Progress 01/01/21 to 10/21/22
Outputs
Target Audience:The target audiences include patients who have conditions such as breast cancer, obesity, metabolic disorders anddiabetes, especially individuals who are at a high risk of developing these conditions with inherited tendency. The targetaudiences also include certain healthy population such as woman of childbearing age,pregnant women and children. The public health communities and medical workers are potential audiences who could apply the scientific knowledge derived from this project in theirpractice to improve public health. The soy farms, soy food producers and the relevant markets can be potential audienceswho may get profits from the results of this project. Extension and outreach activities will help to advocate the efforts to thetarget audiences. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?This project provides training opportunities for graduate students and staff as well as professional development opportunity for the PI. Training activities: The participated graduate students and staff received relevant training in molecular biology research skills and obtained knowledge through conducting the proposed studies under the PI's supervision. Professional development: The PI has built a solid foundation with a wide range of research skills and knowledge through this project. The PI has published several important papers supported through this award. As a results, the PI has been invited to report her research related to this project on several local and national conferences. The PI has developed new collaborations fostered by the project or activity. How have the results been disseminated to communities of interest?To enhance public understanding and increase interest in learning the research outcomes of our study, efforts have been made to reach out potential audiences. Research seminars: I reported my research in several scientific seminars, which audiences include researchers, dieticians and physicians. The public health communities andmedical workers could apply the scientific knowledge derived from this project in their practice to improve public health. Workshops: I presented my research on a workshop "Exploring Research Communities @ Mizzou". This activity attracts potential audiences such as undergraduates who are interested in learning the effects of food on disease and long-term health and also helps to disseminate our study to the community. National conferences: I presented my research on several national conferences including Nutrition 2021 and ACMAP annual meeting. These national conferences have a broader range of audiences such as researchers, physicians, patient advocate, community workers and food producers etc. Participation in these national conferences helps to reach out the communities that are interested in our research or may benefit from our work. What do you plan to do during the next reporting period to accomplish the goals?The PI has started a new Assistant Professor position in the Department of Nutrition and Food Science at the University of Maryland (UMD) starting from September 1, 2022. The PI requests to transfer the remaining fund to UMD andcontinue the proposed studies during the rest of funding period. In the current study, we propose to elucidate the mechanisms regarding how maternal soy diet reshapes the initial gut microbiome in the offspring that may influence developmental origins of obesity and breast cancer as well as interactions between these two maladies. Successful implementation of our study will facilitate exploration of a novel preventive strategy through appropriate consumption of soy-based natural bioactive products and/or an optimized panel of beneficial bacteria via mother's and children's diets leading to improved human health later in life. The animal protocol has been sent to UMD IACUC for approval and we will resume our animal work immediately after the fund is transferedto UMD. The animal number in each treatment set has been carefully calculated and powered based on our previous studies to ensure sufficient biological replicates, and all variables were measured at least 3 times for rigor and reproducibility. In Aim 1, we completed the studies to test the temporal effects of soy GE diet on prevention of breast cancer and obesity in three different mouse models. Although our studies primarily focused on female mice due to the breast cancer factor, we also collected obesity-related data from male mice and are currently analyzing these data. We plan to publish a paper reporting how maternal soybean diet affects obesity programming in male offspring and comparegender difference. In Aim 1, we also propose to administer a combinatorial dietary approach to the mice at a concentration of 250 mg/kg diet of total soy isoflavones including 130mg GE and 120mg daidzein (DA). We plan to test the effects of this combinatorial approach on prevention of breast cancer and obesity in different mouse models in the next funding year. We will also compare the preventive effects by the use of the combinatorial approach with that of by the single GE treatment. In addition, we have extended our research to investigate the impacts of maternal dietary supplement on gestational obesity and pregnancy outcomes by using HFD-induced obese C57 dams. We are currently organizing the relevant animal data and may repeat some of these studies at UMD. In Aim 2, we found that maternal soy GE diet altered offspring gut microbiota and key metabolites. We also did multi-omics analysis in offspring mammary tumors by integrating transcriptomicand methylomicdata and identified several candidate genes. In the next funding year, we plan to: first, perform omics studies such as transcriptome and methylome in liver and adipose tissues; second, evaluate a group of pre-defined key microbially-produced metabolites that have been identified for their contribution to obesity and metabolism such as tryptophan metabolites, bile acids, amino acid metabolites, lipopolysaccharide, bacterial vitamins (e.g., folate, biotin, riboflavin, thiamine, panthothenic acid) and acetyl-CoA through targeted metabolomics; third, determine a full spectrum of metabolite differences and identify novel microbially-produced or diet-induced metabolites through untargeted metabolomics; fourth, test gut microbial changes in different developmental stages; fifth, continue to validate target gene expression, determine epigenetic alterations, analyze gene function and downstream analysis. We developed collaboration with Dr. Tianzhou Ma, a statistical expert in multi-omics, at UMD. Dr. Ma will facilitate processing and analyzing of the microbiome, metabolomics and RNA-sequencing data as well as integrated analysis. In Aim 3, we determined the causal mechanisms linking maternal soy GE to its improved health outcomes by testing the impact of a key microbial metabolite, SB, in cell culture. We also investigated howSB supplementation alone or combined with GE can efficiently inhibit HFD-induced breast tumor development in SV40 mice. Interestingly, we found combination treatment with GE and SB significantly inhibited HFD- induced breast tumor development than any treatment alone in SV40 mice. We are currently organizing the relevant animal data and gut microbiota data. We plan to submit this paper early next year. We identified a candidate bacterium, the genus Bifidobacterium, in response to maternal soybean treatment in our previous study (Chen M., et al, Journal of Nutritional Biochemistry, 2022, Aug 3;110:109119). We will test its efficacy on prevention of obesity and breast cancer when supplementedalone or with GE in mice.Additional causal mechanistic approaches will be performed by introduction of optimized panels of microbiota and their metabolitesto further determine functional mechanisms of the microbiome in improving gut homeostasis leading to health outcome changes later in life. To enhance public understanding and increase interest in learning the research outcomes of our study, further outreach efforts will continue in the next funding period including actively participating in research seminars, conferences, workshops and community activities in order to advocate our research and reach out potential audiences.
Impacts
What was accomplished under these goals?
1. Major issues that our project addresses Obesity and breast cancer affect hundreds of thousands of people world-wide and elucidation of their prevention through natural bioactive products will have global impact. Genistein (GE), a natural isoflavone enriched in soy products such as soy milk, soy protein and tofu, is a robust chemopreventive agent against various types of human diseases. Our study aims to interrogate whether soy GE intake through mother can prevent obesity and breast cancer in mice offspring and to determine the potential mechanisms underlying how maternal bioactive soy diet impacts human health through regulation of the gut microbiome, metabolome and epigenome. The outcomes of our research will immediately help to establish a preventive strategy targeting individuals who are at high risk to develop obesity or aggressive forms of breast cancer. 2. Scientific objectives: Three specific aims are proposed in this proposal. Aim #1. Determine the effects of maternal soy diet on health outcomes in mouse offspring. 1) Major activities completed/experiments conducted: We determined the preventive efficacy of soy GE on obesity and breast cancer by including different exposure windows throughout the mother's lifetime in three mouse models such as transgenic SV40, Her2/neu mice and an obesity-related wild-type C57BL/6J (C57) mice. 2) Data collected: For breast tumor outcomes, we collected tumor-related data such as tumor frequency, latency, tumor volumes and tumor burden. For metabolic related outcomes, we collected data including food intake and body weight, body composition, glucose tolerance test and lipid profiles in the mother and the offspring. 3) Summary statistics and discussion of results: Our studies indicate that long-term exposure to soy GE throughout the mother's early lifetime led to significant inhibition of breast cancer development in the female mice offspring. Our results also showed that maternal soy GE reduced high fat diet (HFD)-induced metabolic disorders in the offspring. In obesity-related breast cancer study, we found that maternal GE diet can significantly inhibit HFD-induced spontaneous breast cancer development and delay tumor latency in mice. These results prove our hypothesis indicating that maternal GE diet can attenuate HFD-induced metabolic disorders leading to prevention of HFD-promoted breast tumor development in mice offspring. 4) Key outcomes or other accomplishments realized: We have published 2 peer-reviewed empirical papers derived from these data (Chen M., et al, Journal of Nutritional Biochemistry, 2022, Aug 3;110:109119; Chen M., et al., Carcinogenesis, 2022,43(3):190-202). The PI served as corresponding authors on both of these publications. Our research delivered an important message to the public that a healthy maternal diet may have long-term beneficial effects on prevention of obesity and breast cancer later in life. Aim #2. Mechanistically assess the impacts of maternal soy diet on early-life gut microbiome, metabolome and potential epigenetic regulations in control of early disease chemoprevention by this dietary regimen. 1) Major activities completed/experiments conducted: We evaluated how maternal GE diet influenced the early-life gut microbiota and beneficial metabolites, gene expression as well as epigenetic profiles under postnatal HFD treatment. 2) Data collected: We tested offspring gut microbiome via 16s rRNA sequencing analysis. We tested the serum metabolite by liquid chromatography-mass spectrometry(LC-MS) analysis. We tested global gene transcriptome and specific gene expression in the offspring tumor or adipose tissues. We also evaluated global DNA methylation profiles and key epigenetic modulator changes. 3) Summary statistics and discussion of results: Our results suggest that maternal GE significantly altered the diversity and compositions of early-life offspring intestinal microbiota in response to HFD. These changes resulted in increased level of beneficial microbial metabolites such as butyrate. Maternal GE also led to significant differential gene expression and genome-wide methylation profile changes in the mouse progenies. Our results showed that maternal GE significantly inhibited a number of pro-inflammatory factors suggesting that maternal GE can potentiate anti-inflammatory effects in the offspring system. 4) Key outcomes or other accomplishments realized: These data have been published on empirical papers as mentioned before. Data derived from these studies will help better understand the mechanistic insight regarding how maternal soybean diets elicit the transgenerational chemopreventive effects. Aim #3. Determine the causal linkage of the early-life gut microbiome with the prevention effects of maternal soy diet by supplementation of the key metabolites and/or candidate bacteria. 1) Major activities completed/experiments conducted: To determine the causal mechanisms linking maternal soy GE to its improved health outcomes later in life, we tested the impact of a key microbial metabolite, sodium butyrate (SB) that has shown significant increment after maternal GE treatment, on in vitro proliferation of breast cancer cells as well as in animal model. 2) Data collected: We tested how SB treatment affected cell growth and tumor parameters in SV40 mice as described before. 3) Summary statistics and discussion of results: We observed that SB inhibited breast cancer cell growth. We also found combination treatment with GE and SB significantly inhibited breast tumor development than any treatment alone in SV40 mice. 4) Key outcomes or other accomplishments realized: These results not only provide mechanistic insights related to soybean effects but also provide first-hand evident for the potential use of a novel chemopreventive or therapeutic approach through combination treatment with GE and SB against obesity and breast cancer in the future clinical trial. 3. Summary of accomplishment During the funding period, we conducted the proposed studies and obtained important results to support our hypothesis. The key outcomes derived from this funding period primarily include: first, our results showed the time-dependent impact of maternal soy diet on breast cancer prevention later in life; second, we found that maternal soy beneficially attenuatedpostnatal overnutrition-induced metabolic disorders and in turn prevented HFD-stimulated early-life breast tumorigenesis in the offspring; third, we found that maternal soy diet can improve offspring gut microbiome and key microbial metabolite profiles that may contribute to its preventive effects on later-life disease development; fourth, mechanistically, maternal bioactive soy diet results in significant genome-wide transcriptomic and methylomic profile changes; fifth, we found that maternal soy may exert its chemopreventive effects through affecting essential regulatory gene expression in control of metabolism, inflammation and tumor development. Taken together, our studies provide significant evidence indicating appropriately consuming soy food through mother's diet can effectively prevent obesity and breast cancer later in the offspring's life, which will facilitate exploration of a novel in utero preventive strategy through natural bioactive products. 4. Transition plan The PI has started a new Assistant Professor position in the Department of Nutrition and Food Science at the University of Maryland (UMD) starting from September 1, 2022. The new institute provides sufficient startup package, excellent academic environment and agricultural resources to support the PI to continue this USDA/NIFA project. The PI commits to continuing the proposed studies after transferring to UMD. After the grant transfers to UMD, we will continue the proposed animal study, analyze omics data, and prepare the papers for publication. This transition will NOTaffect original research plan.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2021
Citation:
Sharma M, Arora I, Chen M, Wu H, Crowley M, Tollefsbol T.O., Li Y, Therapeutic effects of dietary soybean genistein on
triple-negative breast cancer via regulation of epigenetic mechanisms. Nutrients. 2021, 13, 3944.
- Type:
Book Chapters
Status:
Published
Year Published:
2021
Citation:
Li Z and Li Y., Bioactive Dietary Compounds and Epigenetics in Womens Reproductive Cancers. Comprehensive
Pharmacology. https://doi.org/10.1016/B978-0-12-820472-6.00061-X
- Type:
Journal Articles
Status:
Published
Year Published:
2021
Citation:
Arora I, Li Y, Sharma M, Crowley M, Crossman D, Li S, Tollefsbol T.O., Systematic integrated analyses of methylomic and transcriptomic impacts of early combined botanicals on estrogen receptor-negative mammary cancer. Scientific Reports, 2021 May 4;11(1):9481.
- Type:
Journal Articles
Status:
Published
Year Published:
2021
Citation:
Li Y. Modern Epigenetics Methods in Biological Research. Methods. 2021 Mar;187:104-113. doi: 10.1016/j.ymeth.2020.06.022.
- Type:
Journal Articles
Status:
Published
Year Published:
2022
Citation:
Arora I., Sharma M., Li S., Crowley M., Crossman D., Li Y., Tollefsbol T.O. An integrated analysis of the effects of maternal broccoli sprouts on transcriptome and methylome in prevention of offspring breast cancer. PLoS ONE, 2022, 17(3):e0264858.
- Type:
Journal Articles
Status:
Published
Year Published:
2022
Citation:
Chen M., Li S., Arora I., Yi N., Sharma M., Li Z., Tollefsbol T.O., Li Y. Maternal soybean diet on prevention of obesity-related breast cancer through early-life gut microbiome and epigenetic regulation. Journal of Nutritional Biochemistry, 2022, Aug 3;110:109119. doi: 10.1016/j.jnutbio.2022.109119.
- Type:
Journal Articles
Status:
Published
Year Published:
2022
Citation:
Chen M., Li S., Srinivasasainagendra V., Sharma M., Li Z., Tiwari H., Tollefsbol T.O., Li Y. Maternal soybean genistein on prevention of later-life breast cancer through inherited epigenetic regulations. Carcinogenesis, 2022,43(3):190-202.
- Type:
Journal Articles
Status:
Submitted
Year Published:
2022
Citation:
Bankole T., Winn H and Li Y. Maternal nutrition in prevention of gestational diabetes: connection between gut microbiome and epigenetic mechanisms. Nutrients.
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Progress 01/01/21 to 12/31/21
Outputs
Target Audience:The target audiencesinclude patients who have conditions such asbreast cancer, obesity, metabolic disorders and diabetes, especially individuals who are at a high risk of developing theseconditions with inherited tendency. The target audiences also include certain healthy population, especially pregnant womenand children. The public health communities andmedical workers are potential audienceswho could apply the scientific knowledge derived from this project in their practice to improve public health.The soy farms, soy food producers and the relevant marketscan bepotential audiences who may get profits from the results of this project. Extension and outreach activities will help to advocate the efforts to the target audiences. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?
Nothing Reported
How have the results been disseminated to communities of interest?To enhance public understanding and increase interest in learning the research outcomes of our study, efforts have been made to reach out potential audiences. Research seminars: I reported my research in several scientific seminars, which audiences include researchers, dieticians and physicians. The public health communities andmedical workers could apply the scientific knowledge derived from this project in their practice to improve public health. Workshops: I presented my research on a workshop "Exploring Research Communities @ Mizzou". This activity attracts potential audiences such as undergraduates who are interested in learning the effects of food on disease and long-term health and also helps to disseminate our study to the community. National conferences: I presented my research on several national conferences including Nutrition 2021 and ACMAP annual meeting. These national conferences have a broader range of audiences such as researchers, physicians, patient advocate, community workers and food producers etc. Participation in these national conferences helps to reach out the communities that are interested in our research or may benefit from our work. What do you plan to do during the next reporting period to accomplish the goals?In the current study, we propose to elucidate the mechanisms regarding how maternal soy diet reshapes the initial gut microbiome in the offspring that may influence developmental origins of obesity and breast cancer as well as interactions between these two maladies. Successful implementation of our study will facilitate exploration of a novel preventive strategy through appropriate consumption of soy-based natural bioactive products and/or an optimized panel of beneficial bacteria via mother's and children's diets leading to improved human health later in life. The animal protocol has been approved by MU ACUC. The animal number in each treatment set has been carefully calculated and powered based on our previous studies to ensure sufficient biological replicates, and all variables were measured at least 3 times for rigor and reproducibility. The biological tissue samples and the corresponding tests were evaluated in the relevant Core Facilities to ensure robust and unbiased results. The proposed compounds and diets have been examined in house by LC-UV-MS and NMR. In Aim 1, we completed the studies to test the effects of soy GE diet on prevention of breast cancer and obesity in different mouse models including two transgenic mouse models, C3(1)-SV40 Tag (SV40) and Her2/neu mice, and a normal C57BL/6J (C57) mouse model in this funding period. Temporal effects of soy diet have been tested in breast cancer but not in obesity outcomes. Additional maternal exposure windows have been applied in obesity studies and relevant animal works are ongoing. We plan to test the effects of soy protein including primary soy isoflavones, genistein and daidzein, on prevention of breast cancer and obesity in different mouse models in the next funding year. In addition, we have extended our research to investigate the impacts of maternal dietary supplement on gestational obesity and pregnancy outcomes by using HFD-induced obese C57 dams. The relevant animal studies are ongoing. In Aim 2, we found that maternal soy GE diet altered offspring gut microbiota and key metabolites. We also did multi-omics analysis by integrating transcriptome and methylome data and identified several candidate genes such as Trp63, Myc and Rarb, showing significant gene expression and DNA methylation changes. We validated target gene expression, analyzed gene function and downstream cascades as well as epigenetic changes. These tests were performed in mouse mammary tumors. In next funding year, we plan to: first, test gut microbial changes in different developmental stages; second, evaluate metabolomic profile to determine global metabolite changes; third, investigate transcriptomic and methylomic changes in mouse adipose tissues; and fourth, continue to validate target gene expression, determine epigenetic alterations, analyze gene function and downstream analysis. In Aim 3, we determined the causal mechanisms linking maternal soy GE to its improved health outcomes by testing the impact of a key microbial metabolite, SB, in cell culture. We are currently working on SB supplementation and fecal microbiota transplantation in animal models. Additional causal mechanistic approaches will be performed by introduction of optimized panels of microbiota in the offspring to further determine functional mechanisms of the microbiome in improving gut homeostasis leading to health outcome changes later in life. The relevant data involved in soy GE prevention of HFD-induced obesity and breast cancer in SV40 and C57 mice have been submitted to Journal of Nutrition for potential publication. To enhance public understanding and increase interest in learning the research outcomes of our study, further outreach efforts will continue in the next funding period including actively participating in research seminars, conferences, workshops and community activities to reach out potential audiences and advocate our research.
Impacts
What was accomplished under these goals?
1.Major issues that our project addresses: Obesity and breast cancer affect hundreds of thousands of people world-wide and elucidation of their prevention through natural bioactive products will have global impact. Studies have shown that both obesity and breast cancer have strong inherited tendencies and development of these diseases can be influenced by nutrition or dietary factors consumed by the mother. Genistein (GE), a natural isoflavone enriched in soy products such as soy milk, soy protein and tofu, is a robust chemopreventive agent against various types of human diseases. Our study aims to interrogate whether soy GE intake through mother can prevent obesity and breast cancer in mice offspring and to determine the potential mechanisms underlying how maternal bioactive soy diet impacts human health through regulation of the gut microbiome, metabolome and epigenome. 2.Target audiences: The outcomes of our research will immediately help to establish a preventive strategy targeting individuals who are at high risk to develop obesity or aggressive forms of breast cancer. The dietary guideline derived from our study will also benefit the healthy population, especially women in childbearing age, pregnant women and children. In the long run, we expect the outcomes of our study will keep booming in soy-related manufacturing that eventually benefits the soy farmers, soy food producers and the relevant agricultural markets. 3.Scientific objectives: The overall objective of this proposal is to determine the impacts of maternal bioactive soy diet on development of early-life gut microbiota and the subsequent metabolomic profiles that can influence epigenetic control of key regulatory genes leading to improved health outcomes in prevention of obesity and/or breast cancer in adult life of the progenies. 4.Significant results:To achieve theobjective, three specific aims are developed in this proposal. Aim #1. Determine the effects of maternal soy diet on health outcomes in mouse offspring. Temporal effects of maternal soy GE diet on prevention of breast cancer: As timing of exposure is critical to determine the preventive efficacy of the diets, we first determined the preventive effects of soy GE on breast cancer by including different exposure windows throughout the mother's lifetime. Our studies indicate that long-term exposure to soy GE throughout the mother's early lifetime led to significant inhibition of breast cancer development in the female offspring of two spontaneous breast cancer transgenic mouse models including C3(1)-SV40 Tag (SV40) and Her2/neu mice, whereas maternal short-term exposureduring pregnancy showed less protective effects. These studies provide solid evidence in support of time-dependent effects of maternal GE on prevention of later-life breast cancer in mice offspring. Long-term soy GE treatment represents a persistent eating habit and more likely helps to develop a stable and balanced gut microbiome community in the offspring than short-term exposure. Maternal GE diet attenuated high fat diet (HFD)-induced obesity and glucose intolerance in mice offspring: Two mouse models have been applied in this study including transgenic SV40 mice and obesity-related wild-type C57BL/6J (C57) mice. Our results showed that maternal soy GE reduced body weight, significantly decreased body fat accumulation, reversed glucose intolerance and improved lipid profiles in the female offspring of both mouse models when HFD diet was administered in the offspring. Maternal GE diet inhibited HFD-promoted breast tumor development: As obesity and its induced metabolic disorders are major risk factors for breast cancer, we further investigated whether maternal GE diet-improved metabolism functions may contribute to early breast cancer prevention. As a result, we found that maternal GE diet can significantly inhibit HFD-induced spontaneous breast cancer development and delay tumor latency in SV40 female offspring. Similar protective effects were observed in C57 allografts showing maternal GE can reduce engrafted breast tumor growth and tumor weight. Aim #2. Mechanistically assess the impacts of maternal soy diet on early-life gut microbiome, metabolome and potential epigenetic regulations in control of early disease chemoprevention by this dietary regimen. Maternal GE diet altered offspring gut microbiota and key metabolites: We evaluated how maternal GE diet influencedthe early-life gut microbiota and a group of microbially-produced beneficial metabolites, short-chain fatty acids (SCFAs), under postnatal HFD treatment. Our results suggest that maternal GE significantly altered the diversity and compositions of early-life offspring intestinal microbiota in response to HFD. Maternal GE also resulted in an increase in most SCFAs, especially butyrate. Butyrate has been well demonstrated to positively influence energy balance and prevent diet-inducedobesity through regulation of epigenetic mechanisms. The microbial composition changes caused by maternal soy diet may contribute to increased levels of beneficial metabolites such as butyrate. Maternal GE diet led to global gene expression and DNA methylation profiling changes. To further explore the potential mechanisms underlying maternal GE-mediated chemoprevention effects, we tested global gene transcriptome in the offspring mammary tumors. Our studies showed that maternal GE led to significant differential gene expression and genome-wide methylation profile changes in the mouse progenies. We also integrated transcriptomic and methylomic data and identified several candidate genes such as Trp63, Myc and Rarb, showing significant gene expression and DNA methylation changes. Regulation of these genes through epigenetic mechanisms may be responsible for efficacy of maternal GE exposure leading to an altered health outcome in the offspring. Aim #3. Determine the causal linkage of the early-life gut microbiome with the prevention effects of maternal soy diet by supplementation of the key metabolites and/or candidate bacteria. Sodium butyrate (SB) treatment inhibited mammary tumor proliferation in vitro: To determine the causal mechanisms linking maternal soy GE to its improved health outcomes later in life, we tested the impact of a key microbial metabolite, SB that has shown significant increment after maternal GE treatment, on in vitro proliferation of breast cancer cells. We observed that SB induced a time- and dose-dependent inhibition on breast cancer cell growth. In addition, we found SB treatment caused significant down-regulation of important tumor promoting genes and key pro-inflammatory gene. 5. Summary of accomplishment: During this funding period, we initiated our proposed studies and obtained important results to support our hypothesis. The key outcomes derived from this funding period primarily include: first, our results showed the time-dependent impact of maternal soy diet on breast cancer prevention later in life; second, we found that maternal soy beneficially attenuates postnatal overnutrition-induced metabolic disorders and in turn prevents HFD-stimulated early-life breast tumorigenesis in the offspring; third, we found that maternal soy diet can improve offspring gut microbiome and key microbial metabolite profiles that may contribute to its preventive effects on later-life disease development; fourth, mechanistically, maternal bioactive soy diet results in significant genome-wide transcriptomic and methylomic profile changes. Taken together, our studies provide significant evidence indicating appropriately consuming soy food through mother's diet can effectively prevent obesity and breast cancer later in the offspring's life. These results support our proposed hypothesis.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2021
Citation:
Sharma M, Arora I, Chen M, Wu H, Crowley M, Tollefsbol T.O., Li Y, Therapeutic effects of dietary soybean genistein on triple-negative breast cancer via regulation of epigenetic mechanisms. Nutrients. 2021, 13, 3944.
- Type:
Book Chapters
Status:
Published
Year Published:
2021
Citation:
Li Z and Li Y., Bioactive Dietary Compounds and Epigenetics in Women⿿s Reproductive Cancers. Comprehensive Pharmacology. https://doi.org/10.1016/B978-0-12-820472-6.00061-X
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2021
Citation:
Li Y, Maternal Soybean Diet on Prevention of Offspring Obesity and Metabolic Disorders. Nutrition 2021.
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