Engineering the Gut Microbiome to Degrade Meat-Derived Sialic Acids

Sialic acids serve as nutrient sources for commensal anaerobes in the gut microbiome, yet the metabolic pathways involved are poorly characterized. Sialic acids can be derived from meat food sources or host intestinal cells; these sugars are found at terminal positions of cell membrane glycans playing crucial roles in cell-to-cell communication and immune signaling. The meat-derived sialic acid Neu5Gc (n-glycolylneuraminic acid) has been linked to adverse immune responses associated with inflammatory disorders, atherosclerosis, and cancer. Our research seeks to identify or engineer native gut bacteria as putative probiotics capable of degrading Neu5Gc; and thus, mitigate related diseases. Humans cannot convert Neu5Ac (n-acetylneuraminic acid) into Neu5Gc due to an inactivated cmah hydroxylase gene, therefore Neu5Gc is only introduced through meat consumption. Although bacterial sialidases that release sialic acids residues from glycan chains can prevent Neu5Gc-incorporation into the human mucosa, free-sialic acids can be used by opportunistic pathogens triggering intestinal dysbiosis. Publicly annotated genomes from commensals such as Hungatella and Bacteroides encode putative sialic acid catabolic genes similar to the nanAKE pathway reported in E. coli; however, their specificity for Neu5Ac versus Neu5Gc consumption remains unknown. Through extensive screening of existing isolates, we have identified bacterial taxa with different specificities for Neu5Ac and Neu5Gc consumption. Following whole genome sequencing, selected bacterial taxa carrying putative sialic acid-catabolic genes are being characterized in order to identify enzymatic specificity to Neu5Ac or Neu5Gc. Our findings pave the way for the formulation of candidate probiotics that might contribute to mitigate health risks associated with meat consumption.