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Celiac.com 05/10/2004 - Identical twins enter life from the same womb sharing the same genetic code, the same family, the same home, largely experiencing the same environment as they develop from infancy through childhood and mature into adults. When celiac disease strikes one identical twin, the odds are the other twin also has celiac disease. Twin studies lead to the conclusion that celiac disease is strongly linked to genetic factors. Yet one identical twin may develop celiac disease while the other twin may remain completely free of celiac disease for decades if not for a lifetime. One study looked at 20 pairs of identical twins and 27 pairs of fraternal twins where at least one twin of the pair was known to have celiac disease. In 75% of the pairs of identical twins, both twins had celiac disease. In contrast, in only 11% of the pairs of fraternal twins did both twins have celiac disease. However, in 25% of the 20 identical twin pairs studied, one twin of the pair did not have celiac disease1. In another study which followed 5 pairs of female identical twins for 11-23 years (at least one twin of the pair having celiac disease or dermatitis herpetiformis), it was found that two of the twins who began the study with neither celiac disease or dermatitis herpetiformis remained free of the disease throughout the study2. In other words, something beyond genetics, some environmental factor, seems to be responsible for the onset of celiac disease. Exactly what is it that makes one twin intolerant to gluten and not the other? Looking for Answers To find an answer, one might start by asking when do signs of an intolerance to gluten first begin to emerge? A recent study in the UK looked at a screened sample of 5,470 children aged 7 years old and found 54 who tested positive for both tTG antibodies and IgA-EMA (tissue transglutaminase and antiendomysial antibodies) indicating celiac disease is likely present. This 1% prevalence in children is comparable to the 1% prevalence of celiac disease in adults in the UK. Since the prevalence of celiac disease is not greater in adults, this suggests that the onset of celiac disease begins in early childhood, even in cases where celiac disease is not diagnosed until later in adulthood. The authors of this study concluded, “The search for the trigger resulting in the breakdown of immune tolerance to gluten therefore needs to focus on infancy and intrauterine life3.” Breast-Feeding Breast-feeding has long been thought to delay or reduce the risk of developing celiac disease in children. This effect has been attributed to a number of potentially protective milk components and antibodies passed from the mother. Studies relying on questionnaires have found that the onset of celiac disease in children is significantly delayed if gluten is introduced into the diet while the child is still being breast-fed4-7. The effect of epidermal growth factor (EGF), a component of breast milk, was studied in newborn rats. Interferon-gamma and gliadin, a gluten protein, were administered to rat pups to induce gluten enteropathy. Celiac disease-like villus atrophy was found in rat pups fed an artificial milk diet without EGF but not in breast-fed pups or pups supplemented with EGF8. Recent research shows that breast milk also passes bacterial flora from mother to newborn9. Growth factors found in human milk have been shown to aid in establishing predominant species of commensal bacteria in the gut of breast-fed infants10. The makeup of microflora which colonize the gut in early infancy is dependant on many factors, including whether babies are bottle-fed or exclusively breast-fed, whether or not delivered by caesarean section, on treatment in neonatal intensive care units, hygienic conditions, and antimicrobial procedures. Initially, it is the maternal microflora that is the source of bacteria for the newborn gut. A diet of breast milk induces the development of a flora rich in Bifidobacterium in full-term infants11. The possibility that these microflora play critical symbiotic roles in the development of the intestine and its immunological functions has not yet been considered as a factor in the onset of celiac disease. The Beneficial Roles of Gut Bacteria Over 500 species of bacteria may be present in the human gut in concentrations of between 100 billion to 1 trillion microbes per gram adding up to about 95% of the total number of cells in the human body12,13. For many years it has been known that gut bacteria play an important and beneficial role in one’s health. Extraordinary new findings on how commensal microflora participate in early gut development and in the development of the immune system have been uncovered by recent research. Here is sampling of some of these discoveries: A study of 64 healthy formula and breast-fed infants, aged 0-6 months, examined fecal samples for intestinal colonization of Bacteriodes fragilis, Bifidobacterium-like, and Lactobacillus-like bacteria, and compared these results with counts of IgA, IgM, and IgG antibody-secreting cells in blood fluids drawn from the infants. The result was that infants colonized with B. fragilis at one month of age had significantly higher counts of IgA- and IgM-secreting cells at the age of two months than infants not colonized with B. fragilis. It was concluded that colonization timing and the type of bacteria colonizing the gut of newborns may influence the maturation of the naive immune system14. Bacteriodes thetaiotaomicron, a species abundant in the guts of humans and mice, has been the focus of much research, chosen because of its predominance in the microflora and ability to be genetically manipulated. Studies of this microbe introduced into the developing guts of gnotobiotic (germ-free) laboratory mice have found B. thetaiotaomicron seems to communicate with host cells in the intestine, altering and influencing gut development and function. One study has shown gene activity in the host is affected by B. thetaiotaomicron colonization. Using sophisticated DNA microarray devices, a comparison of gene expression of some 25,000 mouse genes was made between germ-free and B. thetaiotaomicron colonized mice. The activity of 118 genes was found to be increased or reduced by colonization. These genes are involved in several important intestinal functions, including nutrient absorption, intestinal permeability, toxin neutralization, intestinal blood vessel development, and postnatal gut maturation suggesting that these functions should be examined further in future studies15. An influence on fructose production in the gut by B. thetaiotaomicron was the first finding uncovered by researchers. Pre-weaned mice produce fructose sugar on the surface of cells lining the intestine providing a food source helping to establish commensal bacteria. B. thetaiotaomicron colonizing the gut of germ-free mice causes intestinal cells to continue fructose production after weaning. If B. thetaiotaomicron is not present after weaning, fructose synthesis stops. B. thetaiotaomicron actually senses when its supply of fructose is low and instructs the host to produce more fructose in response16. Gene activity findings led researchers to look at the development of the intricate network of intestinal blood vessels in mice raised germ-free and in mice raised colonized with B. thetaiotaomicron or normal gut flora. When the mice reached adulthood, capillary development in the intestines was examined. Capillary development in mice colonized with B. thetaiotaomicron or normal flora was normal and complex, but capillary development in the germ-free mice was immature and arrested. Further, it was, found for blood vessel development to occur, these microbes must interact with Paneth cells (epithelial cells located at the base of the “crypts” in the small intestine)17. The relationship of B. thetaiotaomicron with Paneth cells was further studied. It was discovered that Paneth cells produce a protein called angiogenin 4 or Ang4 and that Paneth cells are induced to express Ang4 by B. thetaiotaomicron. Ang4 and other angiogenins were found to exhibit bactericidal and fungicidal activities against certain known pathogens. It appears that B. thetaiotaomicron and other commensal microbes, which are themselves resistant to Ang4, take part in shaping the microbial ecology of the gut and innate immunity18. Another study found a relationship between commensal bacteria and the development of gut-associated lymphoid tissue (GALT) in rabbits. GALT consists of lymphocytes and organized tissues called Peyer’s patches and mesenteric lymph nodes (MLNs) located within the intestinal mucosa, which are involved in the induction of immunity and tolerance. During the first few months after birth, newborn animals and humans rely on antibodies passed maternally to fend off infections until the immune system can mature. After those first few months, a diversification of antibody repertoire normally takes place within the GALT. When, shortly after birth, the appendices of rabbits are tied-off and isolated to prevent colonization by microflora, GALT development within the appendices is arrested. Rabbit pups delivered sterilely, isolated and hand-reared on a sterile diet exhibited underdeveloped GALT and antibody repertoires. In further experimentation, a number of different bacteria species were introduced into surgically-rendered, germ-free appendices of rabbits. No bacteria species alone promoted GALT development. However, the combination of Bacteroides fragilis and Bacillus subtilis consistently resulted in the development of GALT and antibody repertoire. The conclusion is that specific combinations of microflora are required for GALT development19,20. In other research, the composition of commensal flora in rats was shown to alter intestinal permeability. Colonization with Escherichia coli, Klebsiella pneumoniae, and Streptococcus viridans significantly increased colonic wall permeability while colonization with the common probiotic strain, Lactobacillus brevis, significantly reduced permeability of the colon wall. Bacteroides fragilis induced only a slight permeability reduction21. Gut pathogens in combination with stimulation by cytokines such as TNF-alpha (tumor necrosis factor) can cause cells of the intestinal epithelium to respond by releasing proinflammatory cytokines like interleukin-8 (IL-8). A study found that probiotic strains, Bifidobacterium longum and Lactobacillus bulgaricus, can suppress IL-8 secretion in intestinal epithelia when stimulated by proinflammatory cytokines. Hence, some probiotic strains of bacteria may be able to down-regulate inflammation in the gut22. Other beneficial functions of microflora include the fermentation and removal of non-digestible dietary residue and the mucus residue produced by the epithelia; the derivation of energy as short-chain fatty acids by fermentation of carbohydrates in the colon; the production of vitamins, particularly those of the B group and vitamin K; the absorption of minerals and ions including calcium, magnesium and iron; and the formation of a protective functional barrier against pathogens23,24. A Role for Bacteria in Celiac Disease? As can been seen, commensal microflora play a myriad of complex, diverse and important roles in normal health and development. Much remains to be investigated, and new roles and functions microflora play are waiting to be discovered. The possibility that commensal bacteria are involved in the pathogenesis of celiac disease cannot be overlooked. Certainly, differences in the mix of microflora could account for why one identical twin may develop celiac disease while the other does not. Could the mix of commensal bacteria in newborn infants set the stage for the development of celiac disease? Could the onset of celiac disease be triggered by an event such as illness, use of antibiotics, stress, or pregnancy which alters the mix of microflora opening the door to a pathogenic interaction with gluten? One recent study has already found an association between antibiotic use and the development of Crohn’s disease25. Over the course of the last few years, much new understanding of the pathogenesis of celiac disease has come to light, but a fundamental question remains unanswered: Why does the immune system fail to tolerate gluten in some people? A possible mechanism involving one or more unidentified species of commensal bacteria possibly explaining why tolerance to gluten fails will be proposed and discussed here. Tolerance and Immunity The subject of tolerance and immunity is involved and complex, and science remains far from fully comprehending its workings. At heart, is how the immune system decides to react when an antigen is first presented to a naive T cell. The response of the immune system to an antigen is mediated and regulated by cell secretions of numerous proteins called “cytokines” sensed by a multitude of receptors on the various specialized cells of the immune system. Structural components of pathogens are also sensed by immune cell receptors called “Toll-like receptors”. Antigens may be any substance foreign to the body and may or may not actually be harmful. They could be components of food, or could be components of either friendly or pathogenic organisms. In celiac disease, the antigens are those gluten peptides which survive the process of digestion. In the current understanding of celiac disease, these peptides are transported across the mucosal epithelium as polypeptides. In mainly the subepithelial region, gluten peptides undergo a process called deamidation by an enzyme called tissue transglutaminase (tTG). A peptide is a chain of amino acids. Deamidation is a process that converts glutamine amino acid components of a gluten peptide into glutamic acid components. In the lamina propria region of the intestines, deamidated gluten peptides are taken up by antigen presenting cells called dendritic cells and presented by HLA-DQ2 or -DQ8 molecules on the surface of dendritic cells to receptors of gluten-sensitive naive CD4+ T cells (Note celiac disease here refers to a “cluster of differentiation” number, a numbering system for the cell-surface molecules which identify T cell type). Activated CD4+ T cells then differentiate and proliferate. Some T cells interact with B cells which, in turn, then differentiate into plasma cells producing antigliadin, antiendomysial and anti-tTG antibodies. Other T cells become natural killer or cytotoxic T cells, secreting cytokines which cause inflammation and damage to the enterocytes in the epithelium. Connective tissue cells called “fibroblasts” increase their output of matrix metalloproteinase enzymes which may play an active role in villus atrophy. Intraepithelial lymphocytes also increase, but their role is not clear26-29. Human leukocyte antigen (HLA) genes encode the class II molecules DQ2 and DQ8, the key genetic risk factors in celiac disease. The HLA system is the human version of the major histocompatibility complex (MHC). HLA class II molecules are expressed on the surface of antigen presenting cells such as dendritic cells. Virtually all celiac disease patients carry DQ2 or DQ8, but carrying DQ2 or DQ8 alone does not confer celiac disease. DQ2 and DQ8 molecules may be encoded by several different haplotypes. Haplotypes are combinations of alternative genes for the same trait (alleles) occupying different locations on a chromosome which tend to be inherited as a group. These DQ2 and DQ8 molecules play a central role in the pathogenesis of celiac disease. The function of HLA class II molecules is to bind peptide antigens and present them to CD4+ T-cell receptors. The pattern of amino acids in the makeup of the chain that forms the peptide antigen is called an epitope, and that pattern is crucial to the binding between HLA molecule and peptide. It is the misfortune of celiac disease patients that epitopes of deamidated gluten peptides just happen to match up and firmly anchor into the binding grooves of DQ2 and DQ8 molecules. This strong binding results in the activation of CD4+ T cells and the subsequent processes which damage the intestinal epithelia. But why is it that CD4+ T cells are not activated in everyone who possesses the appropriate HLA-DQ2 and -DQ8 haplotypes? The question arises again. Why is one identical twin tolerant to gluten and not the other?26-30 Dendritic Cells Whether an outcome of tolerance or intolerance results when a dendritic cell presents an antigen to a naive T cell depends on many factors. A dendritic cell is a special type of white blood cell (leukocyte) which circulates throughout the body looking to acquire antigens. Dendritic cells engulf and internalize antigens through a process called endocytosis. In receptor-mediated endocytosis, dendritic cells express a variety of surface receptors to capture protein antigens. In macropinocytosis, dendritic cells surround and “drink up” soluble antigens. In phagocytosis, dendritic cells engulf pathogenic bacteria, viruses, fungi, dead or infected cells, or their products. After digestion and processing, the antigens are bound to HLA (or MHC) molecules and expressed on the surface of dendritic cells for presentation to T cells. Antigen presentation occurs after dendritic cells migrate to the lymph nodes which are rich with T cells. T cell activation also requires secondary stimulation by costimulatory molecules expressed on the dendritic cell surface. Dendritic cells have three stages in their life cycle: Precursor, immature and mature. Precursor dendritic cells arise from the bone marrow. Subsets of precursor dendritic cells have been identified that grow and differ with regard to observable characteristics (phenotype), function and anatomical location. Studies have linked dendritic cell subsets with particular functions such as T cell differentiation or tolerance induction. Immature dendritic cells spread throughout tissues seeking antigens. Dendritic cells enter the mature stage when they reach the lymph nodes after antigen capture and having become primed and ready to activate T cells with antigens and costimulatory molecules. The processing of antigens produces roughly 100,000 to 300,000 peptide-laden HLA molecules on the dendritic cell surface, most peptides represented by about 100 copies. A single mature dendritic cell is capable of stimulating 100–3,000 T cells31-34. Immature dendritic cells are capable of phagocytosis of bacteria. Dendritic cell phagocytosis of Salmonella and Borrelia burgdorferi has been observed and studied. Immature dendritic cells roaming the lamina propria below the epithelial cells of the intestine not only capture bacteria which invade and cross the epithelial barrier, but have been observed reaching through the tight junctions between epithelial cells with their dendrite arms to directly sample non-invasive bacteria in the gut lumen and mucosa tissues outside the epithelium34-37. Immature dendritic cells express a variety of surface receptors which when stimulated cause dendritic cells to mature and respond in specific ways which can result in tolerance or immune activity. These receptors include Toll-like receptors (TLR), cytokine receptors, TNF (tumor necrosis factor) receptor, immunoglobulin (antibody) receptors, and sensors for cell death. TNF and other cykotine inflammatory mediators signal infections. In particular, interleukin-1 (IL-1) can prevent oral tolerance in mice by altering the response of normally tolerogenic dendritic cells into an active immune response32,34. Toll-like receptors are known as pattern recognition receptors which identify structural components found only on the surface of bacteria and other pathogens. These components are referred to as pathogen-associated molecular patterns (PAMPs). At least 10 types of TLR have been identified in humans and given the designations, TLR1-TLR10. Examples of PAMP include microbial carbohydrates like the toxin lipopolysaccharides (LPS), flagellin, products from bacterial cell walls, bacterial RNA and DNA. Signaling through different TLR evokes distinct biological responses. TLR expressed differently by different dendritic cell subsets may determine the manner in which dendritic cell subsets respond to particular microbial structures34,39. Mature dendritic cells can produce cytokines while activating CD4+ T cells which may influence T cell differentiation and function. Activated T cells divide and proliferate and differentiate into a variety of types. Tolerance and immunity induction are influenced most by differentiation into type 1 and type 2 helper T cells (Th1 and Th2) and regulatory T cells. The type of cytokines produced by the T cells determine their classification. Th2 responses favor tolerance. Th1 responses favor immunity and inflammation. Regulatory T cells suppress immune responses. IL-10 produced by dendritic cells appears to contribute to Th2 and regulatory T cell responses. Dendritic cell production of IL-12, IL-18, and IL-23 contribute to a Th1 response34,40. Why Does Tolerance to Gluten Fail? Okay. So why does the immune system fail to tolerate gluten in celiac disease? The immune system receives and responds to all kinds of signals from a pathogen, but how can a simple gluten peptide turn this complex immune machinery into a force against itself? Thinking about this leads to a very provocative question: What if instead of responding to gluten peptides alone, the immune system responds to a pathogenic gut bacteria which routinely ingests gluten peptides? A 33 amino acid gluten peptide has been identified as the primary initiator of the inflammatory response in celiac disease. This peptide contains a number of amino acid sequences which correspond to epitopes known to activate T cells and initiate celiac disease response. In particular, this 33-mer peptide was identified because it remained intact in the residue of a solution of gliadin mixed with gastric and pancreatic enzymes. This demonstrates some gluten peptides are difficult to breakdown by normal digestive processes. Another experiment identified a 17 amino acid gluten peptide which also contained epitopes associated with celiac disease41,42. Bacteria do not ingest nutrients in the normal sense. Nutrients are transported across cell membranes via several different mechanisms. Transported nutrients are necessarily limited in size. Nutrients are broken down externally by enzymes and by processes such as fermentation, an oxidation process resulting from acids produced by bacteria. Growth factors consisting of purines, pyrimidines, vitamins and amino acids are required by some bacteria in order to grow. Other bacteria are able to synthesize these essential growth factors. Researchers have found that some bacteria can transport and internalize amino acids in the form of peptides. Studies so far have found peptides up to 18 amino acids in length can be internalized by bacteria43-46. Epitopes of gluten peptides deamidated by tissue transglutaminase (tTG) are believed central to celiac disease pathogenesis. However, a study of gluten response in children with celiac disease found that T cells can respond to native gluten peptides independent of deamidation47. Celiac disease may begin its course without deamidation. As the disease progresses, inflammation may cause an increase in expression of tTG. An increase in tTG expression has been shown during wound healing, in liver injury, and in response to an inflammatory stimulus by lipopolysaccharide48-50. Through a process called epitope spreading and with the increase in tTG expression, deamidation of gluten peptides is more likely to occur and T cell response to deamidated gluten peptides likely develops. tTG is expressed in the epithelial brush border and extracellularly in the subepithelial region26 (The brush border is composed of the microvilli found on each individual epithelial cell). In the course of evolution of bacteria in the gut, it would seem highly plausible that at least one or more bacteria species have evolved and adapted in some way to transport, internalize and utilize gluten peptides as a source of amino acids. Since tTG is expressed in the epithelial brush border, deamidated gluten peptides are available to such bacteria (though in the early stage of celiac disease deamidation may not be required). If these bacteria colonize the gut and exhibit some pathogenic characteristic, such as expressing lipopolysaccharide, dendritic cells may be signaled to reach through the epithelial barrier into the lumen to sample and phagocytize the bacteria. When this bacteria is digested and processed by the dendritic cells, the antigens bound to HLA molecules and expressed on the dendritic cell surface are likely to include the difficult to breakdown, intact gluten peptides that have been internalized by the bacteria. As far as the immune system is concerned, these gluten peptides are indistinguishable from the other bacterial peptides bound to HLA molecules expressed on the dendritic cell surface. When these gluten peptide antigens are bound to HLA-DQ2 or -DQ8 molecules and presented to CD4+ T cells, the T cells simultaneously receive all the signals telling them that the gluten peptide is an antigen from a pathogenic bacteria. The result is that the immune system responds to the presence of gluten as though pathogenic bacteria were present. Such gluten-ingesting bacteria may be the missing link in the pathogenesis of Celiac Disease. If these bacteria exist, there is now a clear explanation as to why one identical twin may develop celiac disease and not the other. Of course, the presence of such a bacteria in the gut of one twin and not the other would fully explain the discordance. It is also possible that such a bacteria may exist in both twins, but is kept under control by the mix of commensal bacteria colonizing the gut of one twin. Some disturbance to this mix, such as an infection or use of antibiotics, might provide an opportunity for this gluten-ingesting bacteria to colonize and proliferate to a level where its pathogenic properties, such as production of endotoxins, are sensed by the immune system initiating the onset of celiac disease. The existence of such bacteria could also explain why there may be varying degrees of gluten sensitivity, even in individuals without DQ2 and DQ8 molecules. The possibility that these gluten-ingesting bacteria may exist raises another intriguing question: If these gluten-ingesting bacteria are controlled or eliminated from the gut, could tolerance to gluten be restored? There could be a very real possibility that celiac disease might be cured by eliminating these bacteria. After all, peptic ulcers can be cured by eliminating Helicobacter pylori. The Future So where should research go from here? The most obvious path would be first to try to find and identify any gut bacteria that has gluten peptides present within its cell membranes. From there, the possible link to celiac disease could be studied. Additionally, it would be quite valuable to initiate a large long-term study of the makeup of commensal bacteria in identical twins beginning at birth via fecal samples. By comparing the differences in microflora and the onset and discordance of diseases in identical twins over many years, the relationships of specific species of bacteria to specific diseases, including celiac disease, could be established. And if it proves to be true that gluten-ingesting bacteria cause celiac disease, a similar mechanism involving bacteria and peptides from other proteins may be the root cause for many other autoimmune diseases. 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Increase in transglutaminase and its extracellular products in response to an inflammatory stimulus by lipopolysaccharide. Mol Cell Biochem 1997 Apr;169(1-2):157-63.

Celiac.com 12/07/2020 - A team of researchers has established the first bioinformatics method to determine and test the potential biological sensitivity of living organisms to glyphosate, the chemical in the herbicide commercially marketed as Roundup. Their research shows that glyphosate may negatively affect more than half of bacteria strains that make up the human gut microbiome. The research team included Lyydia Leinoa,Tuomas Talla, Marjo Helandera, Irma Saloniemia, Kari Saikkonen, Suvi Ruuskanena, and Pere Puigbòacd. They are variously affiliated with the Department of Biology, University of Turku, Turku, Finland, the Biodiversity Unit, University of Turku, Finland, the Nutrition and Health Unit, Eurecat Technology Centre of Catalonia, Reus, Catalonia, Spain, and the Department of Biochemistry and Biotechnology, Rovira i Virgili University, Tarragona, Catalonia, Spain. The team managed to identify the enzyme targeted by the broad-spectrum herbicide, glyphosate, and offers the first bioinformatics method for determining potential glyphosate sensitivity. Glyphosate targets an enzyme called 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) in the shikimate pathway, which synthesizes three essential aromatic amino acids (phenylalanine, tyrosine and tryptophan) in plants. "Based on the structure of the EPSPS enzyme, we are able to classify 80-90% of microbial species into sensitive or resistant to glyphosate," says Docent Pere Puigbò, developer of the new bioinformatics tool. Glyphosate has been regarded as safe to use because shikimate pathway is found only in plants, fungi and bacteria. However, the widespread use of glyphosate may reduce the diversity and composition of microbial communities, including the human gut microbiome. The team's new method has allowed them to create a dataset of EPSPS sequences from thousands of species that will enable major research advances. The method resulted in the classification of sequences from nearly 90% of eukaryotes and more than 80% of prokaryotes. Analysis made with the team's new bioinformatics tool shows that more than half of the human core gut bacterial species are potentially sensitive to glyphosate. "This groundbreaking study provides tools for further studies to determine the actual impact of glyphosate on human and animal gut microbiota and thus to their health," explains Docent Marjo Helander. Read more at the Journal of Hazardous Materials

This article appeared in the Summer 2008 edition of Celiac.com's Scott-Free Newsletter. Celiac.com 06/16/2008 - Do vitamin D deficiency, gut bacteria, and timing of gluten introduction during infancy all combine to initiate the onset of celiac disease? Two recent papers raise the potential that this indeed may be the case. One paper finds that when transgenic mice expressing the human DQ8 heterodimer (a mouse model of celiac disease) are mucosally immunized with gluten co-administered with Lactobacillus casei bacteria, the mice exhibit an enhanced and increased immune response to gluten compared to the administration of gluten alone.[1] A second paper finds that vitamin D receptors expressed by intestinal epithelial cells are involved in the suppression of bacteria-induced intestinal inflammation in a study which involved use of germ-free mice and knockout mice lacking vitamin D receptors exposed to both friendly and pathogenic strains of gut bacteria.[2] Pathogenic bacteria caused increased expression of vitamin D receptors in epithelial cells. Friendly bacteria did not. If one considers these two papers together, one notices: (1) Certain species of gut bacteria may work in conjunction with gluten to cause an increased immune response which initiates celiac disease; (2) The presence of an adequate level of vitamin D may suppress the immune response to those same gut bacteria in such a way as to reduce or eliminate the enhanced immune response to gluten caused by those gut bacteria, thus preventing the onset of celiac disease. Vitamin D has recently been demonstrated to play a role in preserving the intestinal mucosal barrier. A Swedish study found children born in the summer, likely introduced to gluten during winter months with minimal sunlight, have a higher incidence of celiac disease strongly suggesting a relationship to vitamin D deficiency.[3] Recent studies found vitamin D supplementation in infancy and living in world regions with high ultraviolet B irradiance both result in a lower incidence of type 1 diabetes, an autoimmune disease closely linked to celiac disease.[4][5] Gut bacteria have long been suspected as having some role in the pathogenesis of celiac disease. In 2004, a study found rod-shaped bacteria attached to the small intestinal epithelium of some untreated and treated children with celiac disease, but not to the epithelium of healthy controls.[6][7] Prior to that, a paper published on Celiac.com[8] first proposed that celiac disease might be initiated by a T cell immune response to "undigested" gluten peptides found inside of pathogenic gut bacteria which have "ingested" short chains of gluten peptides resistant to breakdown. The immune system would have no way of determining that the "ingested" gluten peptides were not a part of the pathogenic bacteria and, thus, gluten would be treated as though it were a pathogenic bacteria. The new paper cited above[1] certainly gives credence to this theory. Celiac disease begins in infancy. Studies consistently find the incidence of celiac disease in children is the same (approximately 1%) as in adults. The incidence does not increase throughout life, meaning, celiac disease starts early in life. Further, in identical twins, one twin may get celiac disease, and the other twin may never experience celiac disease during an entire lifetime. Something other than genetics differs early on in the childhood development of the twins which initiates celiac disease. Differences in vitamin D levels and the makeup of gut bacteria in the twins offers a reasonable explanation as to why one twin gets celiac disease and the other does not. Early childhood illnesses and antibiotics could also affect vitamin D level and gut bacteria makeup. Pregnant and nursing mothers also need to maintain high levels of vitamin D for healthy babies. Sources: [1] Immunol Lett. 2008 May 22. Adjuvant effect of Lactobacillus casei in a mouse model of gluten sensitivity. D'Arienzo R, Maurano F, Luongo D, Mazzarella G, Stefanile R, Troncone R, Auricchio S, Ricca E, David C, Rossi M. [2] The FASEB Journal. 2008;22:320.10. Meeting Abstracts - April 2008. Bacterial Regulation of Vitamin D Receptor in Intestinal Epithelial Inflammation Jun Sun, Anne P. Liao, Rick Y. Xia, Juan Kong, Yan Chun Li and Balfour Sartor [3] Vitamin D Preserves the Intestinal Mucosal Barrier Roy S. Jamron [4] Arch Dis Child. 2008 Jun;93(6):512-7. Epub 2008 Mar 13. Vitamin D supplementation in early childhood and risk of type 1 diabetes: a systematic review and meta-analysis. Zipitis CS, Akobeng AK. [5] Diabetologia. 2008 Jun 12. [Epub ahead of print] The association between ultraviolet B irradiance, vitamin D status and incidence rates of type 1 diabetes in 51 regions worldwide. Mohr SB, Garland CF, Gorham ED, Garland FC. [6] Am J Gastroenterol. 2004 May;99(5):905-6. A role for bacteria in celiac disease? Sollid LM, Gray GM. [7] Am J Gastroenterol. 2004 May;99(5):894-904. Presence of bacteria and innate immunity of intestinal epithelium in childhood celiac disease. Forsberg G, Fahlgren A, Hörstedt P, Hammarström S, Hernell O, Hammarström ML. [8] Are Commensal Bacteria with a Taste for Gluten the Missing Link in the Pathogenesis of Celiac Disease? Roy S. Jamron

Celiac.com 08/27/2020 - Several thousand strains of bacteria live in the human gut. Some strains are beneficial, while others can promote disease. To make matters more difficult, many of these strains cannot currently be grown in laboratory settings. Certain bacteria species that cannot live in oxygen-rich environments present an even more difficult study challenge. A team of biological and mechanical engineers at MIT have created a device for growing oxygen-intolerant bacteria in tissue in low-oxygen conditions that mirror the lining of the human colon, allowing them to live for up to four days. The research team used the device to grow a strain of bacteria called Faecalibacterium prausnitzii, which lives in the human gut and protects against inflammation. They also showed that these bacteria, which are often diminished in patients with Crohn's disease, appear to exert many of their protective effects through the release of a fatty acid called butyrate. The research team included senior authors Linda Griffith, a School of Engineering Professor of Teaching Innovation in MIT's Department of Biological Engineering, and MIT mechanical engineering professor David Trumper, together with lead authors, Jianbo Zhang and Yu-Ja Huang, both postdoctoral students. The researchers also plan to use their system to study various bacteria linked to Crohn's disease, to assess the effects of each species of the condition. The team plans to joins forces with Alessio Fasano, division chief of pediatric gastroenterology and nutrition at Massachusetts General Hospital, to study mucosal tissue from people with celiac disease, and other GI conditions. Tissues grown using this method could help to reveal the secrets of microbe-induced inflammation in cells with differing genetic composition. "We are hoping to get new data that will show how the microbes and the inflammation work with the genetic background of the host, to see if there could be people who have a genetic susceptibility to having microbes interfere with the mucosal barrier a little more than other people," Griffith says. Griffith says the device can be used to study other types of mucosal barriers, including those of the female reproductive tract, such as the cervix and the endometrium. Better understanding the composition of gut bacteria, and their roles in gut inflammation and other celiac-related conditions could pave the way for major breakthroughs in the understanding and treatment of celiac disease. Read more at News-medical.net

Celiac.com 09/21/2019 (Originally published 04/05/2010) - I am a veterinarian who is doing research on the origins of disease. This came about after my miraculous recovery from multiple ailments following my diagnosis of food intolerance, particularly celiac disease. I have chronicled my recovery and findings on my website, www.dogtorj.com. I’ve come to the conclusion that most of what we call “diseases” are long-term symptoms arising from the “civil war” taking place in our bodies, between its residents—our cells and those entities designed to help and protect those residents (e.g. viruses and bacteria) and the constant barrage of immune challenges that we throw at them (e.g. food lectins, carcinogens, chemicals/preservatives, trans fats, fluoride (an “antibiotic” and carcinogen) air pollution, etc., etc. These, coupled with our horrific fast-food diets, inadequate sleep/exercise/sunlight, and self-induced misery through alcohol/drug abuse and our penchant for sugar have brought all of the plagues of Pandora’s Box on humankind. Yet we keep pointing the finger at microorganisms like viruses and bacteria, including L-forms and mollicutes, as the enemy. Granted, most don’t know or fully understand the true nature of viruses and bacteria - that they are crucial for our survival, being important instruments in our adaptation to this ever-changing environment in which we live. But shouldn’t intelligent people be asking why these guys are so ubiquitous yet a relative few people are suffering from the “diseases” caused by these “culprits? The fact is that viruses and L forms do what they do because they need to survive because they are crucial to our survival. Would you disagree that if we could snap our fingers and make all viruses and bacteria disappear from the planet that the entire ecosystem would collapse? Certainly, we know that the vast majority of these bacteria are not pathogenic? What really distinguishes a pathogen from a saprophyte—or a helper? When huge numbers of the population are infected with various “pathogenic” bacteria and yet remain asymptomatic, shouldn’t it give us pause? Why do they become such culprits of disease in the “unfortunate” few? Are they just unfortunate or have they done something—or lived somewhere, in the case of pollution—that has brought this plague on themselves? We know that the number one risk of developing legionnaire’s disease was/is cigarette smoking. Now there’s a surprise. I believe down to my core that viruses and bacteria work in concert to help us all, especially when it comes to adaptation and survival. Bacteria form L-forms and viruses mutate because they need to survive - they are critical to our survival and only become pathogens when we have forced them into doing so with the laundry list of abuses given above. Cancer is little more than a virus (and/or an intracellular bacteria) forcing that cell to duplicate out of control in a desperate attempt to protect itself, and the cell it was designed to protect, as well as escaping those noxious elements (we call them “carcinogens”) that have forced them into this final phase of adaptation. Our immune systems tried valiantly to deal with this during the preceding “autoimmune” phase, a term I no longer use because the thought of our immune system attacking itself for no reason is preposterous, especially in light of research on L-forms. And, we can’t say we weren’t warned by the broad array of symptoms we were given: the heartburn; IBS; allergies; hives; cough; migraines; seizures; fatigue/depression; etc.; etc. Certainly, there are those who have become so afflicted and immune challenged that they need some pharmaceutical aid to deal with these helper-turned-“culprit” bacteria but to become dependent upon antibiotics for any significant length of time is both potentially dangerous and unnecessary. If we stop the assault we are visiting on these misunderstood and reactionary residents, we can come off the drugs (like I did) and re-establish the status quo, and long before the two or three year mark in most cases, I believe. People simply need to know that we are the culprit, not these microorganisms at which we keep pointing our scientific fingers. Why? Because these organisms—the viruses, bacteria, L-forms and mollicutes—are here to stay! It is we who are the transient visitors. And if we want to enjoy our stay, we’re going to have to learn how to treat ourselves, and those who reside within us, a whole lot better.

Celiac.com 12/26/2018 - The first wave of results are in from the 2015 FDA-mandated post-market surveillance studies of duodenoscopes, and they are not encouraging. The duodenoscopes are designed to be reprocessed, to be cleaned and disinfected, according to manufacturer guidelines. However, reprocessed scopes show "higher-than-expected" rates of contamination with dangerous bacteria. In a recent safety announcement, the FDA revealed that 3% of properly collected samples tested positive for more than 100 colony-forming units of "low-concern" organisms. These bacteria are not likely to cause serious infections, but they do indicate "reprocessing failure." Moreover, an additional 3% of properly collected samples tested positive for "high-concern" bacteria that are more often associated with disease, such as Escherichia coli or Staphylococcus aureus. In 2013, the FDA began to focus on a possible connection between multi‒drug resistant bacteria and reprocessed duodenoscopes. In 2015, FDA ordered duodenoscope makers Olympus, Fujifilm, and Pentax to determine whether healthcare facilities were able to properly clean and disinfect the devices. The mandatory monitoring is part of the FDA’s effort to eliminate patient infections associated with bacteria from contaminated duodenoscopes. The FDA’s order required the companies to conduct two separate studies. First, they were required to sample and culture reprocessed duodenoscopes to learn more about issues that contribute to contamination. Second, they were required to evaluate the training of hospital staff in following the reprocessing instructions as part of a study of “human factors.” When the companies failed to carry out such studies promptly, The FDA sent warning letters citing their failure publicly. All three device makers have now begun collecting the required data. They recently completed testing for the initial human factors, and at least 10% of the samples have been collected for the sampling and culturing study. Initial findings from the human factors study of staff training indicate that staff finds the reprocessing instructions in current user manuals difficult to comprehend and follow, the FDA said. The FDA is working with the duodenoscope manufacturing companies to revise and clarify the user materials to improve reprocessing outcomes and to reduce contamination risk. Source: medscape.com

Celiac.com 11/13/2018 - Ubiquitin is highly conserved across eukaryotes and is essential for normal eukaryotic cell function. The bacterium Bacteroides fragilis is part of the standard human gut microbiome, and the only bacterium known to encode a homologue of eukaryotic ubiquitin. The B. fragilis gene sequence points to a previous horizontal gene transfer from a eukaryotic source. The sequence encodes a protein (BfUbb) with 63% identity to human ubiquitin, which is exported from the bacterial cell. Is molecular mimicry of human ubiquitin by gut microbe linked to autoimmune diseases like celiac disease? A team of researchers recently set out to determine if there was antigenic cross‐reactivity between B. fragilis ubiquitin and human ubiquitin and also to determine if humans produced antibodies to BfUbb. The research team included L. Stewart, J. D. M. Edgar, G. Blakely and S. Patrick. They are variously affiliated with the School of Biological Sciences, University of Edinburgh, Edinburgh, UK; the School School of Biological Sciences, Queen’s University Belfast, Belfast, UK; the Regional Immunology Laboratory, Belfast Health and Social Care Trust, Belfast, UK; and the Wellcome‐Wolfson Institute for Experimental Medicine, Queen’s University Belfast, Belfast, UK. Molecular model comparisons of BfUbb and human ubiquitin predicted likely structural similarity with 99.8% confidence. The team used linear epitope mapping to identify cross-reacting epitopes in BfUbb and human ubiquitin. Also, at least one epitope of BfUbb does not cross‐react with human ubiquitin. The team used enzyme‐linked immunosorbent assay to compare the reaction of human serum to BfUbb and human ubiquitin from 474 subjects among four groups: (1) newly autoantibody‐positive patients, (2) allergen‐specific immunoglobulin (Ig)E‐negative patients, (3) ulcerative colitis patients and (4) healthy volunteers. The team’s data show that the exposure to BfUbb into the human immune system triggers the creation of IgG antibodies. Patients referred for first‐time autoimmune disease testing are more likely to have a high levels of antibodies to BfUbb than are healthy volunteer subjects. From this, the team concludes that molecular mimicry of human ubiquitin by BfUbb could be a trigger for autoimmune disease. Finding and understanding potential triggers for autoimmune conditions helps to take us one step further to understanding and potentially curing celiac disease. Stay tuned for further developments in their arena. First published: 04 August 2018 https://onlinelibrary.wiley.com/doi/full/10.1111/cei.13195

Celiac.com 04/25/2018 - A team of Yale University researchers discovered that bacteria in the small intestine can travel to other organs and trigger an autoimmune response. In this case, they looked at Enterococcus gallinarum, which can travel beyond the gut to the spleen, lymph nodes, and liver. The research could be helpful for treating type 1 diabetes, lupus, and celiac disease. In autoimmune diseases, such as type 1 diabetes, lupus, and celiac disease, the body’s immune system mistakenly attacks healthy cells and tissues. Autoimmune disease affects nearly 24 million people in the United States. In their study, a team of Yale University researchers discovered that bacteria in the small intestine can travel to other organs and trigger an autoimmune response. In this case, they looked at Enterococcus gallinarum, which can travel beyond the gut to the spleen, lymph nodes, and liver. They found that E. gallinarum triggered an autoimmune response in the mice when it traveled beyond the gut. They also found that the response can be countered by using antibiotics or vaccines to suppress the autoimmune reaction and prevent the bacterium from growing. The researchers were able to duplicate this mechanism using cultured human liver cells, and they also found the bacteria E. gallinarum in the livers of people with autoimmune disease. The team found that administering an antibiotic or vaccine to target E. gallinarum suppressed the autoimmune reaction in the mice and prevented the bacterium from growing. "When we blocked the pathway leading to inflammation," says senior study author Martin Kriegel, "we could reverse the effect of this bug on autoimmunity." Team research team plans to further investigate the biological mechanisms that are associated with E. gallinarum, along with the potential implications for systemic lupus and autoimmune liver disease. This study indicates that gut bacteria may be the key to treating chronic autoimmune conditions such as systemic lupus and autoimmune liver disease. Numerous autoimmune conditions have been linked to gut bacteria. Read the full study in Science.

Celiac.com 08/30/2017 - The human gut is home to a huge and diverse number of microorganisms that perform various biological roles. Disturbances in a healthy gut microbiome might help to trigger various inflammatory diseases, such as multiple sclerosis (MS). Human gut-derived commensal bacteria suppress CNS inflammatory and demyelinating disease. Can they improve the treatment of multiple Sclerosis (MS)? A team of researchers recently set out to evaluate evidence that gut commensals may be used to regulate a systemic immune response and may, therefore, have a possible role in treatment strategies for multiple Sclerosis. The research team included Ashutosh Mangalam, Shailesh K. Shahi, David Luckey, Melissa Karau, Eric Marietta, Ningling Luo, Rok Seon Choung, Josephine Ju, Ramakrishna Sompallae, Katherine Gibson-Corley, Robin Patel, Moses Rodriguez, Chella David, Veena Taneja, and Joseph Murray. In a recent article, the team reports on their identification of human gut-derived commensal bacteria, Prevotella histicola, which can suppress experimental autoimmune encephalomyelitis (EAE) in a human leukocyte antigen (HLA) class II transgenic mouse model. P. histicola suppresses disease through the modulation of systemic immune reactions. P. histicola challenge caused a reduction in pro-inflammatory Th1 and Th17 cells and an increase in CD4+FoxP3+ regulatory T cells, tolerogenic dendritic cells, and suppressive macrophages. This study indicates that gut commensals may regulate a systemic immune response, and so may have a role in future treatments for multiple Sclerosis, and possibly other autoimmune diseases such as celiac disease. Source: Cell.com. DOI: http://dx.doi.org/10.1016/j.celrep.2017.07.031

Celiac.com 10/21/2016 - Researchers at Boston University's Henry M. Golden School of Dental Medicine have identified a metabolic enzyme that alerts the body to invading bacteria, which may lead to new treatments for celiac disease. A research team that set out to isolate and identify the enzymes and evaluate their potential as novel enzyme therapeutics for celiac disease, reports that the enzymes exhibit exceptionally high gluten-degrading enzyme activities, and are "naturally associated with bacteria that colonize the oral cavity." Rothia bacteria, found in human saliva, can break down gluten compounds that cause an exaggerated immune response and that are typically resistant to the digestive enzymes that mammals produce. The team was able to isolate a new class of gluten-degrading enzymes from Rothia mucilaginosa, an oral microbial colonizer. The Rothia enzymes in question belong to the same class as food-grade Bacillus enzymes. The researchers noted that "B. subtilis is food safe and has been consumed for decades, e.g. in a product called natto, a Japanese fermented soy bean dish." B. subtilis and its products have been safely consumed by humans for many hundreds of years, with very few problems reported. They add that the "…food-grade status of B. subtilis, and the already widely consumed natto products, open new avenues for potential therapeutic applications of the subtilisin enzymes." The Rothia subtilisins and two subtilisins from Bacillus licheniformis, subtilisin A and the food-grade Nattokinase, efficiently degraded the immunogenic gliadin-derived 33-mer peptide and the immunodominant epitopes recognized by the R5 and G12 antibodies. This study identified as promising new candidates for enzyme therapeutics in celiac disease. Based on these results, the research team concludes that gluten-degrading Rothia and food-grade Bacillus subtilisins are the "preferred therapy of choice for celiac disease," and that their exceptional enzymatic activity, along with their connection to natural human microbial colonizers, make them "worthy of further exploration for clinical applications in celiac disease and potentially other gluten-intolerance disorders." Their study appears in the American Journal of Physiology—Gastrointestinal and Liver Physiology.

Celiac.com 03/24/2014 - Two new studies have confirmed colonization of gluten-degrading bacteria in the human mouth and in the upper gastrointestinal tracts respectively. Both studies come out of the Department of Periodontology and Oral Biology, Boston University Henry M. Goldman School of Dental Medicine in Boston, Massachusetts. The research teams included Maram Zamakhchari, Guoxian Wei, Floyd Dewhirst, Jaeseop Lee, Detlef Schuppan, Frank G. Oppenheim, and Eva J. Helmerhorst. Gluten is notoriously hard for mammals to digest, because gliadin proteins resist mammalian proteolytic enzymes in the gut, so researchers wanted to find sources of gluten-digesting microbial enzymes from the upper gastro-intestinal tract. These microbial enzymes have the potential to neutralize the gluten peptides that act as celiac disease triggers. In the first study the researchers assessed proteolytic activity in suspended dental plaque towards a) gliadin-derived paranitroanilide(pNA)-linked synthetic enzyme substrates a mixture of natural gliadins and c) synthetic highly immunogenic gliadin peptides (33-mer of α2-gliadin and 26-mer of γ-gliadin). In addition, they conducted gliadin zymography to establish the approximate molecular weights and pH activity profiles of the gliadin-degrading oral enzymes and performed liquid iso-electric focusing to determine overall enzyme iso-electric points. Their results provide the first known evidence of gluten-degrading microorganisms associated with the upper gastro-intestinal tract. Such microorganisms may play a hitherto unappreciated role in the digestion of dietary gluten and thus protection from celiac disease in subjects at risk. In the second study, the team employed a selective plating strategy using gluten agar to obtain oral microorganisms with gluten-degrading capacity. They then used16S rDNA gene sequencing to carry out microbial speciations. To determine enzyme activity, they used gliadin-derived enzymatic substrates, gliadins in solution, gliadin zymography, and 33-mer a-gliadin and 26-mer c-gliadin immunogenic peptides. They separated fragments of the gliadin peptides by RP-HPLC, and structurally characterized them using mass spectrometry. They found that strains Rothia mucilaginosa and Rothia aeria showed high gluten-degrading activity. For example, gliadins (250 mg/ml) added to Rothia cell suspensions (OD620 1.2) degraded by 50% after 30 minutes of incubation. Importantly, the 33-mer and 26-mer immunogenic peptides were also cleaved, primarily C-terminal to Xaa-Pro-Gln (XPQ) and Xaa-Pro-Tyr (XPY). The major gliadin-degrading enzymes produced by the Rothia strains were 70–75 kDa in size, and the enzyme expressed by Rothia aeria was active over a wide pH range (pH 3–10). While the human digestive enzyme system lacks the capacity to cleave immunogenic gluten, such activities are naturally present in the oral microbial enzyme repertoire. Taken together, these studies suggest a potential for these bacteria to fuel the development of compounds that can degrade of harmful gluten peptides that trigger celiac disease in susceptible individuals. Source: PLoS One. 2011;6(9):e24455. doi: 10.1371/journal.pone.0024455. http://www.ncbi.nlm.nih.gov/pubmed/20948997

Celiac.com 05/30/2012 - From what we understand about celiac disease, both genetic and environmental factors play a part in its development: eople with certain genetic dispositions are more likely to develop it, but studies of twins at high risk of developing celiac disease have shown that in 25% of cases, only one of the twins will develop the disease. This indicates an environmental effect, and with more research it might be possible to discover what these environmental factors are so that parents with celiac disease can take steps to prevent their children from developing the disease themselves. Breast-feeding has already demonstrated some protective effect on infants at risk of developing celiac disease, but it is still unclear how the modulation of intestinal bacteria affects the formation of the disease. Understanding the role various strains of intestinal bacteria play in the intestine could be the key to understanding why breast-feeding helps prevent celiac disease, and perhaps why celiac disease develops at all. In the present study, 75 newborns with at least one first degree relative with celiac disease were broken into breast-feeding, formula-feeding groups, high (7-28%) and low (less than 1%) genetic risk groups, then tested at 7 days, 1 month and 4 months for prevalence and diversity of intestinal bacteria. Infants at high risk of developing celiac disease had more Bacteroides vulgatus, regardless of feeding methods while infants at low risk of developing celiac disease had more Bacteroides ovatus, Bacteroides plebeius and Bacteroides uniformis. Formula-fed infants had more Bacteroides intestinalis, Bacteroides caccae and Bacteroides plebeius, though prevalence depended on the testing stage. The most striking finding of the experiment seems to indicate that both low genetic risk of celiac disease development and breast-feeding are positively correlated with the prevalence of Bacteroides uniformis in the intestines. This might explain why breast-feeding can help protect against development of the disease, by introducing more Bacteroides uniformis into the infant's intestinal bacteria community. The implications of this research are still unclear, but a follow-up study on these infants is intended. Further research may explain how the prevalence of these bacteria in the intestine actually affects the development of celiac disease in infants. Source: http://www.ncbi.nlm.nih.gov/pubmed/21642397

Celiac.com 05/23/2012 - We know from past studies that the intestinal bacteria communities of children with celiac disease differ greatly from those of healthy children, but there has been little work done to draw such a correlation with adult celiac disease sufferers. Intestinal bacteria could potentially serve as a convenient way of indexing the severity of a patient's celiac disease, but research in adults is limited. A recent study remedies this, showing that adults with celiac disease do, in fact, have different intestinal bacteria from healthy adults, which may lead to a way of testing for the severity of one's disorder based on fecal bacteria tests. Ten untreated celiac disease patients, eleven treated celiac disease patients (those on gluten-free diets for at least two years) and eleven healthy adults were tested for intestinal bacteria in fecal samples. The healthy adults were tested once under normal gluten diet conditions, and additionally, ten of them were tested again after one week of gluten-free dieting. Testing showed that untreated celiac disease patients had much more Bifidobacterium bifidum in their intestinal microbial communities than those of healthy adults. Treated celiac disease patients showed decreased levels of Bifidobacterium bifidum, as well as a reduction in the diversity of Lactobacillus and Bifidobacterium. These results most closely resembled those achieved by healthy adults. It would seem, then, that a gluten-free diet helps to balance and normalize intestinal bacteria populations. While a portion of the treated celiac disease patients displayed restored, normal intestinal bacteria, there were still differences in the presence of short-chain fatty acids. Such SCFAs would appear to correlate with celiac disease, regardless of the diet taken: healthy adults, both on gluten-free diets and on normal diets had significantly fewer SCFAs than both treated and untreated celiac disease patients. Gluten-free, healthy adults had the fewest, but treated celiac disease patients actually had the highest. We can take from this study that gluten-free diets help to lower both the presence and diversity of bacteria associated with celiac disease. A gluten-free diet does not 'fix' the presence of short-chain fatty acids in the intestines though, even though it is not entirely clear what these acids signal as to the health of the individual. Source: http://www.ncbi.nlm.nih.gov/pubmed/22542995