Progress 01/03/22 to 12/08/23
Outputs
Target Audience:The scientific community will benefit from elucidating the role of probiotics in amplifying metformin's benefits, as well as from the deeper understanding of the mechanisms by which probiotics and metformin affect the gut microbiome. The general public and specifically people with Type 2 diabetes could benefit from learning about how probiotics may improve blood glucose, and a press release for the recently accepted manuscript will be published to Penn State media outlets once it is published and available online. Changes/Problems:The major changes and challenges of this proposal were detailed in a letter received by the NIFA cognizant program officer on 2/23/2023 and accepted with an updated Award Face Sheet dated 3/16/2023. Briefly, we learned that for the clinical trial outlined in Objective 2, Institutional Review Board approval would not be feasible. In the place of conducting the clinical trial outlined in Objective 2, PD Van Syoc (Bean) completed an additional internship to gain similar skills and training in clinical and translational research. What opportunities for training and professional development has the project provided?PD Van Syoc (Bean) received training across experimental design, laboratory methods, data analysis, grantsmanship, and scientific communication towards her professional development and career goals of becoming an independent researcher. PD Van Syoc completed an internship with Dr. Steven Hicks at the Penn State College of Medicine and Hershey S. Milton Medical Center where she learned how to screen, recruit, and enroll participants into longitudinal clinical trials and received training in the REDCap and PowerChart applications to extract electronic health data. In addition to clinical science training, PD Van Syoc learned how to plan and execute both animal studies and systematic reviews and meta-analyses. This project presented an opportunity for PD Van Syoc to hone grantsmanship skills by preparing and submitting a Penn State College of Agriculture Competitive Graduate Student Grant. This was a small grant that provided funding for microbiome sequencing towards the analysis ofthe human gut mycobiome. PD Van Syoc identified additional opportunities for scientific communication and providing scientific education. Preliminary results from the research objectives were presented at the Experimental Biology, American Society of Microbiology national conferences, and at regional symposia including the Penn State Huck Life Sciences Colloquium and Harvard Chan Microbiome in Public Health Symposium. PD Van Syoc instructed a 3-hour workshop in collaboration with the Penn State Institute for Computational and Data Sciences to teach other faculty and students how to automate access to metagenomics data in the NCBI Sequence Read Archive and perform high-throughput analyses. How have the results been disseminated to communities of interest?Results from the research objectives have been disseminated to the scientific community via articles in peer-reviewed scientific journals and poster or oral presentations at regional and national conferences. Each article publication has been accompanied with a press release through the Penn State One Health Microbiome Center and associated social media channels. Once published and freely available online, the two systematic reviews on probiotics will be disseminated to the general public and people with Type 2 diabetes with a press release through the Penn State Department of Nutritional Sciences. What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
Objective 1: We discovered during a literature review that the effects of metformin on non-bacterial inhabitants of the gut microbiome had not been investigated. We therefore pivoted this objective to analyze the effects of metformin on the gut mycobiome, the fungal community of the gut microbiome, in people with type 2 diabetes. We additionally conducted a systematic review and meta-analysis to determine the effects of one type of probiotic, Bifidobacterium, on blood glucose in people with type 2 diabetes, metabolic syndrome, or obesity. The results of these projects have been posted as a preprint and accepted to a peer-reviewed scientific journal, respectively. Objective 2: As noted in the 2022 Progress Report, the execution of this sub-aim of the clinical trial was not feasible given additional IRB restrictions. Therefore, PD Van Syoc (Bean) completed an additional internship with Dr. Steven Hicks, a clinician scientist at the Penn State College of Medicine and Hershey S. Milton Medical Center. In this internship, PD Van Syoc (Bean) learned how to screen, recruit, and enroll participants to a longitudinal clinical trial and gained new skills to conduct clinical and translational research. Objective 3: This aim was executed in a mouse study wherein C57Bl/6 mice were fed a high-fat diet to generate diet-induced obesity. The mice were then treated with antibiotics to disrupt the gut microbiome and subsequently administered metformin, probiotics, the combination of metformin and probiotics, or a placebo. The results of this study are currently being prepared as a manuscript that will be submitted to a peer-reviewed scientific journal.?
Publications
- Type:
Journal Articles
Status:
Accepted
Year Published:
2023
Citation:
DiMattia, Z., Damani, J., Van Syoc, E., Rogers, C.J. Effect of probiotic supplementation on intestinal permeability in overweight and obesity: A systematic review of randomized controlled trials and preclinical studies. Accepted in: Advances in Nutrition.
- Type:
Journal Articles
Status:
Published
Year Published:
2023
Citation:
Van Syoc, E., Damani, J., DiMattia, Z., Ganda, E., Rogers, C.J. The effects of Bifidobacterium probiotic supplementation on blood glucose; a systematic review and meta-analysis of preclinical and clinical evidence. 2023. Advances in Nutrition. DOI: 10.1016/j.advnut.2023.10.009
- Type:
Journal Articles
Status:
Other
Year Published:
2023
Citation:
Preprint: Van Syoc, E., Nixon, M., Silverman, J.D., Luo, Y., Gonzalez, F.J., Patterson, A.D., Ganda, E. The gut mycobiome has a consistent relationship with type 2 diabetes mellitus and metformin treatment across populations. Preprint DOI: 10.1101/2023.05.25.542255
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Progress 01/03/22 to 01/02/23
Outputs
Target Audience:The scientific community will benefit from elucidating the role of probiotics in amplifying metformin's anti-inflammatory benefits, as well as from the deeper understanding of the mechanisms by which probiotics and metformin affect the gut microbiome. The general public and specifically type 2 diabetics will benefit from this project by receiving educational materials via the Penn State Extension program Dining with Diabetes. The Extension bulletin published on this project will be shared on the Dining with Diabetes social media outlets and email newsletter list. Many type 2 diabetics struggle to reach optimal glycemic control, and many American adults do not meet the dairy consumption guidelines outlined in the USDA 2020-2025 Dietary Guidelines. Therefore, this study seeks to identify accessible and nutritious dietary supplements to amplify metformin's anti-inflammatory effect and improve overall metabolic health. Changes/Problems:For the clinical trial outlined in Objective 2, we learned during the last reporting period that Institutional Review Board approval would not be feasible. Specifically, Penn State IRB stipulated that to recruit participants with diagnosed type 2 diabetes mellitus and a current metformin prescription, our research team would need to include endocrinologists and additional medical personnel that are not currently a part of the research team. There were additional limitations to the clinical trial including methods by which to monitor blood glucose, that our team was not equipped to conduct. Therefore, we concluded that the addition of type 2 diabetes mellitus participants to the existing clinical trial was not feasible given our resources. To address this gap in PD Van Syoc (Bean)'s training objectives, an additional internship was completed at the lab of Dr. Steven Hicks at the Penn State College of Medicine. During this internship, PD Van Syoc (Bean) shadowed a clinical research manager throughout the recruitment process for a longitudinal cohort and gained training in running clinical trials and translating research into the clinic environment. PD Van Syoc (Bean) will additionally assist in participant recruitment, screening, and visits for the clinical trial on probiotic supplementation in older adults with obesity at risk of metabolic syndrome that is currently under IRB review. What opportunities for training and professional development has the project provided?This project has provided the opportunity for PD Van Syoc (Bean) to obtain the desired training and professional development towards a career in academic research. Specifically, PD Van Syoc (Bean) completed a grantsmanship course at Pennsylvania State University and subsequently submitted a small internal graduate student grant. PD Van Syoc (Bean) presented an oral presentation at the Huck Life Sciences Symposium (Penn State) and poster presentations at Experimental Biology (Philadelphia, PA) and at World Microbe Forum (meeting of the American Society of Microbiology, Washington, D.C.). Towards training in clinical sciences, PD Van Syoc (Bean) completed a brief internship with Dr. Justin Silverman to learn advanced multi-omics statistical modeling, and a second internship with Dr. Steven Hicks at the Penn State College of Medicine, where she shadowed a clinical research manager and recruited participants in a clinic setting. Towards mentoring and training opportunities, PD Van Syoc (Bean) obtained mentoring from Dr. Andrew Patterson, Dr. Connie Rogers, and the Animal Resource Program at Penn State to successfully complete a mouse study, and bioinformatics and statistical mentoring from Dr. Laura Weyrich and Dr. Justin Silverman to complete a meta-analysis. How have the results been disseminated to communities of interest?The results of all three objectives are currently in preparation for publication in peer-reviewed manuscripts, after which dissemination will continue via conference presentations at local, regional, and national conferences, and a bulletin for the Penn State Extension's Dining with Diabetes Program. What do you plan to do during the next reporting period to accomplish the goals?In the next reporting period, work will continue on the dual meta-analyses (Objective 1) and mouse study (Objective 3) with the goal of publishing manuscripts in peer-reviewed journals during spring and summer 2023. The clinical trial of probiotic supplementation in older adults with obesity and criteria of metabolic syndrome (Objective 2) is currently under Institutional Review Board review and is anticipated to start recruitment in spring 2023, which PD Van Syoc (Bean) will assist with. Training and mentoring goals for the upcoming reporting period include mentoring during the writing process for the manuscripts in preparation, editing conference presentations, and recruiting participants for the clinical trial.
Impacts
What was accomplished under these goals?
During the reporting period, preliminary and pilot work was completed on all three objectives: Objective 1: A scoping search was performed to determine the feasibility of completing a meta-analysis on the effects of metformin or probiotics on the gut microbiome of subjects with metabolic syndrome or type 2 diabetes mellitus. We found that while publicly accessible metagenomics data was available for several studies with human subjects and metformin, there was a lack of publicly archived metagenomics data in probiotics studies. Thus, we are pursuing this objective in two parts; to evaluate the effects of metformin on the gut microbiome and eukaryotic community, and to evaluate the effects of probiotics on glycemic control. These dual projects are ongoing and anticipated submission for publication in peer-reviewed journals is expected for both before summer 2023. Objective 2:Due to limitations stipulated by Penn State's Institutional Review Board, the recruitment of participants with type 2 diabetes mellitus and an ongoing metformin prescription was not feasible (this is discussed further in "Major Changes"). The existing clinical trial of probiotic supplementation to older adults with obesity and risk of metabolic syndrome is under Institutional Review Board approval with an estimated start date of March 2023. PD Van Syoc (Bean) will assist in the running of that trial including participant enrollment and clinic visits. Objective 3: The mouse study outlined in Objective 3 was completed in October 2022 and lab assays are currently underway to assess the primary and secondary outcomes.
Publications
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