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October 9, 2014

Science 2014: Gut Feelings

The same Western diet that has helped increase our lifespans to more than 80 years also has introduced several diseases into our microbiome, the organisms that populate not just our gut but other organ systems as well.

That was the message at an Oct. 2 session of Science 2014, Pitt’s annual science and technology celebration.

Stephen J.D. O’Keefe, a faculty member in the School of Medicine, opened the day by demonstrating how his research on African Americans and rural Africans points toward a risk for colon cancer in the Western world’s protein-heavy diet.

“It basically is a Westernized disease,” O’Keefe said of gastrointestinal cancers, blaming 90 percent of GI cancers on our diet heavy in red meat, animal fat and processed meats.

This was demonstrated in a study of Japanese immigrant families to Hawaii, who entered the island with a much lower GI cancer risk but whose members, within one generation, had a GI cancer risk equal to that of longer-term Hawaii residents.

Of course, O’Keefe allowed, Africans have a higher degree of one type of colitis, as well as parasites.

But “the dietary needs of every organism are genetically determined,” he said. Would Westerners be healthier if they ate more fiber and less protein, a diet closer to the fare originally consumed by Homo sapiens? “It’s the balance between these two factors that determines your cancer risk.”

O’Keefe hypothesized that it was the metabolic product of the microbiome digesting our food that affected GI cancers, with high fiber residue in the colon creating smaller amounts of inflammation-causing byproducts than did high-fat residue.

He studied two groups of healthy African Americans and rural Africans to test his theory.

“You don’t need to be a nutritionist to see a different diet” between the two groups, he said, displaying a slide of an American hot dog and fries in all their greasy glory. The food in rural Africa, by contrast, is largely boiled carbohydrates, with three times the amount of fiber of a typical American meal.

The microbiome in each group had a completely different makeup, he found.

Africans had high levels of butyrate, which reduces bowel inflammation and has other positive effects, while African Americans had higher amounts of bile acid-synthesizing bacteria, which are carcinogenic.

To further examine how the diet affected the microbiome, members of both groups were fed each other’s diet for two weeks while living in the testing facility.

“Our results were actually remarkable,” he reported, with markers for each other’s microbiomes increasing in opposite groups, from 50 to 400 percent.

Clearly, he concluded, the Western diet “is setting the type of metabolic pathway … that is likely to increase your risk of cancer.”


O’Keefe’s contention about the Western diet was echoed in the presentation of David G. Binion, visiting faculty member in medicine and co-director of the Inflammatory Bowel Disease (IBD) Center.

IBD has increased throughout the world over the past six decades, paralleling Westernization. But half of the world’s 4 million IBD cases are in the U.S., with the same incidence of ulcerative colitis and Crohn’s disease. The cost of treating these incurable illnesses in the U.S. has increased 10 percent each year over the past three years, he said.

Crohn’s disease and IBD produce ulcers in the colon, which are deep and hard to treat. Ulcerative colitis is a misnomer, Binion said, because it produces no ulcers. But “it looks like you took sandpaper to the mucosa” in the intestine, he noted.

Crohn’s affects the entire body, producing skin sores and other symptoms, and has a “huge morbidity.”

Our digestive system “is the largest immune organ in our body,” he said, with 70 percent of our immunity originating there. If the human gut were flattened it would be as big as a tennis court.

When functioning normally, it allows us to introduce food into our bodies from the environment while protecting us from pathogens. The microbiome, which does a bunch of that work, is made up of only 10 percent human cells. Ninety percent are other organisms that inhabit us.

This gut microbiome works from the earliest age. Infants “have an intuitive behavior to jam everything into their mouths,” he pointed out. In that way individuals develop their immune systems: “You create tolerance.”

But the microbiome is susceptible to negative environmental influences, too. When it comes to Crohn’s disease, Binion said, “we can predict based on Westernization where the disease is going to occur.”


The National Institutes of Health’s Microbiome Project began in 2007, studying the microbiomes of five major body systems that interact with the world: nasal, oral, skin, GI and urogenital.

But, as Alison Morris pointed out, the effort has ignored the other major organ on which our environment has an impact: the lungs.

Morris, a faculty member in pulmonary, allergy and critical care medicine, as well as clinical and translational research and immunology, said study of the lung microbiome is far behind examinations of the GI microbiome, but “there probably is important genetic material in the lung microbiome.”

One challenge of studying the lung microbiome is gaining clean access to the lungs. Getting tissue involves an invasive bronchoscopy, leaving samples very susceptible to contamination from the oral or nasal cavity, through which they must pass on exit. “You have to go through a veritable sewer,” she said.

Another difficulty is the continuity between the upper and lower respiratory tracts. There is a bi-directional transit of materials as we breathe and cough, making it hard to determine what originates in which spot.

Plus, she said, different parts of the system have different temperatures, ventilation, gas tension and other factors, so there is “considerable variation” in microbial populations.

Morris is studying the lung microbiome as part of the National Heart, Lung and Blood Institute’s Lung HIV Microbiome Project, which has enrolled large numbers of participants at eight sites.

She has been surprised to find no significant differences between the microbiomes of healthy nonsmokers and smokers. “Perhaps the lung (microbiome) may be more resilient to changes,” she said. “It may take more to tip the community over to disease.”

She also is examining the possible role of the lung microbiome in diseases such as chronic obstructive pulmonary disease and cystic fibrosis.

She cautioned that, thus far, researchers have been examining only the microbiome’s parts, “which overlooks the web of interactions, the functions, how it affects the host.”

—Marty Levine

Also at Science2014

Jeffrey I. Gordon was awarded the Dickson Prize in Medicine during Science 2014.  He spoke Oct. 2 on “A Microbial View of Human Development: The Gut Microbiota  and Childhood Undernutrition.”

Jeffrey I. Gordon was awarded the Dickson Prize in Medicine during Science 2014. He spoke Oct. 2 on “A Microbial View of Human Development: The Gut Microbiota and Childhood Undernutrition.”

Filed under: Feature,Volume 47 Issue 4