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Celiac.com 10/12/2020 - Researchers have recently begun to understand that gut bacteria play a critical role in keeping people healthy. They are also beginning to understand that our poop offers an excellent glimpse into our gut health. We know that the gut microbiota of children begin to change when they get celiac disease. Low levels of certain gut bacteria correspond with higher rates of celiac disease. We also know that gut microbiomes of children with a high genetic risk for type 1 diabetes are significantly different than those of children with low genetic risk. Moreover, changing gut microbiota could protect against celiac disease. However, there's much to learn about exactly which bacteria is beneficial and which bacteria is harmful, and what the best balance of bacteria may be to help optimize our health. We do understand that one bacteria strain, bifidobacterium infantis, is beneficial to gut health. To learn more, a group of researchers conducted a study to see if they could introduce an important species of good bacteria, known as bifidobacterium infantis, into the guts of babies with deficient levels. When they did so, they found that the stool pH became much more acidic, which is a more normal gut condition. This led the team to hypothesize that lower stool pH could reflect a healthier gut, with more optimal levels of beneficial microbes. To investigate their hypothesis, the team analyzed the pH of infant stool by looking at studies from 1926 to 2017. They found that infant stool pH has risen from 5.0 to 6.5 over the last hundred years or so, meaning that is has become less acidic and more basic over the years. This is a major difference, as the pH scale runs from 0 to 14.0, with 7.0 being neutral. That change could reflect a decrease in bifidobacterium, and a reduction in gut health during that time. Normally, healthy mothers pass bifidobacterium and many other strains of gut bacteria to their babies via their breast milk. The researchers think that the reduction in bifidobacterium in infants may reflect reduced gut health in mothers doing that time. According to researcher Bethany Henrick, of Evolve BioSystems, a biomedical company in Davis, California, and her co-author Jennifer Smilowitz, a nutritional biologist at the University of California, Davis, bifidobacterium is important, because it binds exclusively to human milk oligosaccharides, which are sugars found only in breast milk. Oligosaccharides provides food bifidobacterium needs to grow and reproduce. Healthy levels of bifidobacterium in the gut help to keep bad bacteria from growing in the gut. About 80% of the cells that make up our immune systems are in our guts. "There's this intimate connection between the gut microbiome and our immune system," says Henrick. If bifidobacterium levels are low, bad bacteria can flourish. Higher levels of bad gut bacteria could tax the immune system, and promote allergies and certain autoimmune diseases. Women can promote gut health by eating a diet high in fiber, such as whole grains, nuts, seeds, legumes, fruits, and vegetables. Prior studies have shown that gut bacteria is influenced by three things: How often a baby gets antibiotics, whether they are breastfed, and whether they were delivered naturally, or via cesarean section. The researchers encourage doctors and new mothers to work to promote a healthy gut microbiome in their babies by limiting antibiotics and cesarean sections, and to breastfeed, when possible. By learning more about the role of gut bacteria and a healthy gut biome in the development of celiac disease can help us to better understand the origins of the disease, as well as how we might be able to reduce it in the future. Stay tuned for more on the role of gut bacteria in celiac disease, and related news. Read more at Pediatr Res. 2019; 86(6): 749–757.

Celiac.com 08/08/2019 - A strict gluten-free diet is the only currently accepted treatment for celiac disease. Current treatment guidelines for celiac disease recommend regular dietary interviews and blood tests to gauge dietary adherence. However, those guidelines might not be doing the job. A team of researchers recently set out to see if fecal gluten immunogenic peptides might help support the diagnosis, and determine the adherence to the gluten-free diet in celiac children. The research team included Isabel Comino, Verónica Segura, Luis Ortigosa, Beatríz Espín, Gemma Castillejo, José Antonio Garrote, Carlos Sierra, Antonio Millán, Carmen Ribes-Koninckx, Enriqueta Román, Alfonso Rodriguez-Herrera, Jacobo Díaz, Jocelyn Anne Silvester, Ángel Cebolla, and Carolina Sousa. They are variously affiliated with research institutions in Spain, Canada and the USA. The team's multi-center prospective longitudinal study included 64 children with celiac disease. For each child, the team assessed fecal gluten peptides, and tissue transglutaminase and deamidated gliadin peptide antibodies at diagnosis, and 6, 12 and 24 months afterward. The researchers used gluten peptide levels to estimate patient gluten consumption. A total of 97% of children showed detectable gluten peptides upon diagnosis. For patients on a gluten-free diet, the rate of gluten peptides rose from 13% at 6 months to 25% at 24 months. Average estimated gluten exposure fell from 5543 mg/d at diagnosis to 144 mg/d at 6 months, then rose to about 600 mg/d after two years. In contrast, antibodies to deamidated gliadin peptide normalized and only 20% of patients showed elevated tissue transglutaminase antibody after 24 months. Patients with detectable gluten peptides had longer periods of tissue elevated transglutaminase antibody. Overall, absolute levels of tissue transglutaminase antibody showed low sensitivity for identifying patients with detectable gluten peptides. Evaluation by a dietitian only moderately improved gluten peptide detection. At some point, testing for fecal gluten peptides could help to guide celiac treatment prior to diagnosis and to test adherence to a gluten-free diet. Further studies are needed to determine if spotting gluten exposure early can reduce the need for expensive/invasive investigations for non-responsive celiac disease. Read more in Alimentary Pharmacology & Therapeutics

Celiac.com 09/12/2017 - Are we at the beginning of the end for celiac disease? The last few years have seen numerous advances in celiac diagnosis and treatment. People diagnosed recently and in the future face a very different world than that faced by celiacs just five or ten years ago. In the old days, the process of properly diagnosing involved blood tests, endoscopies, and biopsies. In the near future, a simple blood test may do the trick. In the old days, the only treatment was a life-long gluten-free diet. That is still true, but the writing of change is on the wall. Here are five advances that will change the way celiac disease is diagnosed and treated in the future. These advances may well signal the beginning of the end of celiac disease as we know it. Blood Test Diagnosis (Without Biopsy) Researchers are getting better at identifying likely celiac cases using blood tests alone, without biopsy. As these techniques are refined and integrated into medicine, chances are pretty good that in the near future, large numbers of people will be diagnosed for celiac disease without the need for biopsy confirmation. Can Antibodies Spot Celiac Disease in Kids Without a Biopsy? Kids Can Get Accurate Celiac Diagnosis Without Biopsy Celiac Diagnosis Without Biopsy Can Be Useful in Some Cases Portable Gluten Detectors Imagine a future where you can take a bit of food you're not sure about, and pop it in a portable tester that will tell you if the food is gluten-free. A few years ago, that might have been the future of science fiction. With several companies looking to introduce just such kits, that future looks a lot more certain. Innovative Device Eliminates Gluten-Free Guesswork This Device Can Help Tell You If Your Food Is Actually Gluten-Free nimasensor.com Enzymes Enzymes that break down gluten might help people with celiac disease to enjoy a more normal life by protecting them from minor gluten contamination, and allowing them a bit more confidence when eating away from home. A number of manufacturers are currently working on enzyme treatments that are specifically designed to break down gluten for people with celiac disease. AN-PEP Shows Promise in Breaking Down Gluten in Stomach Enzyme Shows Promise In Dissolving Gliadin Peptides in Celiac Patients Could Carnivorous Plant Enzymes Act Like Beano for Gluten? Could Enzymes from Oral Bacteria Treat Celiac Disease Bio-Therapeutics—Hookworms They sound gross. The thought of having their guts infected with a parasitic worm makes people's skin crawl. However, researchers have documented the gut healing abilities of parasites like hookworm. When hookworms are introduced into the gut of people with celiac disease in the right amount, and kept at therapeutic levels, patients see their celiac symptoms disappear and their guts return to a healthy, normal condition. While still very much in the experimental phase, researchers are keen to investigate various strains and to determine the best therapeutic levels for these treatments. If all goes well, treatments based on parasitic worms will likely become more viable and more common in the future. Celiac Patients Tolerate Wheat Spaghetti After Hookworm Treatment Have Celiac Disease? Try a Little Hookworm with that Pasta! Can Bloodsucking Parasites Help Treat Asthma and Celiac Disease? Controversial Pig Parasite May Soon Be Sold In Germany To Treat Disease Bio-Therapeutics—Fecal Transplant Could fecal transplants be used to cure or to treat celiac disease? Much like hookworms, once you get past the 'yuck' factor, fecal transplants are proving to be cheap, easy, reliable way to treat gut conditions like C-Diff and, possibly celiac disease. The idea is to get some healthy poop in your gut to inoculate it with beneficial microbes. The effects are nothing short of astonishing. As they are studied, developed and refined, look for bio-therapeutic approaches like fecal transplant to play a role in treating gut contains like celiac disease. A Case of Refractory Celiac Disease Cured By Fecal Microbiota Transfer Vaccine A vaccine against celiac disease would be a holy grail of sorts. Receive a dose, or maybe multiple doses over time and become immune to the adverse effects of gluten. Several companies are working on a vaccine that would basically eliminate celiac disease. Many of these have moved through the early trial phases and several have shown enough promise to move to trials in humans. This is a very exciting area of research that may pay huge dividends in the near future. Celiac Disease Vaccine Set to Begin Full Human Trials Would You Try a Vaccine for Celiac Disease? Celiac Vaccine Clears First Big Clinical Trial This Vaccine Could Be a Game-Changer for People with Celiac Disease The main takeaway from these developments is that we are now living in an age where the diagnosis and treatment of celiac disease is the focus of tremendous research and development on numerous fronts. Many of these will likely result in products, tests, or treatments for celiac disease that were unimaginable just 5 or 10 years ago.

Celiac.com 08/31/2017 - A possible mechanism behind the cause of refractory celiac disease and why fecal transplantation (fecal microbiota transfer) may provide a cure was presented in "Synthetic Stool May Advance Fecal Transplant Therapy for Celiac Disease" 02/13/2013.[1] In September 2016, the article "Serendipity in Refractory Celiac Disease: Full Recovery of Duodenal Villi and Clinical Symptoms after Fecal Microbiota Transfer" was published in the Journal of Gastrointestinal and Liver Disease[2] describing the first known case of refractory celiac disease cured by a fecal transplant. The patient in that case was being treated for a recurrent Clostridium difficile infection. This very important milestone article somehow missed the light of the news media at that time. The 68-year old woman patient was a 10-year diagnosed victim of refractory celiac disease on a gluten-free diet. On admission for treatment of severe diarrhea, the patient exhibited Marsh IIIA villous atrophy. The patient was already receiving on-going treatment for refractory celiac disease with drugs. Additional drugs and antibiotics were given to treat the diarrhea. Eventually, the patient tested positive for C. difficile. Antibiotics were ineffective to treat the recurrent C. difficile infection. A fecal microbiota transfer was then performed. The C. difficile infection and diarrhea resolved, and, 6 months after the fecal transplant, villous atrophy resolved and went to Marsh 0. All symptoms of refractory celiac disease were eliminated. The patient remains symptom free on a continuing gluten-free diet. The case clearly demonstrates the need to fully investigate the use of fecal microbiota transfers to treat celiac disease. As suggested in my earlier reference[1], a standardized synthetic stool should be developed to enable full scale clinical trials. Also a full scale research effort into completely healing and restoring the intestinal mucosa with the novel protein R-spondin1 needs to be funded and restarted. Sources: 1. Synthetic Stool May Advance Fecal Transplant Therapy for Celiac Disease. Roy S. Jamron. Celiac.com 2013 Feb 13. 2. Serendipity in Refractory Celiac Disease: Full Recovery of Duodenal Villi and Clinical Symptoms after Fecal Microbiota Transfer. van Beurden YH, van Gils T, van Gils NA, Kassam Z, Mulder CJ, Aparicio-Pages N J Gastrointestin Liver Dis. 2016 Sep;25(3):385-8.

Celiac.com 09/16/2016 - Great news about poop transplants: They work! And now doctors kind of understand how and why they work. This is good news about a humor provoking, but very serious matter. Clostridium difficile infection is one of the most common health care-associated infections, and up to 40% of patients suffer from recurrence of disease following standard antibiotic therapy. C. difficile infection has proven to be very difficult to treat. Fecal microbiota transplantation (FMT) has been successfully used to treat recurrent C. difficile infection. Doctors hypothesize that FMT promotes recovery of a microbiota capable of colonization resistance to C. difficile. However, they didn't really understand how it worked. Recently, a research team investigated changes in the fecal microbiota structure following FMT in patients with recurrent C. difficile infection, and imputed a hypothetical functional profile based on the 16S rRNA profile, using a predictive metagenomic tool. After FMT, they also noted increased relative abundance of Bacteroidetes and decreased abundance of Proteobacteria. The research team included Anna M. Seekatz, Johannes Aas, Charles E. Gessert, Timothy A. Rubin, Daniel M. Saman, Johan S. Bakken, and Vincent B. Young. They are variously affiliated with the Department of Internal Medicine, Division of Infectious Diseases, Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA; Essentia Health, Department of Gastroenterology, Duluth, Minnesota, USA; Essentia Institute of Rural Health, Duluth, Minnesota, USA; and St. Luke's Hospital, Section of Infectious Diseases, Duluth, Minnesota, USA. Their results showed that, after transplantation, fecal microbiota of recipients was more diverse, and more similar to the donor profile, than the microbiota before transplantation. Additionally, they observed differences in the imputed metagenomic profile. In particular, amino acid transport systems were over-represented in samples collected prior to transplantation. These results Indicate that functional changes accompany microbial structural changes following this therapy. Further identification of the specific microbiota, and functions that promote colonization resistance, may help to create better treatment methods for C. difficile infection. Source: mBio. 2014 May-Jun; 5(3): e00893-14. Published online 2014 Jun 17. doi: 10.1128/mBio.00893-14. PMCID: PMC4068257

Celiac.com 02/02/2013 - The possible link between the makeup of gut bacteria and celiac has been a subject of past discussion in "More Evidence Links Gut Bacteria to Celiac Disease"[1] and other articles. Certain gut bacteria appear to enhance the immune response to gluten which may contribute to the onset of celiac disease. Vitamin D may reduce or eliminate this enhanced gluten response, and, therefore, vitamin D deficiency may be a significant factor contributing to the onset and development of celiac disease.[2] "Fecal transplantation", probiotics, and vitamin D have been advocated as possible therapy, treatment, and/or preventative measures against celiac disease. While vitamin D and probiotics may have potential as preventative measures against the onset of celiac disease early in life, the option of a fecal transplant provides the actual possibility of restoring tolerance to gluten or curing celiac disease later in life following long-term intestinal mucosal recovery on a gluten-free diet. In particular, fecal transplantation might make it possible to treat refractory celiac disease which does not respond to a gluten-free diet. Fecal transplant therapy for gastrointestinal disorders was pioneered by the world reknown Australian gastroenterologist, Prof. Thomas J. Borody, M.D., and is now used most successfully for treatment of persistant C. difficile infections of the gastrointestinal tract. Fecal transplantation involves the actual transfer of screened and filtered fecal material from a healthy donor into the gut of a patient, previously treated with antibiotics to clear gut bacteria, replacing the patient's own gut bacteria with a healthy mix of donor gut bacteria. The fecal material may be administered either orally or anally, via tubes. Selecting and screening a healthy donor, usually a spouse or close relative, as well as the "disgust" factor have limited use of this therapy in past years, but its high anecdotal success rate for treating stubborn C. difficile cases is finally bringing fecal transplantation into the mainsteam of routine gastrointestinal practice. The first clinical trial of fecal transplant therapy involving 43 C. difficile patients compared to conventional vancomycin antibiotic therapy has just been published finding fecal transplantation 3 times more effective than vancomycin in resolving C. difficile infections.[3,4] To date, there does not appear any record of an attempt or clinical trial to treat celiac disease via fecal transplant therapy. A big problem preventing any significant clinical trial of fecal transplantation for celiac disease is there is no way to "standardize" the healthy donor fecal material. The mix of bacteria from every donor is unique. Each donor must also undergo careful screening for harmful fecal pathogens. But, now, recent developments may make such a clinical trial feasible. A synthetic stool substitute was successfully used to clear C. difficile infections in 2 patients as part of a "proof-of-principle" study which may lead the way to eliminate the need for individual healthy feces donors and the need for screening tests. The synthetic stool consisted of a mix of 33 bacteria species isolated from the stool of one healthy donor and cultured under simulated intestinal conditions.[5,6] Such a standardized synthetic stool potentially administered orally in capsule form could make large scale fecal transplantation clinical trials possible. An "off-the-shelf" bacteria mixture specifically developed for the treatment of celiac disease might become a reality. In the case of refractory celiac disease, a gluten-free diet does not stop the continued destruction of the intestinal mucosa. Research has not yet found the reason for refractory celiac disease, but "molecular mimicry" may be one possible cause. Celiac disease is an immune response to particular sequences of amino acids in gluten peptides called epitopes. In the absence of gluten, if there exist peptides from other sources with amino acid sequences matching or "mimicking" these gluten epitopes, the destructive immune response may continue to damage the mucosa. This is molecular mimicry in action. It is possible that some gut bacteria may express some of these epitopes on their surface, or, more likely, secrete peptides that contain these epitopes. These bacterial secretions might then coat the lining of the intestine sustaining the immune response. Secreted epitopes are the more likely cause of refractory celiac disease than bacteria surface epitopes because the immune system would eventually destroy the bacteria if bacteria surface epitopes were involved. But if the cause were the bacterial secretion epitopes, the bacteria itself would not be attacked and would continue to produce the secretions indefinitely perpetuating the mucosal damage. Fecal transplant therapy might cure refractory celiac disease by eliminating the gut bacteria producing the epitope mimicking secretions. How likely are such gut bacteria molecular mimics to exist? One study has investigated this for the case of multiple sclerosis and concluded there is a strong likelihood that "normally occurring gut bacterium" could produce epitopes that might cause MS through molecular mimicry.[7] One case of molcular mimicry between human peptides and wheat peptides has been found.[8] In the case of normal celiac disease (non-refractory celiac disease) treatable by a gluten-free diet, after some length of time on a gluten-free diet when the antibodies to gluten epitopes have cleared and when the intestinal mucosa has sufficiently healed, it may be possible to reprogram the immune system to tolerate gluten through fecal transplantation, along with vitamin D supplementation, providing a new healthy gut bacteria mix. One problem, however, is that in many cases the damage to the intestinal mucosa from celiac disease does not entirely heal.[9,10] This means that a long-term or permanent state of increased intestinal permeablity or "leaky gut" exists after beginning a gluten-free diet. "Leaky-gut" is by no means a benign condition. It puts a strain on the liver's detoxification abilities having to continually deal with toxins readily passing through the "leaky" intestinal mucosa. The toxins come from gut bacteria as well as from drugs and environmental chemicals including household products and cosmetics. Inhaled environmental toxins can be ingested when mucus expelled from the lungs is swallowed. The overload on the liver and its inability to keep up with detoxification can lead to long-term debilitating medical conditions such as wide-spread chronic pain, muscle pain and weakness, neuropathies, fatigue, dry mouth, frequent urination, swelling, allergies, and even to other autoimmune disorders[11] due to fat soluble toxins accumulating in adipose tissue where they remain causing inflammation and raising havoc indefinitely. The result is an unfavorable pro-inflammatory immune system environment which could impede any chance of restoring gluten tolerance. A promising treatment that could entirely heal the intestinal mucosa and "leaky gut" is a treatment based on a novel protein called R-spondin1. Prior to January 2009 a small San Francisco pharmaceutical company, Nuvelo, was developing an R-spondin1 therapy drug with the designation, NU206. NU206 had shown some great promise and success in lab studies. Dramatic mucosal healing was demonstrated in an experimental colitis model with mice.[12] Nuvelo's first targets were to use NU206 to heal and reduce intestinal mucosal damage from cancer chemotherapy and radiation therapy and to treat short-bowel syndrome. In December 2008 Nuvelo had actually announced results from Phase 1 clinical safety trials on 32 healthy male volunteers demonstrating administration of NU206 caused no adverse effects.[13] Unfortunately, Nuvelo, which also has other drugs in development, ran short of funding and, in January 2009, merged with a Colorado company, ARCA biopharma.[14] ARCA biopharma is dedicated to developing genetically-targeted therapies for cardiovascular diseases. [Open Original Shared Link] It appears that all NU206 research and development and clinical trials were suspended with the merger. NU206, an extremely promising drug that might enable full intestinal mucosal healing and recovery in celiac disease now sits idly on a shelf with no indication clinical trials will ever resume. While there has been some very limited research on R-spondin1 in other medical applications by other scientists, there has been no new R-spondin1 research on intestinal healing since the merger. Any celiac disease interest group with access to funding for celiac disease research should consider contacting ARCA biopharma to see what efforts might be implemented to restart this very important R-spondin1 research. Sources: 1. More Evidence Links Gut Bacteria to Celiac Disease Roy S. Jamron Celiac.com 2008 Nov 6. 2. Do Vitamin D Deficiency, Gut Bacteria, and Gluten Combine in Infancy to Cause Celiac Disease? Roy S. Jamron Celiac.com 2008 Jun 16. 3. Fecal Transfer Proves Potent Clostridium difficile Treatment Jenni Laidman Medscape Medical News 2013 Jan 16. Open Original Shared Link 4. Duodenal Infusion of Donor Feces for Recurrent Clostridium difficile Els van Nood, Anne Vrieze, Max Nieuwdorp, Susana Fuentes, Erwin G. Zoetendal, Willem M. de Vos, Caroline E. Visser, Ed J. Kuijper, Joep F.W.M. Bartelsman, Jan G.P. Tijssen, Peter Speelman, Marcel G.W. Dijkgraaf, Josbert J. Keller NEJM 2013 Jan 16; Published Online Open Original Shared Link 5. C difficile: Synthetic Stool Substitute Clears Infection Jenni Laidman Medscape Medical News 2013 Jan 10. Open Original Shared Link 6. Stool substitute transplant therapy for the eradication of Clostridium difficile infection: "RePOOPulating" the gut Elaine O Petrof, Gregory B Gloor, Stephen J Vanner, Scott J Weese, David Carter, Michelle C Daigneault, Eric M Brown, Kathleen Schroeter and Emma Allen-Vercoe Microbiome 2013 Jan 9;1:3. Open Original Shared Link 7. Molecular mimicry revisited: gut bacteria and multiple sclerosis. Westall FC. J Clin Microbiol. 2006 Jun;44(6):2099-104. Open Original Shared Link 8. IgA cross-reactivity between a nuclear autoantigen and wheat proteins suggests molecular mimicry as a possible pathomechanism in celiac disease. Natter S, Granditsch G, Reichel GL, Baghestanian M, Valent P, Elfman L, Gronlund H, Kraft D, Valenta R. Eur J Immunol. 2001 Mar;31(3):918-28. Open Original Shared Link 9. Mucosal healing and mortality in coeliac disease. Lebwohl B, Granath F, Ekbom A, Montgomery SM, Murray JA, Rubio-Tapia A, Green PH, Ludvigsson JF. Aliment Pharmacol Ther. 2013 Feb;37(3):332-9. Open Original Shared Link 10. Complete recovery of intestinal mucosa occurs very rarely in adult coeliac patients despite adherence to gluten-free diet. Lanzini A, Lanzarotto F, Villanacci V, Mora A, Bertolazzi S, Turini D, Carella G, Malagoli A, Ferrante G, Cesana BM, Ricci C. Aliment Pharmacol Ther. 2009 Jun 15;29(12):1299-308. Open Original Shared Link 11. Chemical-induced allergy and autoimmunity Marty Bernardus Franciscus Wulferink [s.l.] : [s.n.], 2001 - Tekst. - Proefschrift Universiteit Utrecht Open Original Shared Link 12. R-spondin1, a novel intestinotrophic mitogen, ameliorates experimental colitis in mice. Zhao J, de Vera J, Narushima S, Beck EX, Palencia S, Shinkawa P, Kim KA, Liu Y, Levy MD, Berg DJ, Abo A, Funk WD. Gastroenterology. 2007 Apr;132(4):1331-43. Open Original Shared Link 13. Nuvelo Announces Positive Results from Phase 1 Clinical Trial of NU206 in Healthy Volunteers 2008 Dec 10. Open Original Shared Link 14. Biotechs Arca, Nuvelo complete reverse merger 2009 Jan 28. Open Original Shared Link