Host urine immunological biomarkers as potential candidates for the diagnosis of tuberculosis

CITATION: Eribo, O. A. et al. 2020. Host urine immunological biomarkers as potential candidates for the diagnosis of tuberculosis. International Journal of Inclusive Education, 99:473-481. doi:10.1080/13603116.2019.1619850The original publication is available at https://www.journals.elsevier.com/international-journal-of-infectious-diseasesObjective: To investigate the potential of host urinary biomarkers as diagnostic candidates for tuberculosis (TB). Methods: Adults self-presenting with symptoms requiring further investigation for TB were enrolled in Cape Town, South Africa. Participants were later classified as having TB or other respiratory diseases (ORD) using results from TB confirmatory tests. The concentrations of 29 analytes were evaluated in urine samples from participants using the Luminex platform, and their diagnostic potential was assessed using standard statistical approaches. Results: Of the 151 study participants, 34 (22.5%) were diagnosed with TB and 26 (17.2%) were HIV-positive. Seven biomarkers showed potential as TB diagnostic candidates, with accuracy improving (in HIV-positives) when stratified according to HIV status (area under the receiver operating characteristics curve; AUC ≥0.80). In HIV-positive participants, a four-marker biosignature (sIL6R, MMP-9, IL-2Ra, IFN-γ) diagnosed TB with AUC of 0.96, sensitivity of 85.7% (95% confidence interval (CI) 42.1-99.6%), and specificity of 94.7% (95% CI 74.0-99.9%). In HIV-negatives, the most promising was a two-marker biosignature (sIL6R and sIL-2Ra), which diagnosed TB with AUC of 0.76, sensitivity of 53.9% (95% CI 33.4-73.4%), and specificity of 79.6% (95% CI 70.3-87.1%). Conclusions: Urinary host inflammatory biomarkers possess TB diagnostic potential but may be influenced by HIV infection. The results of this study require validation in larger studies. Keywords: Biomarker; Biosignature; Diagnosis; Inflammatory biomarker; Tuberculosis; Urine.https://www.journals.elsevier.com/international-journal-of-infectious-diseasesPublishers versio

An Archetypical Model for Engrafting <i>Bacteroides fragilis</i> into Conventional Mice Following Reproducible Antibiotic Conditioning of the Gut Microbiota

Bacteroides fragilis is a commonly investigated commensal bacterium for its protective role in host diseases. Here, we aimed to develop a reproducible antibiotic-based model for conditioning the gut microbiota and engrafting B. fragilis into a conventional murine host. Initially, we selected different combinations of antibiotics, including metronidazole, imipenem, and clindamycin, and investigated their efficacy in depleting the mouse Bacteroides population. We performed 16S rRNA sequencing of DNA isolated from fecal samples at different time points. The α-diversity was similar in mice treated with metronidazole (MET) and differed only at weeks 1 (p = 0.001) and 3 (p = 0.009) during metronidazole/imipenem (MI) treatment. Bacteroides compositions, during the MET and MI exposures, were similar to the pre-antibiotic exposure states. Clindamycin supplementation added to MET or MI regimens eliminated the Bacteroides population. We next repeated metronidazole/clindamycin (MC) treatment in two additional independent experiments, followed by a B. fragilis transplant. MC consistently and reproducibly eliminated the Bacteroides population. The depleted Bacteroides did not recover in a convalescence period of six weeks post-MC treatment. Finally, B. fragilis was enriched for ten days following engraftment into Bacteroides-depleted mice. Our model has potential use in gut microbiota studies that selectively investigate Bacteroides’ role in diseases of interest