Most health-conscious people know about celiac disease, in which the wheat protein gluten leads to an immune reaction that causes serious damage to the lining of the small intestine.


Certain features of gluten make it more likely to induce immune responses than other proteins. One key difference is that gluten is less amenable to being broken down by the enzymes that normally digest proteins. Another factor is gluten’s propensity to bind to certain proteins in immune cells that normally detect pathogens (damaging external factors). This leads to a cascade of events that result in the activation of various types of immune cells; in other words, gluten causes inflammation.


However, these features of gluten aren’t enough to explain the development of celiac disease. In most cultures throughout the world, almost everyone eats gluten, but not everyone gets celiac disease. How can this be explained?


Research has raised the intriguing possibility that the gut microbiome – those bacteria that live in the guts of healthy people – has a major impact on a person’s reaction to gluten and their chance of developing celiac disease.


The Helpers in the Gut

The microbiome is increasingly being shown by research to be a vital part of human health. Interestingly, babies are born sterile, meaning that they have no bacteria in their guts at all. Slowly, they acquire bacteria from the environment, and especially from the people around them. The microbiome is fully developed by the time a child is three years old.


These gut bacteria have a significant role to play in digestion, but that’s not all. They also affect the immune system of the person housing them. Mice that are raised in a sterile environment and therefore don’t have any gut bacteria (called sterile mice) have a number of problems with their immune systems. Not only do they have a reduced number of immune system cells within the gut (which are important to protect from infections acquired through the gut), but sterile mice also have alterations in the immune cells circulating in the blood. There are reduced numbers of immune cells, and many of these cells fail to develop and mature properly. Not only does this leave the animal more vulnerable to infections; it could also lead to the development of autoimmunity, in which the immune system attacks the animal’s own cells, because immature immune cells may not recognize the difference between self and other.


It’s also been shown that the intestinal bacteria have an influence on the response to food. In studies, it’s been found that those germ-free mice are more susceptible to developing allergies to cow’s milk or peanuts. (In terms of biochemistry and pathophysiology, celiac disease isn’t the same as a food allergy; however, it is a food sensitivity that’s mediated by the immune system, so it certainly makes sense that celiac disease could have some commonalities with food allergies.)


So the microbiome has an influence on the health of the immune system. Genetics is another crucial factor in immune function. Research indicates that both are important in the development of celiac disease.


Genetic Influences on Celiac Disease

While we’re focusing here on the microbiome, keep in mind that genetics do have a role to play in the development of celiac disease. There are several genetic variations that make an individual more susceptible to getting celiac, including certain variations in important proteins of the immune system. Everyone who gets celiac disease has a particular form of human leukocyte antigen (HLA), a group of proteins on the surface of immune cells.


However, many people with the “right” genes for celiac never develop the disease. This indicates that, while genetics is important, there’s something else going on in the individual’s environment that leads to certain people getting celiac disease. The exact nature of those factors is a subject of much research. With rates of celiac disease rising in the developed world over the past several decades, figuring out which factors are causing this rise is crucial.


Microbial Alterations in Celiac

Those individuals who have celiac disease have several differences in their microbiome compared with those who don’t have the disease. Early studies found that those with celiac disease had increased numbers of potentially harmful bacteria and decreased numbers of the harmless ones, compared with those who didn’t have the disease. Many studies since have corroborated this finding.


An important question is whether eating a gluten-free diet normalizes the bacterial profiles of people with celiac disease. While being strictly gluten-free does cause the small intestinal lining, which is damaged by gluten in people with celiac, to return to its normal healthy structure, studies are mixed on the question of whether the bacteria of people with celiac disease change when on a gluten-free diet. In some studies, they remain more similar to the bacteria of untreated celiac disease patients than to the bacteria of people without the disease. However, in other studies, those celiac patients on a gluten-free diet have bacteria more similar to the healthy control population than to the untreated celiac patients. In fact, in one study, putting normal controls (without celiac disease) on a gluten-free diet caused changes to their bacterial profile. The reasons for the different findings among different studies are not yet clear.


What Influences the Development of the Microbiome?

The development of the microbiome begins at the time of birth. While it isn’t fully developed until age three and is subject to change throughout life, the bacteria that enter the gastrointestinal tract during the first year of life can have a major impact on the bacteria that grow there throughout the lifespan.


When infants are born vaginally, they acquire a significant number of bacteria during the transit through the mother’s vagina. Infants born by cesarean delivery aren’t exposed to the same environment, and it’s been shown in several studies that cesarean delivery is associated with altered development of the gut microbiome, which is slower to develop and may have a different composition. Similarly, antibiotics can change the microbiome significantly, and those who receive a course of antibiotics within the first year of life are shown to have differences in the microbiome when compared with those who didn’t receive any antibiotics. The diet also has an influence on the microbiome, because the bacteria subsist on the food eaten by the host; babies fed breast milk and those fed formula have some differences in the types of bacteria present in the intestines. This is likely due to bacteria that enter via the breast milk, as well as factors within the breast milk that are metabolized by bacteria, encouraging the growth of certain species.


Are the Bacteria the Cause?

An important limitation of such studies is the question of causality. Are the changes in the gut microbes a cause of celiac disease? Or are they a consequence of having the disease? (To make things more complicated, both could actually be true at the same time.) It’s not necessarily clear from the research that the altered intestinal bacteria play a causative role in celiac disease.


However, there is reason to believe that the bacteria are at least partially a cause of celiac disease. Studies have shown that the bacteria in the intestine are able to induce immune cells to become activate and create inflammation; this would damage the small intestinal lining and lead to the symptoms of celiac disease. Bacteria also influence the types of gluten metabolites that are produced in the intestine. This means that some types of bacteria tend to cause more inflammatory metabolites to be produced, while other types of bacteria lead to more benign gluten metabolites. These lines of research show that it’s plausible that the microbiome could be an important factor in the development of celiac disease, although they aren’t definitive.


What Does This Mean?

Research indicates that both genetics and the microbiome are important in the development of celiac disease. If you want to use the results of this research in your life, you’re probably wondering what might be available now.


There is a genetic test available that can tell you whether you carry the genetic variations associated with the development of celiac disease. The test looks for HLA-DQ2 and DQ8; if you have neither of these variations, then your chance of developing celiac disease is extremely low. However, remember that many people have these variations and never get the disease, so if you have them, it doesn’t mean that you definitely have or will develop celiac disease.


While no one can change their genetics, it may be possible to alter the microbiome, to promote the growth of bacteria that are less likely to cause inflammation and disease. This could potentially be accomplished through the use of probiotics. These supplements contain certain types of bacteria that have been shown to be less inflammatory in research studies. If these “good” bacteria are able to colonize the gut, they may decrease symptoms of celiac disease.


While high-quality large-scale studies of this type of treatment have not been completed, there was one small study that gave probiotics to celiac disease patients. They experienced an improvement in gastrointestinal symptoms of the disease (compared to patients who received a placebo), and decreases in the formation of antibodies against gluten proteins, both of which are positive signs. Unfortunately, these patients didn’t show an improvement in intestinal permeability; however, the results of the study are encouraging, and should lead to more research in this area.


Unfortunately, because the research in this area is still very new, it’s difficult to make specific recommendations about how to optimize the mix of bacteria in your gut. Overall, eating a variety of fresh foods, including beans, fruits, and vegetables, is likely to provide your microbes with the material that they need to thrive. While you wait for the development of a probiotic that can treat or prevent celiac disease, that’s a good place to start.