Celiac disease is among the most common food allergies, with it affecting an estimated one in hundred people globally. It is caused by an allergic reaction to a protein present in wheat – gluten – that causes discomfort in the stomach including bloating and diarrhoea.
There is currently no cure to the condition, and it can only be controlled by avoiding all forms of food containing wheat, rye or barley, including staples such as breads and chapatis. But as research into the gut microbiome evolves, some potential avenues for the condition’s treatment could emerge.
Scientists have observed that those with celiac disease show alterations in the composition and function of their gut microbiota. Evidence does not conclusively show that these changes in the microbiota cause celiac disease, but it does support the fact that altering the gut microbiota could be a potential therapeutic.
“The diversity of the gut microbiota is very low in celiac disease. There is reduction of beneficial bacteria in the gut, particularly Bifidobacterium and Lactobacillus which are known for their anti-inflammatory and immunomodulatory properties,” says Dr Raj Vigna Venugopal, gastroenterologist and hepatologist, and head of department of gastroenterology at Manipal Hospitals, Bengaluru.
Moreover, the reduction in populations of helpful bacteria in the gut fuels the overgrowth of harmful bacteria such as Escherichia coli and Bacteroides in those with the condition. These bacteria contribute to the degradation of the mucus layer (mucins) that increases intestinal permeability, a hallmark of celiac disease.
But to understand how experimental treatments targeting bacterial balance restoration in the gut work, we need to understand celiac disease itself.
The basics of gluten intolerance
Celiac disease may cause bloating and diarrhoea when a person consumes any food containing gluten as it causes an immune response that damages the lining of the small intestine. This damage can also lead to the malabsorption of nutrients, ultimately causing vitamins and mineral deficiencies in people with it.
“Celiac disease is a health condition in which people have enhanced immune reaction to gluten,” explains Dr Venugopal, adding that the condition in most cases develops during childhood, but can develop during adulthood as well. Apart from gastric issues, individuals with the condition may also experience weakness, skin problems (dermatitis), low haemoglobin, bone thinning and bone fractures in adults.
It is caused due to a complex interplay of genetic and environmental factors. Genetic predisposition and exposure to gluten may trigger an innate inflammatory response of gut and an inappropriate immune response due to loss of gluten tolerance. Strong genetic predisposition is associated with the expression of human leukocyte antigen (HLA) genes, DQ2 and DQ8, adds Dr Venugopal.
Gliadin, a main component of gluten, is partially broken down into peptides in the intestine. Immune cells bind these peptides and elicit an abnormal immune response leading to production of antibodies against the enterocytes (cells lining the intestine). There is also severe inflammation in the intestine.
“Small intestine has finger-like projections called villi, which are responsible for increasing the absorptive capacity of the intestine. These villi are damaged in celiac disease that reduces the absorptive area of the intestine,” says Dr Venugopal.
The overall effect of these immune and inflammatory response results in damage to the intestinal mucosa, resulting in malabsorption and nutrient deficiencies.
The gut and microbiota connection
Research suggests that alterations in the composition and function of the gut microbiota can contribute to the development and progression of celiac disease. There are a few leading theories as to how this may happen:
Some bacteria exhibit proteins that mimic gliadin and may enhance an immune response in the person. Another theory suggests that some bacteria, such as Pseudomonas aeruginosa, may work in conjunction with gluten to trigger and escalate intestinal inflammation.
Gut bacteria may also directly produce immunogenic peptides or directly increase intestinal permeability or may enhance intestinal inflammation by generating proinflammatory mediators.
Moreover, we also know that acute gastrointestinal infections may affect the normal balance of the gut microbiota. Infections caused by rotaviruses and enteroviruses, particularly in the first 6-18 months after birth, are associated with an increased risk of celiac disease.
“There is indirect evidence that children who were breast fed have less incidence of celiac disease because probably the microbiota found in them have plenty of good bacteria,” adds Dr Venugopal.
Future treatments for celiac disease
As we already know, there is no current cure for celiac disease. “Currently, the treatment involves withdrawal from all gluten diet. Cereals which contain gluten should be completely avoided and person must switch to gluten-free diet,” says Dr Venugopal.
Targeting the gut bacteria in celiac disease is an attractive approach to promote the growth of beneficial bacteria and restore gut functions. Novel therapies able to modulate the gut bacteria are being developed as complementary strategies in celiac disease.
Probiotics: A probiotic mix of Lactobacilli and Bifidobacterium strains has been reported to cause breakdown of gluten. This lowers the inflammation and gluten-induced damage of epithelial cells in the small intestine. Probiotics are also an excellent source of endopeptidases (an enzyme) that digest gluten.
Faecal microbiota transplantation (FMT): This is a method in which gut microbiota from a healthy donor is transferred into the digestive tract of the recipient, with the aim of restoring gut microbial imbalance. The faecal matter of a healthy donor is delivered via either a nasogastric tube, colonoscope or capsule method.
While these methods are yet to make it to clinical practice, they are creating a lot of hope among those who are suffering from celiac disease. However, even these techniques might not be the cure for the condition, only an adjunct therapy after they are approved.