Connie: Good evening, dear friends. It’s great to have you here with us again. Thank you for tuning in to our show. Today, we invited Professor Hofstadter to our program. Thank you for joining us, Dr. Hofstadter.
Dr. Hofstadter: Thanks for having me. Hello everyone. I’m excited to be here.
Connie: Gut microbe, as a general term for the microbial community that resides in the human intestine, is one of the most interesting research focuses in the fields of microbiology, medicine, and genetics in recent years. Research in recent years has gradually revealed the composition and quantity of gut microbiota, how it enters the human body, how to assist digestion, how it affects intestinal development, and how the imbalance of gut microbe affects overall health. But the population of gut microbe is so huge and the interaction with the human body is so complicated. There are still many unsolved problems about the gut microbe. Today, we are going to discuss gut microbe and its’ application in celiac disease treatment. So, Dr. Hofstadter, can you first give us some introductions about celiac disease?
Dr. Hofstadter: Sure. Celiac disease is a type of chronic enteropathy. It’s mainly developed due to particular proteins of our diet which initiates immune response against self-cells in genetically predisposed humans. Symptoms of celiac disease mainly include abdominal pain, weight loss, fatigue, and some indirect consequences such as anemia, osteoporosis, polyneuropathy, and cerebellar ataxia. The causative proteins are known as gluten proteins, commonly available in cereals like wheat, barley, oats, and ray.
Connie: But these proteins are so commonly in our daily diet. Why do they initiate immune responses?
Dr. Hofstadter: Well. There are antigens on the surface of leukocytes named human leukocyte antigen HLA-DQ system on antigen-presenting cells, including human leukocyte antigen Class II with DQ2 and DQ8 molecules. They are associated with the genetic predisposition of celiac disease. These receptors help to recognize self and those which are not self-molecules in the immune system. Gluten is a glutamine-and proline-rich protein and is partially hydrolyzed in the GI tract. In general, the indigested peptides enter the circulatory system and get in contact with the lymphocytes. Recognition of peptides induces the release of cytokines from lymphocytes and T-cells, such as interferon-gamma and tumor necrosis factor-alpha and matrix metalloproteinases. And if these components are activated, there could be severe damage to the villi of the small intestine.
Connie: At present, the lifelong omission of gluten and related grain proteins which is also called gluten-free diet is the only therapy for celiac disease. Any other factors that can contribute to the occurrence of celiac disease?
Dr. Hofstadter: Celiac disease onset is usually favored in subjects carrying genetic susceptibility, under the influence of triggering environmental factors, such as viral infections and dysbiosis of the gut microbiota. Although 30 to 40 percent of the global population carries the HLA DQ2 or DQ8 genotype, only 1 to 1.5 percent of them express the celiac disease phenotype. So I mean, there might be other factors, such as diet and environment, taking part in the illness outbreak.
Connie: I guess it would be hard to predict in some people. I suppose that the composition of the gut microbiota may be different in celiac patients and healthy people?
Dr. Hofstadter: You are right. Environmental factors such as repeated gastrointestinal infections and a major change in the composition of gut microbiota have been seen to be connected with the advancement of celiac disease. In this line, a case-control study on newborns who had one or more first relatives with a history of celiac disease has been done. Researchers configured the components of gut microbiota using 16S ribosomal RNA gene sequencing and found that the infants at high risk of celiac disease had modifications in the early composition of gut microbiota. The findings suggest that relative abundance of Bifidobacterium breve and Enterococcus spp. were associated with celiac disease development.
Connie: Interesting. And I just wanted to add another study that is about the gluten degradation ability of fecal microbiota from healthy and celiac disease human subjects. Researchers found that gut microbiota from celiac disease patients had reduced gluten degradation ability in comparison to gut microbiota from healthy controls. More precisely, celiac disease patients had a higher abundance of general Megasphaera and Helicobacter compared to the pre-disease condition subjects. But both disease and pre-disease condition subjects also had a reduced abundance of Akkermansia and Dorea. Similar observations recorded by several researchers indicate a direct correlation between the composition of gut microbiota and the development of clinical symptoms of celiac disease. And now, let’s move on to the next factor. The knowledge of the relation between the host genetic factors and an individual’s gut microbiota plays an important role in the development of celiac disease and can be used for preventive measures by manipulating the gut environment.
Dr. Hofstadter: Right. And for this reason, probiotics are been thought to be used as an effective tool in the control of celiac disease using dietetic strategies.
Connie: Then what is the mechanism that is associated with the beneficial effect of probiotics?
Dr. Hofstadter: There are a few different possible mechanisms of action. The first one is that probiotic is capable of balancing the composition of the gut microbiota. Secondly, probiotics can inhibit enteric pathogens. Thirdly, probiotics can help degrade bacterial antigens. Fourthly, probiotics can block the inflammatory mediators. The last possible MOA is that probiotics can stimulate local immunity.
Connie: I find that the application of probiotic intervention in the management of celiac disease has been proposed widely. For example, in newly diagnosed celiac disease children, supplementation of probiotic Bifidobacterium longum CECT 7347 in conjunction with a gluten-free diet improved the health of the subjects by influencing the inflammation markers. In later stages also, probiotic treatment has been reported to effectively improve the severity of symptoms of celiac disease patients. Another study also found apparent improvement in lactic acid bacteria, Staphylococcus and Bifidobacterium, in the fecal microbiota of patients receiving probiotic treatment.
Dr. Hofstadter: I can add to your examples. Like we’ve already discussed, the composition of gut microflora can directly influence the stability of intestinal epithelium. The intestinal epithelium is the only shield between the receptors of intestinal immune cells and their ligands. The instability of the epithelial barrier exposes a large number of antigens to the reactive immune cells and subsequently causes inflammation-generated structural and functional damage to the interphase. But we know that probiotics could restore the epithelial dysfunction by modulation of the immune response at the damage site. The generation of pro-inflammatory cytokines in celiac disease patients is a critical step during autoimmune response. Probiotics have been shown to decrease the production of these cytokines in such conditions.
Connie: And another article reported that probiotics can also modulate gluten antigen-generated immune response. The study concluded that in comparison to the placebo group, probiotics temper the immune response of peripheral lymphocytes in children having celiac disease autoimmunity.
Dr. Hofstadter: I want to point out that since evidence on this topic is still scarce, routine use in the clinical practice of probiotics is still not advised by international guidelines for the use of probiotics. So it’s important to note that our discussion today does not constitute practical clinical recommendations.
Connie: Thanks for pointing it out! Ok, so much for our content today. Thanks, everyone, for listening. I hope you enjoyed our discussion today. Thank you, Professor Hofstadter, for providing us with your great insight. We will continue our discussion on probiotics next week. See you then!