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Celiac Disease & Gluten-Free Diet Forums

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Celiac Disease & Gluten-Free Diet Blogs

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  • Research on South African Celiac Tours
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  • Keating's Not-so-Glutenfree life
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  • Coeliac, or just plain unlucky?
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  • Searchin for a Primary Care Dr. In Redlands That is Knowledgeable about Celiac disease
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  • Celiac-Positive
  • Jason's Mommy's Blog
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  • I love my plant Cactus <3
  • Chele's Blog
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  • Blues Boulevard
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  • Michael Fowler's Blog
  • Living in Japan with Ceoliac Disease
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  • MJ
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  • HONG KONG GLUTEN, WHEAT FREE PRODUCTS
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  • Healthy Food Healthy You
  • SydneyT1D - Diabetic and Celiac YouTuber!
  • GFGF's Blog
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  • SMAS: www.celiac.com
  • gardener1's Blog
  • Naezer's Blog
  • JordanBattenSymons' Blog
  • JillianC
  • Sugar's Blog
  • Blanche22's Blog
  • Jason's Blog
  • Gluten-Free Sisters :)
  • Eab12's Celiac Blog
  • ohiodad's Blog
  • Newly Self Diagnosed?
  • misscorpiothing's Blog
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  • Petroguy
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  • WhoKnew?'s Blog
  • Soap Opera Central
  • nurcan's Blog
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  • Mr J's Blog
  • Rachel Keating's Blog
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  • krisb's Blog
  • deetee's Blog
  • CAC's Blog
  • EmilyLinn7's Blog
  • Teri Kiefer's Blog
  • happyasabeewithceliac's Blog
  • quietmorning01's Blog
  • jaimekochan's Blog
  • Cheryl
  • Seosamh's Blog
  • donna mae's Blog
  • Colleen's blog
  • DawnJ's Blog
  • Gluten Challenge
  • twins2's Blog
  • just trying to feel better's Blog
  • Celiac Teen
  • MNBelle blog
  • Gabe351's Blog
  • moosemalibu's Blog
  • Coeliac Disease or Coeliac Sprue or Non Tropical Sprue
  • karalto's Blog
  • deacon11's Blog
  • Nyxie's Blog
  • Swpocket's Blog
  • threeringfilly's Blog
  • Madison Papers: Living Gluten-Free in a Gluten-Full World
  • babinsky's Blog
  • prettycat's Blog
  • Celiac Diagnosis at Age 24 months in 1939
  • Sandy R's Blog
  • mary m's Blog
  • Jkrupp's Blog
  • Oreo1964's Blog
  • keyboard
  • Louisa's Blog
  • Guts & Brains
  • Gluten Free Betty
  • Jesse'sGirl's Blog
  • NewMom's Blog
  • Connie C.'s Blog
  • garden girl's Blog
  • april anne's Blog
  • 4xmom's Blog
  • benalexander60's Blog
  • missmyrtle's Blog
  • Jersey Shore wheat no more's Blog
  • swezzan's Blog
  • aheartsj's Blog
  • MeltheBrit's Blog
  • glutenfreecosmeticcounter
  • Reasons Why Tummy tuck is considered best to remove unwanted belly fat?
  • alfgarrie's Blog
  • SmidginMama's Blog
  • lws' Blog
  • KMBC2014's Blog
  • Musings and Lessons Learned
  • txwildflower65's Blog
  • Uncertain
  • jess4736's Blog
  • deedo's Blog
  • persistent~Tami's Blog
  • Posterboy's Blog
  • jferguson
  • tiffjake's Blog
  • KCG91's Blog
  • Yolo's Herbs & Other Healing Strategies
  • scrockwell's Blog
  • Sandra45's Blog
  • Theresa Marie's Blog
  • Skylark's Blog
  • JessicaB's Blog
  • Anna'sMommy's Blog
  • Skylark's Oops
  • Jehovah witnesses
  • Celiac in Seattle's Blog
  • March On
  • honeybeez's Blog
  • The Liberated Kitchen, redux
  • onceandagain's Blog
  • JoyfulM's Blog
  • keepingmybabysafe's Blog
  • To beer, with love...
  • nana b's Blog
  • kookooto's Blog
  • SunnyJ's Blog
  • Mia'smommy's Blog
  • Amanda's Blog
  • jldurrani's Blog
  • Why choosing Medical bracelets for women online is the true possible?
  • Carriefaith's Blog
  • acook's Blog
  • REAGS' Blog
  • gfreegirl0125's Blog
  • Gluten Free Recipes - Blog
  • avlocken's Blog
  • Thiamine Thiamine Thiamine
  • wilbragirl's Blog
  • Gluten and Maize-Free (gluten-free-MF)
  • Elimination Diet Challenge
  • DJ 14150
  • mnsny's Blog
  • Linda03's Blog
  • GFinDC's Blog
  • Kim UPST NY's Blog
  • cmc's Blog
  • blog comppergastta1986
  • JesikaBeth's Blog
  • Melissa
  • G-Free's Blog
  • miloandotis' Blog
  • Confessions of a Celiac
  • Know the significance of clean engine oil
  • bobhayes1's Blog
  • Robinbird's Blog
  • skurtz's Blog
  • Olivia's Blog
  • Jazzdncr222's Blog
  • Lemonade's Blog
  • k8k's Blog
  • celiaccoach&triathlete's Blog
  • Gluten Free Goodies
  • cherbourgbakes.blogspot.com
  • snow dogs' Blog
  • Rikki Tikki's Blog
  • lthurman1979's Blog
  • Sprue that :)'s Blog
  • twinkletoes' Blog
  • Ranking the best gluten free pizzas
  • Gluten Free Product
  • Wildcat Golfer's Blog
  • Becci's Blog
  • sillyker0nian's Blog
  • txplowgirl's Blog
  • Gluten Free Bread Blog
  • babygoose78's Blog
  • G-freegal12's Blog
  • kelcat's Blog
  • Heavy duty 0verhead crane
  • beckyk's Blog
  • pchick's Blog
  • NOT-IN-2gluten's Blog
  • PeachPie's Blog
  • Johny
  • Breezy32600's Blog
  • Edgymama's Gluten Free Journey
  • Geoff
  • audra's Blog
  • mfrklr's Blog
  • 2 chicks
  • I Need Help With Bread
  • the strong one has returned!
  • sabrina_B_Celiac's Blog
  • Gluten Free Pioneer's Blog
  • Theanine.
  • The Search of Hay
  • Vanessa
  • racecar16's Blog
  • JCH13's Blog
  • b&kmom's Blog
  • Gluten Free Foodies
  • NanaRobin's Blog
  • mdrumr8030's Blog
  • Sharon LaCouture's Blog
  • Zinc, Magnesium, and Selenium
  • sao155's Blog
  • Tabasco's Blog
  • Amanda Smith
  • mmc's Blog
  • xphile1121's Blog
  • golden exch
  • kerrih's Blog
  • jleb's Blog
  • RUGR8FUL's Blog
  • Brynja's Grain Free Kitchen
  • schneides123's Blog
  • Greenville, SC Gluten-Free Blog
  • ramiaha's Blog
  • Kathy P's Blogs
  • rock on!'s Blog
  • Carri Ninja's Blog
  • jerseygirl221's Blog
  • Pkhaselton's Blog
  • Hyperceliac Blog
  • abbiekir's Blog
  • Lasister's Thoughts
  • bashalove's Blog
  • Steph1's Blog
  • Etboces
  • Rantings of Tiffany
  • GlutenWrangler's Blog
  • kalie's Blog
  • Mommy Of A Gluten Free Child
  • ready2go's Blog
  • Maureen
  • Floridian's Blog
  • Bobbie41972's Blog
  • Everyday Victories
  • Intolerance issue? Helpppp!
  • Feisty
  • In the Beginning...
  • Cheri46's Blog
  • Acne after going gluten free
  • sissSTL's Blog
  • Elizabeth19's Blog
  • LindseyR's Blog
  • sue wiesbrook's Blog
  • I'm Hungry's Blog
  • badcasper's Blog
  • M L Graham's Blog
  • Wolicki's Blog
  • katiesalmons' Blog
  • CBC and celiac
  • Kaycee's Blog
  • wheatisbad's Blog
  • beamishmom's Blog
  • Celiac Ninja's Blog
  • scarlett54's Blog
  • GloriaZ's Blog
  • Holly F's Blog
  • Jackie's Blog
  • lbradley's Blog
  • TheSandWitch's Blog
  • Ginger Sturm's Blog
  • The Struggle is Real
  • whataboutmary's Blog
  • JABBER's Blog
  • morningstar38's Blog
  • Musings of a Celiac
  • Celiacchef's Blog
  • healthygirl's Blog
  • allybaby's Blog
  • MGrinter's Blog
  • LookingforAnswers15's Blog
  • Lis
  • Alilbratty's Blog
  • 3sisters' Blog
  • MGrinter's Blog
  • Amanda
  • felise's Blog
  • rochesterlynn's Blog
  • mle_ii's Blog
  • GlamourGetaways' Blog
  • greendog's Blog
  • Tabz's Blog
  • Smiller's Blog
  • my vent
  • newby to celiac?'s Blog
  • siren's Blog
  • myraljo's Blog
  • Relieved and confused
  • carb bingeing
  • scottish's Blog
  • maggiemay832's Blog
  • Cristina Barbara
  • ~~~AnnaBelle~~~'s Blog
  • nikky's Blog
  • Suzy-Q's Blog
  • mfarrell's Blog
  • Kat-Kat's Blog
  • Kelcie's Blog
  • cyoshimit's Blog
  • pasqualeb's Blog
  • My girlfriend has celiacs and she refuses to see a doctor
  • Ki-Ki29's Blog
  • mailmanrol's Blog
  • Sal Gal
  • WildBillCODY's Blog
  • Ann Messenger
  • aprilz's Blog
  • the gluten-free guy
  • gluten-free-wifey's Blog
  • Lynda MEADOWS's Blog
  • mellajane's Blog
  • Jaded's Celiac adventures in a non-celiac world.
  • booboobelly18's Blog
  • Dope show
  • Classic Celiac Blog
  • Keishalei's Blog
  • Bada
  • Sherry's blurbs
  • addict697's Blog
  • MIchael530btr's Blog
  • Shawn C
  • antono's Blog
  • Undiagnosed
  • little_d's Blog
  • Gluten, dairy, pineapple
  • The Fat (Celiac) Lady Sings
  • Periomike
  • Sue Mc's Blog
  • BloatusMaximus' Blog
  • It's just one cookie!
  • Kimmy
  • jacobsmom44's Blog
  • mjhere's Blog
  • tlipasek's Blog
  • You're Prescribing Me WHAT!?!
  • Kimmy
  • nybbles's Blog
  • Karla T.'s Blog
  • Young and dealing with celiacs
  • Celiac.com Podcast Edition
  • LCcrisp's Blog
  • ghfphd's allergy blog
  • https://www.bendglutenfree.com/
  • Costume's and GF Life
  • mjhere69's Blog
  • dedeadge's Blog
  • CeliacChoplin
  • Ravenworks' Blog
  • ahubbard83's Blog
  • celiac<3'sme!'s Blog
  • William Parsons
  • Gluten Free Breeze (formerly Brendygirl) Blog
  • Ivanna44's Blog
  • Daily Life and Compromising
  • Vonnie Mostat
  • Aly'smom's Blog
  • ar8's Blog
  • farid's Blog
  • Sandra Lee's Blog
  • Demertitis hepaformis no Celac
  • Vonnie Mostat, R.N.
  • beetle's Blog
  • Sandra Lee's Blog
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  • totalallergyman's Blog
  • Kim
  • Vhips
  • twinsmom's Blog
  • Newbyliz's Blog
  • collgwg's Blog
  • Living in the Gluten Free World
  • lisajs38's Blog
  • Mary07's Blog
  • Treg immune celsl, short chain fatty acids, gut bacteria etc.
  • questions
  • A Blog by Yvonne (Vonnie) Mostat, RN
  • ROBIN
  • covsooze's Blog
  • HeartMagic's Blog
  • electromobileplace's Blog
  • Adventures of a Gluten Free Mom
  • Fiona S
  • bluff wallace's Blog
  • sweetbroadway's Blog
  • happybingf's Blog
  • Carla
  • jaru24's Blog
  • AngelaMH's Blog
  • collgwg's Blog
  • blueangel68's Blog
  • SimplyGF Blog
  • Jim L Christie
  • Debbie65's Blog
  • Alcohol, jaundice, and celiac
  • kmh6leh's Blog
  • Gluten Free Mastery
  • james
  • danandbetty1's Blog
  • Feline's Blog
  • Linda Atkinson
  • Auntie Lur: The Blog of a Young Girl
  • KathyNapoleone's Blog
  • Gluten Free and Specialty Diet Recipes
  • Why are people ignoring Celiac Disease, and not understanding how serious it actually is?
  • miasuziegirl's Blog
  • KikiUSA's Blog
  • Amyy's Blog
  • Pete Dixon
  • abigail's Blog
  • CHA's Blog
  • Eczema or Celiac Mom?'s Blog
  • Thoughts
  • International Conference on Gastroenterology
  • Deedle's Blog
  • krackers' Blog
  • cliniclfortin's Blog
  • Mike Menkes' Blog
  • Juanita's Blog
  • BARB OTTUM
  • holman's Blog
  • It's EVERYWHERE!
  • life's Blog
  • writer ann's Blog
  • Ally7's Blog
  • Gluten Busters: Gluten-Free Product Alerts by Celiac.com
  • K Espinoza
  • klc's Blog
  • Pizza&beer's Blog
  • CDiseaseMom's Blog
  • sidinator's Blog
  • Dr Rodney Ford's Blog
  • How and where is it safe to buy cryptocurrency?
  • lucedith's Blog
  • Random Thoughts
  • Kate
  • twin#1's Blog
  • myadrienne's Blog
  • Nampa-Boise Idaho
  • Ursa Major's Blog
  • bakingbarb's Blog
  • Does Celiac Cause Sensitivites To Rx's?
  • delana6303's Blog
  • psychologygrl25's Blog
  • Alcohol and Celiac Disease
  • How do we get it???
  • cooliactic_BOOM's Blog
  • GREAT GF eating in Toronto
  • Gluten-free Food Recommendations!
  • YAY! READ THIS!!
  • BROW-FREE DIET BLOG
  • carib168's Blog
  • A Healing Kitchen
  • Shawn s
  • AZ Gal's Blog
  • mom1's Blog
  • The Beginning - The Diagnosis
  • PeweeValleyKY's Blog
  • solange's Blog
  • Cate K's Blog
  • Layered Vegetable Baked Pasta (gluten-free Vegetarian Lasagna)
  • Gluten Free Teen by Ava
  • mtdawber's Blog
  • sweeet_pea's Blog
  • DCE's Blog
  • Infertility and Celiac Disease
  • What to do in the Mekong Delta in 1 Day?
  • glutenfreenew's Blog
  • Living in the Garden of Eden
  • toddzgrrl02's Blog
  • redface's Blog
  • Gluten Free High Protein
  • Ari
  • Great Harvest Chattanooga's Blog
  • CeliBelli's Blog
  • Aboluk's Blog
  • redface's Blog
  • Being in Control of Your Gluten-Free Diet on a Cruise Ship
  • jayshunee's Blog
  • lilactorgirl's Blog
  • Yummy or Yucky Gluten-Free Foods
  • Electra's Blog
  • Cocerned husband's Blog
  • lilactorgirl's Blog
  • A Little History - My Celiac Disease Diagnosis
  • How to line my stomach
  • sewfunky's Blog
  • Oscar's Blog
  • Chey's Blog
  • The Fun of Gluten-free Breastfeeding
  • Dawnie's Blog
  • Sneaky gluten free goodness!
  • Chicago cubs shirts- A perfect way of showing love towards the baseball team!
  • Granny Garbonzo's Blog
  • GFzinks09's Blog
  • How do I get the Celiac.com podcast on my mp3 player?
  • quantumsugar's Blog
  • Littlebit's Blog
  • Kimberly's Blog
  • Dayz's Blog
  • Swimming Breadcrumbs and Other Issues
  • Helen Burdass
  • celiacsupportnancy's Blog
  • Life of an Aggie Celiac
  • kyleandjra.jacobson's Blog
  • Hey! I'm Not "Allergic" to Wheat!
  • FoOdFaNaTic's Blog
  • Wendy Cohan, RN's Gluten-Free and Dairy-Free Cooking Classes
  • Lora Derry
  • Dr. Joel Goldman's Blog
  • The Ultimate Irony
  • Lora Derry
  • ACK514's Blog
  • katinagj's Blog
  • What Goes On, Goes In (Gluten in Skin Care Products)
  • What’s new in hydraulic fittings?
  • cannona3's Blog
  • citykatmm's Blog
  • Adventures in Gluten-Free Toddling
  • tahenderson67's Blog
  • The Dinner Party Drama—Two Guidelines to Assure a Pleasant Gluten-Free Experience
  • What’s new in hydraulic fittings?
  • sparkybear's Blog
  • justbikeit77's Blog
  • To "App" or Not to "App": The Use of Gluten Free Product List Computer Applications
  • Onangwatgo
  • Raine's Blog
  • lalla's Blog
  • To die for Cookie Crumb Gluten-Free Pie Crust
  • DeeTee33's Blog
  • http://glutenfreegroove.com/blog/
  • David2055's Blog
  • Gluten-Free at the Fancy Food Show in San Francisco
  • Kup wysokiej jakości paszporty, prawa jazdy, dowody osobiste
  • Janie's Blog
  • Managing Hives & Gluten Allergies
  • Bogaert's Blog
  • Janie's Blog
  • RaeD's Blog
  • Dizzying Disclaimers!
  • Dream Catcher's Blog
  • PinkZebra's Blog
  • Hibachi Food and Hidden Gluten Hazards (How to Celebrate Gluten-Free)
  • jktenner's Blog
  • OhSoTired's Blog
  • PinkZebra's Blog
  • gluten-free Lover's Blog
  • Gluen Free Health Australia
  • Melissamb21's Blog
  • Andy C's Blog
  • halabackgirl9129's Blog
  • Liam Edwards' Blog
  • Celiac Disease in Africa?
  • Suz's Blog
  • Gluten-Free Fast Food
  • Eldene Goosen
  • mis_chiff's Blog
  • gatakat's Blog
  • macocha's Blog
  • Newly Diagnosed Celiacs Needed for Study in Chicago
  • Elaine Anne
  • Poor Baby's Blog
  • the loonie celiac's Blog
  • jenlex's Blog
  • Sex Drive/Testosterone can be Depleted by Certain Foods
  • Sharon
  • samantha79's Blog
  • 21 Months into the Gluten-free Diet
  • WashingtonLady's Blog-a-log
  • James S. Reid's Blog
  • Living with a Gluten-Free Husband
  • Diane King
  • runner girl's Blog
  • kp3972's Blog
  • ellie_lynn's Blog
  • trayne91's Blog
  • Gluten-free Lipstick!
  • Debado
  • Nonna2's Blog
  • Schar Chocolate Hazelnut Bar (Gluten-Free)
  • Diane
  • pnltbox27's Blog
  • Live2BWell's Blog
  • melissajohnson's Blog
  • nvsmom's Blog
  • Diagnosed with Celiac Disease and Still Sick
  • Coming out having gluten intolerance and celiac disease
  • snowcoveredheart's Blog
  • Gluten Free Nurse
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  1. Celiac.com 06/03/2024 - Celiac disease is a chronic autoimmune disorder affecting around 1% of the global population. It is triggered by the ingestion of gluten proteins found in wheat, barley, rye, and some oats. When individuals with celiac disease consume gluten, their immune system responds abnormally, causing inflammation and damage to the small intestine. This condition requires a strict gluten-free diet to prevent severe intestinal damage and other associated health issues. Recent research has provided new insights into how specific gluten-derived molecules contribute to the disease process in celiac disease, particularly focusing on a molecule known as the 33-mer deamidated gliadin peptide (DGP). This study explores the formation of DGP oligomers and their effect on gut permeability, shedding light on potential mechanisms behind the development of celiac disease. Formation and Characteristics of the 33-mer Deamidated Gliadin Peptide When gluten is consumed, it is not entirely broken down by the digestive system. This incomplete digestion results in the formation of large gluten fragments, or peptides, in the gut. One such peptide is the 33-mer gliadin peptide, which is particularly resistant to further enzymatic breakdown. In individuals with celiac disease, this peptide undergoes a modification by an enzyme called tissue transglutaminase 2 (tTG2), resulting in the formation of the 33-mer deamidated gliadin peptide (DGP). The 33-mer DGP has a high affinity for specific proteins called human leukocyte antigens (HLAs), particularly HLA-DQ2 and HLA-DQ8. This interaction is crucial because it triggers an immune response, leading to inflammation and damage to the intestinal lining. This strong interaction classifies the 33-mer DGP as a superantigen, which means it can elicit a significant immune response even at low concentrations. Oligomerization of 33-mer DGP and Its Structural Properties The study discovered that the 33-mer DGP spontaneously forms nanosized structures known as oligomers. Using advanced microscopy and biophysical techniques, researchers observed that these oligomers have a diameter of approximately 24 nanometers. The peptide displays two main structural motifs: a major polyproline II (PPII) helix and a minor beta-sheet structure. These structural elements are critical because they influence how the peptide interacts with other molecules and cells. The PPII helix is a unique structural motif characterized by its stability and lack of hydrogen bonds. It is common in peptides rich in proline, glutamine, and glutamic acid, which are all abundant in the 33-mer DGP. The beta-sheet structure, although less prominent, also plays a role in the peptide's overall behavior and its ability to form oligomers. Effects of 33-mer DGP Oligomers on Gut Permeability One of the key findings of the study is that the presence of 33-mer DGP oligomers significantly increases gut permeability. This effect was observed using a gut epithelial cell model known as Caco-2 cells. When these cells were exposed to the 33-mer DGP oligomers, researchers noted a decrease in transepithelial electrical resistance (TEER), a measure of cell layer permeability. Lower TEER values indicate a compromised barrier function of the gut lining. Further investigation revealed that the increased permeability was associated with the redistribution of zonula occludens-1 (ZO-1), a critical protein involved in maintaining tight junctions between gut epithelial cells. Tight junctions are essential for preserving the integrity of the gut barrier, preventing harmful substances from leaking into the bloodstream. The mislocalization of ZO-1 in the presence of 33-mer DGP oligomers suggests that these structures can disrupt the tight junctions, leading to a "leaky gut." Implications for Celiac Disease Pathogenesis The findings of this study have significant implications for our understanding of celiac disease. Traditionally, it was believed that chronic inflammation in celiac disease led to increased gut permeability. However, this study supports an alternative hypothesis: that the primary cause of gut permeability issues in celiac disease may be the direct effect of gluten-derived peptides, such as the 33-mer DGP oligomers, on the gut lining. This discovery suggests that the formation of 33-mer DGP oligomers and their ability to compromise the gut barrier could be an early trigger in the development of celiac disease. By allowing other gluten peptides, bacteria, and toxins to enter the bloodstream more easily, these oligomers might initiate the inflammatory response and subsequent autoimmune reactions characteristic of celiac disease. Potential for Therapeutic Interventions Understanding the role of 33-mer DGP oligomers in celiac disease opens up new avenues for therapeutic interventions. If these oligomers are indeed a critical factor in increasing gut permeability and triggering the disease, then targeting them could be a promising strategy for preventing or treating celiac disease. One potential approach could be developing therapies that inhibit the formation of 33-mer DGP oligomers or block their interaction with the gut lining. This could help maintain the integrity of the gut barrier and prevent the cascade of immune responses that lead to celiac disease. Additionally, focusing on the specific amino acids that promote beta-sheet formation within the peptide might offer another strategy to modulate its oligomerization and reduce its harmful effects. Conclusion The study provides crucial insights into the molecular mechanisms underlying celiac disease, particularly the role of the 33-mer deamidated gliadin peptide and its oligomers. By demonstrating how these structures can increase gut permeability and disrupt tight junctions, the research highlights a potential early trigger for the disease. For individuals with celiac disease, these findings are meaningful because they suggest new possibilities for therapeutic interventions that go beyond simply avoiding gluten. By targeting the specific molecules and mechanisms involved in the disease process, future treatments might offer more effective ways to manage or even prevent celiac disease, improving the quality of life for those affected. Read more: onlinelibrary.wiley.com

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  3. Celiac.com 07/30/2019 - Studies have shown increased intestinal permeability in irritable bowel syndrome. Validating serum biomarkers for altered intestinal permeability in irritable bowel syndrome will facilitate research and pathophysiology-based therapy. A team of researchers recently set out to measure serum zonulin and intestinal fatty acid binding protein levels in diarrhea-predominant irritable bowel syndrome and constipation-predominant irritable bowel syndrome, and to compare the results with healthy control and celiac disease subjects. The research team included Prashant Singh, Jocelyn Silvester, Xinhua Chen, Hua Xu, Veer Sawhney, Vikram Rangan, Johanna Iturrino, Judy Nee, Donald R. Duerksen, and Anthony Lembo. They are variously affiliated with the Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, United States of America; the Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, United States of America; and the Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada. The team used enzyme-linked immunosorbent assays to measure serum zonulin and intestinal fatty acid binding protein levels in fifty patients with constipation-predominant irritable bowel syndrome, fifty with diarrhea-predominant irritable bowel syndrome, fifty-three with celiac disease, and forty-two healthy control subjects. Using the irritable bowel syndrome-symptom severity scale as a gauge, they found that patients with constipation-predominant irritable bowel syndrome and diarrhea-predominant irritable bowel syndrome had higher zonulin levels compared with healthy controls. They also found that zonulin levels in patients with constipation-predominant irritable bowel syndrome and diarrhea-predominant irritable bowel syndrome are comparable to levels in patients with active celiac disease. The results showed no correlation between zonulin levels and overall irritable bowel syndrome symptom severity. They did, however, show a positive correlation with weekly stool frequency, and unsatisfactory bowel habits in diarrhea-predominant irritable bowel syndrome. Patients with diarrhea-predominant and constipation-predominant irritable bowel syndrome both had lower intestinal fatty acid binding protein levels compared with celiac patients. In patients with irritable bowel syndrome, serum zonulin is upregulated at levels comparable to those for celiac patients, and match the severity of unsatisfactory bowel habits in diarrhea-predominant irritable bowel syndrome. Irritable bowel syndrome patients show no increase in intestinal fatty acid binding protein levels, which likely means no significant increase in enterocyte death. This is an interesting finding regarding serum zonulin levels in some patients with irritable bowel syndrome, as is the positive correlation with weekly stool frequency, and unsatisfactory bowel habits in diarrhea-predominant irritable bowel syndrome. Read more at the United European Gastroenterology Journal; 2019 Jun; 7(5): 709–715. doi: 10.1177/2050640619826419
  4. “Tight junction function” might sound like a song from Schoolhouse Rock, but it’s a topic that explains a great deal about our immune system and the increasing prevalence of autoimmune disorders. The tight junction (TJ) is an essential element of our intestinal structure, and is part of the body’s defenses against bacteria and toxins. About 70% of the body’s immune system resides in the gut, mostly as lymphatic cells. To prevent the immune system from being overtaxed, the TJ restricts access to these cells. The TJ is a matrix of interlocking proteins that open and close tiny pores between cells. The proteins form a hexagonal pattern, similar to chicken wire. Substances can pass through the intestinal wall, either through cell membranes, or between cells, using a the pores (gaps in the chicken wire). Pores help the body absorb nutrients, but must be selective. They use an electrostatic charge to filter out large particles, and to bind cells close together. Zonulins are messenger proteins that signal the pores to open. When zonulins are released, they bind to specific chemical receptors in the intestinal wall. These receptors tell the body to add a phosphoryl group to one of the proteins in the matrix. This deactivates the protein, disassembling the TJ’s hexagonal structure (like cutting a strand of the chicken wire.) The lymphatic cells address molecules that pass through the TJ, and may mark them as antigens (dangerous substances). The “danger” flag may go up on molecules larger in size than the normal dimension of the pores (typical of bacterial infections), known toxins, or a sudden flood of material that is new to the lymphatic cells in the gut. The immune system remembers each antigen and attacks it when it reappears. While this is an effective way to keep out bacteria and toxins, the problem is overkill. When the TJ is leaky (TJ dysfunction is also known as “leaky gut”), the body attacks all substances marked as antigens, even otherwise benign foods. This stresses the immune system, creating inflammation. Inflammation damages the TJ further, loosening it to admit new substances. This creates a vicious cycle, making the TJ even more permeable. This explains why Celiacs who recently had a gluten exposure tend to become sensitive to other foods they are eating during the time they are suffering from leaky gut. Those foods are passing through the loosened pores, and being marked as antigens. But why do the TJs fail to begin with? Everyone releases some zonulin in response to gluten, but those with a gene for Celiac disease release far more zonulin (two standard deviations above the norm, well beyond coincidence). Bacterial infections can also trigger zonulin release. Some industrial food additives are also zonulin triggers. They include nanoparticles (such as titanium dioxide – check your toothpaste and chewing gum ingredients), microbial transglutaminase (“meat glue”), salt nanowires, organic solvents, and emulsifiers. These new ingredients are increasingly common in the U.S. food supply. If they sound inscrutable, it’s for good reason; they’re not naturally occurring. Elevated zonulin levels and TJ permeability are associated with Celiac disease and Type 1 Diabetes. (A drug that reduces zonulin production also protects against damage to insulin-producing cells in Type 1 Diabetes patients.) Overproduction of zonulin is also found in those with Crohn’s disease, schizophrenia, and chronic kidney disease, and other disorders. The intestinal tight junction, and damage to it, is strongly associated with various autoimmune diseases. We are just beginning to understand the role of this important system in modulating health, and the factors that cause it to fail. Sources Anderson, J.M., and C.M. Van Itallie. (2009). Physiology and function of the tight junction. Cold Spring Harb Perspect Biol; 1:a002584. doi: 10.1101/cshperspect.a002584 Brandner, J.M., M. Zorn-Kruppa, T. Yoshida, I. Moll, L.A. Beck, and A. De Benedetto. (2015). Epidermal tight junctions in health and disease. Tissue Barriers 3:1-2, e974451; January-June 2015. doi: 10.4161/21688370.2014.974451 Fassiano, A. (2012). Zonulin, regulation of tight junctions, and autoimmune diseases. Ann N Y Acad Sci. 2012 July; 1258(1): 25–33. doi:10.1111/j.1749-6632.2012.06538.x Khaleghi, S., J.M. Ju, A. Lamba and J.A. Murray. (2016). The potential utility of tight junction regulation in celiac disease: focus on larazotide acetate. Ther Adv Gastroenterol 9(1): 37–49. doi: 10.1177/1756283X15616576 Lerner, A., and T. Matthias. (2015). Changes in intestinal tight junction permeability associated with industrial food additives explain the rising incidence of autoimmune disease. Autoimmunity Reviews 14 (2015) 479–489. doi:10.1016/j.autrev.2015.01.009 Vighi, G., F. Marcucci, L. Sensi, G. Di Cara, and F. Frati. (2008). Allergy and the gastrointestinal system. Clinical and Experimental Immunology, 153 (Suppl. 1): 3–6. doi:10.1111/j.1365-2249.2008.03713.x
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