Progress 04/01/24 to 03/31/25
Outputs
Target Audience:Similar to our prior progress reports,we expect the target audiences to be our colleagues and scientistswho work in similar field of reseaerch, and who can possibly taking the learned knowledge into additional scientific development. We also expect our results from this study will provide information to stakeholders such as policy makers and health agencies for broad application of personalized nutrition knowledge. Changes/Problems:Due to the complexity of our analyses, we have requested and received approval from USDA NIFA for a one-year non-cost extension to finish the proposed work. We expect this additional year will allow us to fully analyze our samples and provide better interpretation of the results. What opportunities for training and professional development has the project provided?This study in the past year has allowed bothgraduate students andpostdoc scholars to develop their technical skills and exposed to various lab techniques. Students and postdocs have been trained to analyze a variety of biospecimens such as urine, blood, and stool samples to understand both microbial and molecular changes impacted by dietary interventions conducted in the study. They were also trained to work together on manuscript preparation which resulted in the reported publication this year. How have the results been disseminated to communities of interest?As reported, we have published a method paper to detail our clinical trial design and varous sample analyses plans. What do you plan to do during the next reporting period to accomplish the goals?Our ongoing efforts including the analyses of microbiome compositional data and the microbial metabolomics data and comparing the different outcomes induced by WWB vs. WB interventions in vitro. Furthermore, individual microbial members from the gut microbial community will be identified as potential contributing factors and will be analyzed for functional and metabolic contribution to host health.
Impacts
What was accomplished under these goals?
Last year, we have completed a rigorously controlled randomized controlled trial to identify personalized responses to dietary whole grain consumption in adults with prediabetes (n = 40). In a crossover design consisting of two, 2-wk intervention periods, the basal diet was fully prescribed to control fiber and energy while providing 4 daily servings of whole wheat bread (WWB) vs. refined while bread prior to evaluating host plasma metabolomes, outcomes of metabolic and gut health (e.g., blood glucose and lipids, endotoxemia in relation to gut dysbiosis and intestinal permeability), and inflammatory response. In agreement with our hypothesis, we observed a broad spectrum of inter-person variation post WWB intervention as evidenced by the tiered post-intervention blood glucose responses, the red squares and grey dots indicated the different blood glucose changes among study participants who positively or negatively responded to the WWB intervention. Our results also indicated that gut microbes, such as Ruminococcus and Desulfovibro were at significantly different levels in the participants with reduced glucose level vs. participants with no changes at study initiation (day 0), and were also having different changing trends post-intervention on Day 14 (Linear Discriminant Analysis Effect Size cut-off: p-value 0.05, LDA score 2). This result strongly suggested that in the new era of personalized nutrition, incorporating other personalized factors such as one's gut microbiome profile may have the value of predicting dietary intervention outcomes. In addition, our current work involves the data analyses of experiments completed from our computer-controlled three-stage human colonic model (HCM) for in vitro gut bacteria growth and the analysis of bioactive metabolism. The system has been fully validated based on chemical and microbiological measurements according to published recommendations and our study results. The microbial population diversity is also comparable to other successful model systems. It is primarily computer-controlled with minimum operator involvement needed and has three vessels connected in series. The gut microbiota from study participants were used for the inoculation of the colonic model. System reproducibility, repeatability, and stability have been tested by repeated fecal inoculation of different aliquots from the same donor, and analysis of gut bacterial populations. The system is primarily operated in a dark environment to restrict light exposure and mimic the human gut, as our preliminary study showed that light exposure could be a factor influencing gut microbial metabolism.
Publications
- Type:
Peer Reviewed Journal Articles
Status:
Published
Year Published:
2024
Citation:
Sisi Cao, Jillian T. Pierson, Ariana H. Bond, Shiqi Zhang, Andrew Gold, Huan Zhang, Kaitlyn M. Zamary, Palmer Moats, Matthew D. Teegarden, Devin G. Peterson, Xiaokui Mo, Jiangjiang Zhu, Richard S. Bruno,
Intestinal-level anti-inflammatory bioactivities of whole wheat: Rationale, design, and methods of a randomized, controlled, crossover dietary trial in adults with prediabetes,
Nutrition Research,
Volume 131,
2024,
Pages 83-95,
ISSN 0271-5317,
https://doi.org/10.1016/j.nutres.2024.09.010.
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Progress 04/01/23 to 03/31/24
Outputs
Target Audience:The results from our study are intended to provide the precision nutrition knowledge of how gut microbiome could modulate the health benifits of whole wheat intakes in metabolic diseases. Thus, we expect the targeted audiances to be our peer scientists and physicians wo work in related areas and can take the outcomes into further scientific development; and stakeholders from health administration/government agencies who may have the influence to new food and nutrition policies in the US. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?In the past year, we have continued to provide training and learning opportunities for both graduate student and postdocs who are supported by the projects. They have been further exposed to both clinical and basic lab skill training and leveraged these traning outcomes to the actual study. Unpaid undergraduate students have also been involved in the clinical study and were trained on food preparation, nutritional value evaluation, basic biochemistry measurements, etc. How have the results been disseminated to communities of interest?
Nothing Reported
What do you plan to do during the next reporting period to accomplish the goals?We will continue the proposed analyses of biospeciemens (primarily aims 1 and 2 in the original proposal), and leverage these results to cross check/validate our ongoing in vivo bioreactor experiments in which we are inoculating the fecal microbes from strong individuals who responded to the dietary interventions and have positive outcomes into human colonic model systems and to confirm if these microbes are more active in biotransforming the whole wheat ingridients for potential health benefits in human study. Meanwhile, our food chemistry co-PI and his team also started to profile the chemical compositions of the whole wheat which will allow us to connect the bioactive components from whole wheat to gut microbial activities and to the health outcomes in our study participants. We expect multiple datasets from our projects and two to three manuscripts will be produced by the end of next reporting period.
Impacts
What was accomplished under these goals?
We have successfully finished ourrandomized, placebo-controlled, crossover trial in 41individuals with prediabetes for two weeks to evaluate the effect of whole wheat bread on host plasma metabolomes, outcomes of metabolic and gut health (e.g., blood glucose and lipids, endotoxemia in relation to gut dysbiosis and intestinal permeability), and inflammatory response. Biochemical analysis of host health, multiplex metabolomics assays of host metabolome, and analysis of gut microbial composition were performed to understand if microbial composition will have predictive values to the whole wheat-induced improvement of health outcomes and metabolic profiles of different Prediabetes individuals in the study.
Publications
- Type:
Journal Articles
Status:
Under Review
Year Published:
2024
Citation:
Intestinal-level Anti-Inflammatory Bioactivities of Whole Wheat: Rationale, Design, and Methods of a Randomized, Controlled, Crossover Dietary Trial in People with Prediabetes, submitted to Nutrition Research
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Progress 04/01/22 to 03/31/23
Outputs
Target Audience:The study outcomes are meant to provide the state-of-the-art knowledge of how gut microbiome could modulate the health benifits of whole wheat intakes in metabolic diseases. Therefore, we expect the target audiences to be our peer scientists who work in similar field who can possibly taking the learned knowledge into additional scientific development, and stakeholders from government and food industry who may leverage the study outcomes to guide the production of new policies or new food products that will eventually better serve everyone in the US. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?This study provided several layers of training and professional development opportunities for young scientists at all levels. We have involved both unergraduate students and graduate students, as well as postdoc scholars in the study. They were exposed to various skill training, from clinical trial organization, participants' survey, collecitons of clinical samples (urine, feces, and blood), dietary interventions following national guidelines, to analytical chemistry and molecular biochemistry skills. How have the results been disseminated to communities of interest?
Nothing Reported
What do you plan to do during the next reporting period to accomplish the goals?The study team will continue to finish the clinical study of the proposed dietary intervention trial in the next reporting period. Meanwhile, extensive in vitro experiments utilizing the fecal samples collected from the clinical study will be performed in our state-of-the-art human colonical models for detailed dietary components-gut microbiome-metabolite interaction analyses. The food chemistry team are also ready to initiate experiments proposed in aim 3 for detection and isolation of bioactive components from whole wheat that may contribute to the modulation of gut microbes and their metabolism.
Impacts
What was accomplished under these goals?
The study team has fully engaged into the clinical trail proposed in Aim 1 since the beginning of this project. More than three quarter of proposed study participants (31 out of 40) have been recruited and the clinical trial is on its way to be completed in next few months. The team havealso gathered analytical standards to establish compliance biomarkers using HPLC-MS analysis for clinical samples analyses. Meanwhile, we are in the process of upgrading our human colonic model systems for more sophisticated, well-controlled, in vitro gut microbiome metabolome analyses.
Publications
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