Faecalibacterium prausnitizii and IBD

[Igor_Passau]

Good' bug may have a role in bowel disease December 11, 2012 in Inflammatory disorders (Medical Xpress)—A bug thought to be one of the 'good bacteria' in our gut may actually have a role in the development of a bowel disorder that is on the rise in Scotland.

That is the possibility being raised by University of Aberdeen scientists who have published research which found significantly high levels of Faecalibacterium prausnitizii in the colon of children with Crohn's disease. Up until now the bug - one of the most common found in the gut - has been associated with Crohn's disease but in a 'protective' way, because other studies have found it in low levels in patients with Crohn's, and because it has anti-inflammatory properties. The findings have surprised scientists because it goes against current thinking. However they stress more research is needed into F. prausnitzii before they really understand the part the bug may play in the disorder, which has increased five-fold in Scottish children over the last 35 years. Researchers recruited children from Aberdeen, Glasgow and Dundee onto their study which was looking for potential bacterial triggers for inflammatory bowel disease (IBD) - Crohn's disease and ulcerative colitis - which affects around 6% of the Scottish population. Children were recruited when they attended hospital for a colonoscopy to confirm or rule out whether they had IBD. Dr Richard Hansen, Clinical Lecturer in Child Health at the University of Aberdeen, was the study co-ordinator for the work just published in the American Journal of Gastroenterology. He said: "There is a lot of research into inflammatory bowel disease but much of that has focused on Crohn's disease and ulcerative colitis in adults. "We wanted to study as 'pure' a population as possible - by that I mean people who have not yet had an intervention or treatment for their IBD, and are less likely to have other illnesses, or to have made lifestyle choices, such as being a smoker or drinking alcohol.

Ours is a unique study because this type of research cohort has not been studied by IBD researchers before." Blood and tissue samples were taken from patients who were recruited over a three year period and were aged between two and 16 years. Recruits from this study came from the larger BISCUIT- Bacteria in Inflammatory bowel disease in Scottish Children Undergoing Investigation before Treatment - study which recruited a total of 100 children over three years, including 44 presenting for the first time with IBD and 42 who had a normal bowel. Thirty four recruits were selected for a more detailed analysis, including 11 with Crohn's disease, 11 with ulcerative colitis and 12 'controls' with a normal bowel. Bacteria in the samples were then identified using the latest DNA 'sequencing' technology. Dr Georgina Hold, Senior Lecturer in Gastroenterology, at the University of Aberdeen and senior author on the study, said: "We found no significant changes in types of bacteria present across the three groups although there was less variety in the species of bacteria in kids with Crohn's disease. "However we did see a significant increase in the bacterium Faecalibacterium prausnitzii in children with Crohn's disease. "This was a surprise because other studies of patients with Crohn's disease have reported a reduction in levels of this bug which supports current thinking that it is somehow protective. "However our finding suggests that this particular bug may not always be a 'good' bacterium and may actually contribute to the development of the disease." Dr Hansen added: "We now plan to carry out a further study to look at Faecalibacterium prausnitzii specifically and to relate this to a liquid diet treatment that is commonly used to treat Crohn's disease in children. "We also need to understand more about how to restore and retain the normal bacterial communities within the gut."

http://medicalxpress.com/news/2012-12-good-bug-role-bowel-disease.html

 

[Trysha]

Thanks Igor
An interesting and valuable contribution to our knowledge bank
Hugs
Trysha

 

[kiny]

"However our finding suggests that this particular bug may not always be a 'good' bacterium and may actually contribute to the development of the disease."

I don't get how they get from seeing more of F. Prau to a conclusion that it contributes to the development of the disease.

They checked 11 CD children and noticed an increase in F. Prau and then propose F. Prau is causative without explaining why.

wut?

Isn't it just as likely that F. Prau has a protective role?

And it's not even the small intestine they found it, how does a colon commensal explain skip lesions in the small intestine? F Prau upregulates IL-10 and oral administration reduces collitis in mice. How do you jump to causality for crohn from that just because you found more of them in the colon?

How does it in any way even explain the increase in scotland?

nm

 

[RHansen]

Thanks for taking an interest in our study. It's important to say a couple of things, firstly the full discussion is in the paper itself which is available free to read on the American Journal of Gastroenterology website. The text quoted above is from a press release which is not the full story for obvious reasons.

Faecalibacterium prausnitzii is arguably the most important single organism in the Crohn's story at the moment. There is a lot of data supporting this organism as a protective agent and we were surprised to find a contrary result. This is fully discussed in the paper with multiple possible reasons being explored. The bottom line is that more research is needed to find out exactly what "F. prau" does.

Although our numbers may appear small, it's important to state that all these children were recruited at the onset of disease before any treatment, and that the methodology used was "hypothesis-free", showing the bacteria that are present without us having to decide which might be important. The sequencing methodology used is also currently very expensive, though will get cheaper as time goes by.

If you're interested in this study, please follow @biscuitstudy on Twitter where publications and study-related news is posted.

 

[kiny]

Thank you for replying. You mentioned EN a number of times.

I have been on TPN as a little kid and on EN as an adult, both times there was improvement but none ever induced substantial remission, I have no idea why but I assumed because, a low residue EN diet (usually low in fibre and high in very bioavailable glucose and hydrolised protein) would have a number of effects unrelated to gut flora modulation or effect on F Prau, it would increase nutrient uptake, it would lower fecal content especially with stricturing, low in microparticles, it's packaged in a way that makes it low in bacterial load compared to whole food.

EN is low in fibre and some people suggest it's modulation of the flora results in a composition that helps people with CD, but there are studies that show inulin, a prebiotic fiber helps crohn's disease.

EN helps, but it doesn't seem to induce deep remission, for me, in the onset of disease it seems that remission is quite common, it seems plausible to me that remission would have been reached with or without EN. There's two studies people often quote, one where fecal stream diversion in people who had surgery leads to mucosal healing, and another that shows it's not possible to induce collitis in mice without fecal stream and gut flora. But TPN and broad-spectrum antibiotics that target the gut flora, don't put people in remission, it's similar to EN, there is "remission" with subclinical disease, remission that doesn't last. For me it was only when heavy macrophage penetrating antibiotics that can target submucosa and target mycobacteria that antibiotics had an effect on me and others. I have seen pictures of my intestine when I had inflammation as a kid, they were deep uclerations, biopsy showed heavy granuloma reactions, the mucus layer is constantly moving and most commensals are not directly interracting with the epithelial barrier, only a few bacteria I can for myself imagine causing these reactions and skip lesions patterns that make sense to me, Invasive E Coli that are able to interact with submucosa and mycobacteria.

 

[kiny]

I also wonder in respect to gut flora reactions, histological pictures of inflammation often show full thickness inflammation and granuloma, the reaction is seen deep inside submucosa, most commensals come nowhere near the epithelial barrier.

How come people with crohn's disease often get mouth ulcers before there are clinical symptoms of disease in the intestine. I did a poll here once, many many people with crohn's disease have mouth ulcers at the onset of crohn's disease, including me.

Many bacteria can target the mucosa without any gut flora involvement. The connection between crohn's disease and the gut flora is less strong in my eyes than the connection between crohn's disease and bacterial involvement, which is a connection that is rock solid because of the implications of NOD2 and ATG16L1 and other genetic predispositions, they limit bacteria clearance of many bacteria, not just the gut flora.

Pretty hard to explain how reactions in the commensal gut flora would result in specific islands of skip lesions in the mucosa, the disease would be everywhere, it's not.

I mean, can anyone explain how the gut flora would result in skip lesions, randomly placed around in the intestine in skip islands. The dysbiosis is not at those specific places, they're everywhere, skip lesions are not everywhere, the mucosal layer is not static, the gut flora is not static, the skip lesions make no sense and can not easily be explained by reactions against the gut flora. Why do antibiotics like amoxicillin that can target commensals do absolutely nothing for crohn's disease but antibiotics that act intracellulary have effects for crohn's disease.

Probiotics are highly ineffective for crohn's disease. (unless they are engineered to interract with the immune system, but regular lactobasilli or other ileum commensals are highly ineffective)

Gut flora composition also has no geographic regionaility, they don't explain the huge differences in crohn's disease around the world.

-probiotics, useless
-fecal transplants, useless
-using non-macrophage penetrating antibiotics that target gut commensals, useless
-drugs that have low bioavailability, surprisingly useless
-modulation of the gut flora, useless
-diet to modulate gut flora, pretty much useless outside of butyrate that has effects beyond the gut flora

Yup, must be our body attacking the gut flora even though every method known to man to modulate the gut flora is utterly useless.

You can give someone a non-macrophage antibiotic that only targets the gut flora, give that person a fecal transplant and 20 bottles of probiotics, the crohn's disease will not be gone.

Invasive E Coli, sure, but they're not gut flora commensals, they are highly pathogenic in people who can't control autophagy.

 

[Moe.]

King I've seen fecal transplant work in crohns to bring remission

 

[kiny]

Cool. Maybe they had bacterial overgrowth or C Difficile.

Suggesting a simple commensal seen in the colon would result in the rapid cascade of event where there is full thickness inflammation in the small intestine of people with crohn's disease in a matter of weeks does not fit with the clinical symptoms of crohn's disease. The inflammation is localised and is present deep in submucosa like intestinal TB.

I really want to believe that our body decided to one day, launch a huge immune response directed at a commensal for no reason whatsoever or that a single commensal that doesn't interact with the epithelial barrier or lymphatic system suddenly caused full thickness inflammation, and magically did this in skip lesion patterns even though the commensal was found in the colon and many people have localised ileal disease, ignore that the moving mucus layer comes close to commensals everywhwere, not in skip lesions patterns, crohn's disease does not have inflammation everyhwere, it makes no sense at all.

This would be the first and only disease where the immune system turns againt the commensal gut flora and, again, magically does so at localised skip lesions even though the commensal is everywhere. One day our body just said "screw it", lets attack the gut flora, but the idea that the body that interacts with the gut flora, is able to create dysbiosis without disease, might try to modulate infllammation, and would actually know what it's doing is so outlandish right.

The immune system interacts with the gut flora 24/7, it is completely possible that any dysbiosis is a secondary event, the body is completely capable of modulating the gut flora in the absence of disease or in the presence of infmallation, which the study suggested isn't the case, because it claims the discrepancies in a very limited number of CD patients compared to controls is not the result of an inflammatory process. You can create dysbiosis in animals just by making them pshychologically stressed. There is no proof at all that crohn's disease is caused by an uncontrolled immune response directed at commensals or that commensals are causative. Seeing some benefit with use of EN explains nothing, it could be nutritional deficiencies, it could be the low bacterial content of EN, it could be because it's low in microparticles, it could be because it's low in residue, it could be because it has an effect on the fecal stream. That it's method of action is modulation the gut flora is something that would take a really really really long time and it is one of the tens of explanations.

What are they going to do, trying to unravel and check a gazillion people with different gut compositions, genotype millions of commensals, spend a few decades looking for a needle in a haystack with tax payer's money? How about they check why those genes from the Nature study are overlapping with mycobactria susceptibility.

And if you find a commensal that predisposes people for crohn's disease, what are you going to do about it, it was only a couple of weeks ago that the study showed that the Nissle probiotics strain is genotoxic.