<p>Consumption of soy foods has been shown to provide beneficial health outcomes such as reduction of menopause symptoms, reduced risk of breast cancer and prostate cancer, improved cardiovascular health, and improved bone health. The mechanism hypothesized to be driving these outcomes is the conversion of the soy isoflavone daidzein into the metabolite equol by bacteria in the gut microbiome. Equol is an exclusively microbially produced metabolite with a high binding affinity to mammalian estrogen receptors. Not all humans harbor equol-producing microbes in their gut, and less than half of the population can be classified as equol producers. To date, soy feeding research published suffers from confounding factors that make assessing the causal impact of equol production in health difficult due to: (i) large interpersonal variation of the human microbiome and human genomes and that (ii) all lab-raised rodent models harboring natural microbiomes are highly efficient equol producers. In this study, we sought to establish a gnotobiotic mouse model harboring synthetic bacterial communities with divergent equol-producing capacities by designing two communities: the Equol(-) community and Equol(+) community. The Equol(-) community was designed to include ten bacterial strains commonly found within a human microbiome without equol-producing capacity<em>.</em> To create the Equol(+) community, the equol-producing bacteria <em>Adlercreutzia equolifaciens</em> was added to the Equol(-) community<em>.</em> Female and male germ-free C57BL/6 mice were colonized with either the Equol(-) or Equol(+) community for 4 weeks. Daidzein was administered by dietary supplementation (1.5% wt/wt daidzein) in a semi-purified diet containing fermentable fiber starting two weeks prior to bacterial colonization. As expected, equol was detected in the serum of mice colonized with the Equol(+) community, but not detectable in those colonized with the Equol(-) community. There were no sex differences detected in equol production. 16S rRNA gene sequencing of mouse cecal content revealed that ~50-80% of the strains from each community colonized within the mice at detectable levels. Strain-specific qPCR improved the detection of strains not observed consistently through 16S rRNA gene sequencing. Our results demonstrated that this model is reliable in producing the expected equol producing and non-equol producing phenotypes when colonized with the Equol(+) and Equol(-) communities, respectively. This model system can be utilized in a broad range of future studies to conclusively determine the causal impact of endogenous equol production in many areas, such as cardiometabolic health and bone health.</p>
| Identifer | oai:union.ndltd.org:purdue.edu/oai:figshare.com:article/21688415 |
| Date | 17 May 2024 |
| Creators | Lindsay Marie Leonard (14231186) |
| Source Sets | Purdue University |
| Detected Language | English |
| Type | Text, Thesis |
| Rights | CC BY 4.0 |
| Relation | https://figshare.com/articles/thesis/ESTABLISHMENT_OF_A_GNOTOBIOTIC_MOUSE_MODEL_FOR_DETERMINING_THE_MICROBIAL-DRIVEN_HEALTH_BENEFITS_OF_SOY_ISOFLAVONES/21688415 |
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