Changes in the Gut Microbiome Drive Age-Related Intestinal Barrier Dysfunction
Study using fecal transplants and mouse models finds age-associated expansion of Klebsiella aerogenes increases histamine via a histidine decarboxylase variant, which suppresses Nlrp6–LC3–dependent autophagy and worsens intestinal barrier dysfunction in sepsis. Modulating histamine levels or overexpressing Nlrp6 reduced inflammation in septic mice, identifying the HA–Nlrp6–LC3 axis as a potential therapeutic target for aged hosts.
Why it mattersKlebsiella aerogenes–derived histamine drives sepsis gut barrier failure; screen microbiomes for HDC-bearing strains to stratify older patients.