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Updated: Aug 22, 2026
Preparation and Maintenance of Bioexclusion IsoPositive Cage Experiment for Human Fecal Transplantation into Germ-Free Mice
Published on: February 28, 2025
Age-related susceptibility to high-dose fecal microbial administration in young mice
Hui-Ling Chen1,2, Ying-Chen3, Li-Shun Wang4,5
1Center for Traditional Chinese Medicine and Gut Microbiota, Minhang Hospital, Fudan University, Shanghai, 201100, China.
Abstract:
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.
Insights
High-dose fecal microbial transplantation in young mice caused adverse effects. Older mice showed no issues, suggesting early life is a sensitive period needing careful safety evaluations for pediatric fecal microbiota transplantation.
Area of Science:
- Microbiology
- Gastroenterology
- Pediatric Safety
Background:
- Fecal microbiota transplantation (FMT) is a promising therapeutic but its safety in early life is unknown.
- Early life development involves significant changes in the gut microbiome and immune system.
Purpose of the Study:
- To investigate the safety of fecal microbial administration in young versus older mice.
- To determine the impact of different inoculation doses on safety outcomes.
Main Methods:
- Murine models were established using 3-week-old and 8-week-old mice.
- Two inoculation doses (low: 100 μL; high: 400 μL) of fecal microbiota were administered, with saline controls.
- Outcomes assessed included weight gain, body temperature, clinical signs, histopathology, gene expression, serum cytokines, and microbial DNA in tissues.
Main Results:
- High-dose fecal microbial administration in 3-week-old mice led to reduced weight gain, hypothermia, diarrhea, and multi-organ pathology.
- Significant alterations in gut tight junction gene expression, elevated IL-6 and IL-1β, and extraintestinal Proteobacteria DNA were observed in young mice.
- Eight-week-old mice did not exhibit these adverse effects under identical conditions.
Conclusions:
- Early life represents a susceptible window for adverse effects from high-dose fecal microbial exposure.
- Age- and dose-stratified safety evaluations are crucial before considering pediatric FMT applications.
- Further research is needed to define safe parameters for early-life microbial interventions.
