Microbiome Modifies Immune System Behaviour

[Wishful]

https://newatlas.com/science/als-gut-bacteria-microbiome-harvard-study/

This study is about ALS, but it shows that the gut microbiome can modify the inflammatory characteristics of that disease. Changing the microbiome can change the severity of the disease.

It seems reasonable that the gut microbiome (or the nasal microbiome, or maybe the 'stuff between your toes' microbiome) could influence the severity of ME. This doesn't mean that optimizing your microbiome would cure ME, but maybe it could reduce one or more of your symptoms a bit. I *think* it worked for me, curing me of type IV food sensitivity that arose with my ME, but I haven't noticed any other changes due to dietary changes, so I wouldn't consider microbiome modification as a strong prospect for reliable treatment for ME.

 

[ljimbo423]

This new study examined a different genetic animal model, and identified different gut bacteria species.

The fundamental hypothesis building from this growing body of research suggests, not that gut bacteria is a sole cause of ALS, but it instead plays a role alongside genetic predispositions in triggering the development of the disease.

"We made the remarkable discovery that the same mouse model – with identical genetics – had substantially different health outcomes at our different lab facilities.

We traced the different outcomes to distinct gut microbial communities in these mice, and now have an intriguing hypothesis for why some individuals carrying this mutation develop ALS while others do not.”

I think it's very possible that the same basic thing is happening in ME/CFS. We have genetic predispositions to ME/CFS, then our gut microbiome becomes unbalanced and triggers an immune system reaction, oxidative stress and inflammation, causing symptoms.

What causes an unbalanced gut microbiome? Many, many things, here are just some-

Antibiotics, bad diet, food poisoning, food allergies or sensitivities, parasites, viral or bacterial infections in the gut, excessive drinking, excessive exercise, non steroidal anti-inflammatory drugs, excessive or chronic stress, pesticides,

heavy metals, many other toxins, chemotherapy, concussions, repeated systemic bacterial or viral infections, because they cause systemic inflammation and that increases intestinal permeability and disrupts the gut microbiome.

So it could be that both genetics and an unbalanced gut microbiome are both needed to cause ME/CFS.

 

[Wishful]

We have genetic predispositions to ME/CFS, then our gut microbiome becomes unbalanced and triggers an immune system reaction, oxidative stress and inflammation, causing symptoms.

It seems just as likely that we have a genetic predisposition to ME, and then something in our bodies becomes unbalanced, and then other factors, such as microbiome, or epigenetic changes, or how we built our muscles when younger, influence how severe our ME is. At this point there really isn't enough information to suggest that gut microbiome has more influence in most cases of ME than any of these other possibilities.

 

[ljimbo423]

It seems just as likely that we have a genetic predisposition to ME, and then something in our bodies becomes unbalanced, and then other factors, such as microbiome, or epigenetic changes, or how we built our muscles when younger, influence how severe our ME is.

At this point there really isn't enough information to suggest that gut microbiome has more influence in most cases of ME than any of these other possibilities.

Weather there is enough information that shows the gut microbiome is the major driver of ME/CFS depends on what research you believe.

What hasn't happened yet, is that there hasn't been enough research evidence found to have a general consensus among researchers, that the gut is the cause of ME/CFS. Even though at least 4-5 ME/CFS researchers, that I know of, have said they think the gut is the starting point for ME/CFS.

I'm convinced that in time the research will show that this is the case. Until that general consensus among researchers is made, which will only come when enough pieces of the puzzle are found or there is a huge breakthrough in research, it's just a matter of opinion.

There really isn't any "proof" one way or the other. As I said, it all depends on what research one believes.

 

[YippeeKi YOW !!]

I think it's very possible that the same basic thing is happening in ME/CFS. We have genetic predispositions to ME/CFS, then our gut microbiome becomes unbalanced and triggers an immune system reaction, oxidative stress and inflammation, causing symptoms.

I think you're on the right track, and I agree, altho I think there's other, possibly epigenetic, factors involved as well.

I know I've recommended this book elsewhere in these threads, but have no idea exactly where, so here it is again:

The Psychobiotic Revolution
Anderson, Cryan, Dinan
​

It's a fascinating look at what does which, and who and what chats with what and who. Whom. It's a valuable reference, but it's also written for raw recruits who barely know the difference between a pro- and a prebiotic, or what the enteric brain is.

GUT, by Giulia Enders, is also a terrific and witty, well-informed tour through the 4 or 5 pounds of bacteria that pretty much drive us around like a Jeep Wrangler. Or a horse and buggy. Depending on our condition at the time.

 

[YippeeKi YOW !!]

I wouldn't consider microbiome modification as a strong prospect for reliable treatment for ME.

Yeah, probably not the whole answer, but you gotta start somewhere, so why not start with something that does the least possible damage in terms of careful and informed experimentation. The risk/reward ratio is considerably better than most of the other options offered to us .....

 

[ljimbo423]

I think you're on the right track, and I agree, altho I think there's other, possibly epigenetic, factors involved as well.

What other epigenetic factors do you think are involved? How do you think they contribute to the cause or pathology of ME/CFS?

Just to expand a little on my previous comment. I think that the mito. dysfunction is caused by the gut ( immune system activation and oxidative stress).

But that mito. dysfunction also causes a lot of oxidative stress in and of itself, leading to more inflammation and immune system activation, which worsens or keeps a dysfunctional gut in place and worsens mito. function also.

It might be oxidative stress from dysfunctional mito. that causes PEM. Dysfunctional mito. create a huge amount of oxidative stress, that causes cellular damage, immune system activation and more inflammation.

So when we ask our mito. for more energy, through anything that requires energy, they give it but with the cost of additional high levels of oxidative stress, immune system activation, inflammation and symptoms of PEM (possibly).

If there is brain inflammation, as Jarred Younger thinks, that to could contribute to gut dysfunction as well as many other dysfunctions. I think the many dysfunctions we have keep each other locked in place. Making it extremely hard to successfully treat ME/CFS.

Michael Maes has a few good papers about this "locked" feedforward loop-

Abstract
Myalgic Encephalomyelitis (ME) / Chronic Fatigue Syndrome (CFS) has been classified as a disease of the central nervous system by the WHO since 1969. Many patients carrying this diagnosis do demonstrate an almost bewildering array of biological abnormalities particularly the presence of oxidative and nitrosative stress (O&NS) and a chronically activated innate immune system.

The proposal made herein is that once generated chronically activated O&NS and immune-inflammatory pathways conspire to generate a multitude of self-sustaining and self-amplifying pathological processes which are associated with the onset of ME/CFS.

Sources of continuous activation of O&NS and immune-inflammatory pathways in ME/CFS are chronic, intermittent and opportunistic infections, bacterial translocation, autoimmune responses, mitochondrial dysfunctions, activation of the Toll-Like Receptor Radical Cycle, and decreased antioxidant levels.

Consequences of chronically activated O&NS and immune-inflammatory pathways in ME/CFS are brain disorders, including neuroinflammation and brain hypometabolism / hypoperfusion, toxic effects of nitric oxide and peroxynitrite, lipid peroxidation and oxidative damage to DNA, secondary autoimmune responses directed against disrupted lipid membrane components and proteins, mitochondrial dysfunctions with a disruption of energy metabolism (e.g. compromised ATP production) and dysfunctional intracellular signaling pathways.

The interplay between all of these factors leads to self-amplifying feed forward loops causing a chronic state of activated O&NS, immune-inflammatory and autoimmune pathways which may sustain the disease.

Source

 

[smtl]

Have you seen https://www.sciencedirect.com/science/article/pii/S1756464619300684 ? I've purchased some https://www.iherb.com/pr/quality-of-life-labs-probiopure-125-mg-30-veggie-caps/43965 to see if it has any effect

 

[Wishful]

So when we ask our mito. for more energy, through anything that requires energy, they give it but with the cost of additional high levels of oxidative stress, immune system activation, inflammation and symptoms of PEM (possibly).

That doesn't fit my observations of my ME. Significant physical exertion used to trigger PEM, but only when my muscles were used in ways that would damage cells (and thus trigger an immune response), so it didn't seem to be ATP-usage related. Now, serious ATP usage doesn't even trigger PEM. So for me, there doesn't seem to be a link between ATP demand and ME symptoms.

 

[ljimbo423]

That doesn't fit my observations of my ME. Significant physical exertion used to trigger PEM, but only when my muscles were used in ways that would damage cells (and thus trigger an immune response), so it didn't seem to be ATP-usage related. Now, serious ATP usage doesn't even trigger PEM. So for me, there doesn't seem to be a link between ATP demand and ME symptoms.

I wrote that post about a year ago. Since then I've thought a lot about mitochondria causing PEM or a worsening of symptoms. I agree that lack of ATP or dysfunctional mitochondria are not the main cause of PEM.

I think it's much more likely that it's an immune response from the body, affecting the brain (as ME/CFS researcher Jarred Younger has said), causing PEM and other ME/CFS symptoms. Most or all of my symptoms can be explained by the sickness response in the brain being activated.

My worst symptoms are fatigue, malaise, body aches and pains, and brain fog. All of which can be caused by the sickness response. It's no less real than having the flu.

I think we disagree on what's causing the immune response in the body. I think it's toxins from the gut.

 

[YippeeKi YOW !!]

My worst symptoms are fatigue, malaise, body aches and pains, and brain fog. All of which can be caused by the sickness response. It's no less real than having the flu.

Pretty much the same, if you throw in long bouts of insomnia resulting in crabby disposition and inelegant rejoinders to DB's innocent 'Good morning" ........

Oh, yeah, and the occasional bout of deep-seated melancholy and gloom and fear of what nasty little new curve the future can lob at me, but that's more manageable than the above ... I have ways to deal, ways I've worked hard to develop, but not so much with the more physical aspects, which would include hormonal, microbial, muscular, and brain ....

I'm going to dig around for an article I came across and post it either here or in its own thread or maybe both so everyone, including those not participating here, can take a look and see what they think .... I think that there are so many tributaries feeding into this huge river that narrowing it down to just one thing, or two things, or six things, might be too reductive ....

 

[YippeeKi YOW !!]

So for me, there doesn't seem to be a link between ATP demand and ME symptoms.

It's a puzzlement, no matter which way you turn this crappy little Rubik's cube of an illness .....

 

[ljimbo423]

Pretty much the same, if you throw in long bouts of insomnia

Have you tried vitamin B-1? If I take less than 100 mg a day, I start to get insomnia. If I go down to 37 mg a day, my insomnia causes extreme fatigue at least 3-4 days a week.

 

[YippeeKi YOW !!]

Have you tried vitamin B-1? If I take less than 100 mg a day, I start to get insomnia. If I go down to 37 mg a day, my insomnia causes extreme fatigue at least 3-4 days a week.

Still having counter-intuitive, paradoxical reactions to more than very small amounts of B-vits, so am taking teeny doses of B-comp, just to give the embattled system something to work with even if it isnt at optimal levels.

Thanks j-bo .....I'll bookmark this post re B-1 tho for future ref once that particular worm turns

 

[Wishful]

I think it's toxins from the gut.

It might be gut problems for some people, but not for others. I've had lots of different diets and microbiome changes (antibiotics, for example) and none of them altered my ME. That one bout of food poisoning got rid of my type IV food sensitivity, but that immune response simply triggered additional ME symptom severity.

For those whose ME symptoms are affected by gut factors, my guess is that most of those do so through their effects on the immune system, which in turn affects the core dysfunction of ME. There might be some other cases where nutrient absorption or neural signals are involved.

 

[lenora]

To all of you: I'm just glad that I'm not one of the Researchers involved in trying to figure this entire convoluted
mess out. It's tough, isn't it? So many routes to take. Yours, Lenora.