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“The Subset Maker”: Lipkin Chronic Fatigue Syndrome Study Highlights Energy Issues In Gut Subset

Looking for clues to the cause of chronic fatigue syndrome (ME/CFS), Ian Lipkin has, over the years, poked his fingers into a number of different areas. His 2012 XMRV study showed that the virus was not infecting people with ME/CFS. (It was a contaminant). His pathogen studies (unpublished) found no evidence of a viral infection in ME/CFS.

Subsets

Lipkin may have uncovered more potential subsets than any other researcher and has long emphasized the need to break ME/CFS up into its constituent parts.

lipkin subsets ME/CFS

Lipkin believes identifying subsets is critical to the progress in this field

Lipkin and Mady Hornig’s 2015 cytokine study  which found the immune system going gangbusters early in ME/CFS but then pooping out, exhausted, later identified two possible subsets (early and long duration patients.) Lipkin then teamed with the Simmaron Research Institute to document similar findings in chronic fatigue syndrome (ME/CFS) patients’ spinal fluid.  Dr. Peterson, Lipkin and the Simmaron Research Institute then uncovered an atypical ME/CFS subset (the “Peterson subset”.)

In an email Lipkin emphasized the critical need to identify the subsets he believes must be present in this disease.

ME/CFS is not a single disorder and is unlikely to have  single cause or a single treatment. As we learn more about ME/CFS, we are beginning to define subtypes. This is critical to understanding how people become ill and developing practical solutions for management. The challenge is not unique to ME/CFS. It is representative of the Precision Medicine initiative that is sweeping clinical medicine and public health. Just as there is no one cause or cure for all cancers, all forms of heart disease, or all infections, there will be more than one path to ME/CFS and more than one treatment strategy.

Over the past couple of years Lipkin – who has been intensely interested in the role that gut bacteria plays in this illness – has been digging into an ME/CFS plus irritable bowel subset. We’ve learned in the past ten years just how influential the gut is. Gut bacteria and the metabolites they produce don’t stop at the gut. If they leak out of the gut they can directly affect the immune and central nervous system functioning. Some of the metabolites showing up in ME/CFS metabolomic studies originate in the gut.

Last year Lipkin’s group published the most comprehensive gut bacteria study in ME/CFS yet done, which incorporated immune and clinical findings. This year he repeated the gut bacterial analysis and added metabolomics  and clinical findings to the mix. The man clearly likes large, complex studies.

The 2017 Gut Study

The large 2017 Nagy-Szakal/Lipkin gut study was notable for it’s size (n=100) and it’s breadth – it included patients from no less than six ME/CFS practitioners including Dr. Peterson. It found, amongst other things, increased levels of bacteria from a family (Clostridiaceae) known for its abundance of toxic and disease causing bacteria.

One of the few gut studies that’s actually been able to identify individual bacterial species, the study found increased abundances of several bacterial species (Faecalibacterium & Coprococcus spp.) that have been associated in other studies with IBS-like symptoms, including colonic pain, bloating, and GI discomfort.

Using a type of data analysis called topological data analysis (TDA) which is able to incorporate metagenomic, metabolic pathway, immune and clinical data, the Lipkin group found that the presence of irritable bowel syndrome (IBS) was having a major effect on disease severity, gut microbiota, and immune profiles.

That finding led the Lipkin group to split the ME/CFS patient cohort into ME/CFS with IBS and ME/CFS without IBS subsets and examine the differences in microbiota (gut bacteria).

gut bacteria ME/CFS

The gut bacteria in the ME/CFS plus IBS subset was different from the ME/CFS only group and the healthy controls

The results were astonishing. A dissimilarity measure found that gut bacteria differed as much between the ME/CFS + IBS patients and the ME/CFS – IBS patients as between the ME/CFS group as a whole and the healthy controls. That analysis suggested that the guts of the ME/CFS patients with and without IBS featured significantly different bacteria.

The cytokine data in the study did not add to the analysis but the microbiome analysis revealed a number of interesting possibilities,

Metabolic pathway analyses revealed the ME/CFS + IBS and the ME/CFS – IBS groups differed in some important ways. Both groups featured enriched metabolic pathways that produced Vit. B6, but an important part of the energy production process (the pyrimidine ribonucleoside degradation pathway) was enriched in the ME/CFS only group. That same pathway was hit hard in the ME/CFS plus IBS group.

Plus, the abnormalities found in the urea cycle, which is closely linked to aerobic energy production (Krebs or TCA cycle)  occurred mostly in the ME/CFS + IBS group.

The data suggested that people with ME/CFS and IBS group had different bacterial gut makeups and might have more problems with energy production than people with ME/CFS, and it set the stage for Lipkin’s next effort.

The 2018 Gut and Metabolomics Study

Sci Rep. 2018 Jul 3;8(1):10056. doi: 10.1038/s41598-018-28477-9.Insights into myalgic encephalomyelitis/chronic fatigue syndrome phenotypes through comprehensive metabolomics.  Nagy-Szakal D1, Barupal DK2, Lee B1, Che X1, Williams BL1, Kahn EJR1, Ukaigwe JE1, Bateman L3, Klimas NG4,5, Komaroff AL6, Levine S7, Montoya JG8, Peterson DL9, Levin B10, Hornig M1, Fiehn O11, Lipkin WI12.

After striking that rich vein, the Lipkin group expanded their research effort – incorporating metabolomics for the first time into their studies. (Lipkin and the Simmaron Research Foundation are also currently engaged in the first metabolomics spinal fluid study.) Once again incorporating a wide variety of doctors from different locations (Peterson, Bateman, Klimas, Levine, Montoya) and using a fairly large sample set (n=100) Nagy-Szakal/Lipkin, the Lipkin group fused together blood metabolomic, fecal bacterial metagenomic, and clinical data to paint a new picture of ME/CFS.

The study represented the first attempt to meld two potentially important fields in ME/CFS – metabolomics and gut microbiome findings- together.  Lipkin and Hornig have proposed that the gut issues play an important role in ME/CFS, and several studies have found evidence of dysbiosis (pro-inflammatory gut bacteria) in ME/CFS.  Unutmaz is chasing down a T-cell gut connection, and past studies have suggested that bacterial leakage from the gut could help explain at least some of the post-exertional malaise present.

Given the group’s past gut findings – that significant differences in gut bacteria, immune profiles and possibly energy production exist between ME/CFS + IBS patients and ME/CFS patients without IBS, it made sense for the Lipkin group to once again split the ME/CFS group into subsets with and without IBS and analyze the heck out of them.

Study Results

Energy Production Problems Highlighted

The study confirmed past general findings of decreased levels of phospholipids and sphingomyelins – two important findings by Naviaux- and increased levels of triglycerides (TG’s). (Triglycerides have been associated with metabolic problems and hypothyroidism.)

That both the ME/CFS + IBS group and the ME/CFS without IBS group had reduced levels of metabolites associated with the choline-carnitine energy pathway suggested that both groups had similar core metabolic problems.  (Carnitine participates in the TCA cycle, ATP production and energy metabolism).

More Was Better

The Lipkin group’s decision to integrate metabolomics, microbiome and clinical data worked. Not only did incorporating all this data together illuminate a possibly important subset – the ME/CFS IBS subset – but it also allowed the group to better differentiate ME/CFS patients from controls. It suggested that studies which combine multisystemic data together will do a better job in describing this multisystemic disease.

As with the 2017 study, having or not having IBS was the biggest driver in determining the kind of bacterial profile (and bacterial metabolic pathways) present. This time the study found that the metabolomics of the ME/CFS + IBS group were significantly different from the ME/CFS only group as well. That suggested these two subsets of ME/CFS patients might be quite different indeed.

In contrast to Naviaux, the study did not find a “consistent decrease” in ceramide metabolites – the most commonly disrupted metabolite Naviaux found in his ME/CFS group.  When Lipkin controlled for IBS, he found increased levels of ceramides in the ME/CFS plus IBS group but decreased levels of ceramides in the ME/CFS only group. That suggested that key metabolites in ME/CFS might be different in these two ME/CFS subsets.

The Core Problem in Chronic Fatigue Syndrome Identified? Naviaux’s Metabolomics Study Breaks Fresh Ground

Bacterial Toxins Highlighted

Nagy/Lipkin suggested that increased levels of bacterial toxins (IBS connection) in ME/CFS may be triggering an enzyme called sphingomyelinase to produce the ceramides which then may damage the gut lining and possibly interfere with energy production.

gut metabolomics ME/CFS

The metabolomic analysis suggest unique metabolic problems may be present in the ME/CFS plus IBS group

Ceramides are waxy fats that figure in a number of processes that may be important in ME/CFS. Not only can they produce many free radicals (reactive oxygen species) that can damage the gut lining (the IBS connection), they can also interfere with electron transport (the energy connection) as well as contribute to insulin and leptin resistance (metabolism issues).

The authors also proposed that the higher mannitol levels found in the ME/CFS could reflect the breakdown of two important barriers in the body: the gut barrier and the blood-brain barrier.

Several studies suggest a breach in the gut barrier could be contributing to systemic inflammation in ME/CFS, and one suggests that exercise may further widen that breach. Several researchers, including Jarred Younger and Avindra Nath, have also postulated that the suspected neuroinflammation in ME/CFS results from immune cells entering the brain through a weakened blood-brain barrier.

The Gut Shines in Distinguishing ME/CFS Patients From Healthy Controls

Interestingly, for all the focus on metabolomics, a network analysis using differences in gut bacterial abundance was better able to distinguish ME/CFS patients from healthy controls than did metabolomic results.

That suggested that gut bacterial differences may be more prominent than metabolomics differences in ME/CFS patients. That was a surprise, and we’ll see how this all turns out. It stands to reason that the closer we get to the core of the problem, the more striking the differences we’ll see between healthy people and people with ME/CFS.  (Will the gut play a bigger role than we thought?)

Possible Treatment Options

The group suggested that their findings, if validated, could present some possible treatment options. They included using SMAse blockers to reduce ceramide levels and giving carnitine supplementation to increase the low levels of metabolites in the choline-carnitine pathway.  One open-label study found that carnitine supplementation helped over half of ME/CFS patients.

Given the unrevealing cytokine data from Lipkin’s cytokine data and his recent turn to metabolomics I asked Lipkin how important a role cytokines were likely to play in future ME/CFS research and treatment. Lipkin felt they may yet play an important role in ME/CFS indeed:

“Cytokine disturbances can result in fatigue, cognitive and other disturbances. The observation that other biomarkers such as metagenomic or metabolomic profiles are highly associated with disease does not diminish their (cytokines) importance. There may be people who would benefit from drugs, including antibody therapies, that modulate cytokine responses.”

Scheibenbogen is pursuing antibody therapies in ME/CFS, and Nancy Klimas is reportedly using Enbrel (etanercept) – a cytokine (TNF) blocker – plus mifepristone in her Gulf War Illness trial. Other biologics are available and more are coming on the market.  Recent findings in POTS suggest that antibody drugs will probably play an important role in that disease as well.

Since the study also found that taking Vit. B supplements was associated with higher levels of pantothenic acid and lower fatigue scores, taking Vit. B supplements may be a good idea.

The 5-MT Question

Decreased levels of 5-MT, a metabolite associated with tryptophan, serotonin and melatonin metabolism could reflect problems with serotonin/melatonin conversion. This finding, however, was confounded by the high use of antidepressants (50% of the ME/CFS group) which could have produced the decrease.

Correlation studies do suggest, though, that low 5-MT levels could contribute to problems with cognition, sleep and fatigue. Larger studies are needed to determine if the low 5-MT levels are associated with those symptoms in ME/CFS – and if they are – if it might be beneficial to modulate that pathway using drugs in ME/CFS.

Next Up for the Simmaron Research Foundation and Ian Lipkin

The next phase in the Simmaron Research Foundation’s ongoing collaboration with Ian Lipkin is an expanded study which will, for the first time in ME/CFS, analyze the metabolomics of ME/CFS patients cerebral spinal fluid. The study, which will also include immune analyses is the third Simmaron/Lipkin CSF study to date. The first two studies found dramatic evidence of immune activation and the presence of a potential new subset.

Simmaron’s Spinal Fluid Study Finds Dramatic Differences in Chronic Fatigue Syndrome

Lipkin also reported rapid progress from his new NIH research center and a new collaborative effort with ME/CFS researcher and NIH ME/CFS research center leader Derya Unutmaz. The idea of two top labs in the country collaborating in a complementary fashion is an exciting one – one we will hopefully see much more of in this field.

Lipkin and Unutmaz are merging their respective strengths in a collaboration – something we could use much more of in ME/CFS.

We are completing analysis of saliva, blood, and feces for bacteria, viruses and fungi from ME/CFS and control subjects using powerful new sequencing methods. This will be the largest and most comprehensive study to date on the microbiome in ME/CFS. We will soon begin metabolomic, proteomic, and transcriptomic analyses of ME/CFS and control subjects before and after exercise. We are deeply grateful to the patients who are contributing to this work despite the implications for their health. They are true heroes.

We have begun a new collaboration with Derya Unutmaz and Jackson Laboratories that builds on the complementary expertise of our teams in cellular immunology and molecular microbiology and biochemistry.

Dana March and Tony Komaroff are building an app to help ME/CFS subjects and their caregivers track their status. We have had great support in this effort from people in the community.

Conclusions

In the past three years Lipkin’s identified three potential subsets (early/late duration patients, the “Peterson subset”, ME/CFS + IBS subset) and his explorations into the ME/CFS IBS subset continues to reap dividends.

Lipkin has been a vocal advocate for ME/CFS

Dr. Ian Lipkin, Center for Infection and Immunity, Columbia University

His metabolomic study found signs of energy production problems in all ME/CFS patients, but when Lipkin separated out the ME/CFS + IBS patients, he found altered, even at times opposite metabolic findings that could suggest a different source of fatigue was present in the ME/CFS + IBS patients. His earlier study suggested more severe energy production problems may be present in ME/CFS patients with IBS.

The importance of the gut bacteria in ME/CFS perhaps rose to a new level of significance when a network analysis found larger differences in gut bacteria than metabolites. Lipkin’s ability to better differentiate ME/CFS patients from healthy controls using gut bacteria, metabolomic and clinical data suggests that large studies which tie together multiple systems will be the most helpful.

In short, the latest study from the Lipkin group indicates that the gut does matter in ME/CFS and that in those with gut problems it may matter more than we think.

The Simmaron Research Foundation and Lipkin are employing metabolomics in the study of cerebral spinal fluid for the first time, and Lipkin has launched a new collaborative ME/CFS effort with fellow NIH ME/CFS Research Center leader Derya Unutmaz.

 

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33 Comments

  • Nicki

    July 31, 2018 at 1:49 pm - Reply

    The gut ‘may matter more than we think’…. I and MSN other m.e people have been saying this for years! At what point will we be listened to?? I’ve said it since I got poorly over 20 years ago!

    • Cort Johnson

      July 31, 2018 at 3:42 pm - Reply

      We shall see. It’s certainly clear that the gut is an issue. It’ll be interesting to see how it all fits together. Good for Lipkin to delve into this area. You might want to check out this probiotic recovery story – https://www.healthrising.org/blog/2016/01/07/probiotics-cure-my-chronic-fatigue-syndrome/

      • Carol

        August 1, 2018 at 6:25 am - Reply

        Hi. My daughter had rapid onset of symptoms with severe nausea making it impossible to eat. Then as her illness developed (has CFS diagnosis), IBS symptoms became evident. Started using probiotics which improved her IBS (as well as significant skin rashes) but has since changed to having sauerkraut in her diet.

  • konijn

    July 31, 2018 at 2:30 pm - Reply

    thank you cort for giving me a little bit of hope to survive until there is 1 or more treatment(s). I am now 99% bedridden and in very bas shape. Even beginning having trouble with eating.

    Have you any idea when all this research will translate into treatment? I just hope to survive until there is a treatment but research is so slow and treatment even slower.

    They are talking about the IBS-ME-cfs group, etc but my pre-illness started with recurent gastritis with later vomiting and even now I have problems with that because off the heat. the gastritis is probebly caused by slow gastric gut emptying. But have you heard maybe something of Dr Chia and his work on enterovirus in the stomach? Is he still doing research?

    I also was treated 1/2 year with antibiothics and had to take all the time something against diahrrea. It left me mostly bedridden and a bit wheelchairbound. And with much more complaints that never went away anymore. So good for my gut, it will not have been!

    thanks again!

    • Cort Johnson

      July 31, 2018 at 4:06 pm - Reply

      I’ve heard swallowing can be an issue if you’ve been bed bound for awhile. Something about muscle problems and perhaps posture. There are exercises to assist swallowing – https://www.youtube.com/watch?v=H4S1Afq4fps

      So far as I know Chia is still doing research but I haven’t heard anything from him in awhile. It would be good to get in touch with him.

    • Cort Johnson

      July 31, 2018 at 4:11 pm - Reply

      I forgot to mention that Dr. Hanson is doing a fecal transplant study with a European group. Even it it’s just partially successful that would surely particularly for people like you who are having such a difficult time.

    • Gemini

      July 31, 2018 at 7:26 pm - Reply

      Last month at the 2018 Iime Conference in London Dr. Maureen Hanson at Cornell stated Dr. Chia will be collaborating with her and her research team. This is very good news.

      • konijn

        July 31, 2018 at 7:41 pm - Reply

        thank you gemini for reminding me. I saw the DVD’s but am way to ill to remember.

        It is good that docter chia is finally in the running with his enterovirus in the stomach.

        thank you cort for all you’re responses.

        • Gemini

          August 1, 2018 at 1:47 pm - Reply

          konijn, I hope you’re feeling better soon.

  • Erik Johnson

    July 31, 2018 at 2:41 pm - Reply

    I can’t express how glad I am to have just paid attention to the actual evidence at Ground Zero for CFS…

    And not to these totally insane doctors.

  • konijn

    July 31, 2018 at 2:59 pm - Reply

    why do they go from one research to the other instead off looking for treatments about what they found?

    • Cort Johnson

      July 31, 2018 at 4:15 pm - Reply

      Lipkin always keeps his eye on possible treatments given his findings but I think the answer is that the field just hasn’t settled and focused on one area. When it does the search for treatments will gain real intensity.

      That said Jarred Younger recently told me he’s been approached by five or six small drug companies that are interested in ME/CFS over the past year. The Cortene trial is beginning soon and Ron Davis is or will be, I believe, assessing drug effectivness in the lab using the nanoneedle. Plus Dr. Klimas will hopefully get her small ME/CFS trial going.

      Don’t give up hope!

  • Issie

    July 31, 2018 at 3:21 pm - Reply

    I’m sure that gut ecology plays a part in our overall immune system function. I recently completed testing with Thyrve labs and found its findings very educational. They give you percentages of bacteria and tell you which ones are low. Then they give you list of foods to eat to correct the problem.

    I also have pending results with uBiome. Will be interesting to see their findings. Another piece to the puzzle. For sure, my issues, are varied and complex. There is no just one thing. As the puzzle pieces fit – and I work on them – I improve.

    Issie

    • Cort Johnson

      July 31, 2018 at 4:16 pm - Reply

      Is that Kent Lassesen’s site? I’m going to have a blog on that coming up. Interesting stuff!

      • Issie

        August 3, 2018 at 5:22 am - Reply

        We just loaded my Thryve data into Ken site. Is that ever enlightening. I’ve got a lot to work on. This could explain family history with things. Some of my deficiency indicated certain illness that is in my family – but I don’t have. It also gave me suggestions of foods and supplements to try to balance out things as a whole. I’ve got to do more study on this. It’s over my pay grade and with my brain fog not so good these days……it’s a challenge. I have to thank Ken for his amazing work and talents. This should help a lot of people.

        Issie

      • Maximilian Kohler

        August 4, 2018 at 4:58 am - Reply

        Regarding Ken’s site, I would recommend reading this first: https://old.reddit.com/r/HumanMicrobiome/comments/8rivhi/my_conversation_about/

        • Issie

          August 4, 2018 at 5:45 pm - Reply

          I appreciated reading your comments. I am waiting on a uBiome test to compare to my Thryve testing. Taken at same time from same sample. I really like the Thryve report as it gave all sorts of foods as the suggestions of how to “fix” findings of low strains. It didn’t give odd suggestions that I’m told uBiome gives. Though I find those suggestions interesting as they give medicines that can change microbiome and explains why I got some positive results with some of them in the past. I look at it as a whole and analyze what may be of use or not.

          Kens site compared my findings to known illnesses and what is found high or low in those people. Although I don’t personally have some of the illnesses it suggest. It is in my family. That could explain why certain illness is found in families. We probably all have similar gut ecology from foods we eat and our environment. Also they know that our perceptions and thought processes can affect that ecology. It proved to be enlightening to me. If we don’t change what we’ve been doing for generations (foods, medicines, environment, perceptions) then nothing will change. It remains the same. Diet is one thing we can change. Some of the lows that I got with my Thryve test, I don’t find supplements to address. But there are foods.

          I realize this is all in its infancy and we are just learning about ratios and their meanings. But I think this may be a field we can address with whole foods and detox and may get some good results from that.

          Issie

    • Issie

      July 31, 2018 at 4:54 pm - Reply

      Ken site can analyze the data that either of these labs provide. You have to get the testing first.
      Issie

  • elvira

    July 31, 2018 at 3:34 pm - Reply

    Seems that the traditional Chinese medicine, as well as the old Ayurverda medicine knew that almost every disease starts in our guts. Harvard University study now connected gut bacteria with bi-polar disease. I suppose more about our gut bacteria will come with more studies. I wonder how is the serotonin syndrome connected to ME/CFS +IBS. Mine is triggered even with food containing a lot of tryptophan.

    • dejurgen

      August 1, 2018 at 10:32 pm - Reply

      “I wonder how is the serotonin syndrome connected to ME/CFS +IBS.”

      Would your serotonin syndrome episodes go hand in hand with fast bowel movements? Serotonin can speed up bowel transit a lot if the food in the bowel is deemed toxic by the body. See https://en.wikipedia.org/wiki/Serotonin#In_the_digestive_tract_(emetic):

      “Platelets in the veins draining the gut collect excess serotonin.

      If irritants are present in the food, the enterochromaffin cells release more serotonin to make the gut move faster, i.e., to cause diarrhea, so the gut is emptied of the noxious substance. If serotonin is released in the blood faster than the platelets can absorb it, the level of free serotonin in the blood is increased. This activates 5-HT3 receptors in the chemoreceptor trigger zone that stimulate vomiting.”

  • Cort Johnson

    July 31, 2018 at 4:18 pm - Reply

    Check out Dysautonomia’s doctor map her – http://www.dysautonomiainternational.org/map.php?SS=3

  • Alison Wiltbank

    July 31, 2018 at 10:15 pm - Reply

    Cort, again thank you for all your hard work on our behalf. I have had FM/CFS since my 30’s and IBS since my 20’s. I’ve always known they were connected and my own history bears that out. I got diagnosed after having 2 bouts of bronchitis in 6 months and 2 10 day courses of augmentin, followed by a car accident that put me into a fibromyalgia crisis. After a physical therapy program and getting a dog, which forced me to walk daily, and removing wheat from my diet, I was doing fairly well in my 50’s. My husband and I went to Africa, specifically Uganda, and I turned out to be a malaria magnet. I took doxycycline for a year as a malaria preventative, but had to stop because it was messing with my fibromyalgia. When I first went, I could walk 2 miles easily. At the end of 7 years there, I could hardly move. I came back to the US to have a stent and decided not to return. I’ve been trying different diets to see what they would do. Gluten free vegan, which I did for a year, was the best. I lost 50 lbs and was able to walk again. I’ve done 2 years of GAPS, which helped me in stage 1 but once I started adding back foods, it stopped helping. I’ve done 8 months Body Ecology but that didn’t help. I’ve eaten raw organic kefir to improve my gut biome, and done other things. I wish someone would tell me what to eat! I’ve long thought that fecal transplants would be the ultimate cure. I’ll be interested to hear the results of that European study.
    Incidentally, according to Dr. Natasha Campbell-McBride, author of the GAPS diet, a disordered gut biome is responsible not only for bi-polar disease, but autism, schizophrenia, ADD, and ADHD. She also maintains that all the current autoimmune diseases are coming from a disordered gut biome and it makes absolute sense. We have all been brought up on sterile foods, been given antibiotics multiple times, and are addicted to sugar. Is it any wonder that our gut biomes are in disarray? We have dinked with thousands of years of crop growth management and food culture that worked, and are a nation of sickies as a result.

    • Cort Johnson

      August 1, 2018 at 3:55 pm - Reply

      Yes, I wish we knew what to eat. Ken’s microbiome analyses will help. I will have a blog on that soon.

  • Carolyn Richards

    July 31, 2018 at 11:22 pm - Reply

    I am probably a crazy person but think there is still a common denominator. We of course may all go different ways dependent on genes. People who have HIV die from a number of disorders (technically from HIV). Instead of being a subset IBS may be one of the phases. I guess if the person does not overexert they may stay in that phase but if they push themselves it may push them into another. I have been through several exacerbations & talked to others who have been ill for a long time. Once we lost ground we never gained it back & got worse. I still have IBS but am also in the atypical group & had almost all of the different precipitators.

    • Cort Johnson

      August 1, 2018 at 3:53 pm - Reply

      I imagine there are multiple pathways to ME/CFS which end in a similar looking end state. Gulf War Syndrome looks like ME/CFS symptomatically – it’s almost almost and exact match – but Nancy Klimas’s studies indicate that something very different is going on.

      • Carolyn Richards

        August 2, 2018 at 4:48 pm - Reply

        What I find interesting is that Klimas diagnosed me 21 years ago (in her words) “one of the sub-sets. Indicated I was “on the far end”. Sad that subsets were know way back then & 20 years later just now being investigated. It is interesting to see all of the repetitiveness in some of the older studies. Too bad our system alienated Paul Cheney who found numerous discrepancies.

  • Guido den Broeder

    August 1, 2018 at 9:51 am - Reply

    Obviously of you group ME and CFS together, then ME will be a subset of the total. It is, however, much better not to conflate them to begin with.

  • PamC

    August 1, 2018 at 6:49 pm - Reply

    Thank you Cort for a great write up. I can relate so much to the issues with the gut and I believe I have every one of the issues with the disordered bacteria in the gut Dr Lipkin mentions for an ME patient + IBS. This showed up in the UBIOME stool test that I did earlier in the year.

    One thing I have noted is that if I undergo a period of any major stress it immediately hits my colon and causes so many other symptoms but especially insomnia and a rolling gut with an inability to digest my food properly despite digestive enzymes and extra hydrochloric acid. Migraine will also accompany these symptoms.

    I am amazed how quickly these symptoms appear, it is like a switch goes off and doesn’t seem to matter how I deal with it even if I practise various techniques. So for me the gut thing is huge. BTW I first got sick in 1979 after what I thought was a 2 week bout of influenza. Somehow I couldn’t seem to recover my energy and I was never the same after that. Now that I am 70 I can feel quite well and when in a good phase can do 10.000 steps in a day according to my FITBIT. I do have to manage my energy very carefully in order to exercise at least in part of the day.

    However whenever a virus hits everything changes and I feel very ill and unable to exercise. Again it’s like a switch goes off!

  • Issie

    August 1, 2018 at 9:58 pm - Reply

    I’ve recently been looking into not only a low Lectin diet, but low oxalate diet. Research is showing how oxalate changes the microbiology of the gut and can cause all sorts of issues.

  • Jill

    August 1, 2018 at 10:43 pm - Reply

    When I read about cfs patients vomiting and losing weight – turning to skin and bones – I think about the situation we were in. We could never figure out why her cfs suddenly turned into gut problems such as vomiting and the stomach not emptying etc. Turned out she had lyme disease. Please be sure you do not have b. garinii or b. burgdorferi. The gut situation turned around immediately treating for lyme. For heaven sakes, get tested if you are vomiting.

  • Ann Birds

    August 2, 2018 at 4:31 pm - Reply

    Ive got severe M.E and ive had stomach problems from the beginning of having this vile illness, so glad they making progress..Good luck with the research….

  • Nicolette

    August 3, 2018 at 4:07 pm - Reply

    Thanks for writing this article, Cort. I had been wondering what the Gut Microbiome team has been up to, and this answers that question. Interestingly, I didn’t have full blown IBS for the first 9 years of illness, but developed it late (about 3 years ago). When the IBS is acute, I often feel increased fatige quite acutely…all the way into my brain. So, I’m curious where I would be in the IBS or non-IBS parameters. Your reporting is very much appreciated, Cort. These research efforts, and findings are hopeful.

    • Cort Johnson

      August 3, 2018 at 7:34 pm - Reply

      Thanks Nicolette,

      IBS wasn’t present for me earlier in my ME/CFS either. It’s kind of odd that it showed up since my diet has always been good. For me I think its just part of my ME/CFS.

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