P006 Engineered propionate-producing bacteria attenuates murine colitis by modulating the immune function of resident macrophages via histone deacetylase

Abstract Background Most inflammatory bowel disease (IBD) patients are unable to maintain long-term remission by current treatment. Propionate has been proven be able exert anti-inflammatory effects in intestinal inflammation, but direct supplement of propionate actual disadvantages including low bioavailability and poor sustained effect, et. al. Methods In this study, the genes related acetate synthesis metabolism were knocked out through double plasmid CRISPR/cas9 gene editing system increase yield ultimately form engineered propionate-producing bacteria (EPB). The dextran sulfate sodium（DSS）-induced colitis model was used explore protective effect EPB vivo. Flow cytometry evaluate ratio resident macrophage. Peritoneal macrophage RAW264.7 cell lines mechanism on immune function macrophages vitro. Real-time polymerase chain reaction (RT-PCR) performed detect expression several cytokines colon tissue cells. Enzyme-linked immunosorbent assay (ELISA) level supernatant. Western bolt levels histone deacetylase protein transcription factor GATA6. Results exhibited enhanced propionic acid production. vivo results showed that group had less barrier damage infiltration than control groups indicating it could prominently ameliorate DSS-induced colitis. promoted production cytokine IL-10 reduced IL-2、IL-5 IL-6 mice. further exploration EPB, we found increased proportion (F4/80hiCD11bhi) peritoneal cavity, And GATA6, which is specific express macrophages, detected tissue. Moreover, investigated vitro not only affected ability also apoptosis. Further analysis regulatory associated with G protein-coupled receptors 41/43 2 (HDAC2), closely propionate. GPR41/43 inhibitor weakened while HDAC trichostatin A (TSA) exerted a similar EPB. Conclusion (EPB) attenuate mouse modulating classic inflammation-related cytokines, indicates an effective safe treatment strategy for ulcerative