Resolving to eat better in 2020?

Talk to Buck associate professor Dan Winer about vegetables and the immune system and it’s likely you will never see either of them in the same light again. You may also walk away with a new appreciation of a really healthy gut.

“The wall of the gut houses the largest collection of the cells that make up the immune system, a fact that comes as a surprise to most people,” says Winer, who studies the role of the immune system in aging and chronic metabolic diseases such as type 2 diabetes and fatty liver disease. “While conditions such as inflammatory bowel disease are directly linked to immune responses in the gut, most people don’t understand how important the gut is to overall health. The immune system in the gut traffics throughout the body.  If your gut is chronically inflamed, you’re asking for all kinds of health problems.”

Tackling gut inflammation is where the veggies come in – especially cruciferous veggies such as broccoli, cauliflower, Brussels sprouts and cabbage. “When it comes to diet, it’s not just about avoiding the bad stuff like processed foods, sugar and saturated fat,” he says. “Instead it’s about feeding ourselves foods that can improve gut integrity and overall health.” In other words, it’s an opportunity to reframe food choices from a chore to a treat, at least for the gut. 

The magic of cruciferous veggies

What’s the science behind these powerhouse veggies? Eating them activates the aryl hydrocarbon receptor (AhR), a protein that regulates gene expression. A new role for AhR is being recognized - as an essential player in maintaining normal intestinal immune function.

“Not only does AhR help keep the lymph cells in the intestine happy, it also promotes the creation of interleukin-22, a compound that sets off a cascade of protection in the gut,” says Winer, an MD who trained in pathology. Among its many benefits, interluekin-22 helps prevent leaky gut, a condition whereby the junctions between cells lining the gut become weak and permeable, allowing bacteria, their products, and food particles to get into the blood stream. Leaky gut is an invitation to systemic inflammation.

Winer says interleukin-22 also causes other cells in the gut to shoot out molecules which control dangerous bacteria in the gut, helping reshape our microbiome to a more diverse, healthier state. “Our microbiome factors into how well our bodies tolerate toxins (think food poisoning) and it’s involved in food allergies, “says Winer. “So eating these vegetables also helps us maintain good health in the face of challenges.”

Cruciferous vegetables also include sulforaphane, an antioxidant that acts as an anti-inflammatory in the gut. Winer says the compound shows a wide range of biological activities in humans and shows promise in preventing a variety of cancers and is also being studied for its effects against cardiovascular and neurodegenerative diseases and type 2 diabetes.

 Don’t forget the fiber

While cruciferous veggies often get top billing for their nutrient dense health-promoting benefits, there’s good reason to enjoy vegetables and fruit that pack a punch of fiber. Apples, pears, berries, sweet potatoes, carrots, beans, bananas, asparagus, jicama and chicory root are among those making this list.

The trillions of tiny microorganisms living in our intestines literally feed off fiber, increasing in number and kind when we eat a fiber-rich diet. The more beneficial microbes we have in our intestines, the thicker the mucus wall and the better the barrier between our body and our busy bacterial population. That stronger barrier provides a two-for-one benefit; while the mucus barrier lowers inflammation throughout the body, the bacteria aid in digestion.

“Fiber plays a really important role in modulating the immune system in the gut,” says Winer, pointing out that undigested fiber is broken down by the bacteria in the gut into short-chain fatty acids which are a food source for the intestine itself. “Cells that line the gut use short-chain fatty acids for energy. And T-cells, one of the main immune cells in the gut, use those short-chain fatty acids to create Interleukin 10, an important anti-inflammatory which also helps prevent leaky gut.”

Unfortunately, the average American diet is woefully low in fiber. Adults are only eating about 15 grams of fiber on any given day, despite these recommendations from the Academy of Nutrition and Dietetics:

• 25 grams for women, or 21 grams if over 50 years old
• 38 grams for men, or 30 grams if over 50

If you’re aiming to add more fiber to your daily diet, experts recommend going slowly in order to avoid digestive distress, gas and intestinal blockages. Winer says it’s also important to not see fiber as a fix-all for eating badly. “Fiber and saturated fat are not a good combo. Fiber makes the high fat hang around in the colon encouraging bad bacteria to grow – one study showed that it may actually promote liver cancer in mice. We need to eat balanced diets.  You can't just eat ice cream all day and then take chicory root extract and think you're going to be okay.”

The immune system and blood sugar

Given that his lab studies the role of the immune system in type 2 diabetes and other metabolic diseases, Winer is particularly focused on how the immune system controls blood sugar, a topic which brings us back to AhR and cruciferous vegetables.  “I believe that the gut is the center of the universe when it comes to metabolic disease,” says Winer. “And AhR helps mediate how the immune system controls both blood sugar and fat metabolism.”

Winer says visceral fat, which connects our internal organs, is one of the bad actors in a process that leads to insulin resistance and metabolic disease. It’s why obesity is a major risk factor for type 2 diabetes. Winer says fat sends out inflammatory factors, which attract immune cells to cause insulin resistance inside fat.  A leaky gut helps fuel the inflammatory processes in fat. “Obesity sets off a cascade of inflammatory events which make it harder for the body to use natural insulin. It’s not the only factor at play with type 2 diabetes, but it’s important.”

Winer says the immune system also manages hormones that are made in the gut. One in particular is the glucagon like-peptide 1 (GLP-1) which controls insulin production in the pancreas and makes us feel full. T cells in the gut can control the levels of GLP-1 entering circulation for instance and thus represent an attractive target for future therapies against diabetes and metabolic conditions. 

Winer has collaborators working on discovering compounds and developing therapeutics that would mimic the anti-inflammatory properties of AhR, and based on work in mice there’s good reason to think they could work in humans.  In one of his recent works, published in the International Journal of Obesity, his lab fed mice on a high fat, low fiber diet supplemented with an AhR mimetic and their glucose levels didn’t go up as fast as the control group.  “While we would never want people to use a therapeutic as a substitute for eating the right food, there are situations where finding the right type of supplementation could be helpful,” he said.

One of those situations could involve aging. Winer says researchers don’t fully understand how the immune system in the gut changes with aging, or how diet interfaces with the immune system, the microbiome, and the liver and fat in the context of aging. These are all questions that the Winer lab, new to the Buck in 2019, is tackling.  “The Buck, with its expertise in aging and its collaborative environment is the perfect place for my group to explore these issues. Simple observation makes it pretty clear that aging does have an impact on how our gut functions. But we have to understand it at the molecular level if we’re going to design interventions that help people stay healthy.”  

If keeping busy with worthwhile projects is good for the gut, then Winer has nothing to worry about.  He has several collaborations he is pursuing. One with the Campisi lab is looking at the role of individual inflammatory factors in gut health, a project with the Kapahi and Lithgow labs explores gut inflammation and permeability, and another with the Verdin and Melov labs explores mechanisms involved in metabolic tissue inflammation.