Location: Obesity and Metabolism Research
Project Number: 2032-51530-022-03-T
Project Type: Trust Fund Cooperative Agreement
Start Date: Dec 1, 2011
End Date: Mar 31, 2015
1. Determine if consumption of fermentable fiber, provided as soluble oligosaccharide at low or high dose or as a mixture of whole grains, results in a shift in fecal microbiota to enrich Bifidobacteria, increase Bifidobacteria to Firmicutes ratio (B/F), and enhance butyrate-producing Clostridial clusters IV and XIa. 2. Determine if B/F ratio and Clostridial clusters IV and XIa are associated with breath hydrogen, butyrate levels in isolated colonocytes, and postprandial GLP-1. 3. Determine if B/F ratio and Clostridial clusters IV and XIa are associated with (a) glucose tolerance,(b) satiety, (c) inflammatory markers. 4. Measure available energy content of the oligosaccharide and the whole grain foods and determine if total energy harvest from controlled diets is related to B/F ratio and Clostridial clusters IV and XIa.
Healthy subjects (n=20) will participate in a crossover study with 4 treatment arms: i) control diet with low fiber, ii) low dose (20 g) oligosaccharide added to control diet, iii) high dose (40 g) oligosaccharide added to control diet, and iv) comparison diet with adequate fiber from whole grains. Each treatment will be administered for 3 weeks interspersed with washout periods of 2 weeks. Fecal microbiota will be characterized by sequencing of community 16S rRNA genes. The procedure includes extraction of genomic DNA, amplification of V1 to V3 regions of 16S rRNA genes by PCR, and sequencing using the 454/Roche A sequencing primer kit and Roche 454 GS-FLX Titanium chemistry. Meal challenge protocols will be conducted during the 3rd week of each treatment and fermentation products, glucose control, inflammatory markers and satiety will be assessed. In addition coloncytes will be isolated from fecal samples for the analysis of fermentation products. Measurement of digestible and metabolizable energy will be done by bomb calorimetry and proximate analysis of the controlled treatment diets and coinciding complete urine and fecal collections obtained during the 3rd week of treatment. Biological samples will be archived for future metabolomic analyses using 1H NMR- and mass spec-metabolite profiling, both global & targeted.