Excess Dietary Sugar Alters Colonocyte Metabolism and Impairs the Proliferative Response to Damage.

BACKGROUND & AIMS: The colonic epithelium requires continuous renewal by crypt resident intestinal stem cells (ISCs) and transit-amplifying (TA) cells to maintain barrier integrity, especially after inflammatory damage. The diet of high-income countries contains increasing amounts of sugar, such as sucrose. ISCs and TA cells are sensitive to dietary metabolites, but whether excess sugar affects their function directly is unknown. METHODS: Here, we used a combination of 3-dimensional colonoids and a mouse model of colon damage/repair (dextran sodium sulfate colitis) to show the direct effect of sugar on the transcriptional, metabolic, and regenerative functions of crypt ISCs and TA cells. RESULTS: We show that high-sugar conditions directly limit murine and human colonoid development, which is associated with a reduction in the expression of proliferative genes, adenosine triphosphate levels, and the accumulation of pyruvate. Treatment of colonoids with dichloroacetate, which forces pyruvate into the tricarboxylic acid cycle, restored their growth. In concert, dextran sodium sulfate treatment of mice fed a high-sugar diet led to massive irreparable damage that was independent of the colonic microbiota and its metabolites. Analyses on crypt cells from high-sucrose-fed mice showed a reduction in the expression of ISC genes, impeded proliferative potential, and increased glycolytic potential without a commensurate increase in aerobic respiration. CONCLUSIONS: Taken together, our results indicate that short-term, excess dietary sucrose can directly modulate intestinal crypt cell metabolism and inhibit ISC/TA cell regenerative proliferation. This knowledge may inform diets that better support the treatment of acute intestinal injury.

Short-rotation woody crops for bioenergy and biofuels applications.

Purpose-grown trees will be part of the bioenergy solution in the United States, especially in the Southeast where plantation forestry is prevalent and economically important. Trees provide a "living biomass inventory" with existing end-use markets and associated infrastructure, unlike other biomass species such as perennial grasses. The economic feasibility of utilizing tree biomass is improved by increasing productivity through alternative silvicultural systems, improved breeding and biotechnology. Traditional breeding and selection, as well as the introduction of genes for improved growth and stress tolerance, have enabled high growth rates and improved site adaptability in trees grown for industrial applications. An example is the biotechnology-aided improvement of a highly productive tropical Eucalyptus hybrid, Eucalyptus grandis x Eucalyptus urophylla. This tree has acquired freeze tolerance by the introduction of a plant transcription factor that up-regulates the cold-response pathways and makes possible commercial plantings in the Southeastern United States. Transgenic trees with reduced lignin, modified lignin, or increased cellulose and hemicellulose will improve the efficiency of feedstock conversion into biofuels. Reduced lignin trees have been shown to improve efficiency in the pre-treatment step utilized in fermentation systems for biofuels production from lignocellulosics. For systems in which thermochemical or gasification approaches are utilized, increased density will be an important trait, while increased lignin might be a desired trait for direct firing or co-firing of wood for energy. Trees developed through biotechnology, like all transgenic plants, need to go through the regulatory process, which involves biosafety and risk assessment analyses prior to commercialization.