The National Foundation for Celiac Awareness (NFCA) recently covered a study that is exploring the main cause behind celiac disease.
There have been clinical studies suggesting an association between altered gut bacteria and celiac disease. These descriptions have been challenged on the basis that they could be an effect of the disease process. This new study moves us closer to understanding the cause of celiac disease development by showing that in an animal model, bacteria can act as an environmental agent that changes the responses to gluten.
To get more information on this groundbreaking study, NFCA had the pleasure of speaking with the project lead, Elena Verdu, MD, PhD at McMaster University, Canada.
Q. What does it mean to have a gut that consists of “ultra-clean” bacteria?
A. These are mice that are originally germ-free to which we then introduce a defined group of benign bacteria in their gut. We make sure we avoid introducing potentially bad bacteria such as E. coli.
Q. The complex bacteria named in the study (E. Coli, Staphylococcus and Helicobacter) are known to be harmful to humans. Are these bacteria “good for the gut” in small amounts? What function do these bacteria have in the human body?
A. The bacteria I mention in the study are not the typical “harmful” or pathogenic bacteria of outbreaks. They are a mix between being harmful (pathogens) and commensal (the good bacteria) and are officially known as pathobionts or opportunistic bacteria. These opportunistic bacteria are present in the gut and have important roles to instruct our immune system how to fight the real harmful pathogens. However, in some conditions where these particular bacteria outgrow the commensals (the good bacteria), they could cause problems.
Q. What types of reactions did the group with the complex bacteria experience?
A. The mice that reacted more to gluten were those in which the opportunistic bacteria grew after receiving antibiotics that killed other commensals. These mice developed an increased number of intraepithelial lymphocytes, a marker of celiac disease, as well as reduction in the villi height (the fingerlike projections of the intestinal lining).
Q. Your study suggests that the findings could lead to a new treatment for celiac disease. What might this treatment involve and how would it impact gluten that has been digested?
A. The findings suggest that the type of bacteria in the gut could affect the degree of reactions to gluten. While this could lead to a new therapy that a patient would use to supplement the gluten-free diet, the impact would likely be more preventative than therapeutic. In the long run, the holy-grail would be to find the ideal bacterial communities that prevent reactions to gluten and decrease the risk to develop celiac disease in people at risk.
Q. What’s the relationship, if any, between your team’s discovery and the hygiene hypothesis, (which essentially asserts that a lack of childhood exposure to some germs and infections increases a person’s chances of developing an allergic or autoimmune disease)?
A. Our study illustrates the great complexity that exists between gut bacteria and the host, which is also known as an organism that houses those microbes. This relationship is a double-edge sword.
In germ-free mice the reactions to gluten were worse than in mice with the ultra clean bacteria. Having the benign bacteria greatly minimized the reaction to gluten. However, not all bacteria had this protective effect.
When we increased the number of opportunistic bacteria in mice with complex microbiota using selected antibiotics, the reactions to gluten became worse compared to mice with the ultra clean microbiota. So in other words, there may be some benefit to having the proper commensal bacteria.
Q. How do your new findings impact the celiac disease field overall and where will you go from here?
A. The main message is that we should consider bacterial factors, and not necessarily infections with pathogens (harmful bacteria), as potential factors for impacting a person’s celiac disease risk.
It is important to stress that gluten is the trigger of celiac disease, not a bacterium. The main message is that factors that modify the normal balance in our microbiome could tip the balance towards higher risk to develop celiac disease in someone who carries the celiac disease genes. We are working on defining precise mechanisms and the specific culprits to try to prevent celiac disease. This study was a multi-center collaboration where my group worked with the Mayo Clinic (Dr. Joe Murray), Columbia University (Dr. Armin Alaedini), the University of Chicago (Dr. Bana Jabri) and IATA in Spain (Dr. Yolanda Sanz).