ARTICLE products that suppress fungal growth . But we also know very well , that fungi suppress bacterial growth , and that ' s the basis of antibiotics . So how these organisms interact is very , very difficult . We know that they are there , we can pick them up , and we can say something about their distribution . We can say very little about their function .
We do metabolomics where we look at genes expressing functions . So we know that ... for instance if there is a gene making a short chain fatty acid - we can pick that up genetically in the bacteria . We can ' t do any of that for the viruses and the fungus . And the phages are a completely different group of organisms , which make it even more complicated . They sort of parasitise viruses , I mean , viruses eating viruses . Bacteria and funguses control each other in different ways and all living together in the gut , and more importantly , living in different parts of the gut . So your microbiome differs dramatically in your oral cavity , to your stomach , to your small bowel , and then in your colon where the highest concentration of microbiota are found . But there are different gradations of importance among microbiota . So , a bacterium or a fungus in the lumen of the gut is perhaps less important than a bacterium or a fungus right on the wall of the gut . So you get your population , which is right next to the mucosa and the mucosal cells and it ' s very intimately associated with the immune cells of the gut . We know that the gut has more immune cells by far than any other organ in the body . So you ' ve got a very close interaction between organisms that are micrometres away from macrophages and antigenpresenting cells within the gut lining . And if you reduce that gut lining , then these organisms get closer and become more dangerous . And if they penetrate the gut , then obviously different things happen - that ' s the pathology of many of these diseases . Inflammatory bowel disease , for instance , one of the important pathologies is that you get bacterial translocation . Also in patients with hepatic problems , it looks like bacterial translocation going through the gut lining . So the organisms within the gut lining are also a completely different population and perhaps more important than the population in the lumen .
Andrew : We ' ve got a single organism , though , blamed for gastric ulcers , peptic ulcers , and that ' s helicobacter pylori . Do you see a common culprit or culprits with regard to inflammatory bowel diseases , specifically Crohn ' s ?
Johan : No , I definitely don ' t . And when I did some research at St . Marks and then Professor Kamm who was running the research there , he felt that we had to look for this sort of organism . And the same with coeliac disease . There ' s a specific protein , a specific key that unlocks coeliac disease . That ’ s gluten protein . And with helicobacter , for instance , there ’ s a specific organism which unblocked peptic ulcer disease . So is there a specific organism , is there a specific food type , is there a specific antigen ? The first step to Crohn ' s disease and all the other things develop from it . But I didn ' t think there ' ll be one specific organism . I think it ' s an extremely complex disease , which is associated with genetics , with immunology , with food , with bacteria . But certainly , the microbiome is , I think , becoming the more important factor in pushing and driving the immunology of this disease . But to find one organism , absolutely , I would be very surprised . There are organisms that are protective , the prausnitzii group of organisms that produce anti-inflammatory substances and actually run via the NF-Kappa system . Now the NF-Kappa system is the sort of key molecule in inflammation and reducing inflammation . And we know that these organisms increase interleukin 10 , which also reduces inflammation . So certainly organisms that can break through the immune system and stimulate immunity , but then also organisms that reduce immunity and work as a natural sort of steroids , if you would . But the complexity of what ' s going on there is phenomenal . And we ' re only just beginning to understand what bacteria are there . We ' ve got no idea what role viruses like archaea and all these other funny organisms play .
Andrew : Some years ago now Martin Blaser wrote a book called Missing Microbes and of course he doesn ’ t question that helicobacter is implicated in peptic ulcer disease . But what he talks about is the different strains . And you know , we ' re well versed about the strain specificity , denoting the actions of a bacteria . Let ' s concentrate on the bacteria at the moment . And that one , lactobacillus acidophilus ‘ code ’ is not the same as another lactobacillus acidophilus ‘ code ’. Similarly , helicobacter - there ' s a lot determined by the genes , I think there ' s the vacA . So are we blaming a whole organism for something that ' s strain-specific , and should we be identifying the strains to see if that ' s the bugs that we should be eradicating ?
Johan : I think that ' s a very good point . There are different species of helicobacter as we know . And you can get cag type helicobacter and helicobacter heilmannii in humans . But you ' d certainly do get different strains that have got different virulence and we ' ve known that since the beginning of time , as far as microbiology is concerned . I do think we have the tools now to look at the more dangerous types of strains but I don ' t think we really are at a phase where we can target our therapy for these different strains . So if you look at helicobacter pylori , for instance , certain of the strains , and that ' s been well defined , as you point out with the cag , is that some of these are dangerous and others aren ' t . And we know that most people have helicobacter and they never have a problem with helicobacter . And there was a fascinating theory advanced by some African or South African gastroenterologist that it is , in fact , protective . Because they looked at the African population where 95 % of the population had helicobacter and almost none of them had gastric cancer or ulcers . So then they sort of provocatively said that maybe it protects
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