Systematic Review With Meta-analysis

Efficacy of Faecal Microbiota Transplantation for the Treatment of Irritable Bowel Syndrome

Gianluca Ianiro; Leonardo H. Eusebi; Christopher J. Black; Antonio Gasbarrini; Giovanni Cammarota; Alexander C. Ford

Disclosures

Aliment Pharmacol Ther. 2019;50(3):240-248. 

In This Article

Abstract and Introduction

Abstract

Background: Increasing evidence supports the role of the gut microbiota in the aetiology of irritable bowel syndrome (IBS). Faecal microbiota transplantation (FMT) is a highly effective treatment against recurrent Clostridioides difficile infection in randomised controlled trials (RCTs), and may be beneficial in ulcerative colitis. However, its efficacy in IBS is uncertain.

Aim: To perform a systematic review and meta-analysis to examine this issue.

Methods: We searched MEDLINE, EMBASE, EMBASE Classic, the Cochrane Central Register of Controlled Trials, and clinicaltrials.gov through to March 2019. RCTs recruiting adults with IBS, which compared FMT with placebo, were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% CI.

Results: The search strategy identified 322 citations. Five RCTs were eligible for inclusion, containing 267 patients. Overall, 92.2% of included patients had IBS-D or IBS-M, and only 7.8% IBS-C. When data were pooled for all patients, irrespective of stool type, the RR of IBS symptoms not improving was 0.98 (95% CI 0.58-1.66). Placebo capsules administered orally were superior to capsules containing donor stool in two pooled trials (RR = 1.96; 95% CI 1.19-3.20). FMT from donor stool delivered via colonoscopy was superior to autologous stool in two pooled RCTs (RR = 0.63; 95% CI 0.43-0.93). FMT from donor stool via nasojejunal tube showed a trend towards a benefit over autologous stool in one trial (RR = 0.69; 95% CI 0.46-1.02).

Conclusions: Fresh or frozen donor stool delivered via colonoscopy or nasojejunal tube may be beneficial in IBS. Larger, more rigorously conducted trials of FMT in IBS are needed.

Introduction

Irritable bowel syndrome (IBS) is a chronic functional bowel disorder, with a prevalence of 10% globally.[1] The diagnosis is made based on the presence of recurrent abdominal pain related to defaecation, in association with an alteration in either stool form or stool frequency.[2] Although the pathophysiology of IBS is still poorly understood, known proposed aetiologies that could contribute to the development of the disease include genetics, low-grade inflammation, increased gut permeability, abnormal biliary and serotonin metabolism, central neurologic dysfunction, altered gastrointestinal motility, visceral hypersensitivity, and changes in the composition of the gut microbiota.[3]

The hypothesis that the gut microbiota is involved in the pathophysiology of IBS is supported by a wealth of clinical data. Epidemiological surveys demonstrate, consistently, that a considerable proportion of patients develop IBS following an acute episode of infectious gastroenteritis, so-called "post-infection" IBS.[4–6] Moreover, some investigators have demonstrated that patients with suspected IBS may have evidence of small intestinal bacterial overgrowth on hydrogen breath testing,[7–10] and antibiotic therapy appears to improve symptoms in some of these patients.[8,11]

Additionally, therapeutic modulators of the gut microbiota have beneficial effects in unselected patients with IBS. Rifaximin, a minimally absorbable antibiotic, has been shown to be effective in randomised controlled trials (RCTs) in both IBS with diarrhoea (IBS-D) and IBS with mixed stool pattern (IBS-M),[12–15] for both global symptoms and bloating. Numerous different probiotic mixtures and strains have also been evaluated in patients with IBS over the last 15 years. A recent meta-analysis reported a beneficial effect of Lactobacillus plantarum DSM 9843, Escherichia coli DSM1752, Streptococcus faecium, and specific multi-strain probiotic formulations, although the evidence was not robust enough to make any conclusive recommendations as to which individual species or strain was most effective.[13]

This clinical evidence for a role of the gut microbiota in IBS is reinforced by available microbiological data. Firstly, several studies have demonstrated that the gut microbiota are altered in patients with IBS, compared with healthy subjects.[16–20] Secondly, and more recently, one group of investigators has demonstrated a specific microbiota profile that appears to be associated with the severity of IBS symptoms.[21] This profile was also shown to predict clinical response to a diet low in fermentable oligo-, di-, and mono-saccharides, and polyols in a RCT.[22] Finally, preliminary data suggest that rifaximin, apart from having clinical efficacy in IBS, is able to influence the level of beneficial microbes. In one study, abundance of the short-chain fatty acid producer Faecalibacterium prausnitzii was increased in patients with IBS-D or IBS-M following rifaximin,[23] suggesting that manipulation of the gut microbiota could be a therapeutic approach to managing IBS symptoms.

Among other potential strategies to modulate the gut microbiota, faecal microbiota transplantation (FMT) has been shown to be a highly effective treatment against recurrent Clostridioides difficile infection,[24,25] and its efficacy has also been investigated for the treatment of non-infectious gastrointestinal disorders in which there may be a role of the gut microbiota, including ulcerative colitis.[26–29] Some RCTs of FMT in IBS have been published in very recent years,[30–32] so we performed a systematic review and meta-analysis to summarise all the evidence for its efficacy in IBS.

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