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Bugs and the gut: breaking barriers to understanding
  1. PHLS Central Public Health Laboratory
  2. 61 Colindale Avenue, London NW9 5HT, UK
  3. pboriello{at}

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There has been a re-emergence of interest in the interplay between the faecal microbiota and its associated metabolisms and gastrointestinal function. This has recently been driven by the current interest in human and veterinary probiotics, and in the recent past by hypotheses which linked gut bacterial metabolism of ingested foodstuffs and colorectal and other cancers. However, what is less widely known is the extent of involvement of gastrointestinal bacteria in gut function, gut disease, and particularly diseases of other organs.

Some of the less generally well known aspects of this interplay relate to gut bacterial metabolites: for example, the production of volatile fatty acids exacerbating acidaemias such as methylmalonic acidaemia, and the associated role of antibiotics in patient management.1 An area where there has been a resurgence of interest is the production of phytooestrogens from dietary precursors and their possible role in protection from hormone dependent breast cancer.2 3 The role of such metabolites in infertility in humans remains unexplored. There is even evidence that gut bacteria can induce or repress liver cytochrome P450 due to metabolism of dietary glucosinolates.4

There is a great deal of evidence to support the fact that what is considered normal gut structure and function is the end point of a complex set of interactions between the host and microbes colonising the gut.5 Such normal features include gastrointestinal motility, secretion and absorption, cell composition, mitotic activity, and villous length, etc. To this we can now add the fact that normal components of the gut microbiota can alter colonic barrier function by modifying colonic wall permeability (see page 503)6. This interesting observation raises a whole series of questions. The rationale behind the study is the hypothesis that increased intestinal permeability is a key factor in the pathogenesis of idiopathic bowel disease and the proposal that permeability may be affected by gut bacteria. What was found in the rat model used was that none of the test organisms increased permeability to a large molecular probe (dextran) but some altered permeability to a small molecular probe (mannitol). Interestingly, this modification in permeability was not uniform, with reduction, increase, and no significant alteration being detected, dependent on the test organism used. What would be interesting to know is the extent to which such effects are a feature of the bacterial strain used or a feature of the bacterial species represented. For example, do most commensalEscherichia coli increase permeability or only a few strains? This leads to the deeper question of whether or not patients with idiopathic bowel inflammation are more frequently colonised with bacteria that increase gut permeability and/or have a gut microbiota where the net effect is to increase permeability. Both questions can now be answered. I would be particularly interested to see the effect of crude gut “flora” from, for example, patients with Crohn's disease, on gut wall permeability in small and large bowel in the “rat-human flora” model.

Similarly, it would be of interest to know whether or not the decrease in permeability induced by the isolate ofLactobacillus brevis is strain specific or a general feature in the species or genus. This may be of particular relevance in the probiotic field. A minor disappointment with the current paper is that the opportunity was not taken to see if coadministration of the L brevis strain with the E coli strain would reverse or prevent the increased permeability associated with E coli.

There are many other questions which come to mind such as: could an ability to increase permeability be a virulence factor which facilitates translocation of a bacterium or its toxin— for example, verotoxin across the gut wall? Are changes in permeability due to specific factors produced by these bacteria or are they a result of metabolic byproducts? What is the range of degrees of altered permeability induced by different bacteria?

I have little doubt that this paper will stimulate research in these areas and that the results of such studies will offer increasing insights into the complex interplay between the host and its microbiota, and a better understanding of what is normal and what is abnormal.

See article on page 503


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