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oai:figshare.com:article/33772174 2026-09-15T05:41:34Z category_8 portal_316 item_type_3 month_year_09_2026

Table 1_Lung microbial dysregulation and TNF inhibition are associated with worsened nontuberculous mycobacterial lung disease.docx Ethan G. Napier (7542356) Isaac R. Cinco (23893863) Delphine C. Malherbe (8919206) Ethan V. Stuart (23893860) Michael H. Davies (23096371) Caroline N. Leach (24912784) Evan Damron (24912787) Mahmut Gokmen (24912790) Amy Leestemaker-Palmer (24912793) Stephanie Nuss (24912796) Cody Bumgardner (18209528) Steven G. Kohama (4117111) Luiz Bermudez (7863032) Kevin L. Winthrop (2620681) Cristina Fuss (8762739) Eliot R. Spindel (11453530) Ilhem Messaoudi (72928) Microbiology lung microbiome nontuberculous mycobacteria rhesus macaque TNF Introduction<p>Nontuberculous mycobacteria (NTM) are ubiquitous bacteria that cause a spectrum of diseases, most notably pulmonary disease (NTMPD). The host factors contributing to the heightened susceptibility and severity of NTMPD in elderly individuals are poorly understood. Prior studies have reported increased incidence of NTMPD in individuals receiving immune modulatory biologics such as anti-TNF and JAK-STAT inhibitors. Moreover, we recently described that age-related changes in the lung microbiome, notably the loss of a main commensal Tropheryma species, may contribute to increased severity. Therefore, in this study we explore the hypothesis that TNF-inhibition and a disrupted lung microbiome are key factors associated with poor NTMPD outcomes.</p>Methods<p>Young (4–7 years old) rhesus macaques were either pretreated with: (1) nebulized amikacin and vancomycin to disrupt the lung microbiome; (2) the TNF inhibitor Inflectra to suppress Th1 responses; or (3) left untreated. Animals were subsequently inoculated with M. avium subsp. hominissuis (MAH) in the right lung. Bacterial load, radiographic changes, immune responses, and microbiome composition were monitored longitudinally.</p>Results and discussion<p>Antibiotic-treated animals experienced significant microbiome compositional shifts including the depletion of Tropheryma from the lung microbiome. One antibiotic-treated animal developed and resolved cavitary disease after the lung microbiome returned to homeostasis. One Inflectra-treated animal developed chronic granulomatous disease. No control animals showed granulomas. These data suggest that lung microbiome disruption and TNF inhibition are associated with increased susceptibility to NTM granulomatous disease.</p> 2026-09-15T05:41:34Z Dataset Dataset 10.3389/fmicb.2026.1923035.s001 https://figshare.com/articles/dataset/Table_1_Lung_microbial_dysregulation_and_TNF_inhibition_are_associated_with_worsened_nontuberculous_mycobacterial_lung_disease_docx/33772174 CC BY 4.0