Long-Term Efficacy of Fecal Microbiota Transplantation in Patients With IBS

Defining the "healthy gut" microbiota (and what exactly is dysbiosis) remains inherently challenging.¹ There is evidence that the gut microbiota is disturbed in IBS, although no characteristic microbial signature is established.¹ There is also emerging evidence that fecal microbial transfer (FMT) may provide a symptom benefit in a subset with IBS, although the outcomes have been very heterogeneous.² No data on long-term outcomes of FMT trials in IBS have been published until this prospective study by El-Salhy et al.

The findings are encouraging and suggest that FMT can be a safe, efficacious, and durable treatment (up to 3 years) for all subtypes of IBS. Improvement in symptom burden (>60% vs <30% on placebo stool) and quality of life was observed at 2 and 3 years.

This study identified fecal bacteria profiles using 16S rRNA sequencing and 10 bacteria were positively associated with a reduction in IBS symptoms. It is still unclear if these microorganisms have any pathogenic role in IBS; association is not necessarily causation.

Conflicting evidence in recent trials of FMT efficacy in IBS indicate that many methodological factors impact outcomes.² The results from El Salhy et al suggest that finding a super healthy donor with a high (but stable) microbiome diversity may be key, along with applying strict patient selection, careful sample handling, and delivery via esophagogastroduodenoscopy (although colonoscope delivery may be as good).²

The ultimate questions are yet to be answered: does the gut microbiota “cause” IBS (and what exactly), who with IBS should be considered for FMT, who should be the donor, and, as IBS is commonly a disorder of young-to-middle–aged adults, are there any serious longer-term adverse events (eg, Parkinson’s disease transmission)?

References

1. Hugerth LW, Andreasson A, Talley NJ, et al. No distinct microbiome signature of irritable bowel syndrome found in a Swedish random population. Gut. 2020;69(6):1076-1084. https://gut.bmj.com/content/69/6/1076.citation-tools
2. Zhao HJ, Zhang XJ, Zhang NN, et al. Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome: A Meta-Analysis of Randomized Controlled Trials. Front Nutr. 2022;9:890357. https://www.frontiersin.org/articles/10.3389/fnut.2022.890357/full

Fecal Transplant for IBS

This is the longest follow-up study (3 years) to date for evaluating fecal microbiota transplant (FMT) for irritable bowel syndrome. In total, 125 patients were randomized into three groups. They were all given FMT through a gastroscope into the distal duodenum. The placebo group received their stool while the other two groups received either 30 g or 60 g of stool from a single donor.

The donor, let us call him Joe, was a healthy 36-year-old male with a normal BMI who was born via vaginal delivery, breastfed, and who is a non-smoker. He exercises regularly and eats a fiber-rich healthy diet. He has not received recurring courses of antibiotics in his lifetime and was not taking any medications at the time of the donation. I am thinking Joe was a GI fellow.

Joe’s poop did the job. There was a slight benefit of the 60 g dose over the 30 g and a greater improvement with both than placebo. The response rate was 77.8% for the 60-g infusion, 69.1% response rate for the 30 g, and 26.3% for the placebo. At 3 years post infusion, the numbers were sustained with only a slight decrease (see graphic below). The responders also had less fatigue and improved quality of life.

Other than being a little grossed out, the side effects were minimal, with abdominal pain, diarrhea, and constipation being the most frequent, 2 days after the infusion.

Bacterial profiles were collected at baseline and after fecal transplant. This tracking showed some themes in the microbiome that may help us create a probiotic in the future that is less costly without having to mess with fecal matter. However, an oral probiotic may be inactivated by gastric acid requiring duodenal placement after all.

There are two key take-home messages from this study. The first is that fecal microbiota transplant seems to work with sustained effects for both IBS-C and IBS-D. However, the intervention is costly and requires placement with a gastroscope into the duodenum, with a stool from a donor like Joe.

This brings us to our second take-home point: If we live like Joe, we may not need a transplant of his stool. Here is a summary of why Joe had good donor stool.

• He was born vaginally and was breastfed. These are two factors that help establish a healthy microbiome.
• He eats a fiber-rich plant-based diet. Fiber is needed to create mucous in which the microbiota need to live. Eating less saturated fat with a plant-forward diet helps establish a microbiome that results in less obesity with a normal BMI.
• He was not exposed to recurring courses of antibiotics. Peripartum and early exposure to antibiotics have a negative effect on the microbiota.
• Other than long-work hours, Joe is not overly stressed, which can influence the microbiota, resulting in healthy emotions, which improves IBS symptoms.

Joe and his stool have a lot to teach us.