5-HT autoimmunity associated with immune/inflammatory probs & bacterial translocation in ME/CFS

[alex3619]

Interesting to read that there are different forms of LPS. That might explain why we tolerate the LPS that some good bacteria have in our bodies...?

Also, an interesting point to add is that some viruses attach to LPS and it is thought that this helps them to evade the immune system, and be more successful in surviving and infecting cells. Polio is one such virus but there are others as well.

snowathlete, do you have a link for viral attachment? If polio does this, then enteroviruses might too - and given they infect the gut wall, this would give them an evolutionary advantage to reduce the integrity of the gut wall and suppress its immune system.

I don't think we tolerate any form of LPS once its in the general blood stream. However different forms of LPS might modify the severity of the response.

 

[snowathlete]

snowathlete, do you have a link for viral attachment? If polio does this, then enteroviruses might too - and given they infect the gut wall, this would give them an evolutionary advantage to reduce the integrity of the gut wall and suppress its immune system.

I don't think we tolerate any form of LPS once its in the general blood stream. However different forms of LPS might modify the severity of the response.

Enjoy:
http://m.sciencemag.org/content/334/6053/249

 

[alex3619]

Enjoy:
http://m.sciencemag.org/content/334/6053/249

This article can be downloaded with registration. I have not done that yet. However the abstract shows that this is a property of at least two enteroviruses, and possibly all of them. This means that enteroviral infection could indeed trigger the LPS consequences that keep being raised. Given that 83% of us, according to Chia's research, have heavy enteroviral infection of the gut wall, this is important.

 

[Sing]

Fascinating stuff. My serotonin (among other things) is very low in red blood cells, but trying to supplement anything to raise it or taking an SSRI makes me feel absolutely awful. But I'm not sure if my reaction makes sense in the context of 5-HT autoimmunity Will try to read the whole article.

Would one of you scientifically skilled people please comment on this--low serotonin and need for it, but an inability to tolerate SSRIs? Is this because increasing serotonin exacerbates the ongoing autoimmune reactions? Maybe this is obvious but I want to know if others think this is what is going on.

 

[Valentijn]

Would one of you scientifically skilled people please comment on this--low serotonin and need for it, but an inability to tolerate SSRIs? Is this because increasing serotonin exacerbates the ongoing autoimmune reactions? Maybe this is obvious but I want to know if others think this is what is going on.

It might be possible. An SSRI blocks the serotonin from being absorbed back into cells, so it stays floating around the synapses - where it might be more vulnerable to being attacked. But what symptoms would such an attack cause? I've tried to look for information regarding that, but haven't found any.

The only pretty certain result is that an autoimmune reaction to serotonin could cause low serotonin levels. So it would seem that taking an SSRI would have at least some positive effects before the blocked serotonin gets attacked and destroyed, in addition to any hypothetical symptoms caused by the autoimmune reaction itself.

But really, I have no idea.

 

[Bob]

I've never been certain if Herx die-off (Herxheimer reaction) is a real phenomenon, rather than a pseudo-science phenomenon (I've never come across any research, or scientific text on it, but i've never looked). If it is real, then I suppose it would be related to LPS. Certainly when I tried olive leaf extract once (recommended as an anti-pathogen), I got a nasty flare up in my ME symptoms, so I had to stop it immediately. (I didn't know if it was a flare up in ME symptoms, or if it was a Herx reaction.) I seem to remember that Chia says that there is a Herx reaction when taking the herbal supplement that he has created to treat ME patients, including his son.

 

[Bob]

Talking about the permeability of the gut wall, and also of enterviruses living in the gut, made me think of what I posted earlier re serotonin...
That "approximately 90% of the human body's total serotonin is located in the enterochromaffin cells in the alimentary canal (gut)".
Is this a coincidence, or might there be a relationship between 5-HT autoimmunity and a permeable gut wall, or infection of the gut wall?
Just a thought.

 

[natasa778]

This article can be downloaded with registration. I have not done that yet. However the abstract shows that this is a property of at least two enteroviruses, and possibly all of them. This means that enteroviral infection could indeed trigger the LPS consequences that keep being raised. Given that 83% of us, according to Chia's research, have heavy enteroviral infection of the gut wall, this is important.

sorry going more off topic with this, but how interesting ... not only enteroviruses it seems

Successful transmission of a retrovirus depends on the commensal microbiota

To establish chronic infections, viruses must develop strategies to evade the host's immune responses. Many retroviruses, including mouse mammary tumor virus (MMTV), are transmitted most efficiently through mucosal surfaces rich in microbiota. We found that MMTV, when ingested by newborn mice, stimulates a state of unresponsiveness toward viral antigens. This process required the intestinal microbiota, as antibiotic-treated mice or germ-free mice did not transmit infectious virus to their offspring. MMTV-bound bacterial lipopolysaccharide triggered Toll-like receptor 4 and subsequent interleukin-6 (IL-6)-dependent induction of the inhibitory cytokine IL-10. Thus, MMTV has evolved to rely on the interaction with the microbiota to induce an immune evasion pathway. Together, these findings reveal the fundamental importance of commensal microbiota in viral infections.
http://www.sciencemag.org/content/334/6053/245.long

 

[natasa778]

Serotonin in mammals is made by two different tryptophan hydroxylases: TPH1 produces serotonin in the pineal gland and the enterochromaffin cells [...]. Genetically altered mice lacking TPH1 develop progressive loss of heart strength early on. They have pale skin and breathing difficulties, are easily tired, and eventually die of heart failure.

"Easily tired" sounds familiar for ME patients, and I've heard at least one clinician (Cheney or Hyde?) talk about ME being a state of chronic heart failure, with heart dysfunction.

Interesting that they found 5-HT autoantibodies in patients with heart failure

The prevalence of 5-HT(4) receptor autoantibodies was highly significant in patients with chronic heart failure. It was also a significant correlation between these autoantibodies and the female subgroup with coronary heart disease. It is conceivable that the increased prevalence of autoantibodies against the 5-HT(4) receptor in patients with heart failure is more than just an epiphenomenon.

http://www.ncbi.nlm.nih.gov/pubmed/22205572

 

[Bob]

5-HT (serotonin) is derived from Tryptophan.

I just noticed this, when reading a fascinating article (it's not a new article) about Dr Mady Hornig's work:

Proper central nervous system functioning is dependent on having balanced immune and stress responses; throw those responses in just one part of the system- tryptophan degredation – into disarray can cause you to not be able to lay down a memory. Tryptophan is a possible candidate with ME/CFS but she was most interested in the biggest bundle of nerves outside the brain – the enteric nervous system or gut...

http://simmaronresearch.com/2013/03/hornig/

I don't know what evidence there is for "Tryptophan degredation" in ME/CFS, and I don't know if there might be a relationship between Tryptophan degredation and 5-HT autoimmunity, but it seems like an interesting connection.

The rest of the article doesn't mention tryptophan or 5-HT but it's worth a read, or a re-read, anyway.

 

[Esther12]

Isn't serotonin the fun drug?! I don't want to be allergic to that! I've always enjoyed fun.

Oh-oh - I can just imagine a pragmatic biopsychosocial approach to managing that problem.

@anyone who read the paper: was the testing blinded? Was it all done at one lab, or did they have others check their work too?

I've never been certain if Herx die-off (Herxheimer reaction) is a real phenomenon, rather than a pseudo-science phenomenon (I've never come across any research, or scientific text on it, but i've never looked). If it is real, then I suppose it would be related to LPS. Certainly when I tried olive leaf extract once (recommended as an anti-pathogen), I got a nasty flare up in my ME symptoms, so I had to stop it immediately. (I didn't know if it was a flare up in ME symptoms, or if it was a Herx reaction.) I seem to remember that Chia says that there is a Herx reaction when taking the herbal supplement that he has created to treat ME patients, including his son.

From my understanding, the herxheimer reaction is a real thing, but something which has been adopted and misused in dodgy ways. It should only be a very short-term response to treating certain infections, but it's been used to encourage patients to believe that them feeling worse for weeks is a good sign. In variable conditions, if you encourage people to believe that getting worse is a good sign, and getting better is a good sign, you're likely to have a 'good' response to treatment most of the time.

 

[natasa778]

5-HT (serotonin) is derived from Tryptophan.

I don't know what evidence there is for "Tryptophan degredation" in ME/CFS, and I don't know if there might be a relationship between Tryptophan degredation and 5-HT autoimmunity, but it seems like an interesting connection.
The rest of the article doesn't mention tryptophan or 5-HT but it's worth a read, or a re-read, anyway.

Is interferon gamma raised in ME/CFS? if so then there mostly likely is some degree of tryptophan degradation, as interferon gamma raises IDO, which degrades tryptophan. This is the mechanism behind behavioural/personality changes in patients undergoing ifn gamma treatment, and suspected mechanism for the presence of depressive etc symptoms in inflammatory disorders in general.

Would be very interesting to know what, if any, links btw IDO/tryptophan degradation and 5-HT autoimmunity. I've had a quick search but there doesn't seem to be any research on that ...

 

[alex3619]

I've never been certain if Herx die-off (Herxheimer reaction) is a real phenomenon, rather than a pseudo-science phenomenon (I've never come across any research, or scientific text on it, but i've never looked). If it is real, then I suppose it would be related to LPS. Certainly when I tried olive leaf extract once (recommended as an anti-pathogen), I got a nasty flare up in my ME symptoms, so I had to stop it immediately. (I didn't know if it was a flare up in ME symptoms, or if it was a Herx reaction.) I seem to remember that Chia says that there is a Herx reaction when taking the herbal supplement that he has created to treat ME patients, including his son.

I think the Herxheimer reaction is real, due in part to increased bacterial toxins that put the immune system into overdrive. However its come to be synonymous in common use with almost any kind of physiological crash in immune disorders like ME. Most "Herx" reactions are not Herxheimer reactions at all, and there is no science to show they are. Physiological crashes can have many causes, and a Herx reaction is just one of them.

PS What Esther12 said.

 

[Mya Symons]

Anyone have any guesses on what would happen if we took 5-htp and/or SAM-e supplements (precursors to serotonin)? Do you think it would help or cause a crash?

 

[A.B.]

Would one of you scientifically skilled people please comment on this--low serotonin and need for it, but an inability to tolerate SSRIs? Is this because increasing serotonin exacerbates the ongoing autoimmune reactions? Maybe this is obvious but I want to know if others think this is what is going on.

SSRI's lower thyroid function (the mainstream view is that it's all good as long as parameters remain within reference range, but I'm not convinced of the validity of this view, and you'll find a lot of patients aren't either).

There is evidence that SSRI's (all antidepressants actually) lower pro-inflammatory cytokine levels, so broadly speaking, they calm the immune system.

 

[alex3619]

Anyone have any guesses on what would happen if we took 5-htp and/or SAM-e supplements (precursors to serotonin)? Do you think it would help or cause a crash?

Either. It depends on the patient, and what state they are in at the time. Caution is always warranted when messing about with serotonin pathways.

 

[Bob]

Interesting related (but not CFS/ME) research:
http://forums.phoenixrising.me/inde...-tied-to-infections-autoimmune-disease.23782/