P1339 CJRB-201, a promising candidate for microbiome-based therapy with potent anti-inflammatory effects in Inflammatory Bowel Disease
Authors: Shin C , Park J , Lee S , Hyun D W , Kim D H , Jung Y , Kim J M , Kim J H , Baek M , Park Y J , Lee H , Jang H , Hong D H , Lee J , Cho K H , Cha I , Yoo J A , Lee K , Park Y R , Kwon J E , Hong K H , Huh J R , Chun J ,   CJ Bioscience
Published: January 2025

Abstract

Background
Inflammatory bowel disease (IBD) is a chronic inflammatory gastrointestinal condition characterized by immune dysregulation driven by microbiome dysbiosis, with a reduction of beneficial bacteria such as Faecalibacterium, a dominant commensal bacterium comprising 5-10% of the human gut microbiome. Its depletion is a hallmark of Crohn's disease and other autoimmune-related conditions, making it an emerging candidate as a next-generation probiotic.

Methods
CJRB-201 was selected using our BI platform (Ez-Mx), based on more than 500 metagenomic datasets from IBD patients and healthy controls. The immune regulatory efficacy of CJRB-201 was evaluated through in vitro and ex vivo assays, focusing on key cytokine ratios (IL-10/IL-1β, IL-10/TNF, IL-10/IFN-γ) in macrophages and T cells. The induction of T regulatory (T reg) cell populations was evaluated ex vivo and in germ-free (GF) mice. Three pathogenetically different IBD animal models (DSS-induced, IL-10 KO GF, T cell transfer) were examined to assess its efficacy. Lastly, the SHIME system (Simulator of the Human Intestinal Microbial Ecosystem) was applied to test various fibers that promote the growth of CJRB-201.

Results
Among 34 tested anti-inflammatory strains, including those from CJ Bioscience, 4D Pharma, and our Ez-Mx platform, CJRB-201 emerged as one of the most effective. Notably, CJRB-201 and its conforming species showed the highest induction of T reg populations ex vivo among the sixty Faecalibacterium strains, primarily driven by its cell pellet form rather than the supernatant. Administration of CJRB-201 resulted in successful colonization in the colon of GF mice, leading to an enhanced T reg cell population. In the three IBD models with both preventative and therapeutic approaches, CJRB-201 demonstrated significant improvements across five key disease features (body weight, disease activity index, colon length, histopathology, and inflammatory markers such as cytokines and fecal lipocalin-2). Interestingly, CJRB-201 outperformed other potential single and consortia strains and demonstrated efficacy comparable to the α-IL-12p40 antibody, particularly in the T cell transfer model (Figure 1). Lastly, we identified the fiber that stabilizes the engraftment of CJRB-201 in the SHIME system.

Conclusion
CJRB-201 exhibits superior anti-inflammatory efficacy in multiple immune assays and IBD animal models, significantly improving preclinical and inflammatory markers. Given its ability to enhance T reg populations and the promising potential of the identified fiber in supporting its colonization, CJRB-201 holds strong promise as a microbiome-based therapeutic for IBD patients.

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