Progress 05/01/18 to 04/30/19
Outputs Target Audience:The target audeince reached by my efforts during this project includes PhD students, master students, undergradautes, faculty, and staff at my institution. The data collected were presented at a national scientific meeting, reaching individuals from private industry, the public sector, academic institutions, and medical centers. These data were also presented during my dissertation defense, which was open to the public and included an audience of academics and non-scientistsalike. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided? I attended lab meetings and journal clubs in the lab of my collaborating mentor, Dr. Lavanya Reddivari. Dr. Reddivari's lab focuses on the interaction between gut bacteria and bioactive compounds in improving health, using both in vitro and in vivo models of colonic inflammation and metabolic endotoxemia to understand the bioavailability, bacterial metabolism, and health benefits of bioactive compounds, and the inflammatory potential of microbiota. Attending her lab meetings allowed me to read the latest research findings in the field, increased my familiarity of assays utilized to conduct gut microbiome research at the bench, and helped with my understanding of translating bench research to clinical research. I also presented articles at journal club of the relevant clinical research in the gut microbiota and heart disease field to educate her graduate students. This discourse furthered my communication skills tomeaningfully interactwith animal scientists and translating clinical findings. I attended the NRI/AFRI Project Director's meeting at ASN in Boston, Massachusetts. At this meeting, I learned about ongoing AFRI-funded projects via poster presentations and select talks, and also networked with USDA representations, graduate students, and post-doctoral fellows. I attended webinars and in person seminars for academic and professional development, including: Elsevier Research Academy "How to turn your thesis into an article"; Penn State Graduate Writing Center "Drafting and Revising for Publication." I completed CITI trainings during the tenure of this award to further advance my research skills and ethical approaches to clinical trials, including the Responsible Conduct of Research course. I also completed a semester-longcourse in Professional Development in Health and Human Develpment offered through my university. Throughout this project, I received extensive training at the bench as a clinical research scientist. Skill acquired include, but are not limited to:proper collection of human fecal samples; fecal specimen handling, processing, and storage; fecal SCFA extraction and quantification methodology using gas chromatography-mass spectrometry (GC-MS); use of GC-MS instrumentation and interpretation of generatedoutput; general lab maintenance and safety skills. I successfully defended my dissertation in October 2018 and graduated with my PhD in December 2018. I leveraged my skills and knowledge obtained during my PhD to secure my current position as a Post-Doctoral Fellow on a T32 training grant at an NIH-funded research center. TheUSDA Pre-Doctoral fellowship was a vital step in my career to help me achieve my goal of becomingan independentclinical scientist in the food, nutrition, and human sciences. How have the results been disseminated to communities of interest? I presented a talk at Bucknell University in Lewisburg, Pennsylvania to increase the visibility, importance, and application of Nutritional Sciences. My lecture was titled "Ph.D. in Nutritional Sciences: A Research Path to Improve Human Health Through Diet" and focused on mytrajectory from an undergraduate student-athlete at Bucknell to my role as a Ph.D. Nutritional Sciences student at Penn State. I discussed the Penn State Nutritional Sciences graduate program, and provided details on the broad research areas - ranging from basic cellular and molecular mechanisms of nutrients to applied community health promotion programs. I emphasized the research projects within the Cardiometabolic Nutrition Research Laboratory and described ongoing clinical studies on the effects of dietary components on cardiovascular disease risk factors.The completed and ongoing components of my dissertation, including gut-related outcomes from this NIFA project, were described.Science, psychology, and pre-health majors were the primary attendees, and the major piece of feedback was the importance of presenting such scientific research at a liberal arts university to increase interest in non-physician science careers. I presented my findings from this project at the American Heart Association Epidemiology, Prevention, Lifestyle, & Cardiometabolic Health Conference in Houston, Texas. The title of my presentation was "Effects of Diets That Vary in Fatty Acid Composition on Fecal Short-chain Fatty Acid Levels and Their Relationship With Circulating Lipids and Lipoproteins" and was presented in the Nutrition session. The findings presented generated a great deal of interest and productive discussion by attendees, includingphysicians, clinicians, research scientistics, graduate students, post-docs, and representatives frompharmaceutical companies, hospital systems, and private industry. The research findings generated from this project compromised a full chapter of my dissertation, which were presented at my dissertation defense. The defense was opened to the public an announced university-wide, resulting in attendees from both academia and the community. My talk was titled "Effects of diets enriched in conventional and high-oleic acid canola oils compared to a Western diet on lipids and lipoproteins, gene expression, and the gut environment in adults with metabolic syndrome factors." Ongoing data collection and resultswere presented at lab meetings in the Cardiometabolic Nutrition Research Laboratory, with discussion of findings among, post-docs, faculty, PhD students, and undergraduate students. What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts What was accomplished under these goals?
The purpose of the project was to improve our knowledge of the diet, gut, and disease interrelationship to identify dietary strategies to modulate the microbiota and reduce chronic metabolic disease. The project results have a direct impact through contributing knowledge to the expanding diet-gut-health and disease challenge area, andsupporting thegrowing public demand for methods to modify the gut environment forhealth benefits. The short-chain fatty acids (SCFA) acetic acid, propionic acid, and butyric acid are microbial-produced metabolites that can influence host physiology through regulation of hepatic cholesterol metabolism. These biologically relevant gut metabolites may play a role in the hypocholesterolemic effects of select dietary components. We previously reported that diets containing canola oil and HOCO improved circulating lipids, lipoproteins, and apolipoproteins compared to a macronutrient-matched diet with a Western-like fatty acid profile. The biological mechanisms driving this cholesterol-lowering response are unknown. In a double-blind, randomized, controlled, three period crossover, controlled feeding clinical trial, participants with ≥2 Metabolic Syndromemeasures (n=20) were provided with an isocaloric, weight maintenance diet plus conventional canola oil, high-oleic acid canola oil (HOCO), or a control oil (control diet formulated to represent a Western diet fatty acid profile) for 6 weeks followed by washout periods of ≥4 weeks. Fecal samples were collected at the study enrollment and the end of each diet period. SCFA were extracted with ethyl acetate and quantified by gas chromatography-mass spectrometry. Blood was collected at the same time points for analysis of circulating lipids, lipoproteins, and apolipoproteins. After 6 weeks, a trend toward a treatment effect on endpoint fecal propionic acid was observed (P=0.09), with a trend toward a higher concentration following the control compared to the canola diet (P=0.09). Acetic acid was increased from baseline following the control diet (P=0.04). After the control diet only, fecal levels of propionic acid were positively correlated with blood levels of LDL-C, non-HDL-C, and apo B (r=0.52 to 0.64,P=0.003 to 0.02), with a trend in total cholesterol (r=0.39,P=0.10), and acetic acid was positively correlated with LDL-C and apo B (r=0.48 to 0.49,P=0.03 to 0.04), with a trend in non-HDL-C (r=0.44,P=0.06). No significant correlations between fecal SCFA and lipids and lipoproteins were observed after the two canola-based diets. These data suggest that the adverse effects of a contemporary Western diet fatty acid profile (i.e., higher-SFA/lower-USFA) on circulating lipid and lipoprotein parameters compared to diets higher in USFA/lower in SFA may be mediated, at least in part, by gut-derived SCFA. Future research is warranted to confirm these findings.
Publications
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