I just got to read the study results and the full text of the editorial. I thought the editorial did carefully lay out the issues that need study, and the potential for exploitation of desperate patients. The numbers form the larger Canadian FT trial will be very interest, because this study was very small. Very careful longitudinal profiling of patient microbiomes and comparison to donor profile.
While I do not reject the idea FT an be effective for some, I have always thought there was a bit too much irrational exuberance surrounding it. I found myself nodding in agreement with the editorial.
Rubin/editorial said...
Despite the lack of data, theories of bacterial causes of
IBD have “ face validity ” to many, and modern day charlatans
make enthusiastic claims of the effectiveness of their
supplements, probiotics, and dietary plans, and prey on
the desperate and suffering patient looking for answers.
Similarly, there is fervent interest in “ fecal transplantation ”
(or fecal microbiota transplantation, FMT) for IBD by
patients, who believe it to be a “ natural ” treatment ( 3 ). Many
are certain this will be their cure, and will go to great lengths
to find the treatment (and to pay out of pocket for it). Given
the availability of the raw materials (stool from a donor),
websites have sprouted (some with at-home FMT recipes and
kits), weblog accounts of anecdotal success are multiplying,
and patients are seeking providers who can deliver this treatment
to them or just doing it themselves in their bedrooms
and kitchens. Given this exuberance, there is a clear need
for more research of FMT in IBD, and an even more pressing
priority to ensure the safety of patients who are desperate and
forgoing available standard of care medical or surgical therapies
in favor of this unproven approach. To accomplish these
goals, we need scientifically valid studies that answer important
questions about the role of the microbiome in IBD, while
simultaneously rigorously assessing the safety and limitations
of transferring an entire community
I also liked the discussion by the study author about
why only 1 of their 5 patients seemed to get any benefit. They also note that FT might be especially unlikely to work in patients with severe UC, but those are the ones most likely to try it.
Angelberger/Am J Gastroenterol 2013; 108:1620–1630; doi: 10.1038/ajg.2013.257; published online 24 September 2013 said...
In our pilot study, however, only patient 3
responded clinically to FMT, whereas in two other patients
(1 and 5) a clinical deterioration of UC was observed. One reason
for the poor response rate might be patient selection. In
contrast to the six patients reported by Borody et al. ( 37 ), our
patients had a short disease duration of median 3.5 years and in
this period all of the patients had already received at least three
different immunosuppressive drugs, including steroids and biologics,
which reflects a progressive course of disease. The relatively
low calprotectin levels of patient 3 at baseline compared
with other patients in the study support this interpretation
( Table 2 ). Furthermore, patients with severe chronic diseases
might require repeated FMT infusions to induce disease remission
( 13 ). Thus, patients with UC induced into remission via
conventional medical therapy or those with mild disease might
be more likely candidates for future FMT trials. The fact that
patient 3 was the only subject who did not receive pretreatment
with a probiotic might challenge the usefulness of probiotics in
FMT protocols. ...
... In conclusion, the results from this small
case series with five patients indicate that transferred donor
fecal microbiota may be difficult to maintain stably in recipients
with moderate-to-severe active UC, in contrast to the stable
transfer of microbiota observed recently for FMT to treat recurrent
C. difficile infections ( 52 ), and that FMT should not yet be
offered to UC patients outside of study protocols because of lack
of proven efficacy and safety.
Finally, back to the editorial, He underscores the genotypic and phenotypic diversity in UC. This touches on the "actually many diseased" idea that has been kicked around in some threads here.
editorial said...
The observations of the altered gut microbiome in IBD
have led to treatments directed at this component of the
diseases, which would thereby downregulate the inflammatory
process. However, there have been many challenges in
achieving this goal, including the fact that it is not clear if the
dysbiosis seen in IBD is related to the underlying cause of the
disease or instead just a result of the active mucosal inflammatory
condition (or even the treatments for it). ...
... Complicating matters further
is the heterogeneity of disease genotypes and phenotypes,
and that previous studies of probiotics and antibiotics in IBD
(and specifically in UC) have had limited and non-durable
success rates.
... Why did FMT fail in these UC patients? There are several
possible explanations. First, it may be that modification of
the bacterial species is not the right mechanism for treatment
of UC. As theorized, UC may instead be a result of a more
complex unregulated immune disorder, and the dysbiosis is a
downstream result of the disease, rather than the cause. Second,
the choice of patients may be the reason for this negative
result. Patients with more severe disease and who already had
demonstrated a more aggressive and medically refractory
course may be the most difficult to treat with a microbial-based
strategy. Additionally, there are other factors that may have
affected the microbiome and lack of response to FMT in these
patients, including the patients’ dietary intake and the exposure
to cigarette smoking (two of five patients were current smokers
and two of five of these patients were ex-smokers).
... Patient desperation is not the reason to provide patients with this
treatment, and based on these results, the patient with moderate
to severe colitis failing our current medical therapies and facing
surgery may not be the best candidate for FMT. Future studies
should identify a patient population who may be more likely to
respond to this treatment, like the newly diagnosed patient or as
the authors suggest, the patient with milder disease or who has
had a medically induced remission. In addition, we must remember
that it is our first responsibility to protect our vulnerable and
sick patients. Clinicians who wish to provide “off-label ” FMT
to a desperate patient should think twice about it, and patients
who have decided to pursue this on their own should beware the
complexity, uncertain effectiveness and safety issues, and many
unanswered questions.
Personally, I think one of the best reasons for trying some type of FMT (pills, tube, scope, enema) is that there is a high false negative for c.diff. I suspect a lot of people who make anecdotal report of benefit from FT may have had undiagnosed or low-level c.diff. But getting a screened donor, and being mindful that suddenly throwing a lot of bacteria into your body can sometime cause problems.