Fecal microbiota transplantation from elderly human donors into gnotobiotic-style miniature pigs reduced ileal villus height and lowered tight junction proteins (ZO-1, claudin-1, occludin) relative to young-donor transplants, alongside distinct shifts in plasma metabolites and suppression of interferon-stimulated genes in the ileal mucosa. Specific microbial-associated metabolites were shown to act causally on barrier function in epithelial cell culture, with Tyr-Phe strengthening and prostaglandin E3 weakening transepithelial resistance. The work identifies the aging gut microbiome as a transmissible driver of intestinal barrier decline rather than a passive marker of it.
Key Points
- Elderly-donor microbiota reduced tight junction proteins and ileal villus height
- Tyr-Phe raised epithelial resistance; prostaglandin E3 lowered it
- Seven interferon-stimulated mucosal genes downregulated after elderly-donor transplant
Longevity Analysis
Intestinal barrier integrity sits upstream of much of what determines systemic inflammatory tone with age, and these data demonstrate that the aged microbial community alone is sufficient to compromise it in a host with human-like gastrointestinal anatomy. The downregulated interferon-stimulated genes point to a quieter mucosal surveillance posture, meaning barrier loss and reduced immune vigilance move together rather than independently. For practical purposes, the actionable target is not the microbiome as an abstraction but the specific metabolites it produces — dipeptides and lipid mediators that determine whether the epithelium seals or leaks, and which are shaped daily by what reaches the colon.
Original published by Wiley Aging Cell, by Jiaxin Wang, Lingyu Li, Lihua Mei, Zhining Tang, Baorui Liao, Qianye Zhao, Yuzeng Wang, Qingyao Fu, Liu Ren, Zhian Zhai, Yifei Xu, Aoyu Yang, Shuai Duan, Zhengyuan Zhai, Yanling Hao, Yalin Zhou, Yajun Xu, Ying Yang, Zhenlong Wu, Yun Ji .