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Abstract: Observational studies suggest an association between diets rich in whole grains (WG) and a decrease in inflammatory markers. Yet, this is not clearly supported by the conflicting or limited number of interventional studies, few of which have included markers of cell-mediated immunity, which are important functional aspects of the immune system. Furthermore, WG consumption is often accomp... read moreanied by weight loss, which may impact immune and inflammatory markers independent of a WG effect. This study was designed to maintain weight while investigating the effect of a WG rich diet versus refined grains (RG) on immune and inflammatory responses, gut microbiota, and microbial products. Following a 2-wk provided-food run-in period, 49 men and 32 post-menopausal women (40-65 y, BMI < 35) were randomly assigned to one of two provided-food weight-maintenance diets for 6 wk. The diets differed in WG and fiber contents (WG [n=41]: 207±39 g WG/d, 40±5 g fiber/d; or RG [n=40]: 0 g WG/d, 21±3 g fiber/d), but were similar in energy and meal structure. Relative abundances of gut bacteria were measured using DNA extracted from stool samples collected at the end of the run-in phase (PRE) and end of 6 wks of intervention (POST), and by high-throughput sequencing of amplicons of the V4 region of the bacterial 16S rDNA. To assess the impact of WG on immune and inflammatory markers we measured a panel of inflammatory markers, as well as phenotypic, and functional aspects of the immune system. Adherence to study diets was assessed by measuring biomarkers of WG intake, plasma alkylresorcinols (ARs), at PRE and POST study periods. We observed a significant increase in PRE to POST plasma ARs concentration in the WG group, and the PRE to POST change in plasma C19:0 (p=1.58 x 10-14) , C21:0 (p=4.10 x 10-13), C23:0 (p=9.10 x 10-6), and total ARs (p =5.29 x 10-11) was significantly higher in the WG compared to the RG. Consumption of WG versus RG significantly increased stool weight (p=1.77x10-7) and frequency (p=0.02). We noted a modest effect on gut microbiota composition and short chain fatty acid (SCFA) concentrations: WG consumption resulted a significant increase in PRE to POST change in the SCFA-producer Lachnospira and decrease in the pro-inflammatory Enterobacteriaceae (FDR-corrected p=0.25) compared to RG. Moreover, we found a PRE to POST increase in total stool SCFA (p=0.05), and acetate (p=0.02) in WG versus RG. At wk 6, Lachnospira positively associated with acetate (FDR-corrected p=0.002) and butyrate (FDR-corrected p=0.005). Of the peripheral and stool immune and inflammatory markers investigated, WG relative to RG had significantly more change in the percent of total effector memory T cells (p=0.03) and LPS-stimulated ex vivo production of TNF-α (p=0.04). These changes positively associated with plasma ARs concentrations, suggesting that the observed effects resulted from higher WG consumption. In summary, 6-wk consumption of a diet rich in WG compared to RG, when dietary components and body weight are kept constant, increased stool weight and frequency, populations of some beneficial bacteria, percent of total effector memory T cells, and acute innate immune response; while, having no effect on other measures of cell-mediated immunity or systemic and stool inflammatory markers. Supported by General Mills and USDA contract # 58-1950-0-014.
At the request of the author, this graduate work is not available to view in the Tufts Digital Library until August 28, 2018.
Thesis (Ph.D.)--Tufts University, 2016.
Submitted to the Dept. of Biochemical and Molecular Nutrition.
Advisors: Simin Meydani, and Dayong Wu.
Committee: Barry Goldin.
Keywords: Nutrition, and Immunology.read less
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