Age-related susceptibility to high-dose fecal microbial administration in young mice.

The safety of fecal microbiota transplantation in early life remains unclear. We established murine models using two age groups (3-week-old and 8-week-old mice) and two inoculation doses (low, 100 μL; high, 400 μL), with age-matched saline controls. High-dose fecal microbial administration in 3-week-old mice was associated with reduced weight gain, mild hypothermia, diarrhea, and multi-organ pathological changes, together with altered gut tight junction gene expression, elevated serum IL-6 and IL-1β, and increased Proteobacteria-associated bacterial DNA signals detected in extraintestinal tissues. In contrast, these effects were not observed in 8-week-old mice under the same conditions. Our findings suggest that early life may represent a susceptible window for adverse effects to high-dose fecal microbial exposure and support the need for age- and dose-stratified safety evaluation before pediatric application.