Gene mutation and inflammatory GI tract disease

We need to be assessing CLL and its effects on our health in a broad context. This article quite fascinating in possibly linking a frequent gene mutation in CLL to some of the community's reported GI tract maladies. Al Janski had posted on the microbiota and its influence on health in the past and Chris Dwyer was the first to post on fecal transplants to the disbelief and horror of many members. This field is expanding and will yield great health dividends when figured out. This could be the opposite of the saying "when the s#&t hits the fan" when medical science can figure a way to fix this type of defect.

CLL connection to MyD88


12 Replies

  • Now we just eat s#&t... less invasive for C.diff... :-) Remember C.diff kills...

    Every CLL patient should have an urea test for h.pylori... changed my life... simple treatment a PPI and two antibiotics... years of gut pain gone! There is also a fairly strong link between h.pylori and ITP in CLL ...

    H.pylori and ITP

  • How long on the PPI? over six months on acid reducing meds can lead to its own set of problems.

    Thanks for the links. Immunity whether compromised or runaway rogue autoimmune in nature is dynamic and individual.


  • 10 days... eradication therapy...

    Interesting article...

  • I remembered this article as we subscribe to the New Yorker. Thanks for sending as I had forgotten some of the findings. The sheer amount of complexity is daunting but tackling isolated problems like ulcers while considering consequences from all angles is necessary to avoid the trap of too linear thinking.

    I remember a story of a man near the end of his rope dealing with Crohn's or Celiac Disease. He ended up going to a culture in Africa where people were known to be free of these inflammatory ailments. The story goes that the tribes use open pit latrines and the people are all infected with a type of roundworm that enters the body through their feet. He reasoned that these parasites were protective and if one got a certain number of these worms to set up shop in the intestines they would act to control the inflammation and a person would not worry about overpopulation as they do not breed inside the body but rather need to shed eggs outside the host in their natural life cycle. He claimed to have walked barefoot to acquire his cure-quota of worms. Of course this fellow, as I recall, is peddling just the right number of worms for sale;-) to those afflicted with intractable inflammatory bowel disease.

    I think I would have to be pretty sick to follow in his path and I question the ability of the worms to pass through the stomach alive to set up shop in the intestinal tract, though I suppose they could be put into an enteric capsule. Whether a scam or not this may be something akin to the early life benefit to harboring H. Pylori.

    WWW - I'll sticking with yogurt.

  • These just came across on the H.pylori web wire...


    But in Western Australian women with MS...

  • I'm fairly certain ThreeW's, that the medical use of intestinal hookworms for some conditions as you described above is not a scam. Those that are interested can hear how hookworms interact with the human immune system and play a role in treating allergies and asthma in this rather confronting Radiolab episode from WNYC in New York City. The presenters rather amusingly tell the story along with the science behind the story of how 80 diseases can be treated with hookworms in this broadcast from about 5 years ago:


    Basically the idea is to use the hookworm's technique of damping down our immune system (a technique they use so that they can coexist with us), to reduce the over-reaction of our immune system against allergies in very allergic individuals.

    The episode also covers how US "millionaire John D. Rockefeller (founder of Standard Oil) turned an eye to the untapped market of the American South and ended up eradicating the hookworm (and, in the process, a number of other awful afflictions) with an ingenious contraption."

    Plus there's this Australian Radio National Hookworm Therapy Podcast:

    Given the warning about the anaemia, like you, I think I'll stick with yoghurt, but for those that suffer terribly from one of those 80 diseases, I'm sure that they would be very pleased if they can overcome their squeamishness and find relief at last.


  • Thanks Neil for adding to this thread. The idea of using a symbiotic worm has its aesthetic drawbacks as does fecal transplants, none the less, I was intrigued by the idea at the time I heard of it. What made me skeptical was the fellow who was then selling the worms. Miracle cures by folks who are cashing in on the miracle should always be scrutinized very closely.

    Given your notice on anemia is a fine example of how we need to consider the whole patient and understand how any therapy is designed to alleviate the condition it is employed against before using.


  • Correction:

    The original article that got my attention failed to mention that the MyD88 gene was in the "T" cells and not the "B" cell mutation seen in CLL. This is a cautionary tale for me to go back to the original research before making connections based on news reports. I figured if there was a flaw it would be in the animal to human translation of the finding but I give a thanks to Al Janski for noting the error of my post and bringing it to my attention.

    None the less, the effect of MyD88 loss on IgA production and function is interesting and possibly relevant to some CLL cases.


  • WWW -

    Well, it's just one study. Consider the aspect of comorbidity. One may have CLL and an unusual variant in some part of MyD88 that leaves one more susceptible to multiple diseases. A mutation in the B-Cell copy of MyD88 may make it even worse.

    At some point, the full Cell Host and Microbe article will be published online. Maybe someone can post a link here. Here's the abstract:

    The complete loss of MyD88 function seems to be rare - and artificially induced in a strain of mice in order to study MyD88 effects in general.

    The MyD88 protein seems important to multiple aspects of immunity:

    The TLR's are involved in innate immunity - general recognition of large parts of pathogens.

    The NF-kB (NF kappa B)

    looks like where it may come into play for CLL and for bowel disease in general. But I see so many hits on MyD88 when I search PubMed, there could be much more to the story.

    I did 23andMe over a year ago (their V3 chip), and it reports on several DNA nucleotides for the MyD88 gene. The V4 chip does as well. Note that it's probably reporting on MyD88 from epithelial cells in my mouth (it's a spit test). One of the nucleotides it reports on, RS7744, is reported to be more significant in some types of ulcerative colitis if the DNA base pair there is AA or AG. I and a sibling have AA there.

    Neither of us is Japanese, however, and population genetics can be important for such things, too.

    Neither of us have ever been diagnosed with UC - I'm just irritable in bowel, and sometimes demeanor ;^) My sib has generally a lot less digestive trouble than I, since childhood.

    Since the study doesn't say that all AA's and AG's at RS7744 get UC, there has to be another factor. Often, one needs multiple mutations or variants in different genes, plus bad environment (diet, stress, etc) to see the disease. But there is no doubt that MyD88 is important to us CLLers in more than one way - both mutated, and unmutated.

    I haven't yet found doctors that consider such information to be "actionable", though a few find it interesting. For now, it's my intro into the hidden world of microbiology. I'm like the kid with the crystal radio set in 1910.

    Patients see Personalized Medicine (the application of individual genetic tests to an illness) as an army of knights coming to the rescue, while health practitioners often see it as an information tsunami coming ashore.


  • In the tsunami of data that is surely coming from NGS (Next Generation Sequencing) there is a huge hurdle of pleiotropic findings to accurately assess meaning. I do feel that until we get comprehensive and complete data maps of genome, epigenome, transcriptome and while we are at it, microbiome data "dots" we will not be able to connect those dots in meaningful patterns to begin the process of undoing immune function deficiencies and excesses. Theoretically if we could transform defective immune systems into effective healthy responses to pathogens and emerging cancers we would not need cancer drugs or antibiotics/virals.

    I also wonder if there is any willingness on the part of CLLers to form a group interested in crowdsourcing data processing?

    Do you feel the 23andme tests are sufficient to pursue your goals. What are you hoping to accomplish and what is your evaluation of the V3 vs V4 chip? I have been holding off to evaluate options for testing. I am told the testing is going to start if not underway already at OSU where I am in Clinical Trial with Ibrutinib. I was told that the issue of pleiotropic data will limit patient access to data and or any data interpretation. Some findings of clear cut genomic defects directly attributable to disease will be passed on to patients. The gray area of uninterpreted but I am sure interesting findings will be withheld. I want the whole enchilada.


  • WWW -

    (I hope you don't mind that I explad acronyms for others)

    Since coming up with CLL trisomy 12, and doing 23andme, I've taken several online college courses - MOOCs (Massively Open Online Classes -, - in genetics and genomics ethics just to understand a few terms and issues. I'm by no means a researcher.

    I haven't seen signs that 23andMe is interested in CLL - I haven't seen any surveys specific to CLL there. But their database can be referenced by researchers for a fee, and it's the largest database of its type. So if we want to do something crowd sourced, we need to find a researcher who wants that, too.

    At this point, several other -omics databases have been setup, and modelling tools are the rage. The hope is to narrow the set of possible in-vivo experiments by running through better and better models of parts of human biology. I can only say that I understand it from a 10,000 foot altitude.

    I've been run folding@home, Stanford's massively parallel protein folding modeling software for a couple of years:

    It's not particularly informed by the genomics revolution, nor does it focus on CLL. It does show one specific layer that must be modeled. A protein is like a crowd of people holding hands, trying to move to have a better conversation with each other and if another protein comes by, conversations with them, too. How they fold determines how they interact.

    I've also dabbled with Berkley's BOINC software:

    It's less friendly that folding@home - a lot geekier. But it's where unique projects show up. I haven't gone through the list lately.

    I don't think that CLL has been defined as a computational target on either of these levels. What washes ashore in the few research papers Chris and others post here are the occasional GWAS (Genome Wide Assocation Study) that finds another SNP (Single Nucleotide Polymorphism) or two related to CLL. SNP's are the low hanging fruit.

    So the interesting stuff to me is the analysis of the different mutations, and how they interact with everything else in the body - all that interleukin and endo/para/juxta/autocrine signalling.

    I think biologists are still working out a lot of the normal case models, and a lot more work is needed:

    But it's the abnormality that gets the funding, and drives the discoveries in the hopes of treatment - and profits.

    I think we need to fund more basic research.

    We could waste billions of dollars on drug studies (for insanely expensive drugs), when basic research might show a faster path, sooner. Finish the maps, connect the dots, make the models, test the models, get surprised, iterate.

  • Hi ThreeWs,

    I saw a documentary about Adolph Hitler and his addictions to various drugs during the 30s and 40s. His Dr., which every one considered a quack, did indeed give Hitler feces to remedy his bowel issues.


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