Study on the cause of Crohns

[toomey2]

Just found this article on Yahoo. There has been a lot of talk on this forum about the Mycobacterium avium subspecies paratuberculosis (MAP) theory they've been studying in London. If these additives mess with the bacteria in your gut then maybe the two theories are linked?
http://news.yahoo.com/study-links-c...crohns-disease-colitis-191811524--sector.html

 

[wild_one353]

Yes, the extinction of good bacteria in the intestine is considered to be the prime cause of IBD and this is why restoring the diversity of bacteria to a normal state seems to treat the disease and may even be the cure. there are specific groups of bacteria that control inflammation and regulate intestinal barrier function and they are missing in IBD patients.

Here is a quote from another article about the same study.

Transplant of microbiota from emulsifiers-treated mice to germ-free mice was sufficient to transfer some parameters of low-grade inflammation and metabolic syndrome, indicating a central role for the microbiota in mediating the adverse effect of emulsifiers.

source: http://www.sciencedaily.com/releases/2015/02/150225132105.htm

 

[JMC]

Yes, the extinction of good bacteria in the intestine is considered to be the prime cause of IBD

No, it is considered to be one theory which has not been proved conclusively

 

[wild_one353]

No, it is considered to be one theory which has not been proved conclusively

you are correct, my apologies for being unclear. To restate, it is NOT been proven beyond all reasonable doubt or yet to a largest degree of probable certainty. But there is lots of evidence which supports the idea that missing bacteria which regulate inflammation, could be the prime cause of all features of IBD, so there is good support for this idea being founded in reality.

It is a FACT that IBD patients have reduced diversity in bacteria known to be beneficial and regulate inflammation, it is a "theory" that is not yet proven, that replacing these missing bacteria can reverse all features of the disease. But supporting evidence does exist that suggests this is the case, and this would be the current human trials of fecal transplants.

I would also like to add, some things are very difficult, but not impossible to be proven conclusively. We then resort to, the most probable explanation given all the current evidence that exists. Or we generate as much evidence(data) that is possible, then choose the most probable explanation. lets just say things are looking really good for the theory of missing commensal bacteria so far, it's a highly probable and worthy explanation. But we do need lots more evidence to prove it with a higher degree of certainty.

 

[mf15]

Things are just not as simple as they might seem.
Early onset crohns dysbiotic while UC is not.
In UC it takes up to 5 years to become fully dysbiotic I have posted this somewhere.

Old Mike
http://www.ncbi.nlm.nih.gov/pubmed/23044767

 

[xeridea]

I've posted before about Janssen (Remicade folks) acquiring development rights to a proprietary mix of 17 Clostridia species from Vedanta Biosciences that research shows to be super-citizens of the gut. I think they thought there's enough promise that they've forked over $250 million for the mix.

Here's a summary of their findings.

CD4+ T regulatory cells (Tregs), expressing the Foxp3 transcription factor, play a critical role in the maintenance of immune homeostasis. Here, we show that in mice, Tregs were most abundant in the colonic mucosa. The spore-forming component of indigenous intestinal microbiota—particularly clusters IV and XIVa of the genus Clostridium—promoted Treg cell accumulation. Colonization of mice by a defined mix of Clostridium strains provided an environment rich in transforming growth factor–β (TGF-β) and affected Foxp3+ Treg number and function in the colon. Oral inoculation of Clostridium during the early life of conventionally reared mice resulted in resistance to colitis and systemic IgE responses in adult mice, suggesting a new therapeutic approach to autoimmunity and allergy.

This is a brief overview of the acquisition. And here's a good jump point to various research related to this. And Dr. Kenya Honda is the lead researcher who I believe is also a principal at Vedanta.

 

[wild_one353]

Things are just not as simple as they might seem.
Early onset crohns dysbiotic while UC is not.
In UC it takes up to 5 years to become fully dysbiotic I have posted this somewhere.

Old Mike
http://www.ncbi.nlm.nih.gov/pubmed/23044767

yes this study is tricky because they are referring to alpha diversity, and i dont quiet grasp this concept yet. But one other piece of conflicting evidence would be the 6 patients with UC who seemed to be cured from borody's clinic with FMT, which again suggests bacterial species were fully restored reversing the disease, therefore suggesting uc and crohn's have similar cause of missing bacteria.

 

[xeridea]

yes this study is tricky because they are referring to alpha diversity, and i dont quiet grasp this concept yet. But one other piece of conflicting evidence would be the 6 patients with UC who seemed to be cured from borody's clinic with FMT, which again suggests bacterial species were fully restored reversing the disease, therefore suggesting uc and crohn's have similar cause of missing bacteria.

There is currently a phase 2 UC trial underway to assess the CIPAC Therapeutics Full Spectrum Microbiota product. Prof. Borody has consulted with this company.

 

[wild_one353]

There is currently a phase 2 UC trial underway to assess the CIPAC Therapeutics Full Spectrum Microbiota product. Prof. Borody has consulted with this company.

oooookay!!! this is really where it's at!! and I had no knowledge of this before you mentioning it so greatly appreciated. I knew that a full spectrum would be what we(any GI microbiome disease) really needed, although the idea of isolating the clostridia is also a great accomplishment. but I"m wondering how do they know which ones are truly commensals yet? slightly skeptical but excited.

 

[xeridea]

oooookay!!! this is really where it's at!! and I had no knowledge of this before you mentioning it so greatly appreciated. I knew that a full spectrum would be what we(any GI microbiome disease) really needed, although the idea of isolating the clostridia is also a great accomplishment. but I"m wondering how do they know which ones are truly commensals yet? slightly skeptical but excited.

I don't know exactly the way Vedanta isolates the specific Clostridia strains, but it's based on a technique they term "rational selection". What's piqued my interest is that a deficiency in F. prausnitzii is often cited as a player in Crohn's. And guess what class F. prausnitzii belongs to? If you guessed Clostridia, then you got it right.

That they've been able to demonstrate these strains induce substantially detectable levels of FOXP3 CD4 Treg cells is particularly intriguing. As I understand it, these cells are the "off" switch that reign in the inflammatory response.

I think this is an exciting area of research. I know there are other views on the etiology of Crohn's and until research proves a specific cause, I am open to all sound ideas.

 

[xeridea]

Yes, the extinction of good bacteria in the intestine is considered to be the prime cause of IBD and this is why restoring the diversity of bacteria to a normal state seems to treat the disease and may even be the cure. there are specific groups of bacteria that control inflammation and regulate intestinal barrier function and they are missing in IBD patients.

Here is a quote from another article about the same study.
source: http://www.sciencedaily.com/releases/2015/02/150225132105.htm

Just want to post this article which is very relevant to this thread.

http://www.scientificamerican.com/article/among-trillions-of-microbes-in-the-gut-a-few-are-special/

 

[lenny]

Our GI thinks MAP is total B.S.

 

[If*]

I wouldn't rule out any theory as BS, at this point.
It is a learning process, a practice as some call it

 

[wild_one353]

Just want to post this article which is very relevant to this thread.

http://www.scientificamerican.com/article/among-trillions-of-microbes-in-the-gut-a-few-are-special/

Great article, yet i have already read about these studies years ago when they were released in scientific journals and this is why i started the fecal transplant thread in this section of the crohn's forum, so much evidence for the theory that the restoration of the good microbes will treat and even cure IBD and other diseases as well. Another source of evidence for me was my own experince developing IBD after taking the antibiotic augmentin (amoxicillin-clavulanic acid).

here is a quote from the link you mentioned.

In East Asian populations the gene variants associated with inflammatory bowel disease differ from the gene variants in European populations. Yet the same bacterial species—F. prausnitzii—was reduced in the guts of those in whom the disease developed. This suggested that whereas different genetic vulnerabilities might underlie the disorder, the path to disease was similar: a loss of anti-inflammatory microbes from the gut. And although Sokol suspects that other good bacteria besides F. prausnitzii exist, this similarity hinted at a potential one-size-fits-all remedy for Crohn's and possibly other inflammatory disorders: restoration of peacekeeping microbes.

really though, this entire conversation on this thread should probably be taken into the fecal transplant thread, fecal transplant I believe could be the cure because of what the true cause is, missing bacteria. My entire efforts were to follow the science and within this I would find the cause and cure, i do believe there is a high probablity we are just around the corner with this. I already read about genetics and those studies didn't seem to be a big variable in the development of IBD.

 

[JMC]

Our GI thinks MAP is total B.S.

Are those the exact words he used? Please ask him for justification of that view, I would love to hear why.

Then ask him for the list of scientific papers which have been published proving that MAP is not the cause of Crohn's disease. Ask him for an alternative theory that is logically as complete and as well researched. Ask him if Crohn's is an autoimmune disease or caused by a pathogen.

Having spent literally thousands of hours reading the papers, something your gastroenterologist almost certainly has not had time to do, I think he will struggle with those questions. At which point, I would advise seeking out someone whose medical knowledge is up to date and based on the latest scientific evidence, not dogmatic views stuck in the last century.

 

[lenny]

Not sure about his exact words, the message came via his nurse. "We don't even test for that, here..it would be a complete waste of your time and $ to go to NM..every few years MAP pops up..no evidence.." This a doctor who does give respect to the SCD, too.

I know he thinks it's an autoimmune disease. He used to work at CHOP.

 

[JMC]

"We don't even test for that, here..it would be a complete waste of your time and $ to go to NM..every few years MAP pops up..no evidence.."

No clinic is routinely screening for MAP because it is very hard to do accurately. That is why there is so much interest in producing a cheap accurate MAP test so that all Crohn's patients can be tested. My resection samples were tested by Prof John Hermon-Taylor using his new test that is still in development. The results showed patchy MAP infection.

I know he thinks it's an autoimmune disease. He used to work at CHOP.

Just ask him if Crohn's fulfills Witebsky's postulates for an autoimmune disease. (hint: it doesn't...)