Efficacy and Safety of Faecal Microbiota Transplantation for Acute Pancreatitis: A Randomised, Controlled Study

Abstract

Aims: We investigated whether faecal microbiota transplantation (FMT) decreases intra-abdominal pressure (IAP) and improves gastrointestinal (GI) dysfunction and infectious complications in acute pancreatitis (AP).Methods: In this first randomised, single-blind, parallel-group, controlled study, we recruited and enrolled consecutive patients with AP complicated with GI dysfunction. Eligible participants were randomly assigned to receive faecal transplant (n = 30) or normal saline (n = 30) via a nasoduodenal tube once and then again 2 days later. The primary endpoint was the rate of IAP decline; secondary endpoints were GI function, infectious complications, organ failure, hospital stay and mortality. Analyses were based on intention to treat.Results: We enrolled 60 participants and randomly assigned them to the FMT (n = 30) or control (n = 30) group. Baseline characteristics and disease severity were similar for both groups. IAP decreased significantly 1 week after intervention in both groups, with no difference in the IAP decline rate between FMT and Control group [0.1 (−0.6, 0.5) vs. 0.2 (−0.2, 0.6); P = 0.27]. Normal gastrointestinal failure (GIF) scores were achieved in 12 (40%) patients in the FMT group and 14 (47%) in the control group, with no significant difference (P = 0.60). However, D-lactate was significantly elevated in the FMT group compared to the control group, as calculated by the rate of decline [−0.3 (−3.7, 0.8) vs. 0.4 (−1.1, 0.9); P = 0.01]. Infectious complications occurred in 15 (50%) and 16 (53.33%) patients in the FMT and control groups, respectively (P = 0.80). However, interleukin-6 (IL-6) was significantly elevated in the FMT group compared to the control group, as calculated by the rate of decline [0.4 (−3.6, 0.9) vs. 0.8 (−1.7, 1.0); P = 0.03]. One participant experienced transient nausea immediately after FMT, but no serious adverse events were attributed to FMT.Conclusion: FMT had no obvious effect on IAP and infectious complications in AP patients, though GI barrier indictors might be adversely affected. Further multi-centre studies are needed to confirm our findings. The study was registered at https://clinicaltrials.gov (NCT02318134).

Intestinal Microbiomics in Physiological and Pathological Conditions

“…Experimental studies performed on mice suggested that microbiota regulation by fecal transplantation might reduce the damage at the intestinal barrier level and create a more stable evolution, preventing severe forms [80,81]. Ding et al 2021 showed in a randomized, controlled study registered at https://clinicaltrials.gov (NCT02318134) that the fecal microbiota transplantation had no beneficial effects in the evolution of severe forms of AP and moreover, the intestinal permeability might have been adversely affected [82].…”

Acute Pancreatitis

“…31,[60][61][62] No effective pharmacological treatments have been identified despite the completion of several clinical trials. 31,[63][64][65][66] Promising preliminary data from a recently completed study suggest that targeting Ca 2+ signaling in AP patients via the Orai1 inhibitor (Auxora) may improve outcomes; however, more human trials are necessary to determine the safety and efficacy of this therapeutic. 67 Furthermore, existing health inequalities in AP will likely limit the availability of potential therapeutic agents in minorities.…”

“…Antibiotics are recommended only if an infection has been confirmed 31,60–62 . No effective pharmacological treatments have been identified despite the completion of several clinical trials 31,63–66 . Promising preliminary data from a recently completed study suggest that targeting Ca 2+ signaling in AP patients via the Orai1 inhibitor (Auxora) may improve outcomes; however, more human trials are necessary to determine the safety and efficacy of this therapeutic 67 …”

The role of gut microbiota in acute pancreatitis: new perspectives in pathogenesis and therapeutic approaches

“…[72] However, a recent RCT by Ding et al found no effect of FMT on intra-abdominal hypertension and infectious complications of AP patients. [85] Van den Berg et al suggested that FMT increased the mortality of western diet feeding ANP mice and promote the dissemination of pathogenic bacteria in both necrotic tissue and peripheral blood. [9] Liu et al found normobiotic FMT feces from healthy controls may ameliorate the severity of AP through inducing the production of NAD + associated metabolites.…”