Fecal Transplants: 5 Things to Know

Victoria Stern, MA

Disclosures

December 17, 2019

Although fecal microbiota transplantation (FMT) has not yet received approval from the US Food and Drug Administration (FDA), more than 10,000 patients receive FMT in the United States each year to treat Clostridium difficile infection, and hundreds of clinical trials are currently underway to explore whether FMT can treat a range of other conditions, such as ulcerative colitis, irritable bowel syndrome, and obesity. A recent FMT-related fatality, however, has led some experts to question its safety and widespread use. Here are five things to know about the evidence and recent controversy surrounding FMT. 

1. Fecal transplantation cuts bloodstream infection risk.

A growing body of evidence shows that FMT is a safe and effective approach for treating both adults and children with C difficile infections. Now a recent study suggests that its benefits may extend beyond simply eliminating the infection—FMT may also curb C difficile infection-related complications and improve a patient's overall survival odds.

Investigators reported that patients with recurrent C difficile infection had a lower incidence of bloodstream infections following FMT compared with antibiotics. Less than 5% of patients receiving FMT (5 of 109) had a bloodstream infection after 90 days compared with 22% of those who received antibiotics (40 of 181). The difference in the incidence of bloodstream infections was even more pronounced when comparing propensity score–matched patients: 4% of FMT-treated patients (2 of 57) vs 26% of antibiotic-treated patients (15 of 57).

Almost three times more patients in the FMT group had a sustained cure rate (97% vs 38% in the antibiotic group). The FMT recipients also spent fewer days in the hospital and, perhaps most notably, had better overall survival at 90 days. 

2. Early research hints at FMT as a treatment for obesity.

Although the most convincing evidence of efficacy with FMT is in its ability to eliminate C difficile infection, gastroenterologists are also exploring its usefulness to treat obesity. The limited findings to date suggest that gut microbiota can influence a person's metabolism and, more specifically, that the gut hormone glucagon-like peptide 1 (GLP-1) may play an important role in facilitating weight gain or loss.

FMT is potentially promising in this indication because it can alter the gut microbiome in a specific and durable way, possibly aiding in dropping excess pounds. A 2017 study found that FMT from lean donors improved insulin sensitivity and altered intestinal microbiota in overweight and obese recipients 6 weeks after treatment, though the changes in microbiota were not sustained at 18 weeks. More recently, a randomized controlled trial found that obese individuals who received FMT capsules from lean donors over 12 weeks showed stool engraftment of the donor's microbiota throughout the 3-month study period. The treatment, however, did not lead to weight loss or notable differences in GLP-1 levels in the FMT and placebo groups.

Although it is still early days for this research, some experts suggest that FMT could make a bigger mark on weight loss when paired with dietary modifications.

3. FMT may improve the effectiveness of cancer immunotherapy.

Recent evidence suggests that the gut microbiome could influence a person's response to cancer immunotherapy. A 2018 study found that patients who took antibiotics shortly before or after starting anti-programmed cell death ligand-1 (PD-1) immunotherapy to treat advanced lung and kidney cancers had a worse response to the immune checkpoint inhibitor. The patients who received antibiotics did not maintain the same levels of microbiota diversity as their peers who did not take antibiotics, and this antibiotic-related microbial imbalance (or dysbiosis) might limit the effectiveness of an inhibitor, according to the investigators.

But could altering the gut microbiome potentially enhance the efficacy of immunotherapy? Some early data indicate that this is indeed a possibility. A 2018 study found that mice who received FMT from patients with lung and kidney cancer who responded to anti–PD-1 therapy had significantly smaller tumors than mice who underwent FMT from patients who did not respond to therapy.

A recent phase 1 trial also provides initial evidence that the gut microbiome affects drug efficacy. In the trial, three patients with metastatic melanoma who did not respond to initial treatment with a PD-1 inhibitor received FMT from donors who had achieved a durable complete response on anti-PD-1 therapy. The investigators reported that, following FMT, the gut microbiome of the recipients appeared to resemble those of the donors, and two recipients "demonstrated clinical and radiological benefit from treatment."

4. A patient died after receiving FMT.

After two patients became infected with extended-spectrum beta-lactamase (ESBL)–producing Escherichia coli following FMT, some experts are now questioning the safety of FMT and pushing for greater regulation of the practice.

Details of the fatality were first published in The New England Journal of Medicine in November 2019. The report described how two patients participating in different clinical trials ended up receiving contaminated FMT capsules from the same donor. One patient died from the infection, which presented 5 days after the transplant and led to sepsis. The second patient was more fortunate; when he didn't respond to treatment, his clinicians took a blood culture that revealed the ESBL-producing E coli and switched him to an antibiotic that eliminated the infection.

5. Following the patient death, the FDA has issued caution about FMT safety.

Since news of the fatality, some experts have called for more rigorous donor screening to prevent the transmission of serious infections, as well as for in-depth evaluations of the risks and benefits of FMT for different indications.

The FDA has expressed its concern as well. In June 2019, the agency issued a national safety alert, warning patients and providers about the risk for serious infection from FMT. But the FDA did not stop with a safety communication; it also suspended an unidentified number of FMT clinical trials and issued a second notice detailing protections providers should consider when using FMT. Specifically, they recommended carefully screening FMT donors and donor stool for multi-drug-resistant organisms, quarantining all stored FMT products that have not been screened, and discussing the risk for infection with patients during the informed-consent process.

Victoria Stern, MA, is science journalist based in Los Angeles, California. Her work has also appeared in Scientific American Mind, Retraction Watch, and General Surgery News, and she is an editor for a new health care podcast, Tradeoffs.

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