revealed associations between altered bacterial taxa and metabolites involved in amino acid metabolism, bile acid transformation, oxidative stress, and host-microbial metabolic interactions. In contrast, resistome and mobile genetic element profiles demonstrated greater stability throughout treatment. HHCs exposed to index TB cases maintained relative gut ecosystem stability over time. Bacterial-AMR correlation analysis identified taxon-specific resistance associations among gut bacteria. Together, these findings provide a longitudinal systems-level view of gut ecosystem remodeling during TB and highlight that restoration of microbial homeostasis extends beyond pathogen clearance.
Related
- Osteoimmuno-microbial feedback loops in medication-related osteonecrosis of the jaw: from dysbiosis to persistent structural osteonecrosis
- Microbial Dysbiosis, Infection, and Immunometabolic Signaling in Polyendocrine Metabolic Ovarian Syndrome (Formerly PCOS).
- Dense Longitudinal Multi Omics Reveals Microbial Metabolic Immune Succession During Immune Checkpoint Therapy
- The Gut–Kidney Axis in Chronic Kidney Disease: Microbial Dysbiosis, Host–Microbial Metabolism, and Emerging Therapeutic Strategies
- High Initiation but Suboptimal Completion of Tuberculosis-Preventive Treatment Among People Living With HIV on Antiretroviral Therapy, Persistent Tuberculosis Incidence, and Programmatic Implications: Findings From a 2-Year Multicountry Cohort Study
BibTeX
@misc{pant2026longitudinal,
title = {{Longitudinal Multi-omics Reveals Persistent Gut Microbial and Metabolic Dysbiosis Following Anti-Tuberculosis Therapy}},
author = {A. Pant and S. K. Yadav and J. Srinivasan and S. K. Gupta and B. P. Gurjar and P. Jana and D. Talukdar and S. P. Babu and S. Sarkar and Y. Kumar and D. Mohanty and B. Das and G. A. Arimbasseri},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.05.26364754},
url = {https://www.medrxiv.org/content/10.64898/2026.10.05.26364754v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Longitudinal Multi-omics Reveals Persistent Gut Microbial and Metabolic Dysbiosis Following Anti-Tuberculosis Therapy
AU - A. Pant
AU - S. K. Yadav
AU - J. Srinivasan
AU - S. K. Gupta
AU - B. P. Gurjar
AU - P. Jana
AU - D. Talukdar
AU - S. P. Babu
AU - S. Sarkar
AU - Y. Kumar
AU - D. Mohanty
AU - B. Das
AU - G. A. Arimbasseri
PY - 2026
DA - 2026/10/05
PB - medRxiv
DO - 10.64898/2026.10.05.26364754
UR - https://www.medrxiv.org/content/10.64898/2026.10.05.26364754v1
AB - Pulmonary tuberculosis (TB) is associated with systemic alterations extending beyond the lungs, yet the longitudinal impact of anti-tuberculosis therapy (ATT) on gut ecosystem recovery remains poorly understood. Here, we performed a longitudinal multi-omics analysis of gut microbial and metabolic dynamics in pulmonary TB patients (n=8) followed at baseline, 1, 6, and 8 months of ATT, compared with healthy household contacts (HHCs; n=8). Shotgun metagenomics, functional profiling, untargeted fecal metabolomics, resistome, plasmidome, virome, and microbiome-metabolome integration analyses were performed to characterize disease-associated alterations and treatment-associated recovery. Active, treatment-naive TB was characterized by reduced microbial diversity, altered community structure, depletion of beneficial commensals, and disruption of microbial functional pathways and metabolic profiles. During ATT, microbial diversity and functional/metabolic features progressively recovered; however, post-treatment profiles remained distinct from HHCs, indicating incomplete ecological restoration after microbiological cure. Microbiome-metabolome analysis revealed associations between altered bacterial taxa and metabolites involved in amino acid metabolism, bile acid transformation, oxidative stress, and host-microbial metabolic interactions. In contrast, resistome and mobile genetic element profiles demonstrated greater stability throughout treatment. HHCs exposed to index TB cases maintained relative gut ecosystem stability over time. Bacterial-AMR correlation analysis identified taxon-specific resistance associations among gut bacteria. Together, these findings provide a longitudinal systems-level view of gut ecosystem remodeling during TB and highlight that restoration of microbial homeostasis extends beyond pathogen clearance.
ER -