Firstly, sorry, all my referenced on the last post were not added, lost in the copy and paste.
You mix a lot of things up which is why I get annoyed and wanted to reply.
You separate a lot of things that are inextricably linked and focus on a specific breakdown in the third layer of a complex interactive system and completely ignore the breakdown and ineffectiveness of the first two layers which lead to the breakdown of the third.
I think the correct expression is “Can't see the wood for the trees”
People are somehow convinced the gut flora and therefore fecal transplants are going to strongly impact their disease, I don't want to see them disappointed if that's not the case.
That's reasonable, but completely different to what you have been asserting......
That it WON'T do any good.
I also feel that it is only part of a strategy to combat the dis-ease, and I too don't want them disappointed so I recommend that they alter their diet (which has repeatedly been demonstrated effective, and you have also repeatedly denounced) , supplement as required, and then try this if it is still felt to be necessary.
A T cell response doesn't mean the tolerance to the gut flora is lost, it's possible but it's just as likely that an APC presented a pathogen to a T cell in a lymph node.
I agree , might be an APC presenting a pathogen, but my money is on an antigen from something previously tolerated....
“Crohn's disease and graft-versus-host disease are thought to be driven by an abnormal response toward the commensal flora. They have been associated with NOD2 mutations and PP dysfunction........”
“.......Commensal microorganisms are not ignored by the intestinal immune system. Recent evidence shows that commensals actively participate in maintaining intestinal immune homeostasis by interacting with intestinal epithelial cells and delivering tolerogenic signals that are transmitted to the underlying cells of the immune system......”
“........Consequently, mucosal tolerance protects the mucosa from detrimental inflammatory immune response. “[1]
It's not my theory - “mucosal tolerance [of commensal bacteria] protects the mucosa from detrimental inflammatory immune responses” - take it or leave it, I don't care
Regarding the peyer's patches, M Cells sample pathogens that are able to bind to the epithelial barrier or go through the epithelial barrier, they don't sample the indigenous gut flora.
the only reason I brought up Peyer's Patches is because you keep droning on about them and the predominance of inflammation in the terminal ileum and that inflammation here somehow proves that it is not related to bacteria (strangely, because the colon, which is designed to tolerate larger numbers of bacteria, can do so better than the terminal ileum)
These bacteria “that bind to the epithelial barrier or go through the epithelial barrier”,
they just pop out of thin air do they?
I'm no sciency guy, but when I read this.....
“The follicle-associated epithelium (FAE) differs from the epithelium of the villus mucosa: the production of mucus is weak; the membrane-bound digestive enzymes are lightly expressed and the enterocyte brush border glycocalyx has different glycosylation patterns [15–17]. FAE is also characterized by a large number of infiltrated B-cells, T-cells, macrophages and DCs. Finally, the FAE lacks the subepithelial myofibroblast sheath and, the basal lamina is more porous compared with the regular epithelium …...
…....The cellular composition of the FAE (i.e., the proportion of enterocytes and M-cells) may be modulated by bacteria present in the gut lumen........
….....M-cells are specialized in the transcytosis of intact luminal material like soluble proteins, antigens, bacteria and viruses “[1]
…....“transcytosis of intact luminal material” sounds like sampling to me, but hey, big words and all
You're trying to use that as a reason for a directed immune response against the indigenous flora, that's not right.
While I think a “directed immune response against the indigenous flora” may be a possibility, i've never claimed this to be a fact or even the most likely 'cause or causative factor',
If you remember correctly you will recall that I just took exception to your claims....
“and without any proof that the gut flora is related to crohn's disease”,
I see a relationship, I don't claim to understand it, but I can see it
I have posted the studies here about the peyer's patches and talked about them, which I assume is why you mention it, but correctly explain what they do.
I'm so lucky to have you to tell me what is correct and what is not.....
We obviously read different things, as you will see from above,
“transcytosis of intact luminal material” sounds like sampling to me, Whether directly from the lumen or indirectly through the mucosal barrier, who gives a toss?
They are not directing immune responses against the gut flora commensals, they are purely looking for pathogenic bacteria who can pass through the epithelial barrier.
Gut flora commensals and pathogens are not the same thing.
You seem to put bacteria in two categories, commensals and pathogenic,
Firstly commensal implies that one party benefits ant the other is not affected.
This is not the case, both parties benefit.
Secondly you take them from one category to the other without acknowledging that what has changed is the (previously mentioned) 'active tolerance'.
Even in the case of LF82, LF82 in a susceptible host is a pathogen, it is no longer a commensal, that distinction needs to be made if you want to talk about fecal transplants, a fecal transplant is going to do nothing for people if it involves pathogens that penetrate the intestinal wall.
They were 'commensal', now they are 'pathogenic', but that only happens when YOU want it to?
Lets try 4 categories,
-essential/beneficial
-opportunistic
-transitional
-pathogenic,
and all the bacteria in the first three categories can theoretically transition into the forth category, - particularly if the immune system is functioning inappropriately
(which will happen why? Diet and disbiosis?)
The 'susceptible host' became susceptable – why? Diet and disbiosis?
I used the word indigenous gut flora specifically so you won't use them interchargeably but you still do since you make no distinction between peyer's parches sampling pathogens vs gut flora, or infections of the submucosa or a gut flora response.
But as you have shown, there is an interchangeablity, and that seems to be at the discretion of the immune system, and sometimes the immune system does not work properly.
Peyer's patchs (according to my sources) do both, induction of tolerance [to beneficial gut flora] and defence against pathogens
“PPs functions, like induction of immune tolerance or defense against pathogens result from the complex interplay between immune cells located in the lymphoid follicles and the follicle-associated epithelium.....”[1]
Regarding the microbiome in submucosa you mentioned, they tested mycobacteria and invasive E Coli, that's not the gut flora, it has nothing to do with the indigenous gut flora.
There are ALWAYS opportunistic, transitional and pathogenic bacteria present in the lumen, one role of beneficial gut flora is to suppress their growth,
In my world “Gut Flora” means all gut flora, beneficial gut flora means good bugs only (if such a thing can exist as location, quantity and interaction with other bacteria will be what determines if they are good or not)
There are plenty of issues like that which is why there is serious doubt cast over the idea that the immune response would be directed at the gut flora, I really doubt it is.
Not even close to casting doubt, you are focusing on the end of a cascade and ignoring everything that lead to that point
It's not a relationship, learn the difference between a pathogen and a commensal. LF82 is a pathogen in susceptible hosts
really?, so it's a 'commensal' in a host with a healthy microflora, and a pathogen in a host with an unhealthy microflora?
You mean in a healthy gut it is suppressed by 'good' bacteria
Wow, i'm starting to understand that whether something is 'commensal' or 'pathogenic' depends on so many factors, Thank you for helping me understand......
Wait.....
Wasn't that my point?
Do you see the difference and understand that no amount of probiotics, or fecal transplants are going to help you if a bacteria is present in submucosa causing inflammation.
There is a clear difference between directed response against the indigenous gut flora and a pathogenic infection. I keep using the word indigenous so you would start to make that distinction. They are 2 different things. Do not bunch them together, fecal transplants would help the former but not the later.
Ohh, thanks again, indiginous means 'only the good ones', not actually the ones that are indigenous (normally present, suppressed or not), and pathogenic means only the 'bad' ones even though they might be good in someone else or somewhere else or in smaller quantities or if other bacteria were there to modulate their effects or if the immune system wasn't hyperactive.
Wow this is tricky stuff, so glad you can tell me right from wrong.....
So, no amount of probiotics will change any of these factors?
Hmmmm, if you say so....
The distinction is made here too. There is nothing to discuss if you don't make a distinction between commensals and pathogens.
You're still on about this artificial distinction, although I tend to agree, there is nothing to discuss
“........Consequently, mucosal tolerance protects the mucosa from detrimental inflammatory immune responses. “[1]
Impaired immune response (lack of tolerance) mean all bets are off
If you want to discuss fecal transplants you should ask yourself not only if it would work but why it would work, if the gut flora and dysbiosis is not directly involved in the inflammatory process then a fecal transplant would do nothing for people, in fact it could cause a lot of unwanted issues. So it's important to make distinctions and to define what you're talking about
I don't have a problem with any of those eitiologic theories, but I don't see them as being mutually exclusive, and certainly they don't excluding other factors.
I'm still happy with the “Crohn's disease is caused by interactions between environmental, immunological and bacterial factors in genetically susceptible individuals” theory,
All that is needed is to remove the interaction between “unidentified persistent bacterial pathogen” and the host, and
a healthy (varied) gut flora will suppress growth of (potentially) pathogenic bacteria, help maintain an effective physical barrier, and support an effective adaptive response.
I don't give a rat's arse if this “unidentified persistent bacterial pathogen”
turns out to be a good one gone bad or a bad one gone bad.
It doesn't affect the theory at all,
[1]
http://f1000.com/prime/reports/b/1/9/
