Source: Gastroenterology & Endoscopy News



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Ideas About Gut Microbiome and Diet Becoming Mainstream

by David Wild


Source: Gastroenterology & Endoscopy News ISSUE: OCTOBER 2013 | VOLUME: 64:10

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Orlando, Fla.—A growing body of evidence highlighting the interaction between diet, the microbiome and various aspects of health may one day yield diet-based interventions for common diseases, new research, presented at the 2013 Digestive Disease Week (DDW) meeting, has shown.

“We are now beginning to consider that what we eat not only alters the composition of our gut microbiota in several ways, but that foods can also act as a substrate for these microorganisms to produce small molecules that can impact the host,” said Gary D. Wu, MD, professor of medicine in the Division of Gastroenterology University of Pennsylvania Perelman School of Medicine, Philadelphia, who spoke about the subject to DDW attendees.

Dr. Wu’s research is leading to significant revisions of prevailing and limited views about the health effects of food, which until now have been primarily attributed to nutritive components, and it is becoming clear that metabolism by intestinal microorganisms plays a critical intervening role.

For example, Dr. Wu said, the well-documented risk for cardiovascular disease that is linked to high consumption of red meat has been thought to be largely due to its high content of saturated fat. However, earlier this year, Koeth et al showed that intestinal bacteria metabolize meat-derived L-carnitine into atherosclerosis-promoting trimethylamine N-oxide (Koeth RA et al. Nat Med2013;19:576-585). Furthermore, they found that high plasma levels of an L-carnitine–derived metabolite produced by gut microbiota are associated with increased rates of cardiovascular disease, myocardial infarction and death.

Temporal Associations

Studies that document diet-induced microbial changes throughout the lifespan are critical, Dr. Wu said, especially within the context of the growing link between diet, the microbiome and health and disease.

Dr. Wu pointed to results published last year showing that diet influences the microbiome from the time of birth. Those findings revealed that breast-fed infants have higher populations ofBifidobacteria, Lactobacillus and Staphylococcus, whereas formula-fed infants have smaller populations of Bifidobacteria and Lactobacillus and larger populations of Clostridium,BacteroidesEnterobacteriaceae and Enterococcus (Thompson AL. Am J Hum Biol 2012;24:350-360). These early microbial differences have implications for growth, body composition, metabolism and physiology, and can affect an individual’s behavioral responses to food and eating, Dr. Wu said.

In 2011, Dr. Wu and other researchers from the Human Microbiome Project published seminal results from COMBO (Cross-Sectional Study of Diet and Stool Microbiota) showing that individuals have small differences in the composition of their microbiome and tend to have one of three broad “enterotypes” (Wu GD et al. Science 2011;334:105-108). They characterized the different enterotypes according to the balance of Bacteroides, which are associated with long-term protein and fat intake, and Prevotella, which are linked to diets with high amounts of simple carbohydrates. Research presented last year at the International Human Microbiome Congress showed that a Bacteroides-dominated enterotype is associated with obesity and metabolic alterations.

Other findings by Dr. Wu and his colleagues suggest that enterotypes can be altered through diet, but this takes time. In the CaFE (Controlled Feeding Experiment) study by the Human Microbiome Project, 10 healthy volunteers were monitored in a highly controlled inpatient setting and randomized to either a high- or low-fat diet for 10 days. Dr. Wu and his colleagues found that although specific diets led to small but “very significant” microbial alterations within 24 hours, the broader gut microbial composition remained fundamentally similar during and after the 10-day study (Wu GD et al. Science 2011;334:105-108).

“Enterotypes are associated with long-term diets but not with recent diet patterns,” Dr. Wu said.

Precisely how long does it take to meaningfully alter the balance of gut microorganisms?

Although the CaFE study indicated that more than 10 days are needed, another study has suggested that significant alterations can be achieved within one year. The study was a longitudinal investigation of elderly individuals residing in either the community or in long-term care (Claesson MJ et al. Nature 2012;488:178-184). Microbiome analyses revealed profound changes within one year from moving from one living environment to another, and less diverse gut microbial populations among those living in long-term residential care. Those in residential care environments also were sicker, more frail, less nourished and had more inflammation, Dr. Wu said.



Inflammatory Bowel Disease

The widespread use of elemental and defined-formula diets for individuals with inflammatory bowel disease offers a rare opportunity to study the correlation between diet, the microbiome and disease prospectively and in a real-world environment, Dr. Wu said. He and his colleagues are currently examining data from PLEASE (Pediatric Longitudinal Study of Elemental Diet and Stool Microbiota Composition), which is funded by the National Institutes of Health’s Human Microbiome Project.

“Our hypothesis is that there are elemental diet-induced alterations in the gut that are associated with therapeutic efficacy,” Dr. Wu said. “We’re also including a second group of patients treated with an anti–TNF [tumor necrosis factor]-α agent to compare changes in their microbiome.”

Mark Silverberg, MD, PhD, a gastroenterologist and associate professor of medicine at the Zane Cohen Centre for Digestive Diseases at Mount Sinai Hospital in Toronto, Canada, applauded Dr. Wu for his significant contributions to two main lines of inquiry in the study of the intestinal microbiome.

“We’re always asking ‘who are they?’ and ‘what are they doing?’ ” said Dr. Silverberg, referring to the types and function of intestinal microorganisms.

Dr. Silverberg’s own team is examining the relationship between diet and Crohn’s disease, with a focus on how diet affects the risk for disease recurrence after ileal resection. Preliminary findings based on a small group of subjects identified several foods, beverages and nutrients that seem to correlate with delayed postoperative recurrence.



“Ultimately, we should be able to alter our patients’ diets to change the populations of proinflammatory and anti-inflammatory bacteria and potentially manage chronic disease this way,” Dr. Silverberg said.
Drs. Wu and Silverberg reported no conflicts of interest.


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