Hi. My name is Justine Debeluis. I'm a graduate student in lab. I work on the American Gut Project. I also study the way gut microbes affect the development and progression of auto-immune diseases. Auto-immune disease occurs when the body makes a mistake and starts to recognize healthy tissue cells or organs as foreign. Some common auto-immune diseases include Celiacs disease, Crohn's disease, Lupus, Multiple sclerosis, Rheumatoid arthritis, and Type 1 Diabetes. Autoimmune diseases are caused by complex genetic and environmental factors, including the microbial. Let's look at some of the ways microbes may influence of the development of autoimmune diseases. Crohn's disease is an autoimmune disease of the intestines. People with Crohn's tend to have very unique microbiomes with lots of E.Coli and related species. It has been proposed that the E.Coli in Crohns might be a special type that sticks to intestinal cell walls called M cells near the entrance of Peyer's patches. Macrophasias and dendritic cells, which signal an immune response are found in Peyer's patches. The E.coli is thought to activate an inflammatory immune response and may be part of the initial development of Crohn's. An interesting recent study looked at a link between the microbiome hormones and the development of auto-immunity. Autoimmune diseases are more common in women than men, and are frequently diagnosed in adult women before menopause. People with autoimmune diseases tend to have higher levels of estrogen compared to people of the same age. This study used non-obese Diabetic or NOD mice, which spontaneously developed autoimmune Diabetes. The mice were raised under two conditions. Some of the mice were gnotobiotic, like Luke talked about last week. As a review, these are mice without any bacteria. The study also looked at pathogen free mice. Pathogen free mice are raised with a controlled microbiome. There are typically enough bacteria to keep the mice healthy, but nothing that is known to cause illness. In pathogen free nod mice, more females developed diabetes than males. In gnotobiotic mice, the males and females developed diabetes at the same rate. There is also a difference in testosterone between pathogen free and gnotobiotic mice. Pathogen free mice have a larger difference in testosterone between males and females. Gnotobiotic females had higher testosterone than pathogen free females, and gnotobiotic males had lower testosterone than pathogen free males. Transfer of fecal microbiome from adult males to young females was able to protect the young females from diabetes. Recipients of the male to female transfer also had higher testosterone. When a drug was used that decreased the testosterone in female transplant recipients, they developed diabetes. This is exciting because it suggests a mechanism for microbes to regulate the development of autoimmune disease. Hopefully, Microbiome research continues to look at mechanisms behind autoimmunity. Large data sets, like the American Gut project, are important to being able to do this research. It could be very exciting if people with autoimmune diseases like type 1 diabetes, rumotoid arthritis, inflammatory bowel disease, lupus or multiple sclerosis, signed up for the project. >> Hi, I'm Dr. Embriette Hyde, a post doctoral research associate in lab. And now that Justine has told us all about the microbiome and auto immunity, it's time to narrow our focus and discuss a more specific and very common inappropriate immune response, food allergy. Food allergies are inappropriate immune responses to food particles that are mediated by an antibody called immunoglobulin E, or by T cells. Immunoglobulin E and T cells are both important components of the immune system. The most common food allergies are milk, peanut, egg, tree nut, soy, fish, wheat, and shellfish allergies. But, have you ever wondered why some people are allergic to these foods while other people are not? Or have you wondered why someone might be allergic to peanuts while another person is allergic to eggs? Or why some allergies occur in childhood but others develop later in life? Perhaps you've thought that it all has to do with our genetics. Although our own genes do play a role in whether we develop a food allergy, sometimes they are not fully responsible for an allergy. This indicates that things from our environment may have an effect. Because microbes are important for immune system development, an incorrect immune response to something like a specific type of food could mean that the microbiome plays a very important role in the incorrect immune response. Several studies have demonstrated that early exposure to bacteria in pet dander, dirt, and other environmental particles reduces a child's chances of developing skin and respiratory allergies. This is because bacteria play an important role in the development of the immune system. If we are not exposed to bacteria during our childhood, our immune systems cannot develop properly. Therefore, scientists have also wondered whether exposure to microbes could affect whether or not a person develops a food allergy. Agnes Wold was the first person to wonder whether gut microbes could play a role in food allergy when she observed that Pakistani infants who have fewer allergies than Swedish infants, are colonized much sooner by typical gut bacteria than Swedish infants. This delayed colonization is likely due to the Western lifestyle of Swedish people compared to the less hygienic lifestyle of Pakistani people which exposes them to a more diverse microbial community. Importantly, this delayed colonization could compromise the immune system and affect the infant's ability to properly react to food particles and eventually cause food allergy. According to Doctor Sarkis Mazmanian, bacteria's role in allergy development can be thought of as flipping a switch. Bacteria in our digestive tracks flip important switches that enable correct immune responses. If those bacteria are not in the GI tract at the right time, the switch does not get flipped, and allergies can develop. This may explain why Pakistani children who are colonized with switch flipping bacteria sooner than Swedish children develop allergies less often. Molecules called Toll-like receptors, which recognizer foreign molecules such as bacterial proteins, appear to be an important immune switch flipped by bacteria. Mice that do not have toll-like receptors are much more susceptible to food allergies. Mice was a properly functioning tool-like receptor that are treated with antibiotics are also more prone to develop food allergies, which is highly suggestive that intestinal bacterial play an important role in the development of food allergies. However, not all bacteria flip toll-like a separate switch, suggesting that the relationship between host genetics, the microbiome, and food allergies is quite complex. A study by Novel Rivas et al, demonstrated that in mice with a genetic predisposition for food allergies, food allergies are associated with a specific gut microbial signature. Firmicutes are decreased and proteobacteria are increased in allergic mice with a genetic predisposition for food allergy, but are unchanged in mice without a genetic predisposition for food allergy. As discussed a few weeks ago, germ free mice are a useful tool for studying the microbiome. Germ free mice are born without bacteria in their bodies. When bacteria from another mouse or another organism such as a human are transferred to germ free mice, these mice are called gnotobiatic mice. In this study performed by Novel-Rivas et al., when the gut microbial of allergic mice was transferred to germ free mice without a genetic predisposition for food allergy. These gnotobiotic mice developed food allergies and produced antibodies specific for the food particle. So, microbiome imbalances seem to promote food allergies, especially in genetically predisposed individuals. So, next time you are wondering about food allergies and why some people get them and some do not,. Remember that food allergies are the result of a complex relationship between our own genetics and the microbes that live within us. And remember the old adage that a little dirt never hurt.
