The importance of functional testing?

[Keyhole]

Gut dysbiosis as a protective adaptation in certain circumstances?

This idea runs contrary to what I thought I understood about gut health, but there are some data to back it up:

The following study showed that pro-inflammatory changes in gut flora WERE NECESSARY to prevent metabolic dysfunction in obese rats:

Adipocyte inflammation is essential for healthy adipose tissue expansion and remodeling.

Chronic inflammation constitutes an important link between obesity and its pathophysiological sequelae. In contrast to the belief that inflammatory signals exert a fundamentally negative impact on metabolism, we show that proinflammatory signaling in the adipocyte is in fact required for proper adipose tissue remodeling and expansion. Three mouse models with an adipose tissue-specific reduction in proinflammatory potential were generated that display a reduced capacity for adipogenesis in vivo, while the differentiation potential is unaltered in vitro. Upon high-fat-diet exposure, the expansion of visceral adipose tissue is prominently affected. This is associated with decreased intestinal barrier function, increased hepatic steatosis, and metabolic dysfunction. An impaired local proinflammatory response in the adipocyte leads to increased ectopic lipid accumulation, glucose intolerance, and systemic inflammation. Adipose tissue inflammation is therefore an adaptive response that enables safe storage of excess nutrients and contributes to a visceral depot barrier that effectively filters gut-derived endotoxin.

To understand the biology behind this and for a great overview of the study, you can listen to this podcast by Chris Masterjohn PhD. here is an excerpt:

one of the things that they’re showing here is that healthy adipose tissue expansion needs the inflammatory signaling that starts in the gut. So those changes in the gut apparently are not exclusively bad, and rather they actually play an essential role in helping adipose tissue respond to accommodate the obesogenic diet to store the excess energy and thereby help prevent metabolic dysfunction.

Basically, visceral adipose tissue requires inflammation to undergo remodelling so that it can store more fat. When it can no longer expand, metabolic dysfunction/syndrome ensues. The inflammation which helps the adipose tissue to remodel (and essentially prevents metabolic syndrome) come from the proinflammatory gut microbiome. Hence, the "dysbiosis" appears to be a protective adaptation, and so is the chronic inflammation for a short period of time.
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I was reminded of Gerald Pollack's work on water and Stephanie Senneff's work on cholesterol sulfate and her various papers on atherosclerosis and cardiovascular disease pathophysiology. The recent work in this area shows that blood flow and lymph flow are potentially facilitated by proteins/molecules located on the surface of the capillary wall structuring the water on the surface of the capillaries, to create a "streaming potential" which can effectively propel negatively charged red blood cells though the vasculature.

Senneff has detailed the critical role of sulfated glycosaminoglycans in this process, and a lack of sulfate could potentially contribute to multiple pathologies we see today, especially cardiovascular related.

Here is a great article she wrote for the WAPF detailing the information of cholesterol sulfate, and here is one of her papers for the more technically minded.

A brief summary provided in the article:

-Impaired sulfate supply to the heart is a key factor in cardiovascular disease.
-Red blood cells, platelets and cells in the skin synthesize cholesterol sulfate catalyzed by sunlight.
-Cholesterol sulfate, unlike cholesterol, is water soluble, so it can travel freely in the blood rather than packaged up inside an LDL particle.
-Glyphosate, the active ingredient in the pervasive herbicide Roundup, disrupts sulfate synthesis in the skin and disrupts bile flow from the liver, leading to a systemic deficiency in cholesterol sulfate.
-Sulfate provides negative charge in the blood vessel wall and for the red blood cells and platelets, promoting flow.
-Sulfate also maintains the structured water that lines the vessel walls and presents a slick, frictionless surface to the red blood cells.
-The atheroma actively recruits cholesterol to be ready to produce cholesterol sulfate when sulfate becomes available.
-Inflammation, while damaging to surrounding tissues, performs a useful service by promoting an oxidative environment necessary to make sulfate.
-A heart attack is a well-choreographed sequence of events aimed to restore sulfate supplies by oxidizing taurine, which is stored in large amounts in the heart.
-Statin drugs, by reducing the supply of cholesterol sulfate to the heart, will lead to heart failure down the road, a worse prognosis than cardiovascular disease.

Senneff explains that a certain bacterial species (C.pneumoniae) are commonly found in the atheroma, and that they are the only known species to be able to supply heparan sulfate to the host cells!:

Atheromata (plural of atheroma) harbor various pathogenic microbial species, the most significant of which is probably Chlamydia pneumoniae.34,35 The strong association between chronic C. pneumoniae infection and atherosclerosis has prompted some researchers to identify it as the pathogen implied in a chronic infection theory of heart disease. While many proponents of this hypothesis enthusiastically have embraced the concept of antibiotic treatment specific to C. pneumoniae, clinical trials have been disappointing.36

C. pneumoniae are dormant except when internalized into host cells. Within these cells, they produce a unique form of heparan sulfate, using a set of enzymes that are not found in any other known bacterial species.37 I hypothesize that C. pneumoniae play a special role in enhancing the supply of heparan sulfate to an atheroma, and they may well be able to do so in the absence of functional CYP enzymes.

Senneff theorises that the body may specifically select for this bacteria to populate the site of pathology to supply sulfate. In other words, the human body is working together in a mutually beneficial relationship with this specific bacteria. Contrary to the 'pathogenic infection' theory of the atheroma development, she suggests that it is protective and is perhaps evidence of the innate intelligence of the human-microbiome system.

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So we have two interesting pieces of information here:

1. The body appears to facilitate passage of certain bacteria into the blood-stream (C. Pneumoniae) as a last ditch attempt to replenish a deficient resource (in this case, sulfate).
2. Dysbiosis/pro-inflammatory changes to the microbiome appear to be selected for by obese rats to prevent metabolic syndrome. Dysbiosis=helpful

It is starting to look like the body has some control over the microbiome, or is in communication with it at least (well duhh?)

So this left me thinking about chronic digestive issues, dysbiosis, and small intestinal bacterial overgrowth.

WHY do these problems just keep recurring in so many people who appear to have exhausted every avenue? This is a common issue that practitioners face, and Chris Kresser recently did a podcast on it basically admitting that he is unable to work it out, even after like a decade attempting treating it. It is very, very common for SIBO to return shortly after treatments in some people. Additionally, why do 95% of autistic children have rampant Clostridia overgrowth in their gut (according to great plains lab)?

How might this all tie in together and relate to Senneff's work on sulfate?.........

 

[Keyhole]

Connecting the dots: Microbiome selectivity as a method to replenish low sulfate stores??

Might the dysbiotic changes be intended as a short-term survival strategy with long-term negative health consequences?

In many cases of dysbiosis/small intestinal bacterial overgrowth - the bacteria produce excess Hydrogen/ Hydrogen Sulfide gas. This gas typically produces smelly farts when expelled, but a lot of it is actually absorbed directly into the blood stream.

According the Senneff, one of the ways that the body can effectively supply sulfate to cholesterol is via the production of hydrogen sulfide gas, which passes into the blood and can later be converted back to sulfate:

Another available pathway is to produce hydrogen sulfide gas (H2S) from cysteine by enzymatic action of cystathionine γ lyase(CSE). H2S has only relatively recently been recognized as a signaling gas on par with nitric oxide [68], and it has been shown to induce vascular relaxation as well [140]. H2S offers similar protective effects as NO without the issue of reacting with superoxide to produce the toxic metabolite ONOO− [141–143]. H2S in small concentrations promotes angiogenesis and protects against both atherosclerosis and hypertension [144]. CSE is present in both vascular smooth muscle cells (SMCs) [145] and blood lymphocytes [68]. It has only recently been realized that H2S can be used by mammalian mitochondria as an energy source during times of hypoxia.

Several enzymes working in conjunction with the mitochondrial electron chain are involved in oxidizing hydrogen sulfide to sulfate and thiosulfate.80

The bacteria responsible for producing the hydrogen sulfide gas are called "Sulfate Reducing Bacteria":

The most extensively studied of the microbes involved in colonic sulfur metabolism are the sulfate-reducing bacteria (SRB), which are common colonic inhabitants. Many other microbial pathways are likely to shape colonic sulfur metabolism as well as the composition and availability of sulfated compounds, and these interactions need to be examined in more detail. Hydrogen sulfide is the sulfur derivative that has attracted the most attention in the context of colonic health, and the extent to which it is detrimental or beneficial remains in debate.

This paper goes on to say:

Most of the SRB belong to the Deltaproteobacteria with more than 25 genera, followed by the Gram-positive SRB within the Clostridia (Desulfotomaculum, Desulfosporosinus, and Desulfosporomusa genera).

Interesting! So Clostridia seem to be key players in converting sulfate into hydrogen sulfide.
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Is this partly why clostridia is so freakin common among autistic children? As a method to supply sulfate to a sulfate deficient system?

I don't currently have time to paste all of the details about Senneff's theory of autism here, but it seems to link in nicely with the rest of the research regarding aluminium and mercury in vaccines (inhibit sulfate production in brain) and excess dopamine (to transport sulfate as a backup - and surprisingly upregulated by clostridia).

My line of thinking is that gut dysbiosis (perhaps specifically clostridia infection) is preserved and actually selected for by the body system - intelligently. This could help to explain why it is so notoriously difficult to treat long-term. What is the reason for wanting excessive sulfate reducing bacteria in the gut? Because something is disrupting the bodies ability to synthesise it itself. This idea is completely new to me, but makes a tonne of sense. I will run it by Senneff and see if she thinks its plausible or not.

Senneff's work suggests primary factors involved in disrupting cholesterol sulfate are:
-Glyphosate
-Aluminium, Mercury, Cadmium, and some other metals
- Lack of UV light
-Lack of dietary sulfur

Ofcourse, if you think with a cholesterol sulfate hammer, everything looks like a cholesterol sulfate nail. However, I think this is an interesting way of looking at things. I am going to investigate further by doing the DMSA provocation urinary toxic elements profile, and perhaps testing glyphosate contamination also.

 

[Keyhole]

On that note, have you been following the NeuroFeedback and Healing Developmental Trauma threads?
My thinking is that the emotional/nervous state of the body is selecting for these types of bacteria (and the bacteria is reinforcing/sustaining the emotional/nervous state).
I was reading the NeuroFeedback thread before this one, and wondering if (because of the gut/brain connection) things like gut bacteria would change as a result of changing the brains set state?
The NeurOptimal system looks quite promising based on peoples feedback so far. fwiw

I have been following them roughly, but not in much depth so I will need to go over the information at some point. I think what you said is possible and would probably make sense, and I never really gave it much thought before now - other than based on the effects of stress on digestive function etc. Agree that NeurOptimal looks interesting, and seems to be a fruitful endeavour for those with access to the system - especially long-term.

On the topic of my previous two posts

I contacted Dr Stephanie Seneff and asked her about my "theory" that dysbiosis is protective, and it turns out she was already 10 steps ahead! She is in agreement that gut dysbiosis/SIBO is protective in many cases, especially for autistic kids, and stated this in several papers within the last 5 years of so.

My idea that clostridia were (predominantly) selected for by autistic children because they produce hydrogen sulfide was incorrect, because the populations of clostridia populating the gut are not the major hydrogen sulfide producers.

Instead, Seneff explained that the dreaded "phenols" spoken about earlier in the thread (which mess with brain chemistry) are actually USEFUL, because they transport sulfate to the liver and manage to bypass glyphosate within the vasculature. However, they are also highly toxic when they have dumped off the sulfate, so it is a shabby backup mechanism.

Hydrogen sulfide producing bacteria do overpopulate the gut in times of sulfur deficiency, it is just not clostridia producing the hydrogen sulfide.

What does this suggest? ====> "Healing the gut" may be impossible if the body wants/needs inflammation in the gut.

Here is my experience: Since my gut has been good, my circulation in my hands has gotten seriously bad. My thoughts are that killing off the clostridia has put the brakes on my sulfate availability (probably due to glyphosate in the hepatic portal vein or something), so now my vascular system is feeling the hit.

I'm now starting to believe that trying to "outsmart" the body is a stupid idea.

 

[whitecoast]

Gut dysbiosis as a protective adaptation in certain circumstances?

This idea runs contrary to what I thought I understood about gut health, but there are some data to back it up:

The following study showed that pro-inflammatory changes in gut flora WERE NECESSARY to prevent metabolic dysfunction in obese rats:

To understand the biology behind this and for a great overview of the study, you can listen to this podcast by Chris Masterjohn PhD. here is an excerpt:

Basically, visceral adipose tissue requires inflammation to undergo remodelling so that it can store more fat. When it can no longer expand, metabolic dysfunction/syndrome ensues. The inflammation which helps the adipose tissue to remodel (and essentially prevents metabolic syndrome) come from the proinflammatory gut microbiome. Hence, the "dysbiosis" appears to be a protective adaptation, and so is the chronic inflammation for a short period of time.

Correct me if I'm wrong but that paper seems to be saying that adipose tissue is getting inflamed by dysbiotic xenotoxins, which causes it to restructure and expand to incoroproate and sequester those toxins away from more sensitive tissues. I'm not sure how that depicts dysbiosis as a protective adaptation, since it still seems to be the source of those toxins, at least in the scenario depicted.

 

[Keyhole]

Correct me if I'm wrong but that paper seems to be saying that adipose tissue is getting inflamed by dysbiotic xenotoxins, which causes it to restructure and expand to incorporate and sequester those toxins away from more sensitive tissues. I'm not sure how that depicts dysbiosis as a protective adaptation, since it still seems to be the source of those toxins, at least in the scenario depicted.

Adipose tissue needs to be remodelled so it can incorporate more fatty acids/triglycerides into its "shell". When excess fatty acids remain in the blood, this paves the way for ectopic fat accumulation, metabolic dysfunction, and fatty liver etc. Remodelling prevents that from happening, because it sucks up all that extra fat floating around in the blood to maintain homeostasis. If the adipose tissue can't remodel, it means that this fat cannot be sucked up and stays in circulation. So it was once thought that inflammation was solely BAD. However, this study was interesting because it showed that lipopolysaccharide coming from the gut and causing inflammation was necessary for the remodelling process - to prevent all of the subsequent metabolic dysfunction and ectopic fat.

Just to be clear, the source of the toxicity/burden was not the gut derived lipopolysaccharide. The toxicity was coming from over-feeding mice a fattening diet. The lipopolysaccharide coming from the gut was beneficial for the mice in this context.

Now, this study did not focus on dysbiotic changes in the gut microbiota. However, it provides evidence that LPS/inflammatory changes in the gut microbiota can be beneficial in some instances.

I'm not sure if you caught my article on this topic, but I will post a link to it below. After speaking to Dr Senneff and refining some of the ideas in this thread, I put together some information on how this may play out in real life. Here is an excerpt of a study demonstrating adaptive changes by the gut bacteria to produce extra hydrogen sulfide. FWIW, high levels of hydrogen sulfide are generally inflammatory to the gut, and are often involved in dysbiosis. They produce the horrid rotten egg smell, and other associated symptoms such as brainfog etc.

Another study titled “Eukaryotic and prokaryotic contributions to colonic hydrogen sulfide synthesis” (9) set out to measure the contribution of gut bacteria to the total quantity of hydrogen sulfide gas produced in the gut. The researchers fed one group of mice a normal diet, and fed the other group a vitamin B6-deficient diet. After two weeks, the fecal content of hydrogen sulfide was significantly reduced in the B6-deficient mice (which was likely due to the inhibition of CBS and CSE enzymes). Though, after six weeks the fecal hydrogen sulfide content returned to the same levels as the control group. In these mice, it is likely that the B6 deficient diet led to an increased growth of the “sulfate reducing bacteria” which are able to produce hydrogen sulfide gas without the need for B6 (9).The author of the study goes on to say:

“[these findings] may suggest changes in the microflora of these rats or in the production of H2S via alternative pathways by colonic bacteria.” ​

In other words, this was an adaptive response to make up for the deficit of B6 in the diet. The population of gut bacteria shifted to meet the needs of the host.

To read the whole article for an overview of the theory, you can find it here:
Sulfate IV: Chronic SIBO/Gut Dysbiosis As A Protective Adaptation To Supply Sulfate

 

[whitecoast]

Thanks for the clarification keyhole. I did some gut and organic acid testing, so I'm doing me best to try and grok all the information in here on how to best interpret the results. There's a lot of information to stay on top of.

 

[whitecoast]

I found a couple of interesting review papers talking about organic acid testing and what some it can indicate about cellular metabolism, detox, etc.

Clinical Applications of Urinary Organic Acids. Part 1: Detoxification Markers
Clinical Applications of Urinary Organic Acids. Part 2. Dysbiosis Markers
Some overlapping information was also contained in a powerpoint presentation here. It is just one lesson out of many though, so doesn't have as much detail.

 

[monotonic]

Keyhole, Ge-132 or Germanium Sesquioxide is said to improve or even cure Raynaud's syndrome. It basically releases oxygen while in the blood stream and can prevent hypoxia and preserve tissues during a stroke or other kind of circulation problem (also drowning). I'm not an expert by any stretch, but I thought I would throw that out there.