Adverse events of intestinal microbiota transplantation in randomized controlled trials: a systematic review and meta-analysis

Abstract

Background Intestinal microbiota transplantation (IMT) has been recognized as an effective treatment for recurrent Clostridium difficile infection (rCDI) and a novel treatment option for other diseases. However, the safety of IMT in patients has not been established. Aims This systematic review and meta-analysis was conducted to assess the safety of IMT. Methods We systematically reviewed all randomized controlled trials (RCTs) of IMT studies published up to 28 February 2021 using databases including PubMed, EMBASE and the Cochrane Library. Studies were excluded if they did not report adverse events (AEs). Two authors independently extracted the data. The relative risk (RR) of serious adverse events (SAEs) and common adverse events (CAEs) were estimated separately, as were predefined subgroups. Publication bias was evaluated by a funnel plot and Egger’s regression test. Results Among 978 reports, 99 full‐text articles were screened, and 20 articles were included for meta-analysis, involving 1132 patients (603 in the IMT group and 529 in the control group). We found no significant difference in the incidence of SAEs between the IMT group and the control group (RR = 1.36, 95% CI 0.56–3.31, P = 0.50). Of these 20 studies, 7 described the number of patients with CAEs, involving 360 patients (195 in the IMT group and 166 in the control group). An analysis of the eight studies revealed that the incidence of CAEs was also not significantly increased in the IMT group compared with the control group (RR = 1.06, 95% CI 0.91–1.23, P = 0.43). Subgroup analysis showed that the incidence of CAEs was significantly different between subgroups of delivery methods (P(CAE) = 0.04), and the incidence of IMT-related SAEs and CAEs was not significantly different in the other predefined subgroups. Conclusion Currently, IMT is widely used in many diseases, but its associated AEs should not be ignored. To improve the safety of IMT, patients' conditions should be fully evaluated before IMT, appropriate transplantation methods should be selected, each operative step of faecal bacteria transplantation should be strictly controlled, AE management mechanisms should be improved, and a close follow-up system should be established.

Hot topics on fecal microbiota transplantation for the treatment of inflammatory bowel disease

“…The remission rate of patients in the FMT group was significantly higher than that in the placebo group, which led to interest in the negative results of a study involving two administrations published by Rossen et al ( 17 UC who received more than 10 administrations and achieved clinical remission was 49%, significantly higher than the remission rate (27%) for patients with UC who received fewer than 10 administrations (p = 0.001) (54). There have been reports that there was no significant difference in adverse events (both severe and common adverse events) between the FMT and placebo groups in RCT studies involving the use of either single or multiple FMT administrations (75). However, too many administrations of FMT will bring inconvenience and psychological burden to patients; therefore, getting the best therapeutic effect under the premise of the least number of administrations is a topic worthy of further study.…”

“…The occurrence of these adverse events makes every doctor distressed, and the operation regimen is constantly improving. Moreover, a recent meta-analysis article analyzed published RCTs using FMT for various diseases and no significant difference in the incidence of serious adverse events was observed between the FMT and placebo groups (75). This suggests that FMT is a safe treatment modality.…”

Human gut microbiome: Therapeutic opportunities for metabolic syndrome—Hype or hope?

“…It seems that administration via oral capsules or endoscopically via the lower gastrointestinal tract is less prone to adverse events. Translocation and infection with transplanted bacteria can occur, the risk seems to be higher in patients with an altered intestinal barrier 136 . In the studies related to metabolic diseases no events of bacteremia or sepsis have been described so far.…”

“…Translocation and infection with transplanted bacteria can occur, the risk seems to be higher in patients with an altered intestinal barrier. 136 In the studies related to metabolic diseases no events of bacteremia or sepsis have been described so far.…”

Liver-Gut-Interaction: Role of Microbiome Transplantation in the Future Treatment of Metabolic Disease

“…It seems that administration via oral capsules or endoscopically via the lower gastrointestinal tract is less prone to adverse events. Translocation and infection with transplanted bacteria can occur; the risk seems to be higher in patients with an altered intestinal barrier [ 37 ]. In the studies related to metabolic diseases, no bacteremia or sepsis events have been described so far.…”