The high utilization of human milk oligosaccharides with glycoside hydrolase family exsH gene in Akkermansia species

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This study investigated the role of glycoside hydrolase (GH) genes in Akkermansia species in the utilization of human milk oligosaccharides (HMOs), particularly 2′-fucosyllactose (2′-FL). Through genetic and functional analyses of 30 isolated Akkermansia strains, we identified significant differences in 2′-FL utilization among Akkermansia muciniphila, Akkermansia muciniphila _E, and Akkermansia massiliensis . Notably, Akkermansia muciniphila exhibited superior 2′-FL utilization compared to Akkermansia massiliensis . We discovered that the exsH gene, belonging to the GH16 family, plays a crucial role in 2′-FL metabolism in Akkermansia massiliensis . Strains with high exsH expression demonstrated enhanced 2′-FL utilization, while those lacking exsH showed reduced efficiency. Interestingly, Akkermansia muciniphila _E, despite possessing more GH29 and GH95 genes, exhibited poor 2′-FL utilization, suggesting that factors beyond these genes, such as exsH expression, are critical for efficient HMOs metabolism. These findings highlight the genetic diversity within the Akkermansia species and provide insights into the mechanisms underlying HMOs utilization, offering potential avenues for developing targeted probiotics to enhance gut health.