IDDF2021-ABS-0212 Fecal microbiota transplantation ameliorates experimental colitis by regulating autophagy

Background Autophagy is an important regulatory process to coordinate the homeostasis of intestinal epithelial cells under stress and mediate pathogen clearance. Fecal microbiota transplantation(FMT) is an important treatment for ulcerative colitis. In this study, we constructed autophagy activated/inhibited dextran sulfate sodium (DSS) induced colitis mice and observed whether FTM improve experimental colitis by regulating autophagy. Methods Thirty male BALB/c mice were randomly divided into five groups: healthy control group (Control), DSS induced colitis group (DSS), autophagy activated colitis group (DSS+RAPA), autophagy inhibited colitis group (DSS+CQ) and autophagy inhibited and FMT intervention group (DSS+CQ+FMT). 3% DSS drinking water was used to induce colitis, and the following interventions were given daily for seven days: Control group and DSS group were administered with PBS by gavage and intraperitoneal injection, DSS+RAPA group were administered with PBS by gavage and rapamycin (4mg/kg) by intraperitoneal injection, DSS+CQ group were administered with hydroxychloroquine (40mg/kg) by gavage and PBS by intraperitoneal injection, DSS+CQ+FMT group were administered with hydroxychloroquine (40mg/kg) and PBS by intraperitoneal injection, and eight hours later administered FMT from healthy mice (100µL/10g) by gavage. Disease activity index (DAI) were monitored daily. On the eighth day, colonic tissues were resected after the mice were euthanized. The colon length was recorded, and some tissues were collected for histopathologic evaluation, while some tissues for observing autophagy expression (P62, LC3B and TFEB) by PCR Results DAI (P=0.0128), colon length (P=0.043), and colon histopathologic score (P=0.0392) of colitis mice were effectively improved by autophagy activation (rapamycin), while DAI (P=0.4178), colon length (P=0.0393) and colon histopathologic score (P=0.765) were worsened markedly by autophagy inhibition (hydroxychloroquine); After autophagy inhibition, the following indexes of colitis were still significantly improved by FMT: DAI (P=0.0205), colon length (P=0.0008) and colon histopathologic score (P=0.0015)(IDDF2021-ABS-0212 Figure 1A. Fecal microbiota transplantation ameliorated experimental colitis and up-regulated autophagy expression, IDDF2021-ABS-0212 Figure 1B. Fecal microbiota transplantation ameliorated experimental colitis and up-regulated autophagy expression, IDDF2021-ABS-0212 Figure 1C. Fecal microbiota transplantation ameliorated experimental colitis and up-regulated autophagy expression, IDDF2021-ABS-0212 Figure 1D. Fecal microbiota transplantation ameliorated experimental colitis and up-regulated autophagy expression), and the expression of the following autophagy genes were changed: P62 was significantly down-regulated (P=0.006), while LC3B and TFEB were significantly increased (P=0.0033; P=0.0039)(IDDF2021-ABS-0212 Figure 1E. Fecal microbiota transplantation ameliorated experimental colitis and up-regulated autophagy expression). Conclusions Autophagy activation may be one of the mechanisms by which FMT improves DSS induced experimental colitis.