Very little is known about disease transmission via the gut microbiome. We hypothesized that certain inflammatory features could be transmitted via the gut microbiome and tested this hypothesis using an animal model of inflammatory diseases. Twelve-week-old healthy C57 Bl/6 and Germ-Free (GF) female and male mice were fecal matter transplanted (FMT) under anaerobic conditions with TNF^ΔARE−/+ donors exhibiting spontaneous Rheumatoid Arthritis (RA) and Inflammatory Bowel Disease (IBD) or with conventional healthy mice control donors. The gut microbiome analysis was performed using 16S rRNA sequencing amplification and bioinformatics analysis with the HIVE bioinformatics platform. Histology, immunohistochemistry, ELISA Multiplex analysis, and flow cytometry were conducted to confirm the inflammatory transmission status. We observed RA and IBD features transmitted in the GF mice cohort, with gut tissue disruption, cartilage alteration, elevated inflammatory mediators in the tissues, activation of CD4/CD8+ T cells, and colonization and transmission of the gut microbiome similar to the donors’ profile. We did not observe a change or transmission when conventional healthy mice were FMT with TNF^ΔARE−/+ donors, suggesting that a healthy microbiome might withstand an unhealthy transplant. These findings show the potential involvement of the gut microbiome in inflammatory diseases. We identified a cluster of bacteria playing a role in this mechanism.

The particularly unique composition of the gut microbiota has the potential to influence the health or disease status of animal and human hosts. Altering the homeostasis of the host-bacteria could lead to changes in gut flora that result in disease or activation of a specific immunological response, which could explain the variations observed in patient responses to current therapies. A standardized model is crucial for studying the influence of the gut microbiota on therapeutic modalities. A step by step mouse model and sterility management system that compares a control strain of C57BL/6 mice to the established C57BL/6 germ-free (GF) strain has been developed. The GF BL/6 mouse phenotype is well established, and the anatomical differences between the GF and control mice were evident in this model. This method could be applied to research studies investigating the microbiome impact, the response to various therapies, or disease transfer via fecal transplants. A standardized sterility maintenance method is crucial in this context.