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://ichgcp.net/clinical-trials-registry/NCT02318134" title="See in ClinicalTrials.gov">NCT02318134).

Keywords: acute pancreatitis; faecal microbiota transplantation; gastrointestinal dysfunction; gut microbiota dysbiosis; infected pancreatic necrosis.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Ding, He, Li, Huang, Lei, Ke, Chen, Yang, Cai, Liao, He, Xia, Xiong, Lu and Zhu.

Figures

Figure 1

Flow chart of patients included and excluded from analysis according to CONSORT 2010. CONSORT, Consolidated Standards of Reporting Trials; GI, gastrointestinal; AP, acute pancreatitis; FMT, faecal microbiota transplantation. *GI dysfunction was defined as intra-abdominal hypertension and GI symptoms or signs including obvious abdominal distention, abdominal rumbling sound weakening or disappearance and no self-defecation. †Multiple organ failure was defined as two or more organ failures of the respiratory, cardiovascular and renal systems, which were defined according to the 2012 Atlanta Classification criterion.

Figure 2

Gastrointestinal function and inflammatory indicators were examined and compared before and at 1 week after intervention in the two groups. The decline rate of those indicators was also compared between the FMT group and the control group. Gastrointestinal function indicators included IAP (A), the level of DAO (B), the level of D-lactate (C), and the level of endotoxin (D); inflammatory indictors included the level of CRP (E), the level of PCT (F), the level of THF-α (G), and the level of IL-6 (H). FMT, faecal microbiota transplantation; IAP, intra-abdominal pressure; DAO, D-amino acid oxidase; CRP, C-reactive protein; PCT, procalcitonin; TNF-α, tumour necrosis factor-α; IL-6, interleukin-6; ns, not significant. *P < 0.05, **P < 0.01, ***P < 0.001.