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%20SystemSorry to be so long winded. Just some food for thoughts.
Kevin
