Tropheryma whipplei as the Dominant Organism in Bronchoalveolar-Lavage Metagenomic Next-Generation Sequencing: A Single-Centre Case Series of 28 Patients

Background/Objectives: Metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) increasingly reports Tropheryma whipplei (T. whipplei) in patients without classical Whipple disease, but the significance of these detections is often uncertain. We aimed to quantify relative sequencing abundance, characterise the accompanying clinical, radiological, and routine laboratory phenotype, and develop a structured framework for interpretation. Methods: We retrospectively reviewed 944 consecutive BALF-mNGS tests performed at Tianjin Chest Hospital between October 2022 and March 2026. T. whipplei was detected in 47 tests; the primary analytic cohort comprised the 28 patients in whom it was the most abundant detected microorganism. Demographics, comorbidities, symptoms, chest computed tomography findings, co-detected organisms, species-level read counts, and routine laboratory indicators were summarised descriptively. Results: T. whipplei was detected in 47/944 tests (4.98%) and was the predominant (most abundant) detected microorganism in 28/47 (59.6%). In these 28 patients, the mean age was 60.2 ± 12.3 years and 15 (53.6%) were women. Cough (18/28, 64.3%) and expectoration (14/28, 50.0%) predominated, whereas fever occurred in 4/28 (14.3%); pulmonary nodules were the most common CT finding (15/28, 53.6%). T. whipplei was the sole microorganism in 11/28 (39.3%) and was co-detected in 17/28 (60.7%); it was sole or ≥10-fold more abundant than the strongest co-detected organism in 25/28 (89.3%). Leukocyte counts were within reference in 26/28, C-reactive protein was ≤5 mg/L in 19/25, and procalcitonin was at or below the assay limit in 12/14. Conclusions: Predominant (most-abundant) BALF-mNGS detection of T. whipplei commonly accompanied nonspecific respiratory presentations and a relatively indolent laboratory phenotype. Because sequence dominance cannot by itself distinguish infection from heavy carriage, interpretation should integrate read burden, orthogonal confirmation, competing pathogens and diagnoses, and systemic features.