It’s shitty treatment: transplanting microbes present in the poop of a healthy donor to patients with chronic and severe inflammation of the lower digestive tract.
Such inflammation leads to diverse medical conditions, collectively called irritable bowel syndrome. This includes Crohn’s disease and ulcers of the colon, or ulcerative colitis. Typical symptoms of Crohn’s disease include persistent diarrhoea, rectal bleeding, an urgent need to go to the toilet, incomplete evacuation, abdominal cramps and pain and, sometimes, constipation.
Clinical trials have suggested that faecal microbiota transplantation (FMT) – transplanting some faecal matter from a healthy donor to a sick one – could treat ulcerative colitis. The idea of FMT is akin to ‘good’ bacteria in natural curd helping restore the microbial contents of one’s digestive tract after an antibiotics regime.
Researchers have also found that FMT can safely and effectively treat recurrent Clostridium difficile infections, and continues to be the subject of research among people with Crohn’s disease. A new study adds to the latter body of knowledge, but not in a good way. An American group of scientists has found that FMT may have limited effects, and even “potential for harm”, among people with Crohn’s disease.
A case series
However, other gastroenterologists have been quick to point out that it this is a premature because the findings are based on a small study group of 10 people, and observations of 10 cases. The trial also lacked a control group[footnote]A matching group of people who are randomly selected from the total cohort to receive alternate treatment.
Their outcomes serve as a sort of baseline against which to judge the treatment’s effectiveness in the other group.[/footnote].
But for the frailty of the study’s results, they have been noted by multiple observers and experts because the microbiome and its manipulation for treatment “are hot topics now, and research in this field is increasing day by day,” according to Gianluca Ianiro, a gastroenterologist at the Agostino Gemelli University Polyclinic, Rome.
In their study, the scientists – from the University of California and the Zuckerberg General Hospital, both in San Francisco – tested whether a single dose of FMT improved clinical outcomes in people with Crohn’s disease, and attempted to identify what changes occurred in the microbiome in response.
They were able to enrol 10 people with Crohn’s disease for their test. After they underwent FMT, their clinical response and microbiome profiles were evaluated a month after the procedure.
They reported in the United European Gastroenterology Journal that only three of the 10 people responded to FMT. They also found there was “no significant improvement” in the inflammation among the people who had clinically responded to FMT. Finally, those who responded to FMT also tended to have lower microbial diversity, suggesting that FMT could provide some relief to people who had Crohn’s disease with more perturbed microbiota.
The symptoms of two of the 10 people worsened shortly after undergoing FMT, “highlighting the potential for harm with FMT and the need for controlled trials to assess the safety,” according to their report. In effect, the scientists concluded that single-dose FMT in the group studied showed “modest effect and potential for harm.”
Also read: It’s Time for Indian Medicine to Give Poop Transplants a Fair Chance
This hasn’t gone down well with other scientists. Some say the treatment’s long-term success depends on several factors, including donor selection and procedure for transplant, while others say there need to be large, multi-centric, randomised controlled trials before anyone can reach any conclusions.
“This study shows that three out of 10 [participants] benefited whereas two had increased disease activity, which does not give any conclusive message,” Vineet Ahuja, a professor at the department of gastroenterology at the All India Institute of Medical Sciences, New Delhi.
He added that people with Crohn’s disease have a fluctuating course that, in the absence of therapy, could spontaneously relapse. As a result, it is hard to say anything very meaningful without being able to compare results with a controlled study in which an equal number of participants receive non-FMT treatments.
Further, Crohn’s disease is a chronic condition and it seems unreasonable to believe a single dose of FMT can suffice.
As Bhabatosh Das, an assistant professor at the Translational Health Science and Technology Institute, Faridabad, explained, the gut microbial ecosystem is highly complex. It is home to a diverse array of microbes and this richness varies greatly between individuals, over time, according to a variety of factors. Some of them are dietary habits, use of medicines, age, sex, body mass index, ethnicity, geography and altitude. So FMT’s success also depends on the receiver’s dietary patterns and lifestyle.
So, Ahuja said, “This study adds to the existing information but not in a way that would alter our understanding at this stage,” and Ianiro agrees. With a small cohort and without a control group, the study is effectively a case series, and such series already exist vis-à-vis FMT in Crohn’s disease.
A better alternative
Just as much as it would be unfair to suspect FMT’s usefulness based on an incomplete experiment, it would be appropriate to note that there are other factors that make the procedure particularly desirable.
For example, “to date, we have enough evidence to use FMT in clinical practice only for Clostridium difficile [infections],” Ianiro said, but a growing volume of research data “suggests that it could be a promising therapy for ulcerative colitis and metabolic syndrome.”
In March this year, Ianiro’s team had penned a review report in the Human Microbiome Journal saying that, despite successes with treating recurrent Clostridium difficile infections, “there remain many unknowns about how best to optimise [FMT’s] preparation, regulation, mode of delivery and safety.” In other words, we still don’t know many things about how to make FMT work perfectly, or even nearly so, so to dismiss it before getting them right would be to jump the gun.
There is also the cost advantage. According to Das, FMT “is definitely going to be-cost effective, though the initial investment to identify and characterise the donor may be expensive.”
Ianiro also said the procedure “would be a perfect option for developing countries”, with the caveat that it has thus far been tested against only one kind of infection. “But I also believe that it would be a highly effective option to decrease healthcare costs related to Clostridium difficile infections, and so the dissemination of FMT in these countries is advocated.”
At the moment, people with Crohn’s disease who don’t respond to first-line therapy are treated with a combination of large complex sugars, proteins and/or nucleic acids, all produced from living organisms. Collectively called ‘biologics’, it costs “at the most optimistic estimate … approximately Rs 2.5 lakh a year,” per Ahuja. “Plus they don’t cure the disease; they only control it. So it is not a finite therapy.”
Doctors have also noted that about 10% of people are hospitalised due to severe reactions to biologics.
But in the meantime, Das warns that it would be prudent to not assume FMT will “have 100% efficacy [against] Crohn’s disease and other gastric illnesses”, so “equal importance should be given to the post-treatment phase for a sustainable cure of Crohn’s disease”.
T.V. Padma is a freelance science journalist.