"You are what you eat" is familiar enough, but how deep do the implications go? An interdisciplinary group of investigators from the Perelman School of Medicine at the University of Pennsylvania has found an association between long-term dietary patterns and the bacteria of the human gut.

In a study of 98 healthy volunteers, the gut bacteria separated into two distinct groups, called enterotypes, that were associated with long-term consumption of either a typical Western diet rich in meat and fat versus a more agrarian diet rich in plant material. A subsequent controlled-feeding study of 10 subjects showed that gut microbiome composition changed detectably within 24 hours of initiating a high fat/low fiber or low fat/high fiber diet, but that the enterotype identity of the microbe group remained stable during the 10-day study, emphasizing the short-term stability of the enterotypes. The findings were published online in the journal Science, and may have implications for exploring the relationship between diet and therapies for gastriinstesinal dosirders.

"It's well known that diet strongly affects human health, but how diet influences health is not fully understood," says Frederic D. Bushman, PhD, professor of Microbiology , who led the study together with co-principle investigators James Lewis, MD, MSCE, professor of Medicine in the Division of Gastroenterology and professor of Epidemiology, and Gary Wu, MD, professor of Medicine in the Division of Gastroenterology. "We found that diet is linked to the types of microbes in the gut, which provides a potential mechanism connecting diet with health."

Wu noted, "Although the mechanisms by which diet influences gut microbes remain to be fully characterized, our findings also provide insights into the differences in the types of gut bacteria observed in various societies across the globe."

The team used diet inventories -- surveys that catalog what people have eaten in the last 24 hours and also what they usually eat long-term -- and compared that to sequenced DNA from stool samples from 98 healthy individuals. The sequencing allowed the researchers to count and identify gut bacteria. Fecal bacterial communities clustered into two broad groups, or enterotypes, distinguished primarily by levels of Bacteroides and Prevotella.

The enterotypes were strongly associated with diet, particularly protein and animal fat (Bacteroides genus) versus carbohydrates (Prevotella genus). Both Bacteroides and Prevotella are broad genera of bacteria species that typically live in the human gut. Humans tend to have mostly a species from one bacterial group but not both. Vegetarians were more likely to be in the Prevotella group, the enterotype associated with diets enriched in carbohydrates and lacking meat, and the one vegan was also in the Prevotella group.

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Subsequently, 10 healthy volunteers were enrolled in a controlled feeding experiment in which their diets were fixed for a 10-day period. All ten subjects in the controlled-feeding experiment were in the Bacteroides group at the start, during, and at the end of the experiment. Their gut microbiomes changed within one day but stayed within the same broad Bacteroides group, even if they ate a diet high in carbohydrates over the 10-day period, emphasizing the short-term stability of the enterotypes.

There are several potential applications of this research. The Penn investigators are currently exploring the relationship between dietary therapies for Crohn's and the composition of the gut microbiome.

"Crohn's disease is caused in part by the way our body responds to the microbes in our intestines," explains Lewis. "Dietary therapies are different from most other Crohn's disease therapies because the dietary therapies don't suppress the immune system. One hypothesis is that these dietary therapies work by changing what organisms live in the intestines."

Roughly 1.5 million people in the United States suffer from ulcerative colitis or Crohn's disease, whose symptoms include abdominal pain, bleeding, nausea, and diarrhea.

The next line of study will be to identify changes in microbial composition associated with successful dietary intervention for these diseases , then optimize ways of creating these changes for improved therapy.

Other co-authors were Jun Chen, Christian Hoffmann, Kyle Bittinger, Ying-Yu Chen, Sue A. Keilbaugh, Meenakshi Bewtra, Dan Knights, William A. Walters, Rob Knight, Rohini Sinha, Erin Gilroy, Kernika Gupta, Robert Baldassano, Lisa Nessel, and Hongzhe Li.

This work was funded as a Human Microbiome Project by the National Institute of Diabetes and Digestive and Kidney Diseases, the NIH Common Fund, and the Joint Penn-CHOP Center for Digestive, Liver, and Pancreatic Medicine.