The concept of colonic health has become a major target for the development of functional foods such as probiotics, prebiotics, and synbiotics. These bioactive agents have a profound effect on the composition of the microflora, as well as on the physiology of the colon, and display distinct health benefits. Dietary carbohydrates escaping digestion/absorption in the small bowel and prebiotics undergo fermentation in the colon and give rise to short-chain fatty acids (SCFA). As the main anions of the colon and the major source of energy for colonocytes, SCFA are rapidly absorbed by nonionic diffusion mostly but also by active transport mediated by a sodium-coupled transporter, thereby fostering the absorption of sodium and water. SCFA in general and butyrate in particular enhance the growth of lactobacilli and bifidobacteria and play a central role on the physiology and metabolism of the colon. The effect of prebiotics on cell proliferation, differentiation, apoptosis, mucin production, immune function, mineral absorption, lipid metabolism, and gastrointestinal (GI) peptides has been well documented experimentally. These effects seem to be largely mediated by SCFA, but evidence from human studies remains inconsistent. The food industry is making a leap of faith in their efforts to commercialize prebiotics and exploit potential health benefits. The future lies with the design of studies to further explore basic mechanisms, and gene expression in particular, but emphasis should be placed on human intervention trials.

Late-onset multiple carboxylase deficiency is characterized clinically by skin rash, alopecia, seizures and ataxia and occasionally by candidiasis and developmental delay. Biochemically, these individuals exhibit findings consistent with a combined deficiency of the biotin-dependent carboxylases. We have found that the activity of the enzyme biotinidase is also deficient in the sera of five affected children (0 to 3% of mean control activity, 5.80 +/- 0.89 nmol X min-1 X ml-1 serum), and believe that it represents the primary biochemical defect in this disease. Biotinidase catalyzes the removal of biotin from the epsilon-amino group of lysine, through which biotin is covalently bound to the four known human carboxylases, thereby regenerating biotin for reutilization. The deficient activity in our patients was not due to an inhibitor, particularly biotin. It is also not a consequence of feedback control in affected individuals under treatment with pharmacologic doses of biotin. The biotinidase activities of the parents of those children who were available for study were intermediate between deficient and normal values (46% to 65% of mean normal activity). Children lacking biotinidase activity are unable to recycle biotin, and are thus entirely dependent upon exogenous biotin to prevent deficiency. Our findings indicate that the primary biochemical defect in late-onset multiple carboxylase deficiency is in biotinidase activity which is inherited as an autosomal recessive trait.

Although the group average for PAR-PAEE agreed with DLW-PAEE, there were differences in the methods among the subjects. PAEE determined by Tritrac, CSA, and Yamax significantly underestimate free-living PAEE in women.

Relative to diets enriched in palmitic acid (PA), diets rich in oleic acid (OA) are associated with reduced risk of type 2 diabetes. To gain insight into mechanisms underlying these observations, we applied comprehensive lipidomic profiling to specimens collected from healthy adults enrolled in a randomized, crossover trial comparing a high-PA diet to a low-PA/high-OA (HOA) diet. Effects on insulin sensitivity (SI) and disposition index (DI) were assessed by intravenous glucose tolerance testing. In women, but not men, SI and DI were higher during HOA. The effect of HOA on SI correlated positively with physical fitness upon enrollment. Principal components analysis of either fasted or fed-state metabolites identified one factor affected by diet and heavily weighted by the PA/OA ratio of serum and muscle lipids. In women, this factor correlated inversely with SI in the fasted and fed states. Medium-chain acylcarnitines emerged as strong negative correlates of SI, and the HOA diet was accompanied by lower serum and muscle ceramide concentrations and reductions in molecular biomarkers of inflammatory and oxidative stress. This study provides evidence that the dietary PA/OA ratio impacts diabetes risk in women.

Increases in dietary PA decrease fat oxidation and daily energy expenditure, whereas decreases in PA and increases in OA had the opposite effect. Increases in dietary PA may increase the risk of obesity and insulin resistance.