# Pathogenesis of Crohn's disease: Bug or no bug



## mf15 (Feb 23, 2015)

Interesting,explains some current thinking on gut bugs.

I still find it fascinating that many of the mainstream drugs suppress MAP,
and since 1942 the docs did not know it,until a few years ago.
Old Mike
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4325296/


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## kenvh (Jun 9, 2015)

I dont believe that much in MAP.

a lot of people have multiple auto immune diseases.
I have also 2 of them.
bladder and GI tract.

my IBD was triggered by campylobacter. 100% sure.
campylo isnt the same as the MAP  bacteria.
So MAP isnt my cause. campylobacter trigger an auto immune reaction and my body keeps attacking the campylobacter pathogen that is already gone.

Just like my bladder..
I had a normal infection..
Infection went away.. and bladder immune inflammation started..

so the immune system doesnt switch of the attack mode.
Its simple as that.

I DO BELIEVE IBD HAS MULTIPLE CAUSES.
People who have MAP as cause..
they can heal the GI tract by first wiping the gut with antibiotics.. then replanish the gut with.. fecal therapy and probiotics and diet..
These people are "easier" to heal.

In my idea.. just 20% have MAP as cause.
Most people will have immune reaction as cause.
Im very positive about this theory


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## D Bergy (Jun 9, 2015)

I have found through using an alernative treatment method that four pathogens make up the bulk of my Crohns symptoms.  Possibly a couple of others that I am not sure of.

MAP is one of them, but not the worst one.

Mycoplasma is the worst offender. It may even be responsible for the start of the disease but I have no way to test that.  Its just a possibility. 

H-Pylori is another one of my offenders as well as E-Coli.  These two are not as problematic but certainly add to crohns like symptoms.

I do believe that various other pathogens can be involved, and some I have may not be involved in every case.  I also believe that mycoplasma and MAP are often involved.

Since I likely have not found all the likely offenders, I am interested in how you came to find camphylobactor as a suspect, and how you know you have it?

I will be testing for this by treating it directly based on your post. I have never treated for that particular pathogen before.  

It is possible, even likely that you still have camphylobactor.  Some of these pathogens are difficult to eliminate entirely. 

Dan


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## JMC (Jun 9, 2015)

kenvh said:


> I dont believe that much in MAP.
> 
> a lot of people have multiple auto immune diseases.
> I have also 2 of them.
> ...


Let's start with the basics.  Crohn's is _*not *_an autoimmune disease.  It does not meet Witebsky's postulates and no doctor of any credibility will tell you in 2015 Crohn's is an autoimmune disease.

Where there is growing consensus, is that Crohn's is caused by:

A deficiency in the innate immune system caused by genetic mutations, specifically with autophagy and the clearance of intracellular bacteria
Infection with a pathogen which is not cleared due to the deficient innate immune system - MAP and AIEC are the prime candidates
Activation of the adaptive immune system which is not switched off causing chronic inflammation
A cascade of other problems as the gut wall is damaged and the gut microbiome becomes deranged

Increasingly, there is also evidence that _many_ "autoimmune" diseases have a pathogenic element.  As analytical techniques improve, I suspect these will be shown to be caused by genetic mutations causing immune deficiencies which prevent effective clearance of certain pathogen.


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## kenvh (Jun 11, 2015)

JMC said:


> Let's start with the basics.  Crohn's is _*not *_an autoimmune disease.  It does not meet Witebsky's postulates and no doctor of any credibility will tell you in 2015 Crohn's is an autoimmune disease.
> 
> Where there is growing consensus, is that Crohn's is caused by:
> 
> ...


Activation of the adaptive immune system which is not switched off causing chronic inflammation??? This means a bad immune response right?? so its auto immune disease?

MAP isnt my cause. Campylobacter is. So u mean there is still campylobacter even if they dont find it in stool samples?
Then we all should take anti biotic mixes to clear the rest of the hidden campylobacter. then i would cure crohn in 2 months?
I really dont understand this too well then.
Isnt my immune reponse faulty?? I did think that my immune response did not switch of after the campylobacter is cleared. that my immune system still is attacking.. even the campylo is gone.

Please explain me some more if u can.


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## kenvh (Jun 11, 2015)

ALSO: MAP & AIEC?? my crohn is triggered by campylobacter.
No MAP or no Ecoli was the trigger.
Many many UC and crohn patients are triggered by samonella or campylobacter.
so I really dont get all the MAP hype.. when so many people are triggered by another bacteria.


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## ppk (Jun 11, 2015)

kenvh said:


> ALSO: MAP & AIEC?? my crohn is triggered by campylobacter.
> No MAP or no Ecoli was the trigger.
> Many many UC and crohn patients are triggered by samonella or campylobacter.
> so I really dont get all the MAP hype.. when so many people are triggered by another bacteria.


Hi kenvh, 

Just wondering - how do you know your Crohn's was triggered by Campylobacter? Did you get a stool test? Not trying to attack/question you - I'm genuinely curious.


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## MarkC (Jun 11, 2015)

Edit - will repost in a moment as I am trying to figure this out.  Sorry.


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## D Bergy (Jun 11, 2015)

There are many possibilities other than autoimmunity that could explain crohns disease and many other diseases supposedly caused by autoimmunity.

Anything that can alter the immune response could be responsible. Chemicals, vaccines,bacteria,viruses,lack of certain bacteria that may compete for space with Crohns related pathogens.  That is just the beginning. 

When you are treated with antibiotics you kill off a whole host of bacterial species in addition to the one you are after.  This void of bacteria allow those remaining to increase.  The whole population mix and ratio is suddenly changed.

You may of rid yourself of camphylobactor but you also rid yourself of a whole lot of other bacteria with it.  Given that, it's pretty hard to nail down the exact cause.

Testing for any pathogen has its limits.  These tests can find a certain level of a pathogen, but only if there is enough to detect.  Kind of like taking a big bucket of water out of a lake to determine if there are fish in it.  

That said, it does not mean camphylobactor might not have been related to your crohns symptoms.  I am quite sure there are many species of bacterium that contribute to symptoms, but are not necessarily the cause of the disease. Just like someone slapping you on the back when you are sunburned. It didn't cause the sunburn, but it makes it hurt more all the same.

I hope you can get it all worked out.  Don't give up, I think you are thinking in the right direction.

Dan


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## MarkC (Jun 11, 2015)

Here OM - Might be of interest to you to read the responses from the MAP research folks.

A response to a similar question asking the "bug or no bug question" to a Surgical Pathologist specializing in identifying and culturing pathogens that may be involved in Crohn's disease - Specifically Mycobacterium Avium Subspecies Paratuberculosis.

--------------

Crohn's is not homogeneous, and rather it is heterogeneous.  I got to know some patients that respond to triple antibiotics, some that respond to macrolide, or vancomycin, or some simply responds to Flagyl.  Clarithromycin is the classic treatment for MAP and it is commonly used in UK since our UK patients are almost all on clarithromycin. Also Imuran and methotrexate inhibit the growth of MAP somewhat.  We have also found some other mycobacteria that may be involved in Crohn's, not simply MAP alone.  

There is a lot to the issue of MAP being "the" pathogen.  When we culture MAP, it becomes easy if the blood grows MAP as we have means to test and confirm it.  If it turns out not to be MAP then it is a problem of investigation.  From my conversation with a number of patients and investigators about the testing many have said they have MAP from their cultures, but not confirmed by genetics or molecular techniques.  Unless it is confirmed by PCR and sequencing, it remains a possibility that whatever growing is not MAP - (or is a different mycobacterium)

The key histologic changes of Inflammatory Bowel Disease are neutrophilic infiltrate and chronicity.  Neutrophilic infiltrate is almost always associated with infection.  

Searching for pathogen is almost definitely correct both in "concept" and in "practically".

When a IBD patient flares up and is hospitalized the patient almost always get antibiotics and fluid for a few days.  What happens to the patient?  they almost always get better... 

Just remember if you are an IBD patient, statistics doesn't matter to you.  Anything that works for you, do it... 

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Another MAP researcher offered this advice about the triple antibiotic therapy:

Conventional therapy in Crohn's disease (except for a few lucky ones) is supportive at best and effective in lasting remission (>1 year) in about 30% of patients. That includes all the new biologics at $7-10,000 a treatment. With those odds and success rates, why not try unconventional treatments – they cannot be much worse.

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Interestingly MAP treatment seems to have one of the highest remission success rates when properly accounted for. 

And lastly there is this:

A large genetic study which seem to show shared changes between IBD's.

Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease:  Copy and Google this title to read it as I cannot post a link yet.

"We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD."

"Most of the evidence relating to possible causal genes points to an essential role for host defence against infection in IBD"

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I think it has become virtually impossible now to simply dismiss MAP/Mycobacteria as playing a role in Crohn's Disease and possibly other IBD/IBS.


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## JMC (Jun 11, 2015)

kenvh said:


> Activation of the adaptive immune system which is not switched off causing chronic inflammation??? This means a bad immune response right?? so its auto immune disease?


No, that is not the definition of an autoimmune disease.  This is an excellent video, I cannot expain it better than Prof Marcel Behr.

https://www.youtube.com/watch?v=7x3lq8QEg5g




kenvh said:


> MAP isnt my cause. Campylobacter is.


I am interested to know how you know campylobacter is the cause?  Have you been tested for MAP infection?  Very few people have been tested for MAP as there is no standard test available, but I have and I was positive.

The mechanism I described above as the cause of Crohn's does not exclude other bacterial pathogens (such as campylobacter) as important factors.  The root cause is _immune deficiency_ which is exploited by MAP and AIEC, but there will no doubt be other nasty bacteria which cause problems.


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## mf15 (Jun 11, 2015)

Thanks Mark interesting. I have posted lots on MAP, not here so much but on healingwell.
That is where I normally hang out,since I have UC.
There are many here who know more about crohns than I do, but I have been researching
the literature on IBD since 1980,now if I could only remember the thousands of articles
I have read.
I did post some info on here awhile back which indicates that many of the IBD meds
used since 1942 suppress MAP,even biologics. No docs knew this until they were tested.
So happy to see in the above response that they take notice of this.
I post info here, that I think might be of interest to you guys,that I run across
in my daily searches or what pops up on medical express that might not be posted yet.
OM


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## D Bergy (Jun 11, 2015)

Conventional therapy in Crohn's disease (except for a few lucky ones) is supportive at best and effective in lasting remission (>1 year) in about 30% of patients. That includes all the new biologics at $7-10,000 a treatment. With those odds and success rates, why not try unconventional treatments – they cannot be much worse."

Exactly.  Why not?  

Dan


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## kenvh (Jun 12, 2015)

JMC said:


> No, that is not the definition of an autoimmune disease.  This is an excellent video, I cannot expain it better than Prof Marcel Behr.
> 
> https://www.youtube.com/watch?v=7x3lq8QEg5g
> 
> ...


Campylobacter is 100% my cause. 1000% my cause.
My GI tract was fantastic before!
People could have upset stomache after french fries and mayonaise.
I never had any problems..
Then I eated chicken or milk and campylobacter infection came.
I had diarrhea for 1 week with blood instantly!
I did stooltest and doctor said that i was hit by campylobacter jejeuni.
After 10 days the campylobacter was gone.
I did 3 stool tests after the infection! Infection was gone.
2 weeks after infection I was 99% fine. Normal bowels.
Then after those 2 good weeks.. I started my body was making some post infection reaction.. GUT and nerves started to have a tension feeling. The gut started to come more tense and tense. then I would get some STINGS. It was the immune inflammation post reaction! After 30 days i had again diarrhea and loose stools and calprotectin test scored 107 and confirmed inflammation. The 2 good weeks after the campylobacter my calprotectin test was 20! This means my gut flora was restored and I felt pretty OK in those 2 weeks! Im 100% sure this is an post immune reaction to the campylobacter.

The same thing happend to me 2 years ago in my bladder.
Some pathogen.. Killed it.. then is was 1.5 months very OK! Then i created post inflammation in bladder. Saying MAP is my cause is crazy. CAMPYLOBACTER was the cause. Also: A lot of studies come up that a lot of people get crohn or UC after samonella and campylobacter.
Im not so sure crohn isnt an auto immune disease.
I have a strong feeling crohn IS an auto immune reaction after some pathogen.

1 option is possible like u guys say: maybe the bacteria changes the balance.. and that change confuses immunity and the system sees those flora as an invader. Or the bacteria is killed 99% but has let straces and toxins into the cells.. those toxins are invaders and the system needs to kill it. For me its some immune reaction.


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## kenvh (Jun 12, 2015)

another thing i doubt MAP:
There are people who have Crohn and take no meds at all..
They go into remission for 1, 5 or even 10 years.
Then BAM.. The crohn comes hard back.
Then they go back into remission.
Thats not possible if MAP was the root cause.
I see women go into remission when they are pregnant.
they can even go without meds.
After pregnancy.. the crohn comes back.
for me.. thats hormonal and immune related. no MAP.
I think all of those inflammation diseases have MULTIPLE causes.
some are MAP. others are hormonal. other are immune reaction related.
I dont believe in 1 crohn cure. Just like Interstitial cystitis.
It has multiple causes and it must have multiple cures.
Thats why 1 therapy doesnt work for someone else.


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## JMC (Jun 12, 2015)

kenvh said:


> another thing i doubt MAP:
> There are people who have Crohn and take no meds at all..
> They go into remission for 1, 5 or even 10 years.
> Then BAM.. The crohn comes hard back.
> ...


No, that is not correct.  MAP can go into a dormant state and remission without medication is quite possible.  Many papers have been written on this.

At no point has anyone said 100% of the cases of Crohn's disease are caused by MAP infection.  Crohn's is an umbrella term for a syndrome, there is no definitive test that shows you do or do not have Crohn's.  What some scientists like Borody, Hermon-Taylor and Naser predict is that the majority of Crohn's cases are due to MAP infection, maybe as high as 90%.  When the results from the Redhill Biopharma RHB-104 trial are published next year, we will get a much clearer picture on this and the role of MAP.

Your problems caused by Campylobacter do not disprove the theory that MAP is the dominant factor in most cases of Crohn.  What you demonstrate is that Campylobacter can cause Crohn's like symptoms.


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## D Bergy (Jun 12, 2015)

That is really a huge clue as to how to go about treating your particular case of crohns.  

A person does not typically have that smoking gun type of experience. Now you need a way of directly treating what you suspect is the direct cause of your symptoms to see if your hypothesis is correct.

That method of treatment doesn't exist in conventional medicine. It does exist in the alternative realm.  

I will do a little digging an post later and see what your options are. 

Dan


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## kenvh (Jun 12, 2015)

Thx everyone. I appreciate the explaining!
Yeah, i really hope this MAP will give us more answers to Crohn.
Even campylobacter is my cause. Its also a bacteria.. so is MAP.
So if MAP is proven and if they can cure crohn..
Then maybe the other bacteria causes will also be curied easier?

This redhill.. I also did read the whole website some weeks back.
Isnt this mix of antibiotics already available?
I hear people say they are using MAP antibiotics.
I suppose this is a combination of antibiotics in long term?

How is the redhill diffrent? will this be a lot diffrent?

DBergy: thx for searching.. but i have readed many posts that says that Campylobacter is a high risk for developing crohn disease.
So I suppose the therapy is still trial and error like most people.

Im on budesonide + asacol now. (it works 50%)
Im willing to try maybe Humira.

But first of all.. Im trying REISHI mushroom + cats claw.
If those fail me.. Im trying humira i think.


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## kiny (Jun 16, 2015)

Outside of what Doctor Behr already mentioned. If the inflammation was directed at a self-antigen, as in the case with an autoimmune disease, you would not expect the type of inflammation crohn's disease has. Crohn's disease has patchy inflammation, unlike UC which has inflammation all over the colon. The immune response does not have the hallmarks of an autoimmune disease, the granuloma look like intestinal TB, unlike UC, which doesn't feature any granuloma.


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## mf15 (Jun 18, 2015)

I missed this one which is pretty new.
Also remember my thread that just about all the IBD drugs suppress MAP, even biologics.
Well here is more proof and just not test tube samples, on biologics.
Notice where it says  Infliximab treatment resulted in decreased MAP detection. 

I really have to guess that the resistance/dogma from the GI medical community that
MAP is not a cause of IBD, is whether it is a bystander or not.
Old Mike
http://www.ncbi.nlm.nih.gov/pubmed/25994082

Mycobacterium avium subsp. paratuberculosis (MAP) and adherent-invasive Escherichia coli (AIEC) have been implicated as primary triggers in Crohn's disease (CD). In this study, we evaluated the prevalence of MAP and E. coli (EC) DNA in peripheral blood from 202 inflammatory bowel disease (IBD) patients at various disease periods and compared against 24 cirrhotic patients with ascites (CIR) (non-IBD controls) and 29 healthy controls (HC). MAP DNA was detected by IS900-specific nested PCR, EC DNA by malB-specific nested PCR and AIEC identity, in selected samples, by sequencing of fimH gene. CD patients with active disease showed the highest MAP DNA prevalence among IBD patients (68 %). Infliximab treatment resulted in decreased MAP detection. CIR patients had high individual and coinfection rates (75 % MAP, 88 % EC and 67 % MAP and EC), whilst HC controls had lower MAP prevalence (38 %) and EC was undetectable in this control group. EC DNA prevalence in IBD patients was highly associated with CD, and 80 % of EC from the selected samples of CD patients analyzed carried the fimH30 allele, with a mutation strongly associated with AIEC. Our results show that coinfection with MAP and AIEC is common and persistent in CD, although the high MAP and EC detection in CIR patients suggested that colonization is, at least, partially dependent on increased gut permeability. Nevertheless, facilitative mechanisms between a susceptible host and these two potential human pathogens may allow their implication in CD pathogenesis.


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## InstantCoffee (Jun 18, 2015)

mf15 said:


> I missed this one which is pretty new.
> Also remember my thread that just about all the IBD drugs suppress MAP, even biologics.
> Well here is more proof and just not test tube samples, on biologics.
> Notice where it says  Infliximab treatment resulted in decreased MAP detection.
> ...


So this seems to suggest that Crohn's is the chicken and MAP / AIEC are the egg?


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## kiny (Jun 18, 2015)

InstantCoffee said:


> So this seems to suggest that Crohn's is the chicken and MAP / AIEC are the egg?



This is a question Behr has wondered before: http://www.ncbi.nlm.nih.gov/pubmed/?term=behr+inside+out+outside+in

Is the mucosal inflammation in crohn's disease a secondary or primary event. Crohn's disease inflammation is transmural, it's possible that mucosal inflammation is just a secondary event. 

The immunodeficiency in crohn's disease revolves around handling of  _*intracellular*_ bacteria and the interactions with macrophages that reside in large numbers in intestinal tissue, the innate immune response. It doesn't revolve around the intestinal flora. That doesn't mean the intestinal flora isn't involved, but it's possible that dysbiosis is a secondary event.

AIEC interact with peyer's patches. I think one of the interesting things about peyer's patches and crohn's disease, is that they are exclusive to the ileum, and peyer's patches are most active during teenage years. 

AIEC would solve a few mysteries, it would solve why crohn's disease is often isolated to the ileum, and it would explain why crohn's disease is often diagnosed during teenage years.

The prevailing idea has always been that crohn's disease manifests itself in the ileum, because that's where the gut flora is concentrated (the jejunum and duodenum doesn't have a high concentration of bacteria, the ileum does).  But many have pointed out this doesn't make a whole lot of sense. Because the highest concentration of gut flora is in the colon, and many people with crohn's disease don't have any inflammation in the colon. It also doesn't explain the patchyness of the inflammation, if there was a reaction against the gut flora, you'd expect widespread inflammation, not localized to small patches, often with very specific granuloma. It doesn't explain the transmural inflammation of crohn's disease either.

It also doesn't explain the sudden onset of crohn's disease during teenage years, the gut flora is a very resilient and stable community, even after antibiotics use, these same communities recolonize unscathed. It takes a major infection to disturb these communities.

A better explanation, I think, is that the inflammation is localized in the small intestine because of the peyer's patches that AIEC interacts with (M cells), that crohn's disease manifests itself during teenage years because of the activity of the peyer's patches during those years, and that the mucosal inflammation and dysbiosis is just a secondary event (that possibly makes the colonization of AIEC worse).


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## kiny (Jun 18, 2015)

I also think it's not helpful that many studies, for years, made the connection between the gut flora and crohn's disease, simply on the basis of dysbiosis.

Maybe the dysbiosis is a primary event, maybe it's a secondary event. But intestinal TB also features dysbiosis, mucosal inflammation and granuloma, and the disease itself is caused by a pathogen, not by dysbiosis.


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## Mr chicken (Jun 18, 2015)

I think a lot of the answer is in kids like mine dx at age 7 but symptoms since birth  and younger who start symptoms very early since that would be a purer form of the disease mechanisms .


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## ppk (Jun 18, 2015)

Thanks for those posts, kiny. So, then, do you believe Qu Biologics' QBECO is made with AIEC? If so, then its mechanisms of action would be both as a site-specific immunomodulator and as a whole killed cell AIEC vaccine.


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## kiny (Jun 18, 2015)

ppk said:


> So, then, do you believe Qu Biologics' QBECO is made with AIEC?


No, but there is interest in E Coli vaccines, AIEC shares similarities with ExPEC, both very pathogenic. There are pathogenic and non-pathogenic E coli strains (they can become pathogenic in immunocompromised people), but some of the pathogenic strains are genetically similar. There's more and more E coli outbreaks, and E Coli is becoming more and more antibiotics resistant, many people have suggested there should be an all-encompassing E Coli vaccine. And because there are these similarities between some strains, that is possible.


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## ppk (Jun 19, 2015)

kiny said:


> No, but there is interest in E Coli vaccines, AIEC shares similarities with ExPEC, both very pathogenic. There are pathogenic and non-pathogenic E coli strains (they can become pathogenic in immunocompromised people), but some of the pathogenic strains are genetically similar. There's more and more E coli outbreaks, and E Coli is becoming more and more antibiotics resistant, many people have suggested there should be an all-encompassing E Coli vaccine. And because there are these similarities between some strains, that is possible.


A cross-strain E. coli vaccine would solve many problems. One could be developed with a whole killed cell E. coli inactivated via sonication. Sonication disrupts the surface membranes of the bacteria and exposes both capsular and sub capsular antigens. In this way, the resulting vaccine causes a “richer” immune response, and more cross-strain immunity than a vaccine inactivated via gamma or UV radiation. Keep in mind, such a vaccine would likely cause one to react to non-pathogenic strains of E. coli. That said, E. coli constitutes a relatively small portion of your average person's microbiome (about 1%), and its only apparent benefit is its vitamin K production, so I don't think we'd be missing out on much if we wiped E. coli out altogether.


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## amber_griffin (Jun 19, 2015)

Kiny, You referenced Intestinal TB and Crohns having many similarities. How do you distinguish the two?


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## kiny (Jun 19, 2015)

amber_griffin said:


> Kiny, You referenced Intestinal TB and Crohns having many similarities. How do you distinguish the two?


With biopsies taken during colonoscopy，biopsy histopathology and culturing will help rule out intestinal TB. But it's not fail proof, the only reason misdiagnosis isn't more common is because for some reason, places on Earth where intestinal TB is common, have low rates of crohn's disease, and vice versa. The chance someone in the West developed intestinal TB is low, but it's still possible, which is why almost everyone agrees that a diagnosis needs to include a biopsy report. （people hesitant of these biopsies, should consider that it's a tiny piece of tissue, a pindrop in size, it's nothing)

Before you can take an anti-TNF blocker, you should also have gotten a mantoux test on your arm, and a test of your lungs, to rule out latent TB.


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## ppk (Jun 20, 2015)

The following paper delves into the differences between CD and intestinal TB too:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3027009/


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