Stool microbiome in TB therapy, Port-au-Prince, Haiti

The lifecycle of M. tuberculosis within the human host is marked by critical transition points between the major phases of infection: Initial infection, latent disease, active tuberculosis, and resolution with antibiotic therapy. Through observation of patients in each of these stages, we have some knowledge about host determinants that maintain each of these stages, such as the need for sufficient CD4 T cells, interferon gamma and tumor necrosis factor alpha in the control of latency. However, the vast majority of HIV negative TB patients do not have defined deficiencies in these immune factors and therefore the host determinants of the heterogeneous ability of TB patients to control M. tuberculosis infection, either in the context of initial infection after exposure, reactivation of latent infection, or relapse-free elimination of M. tuberculosis after antimicrobial therapy, are unknown. To address these knowledge gaps, we have assembled a set of patient cohorts to examine three interrelated host factors that we hypothesize may contribute to the heterogeneity in host control of M. tuberculosis during the transition from uninfected> LTBl and infected>cured. These factors are Mucosal Associated Invariant T (MAIT) cells, whole blood transcriptomic signatures, and stool microbiomic composition. We will initially examine these factors in two cohorts of TB patients: 1) Patients either resistant to initial infection or recently infected from a household contact, a comparison which will yield correlates of innate resistance to infection and 2) Patients undergoing therapy for active pulmonary tuberculosis, either with short course monotherapy or standard multidrug therapy, to determine correlates of clearance of replicating and persister M. tuberculosis. We anticipate that these studies will provide a set of quantitative molecular assays that will both expand our knowledge ofthe heterogeneity of host control of M. tuberculosis infection, and potentially supply biomarkers that will allow identification of patients resistant to infection, destined to reactivate from latency, or to relapse after antimicrobial therapy.

Classified as human gut / stool shotgun DNA metagenome of adult and adolescent by sonnet_x2 with confidence 0.65. Assay shotgun_dna.

• host study.description · “lifecycle of M. tuberculosis within the human host”
• body site run.scientific_name · “human gut metagenome”
• life stage study.description · “active tuberculosis, and resolution with antibiotic therapy”
• life stage sample.attr.age · “13 (n=12/92)”

92 runs over 92 samples · mean 0.80 Gbp per run (median 0.69 Gbp, total 73.70 Gbp; 92 runs with a base count) · layout PAIRED 92 · platform ILLUMINA 92 · models Illumina HiSeq 4000 (92) · 91% of runs with a Sandpiper profile · first public 2018-03-30

Wipperman MF first · Fitzgerald DW · Juste MAJ · Taur Y · Namasivayam S · Sher A · Bean JM · Bucci V · Glickman MS last · Vorkas CK first · Li K · Bean J · Bhattarai SK · Adamow M · Wong P · Aubé J · Maringati VS · Mathurin L · McAulay K · Vilbrun SC · Francois D · Walsh KF · Nathan C · de Araujo LS first · Ribeiro-Alves M · Pessler F · Saad MHF last · Mancabelli L first · Milani C · De Biase R · Bocchio F · Fontana F · Lugli GA · Alessandri G · Tarracchini C · Viappiani A · De Conto F · Nouvenne A · Ticinesi A · Bussolati O · Meschi T · Cecchi R · Turroni F · Ventura M last

2 of the 4 core fields are below 50% coverage: health_condition, subject_id. Share metadata

PRJNA445968.csv.gz (3.9 KB) · parquet (75.0 KB) — all 92 samples, every field with route and confidence · PRJNA445968_determinations.csv.gz (5.7 KB) — 673 evidence rows