Discussion in 'BioMedical ME/CFS Research' started by Dolphin, Apr 14, 2020.
Some more information in English
Unfortunately it seems the full text of the thesis is under embago
Would have been nice to see the data in tables and figures.
35 people with Fukuda CFS, plus cohort of relatives living in the same houses and a cohort of healthy volunteers.
the dates are 2018-2019 on the above document, so it is not very recent. But their conclusion that ME may be autoimmune comes from this sentence:
"these results add new information and support the autoimmune hypothesis for CFS/ME condition in that in this study the intestinal microbial profile recorded in CFS/ME patients is consistent with that reported for autoimmune conditions, such as Chron’s disease (Manichanh et al., 2006), ulcerative colitis (Maukonen et al., 2015) and Systemic Lupus Erythematous (Hevia et al., 2014)."
There is discussion of leaky gut too, but I'm not sure how leaky gut is autoimmune.
published in Nature
Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is a severe multisystemic disease characterized by immunological abnormalities and dysfunction of energy metabolism. Recent evidences suggest strong correlations between dysbiosis and pathological condition. The present research explored the composition of the intestinal and oral microbiota in CFS/ME patients as compared to healthy controls.
The fecal metabolomic profile of a subgroup of CFS/ME patients was also compared with the one of healthy controls. The fecal and salivary bacterial composition in CFS/ME patients was investigated by Illumina sequencing of 16S rRNA gene amplicons. The metabolomic analysis was performed by an UHPLC-MS. The fecal microbiota of CFS/ME patients showed a reduction of Lachnospiraceae, particularly Anaerostipes, and an increased abundance of genera Bacteroides and Phascolarctobacterium compared to the non-CFS/ME groups.
The oral microbiota of CFS/ME patients showed an increase of Rothia dentocariosa. The fecal metabolomic profile of CFS/ME patients revealed high levels of glutamic acid and argininosuccinic acid, together with a decrease of alpha-tocopherol. Our results reveal microbial signatures of dysbiosis in the intestinal microbiota of CFS/ME patients. Further studies are needed to better understand if the microbial composition changes are cause or consequence of the onset of CFS/ME and if they are related to any of the several secondary symptoms."
It's actually Scientific Reports (a Nature Publishing Group journal), which is a journal that often publishes work rejected by the top-tier journals, such as Nature. But, it's still a high-profile journal.
What a waste of time...some people with CFS had different poo than some other people...this tells us very little I’m afraid. Especially at the genus level. The fact that they are talking about leaky gut is a red flag for me...trash upon trash.
classic end here caveating the whole thing ....not even interesting when we don’t even know what a healthy gut looks like and this is almost certainly decades away before we even have a proper reference.
All this can show is that some people with ME can have a different microbiome at any one point. With a disease that people have for years this sort of research can say nothing about conditions when things first went wrong.
A better approach would be to look at what happens if the gut microbiota are changed.
Most likely consequence not cause. Improvements following FMT should be permanent if it was the cause, but people who have trialed FMT and improved typically report they need to repeat the procedure to maintain benefits. I also can see how having autonomic dysfunction, restricted diets, limited activity and lots of other factors could have a big impact on the microbiome in ME/CFS patients.
Leaky gut is seen in many autoimmune conditions and is believed to worsen symptoms, and in the case of inflammatory bowel disease changing your diet can lead to remission (various methods, which if I remember correctly is mostly researched in kids - the theory being that the poorer results in adults is because of poor compliance). Of course, with IBD the actual problem is in the gut and many of the beneficial compounds found i foods can only work here (like some antioxidants that are not absorbed into the body, but can reduce oxidative/nitrosative stress in the gut).
I wish studies like these looked more at what lfiestyle factors could cause these changes, such as changes in dietary habits, oral care routines etc., agree with JES this is more likely a consequence not a cause.
I believe the evidence base for this is weak? ...could you post something that shows the evidence that so called leaky gut is responsible for symptoms in many autoimmune conditions? I see quite a bit of nonsense in this area quite regularly and I’m keen to see whether there is anything more tangible than I’ve seen so far (theory with not a lot of compelling evidence).
"Believed to" is not exactly arguing for a strong evidence base
It's present in many conditions, if I remember correctly some studies on rodents have shown impaired gut integrity occurs before other signs of disease manifests itself, but that's not saying much and might not be relevant in humans. In humans I've seen this one case study referenced a lot, a woman with inflammatory bowel disease (IBD) who showed impaired gut integrity before having a relapse of her condition, and then you have the (few) dietary intervention studies on IBD that focus on improving various aspects of intestinal health that can improve the condition and lead to remission - but again IBD is special. There was one study that tried one of these diets on Hashimotos patients and besides claiming they felt better on a questionnaire there was no improvement on objective disease markers besides a sligh reduction in high-sensitive CRP (which was already low in the participants).
So, not a lot of data, and depending on what you read a lot of hype.
Yes that’s pretty much what I see...an interesting anomaly that can’t quite be linked to anything in terms of causation or symptoms. I’ve also seen some studies that look at the rise of non coeliac self-reported intolerance claims (sharp rise over the last 10 years or so) and try to link it to gluten sensitivity and then leaky gut but so far these are only a few weak self reported surveys that don’t even show that the diet changes are down to gluten as opposed to anything else (e.g. lower starch/just altering gut biome by change in diet).
I agree Coeliac and possibly Crohns are going to be different due to observed damage to gut lining/difficulty absorbing nutrients.
But coeliac cases are not on the rise it’s this pesky sensitivity without inflammation that seems to be causing the rise in the popularity of leaky gut, despite there being no direct evidence.
A few human studies which so far are just self reported questionnaires following a non supervised diet change doesn’t seem to say anything. Doesn’t stop people muddling causation/correlation though. It would be good to have a few studies that actually had some objective measures.
Gliadin in gluten can change tight junction expression levels and/or localisation at the cell membrane by stimulating zonulin expression, causing "leaky gut". Increased zonulin has been found in non-celiac-gluten-sensitivity, and some (not all) patients have anti-gliadin antibodies, I think I've seen ~50% mentioned in studies.
A problem is that if one doesn't react to gluten, but something else in grains (trypsin inhibitors or FODMAPs comes to mind) or are lacking in protective factors (certain vitamins/minerals are important for the integrity of our epithelial barriers, and some compounds found in different foods such as isoflavanoids could also be protective if the concentration is high enough, maybe also compounds secreted by certain bacteria), just removing wheat, barley and rye is not going to fix things.
This study found increased levels of zonulin in their non-celiac gluten sensitive participants.
AC = Asymptomatic controls, IBS-D = Irritable Bowel Syndrome D-type, NCGS = Non Celiac Gluten Sensitivity, CD = Celiac Disease
However in the same study, the subsample (of which 3/4 had been part of a previous study by the same authors) that followed a gluten free diet for six months did not change their zonulin levels in a significant way (how well they followed the diet is unknown, though, it's only stated that they were asked to follow a diet free of "wheat, rye and barley". Many people need a bit more guidance than that):
To me, we know too little about these people's diet to say if going gluten free has any point, I would be worried they are consuming a less nutrient dense diet after going gluten free as many gluten-free replacement foods have appalingly low nutrient quality. If gut dysbiosis was the initial problem (bacteria has also been associated with increased levels of zonulin, at least in cell culture) going gluten free is not going to solve the issue, and I'd say especially not a nutrient poor gluten free diet (how much cr*p is sold as "healthy" because it has a "gluten free!" label on it?).
Yes but zonulin as a biomarker has been hotly disputed with other studies calling the validity of it into question.
This is about the non specificity of the assays as the main point I think (feels sort of valid). I’m not sure what assay the above study used?
Yes agreed it is clearly not as simple as being portrayed. I think flavanoids also has quite a bit of guff around it...last I heard, the amounts you would need to be “protective” (not that there is any clear evidence for the actual amount or it being directly beneficial) is beyond our natural diet concentration anyway or just plain impractical to apply and would cause imbalance in the diet that would probably lead to malnutrition. Most of the work on this stuff is quite early days from what I’ve read?
I agree though that there may be something in eating an imbalanced amount of wheat-based products (perhaps together with a lack of fibre from fruit and veg) initially that may just push things out of whack. Phytic acid is something often touted as bad but I’m thinking very few of us eat wheat or wheat flour raw without it being baked or processed first so that also feels like a blind alley. Fodmaps are also a bit strange. I think a lot of the noise has spun out of the use of high fructose corn syrup in the states (and then subsequently branched into oligosaccharides etc). The science is shaky here too, and appears to be more misinformation using correlation studies and a bit of pseudoscience around normal organic molecules naturally found in a wide variety of foods we should be eating for a balanced diet.
However there are enough reports of people feeling better on a gluten free diet or after doing a low fodmap diet to suggest there is something going on. I think this may then take us back to gut flora where the change of diet restores or partially restores an imbalance. Also there is secretion regulation as another possible contender? People with pernicious anaemia often have problems with IBS symptoms which is put down to low stomach acid causing imbalance in the flora in the upper small intestine. A key “stress” response is to halt digestion temporarily (particularly stomach acid secretion) to divert energy away from digestion. Perhaps this off and on response makes for a disrupted gut flora? That might explain why ibs pops up in a variety of different chronic conditions? All speculation though...we need much better studies on diet over time together with objective as well as subjective studies.
yes it is ironic that many gluten free foods just replace wheat with corn flour which would be pretty pointless if gut flora and too much readily available starch were the main problem?
Another problem is that zonulin is expressed by other cells as well, and when you look at the serum you would not know if it comes from the gut or from say adipose tissue.
The study I mentioned used an ELISA kit from Cusabio. I'm not familiar with it. I do wholeheartedly support more focus on looking at actual tight junction proteins in the gut, but there is a slight peoblem with this as it's not just the amount of tight junction proteins that is important, but how they are organized at the cell membrane. Just looking at expression levels can give the wrong impression, so as they suggest in your letter, it should be combined with dual sugar test.
I've heard different stories on this, with some arguing that it is possible to achieve high enough concentrations of these compounds in the gut for them to have an effect on tight junction proteins (I think based on the concentration needed in cell-studies to cause an effect, possible also rodents). I'm mostly familiar with Norwegian diets, and the generic Norwegian person would probably not consume a high amount of flavanoids, and it might be impractical to change the diet in such a way to increase flavanoid intake (that said, the Norwegian government are really keen on us increasing our intake of whole grains, legumes, nuts, fruit and vegetable intake). An issue for me is that focus is usually on a select few of these compounds, likely because they are easy to work with and research has been done previously and can be used in funding applications. When it comes to flavanoids and tight junctions I guess it could be said it's early days, flavanoids and health in general is older.
Phytic acid has some good and some bad qualities, some claim it protects against cancer (but I don't remember if that was baed on observational studies where diets rich in phyitc acid of course is also rich in fiber and quite likely fruit and veg). When it comes to FODMAPs I'm a bit torn, I do believe the low FODMAP diet is useful for some, but some of the trials done to prove people are reacting to FODMAPs and not gluten (or something else) are just not really showing that. There is also the problem that people forget that with a low FODMAP diet, there is a very important step of reintroducing foods after following the diet for a while, it's not supposed to be a life-long diet like gluten free for celiacs.
Yes, that is a very interesting point and I've been thinking the same. I do wish for better studies on nutrition, the field has so many problems
And likely add some gum or other thickener that may or may not be problematic (carrageenan comes to mind). Zero nutritional value. It's frustrating when studies on nutrition and diet change don't actually say what the participants ate, I need a bit more than "gluten free" to make an assessment on diet quality and nutrient status.
yes that’s my main problem with the whole thing, the way it’s misused/misrepresented ...I think the original intention was 8 weeks abstinence followed by slow reintroduction (can’t remember exactly)...I.e just long enough time to reset gut flora ?
A big problem with gums and thickeners (e.g. carrageenan and the galactomannans such as guar and locust bean) is their slimy texture in the mouth. The main challenge really is trying to replace starch as well as gluten and how it cooks. I spent around 5 years as part of a bio polymer research team back in the early 90’s ...there was nothing really available at that time that could mimic the way starch/gluten worked together in baked products. I think we came to the conclusion then that we would need “more research” into protein polysaccharide interactions. Fundamentally starch is unique in how it hydrates and cooks out. There are different types in terms of amylose amylopectin ratios but regardless of this, it’s pretty challenging to replace in recipes.
what should be possible is leveraging the film forming and gelling properties of some of the gums and stabilisers to improve satiety and speed of nutrient absorption. I think there should be a lot of mileage to further the b-glucan work and how other polysaccharides/polysaccharide molecular weight fractions may affect the coating effect in the gut and how this may affect speed of absorption. The ‘slimy mouth’ challenge is still there though, but I guess that is subjective and the quantities needed are not fully understood yet? But I digress completely away from the thread subject.
I have been gluten free for years. The simplest way to create gluten free diets is to eat naturally gluten free foods, not try to manufacture imitations of gluten containing products. Just as with vegetarian and vegan diets, there is no need to try to manufacture imitation meats.
So you don’t eat baked products with starch in them?
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