The Genetic Basis for the Cooperative Bioactivation of Plant Lignans by a Human Gut Bacterial Consortium

Plant-derived lignans, consumed daily by most individuals, are inversely associated with breast cancer; however, their bioactivity is only exerted following gut bacterial conversion to enterolignans. Here, we dissect a four-species bacterial consortium sufficient for all four chemical reactions in this pathway. Comparative genomics and heterologous expression experiments identified the first enzyme in the pathway. Transcriptional profiling (RNAseq) independently identified the same gene and linked a single genomic locus to each of the remaining biotransformations. Remarkably, we detected the complete bacterial lignan metabolism pathway in the majority of human gut microbiomes. Together, these results are an important step towards a molecular genetic understanding of the gut bacterial bioactivation of lignans and other plant secondary metabolites to downstream metabolites relevant to human disease.