Gut Microbiome in Human Melioidosis: Composition and Resistome Dynamics from Diagnosis to Discovery.

Abstract

Background: Melioidosis, attributable to the soil-dwelling bacterium Burkholderia pseudomallei, stands as a paramount global health challenge, necessitating extended courses of antibiotics. While murine studies identified the gut microbiota as a modulator of bacterial dissemination during melioidosis, the human intestinal microbiota during melioidosis remains uncharacterized. Here, we characterized gut microbiota composition and antimicrobial resistance (AMR) genes at diagnosis, during treatment, and postdischarge for melioidosis. We hypothesized that the gut microbiota of melioidosis patients would be extensively distorted.

Methods: In this prospective observational cohort, stool samples of patients with culture-confirmed melioidosis admitted to a tertiary care hospital in India were collected at diagnosis, 14 days after diagnosis, or discharge (whichever occurred first) and at 6 months postinfection. Family members or neighbors served as community controls. The gut microbiota and resistome were profiled by shotgun metagenomic sequencing.

Results: We longitudinally analyzed the gut microbiota of 70 fecal samples from 28 patients and 16 community controls. At diagnosis, the gut microbiota of patients differed from that of controls, characterized by high abundances of potentially pathogenic bacteria, a loss of butyrate-producing bacteria, and higher levels of AMR genes. Microbiota composition and resistome remained different from community controls at 6 months, driven by total antibiotic exposure. During hospitalization, gut microbiota profiles were associated with secondary Klebsiella pneumoniae infections.

Conclusions: This first study on gut microbiota composition and resistome in human melioidosis showed extensive disruptions during hospitalization, with limited signs of restoration 6 months postinfection. Given the adverse outcomes linked with microbiome perturbations, limiting microbiota disruptions or using microbiota-restorative therapies (eg, butyrate-producing probiotics) may be beneficial.