Poisoning with Soman, an Organophosphorus Nerve Agent, Alters Fecal Bacterial Biota and Urine Metabolites: a Case for Novel Signatures for Asymptomatic Nerve Agent Exposure

• DOI: 10.1128/aem.00978-18
• Publication Date: 2018-09-12T10:11:51Z
• Authors: Derese Getnet; Aarti Gautam; Raina Kumar; Allison Hoke; Amrita K. Cheema; Franco Rossetti; Caroline R. Schultz; Rasha Hammamieh; Lucille A. Lumley; Marti Jett
• Keywords: Biota; Metabolome

The experimental pathophysiology of organophosphorus (OP) chemical exposure has been extensively reported. Here, we describe an altered fecal bacterial biota and urine metabolome following intoxication with soman, a lipophilic G class warfare nerve agent. Nonanesthetized Sprague-Dawley male rats were subcutaneously administered soman at 0.8 (subseizurogenic) or 1.0 (seizurogenic) the 50% lethal dose (LD50) evaluated for signs toxicity. Animals stratified based on seizing activity to evaluate effects metabolites. Soman reshaped by altering Facklamia, Rhizobium, Bilophila, Enterobacter, Morganella genera Firmicutes Proteobacteria phyla, some which are known hydrolyze OP chemicals. However, analogous changes not observed in ileum, remained same irrespective status animals after intoxication. 75 days exposure, stabilized no differences between groups. Interestingly, considering just animals, found that metabolomes markedly different. Leukotriene C4, kynurenic acid, 5-hydroxyindoleacetic norepinephrine, aldosterone excreted much higher rates 72 h consistent early multiorgan involvement during poisoning. These findings demonstrate feasibility using dysbiosis combination alterations as forensic evidence presymptomatic temporally enable administration neuroprotective therapies future.IMPORTANCE paucity assays determine physiologically relevant presents opportunity explore use bacteria sentinels assess exposed host. Recent advances sequencing technologies computational approaches have enabled researchers survey large community-level gut metabolomic various biospecimens. profiled agent exposure. significance this work is proof concept metabolites two separate biospecimens rich surrogate indicators suitable monitoring larger value such approach developed basis these observations can be deployed any setting moderate clinical chemistry microbiology capability. This estimation affected radius well screening, triage, ruling out suspected cases exposures mass casualty scenarios, transportation accidents involving hazardous materials, refugee movements, humanitarian missions, training settings when coupled established validated decision tree features.