Endothelial Senescence and Chronic Fatigue Syndrome, a COVID-19 Based Hypothesis

[ljimbo423]

This paper was published online June 25, 2021. I did a search and couldn't find it anywhere here.

Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome is a serious illness of unknown etiology, characterized by debilitating exhaustion, memory impairment, pain and sleep abnormalities. Viral infections are believed to initiate the pathogenesis of this syndrome although the definite proof remains elusive.

With the unfolding of COVID-19 pandemic, the interest in this condition has resurfaced as excessive tiredness, a major complaint of patients infected with the SARS-CoV-2 virus, often lingers for a long time, resulting in disability, and poor life quality.

In a previous article, we hypothesized that COVID-19-upregulated angiotensin II triggered premature endothelial cell senescence, disrupting the intestinal and blood brain barriers.

Here, we hypothesize further that post-viral sequelae, including myalgic encephalomyelitis/chronic fatigue syndrome, are promoted by the gut microbes or toxin translocation from the gastrointestinal tract into other tissues, including the brain.

This model is supported by the SARS-CoV-2 interaction with host proteins and bacterial lipopolysaccharide. Conversely, targeting microbial translocation and cellular senescence may ameliorate the symptoms of this disabling illness.

Full paper here

 

[andyguitar]

This paper was published online June 25, 2021.

A good find Jim! Interesting what they say about Lipolysaccharides (LPS).

 

[Rufous McKinney]

A good find Jim! Interesting what they say about Lipolysaccharides (LPS).

that all made lots of sense, based upon my n=1 experience here.

I can see the PEM start up, I see the gut starts to have all these issues. And not always the same issues.

 

[ljimbo423]

A good find Jim! Interesting what they say about Lipolysaccharides (LPS).

Thanks Andy.

I'm pretty confident that research will eventually show that lipopolysaccharides from the gut, are what's causing the chronic immune system stimulation in ME/CFS and all other issues.

I think this can lead to parts of the immune system becoming exhausted, like Natural Killer cells loosing their cytotoxicity or causing low IGG's, etc. I also think this is why they can't find viruses, other pathogens or other reasons for the chronic immune system activation/exhaustion.

 

[Rufous McKinney]

are what's causing the chronic immune system stimulation in ME/CFS and all other issues.

we will forever debate who is on First. We will all laugh- when we finally find out!

I'm reflecting on WHY food allergies- that was the beginning for me. One year old.

Reading about that, they don't know what causes these food allergies. Add to the list of medical mysteries.

 

[junkcrap50]

If gut LPS is causing CFS, shouldn’t larazotide acetate at least improve CFS if not cure it? (Probably not cure it as there are likely multiple ways for LPS to leak through the gut besides tight junctions.)

 

[ljimbo423]

I'm reflecting on WHY food allergies- that was the beginning for me. One year old.

Reading about that, they don't know what causes these food allergies. Add to the list of medical mysteries.

From what I understand, a leaky gut can cause food allergies/sensitivites. Because over-sized food particles get into the bloodstream and the immune system sees them as a pathogen. Causing an immune system reaction.

Why would you have a leaky gut, at one year old though?

 

[ljimbo423]

If gut LPS is causing CFS, shouldn’t larazotide acetate at least improve CFS if not cure it? (Probably not cure it as there are likely multiple ways for LPS to leak through the gut besides tight junctions.)

I don't know enough about larazotide to the answer to your question with any certainty.

How well it works might have to do with what's causing the leaky gut. If it's dysbiosis or something else, I don't think larazotide would work until the underlying cause of the leaky gut was treated.

 

[Rufous McKinney]

Why would you have a leaky gut, at one year old though?

I was breast fed, until about one year, but they introduced food , starting at two months, which was the "reason" we were given back in the day. The gut could have been affected, it seems.

Somewhere around 11% have IBS Issues, but a far smaller percentage have ME. So I wish they would actually look at: all that, wake me up later.

 

[kangaSue]

Cort at healthrising has an article on this paper;
https://www.healthrising.org/blog/2021/07/29/long-covid-chronic-fatigue-syndrome-hypothesis-merging/

 

[ljimbo423]

Here is a quote from Cort's blog about this paper.

"Ang ll" is Angiotensin II

"RAS" is the renin–angiotensin system

To the Gut We Go

In the current paper, the authors move from their focus on the blood vessels to the gut. The epithelial part of the intestinal barrier is a fragile one – a single layer of epithelial cells covered up with mucous.


Besides all the other things it can do, Ang II can apparently trigger the death of that fragile line of intestinal epithelial cells. It also may be able to alter the junction molecules (claudins) that control barrier permeability.

Either way, the intestinal barrier breaks down, allowing bad actors like lipopolysaccharides (LPS) to move into the bloodstream – sparking an immune response that may reach all the way to the brain.


The authors write that the fact that:

“… a dysfunctional RAS can trigger barrier disruption, dysbiosis and amino acid malabsorption…(makes it) not surprising that COVID-19 and ME/CFS have been associated with both aberrant immune responses and dysfunctional intestinal permeability.”​

Several studies suggest a leaky gut may be present in ME/CFS, including one which concluded that exercise exacerbated it.

One wonders if the authors missed a beat by not including fibromyalgia (FM) in their hypothesis. It’s taken longer to get to the gut connection in FM, but a recent study suggested similar bacterial problems occur in FM.

https://www.healthrising.org/blog/2021/07/29/long-covid-chronic-fatigue-syndrome-hypothesis-merging/

 

[ljimbo423]

This quote is from the original paper I posted in the first post-

Autoantibodies in ME/CFS

Another manifestation of the ME/CFS-associated immune dysregulation is the presence of autoantibodies directed against cholinergic and β2 adrenergic receptors (β2AdRs) documented by numerous studies (Loebel et al., 2016; Wirth and Scheibenbogen, 2020).

Autoantibodies are believed to reflect the presence of altered “self” proteins that are unrecognized and therefore attacked by the immune system.

An alternative explanation could fathom autoantibodies in ME/CFS patients as being directed at microbial molecules translocated from the host GI tract.

Indeed, many gut microbes express muscarinic and adrenergic receptors, suggesting that autoantibodies may target these molecules (Furukawa and Haga, 2000; Karavolos et al., 2013; Moreira et al., 2016).