The Sherman Prize: Gary Wu, MD

Dr Wu, one of the Sherman Prize winners for 2020, discusses his work in the effects of diet on inflammatory bowel disease and his career-long collaboration, as a wet bench molecular biologist, with researchers and clinicians to translate basic science into improvements in the care of patients.

Gary Wu, MD, is the Ferdinand Weisbrod professor of gastroenterology at the Perelman School of Medicine at the University of Pennsylvania, the director of the Penn Center for Nutritional Science and Medicine, a codirector of the PenCHOP Microbiome Program, and the codirector of the Digestive Disease Center,

Transcript:

Dr. Gary Wu: Hello, everybody. My name is Gary Wu. I'm professor of gastroenterology, the Ferdinand Weisbrod professor at the Perelman School of Medicine. I'm the director of the Penn Center for Nutritional Science and Medicine, a codirector of the PenCHOP Microbiome Program, and the codirector of our Digestive Disease Center, NIH-funded.

I am one of the 2020 Sherman Prize awardees, and I'm deeply honored to be the recipient of this award amongst a field of really outstanding investigators and clinicians. It's just a wonderful award and I give a tremendous amount of credit to both Bruce and Cynthia Sherman for raising awareness and providing support to this award. I'm truly honored.

I have to say that I’m a wet bench molecular biologist but I share this prize equally with so many of my collaborators that I've worked with over the many years, trying to translate basic science research into human subject studies that are relevant to human biology, particularly focused on inflammatory bowel disease.

With that as an introduction, I began studying the microbiome with my colleagues at Penn almost 15 years ago as the field was beginning to accelerate. We did some studies very early on showing the impact of diet on the composition of the microbiome. What was different about our research was that we were beginning to do studies in humans.

When thinking about diet and its impact on health and disease, particularly focused on inflammatory bowel disease, we're very intrigued by the observation that certain types of diets, particularly exclusive enteral nutrition diets, are an effective modality for the treatment of Crohn's disease.

It emphasized the fact that environmental factors play a very strong role in the pathogenesis of inflammatory bowel disease. There are genetic factors, and then there are environmental factors. We know that environmental factors are very important, because there's been a rapid rise in the incidents of inflammatory bowel disease that are associated with industrialization or with Westernization of societies.

This became obvious about 150 years ago in Europe and now in Western society, in Asia, in China, and in India. It's all tied to a Westernized lifestyle. One of the most important factors of a Westernized lifestyle is the food that we eat.

The current notion is that perhaps the way that our food is processed or the way that we consume our food is somehow deleterious in patients with inflammatory bowel disease. With this notion in mind, after initially characterizing the way that diet influences the composition of microbiome, we then went on to do a study in omnivores and vegans because their diets are extremely different from each other.

We could show that not only does the microbiota respond to what you eat, but it also leads to the production of many different types of small molecules that we can detect both in the stool and in the blood. Many groups have been studying the notion that diet is a substrate that allows the microbiota to produce a lot of these small molecules that can activate various types of pathways, physiologically relevant pathways, by engaging receptors that can have a deep effect on physiology of the host.

With that understanding, we then undertook a number of studies investigating the impact of exclusive enteral nutrition. These are primarily liquid diets. Some of them are elemental, meaning they're very simple in composition -- simple sugars, amino acids, and lipids. Some are a little bit more complex.

At the end of the day, they all seem to work well only if you exclude whole food. That's why we call it exclusive enteral nutrition. We've done a number of studies looking at the impact of these enteral nutrition diets on the composition of the microbiota, and they do have a significant effect on the composition of the microbiota.

We also understand that it also has a very significant effect on the metabolites that you can see in the stool as well as circulating in the blood. One of our newer findings with these enteral nutrition diets is that it appears that fiber is very important in the composition and function of the gut microbiome.

We've known this for many years in mouse studies. I'm a wet bench scientist, and those are the model systems that I tend to use. We could also show this in humans.

Fiber is felt traditionally to be good for inflammatory diseases because they produce small molecules like short-chain fatty acids, butyrate, that seemed to help regulate the immune response and fortify intestinal barrier function.

However, these enteral nutrition diets do not contain any fiber in them, yet they're still effective. We can see significant changes in the composition of the microbiota and in the small molecules that they make, despite the fact that they don't actually have fiber in them.

I think that that's a very important thing. It doesn't mean that fiber is not important. I personally believe that fiber is very important for the microbiota and can promote beneficial effects on health, but it does mean that these exclusive enteral nutrition diets work through a different mechanism.

That's what we're trying to understand. Currently, the evidence points to the fact that they may be excluding something that you'd normally eat in whole food that is deleterious for patients with inflammatory bowel disease.

As we progress with these types of studies, we hope to understand what it is in a whole food diet that is bad for patients with IBD. If we could understand that, then we can have better insights into what might be prudent and good diets for patients with inflammatory bowel disease that might work together with the drugs that are currently available to get better responses and improve remission rates.

That's ultimately our hope. I'm looking forward to seeing all of you at AIBD. With that, thank you very much for spending the time with me and hearing about the research that we've been doing.