Effect of β-glucan molecular weight and viscosity on the mechanism of cholesterol lowering in humans

dc.contributor.authorWang, Yanan
dc.contributor.examiningcommitteeTaylor, Carla (Human Nutritional Sciences) Alfa, Michelle (Medical Microbiology) Khafipour, Ehsan (Animal Science) Marquart, Leonard (University of Minnesota)en_US
dc.contributor.supervisorAmes, Nancy (Human Nutritional Sciences) Jones, Peter (Food Science)en_US
dc.date.accessioned2016-01-13T16:26:54Z
dc.date.available2016-01-13T16:26:54Z
dc.date.issued2015
dc.degree.disciplineHuman Nutritional Sciencesen_US
dc.degree.levelDoctor of Philosophy (Ph.D.)en_US
dc.description.abstractThe cholesterol-lowering effect of mixed linkage (1→3) (1→4)-β-D-glucans (β-glucan) from barley has been documented, yet the underlying mechanism responsible for this action and factors influencing it, such as physicochemical properties of β-glucan and genetic background of an individual, remain unclear.As a component of dietary fibre, β-glucan also has the potential to shift the gut microbial community, however, whether alterations in the gut microbiota are associated with the physiological effects of β-glucan have yet to be determined. This study was designed to assess the effects of β-glucan molecular weight (MW) and dose on loweringserum cholesterol levels and to elucidate its mechanism of action in human subjects. Additionally, this study examined gene-diet interactions as well as changes in the gut microbiota profile following consumption of barley foods. In a controlled four phase crossover trial, mildly hypercholesterolemic but otherwise healthy subjects (n =30) were randomly assigned to receive breakfasts containing 3g high MW (HMW), 5g low molecular weight (LMW), 3g LMW barley β-glucan or a control diet with wheat and rice (WR control), each for 5 weeks. The washout period between the phases was 4 weeks. The consumption of 3g/d HMW diet lowered total cholesterol (TC) compared with WR control diet (P =0.0046), but not the LMW diet at either 3g/d or 5g/d. Individuals with the SNP rs3808607-G allele of CYP7A1 had greater TC reduction in response to 3g/d HMW β-glucan diet compared to the individuals carrying homozygous TT alleles (P<0.01). Cholesterol absorption and synthesis were not changed, but bile acid synthesis increased by 3g/d HMW diet compared to the control. Consuming 3g HMW/d β-glucan altered gut microbiota at the phylum and genus levels and the impacted microbial members was correlated with favorable shifts of cardiovascular disease risk factors. In conclusion, physicochemical properties of β-glucan play critical roles in the cholesterol-lowering effect and gut microbiota alteration ability of β-glucan. The results suggest the increasing bile acid synthesis rather than inhibiting cholesterol absorption and synthesis is the mechanism responsible for the cholesterol reducing property of β-glucan.The altered microbiota profile by HMW β-glucan is associated with its physiological effect.  en_US
dc.description.noteFebruary 2016en_US
dc.identifier.urihttp://hdl.handle.net/1993/31048
dc.language.isoengen_US
dc.rightsopen accessen_US
dc.subjectβ-glucanen_US
dc.subjectmolecular weighten_US
dc.subjectviscosityen_US
dc.subjectcholesterolen_US
dc.subjectCYP7A1en_US
dc.subjectbile aciden_US
dc.subjectmechanismen_US
dc.subjectmicrobiotaen_US
dc.subjectcardiovascular diseaseen_US
dc.subjectcholesterol absorptionen_US
dc.subjectcholesterol synthesisen_US
dc.titleEffect of β-glucan molecular weight and viscosity on the mechanism of cholesterol lowering in humansen_US
dc.typedoctoral thesisen_US
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