Review for 10.1186/1471-230X-10-58 (2010)

Reviewer's report
Title:Effects of mannoprotein E1 in liquid diet on inflammatory response and
TLR5 expression in the gut of rats infected by Salmonella typhimurium
Version: 1Date:10 August 2009
Reviewer: Theo Niewold
Reviewer's report:
The aim of the study was to investigate the effects of mannoprotein containing
diets on S. typhimurium infection in rats. Authors claim that mannoprotein
protects against infection in a dose-dependent way. Furthermore, they analyzed
intestinal expression differences of selected genes between a mannoprotein fed
group vs the non-mannoprotein control, comparing only the infected animals from
both groups. Expression differences found are interpreted by the authors as
being related to protection against S. typhimurium infection. They conclude that
these results suggest a therapeutic potential of mannoprotein against microbially
induced intestinal inflammation.
There are several major problems with this manuscript. The first problem is that
the authors claim that mannoprotein protects against infection, whereas they
themselves state in the Results section that there was no significant difference
between the control and the 10% mannose group. There was a significant
difference between the control and the 15% mannose group, but the authors then
proceeded to further analyze the infected animals from the control vs the 10%
mannose group. Even if these two groups were significantly different (which they
are not), the infected animals from both groups are evidently not significantly
different in the degree of protection. It is therefore totally unclear how the authors
arrive at their conclusions about protective effects of gene expression differences
found. These differences (in interleukin, TLR5 expression, and apoptosis) are
interpreted by the authors as reduction of flagellin induced responses by
mannoprotein. In the absence of appropiate controls (e.g. the effect of
mannoprotein alone on intestinal expression), it is very dubious to draw
conclusions like this. The authors also fail to make clear why flagellin and not
other components such as LPS are important in their Salmonella infection model.
Another major point is the absence of information on the actual diet and feed
intake of the experimental animals. The supplementation with 10 or 15%
mannoprotein very likely means that these diets are reduced in protein or energy
content. Protein and caloric restriction can have a large effect on a host of
physiological functions, including immune function. A large body of literature is
available on this topic in general, and also some piublications on the influence on
Salmonella infections in animals. This should have been discussed. In the
absence of appropiate controls and further information, it can not be excluded
that the lower pro-inflammatory response in the mannoprotein group is rather the
result of protein or energy restriction than of the mannoprotein itself.
Furthermore, the manuscript is poorly written, and the results are poorly
discussed. Most of the discussion is highly speculative for the above reasons.
Also, sweeping statements are made without references, whereas contradictory
publications are available. As an example, in the second paragraph authors state
that "it is generally assumed that induction of an intestinal proinflammatory
response is a property of pathogenic intestinal bacteria" (and not of
commensals). From a conceptual point of view, it is clear that some pathogens
may use anti-inflammatory stategies. Our own research on Salmonella has
shown such indications (Niewold et al 2007). Furthermore, the interaction with
commensals is clearly more complex than depicted here, and should be
discussed for instance in the light of recent publications of the group of
Rodenburg, references which are curiously missing from the manuscript.
In conclusion, the manuscript is unacceptable for publication.
Level of interest: An article of insufficient interest to warrant publication in a
scientific/medical journal
Quality of written English: Not suitable for publication unless extensively edited
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests