The Long-term Effects of Faecal Microbiota Transplantation for Gastrointestinal Symptoms and General Health in Patients With Recurrent Clostridium Difficile Infection

J. Jalanka; A. Hillamaa; R. Satokari; E. Mattila; V.-J. Anttila; P. Arkkila

Disclosures

Aliment Pharmacol Ther. 2018;47(3):371-379. 

In This Article

Abstract and Introduction

Abstract

Background Faecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection. In short-term the treatment has been shown to be safe, however, there are no large, long-term follow-up studies looking into the potential adverse effects.

Aim To analyse the long-term effect of FMT treatment in patients with recurrent C. difficile infection and to compare the outcome to antibiotic treated patients.

Methods Altogether 84 patients of which 45 received a FMT treatment and 39 served as controls receiving antibiotics for the infection were followed on average for 3.8 years. Their recovery and medical status was evaluated using a retrospective questionnaire, determining their quality of life, gastrointestinal symptoms and new diseases potentially related to the FMT.

Results There was no difference in the incidence of severe diseases (inflammatory bowel disease, cancer, autoimmune disease, allergy, neurological diseases) between the patient groups. In addition, weight gain did not differ between treatment groups. The FMT treated patients reported that their bowel habits improved significantly faster, they had less irregular bowel function and less symptoms of upper GI-tract when compared to the patients treated with antibiotics. Significantly more patients in FMT-group reported that their mental health improved after the treatment. The willingness to receive FMT treatment for potential new C. difficile infection was significantly higher in both treatment groups compared to other treatment options.

Conclusion Our study highlights that FMT is a durable, safe and acceptable treatment option for patients with recurrent C. difficile infection also in long term, and it shows potential benefits over antimicrobial treatment.

Introduction

Faecal microbiota transplantation (FMT) is proven to be a highly effective treatment for patients suffering from recurrent Clostridium difficile infections unresponsive to antibiotic treatments, with a success rate of 81%-94%.[1–4] In addition, the FMT has been rising hopes as a new treatment avenue for other diseases such as irritable bowel syndrome and more systematic conditions such as metabolic syndrome.[5,6] Regardless of the high interest towards FMT treatment, there are still some concerns regarding the risk of transmission of other diseases to patients via the microbiome. Moreover, longitudinal follow-up of the patient's GI symptoms and general wellbeing is lacking. The short-term safety of the FMT treatment to patients with recurrent C. difficile infection has been clearly demonstrated. A systematic review of 536 patients treated with FMT, reported no transmission of infective agents or severe adverse effects. Since the majority of these patients were followed up for less than 1 year, these results cannot be directly extrapolated to long-term effects.[7] Several case reports have reported short-term adverse effects such as mild fever, abdominal pain, diarrhoea, exhaust, flatulence, fatigue, diverticulitis, bacteraemia, norovirus gastroenteritis, cytomegalovirus infection and activation of ulcerative colitis.[8–14]

The long-term implications of FMT treatment or how it compares to the long-term recovery of patients treated with antibiotics has so far not been fully addressed. Despite rigorous testing of the donor's stool and blood, there still remains a potential risk of transmitting agents that do not cause immediate infection, but may complicate the patient's treatment in the future. For example, contracting multidrug-resistant, Gram-negative bacteria or developing or aggravating autoimmune diseases have been a cause of concern.[15] Moreover, because of the possible systemic effects of the transplanted microbiota, conditions such as metabolic syndrome, neuro-psychiatric conditions, autoimmune and atopic diseases are sometimes used as reasons for excluding donors,[15–18] although the basis for these potential adverse effects is controversial. Therefore, long-term analysis of this patient group and comparison to controls is vital for understanding of the long-term implications of FMT treatment.

A recent systematic review emphasised that there is not enough consistency in the long-term follow-up of adverse events after FMT.[17] In previous studies, the duration of the follow-up period has ranged from 3 weeks to 8 years.[19–24] However, the study with the longest follow-up period only had 12 patients.[21] Moreover, the previous studies have not concentrated on the GI symptoms or compared the recovery of the patients to a control group. There is some evidence of the safety of the procedure itself, but the long-term safety to the patients' health has not been well described. The majority of the studies reported little or no adverse effects during the follow-up period. Some of these included reports of new medical conditions after FMT (four patients)[25] such as peripheral neuropathy, Sjögren's disease, idiopathic thrombocytopenic purpura, and rheumatoid arthritis. In these long-term follow-up studies, the treatment efficiency has been very good with primary cure rates ranging from 88.2% to 100%.

The high success rate of FMT to patients with recurrent C. difficile infection makes this an attractive treatment and raises hopes that microbial transplants could be effective also for other indications. However, the potential adverse effects of this line of treatment remains to be determined in large scale and the findings should be contrasted with a control group. The main objective of this study was to determine the long-term safety of FMT in the treatment of C. difficile infection and also evaluate the effect of FMT on GI symptoms and general well-being and to contrast the results to a group of patients successfully treated with antibiotics.

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