Review for 10.1186/1471-230X-13-117 (2013)

Reviewer's report
Title:The protective effect of recombinant lactococcus lactis to Clostridium
difficile infected animal model
Version: 3Date:29 October 2012
Reviewer: Elizabeth Mann
Reviewer's report:
Major compulsory revisions:
-The novel findings of this study are that the membrance anchored L.lactis group
was more effective at preventing C.diff infection compared to secreted L. lactis
group - this is actually very interesting and clinically relevant but has not been
mentioned in the abstract or until the very end of the paper. In my opinion this
should be the main highlight of the study. The LL-pNBCL2003 (membrance
anchored) group prevented symptoms, however authors have stated in
discussion this is due to L. lactis being taken in by M cells of the intestinal wall
and presentation to the immune system but there is no evidence in the results to
confirm this so this is based on speculation.
-Question posed by authors is not well defined. It is stated in the discussion that
Lactobacillus lactis can prevent and treat C.diff associated diarrhea from other
studies, though unclear from discussion whether this refers to humans or animals
(not sure if reference 13 is correct either). In which case, if L.lactis has already
been shown to be effective for C.diff treatment and prevention, what is the novel
impact of this research and the relevance of using animal models? what is the
clinical relevance - to vaccinate patients at high risk of C diff infection?
-Abstract does not get main message across about what is important and novel
about this research to the field of gastroenterology. The groups needs to be
expained better and there is no mention of the Clostridium A toxin treatment
group in methods of abstract but then it is referred to in the results in abstract.
What is this group? Are the "cells" referred to intestinal epithelial cells?
Determine whether focus is on treatment or vaccination as they are two different
approaches.
-Methods confusing for a non-specialist in animal models of infection and
vaccine/vectors. This is a general scientific gastro journal but there is no
description of how the groups were specifically defined e.g. how were the empty
L.lactis plasmid group and secreted L.lactis etc groups generated and what does
this mean?
- Layout of results confusing , include statistics and pathology into well-defined,
headed sections stating what findings are.
-In general confusing referring to hamster groups by their codes, much clearer to
call them "L.lactis secreted" or "membrane bound" etc.
-Discussion included very little discussion of the actual results and implications of
results of this study but went into a lot of detail about the implications of research
from literature that was not entirely relevant. There is no mention of the epithelial
cell apoptosis or the mRNA expression of adhesion markers and cytokines, even
though it would appear there is less IL-6 and ICAM-1 with the membrance
anchored group. Is this significant? Unclear. What are the implications of this?
Microbial translocation? There is no mention of why this study is novel and
relevant to the field of research; nor much discussion on the use of probiotics on
GI infections, particularly C.diff. One of the most striking and relevant results from
literature is surely is that faecal transplants (replacement of gut microbiota with
"healthy microbiota") can be effective for C.diff treatment in humans. As
mentioned above, the novel findings of this study are that membrane anchored L.
lactis is more effective at preventing C.diff infection that secreted - the discussion
should revolve around this as a vaccine approach and speculate why this might
be, and find evidence from the literature to support this. E.g. M-cell section is
logical speculation but there is no evidence from this study supporting this. What
about the literature? Could the mechanisms involve action of L.lactis on antigen
presenting cells of the immune system, making them more able to sample C.diff
antigen?
-In general, there are a few sentences throughout that are not finished or do not
make sense.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests