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Comment by el_cujo | Hacker News Reader

This has been my experience more-or-less as well. Any graduate student that does anything even alzheimer's adjacent at the school I used to work at absolutely had to have a certain two researchers on their dissertation committee and they would 100% not let you progress without throwing a bone to beta-amyloid in your proposal (along with heavily pushing you to pander to some of their personal pet theories).

It's a sunken cost fallacy at this point, people have build entire careers on the beta-amyloid stuff and they will NEVER accept an alternative because it would make them irrelevant. These same people hold a lot of power in the field.

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It's the same with autoimmunity. Some researchers are obsessed with genetics. But it's mostly about self misclassification due to infections and dysbiosis. Luckily, some top journals have started accepting this, but it's still an uphill battle against the establishment:

* Type 1 diabetes: https://www.biorxiv.org/content/10.1101/2019.12.18.881433v1

* Multiple sclerosis: https://stm.sciencemag.org/content/10/462/eaat4301

* Lupus: https://stm.sciencemag.org/content/10/434/eaan2306

* Sjogren's: https://www.sciencedirect.com/science/article/abs/pii/S15216...

* Anti-phospholipid: https://www.sciencedirect.com/science/article/abs/pii/S19313...

* Parkinson's: https://onlinelibrary.wiley.com/doi/full/10.1002/mds.27105

* Alzheimer's: https://advances.sciencemag.org/content/5/1/eaau3333?intcmp=...

It's like the old joke that science progresses one funeral at a time.

Are you saying many diseases we believe to be autoimmune may be caused by infections?

Yes. Or dysbiosis, i.e. your own commensal bacteria, fungi and phages going out of control in different ways. The consequence of this in both cases is that your immune system mis-classifies some of your own tissues as non-self and attacks them (autoimmunity). See introduction in:

https://www.biorxiv.org/content/10.1101/2019.12.18.881433v1

The reason is that both pathogens and your own microbiome mimic your tissue components. Especially proteins. They want to avoid being recognized as non-self, either to infect you or to keep their symbiotic relationship.

Hence, in some scenarios it's hard for the immune system to classify a virus or a commensal as foreign and the mimicked tissue in your own body as self at the same time.

The first reference in my previous post explains it well. Viral mimicry is quite old and well established in the literature both as an infection strategy and as a cause of autoimmunity [1-3]. But microbiome (commensal) mimicry is surprisingly unexplored, except for a few recent studies. Some are those I referred to in my previous post.

Note in many ways tumors are also an immune problem. They should have been caught by the immune system. There is growing evidence that this is also related to mimicry and dysbiosis.

[1] https://link.springer.com/chapter/10.1007/978-3-642-74594-2_...

[2] https://www.nejm.org/doi/full/10.1056/NEJM199912303412707

[3] https://science.sciencemag.org/content/279/5355/1344

I have subscribed to the theory that humans are first and foremost a host for bacteria, and that whether that relationship is symbiotic or dysbiotic is largely a factor of how happy your bacteria are.

Happy microbiome, happy human. Unhappy microbiome, unhappy human.

It seems like more research is published every day that links the microbiome to common disorders and diseases.

Do you have any solid resources for someone without an academic background who has an interest in this area?

I'm afraid we still know little about dysbiosis, but most decent findings are in the literature. I'd encourage you to take a look at good recent papers. Once you get used to the jargon, you will start learning a lot.

Quick entry point, take a look at references in the introduction section of: https://www.biorxiv.org/content/10.1101/2019.12.18.881433v1....

Some other entry points:

* Commensals in hunter gatherers: https://advances.sciencemag.org/content/1/3/e1500183.short

* Commensal extinction: https://www.sciencedirect.com/science/article/pii/S096098221...

* Fiber, metabolites and the microbiome: https://www.nature.com/articles/nature12726

* Leaky gut and immune responses: https://www.pnas.org/content/116/30/15140

If you are not affiliated with an academic institution, use Sci-hub to get access to any paper behind a paywall.

Do you have any references to crohn's? Thanks

This one discusses IBD and Crohn's: https://www.nature.com/articles/nmicrobiol20174

Thanks!

Dear Gavinray

What you said is very intuitive however not entirely true. Let me explain: Bacteria are happy no matter what as they (as community of different bacteria) can adjust to content of the human gut; i.e. when we feed simple sugars (in contrast to fibre that is a polymer made of many sugars) some microorganisms will be more than happy to go on simple sugar-diet that requires less energy to consume it. However it can disregulate metabolic network of microbiome that has been co evolving with fibre based diet rather than simple sugars. Early humans consumed much more plant based fibre and therefore we hardwired our human metabolism and twicked immune response to co exist with microbiome that consumes fibre. Let me give you an example: when microbiome gets fibre from our diet it returns us side products of fibre metabolism including short chain fatty acids (scfa). They(scfa) stimulate many receptors in our body and keep us healthy. So in summary: microbiome will adjust its metabolism to what is available and will be always happy given there is any food. Microbes can even consume our own mucosa when we starve or when we die. It is more about keeping the community of microbes at homeostasis (in contrast to dysbiosis). Keeping them on diet that we used to feed them for hundreds of thousands years of our co evolution even preceding primates appearance. Our bodies depend on side products of microbial metabolism of what we used to feed them and definitely not of what western like diet feeds them nowodays. We live in the world of disregulated microbial metabolism. It disregulates us, our own metabolism, our brains, our immune responses, almost all tissues. We cause dysbiosis of the global ecosystems on the planet. This is reflected in the dysbiosis of our own gut. We are degenerating our microbial shield and degenerate our and other species.

Furthermore, as presented below recent study has linked microbial metabolism of sugar, dysbiosis and antigen-specific immune responses to insulin. This is the first study that identifies precisely the cause of autoiimmunity in type 1 diabetes.

https://www.biorxiv.org/content/10.1101/2019.12.18.881433v1

A large percentage of cancers have infectious origins as well.

Old Nero-ophthalmologist diagnosed me with Sjogrens because I mentioned my symptoms always improved for several weeks following a round of antibiotics. He has noticed that’s a common trend in Sjogrens patients. He’s never heard of the marshal protocol, just something He had noticed.

Can’t find a single doctor that will take the infection theory seriously. a Year later I can’t get a prescription to even try it.

My vit D is very low. Modern med just say take supplement. Mars shall protocol says that’s just feeding the infection. Supposedly bacteria loves vit D.

Love to find a doctor that doesn’t automatically dismiss me for bringing it up.

As shown in my references above, Ro60, a potentially causal autoantigen for Lupus and Sjogren's has been linked to commensal bacteria. The study is published in Science Translational Medicine, which is a high end journal, and quite conservative. Plus other studies have reproduced equivalent results.

So these doctors should both update their knowledge and also give you the benefit of doubt.

There is a growing network of doctors that treat multiple sclerosis with high vitamin D doses. Look for the Coimbra Protocol. They also deal with other autoimmune patients. While their protocol is quite experimental, and it poses some safety concerns, it might be helpful to get in touch with more open minded MDs.

Vitamin D influences so many immune pathways. I tend to think most of the effect comes from altering T regulatory / effector ratios. Others argue for regulation of HLA elements. Irrespective of that, low vitamin D is a big risk factor for many autoimmune disorders so I would question that statement.

Hmm. Been avoiding vit D. But really unsure if that’s a good idea or not. Have a bottle of it on counter.

Thanks for the information. Will research that protocol.

Also, psoriasis:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369634/

https://www.ncbi.nlm.nih.gov/pubmed/30222202

https://www.ncbi.nlm.nih.gov/pubmed/29908580

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881942/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048199/

etc.

I went on a soylent-like diet a few years ago and my psoriasis completely went away for the first time ever. I also felt better than ever.

Eventually I went back to just eating regular food and within a month it was coming back along with not feeling as great.

I have still never been able to nail it down, and my dermatologist is pretty dismissive of it.

Your dermatologist doesn't know any better than you in this case, though I think he's wrong to be dismissive.

This stuff about the gut-skin axis has only been coming out the last 2-3 years, although there are a few lone researchers who have been thinking this for decades.

For myself, I experienced roughly 80% reduction in symptoms after switching to a strict vegetarian diet two years ago, and it's stayed that way.

You might want to look into trying an elimination diet. There are quite a few resources online for this and gist of it is that you cut out a whole bunch of food types that have been known to cause issues with some people. After a few weeks of that you add back in a single group of food every few days and check if any symptoms return.

Some people have had luck using this method to find issues that doctor visits weren't able to surface.

Posts like this one are exactly why I keep coming back day after day to this forum. Thank you for this amazing informational share.

I've long wondered if infections are behind many of the unexplained mid and late life disorders. It's exciting to see that it's finally being recognized as a credible explanation in the literature. As someone with a family member suffering from autoimmune, I'm hopeful that this trend will continue and result in antigen mediation therapies that can help.

Worth mentioning that the family member I am thinking of developed these symptoms within a year after getting a bad stomach/GI infection.

Thanks for your kind reply.

Just to clarify, it's both infections OR dysbiosis (your own commensal bacteria, fungi and virus going out of control).

The infection + molecular mimicry theory of autoimmunity was already quite well established in the 80s, but commensal dysbiosis + molecular mimicry is only starting to emerge now, and it's likely to be even more important. See section 1 (introduction) of this paper for a whole overview:

https://www.biorxiv.org/content/10.1101/2019.12.18.881433v1....

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