On her refrigerator at home, Jennifer Wargo has put up a chart that lists the fiber content of various foods: 15 grams in a cup of black beans, 8 grams in a cup of raspberries, 4.5 grams in a medium apple with skin. Each day, the surgical oncologist and cancer researcher encourages her three kids, ages seven, 11, and 13, to eat enough foods from the list to add up to 50 grams.
The goal: to take charge of the family’s inflammation.
In the last few decades, researchers including Wargo have accumulated evidence to support some key ingredients in a healthy diet that most effectively control inflammation and reduce the risk of cardiovascular disease, cancers, and other illnesses. Now, scientists are zeroing in on the community of bacteria that lives in our digestive systems—the gut microbiome—as the place where specific foods and ingredients, including fiber, elicit or inhibit inflammatory reactions that ultimately affect the trajectory of diseases and response to cancer treatment. By focusing on the gut, they are generating new insights into ways that people can use diet like medicine to both prevent and treat chronic illnesses.
Wargo, who is based at the MD Anderson Cancer Center in Houston, copied the chart from a cookbook published by America’s Test Kitchen called Cook for Your Gut Health: Quiet Your Gut, Boost Fiber, and Reduce Inflammation. She often gives it to people for Christmas. “I didn’t necessarily pay a lot of attention to this until we really started to study it,” Wargo says. “And I was like, ‘Oh my gosh, this is really profound.”
An apple a day
Good nutrition has been a cornerstone of health advice for thousands of years, based on longstanding observations linking certain eating patterns with longer, healthier lives.
In modern times, inflammation has become a popular target for healthy eating, as a bulk of studies have accumulated to link a variety of foods and diets with both lower rates of disease and lower levels of inflammatory molecules circulating in the blood. Many of those studies focus on Mediterranean-style eating, which is full of fruits, vegetables, fish, and whole grains; low in saturated fats in favor of olive oil; and includes dairy in moderation.
Over decades of research, Mediterranean eating has been associated with lower risks of cardiovascular disease, type 2 diabetes, and other diseases, including mental health conditions. Research suggests a Mediterranean eating pattern can reduce the risk for depression by 33 percent, says Wolfgang Marx, an expert in nutritional psychiatry at Deakin University’s Food & Mood Centre in Melbourne, Australia.
Studies have found more nuanced benefits from variations on the Mediterranean diet. The DASH diet, which stands for Dietary Approaches to Stop Hypertension, may help lower blood pressure, for example. The MIND diet, which is like DASH with an extra focus on brain-healthy nutrients such as omega-3 fatty acids and vitamin D, and rich in plant-based foods such as berries and leafy greens, may be protective for the brain. In an analysis of multiple studies, people who most closely followed the diet had a 17 percent lower risk of dementia than people with the lowest adherence, found a 2023 study, though recent clinical trial results have cast some doubt on the link.
Although the true magnitude of these benefits remains a topic of debate—in part because studying diet is complicated and because people who eat healthier diets also often adopt other healthy behaviors—numerous studies have found lower levels of inflammatory molecules in the blood in people who eat Mediterranean-style diets. Studies in lab dishes, animals, and people also find anti-inflammatory responses to specific nutrients and ingredients, including turmeric, oily fish, apples, avocados, carrots, and leafy greens.
Overall, foods and nutrients likely interact to affect health more than any one hyped superfood or spice, says Fred Tabung, a cancer researcher at The Ohio State University College of Medicine and Comprehensive Cancer Center in Columbus. In a 2023 analysis that used inflammatory molecules as one kind of measure for the health effects of foods, he and colleagues found that these molecules, or biomarkers, responded differently based on the combinations of foods and beverages in people’s diets. Results suggest, for example, that eating a tomato salad with a source of fat such as avocados and a little cheese might be better for lowering chronic systemic inflammation than eating tomatoes alone, Tabung says.
Preparation matters too: Baked potatoes affect the immune system differently than French fries. Tabung is considering developing a tool to help guide meal planning. “The same nutrient can interact with its different sources of food to affect the same biomarkers differently, and these biomarkers are the causal factors in chronic disease,” he says. “Where we obtain the nutrient is more important than the nutrient itself.”
On the flip side, diets heavy in highly processed foods, red meat, and saturated fats appear to boost inflammation and accelerate the development of disease. In 2021, Marx and colleagues looked at 15 reviews of studies that encompassed data on four million people worldwide and found that people who ate more ultra-processed foods had a higher risk of heart attacks, cancers, depression, and premature death. Ultra-processed foods are defined as shelf-stable convenience foods containing five or more ingredients that are almost never used in home kitchens, such as preservatives, artificial colors, and compounds that add texture or enhance taste.
For every 100-gram increase in industrially manufactured foods, the research showed a 4 percent rise in levels of C-reactive protein, which the liver makes in response to inflammation and is often used as a general marker of inflammation in the body. According to some estimates, those kind of foods make up nearly 60 percent of calories consumed in the U.S. and as much as half of calories in a number of other countries. “From a healthy diet, it’s an anti-inflammatory effect, but now we’re seeing from an unhealthy diet, it’s a pro-inflammatory effect,” Marx says. “We’re seeing it from both sides.”
Good bugs, bad bugs
As work continues to assess which foods help or hinder inflammation in which combinations, the gut microbiome has become a focus of efforts to understand how it is that food might cause or inhibit inflammation in the first place.
Scientists have known for a long time that many hundreds of kinds of bacteria live on and inside us. In our intestines, those microbes help digest our food, and in the process produce molecules that communicate with our immune systems. Those messages, in turn, influence how much inflammation our bodies produce. What we eat alters the composition of microbial species, studies show, and the bacterial communities we cultivate has been linked with the likelihood of developing cancers, depression, autism, arthritis, and inflammatory bowel disease, among other conditions.
Diversity and variety in the gut microbiome appear to be particularly important, Wargo says. When the gut contains many species of microbes that include the most desirable varieties, the immune system can function at its best to regulate inflammation and maintain health. When that balance gets thrown off, certain species can start to dominate the ecosystem, making the immune system less able to respond appropriately or fight off diseases.
Diet might be one way to tinker with the microbiome to treat diseases, including cancer, studies show. And fiber appears to be one major piece of the puzzle. In 2017, after years of work, Wargo, colleague Carrie Daniel-MacDougall, and others established a link between the composition of gut microbes, which help digest fiber, and responsiveness to a type of cancer immunotherapy called immune checkpoint blockade, or ICB. In animal trials, they found that mice on a low-fiber diet failed to respond to immunotherapy, while those given more fiber did fine. The composition of their microbiomes correlated with those differences.
Now they are finding the same kinds of results in people. After analyzing the diets and gut microbiomes of 128 melanoma patients on ICB, they found that, for every five-gram increase in daily fiber intake, there was a 30 percent lower risk of progression or death from the disease. That paper, which was published in late 2021, was a breakthrough toward a new understanding of how diet might not just prevent cancer, but also help enhance treatment. “It was a blockbuster,” says Wargo. “That’s opened up a whole new kind of line of treatment.”
Scientists are now trying to unravel the ways that different diets target the microbiome in different groups of people, not just cancer patients, and fiber is likely not the only important nutrient. A Mediterranean diet was associated with enhanced responsiveness to ICB in people with advanced melanoma, suggests work by dietitian Laura Bolte at the University of Groningen in the Netherlands. And fermented foods such as yogurt, kimchi, and kombucha reduced inflammatory markers and boosted diversity of the gut microbiome in a 2021 trial of 36 healthy adults done at the Stanford School of Medicine.
There is a lot left to work out. The fermentation study, for example, found few to no benefits from a high-fiber diet, possibly because people in the trial already ate a reasonable amount of fiber when the study began, says Daniel-MacDougall, a nutritional epidemiologist at the MD Anderson Cancer Center in Houston and one of Wargo’s collaborators.
Paradigm shift
Still, putting a lens on the microbiome, the researchers say, has created a paradigm shift in the field of nutrition and disease. More than a decade ago, Daniel-MacDougall says she didn’t have evidence-based advice to give to cancer patients who asked her what they should eat to help fight their disease. Now evidence is building to recommend eating a wide variety of fruits, vegetables, and high-fiber foods including avocados, berries, and leafy greens, and to eat fewer ultra-processed foods, red meat, sugar, and saturated fat—with some nuances depending on a person’s condition and nutritional needs.
Whole foods may be more effective than supplements, Daniel-MacDougall adds, because they contain compounds that stimulate the bacteria that are best at keeping the microbiome in balance. “When you don’t have enough of the good guys is when these bad bugs can really flourish,” she says.
Anti-inflammatory diets have been trendy for a long time, but they often put a misguided emphasis on lowering inflammation instead of optimizing how the body regulates the process, experts say, while also putting too much value on specific foods or nutrients instead of overall healthy eating.
Although much of the advice emerging from new research echoes age-old advice about what to eat, there are now more reasons than ever to explain why. “Choose a diet that is rich in fiber-rich plant foods,” Daniel-MacDougall says. “Put more of that on your plate and shove the other crap off.”