Dutch researchers have identified what they say is the first human transmission of Blastocystis subtypes (ST) 1 and 3 from donors to patients undergoing fecal microbial transplant (FMT) for recurrent Clostridium difficile infection (rCDI).

Elisabeth M. Terveer, PhD, of Leiden University Medical Center in the Netherlands, and colleagues said that since transmission did not result in gastrointestinal symptoms or have any significant effect on rCDI treatment outcome, the presence of this common unicellular intestinal parasite might not disqualify an FMT stool donor.

"This study is an important step towards a possible exempt of Blastocystis sp. (ST1 and ST3) as donor exclusion criterion in FMT," the team wrote in the study online in Clinical Infectious Diseases.

Terveer's team tested the stool of patients before FMT and found them all to be Blastocystis-negative. But within a median of 20.5 days after FMT was performed with stool from two different donors in the Netherlands Donor Feces Bank, eight of 16 patients were intestinally colonized with Blastocystis showing ST-sequences identical to those of their respective donors. One donor carried ST1, the other ST3.

The findings emerged from the treatment of 110 patients with 113 FMTs during May 2016 to December 2018 using fecal suspensions from 10 different donors. In two of these, Blastocystis testing was negative on stool microscopy but positive on polymerase chain reaction. The Blastocystis-containing suspensions were used to treat 31 rCDI patients, with an FMT success rate of 84%. This success rate was not statistically different from the rate in patients treated with negative donor feces (93%, 76 of 82 patients). Moreover, patients transferred with Blastocystis sp.-positive feces reported no significant difference in bowel complaints in the first week, after 3 weeks, and in the months following FMT.

There was, however, a non-significant trend toward an increased rate of CDI events, both relapses and new episodes, in patients treated with Blastocystis sp-positive stool (eight of 31) versus Blastocystis sp-negative stool (12/82).

The unintended transmission of potential pathogens to FMT recipients is a growing concern, sparking calls for stricter screening and exclusion criteria for stool donors.

As the authors pointed out, many centers do not screen for Blastocystis sp., and according to a 2019 systematic review, only 14.5% of 168 studies reported specific Blastocystis sp. screening.

Symptoms of colonization with the simple parasite, which has 17 subtypes and is often associated with traveler's diarrhea, include nausea, anorexia, cramping, abdominal pain, flatulence, and acute or chronic diarrhea. The high prevalence of Blastocystis sp. in healthy individuals, however, suggests that the protozoan does not harm most hosts and appears to be a constituent of a healthy gut microbiota.

In a large cohort of 1,106 healthy Flemish individuals, Blastocystis sp. carriership was associated with higher microbial diversity, richness, and composition, a general prerequisite for a good stool donor, the authors noted. It might, however, pose a risk for immunocompromised individuals.

Still, Some Caveats

Asked for his perspective, Purna Kashyap, MBBS, of the Mayo Clinic in Rochester, Minnesota, who was not involved with the study, said, "I am not sure we can exclude Blastocystis based on this study. It was not powered to address exclusion, and it is unclear if this was an a-priori endpoint and if a standardized follow-up questionnaire was used."

In addition, he said, while the presence or absence of the parasite did not impact FMT effectiveness, follow-up was limited and did not appear to include immunosuppressed patients. Furthermore, the long-term implications are unclear: "We don't know how long patients remain colonized. What happens if patients need immunosuppression or if they develop inflammatory conditions where intestinal permeability is increased?"

Elizabeth Hohmann, MD, of Massachusetts General Hospital in Boston, also not involved with the study, commented: "There is some debate about whether Blastocystis is truly a pathogen and it can be present in some without causing any symptoms. We do screen for it, however, and would not accept a donor with this organism found, and I believe most would not wish to knowingly use stool containing this organism."

Limitations of the study, Terveer and co-authors said, included its examination of a single pathogen and the voluntary reporting to the stool bank by treating physicians of late CDI relapses after three weeks or new CDI episodes after 2 months.