Ecological studies and results from our low-fat, high-carbohydrate dietary intervention trial suggest that different carbohydrates are associated with breast cancer risk in different ways. We examined the association of diet glycemic index (GI), a ranking of carbohydrate containing foods based on their blood glucose raising potential, with breast cancer risk and phenotype. GI was calculated from multiple food records from subjects in our intervention trial using a nested case-control design (220 cases, 440 controls). GI was not associated with risk of total or estrogen receptor positive breast cancer, tumor size or nodal status. GI was strongly positively associated with hormone negative breast cancer. This finding is potentially important as little is known about the etiology of hormone negative breast cancer, which has a worse prognosis than hormone positive breast cancer. However, this finding is based on a small number of cases and should be replicated in a larger sample.

The objectives were to explore cognitive function in older adults with Type 2 Diabetes Mellitus (T2DM) through two studies: 1) a pilot study involving the metabolic stress of glucose ingestion and the environmental stress of a functional magnetic resonance imaging (fMRI) environment and 2) an fMRI study exploring the neural mechanisms through hippocampal and prefrontal functional imaging during memory and executive functioning tasks. In T2DM subjects, environmental stress produced greater impairment in memory performance and metabolic stress produced overestimation of memory performance, with similar executive functioning, relative to healthy subjects (pilot study). T2DM subjects also sowed reduced hippocampal and greater prefrontal activation compared to healthy subjects (fMRI study). Moreover, the metabolic stress caused greater hippocampal and prefrontal activation in healthy subjects relative to placebo (fMRI study). These results indicate plausible neural mechanisms behind T2DM- and stress-associated cognitive impairments that can be used for future improvements in cognitive retention and rehabilitation.

Bifidobacterium bifidum MIMBb75 is a novel strain whose behavior within the intestinal tract is not known. This work attempts to determine the survival and molecular determinant responsible for its colonization through two studies involving administration to mice of 1) B. bifidum MIMBb75 or 2) engineered B. longum NCC2705 expressing the B. bifidum-specific surface protein BopA. MIMBb75 was able to transiently colonize the murine intestinal tract. As a result, endogenous bifidobacteria increased significantly in the proximal colon whereas Clostridia clusters were differentially affected in a region-dependent fashion. Genetically engineered B. longum NCC2705, expressing the BopA gene, did not impact endogenous bacterial groups in the proximal colon or feces, albeit, it down-regulated the gene expression of KC and mucin 4 in the proximal colon. These outcomes indicate that MIMBb75 encompasses characteristics of a probiotic, but further studies are required to assess the role of BopA as the molecular determinant of its action.

Cilantro, the leaf of the Coriandrum sativum plant, has been documented as being one of the most polarizing and divisive foods known. It has been proposed that extreme disliking of this herb may be explained by genetic variation. The objectives of this thesis were to quantify the prevalence of cilantro disliking in various ethnocultural groups, to identify genetic polymorphisms that are associated with this trait using genome-wide association studies, and to analyze the associations of these polymorphisms within different ethnocultural groups. Prevalence of cilantro disliking was found to range from 3%, among Middle Eastern subjects, to 21% among East Asians. Two polymorphisms, one in the OR4N5 olfactory receptor gene and the other in the TAS2R1 taste receptor gene, were found to be associated with cilantro preference in the Caucasian subset of the study population. No statistically significant associations were observed within other ethnic groups.

Ecological studies and results from our low-fat, high-carbohydrate dietary intervention trial suggest that different carbohydrates are associated with breast cancer risk in different ways. We examined the association of diet glycemic index (GI), a ranking of carbohydrate containing foods based on their blood glucose raising potential, with breast cancer risk and phenotype. GI was calculated from multiple food records from subjects in our intervention trial using a nested case-control design (220 cases, 440 controls). GI was not associated with risk of total or estrogen receptor positive breast cancer, tumor size or nodal status. GI was strongly positively associated with hormone negative breast cancer. This finding is potentially important as little is known about the etiology of hormone negative breast cancer, which has a worse prognosis than hormone positive breast cancer. However, this finding is based on a small number of cases and should be replicated in a larger sample.

The objectives were to explore cognitive function in older adults with Type 2 Diabetes Mellitus (T2DM) through two studies: 1) a pilot study involving the metabolic stress of glucose ingestion and the environmental stress of a functional magnetic resonance imaging (fMRI) environment and 2) an fMRI study exploring the neural mechanisms through hippocampal and prefrontal functional imaging during memory and executive functioning tasks. In T2DM subjects, environmental stress produced greater impairment in memory performance and metabolic stress produced overestimation of memory performance, with similar executive functioning, relative to healthy subjects (pilot study). T2DM subjects also sowed reduced hippocampal and greater prefrontal activation compared to healthy subjects (fMRI study). Moreover, the metabolic stress caused greater hippocampal and prefrontal activation in healthy subjects relative to placebo (fMRI study). These results indicate plausible neural mechanisms behind T2DM- and stress-associated cognitive impairments that can be used for future improvements in cognitive retention and rehabilitation.

Bifidobacterium bifidum MIMBb75 is a novel strain whose behavior within the intestinal tract is not known. This work attempts to determine the survival and molecular determinant responsible for its colonization through two studies involving administration to mice of 1) B. bifidum MIMBb75 or 2) engineered B. longum NCC2705 expressing the B. bifidum-specific surface protein BopA. MIMBb75 was able to transiently colonize the murine intestinal tract. As a result, endogenous bifidobacteria increased significantly in the proximal colon whereas Clostridia clusters were differentially affected in a region-dependent fashion. Genetically engineered B. longum NCC2705, expressing the BopA gene, did not impact endogenous bacterial groups in the proximal colon or feces, albeit, it down-regulated the gene expression of KC and mucin 4 in the proximal colon. These outcomes indicate that MIMBb75 encompasses characteristics of a probiotic, but further studies are required to assess the role of BopA as the molecular determinant of its action.

Cilantro, the leaf of the Coriandrum sativum plant, has been documented as being one of the most polarizing and divisive foods known. It has been proposed that extreme disliking of this herb may be explained by genetic variation. The objectives of this thesis were to quantify the prevalence of cilantro disliking in various ethnocultural groups, to identify genetic polymorphisms that are associated with this trait using genome-wide association studies, and to analyze the associations of these polymorphisms within different ethnocultural groups. Prevalence of cilantro disliking was found to range from 3%, among Middle Eastern subjects, to 21% among East Asians. Two polymorphisms, one in the OR4N5 olfactory receptor gene and the other in the TAS2R1 taste receptor gene, were found to be associated with cilantro preference in the Caucasian subset of the study population. No statistically significant associations were observed within other ethnic groups.

Intrauterine exposures to environmental factors have been hypothesized to influence the risk of breast cancer in adulthood. The majority of epidemiological studies suggest that dietary folate intake is inversely related to breast cancer, however, the evidence have been inconsistent. An animal study was performed to determine the relationship between in utero and postnatal dietary folate intervention and the risk of breast cancer in the DMBA rodent model. Supplementation of maternal and offspring diet with folic acid (5 mg/kg diet) was observed to significantly increase the risk of mammary tumor development in the offspring compared to controls (2 mg/kg diet). Maternal diet and tumor status were also found to be significant predictors of global DNA methylation. Our data suggests that high intrauterine and postnatal exposures to folic acid increases the risk of breast cancer development. Epigenetic modifications may be an underlying mechanism by which folate mediates mammary tumorigenesis in the offspring.

Three studies were designed to investigate the hypothesis that physiological and environmental variables are both independent and interactive in determining food intake (FI) in children and adolescents during puberty (8 – 18 y old). Study 1 investigated the effect of obesity, sex and pubertal status on appetite hormones in response to a mixed glucose and whey protein (WP) drink in adolescents. Obese adolescents had higher insulin, PYY and lower ghrelin than normal weight (NW) controls, with a more pronounced effect in males. Puberty did not affect insulin, but the change in PYY in response to the drink was greater and ghrelin was lower in mid-late pubertal than pre-early pubertal obese males. To further describe the role of puberty, Study 2 examined the effect of pubertal status on FI following consumption of glucose and WP drinks in male and female children. In mid-late pubertal children, mealtime compensation for energy from glucose was less at 60 than at 30 min, but not for whey. However, compensation for either drink was not different at 30 and 60 min meals in pre-early pubertal children. Finally to demonstrate the interaction between puberty and environmental influences on FI, Study 3 examined the effect of distraction (television viewing, TVV) while eating and pubertal status on food intake after a pre-meal glucose drink in girls. In Study 3, TVV had no effect on FI, however, glucose suppressed FI more with no TVV compared with TVV (24% vs. 10%). In postpubertal girls, glucose reduced FI by ~27% in both the no TVV and TVV conditions, but in peripubertal girls, reduction in FI was 22% without TVV and only 1% while TVV. Thus, the results of this research support the hypothesis that physiological and environmental variables are both independent and interactive in determining FI in children and adolescents during puberty.