Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Auto-immune diseases are in constant progression in the US. Biologic therapeutics have been used successfully to treat these diseases, but have presented some unique regulatory challenges. Although they can be very efficacious, the response to these therapeutics can initially be quite variable among patients and patients who are initially responsive can develop resistance to them over time. We propose that the gut microbiome could play a role in the initial variability and impact the response to treatments.
Methods: Germ Free (GF) mice colonies have been successfully developed in a sterile environment in the CBER/CDER Animal Facility. We used these GF mice to test human monoclonal antibodies and fusion proteins, following a treatment regimen consistent with patient regimens, to evaluate the role of the microbiome when GF mice are compared to conventional mice controls treated in parallel. Our pilot study is analyzed from two different approaches: assessment of taxonomy changes and an immunologic variation in the mouse gut.
Results: Our results show a break in the symbiosis of the commensal bacteria communities after TNF antagonist treatment. These mice present a shift in the ratio Firmicutes/Bacteroidetes with a statistically significant increase in this latter family over uncultured bacteria. Differences are reported between males and females and between young (3 month-old) and old (9 month-old) mice. When the mucosal immune system is explored, comparing conventional and GF mice, it appears that the Innate Lymphoid Cells (ILCs) colonizing the lamina propria of the gut have two very different profiles and therefore, are likely to respond differently to cross-talk with commensal bacteria in the gut. A preliminary mechanistic link to the plasticity between ILC1 and LC3 is suggested in older mice.
Conclusion: Our results show that the Microbiota indeed plays a regulating role in TNF antagonist treatment, involving a dysbiosis and a regulation through ILCs. This observational study should be followed by in vivo functionality studies.
To cite this abstract in AMA style:Gabay O, Vicenty J, Wunderlin G, Tiffany L, Wu W, Simonyan V, Clouse KA. Impact of TNF Antagonist Treatment on the Gut Microbiome In Vivo [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/impact-of-tnf-antagonist-treatment-on-the-gut-microbiome-in-vivo/. Accessed January 22, 2022.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/impact-of-tnf-antagonist-treatment-on-the-gut-microbiome-in-vivo/