Discussion in 'General ME/CFS News' started by AndyPR, Feb 21, 2017.
This is an extensive piece. I have read about a quarter of it and now my brain has given up so I cant post anything worthwhile to a discussion, but i'll come back to it later.
I tried reading that article but gave up. I found it very confusing and my scientific/medical knowledge is not up to it. Are they saying ME is a form of sepsis?
I seem to remember the Melbourne group comparing some of the metabolic findings to sepsis and to starvation, whereas Naviaux compared it to hibernation. For me these are simply indicators that the metabolism isn't functioning normally. If by making parallels, new and fruitful avenues of research and treatment are opened up, that's good.
To be honest I gave up as well. One of the reasons for posting was in the hope that some our more scientifically minded and less brainfogged members could critique it for me.
From the article above-
Chris Armstrong said this-
Stanford University Medical Center paper-
Sepsis causes systemic inflammatory response syndrome (SIRS). Notice that Chris Armstrong uses the term "chronic sepsis", meaning ongoing. Also, the article above says "There are after all no biomarkers yet for SIRS, Sepsis or ME/CFS, and all three are diagnosed by symptomatic observation."
Chris Armstrong also thinks it's the (mild) sepsis that causes Immune system activation and oxidative stress, causing mitochondrial dysfunction. I think the oxidative stress also causes methylation dysfunction as well. It just makes sense to me (after 10 years of reading, research and thousands of dollars in supplements-lol) that a leaky gut is causing my symptoms. In my case the leaky gut was caused primarily by 30-40 courses of anti-biotics (EDIT-over many years) leading to severe dysbiosis and a leaky gut (mild sepsis).
ME is not like a systemic inflammatory response. Perhaps the most interesting finding from Mady Hornig is that IL-6 tends to be low - which would fit with ESR being low. I am afraid this is a hodge podge of all the usual trendy theories rolled into a quattro stagioni pizza. The one thing ME is not is sepsis.
A cunning and evil plan...
This article refers to Dr Bell's view that ME could be described as a 'slow sepsis'
My most positive traits I feel..
Thank you @Jonathan Edwards for the analysis, unfortunately I'm now hungry.
Slow sepsis could fit the bill as opposed to your typical doctor's assumption that sepsis has to be full blown and draw a powerful systemic response that can easily be identified through common blood work. Something which Maes has touched on in regard to ME/CFS that can't be ruled out until such time as there has been more extensive testing is that mesenteric lymphatics is a system that can spread bacteria which can spread to the blood circulation. It needs invasive laparotomy to get mesenteric lymphatic samples so not something that would fit into routine screening.
Intestinal ischaemia/reperfusion injury and barrier failure are generally implicated in the development of multiple organ failure as a major cause of SIRS in the critical care arena be it as a consequence of serious injury or post-operative complications. Researchers using more sensitive means has found that the mesentery lymph system can spread bacteria that is not detected in typical blood cultures.
Though widely reported in the medical literature, it is even lesser known that chronic intestinal (mesenteric) ischemia can occur with chronic GI dysfunction in an outpatient population in a wide variety of conditions including IBS and IBD, something which could be a means to infect mesenteric lymphatics. This ischemia is often microvascular in nature which also is very hard to establish as there is no gold standard test for detecting it.
[Many of these infections are initiated by translocation of intestinal bacteria and usually result in bacteremia and, in more severe cases, sepsis . Bacterial translocation can be demonstrated by analysis of mesenteric lymphatics or portal vein blood samples. It is important to point out here that, in a classic study, portal vein sampling in trauma patients undergoing laparotomy did not provide evidence for bacterial translocation by blood cultures . Subsequent studies with trauma patients confirmed that blood cultures generally failed to show bacterial growth [44, 45]. However, more sensitive methods, such as immunostaining for E. coli beta-galactosidase  or electron microscopy , provided direct evidence for bacterial translocation to mesenteric lymph nodes (MLNs) in most patients. While the presence of bacteria in MLNs as a pathological event has been debated [46, 47], multiple studies have shown that positive cultures from MLN samples obtained from laparotomy patients occurred in 10–15 % of patients, which correlated with an increased risk of postoperative sepsis [48, 49] or postoperative infection .]
One Maes study found that "loosening of the gut barrier may allow poorly invasive Gram-negative bacteria to translocate from the gut into the mesenteric lymph nodes and sometimes into the blood stream. Once translocated, the LPS is recognized by the Toll-like receptor 4 (TLR4) complex, which primes immune cells and consequently activates inflammatory and Oxidative & Nitrosative Stress pathways."
There is no such thing as slow sepsis, any more than there is slow high blood pressure. High blood pressure is not slow or quick, it is high. If the blood pressure is normal it is not high. Sepsis is the presence of high numbers of viable bacteria in blood (a tiny number get into blood in all of us) and high levels of LPS-responsive cytokines (we all have some cytokine circulating). In ME, blood cultures are negative and the relevant cytokines are NORMAL or LOW, so there cannot be 'sepsis'. Dr Maes has 'shown' nothing. He has merely speculated, based on some pretty unconvincing data not replicated by anyone else as far as I know.
The whole idea seems a bit like homeopathy - there is nothing there but it is wickedly powerful stuff.
I agree that there isn't such a diagnosis yet. There are however, 3 different levels of sepsis that are already recognized, sepsis, severe sepsis and septic shock - link
Here is a study from 2015 -
Edited to break up paragraphs.
There seems to be a significant correlation here to increased bacterial translocation in cfs patients after exercise and the PEM window of up to 3 days (72 hours), for many people with cfs.
This is a link to the full paper.
If you break up the longer paragraph, it makes for easier reading.
Edit. It's a good idea to mention that you've done this lest someone think you've done some "creative editing".
Yes I am familiar with that paper, but it does not actually say that ME patients have more bacteria than normals after exercise, as far as I am aware. It reports some differences between specific types of bacteria but who knows if these are important.
In any case this is not sepsis. We all have bacteria in the blood. I am pretty sure this study measured bacterial DNA, so there is no indication that the bacteria are alive. We need to be precise about this. When live bacteria in the blood make people feel ill the CRP level is sky high due to IL-6 production. In ME IL- 6 is not high, yet people feel terrible. It does not add up.
Fair enough, one can accept a medical expert's opinion that it is the wrong use of medical jargon to call it slow sepsis but splanchnic circulation is considered a major factor in spreading bacterial infection in the sepsis process however it is not fully elucidated how the sepsis process works even in an acute situation so, as that is where all the research focused, the possibility that it can occur by similar mechanism in chronic conditions too hasn't got a look in yet.
The physiological response is to prioritise blood flow to vital organs at the expense of the splanchnic circulation thus activating intestinal ischemia when the right conditions are met (likely to be microvascular ischemia which isn't fully understood either) and there are two hypotheses around the flow on effects of that, the ‘gut starter’ and the ‘gut motor’ hypotheses.
The ‘gut starter’ hypothesis is also called the ‘two hit model of MODS’ and focuses on the role of the neutrophil. Neutrophils are primed as they pass through the mesenteric circulation during reperfusion of the ischaemic intestine. They continue to circulate around the body in this primed yet inactive state until they are provoked by a second insult such as exposure to endotoxin 20. Priming of the neutrophil is initiated by mesenteric lymph rather than portal blood and it is the lipid fraction generated by phospholipase A2 that appears to be most important in priming neutrophils 21. Neutrophils primed in this way exhibit an increased oxidative burst, augmented release of proteases and cytokines 22, and reduced apoptosis 23 so becoming potent mediators of distant organ dysfunction when activated.
The ‘gut motor’ hypothesis focuses on the role of the intestinal barrier in the development of SIRS and MODS. When this barrier is disrupted the luminal content invades the portal venous and lymphatic systems. This translocation activates immune cells downstream from the intestinal mucosa, i.e. Peyers patches, macrophages in the lamina propria of the gut, mesenteric lymph nodes and Kuppfer cells in the liver. These activated immune cells release inflammatory mediators that drive the onset of SIRS and MODS even though a focus of infection may not be evident].
Is it possible then that PEM cause a diversion of blood flow from splanchnic circulation to preserve skeletal muscle and does that then lead on to the spread of bacteria in mesenteric lymphatics which can be activated into circulation by other insult.
If ME isn't sepsis, could it be Post-Sepsis Syndrome? I ask this since I imagine, unlike sepsis, PSS isn't characterized by high numbers of bacteria in the blood.
I am not sure what post sepsis syndrome is but I suspect it is the sustained catabolic state that can follow a large number of insults to the body, like surgery or trauma. That is not specific to sepsis and I cannot see the point in bringing in sepsis if we have good evidence that there is none in ME.
Chronic sepsis is just sepsis lasting along time, so it still has to be defined in terms of an increase in the number of live bacteria in the blood and an acute phase response via the LPS or related pathways. In ME we have clear evidence that these are not present. So it cannot be sepsis, whether acute, chronic, slow or quick.
Grumbling sepsis in bronchiectasis will produce a CRP level of 10 with the person feeling just slightly tired or off colour. With the level of symptoms in ME that confine people to bed one would expect a CRP of 50 if the problem was due to sepsis. And that is not the case. As I understand it PEM is a set of symptoms- an effect, not a cause. If sepsis were involved I would expect it to cause the PEM, not the other way around.
Whichever way one looks at it, ME is not sepsis.
As a person diagnosed with CFS over 10 years ago, my consultants in different specialities now believe I have had major episodes of sepsis. I have all the criteria of sepsis but never understood the difference between the 2 conditions. I have no medical background. Please could you advise me as to how I find out the difference. Each episode has been related to infection but caused confusion before symptoms were recognised. Due to 30 years ago being placed in a psychiatric ward with no tests done I've been treated as mental health as opposed to critical care. The psychiatrists at the time said they didn't know what was wrong and found no evidence of mental illness so called it an affective disorder.
In 2014 I was again admitted to a mental health ward to discover I'd had an e coli infection which caused the symptoms of sepsis. Again no testes were done for infection at the time. The psychiatrist said what I had was very rare and he called it 'brief psychosis' but he said others may call it something different. He said it was undoubtedly caused by the infection.
I had a kidney infection after youngest daughter was born 36 years ago but got antibiotics and sepsis symptoms definitely present on that occasion, with no confusion.
Each following episode my temperature drops well below 36 e.g. 34.5 last year but got antibiotics which cleared it before things became worse.
I know now that I have had infections each time and TIA with a throat infection, but not sure if that was connected just to the vascular problems. No confusion.
I don't understand the explanations above so wondered if you can help in layman's terms please Jonathan?
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