Analyzing the Role of Gut Microbiota on the Onset of Autoimmune Diseases Using TNFΔARE Murine Model

Vivienne Edwards; Dylan L Smith; Francoise Meylan; Linda Tiffany; Sarah Poncet; Wells W Wu; Je-Nie Phue; Luis Santana-Quintero; Kathleen A Clouse; Odile Gabay

doi:10.3390/microorganisms10010073

Analyzing the Role of Gut Microbiota on the Onset of Autoimmune Diseases Using TNF^ΔARE Murine Model

Microorganisms. 2021 Dec 30;10(1):73. doi: 10.3390/microorganisms10010073.

Authors

Affiliations

¹ Division of Biotechnology Review and Research I, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Office of Biotechnology Products, Office of Pharmaceutical Quality, Silver Spring, MD 20993, USA.
² Translational Immunology Section, NIH, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892, USA.
³ Facility for Biotechnology Resources, Center for Biologicals Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA.
⁴ U.S. Food and Drug Administration, Center for Biologics Evaluation & Research, Office of Biostatistics and Epidemiology, HIVE, Silver Spring, MD 20993, USA.
⁵ U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of New Drugs, Office of Hematology and Oncology Products, Silver Spring, MD 20993, USA.

Abstract

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.

Keywords: Fecal Matter Transplants/Fecal Matter Transplanted (FMT); auto-immune diseases; dysbiosis; gut microbiome.

Grants and funding

P30 DK097948/DK/NIDDK NIH HHS/United States