If you give a mouse a poopsicle: a novel fecal microbiota transplant method for exploring the role of the gut microbiome in stress-related outcomes in mice.
Publication Title
Front Immunol
Document Type
Article
Publication Date
1-1-2026
Keywords
washington; isb
Abstract
BACKGROUND: The microbiome-gut-brain axis is a mediator of stress-related disorders. The number of preclinical studies exploring the potential causal mechanism of this connection using fecal microbiota transplantation (FMT) is growing. However, the most common method for delivering fecal transplants in rodent models is still oral gavage, which creates an adverse experience that may confound stress-related outcomes. Here, we establish an alternative methodology for FMT that decreases stress induced by traditional experimental procedures.
METHODS: We first used preference and anxiety behavior assays to identify antibiotic therapies having maximal tolerability and minimal anxiolytic properties. We then collected feces from donor mice and homogenized them with a microbe-stabilizing buffer to create a slurry, which was frozen into aliquots ("poopsicles") for subsequent FMT. Recipient mice voluntarily consumed the frozen aliquots, and blood was collected to compare corticosterone relative to that after delivery via traditional gavage.
RESULTS: Plasma corticosterone levels were found to be significantly lower in mice receiving frozen aliquots compared to oral gavage. Furthermore, relative to controls, microbial signatures of mice receiving FMT via frozen aliquots were more similar to those of the donors at one week following final FMT and were sustained for up to six weeks, as assessed by comparing Bray-Curtis beta diversity distances.
CONCLUSION: Together, these results establish antibiotic and FMT methods that minimize treatment-induced stress, while effectively transplanting fecal microbes between murine conspecifics.
Area of Special Interest
Digestive Health
Area of Special Interest
Mental Health
Specialty/Research Institute
Gastroenterology
Specialty/Research Institute
Institute for Systems Biology
DOI
10.3389/fimmu.2026.1816919
