Summary Retinoic acid (RA), a vitamin A metabolite, regulates transcriptional programs that drive protective or pathogenic immune responses in the intestine, in a manner dependent on RA concentration. Vitamin A is obtained from diet and is metabolized by intestinal epithelial cells (IECs), which operate in intimate association with microbes and immune cells. Here we found that commensal bacteria belonging to class Clostridia modulate RA concentration in the gut by suppressing the expression of retinol dehydrogenase 7 (Rdh7) in IECs. Rdh7 expression and associated RA amounts were lower in the intestinal tissue of conventional mice, as compared to germ-free mice. Deletion of Rdh7 in IECs diminished RA signaling in immune cells, reduced the IL-22-dependent antimicrobial response, and enhanced resistance to colonization by Salmonella Typhimurium. Our findings define a regulatory circuit wherein bacterial regulation of IEC-intrinsic RA synthesis protects microbial communities in the gut from excessive immune activity, achieving a balance that prevents colonization by enteric pathogens.

This report is concerned with the prediction of natural killer (NK) cell activity in 61 Stage I and II breast cancer patients, between the ages of 25 and 70, who were accrued to this project. All baseline interview and testing data were obtained either just before patients were discharged from the hospital, or at their first outpatient visit, within two weeks of discharge. A major interest of this project is the predictive value of perceived social support, as a potential "stress" buffer, related to NK activity. In the main model reported here, we found that a significant amount of NK activity variance could be explained by five variables. Higher NK activity could be predicted by the perception of high quality emotional support from a spouse or intimate other, perceived social support from the patient's physician, estrogen receptor-negative tumor status, having an excisional biopsy as surgical treatment, and actively seeking social support as a major coping strategy (R2 = 0.33, F(5,55) = 5.5, p less than 0.0004). Findings are discussed in terms of host interaction with tumor endocrine status, and the role that social support might play in modulating such activity.

Scope Heat-stabilized rice bran and cooked navy bean powder contain a variety of phytochemicals that are fermented by colonic microbiota and may influence intestinal health. Dietary interventions with these foods should be explored for modulating colorectal cancer risk. Methods and results A randomized-controlled pilot clinical trial investigated the effects of eating heat-stabilized rice bran (30g/day) or cooked navy bean powder (35g/day) on gut microbiota and metabolites (NCT01929122). Twenty-nine overweight/obese volunteers with a prior history of colorectal cancer consumed a study-provided meal and snack daily for 28 days. Volunteers receiving rice bran or bean powder showed increased gut bacterial diversity and altered gut microbial composition at 28 days compared to baseline. Supplementation with rice bran or bean powder increased total dietary fiber intake similarly, yet only rice bran intake led to a decreased Firmicutes:Bacteroidetes ratio and increased short chain fatty acids (propionate and acetate) in stool after 14 days but not at 28 days. Conclusion These findings support modulation of gut microbiota and fermentation by-products by heat-stabilized rice bran and suggest that foods with similar ability to increase dietary fiber intake may not have equal effects on gut microbiota and microbial metabolism.

Background: Xanthohumol may be beneficial for obesity-related conditions, but mechanisms are unknown. Results: XN lowers ROS and dysfunctional lipid metabolism in animals, and XN uncouples respiration and induces oxidant defense systems in myocytes. Conclusion: XN may ameliorate metabolic syndrome by these mechanisms. Significance: Metabolomics helped reveal potential XN anti-obesity mechanisms.

Background:We investigated the effects of vitamin C status on the metabolome of adult zebrafish. Results: Levels of inosine monophosphate (IMP) and AMP deaminase (AMPD) activity were enhanced in vitamin C-deficient zebrafish. Conclusion: Vitamin C deficiency activates the purine nucleotide cycle in zebrafish. Significance: The link between vitamin C deficiency and elevated AMPD activity is relevant to metabolic diseases.