This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Equol is an important metabolite made in the body when soy is eaten. It is made by intestinal bacteria and not found in the urine and blood of infants before 4-months of age. We will determine when equol first appears in early life and whether it is breast feeding, cows milk formula or soy formula, or the composition of the post-weaning diet that predispose to the production of equol. Breast-feeding leads to differences in intestinal bacterial colonization and a lower pH compared with bottle-feeding, and this is expected to facilitate equol formation. In adults we will examine three broad dietary groups those consuming low, medium and high fiber as determined by a validated diet history questionnaire, to determine the role of adult diet in predisposition to make equol. We will also determine the pharmacokinetics of equol formation, and the long-term stability of equol-production in adults and its response to antibiotic use. For unknown reasons only one-third of adults consuming soy foods make equol. Recent studies of osteoporosis prevention, cardiovascular health, and menopause have shown that beneficial effects from soy foods are significantly greater in people who are 'equol-producers' compared with those unable to make equol. Since there are advantages to being an equol-producer it is important to understand the factors governing equol production. Given the clinical relevance of equol a greater understanding of factors governing its production is essential. This will facilitate future strategies to manipulate equol production and enhance the overall clinical effectiveness of soy foods. Purpose of Aim 1-- Developmental aspects of Equol Production The primary goal of this study is to determine the age at which equol is first produced and then to determine whether it is pre-weaning or post-weaning dietary factors that regulate its production. The age when equol production by intestinal bacterial first occurs is not accurately known, but can be determined by analyzing serum and urine. The gastrointestinal tract is sterile at birth and gradually acquires active microflora capable to equol production (Mykkanen et al., 1997). There is consequently a slow developmental expression of many key intestinal bacterial enzymes, and the type of early feeding regimen influences this diversity in types and numbers of bacterial flora. (Mountzouris et al., 2002). We have hypothesized that early nutrition influences the ability of an individual to make equol later in life by influencing what microflora colonize the intestine. The type of early nutrition may provide optimal conditions to 'seed' the intestine with the required flora for equol production, and once colonized these gradually express their enzyme activities with aging, especially if high fermentation rates are produced in the intestine. Alternatively, if early nutrition is not important and frequency of equol-producers is independent of the type of early diet, and then it is likely that it is the macro-composition of the post-weaning diet is the determinant of equol production. Both of these scenarios are testable by our study design. Understanding factors that regulate equol production will lead to strategies to enhance its production and therefore increase the life-long effectiveness of soy isoflavones.
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