Preidis receives 2-year NASPGHAN research grant for microbiome nutrition study

November 17, 2015

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Dr. Geoffrey Preidis, a pediatric gastroenterology fellow at Texas Children’s and Baylor College of Medicine, received the 2016 Young Investigator Development Award from the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Foundation and Nestlé Nutrition Institute.

His award-winning study titled, “Glycan metabolism shapes the undernourished intestinal microbiome and influences weight gain,” explores the mechanisms by which undernutrition alters the bacterial balance in the gut microbiome and how this imbalance may impact weight gain potential in children with poor nutritional status.

Dysbiosis refers to disturbances in the bacterial composition of the gut microbiome. Intestinal bacteria transform glycans, non-digestible complex sugars, into short chain fatty acids that provide energy to epithelial cells lining the digestive tract. There are two types of glycans in the intestine – N-glycans derived from diet and O-glycans produced by the host that comprise intestinal mucus.

Since most bacteria metabolize only a small subset of glycans, the limited availability of key glycans could induce dysbiosis, which may impair weight gain by causing microbes to compete with the host for nutrients, transform fewer luminal contents into bioavailable energy or induce epithelial cell gene expression changes that decrease nutrient uptake.

To explore these possibilities, Preidis and his research team established a model of protein-energy undernutrition in neonatal mice. The undernourished microbiome in mice contained fewer N-glycans and fewer bacteria that metabolize N-glycans compared to the control group. The undernourished microbiome also was enriched with a plethora of Akkermansia muciniphila, a bacterium that lives and feeds on O-glycans in the intestinal mucus lining and is found in smaller quantities in obese humans and obese mice.

Preidis and his team hypothesize that loss of dietary N-glycan energy sources in the calorie-restricted diet causes a bloom of microbes including A. muciniphila that feed on mucus layer O-glycans. The resulting dysbiosis in the undernourished intestinal microbiome thins the mucus, decreases expression of epithelial cell genes that drive nutrient uptake and impairs weight gain.

“Uncovering the mechanisms by which dysbiosis contributes to poor nutrition – and can possibly be corrected – has enormous potential to improve global child health,” Preidis said. “Our long-term objective is to improve our understanding of how the microbiome contributes to metabolism and which microbes are potentially harmful or beneficial to weight gain and growth. This knowledge will enable us to develop therapies that target the microbiome to promote rapid recovery following periods of undernutrition and weight loss.”