Peer review of: Faecal microbiota transplantation for the treatment of diarrhoea induced by tyrosine-kinase (2020)


REVIEWERS' COMMENTS: 

Reviewer #1 (Remarks to the Author): 

I have no further comments following a review of the authors’ response to reviewers’ comments 

Reviewer #2 (Remarks to the Author): 

1. One of my primary concerns was that all patients underwent a bowel prep which puts the sham 
group at a disadvantage as it will decrease the diversity of an already disrupted community. That 
is likely why we see nearly no improvement in the sham group. 
The authors have responded to this by providing a separate explanation for each of these using 
two arguments that 1) bowel prep does not affect gut microbiota by referencing a study that used 
PCR-DGGE method and 2) other groups have used water as a control. 
There is sufficient data that bowel prep does indeed alter gut microbiome in studies that use next 
generation sequencing platforms as the one used by the authors 
(https://pubmed.ncbi.nlm.nih.gov/27015015/). The authors did not measure the microbiome 
before and after bowel prep in their cohort so they cannot definitively establish this. The authors 
then described several large trials that have used water as a sham placebo but fail to mention that 
none of them gave a bowel prep prior to treatment and my concern was not based on the fact that 
water cannot be a placebo but rather that the authors could have further disrupted an already 
vulnerable community with bowel prep and that can explain the lack of any response in the sham 
group. 
The authors then argue against using autologous stool as a comparator group and I am not sure if 
they got confused with my comment “sham FMT refers to patients own stool”. I had suggested 
that they should have used the patient’s own stool (allogenic FMT) as a control group and all the 
examples provided by the authors do exactly that- use the patient’s own stool as the comparator 
and not autologous stool as the authors mention in the rebuttal. I am not sure what the authors 
mean by lack of protocol for collecting stool from the patients with diarrhea. A sham/allogenic FMT 
would follow the exact same protocol for collection and processing as the donor and all the 
examples outlined by the authors in fact do this. 
2. The authors did not respond to my comment 
“The data is too preliminary to discuss the role of engraftment in driving improvement as the study 
lacks an appropriate control group. Moreover it would be helpful if the authors consider tracking 
the microbes longitudinally (given they have the samples) to determine if changes in relative 
abundance of microbes such as Akkermansia correspond to recurrence of diarrhea.” Further the 
authors did not perform longitudinal sampling on the sham group and compare the active FMT to 
time point 0 of the sham group so we do not know the level of variability/changes in the 
microbiome in the sham group following intervention. 
Overall my enthusiasm is in fact further dampened following author’s response as it highlights 
additional drawbacks in the study design and the interpretation of the results. 

Reviewer #3 (Remarks to the Author): 

Authors have satisfactory assessed all my queries. 

Reviewer #4 (Remarks to the Author): 

All my comments have been addressed appropriately. Looks good!