Mucins create a physical barrier that protects human and animal tissues from microbial pathogens. Here, we provide evidence that mucin degradation can be mediated by unique mucinolysomes, defined as extracellular cellulosome-like multi-enzyme complexes specializing in mucin degradation. We predicted the presence of mucinolysomes across 63 metagenome-assembled genomes (MAGs) and two isolated genomes of three anaerobic species of Limousia, including seven MAGs from human gut microbiome samples from six countries. We validated that mucins can support the growth of the Limousia strain ET540 as its sole carbon source, triggering the upregulation of most mucinolysome-related genes in ET540. We modeled the mucinolysome assembly by predicting cohesin‒dockerin interactions among most of the mucinolysome proteins using AlphaFold3. We performed metagenomic read mapping of 2897 fecal samples from various human cohorts and wild/domesticated animals against Limousia MAGs. We found that Limousia has a greater abundance and prevalence in farm animals than in humans. This study characterizes and adds the Limousia bacteria as unique member to the list of human and animal gut mucin glycan-degrading bacteria. Overall, we discovered that this novel gut bacteria genus (Limousia) uses a previously unrecognized molecular mechanism for highly organized mucin glycan degradation, shedding new light on microbe‒host interactions in the gastrointestinal tracts of diverse animal hosts, including humans.
Akresi et al. (Tue,) studied this question.