2024 AIChE Annual Meeting
A Bioinformatic Pipeline for Identifying Differentially Abundant Biosynthetic Gene Clusters in IBD Patients
Bacterial secondary metabolites play crucial roles in environmental adaptation, microbial defense, and interspecies communication. Inflammatory Bowel Disease (IBD) is a complex disorder with a significant microbial component, yet the role of secondary metabolites in disease progression remains poorly understood. This study investigates the potential involvement of ribosomally synthesized and post-translationally modified peptides (RiPPs), a major class of secondary metabolites, in IBD. We focused on two important classes of RiPPs: lanthipeptides and lasso peptides. We developed a novel computational pipeline using hidden Markov model (HMM) profiles to identify RiPP biosynthetic gene clusters (BGCs) in genomic sequences, overcoming limitations of current machine learning-based methods, which are often trained on limited datasets. We applied this tool to analyze gut microbiome metagenomes from a cohort of IBD patients and healthy controls. The abundance of each identified lanthipeptide and lasso peptide BGC was quantified for each individual, followed by statistical analyses to determine significant differences between groups. Our analysis revealed that four RiPP BGCs were underrepresented in IBD patients compared to healthy individuals, suggesting a protective role for these secondary metabolites in maintaining gut health. These findings provide new insights into microbial contributions to IBD and identify potential biomarkers for disease diagnosis and progression. This work establishes a foundation for future studies on the mechanisms of RiPP-mediated effects in IBD and opens avenues for developing novel therapeutic strategies targeting the gut microbiome. Future work will focus on experimentally characterizing the identified lanthipeptides and lassopeptides to determine their structures and bioactivities, as well as expanding our analysis to other RiPP classes and microbiome-associated diseases.