A single faecal microbiota transplantation modulates the microbiome and improves clinical manifestations in a rat model of colitis

Abstract

Inflammatory bowel disease; Faecal microbiota transplantation; Rat model of colitis

Enfermedad inflamatoria intestinal; Trasplante de microbiota fecal; Modelo de colitis en ratas

Malaltia inflamatòria intestinal; Trasplantament de microbiota fecal; Model de colitis en rates

Background: Faecal microbiota transplantation (FMT) is a novel potential therapy for inflammatory bowel diseases, but it is poorly characterised. Methods: We evaluated the performance of the mouse and rat as a pre-clinical model for human microbiota engraftment. We then characterised the effect of a single human stool transfer (HST) on a humanised model of DSS-induced colitis. Colonic and faecal microbial communities were analysed using the 16S rRNA approach and clinical manifestations were assessed in a longitudinal setting. Findings: The microbial community of rats showed greater similarity to that of humans, while the microbiome of mice showed less similarity to that of humans. Moreover, rats captured more human microbial species than mice after a single HST. Using the rat model, we showed that HST compensated faecal dysbiosis by restoring alpha-diversity and by increasing the relative abundance of health-related microbial genera. To some extent, HST also modulated the microbial composition of colonic tissue. These faecal and colonic microbial communities alterations led to a relative restoration of colon length, and a significant decrease in both epithelium damage and disease severity. Remarkably, stopping inflammation by removing DSS before HST caused a faster and greater recovery of both microbiome and clinical manifestation features. Interpretation: Our results indicate that the rat outperforms the mouse as a model for human microbiota engraftment and show that the efficacy of HST can be enhanced when inflammation stimulation is withdrawn. Finally, our findings support a new therapeutic strategy based on the use FMT combined with anti inflammatory drugs.

Study funded by the Instituto de Salud Carlos III/FEDER (PI17/00614), a government agency. The funder had no role in study design, data collection, data analysis, interpretation or writing of the report.