Mucinolysome in gut microbiomes of farm animals and humans

Area of Science:

• Microbiome Research
• Glycobiology
• Structural Biology

Background:

• Mucins form a crucial protective barrier in host tissues, essential for maintaining health.
• Degradation of mucin glycans is a key process influencing gut health and host-microbe interactions.
• Understanding the mechanisms of mucin degradation is vital for exploring gut ecosystem dynamics.

Purpose of the Study:

• To identify and characterize novel mechanisms of mucin glycan degradation in the gut.
• To investigate the prevalence and function of extracellular multi-enzyme complexes involved in mucin breakdown.
• To explore the role of these complexes in the gut ecosystems of various hosts, including humans and animals.

Main Methods:

• Computational prediction of mucinolysome components across 65 bacterial genomes (63 MAGs, 2 isolated).
• Experimental validation using a cultivated *Limousia* strain (ET540) to assess growth on mucins and gene expression.
• Protein structure modeling using AlphaFold3 to predict cohesin-dockerin interactions and complex assembly.

Main Results:

• Discovery of mucinolysomes, extracellular multi-enzyme complexes with core components (scaffoldins and CAZymes) in *Limousia* bacteria.
• Demonstration that *Limousia* ET540 utilizes mucins as a sole carbon source, upregulating mucinolysome gene expression.
• Prediction of complex assembly via cohesin-dockerin interactions, with higher abundance of mucinolysome-encoding bacteria in farm animals than humans.

Conclusions:

• Mucinolysomes represent a novel mechanism for mucin glycan degradation in the gut.
• These complexes are conserved across diverse *Limousia* genomes, suggesting a significant functional role.
• The findings highlight the importance of mucinolysomes in livestock gut ecosystems and provide a framework for studying host-microbe interactions.