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07-25-2013, 06:32 AM   #1
xmdmom
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Crohn's biotypes

J Clin Gastroenterol. 2013 Aug;47(7):612-620.
Crohn's Disease May Be Differentiated Into 2 Distinct Biotypes Based on the Detection of Bacterial Genomic Sequences and Virulence Genes Within Submucosal Tissues.

Chiodini RJ, Dowd SE, Davis B, Galandiuk S, Chamberlin WM, Kuenstner JT, McCallum RW, Zhang J.
Source *Division of Gastroenterology #Division of Gastroenterology **Department of Internal Medicine ††Department of Anesthesiology ‡Department of Surgery, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso †Molecular Research (Mr. DNA), Shallowater, TX §Department of Surgery, University of Louisville, Louisville, KY ∥St. Vincent Physician Network, Sisters of Charity of Leavenworth Health System, Gastroenterology Associates, Billings, MT ¶Clinical Laboratories, Charleston Area Medical Center, Charleston, WV.


Abstract
OBJECTIVE::
To determine whether bacterial pathogens can be detected within the diseased submucosal tissues of patients with Crohn's disease by molecular techniques independent of cultural methods.

DESIGN::
We designed a quantitative polymerase chain reaction to detect 32 virulence genes and transposons within submucosal tissues of patients with Crohn's disease and controls and compared the microbiome of the submucosa with mucosal bacterial populations.

RESULTS::
Within submucosal tissues, the bacterial invasion/adherence genes eaeA and invA were detected in 43% of patients (P=0.01 and 0.008 vs. mucosa and controls, respectively) and the Mycobacterium-specific IS900 and 251F genes detected in 50% of patients (P=0.03 vs. mucosa and controls). These findings were mutually exclusive: invasion/adhesion genes and Mycobacterium-associated transposons were not detected in the same patient. Metagenomic sequencing and quantitative polymerase chain reaction results confirmed effective separation of the submucosal and mucosal microbiome and the existence of a submucosal bacterial population within diseased tissues.

CONCLUSIONS::
This study is the first to examine the microbial populations of submucosal tissues during intestinal disease and provide evidence of a distinct submucosal microbiome and biotypes within Crohn's disease. These data suggests that Crohn's disease may not be a single disease, but a spectrum that can be divided into distinct biotypes based on the presence of invasion/adherence genes or Mycobacterium-associated transposons. If corroborated by larger population studies, these findings could revolutionize the diagnosis, management, and treatment of Crohn's disease by the identification of patient biotypes and the application of targeted chemotherapeutic treatments that go beyond supportive in nature.
PMID: 23426447 [PubMed - as supplied by publisher]
07-25-2013, 07:06 AM   #2
kiny
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Thank you. I posted the study a while back too, but I don't understand everything.

The thing with doing biopsies looking for pathogens, instead of looking at transmural tissue, like this study did, is that a biopsy is the size of a pindrop, whatever is causing the inflammation has probably entered deep into tissue, otherwise people wouldn't be getting fistula and deep transmural inflammation.

I don't believe the indigenous gut flora has anything to do with crohn's disease.
07-25-2013, 07:09 AM   #3
xmdmom
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oh sorry I didn't see your prior post.
07-25-2013, 07:11 AM   #4
kiny
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No worries, here are the tables:



07-25-2013, 07:20 AM   #5
kiny
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If they want to find the transmural bacteria that is causing inflammation, they would look at intracellular bacteria:

-food borne bacteria: yersinia, listeria, salmonella
-mycobacteria: MAP, maybe others
-E Coli: AIEC
-Campylobacter: jejuni and concisus

the ones in dark have been isolated in CD patients that I know of

You'd look for an intracellular one because of the autophagy deficiencies in ATG16L1, IRGM and NOD2, NOD2 is specific for intracellular bacteria.

This is very different from trying to find an immune response to the indigenous gut flora, I don't know why people keep mixing these things up like they're the same, infection =/= autoimmunity directed at the gut flora....that's a very very different theory, and I think a wrong one. People with crohn's disease are severely deficient in clearing certain type of bacteria, this has been shown time and time again.

Last edited by kiny; 07-25-2013 at 07:44 AM.
07-25-2013, 09:31 AM   #6
rollinstone
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"This study is the first to examine the microbial populations of submucosal tissues during intestinal disease and provide evidence of a distinct submucosal microbiome and biotypes within Crohn's disease. These data suggests that Crohn's disease may not be a single disease, but a spectrum that can be divided into distinct biotypes based on the presence of invasion/adherence genes or Mycobacterium-associated transposons.

thanks for posting this kiny, I am happy for this finding, but saddened that its the first study to examine submucosal tissue, if they had gone this route years back as opposed to the "auto immune" route, we could be far closer to a cure for this "infection" as I believe it is.
07-25-2013, 03:42 PM   #7
kiny
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Yersinia and Listeria are part of the cold-chain hypothesis.

The cold-chain hypothesis tries to explain crohn's disease through the rise of refrigeration and psychrotrophic bacteria (bacteria that thrive in the cold)

It's always been a decent hypothesis I could consider I feel. The first cases of crohn's disease, were in 1913, from Dalziel's paper in the British medical journal (there might be ones before them, but we can't be sure because they might have been intestinal TB). They could distinguish intestinal TB from crohn's disease in 1913, and as Dalziel explains, these people were all negative for intestinal TB.

Refrigeration at home started in 1875 with ice containers. The first domestic refrigerator in the US is from 1918.

'Westernisation' results in increased use of domestic refrigerators.

At least it's a theory that makes some sense, unlike the autoimmune reaction against the gut flora, which has so many problems with it.
07-25-2013, 06:11 PM   #8
rollinstone
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Are their currently anti biotics that can kill those two strains off?
07-25-2013, 08:57 PM   #9
kiny
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In immunocompetent people yes, but I have no idea how that would work in a patient with crohn's disease with macrophage deficiencies. When not all of those bacteria are killed, they would just reinfect the host, in an immunocompetent person, the adaptive immune system would take care of the rest.

You can kill AIEC also, with cipro for example, but obviously it doesn't work since they find AIEC again in people after antibiotics use because the bacteria becomes resistant very quickly, they likely simply stay dorment for a while and they start multiplying again.

You can kill MAP too, with macrolides and quinolones, but they're slow dividing, so you would need antibiotics that target non-dividing cells. If you do it with regular antibiotics you'll just run into resistance again. And if you use regular antibiotics like they do in studies, it would take years to kill it, because it's so slow dividing, and most antibiotics are effective against dividing cells. Before you kill MAP, you will have resistance.

Also, it's possible that if it an infection, that people are getting reinfected from the environment. People with crohn's disease are vulnerable to specific bacteria other people aren't vulnerable for, because of macrophage deficiencies, autophagy in particular.

None of these antibiotics that they use for crohn's disease are specific for any of these bacteria. All those studies they do with those antibiotics all work for a while and stop working, they all run into resistance. But the fact some antibiotics do work for a while in many people with crohn's disease, just gives more credibility to the infection theory, and the fact that only the macrophage-penetrating types work, like cipro, means it's something intracellular that's being killed.

Last edited by kiny; 07-25-2013 at 09:14 PM.
07-26-2013, 07:20 AM   #10
rollinstone
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I think its too early to tell, but based on the above, new macrophages working correctly could kill the infection?
07-26-2013, 08:21 AM   #11
kiny
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In theory yes, combined with medication, I posted a study about an anti-adhesive that might help for AIEC infections. AIEC lives in biofilms and it sticks to the intestinal wall and infiltrates like that. An antibiotic is very ineffective against a bacteria that lives in a strong biofilms, you would need an antiadhesive,...and you'd need correctly working autophagy to clear it I think.
07-26-2013, 08:37 AM   #12
rollinstone
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you should really get in contact with Doctor Hal Gun, (the creator of the SSI vaccine), I think the articles you have found on this would help connect the dots. I have a lot of hope in the vaccine, so far only ten people with crohns have used it so its too early too tell, but of those 10, all 10 went into remission though 7 out of 10 have been in sustained clinical remission and are off all meds including the vaccine, the longest is 3.5 years and counting. but as I said, still too early to tell, I am reallllly really looking forward to seeing the results of the current trial, and am praying for good results.
07-31-2013, 04:59 PM   #13
David
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Yersinia and Listeria are part of the cold-chain hypothesis.

The cold-chain hypothesis tries to explain crohn's disease through the rise of refrigeration and psychrotrophic bacteria (bacteria that thrive in the cold)

It's always been a decent hypothesis I could consider I feel. The first cases of crohn's disease, were in 1913, from Dalziel's paper in the British medical journal (there might be ones before them, but we can't be sure because they might have been intestinal TB). They could distinguish intestinal TB from crohn's disease in 1913, and as Dalziel explains, these people were all negative for intestinal TB.
Interesting hypothesis Kiny. My hypothesis starts here: http://en.wikipedia.org/wiki/Fertilizer#History -- commercial fertilizers allowed us to begin to not worry about soil fertility. You could grow food in dead soil, soil without any organic matter, without any humus. The problem there is, plants begin to take up much higher concentrations of heavy metals. Metals such as nickel. Even, "organic" food production is often done in dead soil. Where I live, there are organic producers who put black plastic around the plants to sterilize the soil then simply use organic fertilizer. Of course, some of even our organic fertilizer are high in heavy metals! Our food sources begin to take up increased levels of heavy metals and those heavy metals then cause havok with our immune systems and bodies. How it manifests is different based upon a variety of variables from genetics to vitamin and mineral deficiencies, to what strains of bacteria we have in our intestinal tracts. In some unlucky souls, it results in Crohn's disease.

Just a theory of course
07-31-2013, 07:26 PM   #14
kiny
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Thankies. There's some studies from the 80s and 90s that checked if people with crohn's disease are hypersensitive to certain metals, I don't remember what they said though.
07-31-2013, 07:38 PM   #15
David
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If you come across them, please let me know.
07-31-2013, 08:10 PM   #16
my little penguin
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Gut 1996;39:231-233 doi:10.1136/gut.39.2.231
Research Article
Absence of skin sensitivity to oxides of aluminium, silicon, titanium or zirconium in patients with Crohn's disease


http://gut.bmj.com/content/39/2/231.abstract
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07-31-2013, 08:11 PM   #17
David
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Thanks MLP. I'm not surprised that there wasn't an aluminum sensitivity on the skin. However, they find aluminum in Peyer's Patches of people with Crohn's and some suspect it may play a role.
08-01-2013, 04:58 AM   #18
sir.clausin
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David: Aluminum in the patches, really? Wow did not know that, so what are we saying, that our bodies are harmed by excess heavy metals?
08-01-2013, 03:55 PM   #19
David
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David: Aluminum in the patches, really? Wow did not know that, so what are we saying, that our bodies are harmed by excess heavy metals?
Our bodies are most definitely harmed by excess heavy metals. Do they cause or contribute to Crohn's disease? Only time will tell on that. As for aluminum, we have a good wiki entry you can read on it here.
08-01-2013, 04:25 PM   #20
sir.clausin
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David: Thanks for the wiki-link. I noticed now that I wrote my answer in a rush, yes offcourse our bodies will be harmed by excess metals, just that I never thought of it as a "contender" in crohns disease.

I wonder if a hairanalyze would be a correct method to measure your levels. This Place is suppose to be good: http://www.greatplainslaboratory.com...etals_hair.asp

I might just give it a go.
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