Reinhard Hinterleitner is an assistant professor in the Department of Immunology at the University of Pittsburgh. He studied biotechnology at the University of Applied Sciences in Vienna and received his PhD from the Medical University of Innsbruck, Austria. Supported by an Erwin Schrödinger Postdoctoral Fellowship, Hinterleitner joined the laboratory of Bana Jabri at the University of Chicago where he studied the role of enteric viral infections on oral tolerance in the context of celiac disease. Hinterleitner’s research focuses on the cross talk between gut microbes and the host mucosal immune system in the context of food sensitivities and intestinal inflammation.
What is the background to your research?
Incidences of immune-mediated food sensitivities, including celiac disease and various food allergies, are rising globally, and we need to understand why. At present, the only real treatment is to stop eating the food that causes symptoms. Food avoidance means that people with severe allergies have a restricted diet and risk a potentially lethal allergic reaction if there is any contamination. We know that gut microbes play an important role in food sensitivities. Dendritic cells constantly sample food antigens from the intestines and, through the induction of regulatory T cells, they help the immune system establish ‘oral tolerance’ to food antigens. There have been studies that show that imbalances in gut microbial communities (‘dysbiosis’), lack of certain microbial products, and external factors, such as viral infections, can all trigger loss of oral tolerance. Dysbiosis can be caused by modern lifestyle practices, including high-fat low-fibre diets, antibiotic overuse, and urban living. If we can learn how to carefully modulate the gut microbial population using probiotics or other therapies, we might be able to quell the overreaction of the immune system and prevent inflammatory responses to certain foods.
How does your project differ from previous microbiome work?Most previous research has investigated the associations and correlations between gut bacterial communities and disease. Bacteria are in the majority in the gut microbiome; other significant inhabitants — archaea, viruses, protists and fungi — have been studied far less. Our project will focus on protists: unicellular eukaryotic microbes that are actually quite large — you can see them swimming around under the microscope. Research has been mainly focused on disease-causing parasitic protists, and very little is known about commensal protists and their potentially beneficial role in our health. No-one has really studied protists in the context of food sensitivities. We will explore the function and mechanisms of gut protists in modulating immune responses in the context of food sensitivities. There are some interesting immune pathways we think that protists can induce, and we hope to pinpoint these.
How will you examine the role of protists?
We will use different mouse models of celiac disease and food allergies to study how protists are modulating immune responses and whether the process is protective in these animal models. We are also using mice that are germ free — bred with sterile guts. They live in a bubble, effectively, until we come to work with them. This means we can control precisely what microbes we introduce to their gut and find out how the mice respond. It is a really powerful tool.
We hope to determine which immune cells and pathways are moderated by protists and whether the moderation is beneficial. We also want to know how protists are interacting with immune cells: are they producing a specific metabolite, for example? To visualize how the immune cells are behaving in response to the protist activity, we will stain different immune cells and use flow cytometry to monitor how they respond and interact with protists. We will also investigate whether protists can protect against viral-induced loss of oral tolerance, which we showed is linked to celiac disease development.
What will be the main application of your findings?
This grant will enable us to highlight the importance of the protective function of protists in the context of food sensitivities, and this will be the foundation of future projects. The hope is that we can show promise in the animal models, which will then facilitate collaborations to see if we can translate our findings to humans. There is also the possibility of commercializing some of our findings, and using protists in novel probiotic treatments.
What are your longer-term research goals?
My team and I will continue looking at the mechanisms by which gut microbes affect food sensitivities. Better understanding of the interactions between gut microbes and the immune system will give us the ability to fine-tune immune responses to prevent food sensitivities without causing side effects. Ideally, we want to accomplish that by either using probiotics or microbe-based products. These studies will also be helpful for us to unfurl the complexities of other bowel conditions, like inflammatory bowel disease, as well as for other extra-intestinal conditions influenced by the microbiome. Scientists have recently uncovered associations between gut microbes and autoimmune conditions, such as multiple sclerosis, and various cancers. The different populations of microbes in the gut help to train the immune system. If there are chronic microbial imbalances then your immune system is not fully charged, and it opens you up to all kinds of diseases and conditions.
Any advice for researchers who might apply for this grant in future?
It’s important to be brave and follow your own ideas and not necessarily follow the lead of others; set your own trend and choose something that no-one else has looked into before.
What do you enjoy doing in your free time?
I play computer games and I like to think I’m honing my problem-solving skills! If you’re too preoccupied with work, your ideas soon dry up and you become a bit robotic. My partner and I also love hiking in the mountains and visiting the beautiful national parks here in the United States.
Find out more about the Global Grants for Gut Health here.