Longevity & Aging

Gut Enzyme ST8Sia6 Acts as a Molecular Brake on Intestinal Inflammation

Researchers at Mayo Clinic discovered that the enzyme ST8Sia6, which adds sialic acid sugar modifications to immune cell proteins, is essential for preventing chronic gut inflammation. Mice without ST8Sia6 spontaneously accumulate activated immune cells in the small intestine, develop shortened bowels in adulthood, and suffer more severe colitis when chemically challenged. Loss of the enzyme amplifies pathogenic Th1 and Th17 T cell programs, boosts inflammatory chemokines CCL3, CCL4, and CCL5, and alters glycosylation of key immune regulators CD43 and CD45. Importantly, even partial loss of ST8Sia6 in heterozygous mice produced an intermediate inflammatory phenotype, suggesting that gut immune homeostasis is exquisitely sensitive to this enzyme's activity level.