Kickas.org Forums Ankylosing Spondylitis General Discussion #1 AS Web Support Group Gut bacteria and AS

Good article, well spotted Grumpally. Thanks for posting

Hi All!

Regarding poop transplants (FMT -- fecal microbiota transplant)...

The bottom line of my following post is that a fecal transplant could be short lived so long as a person's body likes killing the "good guys".

I did not read all the referenced articles but http://thepowerofpoop.com/why-fmt-doesnt-always-work/ had the scoop on the poop! Besides checking the health of the donor and their poop I did not see anything about "donor matching" to avoid rejection. I wonder how important that would be. Trying the feces from just any healthy donor might just be too much of a crap-shoot after all the time and preparation in the protocol. The healthy donor microbiome may not even be compatible with the recipient!

Each person will support a different family of microbiomes. Depending on the season, what a person is eating, who gave them their first French kiss, what their boss is like, each person's microbiome will vary within the family that their immune system has learned to accept in the beginnings of life.

Furthermore, there may be no more "matches" since the recipients system has become very rejectful.

We can't assume that we have "bad bacteria" that we want to get of; it's a partial truth. Something may have changed in some of us that has made us unfriendly to certain good guys. I was exposed to things ranging from industrial toxins at work to viruses and bacteria from sea water in a scuba diving mishap that my body has never seen before thus possibly triggering my immune system to attack the good guys that reduce inflammation (put in its simplest terms.); the problem is not necessarily having entities that directly increase levels inflammation. I've recently read that there are considerations to recategorize AS as an auto-inflamatory disease instead of an auto-immune disease. But if the immune system is attacking bacteria that we need then I would consider that auto-immune, and a consequence is inflammation.

If my body does not "unlearn" its hatred for the good guys then I would have to take large doses of probiotics on a life-long basis. My immune system would be busy killing them, but for as long as I take the probiotics the good guys are there providing me with the benifical effect. A fecal transplant would be short lived so long as my body likes killing the good guys.

My hope is that if the triggers are removed for long enough and my body repairs itself then my immune system would have had long enough to forget its hatred for the good guys. This could be possible in rare instances but we are more likely going to need medicine.

But still... maybe the microbiome is not the problem but their byproducts are. I can not clearly bring the effects of starch into this picture.

PS: I was in remission for a period of time while taking a brand of probiotics that had single doses of 50 billion CFUs. There were many other factors that I was doing then and many of which I am doing now but are not working. I long to get those probitoics again.

In AS there don't appear to be any readily identifiable antibodies formed that are associated with disease (compared to RA which has Rheumatoid Factor (Abs) and Anti-CCL). Instead in AS the innate arm of the immune system (also called cell mediated immune system) is causing the problem. The innate immune system is designed to make a rapid response to an infectious threat - no antibodies are produced. By contrast, the humoral immune system is slower acting and is characterised by the production of antibodies (hence also called antibody mediated immunity). It is for this reason that some people refer to AS as an auto-inflammatory disease.

Once the body 'decides' that a component of the microbiome which it once tolerated, but which it has subsequently come to regard as a pathogen, then this can't be 'unlearned'. Unfortunately, there are cells called memory T cells which never forget - they are just waiting to see that bacteria again before unleashing an inflammatory storm.

Removing starch is probably putting the offending bacteria into dormancy so that the immune system sees nothing that offends it - until the next donut comes along.

Cheers David

Hello, I'm wondering how you make coconut kefir? I tried using water kefir grains and it tasted awful. If using milk grains, do they need to be refreshed in dairy milk periodically? Used to drink lots of water kefir but have been advised to stop due to the residual sugar, just in case. Similarly have stopped kombucha and JUN.

Thank you for the clarification David even though it burst my bubble! HAHAHA

So, the behavior of AS is due to the innate immune system which will not unlearn that there are inhabitants in my gut that feed on the broken down starch, produce cytotoxins that get into my blood stream causing certain tissue types to become inflamed. Or something like that; close enough. Is it only the adaptive immune system that can forget?

But why do I need booster shots for tetanus or rabies but don't need booster shots for hepatitis? Why do people sometimes loose allergies? Can some part of the immune system "forget"?

Peace!
Kevin

Hi Kevin,

The adaptive immune system doesn't forget either.

Just how the innate immune system causes AS is still not understood. Forty years of intense efforts by immunologists have come up with some theories, but it's fair to say that the biochemical pathway leading to disease is far more complicated than anyone could have imagined.

Courtesy Wikipedia : The type of vaccination for tetanus (which is caused by Clostridium, an anaerobic bacteria) is called artificial active immunity. This type of immunity is generated when a dead or weakened version of the disease enters the body causing an immune response which includes the production of antibodies. This is beneficial to the body because this means that if the disease is ever introduced into the body, the immune system will recognize the antigen (due memory cells present in very low numbers) and produce antibodies more rapidly (by rapid clonal expansion).

Your question is a good one - having said that the immune system has memory cells that never forget and can quickly relaunch antibody production - then why the need for a ten year booster - I don't know - it seems that eventually the adaptive immune does forget - but that may take 10 or more years.

Cheers again - David

Hi Kevin,

Below I've pasted in a some more detailed comments drawing distinctions between the innate and adaptive immune systems.

The innate immune system represents a critical host response operational as the first line of defence against pathogens and a system that precedes the adaptive immune response. Whilst the adaptive immune system has elegant specificity and recall potency the system is sluggish in the face of an urgent invasion by a pathogen. The innate immune system on the other hand offers a predefined or prefabricated immediate response to the challenge, and it is critically dependent upon non-variant, genetically encoded receptors for highly conserved microbial structures known as pathogen associated molecular patterns (PAMP). These innate immune system receptors are called pattern-recognition receptors (PRR). The innate immune system also affects the outcome of infection by promoting in a complementary sense the generation of an adaptive immune response by the up-regulation of co-stimulatory molecules.

Among the PRR, toll-like receptors (TLR’s) play a central role. Once microbes have breached physical barriers such as the skin or intestinal tract mucosa, they are recognized by TLR’s and an immune response initiated. TLR’s are membrane surface receptors that recognize molecules that are broadly shared by pathogens but distinguishable from host molecules. They are present in vertebrates and invertebrates, as well as plants, and thus appear to be one of the most ancient conserved components of the immune system.

Because the specificity of Toll-like receptors (and other innate immune receptors) cannot easily be changed in the course of evolution, these receptors recognize molecules that are constantly associated with threats and are highly specific to these threats, that is, cannot be mistaken for self molecules. Pathogen-associated molecules that meet this requirement are usually critical to the pathogen’s function and cannot be eliminated or changed through mutation; they are said to be evolutionarily conserved.

In 2010 it was shown by peripheral whole blood cell gene expression profiling of AS patients that there was an up regulation of TLR4 and TLR5, supporting the importance of these TLR subtypes in AS pathogenesis, in particular the TLR sub-types responsible for the innate immune response against Gram-negative bacteria.

Lipopolysaccharide (LPS) in the outer membrane of Gram-negative bacteria is the main ligand of TLR4 and the main ligand for TLR5 is flagellin, a primary component of bacterial flagella that extends from the outer membrane of Gram-negative bacteria.

Hi David,

it is interesting that TLR4 and TLR5 are up-regulated in the blood of AS patients, likely implicating LPS from Gram-negative bacteria (Klebs and cousins). Obviously there could be other sources of LPS, such as just foods (cooking with oils, processed foods, certain high fat diets that create "rafts" to help LPS into the the blood stream, etc.) and those LPS macromolecules easily get through a leaky gut. But are there other TLR's, or other PRR's in general, that are associated with the inflammation in AS; i.e, TLR2 associated with fungi and TLR8 (in intestinal epithelium like TLR4 & 5)? Did the article possibly exclude other TLRs that your excerpts came from?

In all I have read, which is still too little, there is obvious interplay between the innate (the inflammation) and adaptive immune system. My first impression is that cytokine and chemokine production, dendritic cells alterations, fibroblast behaviour, and changes in the connective tissue play the largest parts in how we feel and autoimmunity. It is a messy web of interconnections with feedbacks and pleiotropic properties that really confuse cause and effect; fundamental physics is easier!

Aside from all that, perhaps there is a quorum sensing effect on AS flare-ups. Sometimes I feel that there are microbes that are naturally in my gut but have had the occasional opportunity to get from my gut and into my organs and stay there, just waiting for messages from the outside (coming from the gut lumen). And over the years the microbes in the organs slowly gain ground, protected in their biofilms. This could increase sensitivity to starch even though the gut has not worsened. A factor in aging might be that as we get older the growing biofilms increasingly disrupt metabolic balances and simply wear us out, weaken us, and we eventually die from "natural causes." But I digress.

One flare up mechanism I imagine that can be caused by starch is how microbes communicate using quorum sensing signalling molecules. Perhaps when we eat starch the bacteria in our gut just become very active and/or their populations will temporarily swell. The quorum sensing signalling molecules rise in concentration. If the signalling molecules pass through healthy gut membranes with ease in comparison to the bacteria themselves or their exotoxins then the signalling molecules can change the behaviour of bacteria that have colonized organs or interstitial areas hence increasing the intensity of the immune system. This can explain why the 30% or so of people having AS without gut issues may be effected by diet starch. This also can explain why some people report that continual use of antibiotics reduces their symptoms. For those that do not feel better when removing starch then perhaps their load of organ microbes is very high but not high enough for detection or noticeable organ damage; or there is a different factor that is sustaining their flare up.

If the quorum sensing hypothesis is correct, and is a significant contributor to inflammation in AS, then I would think that in addition to healing the gut barrier and its functioning that reducing the colony sizes of microbes in the organs is essential. The long-time-established microbes probably protect themselves well in cysts, biofilms and the like. My 93 year-old GP told me that if I have an infection then it would show up in the blood as puss. I disagree because it is known that infections can suppress the immune system without killing the host, just keeping the host alive for its own benefit. In the case of biofilms then perhaps the consumption of biofilm disruptors along with a healthy lifestyle will eventually bring remission. But this approach may not help in cases where viruses or other processes modified connective tissues or their progenitors, like fibroblast, that are now hypersensitive if the quorum sensing molecules directly effect the immune system even when microorganisms have been cleared out.

I am finding that old injuries are slowing being effected by AS. It seems that muscle damage or other soft tissue damage that happened to me at a younger age takes longer to start to suffer from pain and inflammation. I injured my left shoulder half a year ago and it immediately was effected with burning and pain and rarely settles down. I partially tore ligaments and tendons in my knee 40 years ago and it is only just being effected but mildly and intermittently so. I think that proximity of connective tissue to lymph drainage has a strong influence. I.e, the effect on the sacrum is due to proximity to lymph drainage from infection-like gut activity or the high levels of bacteria that can be in the rectum.

In my case there is high probability that there were a series of environmental triggers and there continues to be environmental triggers which can be reduced.

In my 20s the symptoms were between the spine which may have been due to frequent bronchial infections in life. Then the next place the spine was effected was at the based of the skull after a massive infection that creeped there from the sinuses, eustachian tubes and nasal area after a SCUBA diving mishap. There was even a strange inflammation in the throat after the scuba incident that doctors could not explain. Then finally the lumbar and sacrum has been effected through gut damage after daily and long term use of ibuprofen to reduce the pain and inflammation in the earlier effected spinal areas.

I think I obsess about the relationship between microbes and AS because the two rhumatologists I saw, that work closely together (I think one was the student of the other) both strongly believe, and one has clearly stated to me many times, "there is no association between AS and bacteria!"

I found a good website (AK lectures) that has lecutres on immunology for those that would like a course on it.
http://www.aklectures.com/subject/biology/#173-Immune%20System

Sorry to be so long winded. Just some food for thoughts.

Kevin

I think a lot of scientists are finding that many chronic diseases are actually infectious diseases. Here is just one example:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4894645/

Which bacteria or bacterium cause which disease can be the challenge.

Thanks for the article Sue.

What stood out to me was the issue of reinfection. But perhaps that shouldn't always be a concern if a person has developed immunity to it or other mitigating circumstances are no longer present that allowed the pathogen to get in.

Also, each person will have a different set of triggers and so cause and effect will not be one-to-one but instead many-to-many.

I worked in biodiagnostics 15 years ago and saw the potential for AI/machine-learning solving these problems. It was very exciting. I hope it takes off exponentially in the near future.

Cheers!
Kevin