Study sheds light on bowel disease

[pb4]

study sheds light on bowel disease

anyone see this yet?

Public release date: 8-Dec-2008
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Contact: Ronnie Kerr
[email protected]
01-316-509-547
University of Edinburgh

Study sheds light on cause of bowel disease
Scientists have uncovered vital clues about how to treat serious bowel disorders by studying the behavior of cells in the colon
Scientists have uncovered vital clues about how to treat serious bowel disorders by studying the behaviour of cells in the colon.

Researchers at the University of Edinburgh believe a chemical messenger that is essential for developing a baby's gut in the womb could hold the key to new treatments for inflammatory bowel disease (IBD), a condition which affects 1 in 250 people in the UK.

The team studied a chain of chemical reactions inside colon cells, called the Hedgehog signalling pathway, which controls the way it behaves and communicates with other cells.

The researchers found that some patients with IBD inherit a defective copy of one of the important links in this chain, a gene called GLI1. This defective GLI1 is only half as active as normal. Additionally, the Hedgehog pathway itself signals at lower levels than normal when the large bowel is inflamed.

The results suggest that the GLI1 protein may calm inflammation within the healthy colon, and that this process appears to go wrong in IBD patients, causing their gut to become inflamed.

The researchers now hope to test whether strengthening this weakened protein will help to prevent or treat inflammatory bowel diseases like Crohn's disease and ulcerative colitis.

Dr Charlie Lees from the University's Institute of Genetics and Molecular Medicine, who led the study, said: "Everybody has billions of bacteria in the gut, the vast majority of which do us no harm. Our body's natural immune responses identify and eliminate harmful bacteria, whilst living in harmony with the healthy bacteria. But in people with inflammatory bowel disease, that response goes wrong and an over-active immune response against these healthy bacteria leads to chronic inflammation in the gut.

"It now seems that the Hedgehog signalling pathway, and specifically the GLI1 protein, is crucial to that response. We think it provides an important signal to certain types of immune cells in the gut wall, instructing them to adopt an anti-inflammatory state. If we can find ways to bolster these responses in people with IBD, we may be able to help prevent the painful attacks which are so devastating to patients."

 

[fenway1971]

I hadn't seen this. Very interesting. Fingers crossed someone finds alternative treatments that get at the root cause of our disease instead of just the symptoms.

 

[D Bergy]

Interesting findings.

I totally disagree with their conclusion of how the immune system works though.

But in people with inflammatory bowel disease, that response goes wrong and an over-active immune response against these healthy bacteria leads to chronic inflammation in the gut.

If that was the case, Low Dose Naltrexone would never work. It would make symptoms considerably worse.

The immune system rarely, if ever attacks without reason. It may not be able to kill what it is after, but it is attacking a pathogen of some kind.

I am convinced that the immune system is compromised in some way, but it is not mistakenly attacking harmless bacteria or our own body.

Non the less, the research could lead to an immune system fix down the road.

Thanks for posting this research.

Dan

 

[pb4]

Interesting Dan that you see it that way...research has shown time and time again that CDers actually have certain strains of bacteria that healthy people don't even have and they've also show that infact the immune system is attackin bacteria that it believes is harmful when infact it isn't...but maybe for a CDer it is especially in conjunction with the other type(s) of bacteria that is specific to CDers.

Much still needs to be learned of course but every article is a stepping stone.

 

[fenway1971]

Dan and pb4....you seem to follow research quite a bit.

I'm curious your opinion on which research foundations, doctors and hospitals are the best for CD.

 

[pb4]

I'm a member of the CCFC and a few times a yr I get their journals with detailed articles on current and upcomming research...Dr.Remo Paniccione is about the best GI (he's my GI, I've had 4 including him over my 17 yrs of having CD), he's also a lead researcher for crohn's and colitis and answers the "Ask the Doctor" in the CCFC journal (it can be veiwed at the ccfc website as well).

 

[D Bergy]

Maybe I should rephrase what I mean exactly. Our bodies are attacking a bacteria that may not be harmful to a normal person. These same bacteria which I believe are mostly responsible are one or more strains of E-Coli and MAP.

If your intestinal tract is fully intact and working properly, it may not have any effect on your health. If the amount of these bacteria are below a certain threshold they may not cause much trouble even if you have the genetic make up for Crohn's.

MAP causes the same symptoms in cattle that it does in humans. It may always be present in cattle or not. It does not matter to me one way or the other, but given the lack of knowlege about how and why this bacteria causes a problem certainly does not automatically mean it is harmless. I would say at best it is inconclusive. If I am forced to decide which theory is correct I will trust that my immune system is smarter than I am and has its reasons for trying to kill this bacteria when it reaches a certain level.

The reasearch I have seen on Crohn's shows levels of these bacteria are different in Crohn's patient vs the general population. Sometimes entirely different bacteria are indicated. Sometimes the research contradicts each other.
I would hazard to guess that we are unable to kill these two bacteria strains to acceptable levels. Our immune system tries its best but just falls short of eliminating them. The big D and inflammation is the bodies attempt to purge these bacteria which is on going since it is ineffective.

The chronic inflammation is the tertiary problem. The lack of ability of our bodies to kill the bacteria is the secondary problem. The faulty immune system is the primary problem. I do not present this as iron clad facts, but the most likely scenario based on a whole of the research. A meta analysis in my own mind.

That is the basis for my treatment program. It addresses the immune system problem with LDN. I address the bacteria problem directly with Chlorine Dioxide.
The chronic inflammation is eliminated by the addressing the first two problems.
This is substantially different from standard treatment that addresses only the third problem by weakening the immune system to prevent a response.

I do not use standard treatment because it is too allopathic in nature. It only addresses the symptoms and not the cause in my opinion. Of course if it turns out that it is in fact, a hyper immune system is the cause then this would be the best way to treat it. But here again, that flies in the face of LDN working and my own personal experimentation. It is too contradictoty to real life examples to be correct in my opinion. I trust real life results vs theory.

I really do not know who or what institutions are the best with this disease. I do not use that approach personally. I read all of the research and combine it with your experiences and my own, my own experimentation and the experimentation of others like me. I sort through it all in my mind and rank the likelyhood of one theory over the other and if non fit completely, I fill in the gaps with what is probable based on what I have learned. Then I come up with my treatment program and I find a way to implement the program using doctors that will help me or no doctors at all. I have been treating my wifes undiagnosed Lyme diseae using this very approach for a few years. Not because I wanted to do it, but because it was better than watching her decline in health month after month.

Once you find out how faulty the medical system is, and how often they are wrong, you simply cannot go back to trusting others with your health. I have been burned too many times to go back to the standard doctor patient relationship.

The harmless bacteria does not fit in my mind because it contradicts the results of LDN in many users. If the harmless bacteria are some sort of allergy, then LDN would resolve other allergies. I have allergies and it does not correct them. I could be wrong, but the logic does not fit for one reason or another. It could be a missing piece of the puzzle would explain it but based on the information I have today, it does not fit. I am making the assumption that it does not fit because it is wrong.

I do not have to be 100% correct. I do not really even need to know exactly what bacteria are responsible. I know that acidic bacteria are not normally beneficial to the body so I try to eliminate them. It could be several for all I know. I will let the real researchers sort that out over time. I just need to stay well. I need to know enough to do that and that is good enough for my purposes.

Since it is working me, as it should if my theory is correct, I will assume it is correct enough. If it quits working, then the whole theory will have to go into the trash and I will have to go through the process over again and find the flaws.

My real life experience of no symptoms and no relapses (so far) takes precidence over a convincing but contradictory theory. I could also be real lucky, but I have never won the lottery so that contradicts my actual results also.

Dan

 

[sh!+_stains]

I could not agree more about needing to take control of your own health and not relying on your doctor. I am not saying all doctors are bad or don't know, but the truth is many don't stay up on the latest research (either no time or don't care to or are receiving biased information from the few ongoing research sessions they do attend which are put on and sponsored by drug companies), also, the system has tied their hands with what they can prescribe; they have to stay within their cookbook, which is developed through clinical trials that usually only big companies can afford to go through, with the exception of some trials like LDN.

I tried LDN twice. Once more or less on its own and once while on anti-MAP. Neither were perfect goes for me but it did seem to help at least in the short term. However, there is some uncertainty as to what its mechanism of action is: boost the immune system (what most think), suppress inflammatory cytokines or promote the repair of tissues...? No one really knows at this point:

A recent paper came out showing that cattle with the NOD2 polymorphism (the major CD mutation) are more susceptible to Johne's; chalk more plausibility up to the MAP hypothesis:

pb4, the responding to our commensal flora as the primary cause of IBD just does not make sense. Most people's bowels were balanced a year before they get sick, it is not some miracle that our bodies start attacking the bacteria that has always been there, something else happens such as an infection. While IBD patients often have different flora compositions, it is a result of the disease and not the cause.

Dan, do you follow any restricted diet?

 

[D Bergy]

I do not eat Onions or Malt. I am allergic to both.

I also do not drink milk because of the MAP bacteria. Other than that I eat what any normal person does.

Dan

 

[pb4]

Don't forget that not all CDers have major D as a symptom, some have issues with constipation (so I don't see the theory of the body trying to purge via D to get rid of those bacteria), but I certainly see some points that you make.

 

[pb4]

Sh!it Stains wrote;
pb4, the responding to our commensal flora as the primary cause of IBD just does not make sense. Most people's bowels were balanced a year before they get sick, it is not some miracle that our bodies start attacking the bacteria that has always been there, something else happens such as an infection. While IBD patients often have different flora compositions, it is a result of the disease and not the cause.



I never said that it was the primary cause of IBD...but I would like to know how anyone would know that most peoples bowels were balanced a yr before they got sick?

The cause is our immune system going awry due to it being triggered and setting off the symptoms of the disease. This of course only happens to those that are predisposed to getting CD and the combination of it being triggered (smoking, including second-hand smoke BTW is one KNOWN trigger for crohn's). Plus, it's already been determined that those with crohn's do have some strain(s) of bacteria present in our gut flora that healthy people do not have, does that happen just before or after the CD has been triggered? I don't know but it happens or maybe we're born with those specific bacteria(s) and it's a matter of our disease being triggered that sets off the immune system.

There could be thousands that are predisoposed to getting CD but live their whole life perfectly normal because it never gets triggered for them (that's why I always laugh when CDers go on about how no one in their entire family has ever had an IBD, like they new every single relative, great, great grandparents, great, great uncles and aunts and so forth), it's genetic that's been confirmed, it's just they don't know exactly how the gene gets passed on like they do with MS for example.

This is also why if you were to get a colon/intestinal transplant, it wouldn't make any difference, the disease would still come back at some point and affect the new intestines...because it all starts with the immune system.

This disease is much more complex than what most give it credit for, it's by no means black and white, cut and dried.

 

[pb4]

Also, look at this for example...

Chocolate craving 'caused by bacteria'

05:39 PM CDT on Friday, October 12, 2007

Associated Press

WASHINGTON — If that craving for chocolate sometimes feels like it is coming from deep in your gut, that's because maybe it is.

A small study links the type of bacteria living in people's digestive system to a desire for chocolate. Everyone has a vast community of microbes in their guts. But people who crave daily chocolate show signs of having different colonies of bacteria than people who are immune to chocolate's allure.

That may be the case for other foods, too. The idea could eventually lead to treating some types of obesity by changing the composition of the trillions of bacteria occupying the intestines and stomach, said Sunil Kochhar, co-author of the study. It appears Friday in the peer-reviewed Journal of Proteome Research.

Kochhar is in charge of metabolism research at the Nestle Research Center in Lausanne, Switzerland. The food conglomerate Nestle SA paid for the study. But this isn't part of an effort to convert a few to the dark side (or even milk) side of cocoa, Kocchar said.

In fact, the study was delayed because it took a year for the researchers to find 11 men who don't eat chocolate.

Kochhar compared the blood and urine of those 11 men, who he jokingly called "weird" for their indifference to chocolate, to 11 similar men who ate chocolate daily. They were all healthy, not obese, and were fed the same food for five days.

The researchers examined the byproducts of metabolism in their blood and urine and found that a dozen substances were significantly different between the two groups. For example, the amino acid glycine was higher in chocolate lovers, while taurine (an active ingredient in energy drinks) was higher in people who didn't eat chocolate. Also chocolate lovers had lower levels of the bad cholesterol, LDL.

The levels of several of the specific substances that were different in the two groups are known to be linked to different types of bacteria, Kochhar said.

Still to be determined is if the bacteria cause the craving, or if early in life people's diets changed the bacteria, which then reinforced food choices.

How gut bacteria affect people is a hot field of scientific research.

Past studies have shown that intestinal bacteria change when people lose weight, said Dr. Sam Klein, an obesity expert and professor of medicine at Washington University in St. Louis.

Since bacteria interact with what you eat, it is logical to think that there is a connection between those microbes and desires for certain foods, said Klein, who wasn't part of Kochhar's study.

Kochhar's research makes so much sense that people should have thought of it earlier, said J. Bruce German, professor of food chemistry at the University of California Davis. While five outside scientists thought the study was intriguing, Dr. Richard Bergman at the University of Southern California School of Medicine, had concerns about the accuracy of the initial division of the men into groups that wanted chocolate or were indifferent to it.

What matters to Kochhar is where the research could lead.

Kochhar said the relationship between food, people and what grows in their gut is important for the future: "If we understand the relationship, then we can find ways to nudge it in the right direction."


Imagine that!!! Don't under estimate the power of bacteria in the gut, espceially the more bad bacteria the more complex it makes things.

 

[pb4]

I do not eat Onions or Malt. I am allergic to both.

I also do not drink milk because of the MAP bacteria. Other than that I eat what any normal person does.

Dan

So you also avoid other dairy products made from milk as well (cheese, yogurt, butter, ect)?

As informed that you are about MAP, you must also be aware that MAP is not limited to cows milk, but that it is also in soil and water?

 

[sh!+_stains]

Hearing about some environmental triggers is a joke. Smoking and the birth control pill are favorites for GIs to ring off - all those seven year old boys smoking and taking the birth control pill (i haven't seen large studies showing second hand smoke to be a trigger, but maybe there are?).

All there is to know about the flora is that it plays a secondary role in perpetuating the symptoms, driving the pathogenesis but not the cause or trigger, and that yes, eating certain foods can feed the bad bugs and worsen symptoms, and starving the bad bugs can return one to an asymptomatic state.

 

[pb4]

Actually yes there have been studies about smoking, including second-hand smoke and it's link to triggering CD, a 7 yr old boy doesn't have to be smoking to get CD if he's predisposed, just being around second-hand smoke can be the trigger (that said there could also be more than one trigger involved in order to bring the disease to surface).

Dr. Kevin Rioux and IBD research fellow at the university of Alberta specifically has done research on The Genetics and Inheritance of IBD....

He's the one (who's paper I read sent with one of my CCFC journals) that stated smoking is one known trigger for crohn's including second-hand smoke...he also states that genetic influences have long been suspected to play a role in IBD based ont the following clues;

1) a significant percentage (~20%) of IBD patients have a relative that also suffers from IBD.
2) certain ethnic groups are at substantially higher risk for IBD than the general population.
3) there are extream cases of familial IBD where nearly every member of a family suffers from the condition.
4) in studies of identical twins, if one twin has CD there is a 40-60% chance that the other twin will also have the disease.

He goes on to say that cigarette smoking is one of the strongest known environmental risk factors for the development of CD. And that, in the past few yrs advanced genetic techniques had allowed scientists to discover at least 9 different gene clusters that contribute to the development of IBD and define the severity and behavior of the disease (mild to severe cases) over time. Some of these genes encode factors involved in recognition and defense against bacteria. Mutations in immune response reacts to harmless bacteria and this likely contributes to the development of IBD.

Genetic alterations in CD cause the immune system to respond inappropriately to triggers such as intestinal bacteria resulting in uncontrolled inflammation.

People can believe what they want but science has definitely got more proof than what someone just chooses to believe because it simply makes sense to them.

I find it interesting sh!t stains that you don't believe that environmental triggers are involved in the process of IBD??? If they weren't involoved then it only seems logical that those of us that have IBD would have symptoms of the disease from the first day of birth, but that's not the case, many people live IBD symptom free for many yrs before it gets triggered for them.

If you don't believe in environmental triggers then what do you believe the trigger(s) are?

 

[D Bergy]

I only avoid milk since you certainly are going to be exposed to MAP if you drink it regularly.

I know it is in many other places also, but I do not know what the concentrations are. It is virtually impossible to avoid it altogether, but not drinking Milk is easy for me since it does not digest that well and I do not even like it much.

If symptoms arise, I just have to kill it again. I hope the LDN will prevent this, but I do not trust the LDN as much as the Chlorine Dioxide.

Who knows what environmental factors, if any, play a role. We are exposed to so many things that did not exist 100 years ago it is difficult to pin anything down.

I still would like to know if the Amish get Crohn's. I suspect vaccinations could be a possible culprit in a dysfunctional immune system. No way to prove it or disprove it but something that directly tinkers with the immune system would be the first place I would look.

There is no doubt in my mind that there is an immune system problem. Just not sure why it happens.

Dan

 

[pb4]

But researchers know that smoking is an environmental trigger for CD just as they know the carbon monoxide from smoking actually reduces inflammation in the colon for UCers...it's kinda odd that you would discredit what research knows because it's too hard for you to fathom that doesn't make it untrue.

BTW, IBD was virtually unknown in asia but it's becomming more prevalent there, same with in africa.

 

[D Bergy]

I am not disputing anything. Smoking alters the whole physiology of a person. I am quite sure it influences various functions and diseases. It obviously increases he risk of cancer, so I do not see why it would not influence other diseases as well.

When my father quit smoking he immediately had lung problems. Just the opposite of what I would have expected. Bacteria took off in his lungs and he is still having some congestion, although now it is better. It seems that his body was so well adapted to the smoking that now it does not operate as well without it. I am hoping that will change with more time.

Dan

 

[pb4]

Oh, it's just when I saw you wrote this;

"Who knows what environmental factors, if any, play a role. We are exposed to so many things that did not exist 100 years ago it is difficult to pin anything down."

I thought you were disagreeing that researchers found smoking to be a known trigger for crohn's.

Sorry about your dad, that's so strange, really bad luck...I used to quit smoking often in my younger yrs just to take a break from it from time to time and never experianced anything like that...but age and maybe in combination with the longer you smoke before quitting and such might have had an influence on your dad having lung problems after quitting...it could be coincidence too and on the verge of happening even if he hadn't quit, who knows, hard to say i suppose. I hope he continues to improve, one thing is the longer you've quit the more yrs it can add to your life, but then there's always something isn't there...seems like everyone has some health issue be it minor to severe.

 

[sh!+_stains]

I've been talking about cause. When did i ever say that i did not think that environmental factors are the cause?

I simply said that it is a joke hearing GIs talk about smoking and the birth control pill as though they are THE potential causes of CD. Good for them, give them a tap on the shoulder for finding an association between smoking and developing CD; it is not the cause.

And yes genetics are involved in every disease: quoting Dr. Behr "[leprosy is a genetic disease]"

So would anyone contend that leprosy was not CAUSED by M. Leprae because there is genetic susceptibility?

I believe what i believe based on the science i have read and been able to interpret given my non-science background. But when something simply does not make sense and is just a parade of reductionist research then i don't buy it; it does not fly with Ockham's razor then throw it in the garbage, which is most of the IBD research analyzing all these specific pathways and trying to draw broad conclusions. A doctor/researcher said it best to me: "[they're all standing there analyzing the debris and rocks and sides of the crator, forgetting that a meteor hit]". The meteor being MAP and the debris, rocks and sides being the inflammation and pathways and processes.

 

[pb4]

Ah, well I guess I misunderstood your post then...guess the bottom line so far is, until they know for sure what all the triggers are and learn more about IBD in general they may not find a cure, except the stem cell therapy does sound promissing even though most of the articles I've read about stem cell and IBD are geared towards the more severe patients and all I can think is what about the rest of us that are still very inconvienced/suffering with this DD.

I just wish they'd hurry up already I've spent 17 yrs in misery and there are many who've been sick much longer...it would be nice to live to be cured and have some life left to live, the longer I have to wait, the older I'm getting LOL!

 

[D Bergy]

I agree a complete cure would be the best for everyone concerned. I can only recall a few cures for anything in our history. None of which have happened recently.

Not very encouraging, but who knows what the future holds. At least there are some researchers working on it.

Dan

 

[sh!+_stains]

Yeah, 'talking' on the internet can be 'fuzzy'. I wasn't necessarily the clearest.

Personally I don't think stem cell therapy holds much promise. The allogeneic is too risky for pretty much any IBD case (reserve it for those about to 'check-out' from cancer or something), and the autologous don't work very well and still carry significant risks (death). Most patients that have had the autologous go on to relapse after say five years; presumably after they encounter the environmental trigger, and because the autologous does not remove your underlying genetic defect, you simply fall back into disease. I really hope CCFC and other organizations do not waste money on this type of extremely expensive research, but it seems like they are heading in this direction, running into the autoimmune theories' hands with 'cutting-edge' therapies that just sound promising and futuristic.

I could not agree more about wishing they'd hurry up pb4. This is why i wished they'd research MAP more; every single study says that there is not enough evidence to disprove MAP as the cause of a significant majority of CD, so then why is there not a single MAP research project in CCFC's current list of research projects (who knows about CCFA - they are NOT big on MAP)? CCFC's slogan is "find the cure"; how about we "find the cause" first, so that our supposed cure is not more broad, non-specific, immune suppressing therapies that merely act as bandaids which happen to have deadly and other undesirable side effects. A new biologic that achieves 90% remission or something but has terrible side effects is not a cure in my mind.

The simple message i am trying to convey with the IBDvideos is that we need more research, urgently. To think that the current number one candidate cause of a significant majority of crohn's is practically being ignored, is unbelievable.