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Healthcare professional Resource for Gluten Related Disorders.

Dr. Schär Institute

The importance of the microbiota in the pathogenesis and treatment of celiac disease

Dr. Schär Institute Intestinal microbiome Gluten intolerance
The composition of the gut microbiome is influenced by many factors. The microbiota may also be a key influencer in overall health and disease outcomes.
Man is not a single living being; he lives in a community with trillions of bacteria and other micro-organisms. The gastrointestinal tract is most densely populated: it has an estimated 100 trillion (10^14) micro-organisms, which are referred to in their entirety as the intestinal microbiota (formerly intestinal flora). The number of microbial cells in the intestine is ten times greater than the number of human somatic cells. Because they have about 150 times more genes than the human body, they have an enormous metabolic activity. Their metabolic products and neurotransmitters have a close interdependency with the somatic cells both inside and outside the gastrointestinal tract. They support the digestive functions, help ward off pathogenic micro-organisms and contribute to the development and maintenance of the immune system and the intestinal barrier. The intestinal barrier is a complex system that separates the intestinal lumen from the inside of the body and is composed of the following elements:
  • Mechanical: Epithelial cells with tight junctions, mucus
  • Humoral: Defensins, immunoglobulins, cytokines
  • Immune cells: Specific and non-specific immune cells
  • Muscle cells
  • Nerve cells

The intestinal microbiota is involved in metabolic processes and can modulate the barrier function. In addition to a balanced microbiota, another important protection mechanism for a functioning intestinal barrier is the regulation of paracellular passage through tight junctions.

In recent years, scientists have achieved great progress in the study of microbiota thanks to the application of methods of analysis from molecular biology. The 1000 types of bacteria that occur in the intestine can be divided into a total of six different subgroups. Up to 90% of the intestinal bacteria belong to the groups of firmicutes and bacteroidetes, followed by proteobacteria, actinobacteria, verrucomicrobia and fusobacteria. The majority of micro-organisms are found in every human intestine. These are referred to as the core microbiome. Every person also has a variable part. This makes up the individual microbiota. The composition and activity of the microbiota are influenced by several factors, including type of birth (vaginal or C-section), genes, age and lifestyle. Medicines (e.g. antibiotics) and diet play an important role: factors such as quantity and type of fiber and fermented foods consumed are important. According to recent studies, the composition of the microbiota plays an important role in the maintenance of health. The different species of bacteria can have both protective and harmful effects. Certain pathogenic bacteria can, for example, cause local inflammation, weaken the intestinal barrier and increase permeation of substances including gluten.

Celiac disease and microbiota

It is known that missing peptidases in the human intestine mean that gluten is incompletely digested and that gluten peptides are absorbed via Tsmall intestine mucosa. Furthermore, there is growing evidence that a change in intestinal permeability due to increased permeability of tight junctions (TJ) is a major factor in the pathogenesis of celiac disease. This makes it simpler for the remaining oligopeptides to be absorbed into the lamina propria and trigger the inflammation typical of celiac disease. It is still unclear whether disorders of the intestinal barrier are the primary cause or the consequence of celiac disease. However, it has been possible to demonstrate that in the case of persons suffering from celiac disease, gliadin is a strong stimulus for the release of zonulin. This protein increases intestinal permeability by facilitating the absorption of macromolecules via TJs.

On the other hand, there is evidence that changes in the intestinal microbiota can lead to increased intestinal permeability and therefore may be involved in the pathogenesis of celiac and allergic diseases. There are, however, only a few studies on the role of the microbiota in the pathophysiology of celiac disease. It is believed that in the case of genetically susceptible patients, gram-negative bacteria are involved in the loss of gluten tolerance. Comparative studies between children with celiac disease and healthy control groups detected a lower number of lactobacilli and bifidobacteria in the children with celiac disease. However, it is unclear whether a change in the microbiota is the primary cause or the consequence of celiac disease. In biopsy specimens of the duodenum of untreated children with celiac disease, more gram-negative bacterial strains were detected compared to treated children and healthy control groups, which suggests a change in the microbiota as a result of this disease.

Celiac disease and probiotics

Currently, the only therapy there is for celiac disease patients is a strict lifelong gluten-free diet (GFD), which includes avoiding traces of gluten. In the long term, this is difficult for many of those affected, especially without concomitant dietary advice. Despite complaints and the risk of complications and long-term consequences (e.g. malignancies, refractory celiac disease) 30% to 50% of patients do not maintain a strict gluten-free diet. Given the knowledge of changes in the intestinal microbiota in persons with celiac disease, the following studies have demonstrated that the use of probiotics may constitute a promising approach to concurrent therapy of celiac disease:
  • In 2006, De Angelis et al. examined combination preparation VSL#3, which contains 8 different probiotic strains (e.g. bifidobacteria and lactobacilli). They demonstrated that compared with isolated strains and other commercially available products that were tested, the combination of these probiotic strains can split gliadin peptides more effectively, i.e. gliadin peptides are easier to digest with the aid of this probiotic combination preparation.
  • In the case of PBMCs*, De Palma's research group (2010) was able to reduce the secretion of interleukin-12 and IFN-gamma (pro-inflammatory cytokines) under the influence of gluten in-vitro, using specific bifidobacteria. This observation suggests an anti-inflammatory effect of the investigated bifidobacteria.
  • Lindfors et al. (2008) demonstrated that the bacterial strain b. lactis can prevent the toxic effect of wheat gliadin on epithelial cell cultures at doses of 106 and 107 CFU** per ml, but not at 105 CFU per ml.
  • In a mouse model by D`Arienzo et al. (2011), a milk product with the l. casei ATCC 9595 strain (Actimel) enhanced the intestinal barrier function and prevented the intake of gliadin in the lamina propria.

          * PBMC: peripheral blood mononuclear cell
          ** CFU: colony-forming units

NCGS and probiotics

As yet there is no practical study on the influence of the microbiota on the pathogenesis of this new disease in the specific case of gluten/wheat sensitivity. Unlike celiac disease, an innate immune response is suspected in the case of NCGS. This is activated by gluten or wheat, but does not alter the intestinal mucosa or its permeability. However, there are indications of increased intestinal permeability in patients with neurological symptoms such as schizophrenia or autism and suspected NCGS.

The aforementioned studies demonstrate that certain strains of bacteria aid the digestion of gliadin peptides. This may mean that patients with NCGS can as in the case of celiac disease benefit from a concomitant course of probiotics. Further studies are required for specific recommendations.

In the case of some diseases (e.g., antibiotic-associated diarrhoea, irritable bowel syndrome, ulcerative colitis, pouchitis) there are studies that demonstrate clinically relevant efficacy of probiotics. However, the underlying mechanisms are still unclear. There are currently few studies on the relationship between celiac disease and microbiota and the use of probiotics in the treatment of celiac disease. Since many effects of probiotic micro-organisms are strain-specific, evidence that has been obtained with a specific bacterial strain or preparation/product for celiac disease cannot necessarily be transferred to other strains of probiotics. Further investigation of the underlying mechanisms of action is necessary. Due to the many positive experiences and lack of side effects, the trial use of probiotic foods is recommended.

Advice for the selection and the use of probiotics:

Choosing the right probiotic! Duration of use:
Effects are strain-specific Continuously for at least 4 to 8 weeks
Sufficiently high bacterial count of 10 (8) and 10 (9) CFU per day Change the preparation or product if there is no significant effect after 8 weeks
Recommend products that also contain bifidobacteria  
At the beginning of therapy: Take with meals and refrain from products with prebiotics such as inulin and oligofructose; to decrease the potential of simultaneous malassimilation of carbohydrate. Refrain from those with lactose or fructose  
Slowly increase dosage (start with ½ the amount)  
is a qualified Nutritionist specializing in Allergies. Since completing her qualification in Nutritional Science, she has worked as a nutritional therapist, lecturer, journalist and writer, mainly in the field of Allergology and Gastroenterology. She writes books and speaks at lectures, training seminars and further education courses for doctors on the subject of food allergies and intolerances.

is a qualified Nutritionist and has worked as a freelance nutritionist, lecturer and writer for over 20 years. She advises both patients and companies on nutritional issues, and as a professional writer publishes books, brochures, specialist publications and internet articles.
  • Binns N: Probiotics, prebiotics and the gut microbiota. ILSI Europe Concise Monograph Series 2013.
  • Bischoff, SC (Hrsg.): Probiotika, Präbiotika und Synbiotika. Georg Thieme Verlag, Stuttgart, 2009.
  • Bischoff SC, Köchling C: Pro- und Präbiotika. Akt Ernährungsmed 37, 287-306, 2012.
  • Bischoff SC, Barbara G et al.: Intestinal permeability – a new target for disease prevention and therapy. BMC Gastroenterology 14: 189, 2014. doi: 10.1186/s12876-014-0189-7.
  • Blaut M: Interaktion von Ballaststoffen und Mikrobiota. Aktuel Ernahrungsmed 40, 43–49, 2015.
  • Catassi C, Bai JC, Bonaz B et al.: Non-celiac gluten sensitivity: The new frontier of gluten related disorders. Nutrients. 2013, 5, 3839-3853; doi:10.3390/nu5103839.
  • Catassi C, Elli L …. : How the diagnosis of non celiac gluten sensitivity …. In Vorbereitung 2015.
  • Charisius H, Friebe R: Bund fürs Leben. Warum Bakterien unsere Freunde sind. Carl Hanser Verlag München, 2014.
  • De Angelis, M, Rizzelo C. G., Fassano A et al: VSL#3 probiotic preparation has the capacity to hydrolyze gliadin polypeptides responsible for celiac sprue. Biochim. Biophys. Acta. 2006; 1762: 80-93.
  • Drago S, El Asmar R, Di Pierro M et al.: Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Scan J Gastroenterol. 2006; 41: 408–419.
  • Fasano A: Physiological, pathological, and therapeutic implications of zonulin-mediated intestinal barrier modulation: living life on the edge of the wall. Am J Pathol. 2008: 137: 1243–1252.
  • FAO/WHO: Probiotics in food. Health and nutritional properties and guidelines for evaluation. FAO Food and nutrition paper 85, 2002.
  • Felber J, Aust D, Baas S et al.: S2k-Leitlinie Zöliakie. 2014. URL:
  • Körner U, Schareina A: Nahrungsmittelallergien und -unverträglichkeiten in Diagnostik, Therapie und Beratung. 2. überarb. u. erw. Auflage. 2015 (in Vorbereitung).
  • Meddings J: The significance oft the gut barrier disease. Gut. 2008: 57: 438–440.
  • Moraes L. F. de Sousa, Grzeskowiak L.M. et al: Intestinal Microbiota and Probiotics in Celiac Disease. Clinical Microbiology Reviews 2014; 27: 482-489.
  • Sapone A, Lammers KM, Casolaro V et al.: Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity. BMC Medicine. 2011, 9:23 (9 March 2011).
  • Sapone A, Bai J, Ciacci C: Spectrum of gluten-related disorders: consensus on new nomenclature and classification. BMC Medicine. 2012, 10:13 (7 February 2012).
  • Schuppan D, Zimmer KP: Diagnostik und Therapie der Zöliakie. Deutsches Ärzteblatt 2013; 110: 835-846.