Interview with Gary Wu: Reducing the incidence of metabolic and immune diseases through a better understanding of diet and microbiota

Gary Wu

‘You are what you eat’ is something we have heard for years, and not only at the doctor’s office. Nevertheless, science is now backing this up – for example, just recently Dr. Gary Wu, of the Perelman School of Medicine at the University of Pennsylvania, completed a study that supports this idea. Leading a team of researchers, Wu observed that bacteria inhabiting our intestinal tract grow differently depending on the person’s diet.

Besides being a Professor in Gastroenterology at the University of Pennsylvania, Wu was the immediate past Director and Chair of the Scientific Advisory Board for the American Gastroenterological Association Center for Gut Microbiome Research and Education. He is an expert on the interactions between the gut bacteria and the host and focuses his research, overall, on diet and metabolism. We attended the Bdebate conference on the human gut microbiome, held at the Cosmocaixa Science Museum in Barcelona, on June 30 and July 1. There, GMFH editors spoke with him about diet and how to take care of our microbes.

Are we what we eat? Or should we say, what our gut microbiota eat?

Largely what we eat has an effect directly on us, independently of gut microbiota, because it is obviously food and nutrients. Some of what we eat is actually use[d] by the microbes in the intestinal tract to produce all different types of small molecules; in fact, bacteria have specific genes that allow them to produce these exact molecules we cannot [produce]. And these small molecules circulate through our bodies, which is why microbiota have an effect on bodily functions separate from where the microbiota is really located. So yes, in a way you are what you eat, but you are also what your microbes eat [and] produce, [what] we end up absorbing.

Does a different diet translate into a different gut microbiota composition and diversity?

There are studies that show that individuals living, for example, in agricultural societies in Africa have a different microbiota composition than people living in industrialised nations, like for example in Europe or the United States. We actually did a study about two years ago in which we looked at the composition of the gut microbiota in vegans, eating largely a plant-based diet, and omnivores eating the [typical] diet. Surprisingly we found there was in fact a difference in the composition of gut microbiota, but it was really, really small.

How can that be?

I personally believe that diet does have an effect [on] the microbiota, but based on previous publications, that effect of diet is very rapid, within 24 hours, although relatively small. However, if you feed your gut microbiota different food, based on your own diet, your microbes will produce different types of small molecules. So, although a vegan’s and an omnivore’s microbiota are not dramatically different, the types of small molecules their microbes produce due to eating largely a plant-based diet or an omnivorous diet would be different.

For example, plant-based products contain a lot of molecules we don’t have the enzymes to digest but the gut bacteria are really fermenters [of], so they can release those molecules. And if you are eating a largely plant-based diet, like a vegan diet, the microbiota would release those small molecules in higher levels than if you are eating less plants, for example, in an omnivorous diet.

So, does eating a healthy plant-based diet favour a healthy gut microbiota?

There is a lot of interindividual variability: my microbiota is very different from your gut microbiota. And diet has a small impact in the composition of the gut microbiota relative to how different we are from each other. Will eating a healthy diet change your gut microbiota? It is a little bit hard to say.

The key message is we already know that a healthy diet, largely plant-based, [there’s] plenty of epidemiological evidence that [it] is linked to lower heart disease, metabolic syndrome, obesity rates. Many things about diet are beneficial or deleterious independently from the microbes that live in the gut. Perspective is very important.

In a 2011 study, you discovered that those people following a meat-rich diet had a greater amount of the Bacteroides genus making up their gut microbiota while those who had a high fibre diet had more Prevotella bacteria.

Prevotella tends to be predominant in individuals that live in Africa in agricultural cultures, whereas Bacteroides is a genus that tends to be predominant in people living in industrialised nations. A paper published last year showed that the predominance of Prevotella or Bacteroides predict a better response to the consumption of complex carbohydrates and glucose tolerance, which is important in metabolic syndrome and diabetes.

In that study, if you had predominantly Prevotella then your chances of responding favourably to a complex carbohydrate diet with respect to glucose tolerance were enhanced rather than having [a] predominantly Bacteroides type of microbiota. And that makes sense, because Prevotella is a genus very good at fermenting complex carbohydrates. But, we have to be cautious. Right now, this is one of the first publications showing an effect on metabolic syndrome. Can we apply those results to everybody? We don’t know, it is too early. I am really optimistic that within the next couple of years we will have much more information.

What about the impact of antibiotics on gut microbiota?

The use of antibiotics has been transformative in the field of medicine. They have saved more lives than almost any other interventions, more than vaccines or clean water. And used in a proper medical context, they are very important. The problem is that because they are so available they are very used in the practice of medicine. And that may disrupt early life gut microbiota and increase the risk for some immunological diseases like asthma. But the overuse of antibiotics leads to antimicrobial resistance too, which I believe is a much bigger problem.

Can we use antibiotics and probiotics to shape gut microbiota?

I am very optimistic that there will be new types of probiotics, next generation probiotics that will have a bigger effect on health. But now it is too early to say whether we can use antibiotics to kill the bad bacteria and probiotics to replenish or augment the good bacteria. I am, though, optimistic. It is just [that] we need more time to come up with ways to model the microbiota using antibiotics or probiotics or prebiotics in a way that will favour health.

In your opinion, what are the most exciting results we are going to see in the next years in the field of gut microbiota and nutrition?

I am particularly interested in diet and prevention of disease. In the last five or six decades we have seen such a rapid increase in immune diseases, like asthma, inflammatory bowel disease, metabolic syndrome. And that’s not a genetic effect on us, but an environmental one. And the microbiome and diet are two fundamental components of the environment. So I am hopeful that, although I don’t know when this will happen, maybe in a couple of years or maybe the next decade, we will begin to understand enough about diet and microbiome and that will help us reduce the increasing incidence of these metabolic and immune system diseases. In my opinion, prevention of diseases is really the Holy Grail, because it is going to have the largest impact on populations.

 

Cristina Sáez
Cristina Sáez
Cristina Saez is a freelance science journalist. She works for several media, for instance the Spanish newspaper La Vanguardia, where she coordinates the science section, Big Vang; as well as research centres and scientific societies. She has been awarded for her journalistic work, among others, with the Boehringer Ingelheim Award in Medical Journalism 2015. Follow Cristina on Twitter @saez_cristina