Commensal gut bacteria inhibit viral replication by converting dietary tryptophan into a metabolite that activates cellular defense receptors, according to a study published in Nature Communications.
Researchers from Duke University School of Medicine, Weill Cornell Medicine, and partner institutions discovered that specific bacterial species rely on the enzyme aromatic amino acid aminotransferase (ArAT). This enzyme metabolizes tryptophan into 3-indolelactic acid, a compound that agonizes the host aryl hydrocarbon receptor (AhR). In laboratory assays using HIV as an experimental model, this metabolic pathway directly inhibited viral replication.
Because the aryl hydrocarbon receptor regulates multiple viral infections, the investigators evaluated other pathogens and found that commensal bacteria also suppress cytomegalovirus (CMV) in an ArAT-dependent manner. Bioinformatic analysis of fecal shotgun metagenomic data showed that the presence of ArAT correlated with improved disease outcomes across three human cohorts at risk for HIV, CMV, or symptomatic COVID-19.
The Duke Compute Cluster provided high-performance hardware for the metagenomic bioinformatic analysis, while the Duke Microbiome Core Facility and the Duke Sequencing and Genomic Technologies Shared Resource completed 16S rRNA gene library preparation and shotgun metagenomic sequencing. Cellular assays utilized TZM-bl cells and monoclonal anti-HIV-1 gp120 protein obtained through the National Institute of Allergy and Infectious Diseases BEI Resources.
Duke University submitted a patent application covering the therapeutic use of ArAT-expressing bacteria and their metabolites in viral infections, naming researchers Danting Jiang, Chin Yee Tan, Sallie R. Permar, Ria Goswami, and Neeraj K. Surana as inventors. The research received grant support from the National Institutes of Health, the Gilead Sciences Research Scholar’s Program in HIV, and the Duke Center for AIDS Research.
