This is the second in a series of blogs exploring potential gut treatments for chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), and allied disorders.
The first fecal transplant study in ME/CFS was light on methodology and needs to be validated with a more rigorous study, but it got good results. Recently an ME/CFS patient reported on his remarkable recovery from a ten-year bout of ME/CFS with ten fecal transplant treatments.
While at least two fecal transplant studies are underway in ME/CFS, in Finland and Norway a much larger fecal transplant study, “Long-Term Follow-Up Results of Fecal Microbiota Transplantation for Irritable Bowel Syndrome: A Single-Center, Retrospective Study“, just finished up in irritable bowel syndrome (IBS).
IBS is the most commonly diagnosed gastrointestinal disorder and appears to be common in ME/CFS and fibromyalgia. Sixty percent of people with chronic fatigue syndrome reported IBS symptoms (abdominal discomfort) in one study. A similar percentage of people with fibromyalgia have been reported to have IBS symptoms, and up to 60% of IBS patients reportedly meet the criteria for fibromyalgia.
Irritable bowel syndrome (IBS) may not be as debilitating as chronic fatigue syndrome (ME/CFS) (but what is?), but it’s no walk in the park either. Characterized by repeated pain in the abdominal area that is often associated with bloating, constipation and/or diarrhea, fatigue is also common.
It causes a high illness burden, low quality of life, high rates of absenteeism at work, and high direct and indirect healthcare costs. One study stated that IBS “imposes a huge economic burden on patients and healthcare systems” and the IBS treatment market has been valued at over $2 billion a year. Demonstrating once again its remarkable negligence of the so-called “functional diseases”, the NIH does not even bother to track its IBS funding.
The Long-Term IBS Fecal Transplant Study
The authors of the “Long-Term Follow-Up Results of Fecal Microbiota Transplantation for Irritable Bowel Syndrome: A Single-Center, Retrospective Study” reported that efforts to treat IBS with probiotics and antibiotics have met with limited success.
While the study was a large and long one – following 227 people with IBS over five years – it was truly the tip of the iceberg: this Chinese group reported that it’s treated over 2,000 people with various gut disorders with fecal transplants over time.
First, an oral antibiotic (500mg vancomycin orally twice per day) was administered for 3 consecutive days. Next, the patients received 100 grams of fecal matter via colonoscopy, a nasointestinal tube, or via oral capsules for 6 consecutive days.
Twelve months later, their total IBS-SSS score (abdominal distension/bloating, abdominal pain frequency, abdominal pain severity, satisfaction with bowel habits, and quality of life) was assessed. Bristol Stool Scale for IBS-C and IBS-D symptom and fatigue and quality of life questionnaires were also given.
If the score had dropped but was still high, another treatment was given. If no change had occurred, another treatment was not given. The study also assessed whether providing the fecal treatment with a nasointestinal tube, capsule, or colonoscopy produced better results. This went on for five years.
Past studies have found that fecal microbiota transplant (FMT) was more effective than placebo (even with high rates of placebo success (43%)). After 12 months, though, the placebo and transplant rates of success were similar, suggesting that the effects of the fecal transplants wore off over time.
The Chinese researchers concluded that the capsules worked best mostly because the participants tolerated them better. The study reported efficacy rates (ranging from @60-70%) over time. Fatigue and mental health scores improved by roughly 30-40% and were largely maintained over the five-year study. Periodic (apparently yearly) fecal transplants were generally needed to maintain efficacy, and capsules were the preferred choice.
The results, then, were good. A 2020 review, “Current status of fecal microbiota transplantation for irritable bowel syndrome“, however, reported that the results of fecal transplant studies in IBS are mixed with four positive studies and three negative ones. Concluding that the person donating the fecal matter had an outsized effect on the success of the poop transplants launched the researchers on the hunt for “super-donors”: people with the most effective poop. They do not believe having several donors – an approach some clinics use – is effective. Finding super-donors is the way to go.
They believe fecal matter super-donors were: 50 years of age, had never smoked, were not born using cesarean section, were not formula-fed, had not undergone frequent treatment with antibiotics, were regular exercisers, had a good diet, and were not first-degree relatives of the person getting the transplant.
They had high microbial diversity, which was particularly high in bacteria from the Firmicutes phylum – the same phylum that studies show people with ME/CFS are deficient in. If possible, their bacterial load should markedly differ from those being given the transplant.
Dose appears to matter and more seems to be better. Increasing the dose of the fecal transplant from 30g to 60g increased the response to FMT in IBS patients. (Seventy percent of the patients that did not respond to a 30g fecal transplant responded to a 60g fecal transplant.) How many doses are needed is not clear. While the ME/CFS studies underway appear to be delivering one dose, the retrospective ME/CFS study used six and the ME/CFS patient who recovered received ten (!)
In contrast to the Chinese study, the authors concluded that using capsules to deliver the transplants has not been effective but left open the possibility that other factors in the capsule studies could have impacted their results.
Side effects were generally mild and included cramping, pain, tenderness, diarrhea, and constipation that can occur but resolve within a few days.
While it’s not clear how fecal transplants are doing what they are doing, the evidence thus far suggests they are increasing short-chain fatty acids – which improve motility – and increase butyrate-producing bacteria. If that’s happening, they might be helpful in ME/CFS as both short-chain fatty acids and butyrate-producing bacteria have been found depleted in ME/CFS. (Short-chain fatty acids are produced when bacteria in the gut ferments indigestible foods and are an important energy source for cells in the gut. They have been called “crucial to gastrointestinal health“.) As noted in a previous blog, Gulf War Illness researchers have been using treatments that increase butyrate-producing bacteria in their mouse models.
Many fecal transplant studies are underway – some in diseases not traditionally associated with the gut such as depression, multiple sclerosis, Parkinson’s disease, and diabetes. As noted earlier, at least two fecal transplant studies in Finland and Norway are underway in ME/CFS
While it’s not at all clear how fecal transplants or other efforts to alter the gut microbiome will fare in ME/CFS, the gut-brain axis is a real thing. The gut flora appears able to even affect the functioning of the microglial cells that are largely responsible for neuroinflammation.
The Chinese study had several limitations but did suggest that fecal transplants may be able to improve gut and other symptoms such as fatigue over the long term. As the effects can decline over time, a fecal transplant or transplants may be needed yearly.
Another review reported mixed results with IBS fecal transplant studies, suggesting that having a good donor is critical, and laid out the characteristics of a good donor, providing the intriguing possibility of matching donors to patients by assessing their microbial composition.
At least 60 grams of poop appear to be needed to achieve a good effect across a broad swath of people. While the Chinese study found that capsules worked, other studies have found that colonoscopy/nasointestinal tubes worked better. How many fecal transplants are needed to have an effect is unclear. The Chinese study first used an antibiotic for three days, followed by fecal transplants for six days. Some studies provide only one fecal transplant.
It’s remarkable that one or several fecal transplants could possibly have long-term effects on IBS, fatigue, and other symptoms. Fecal transplants also interestingly appear to enhance the same elements of the gut flora that studies found depleted in ME/CFS. One ME/CFS patient reported that he’d completely recovered (after ten transplants). The first ME/CFS fecal transplant study, while not very rigorous, had good results, and two better produced studies are underway.