Doctoral Dissertations

Date of Award

12-2021

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Chemistry

Major Professor

Shawn R. Campagna

Committee Members

Bhavya Sharma, Michael D. Best, Brynn H. Voy

Abstract

For all biological systems nutrients, including small molecules, are necessary for life. Small molecules in particular are used for biological processes such as energy metabolism and as building blocks for larger biomolecules like DNA, proteins, and lipids. Because of this, nutrition and metabolism are intrinsically linked, making metabolomics advantageous to nutritional studies. This work describes three separate studies using metabolomics to probe the effects of specific nutrients and diets in different conditions.

While exercise is documented to provide health benefits, the underlying metabolic mechanisms are not well known. Additionally, exercise is often used to reverse or prevent the negative effects of an unhealthy diet, such as gut dysbiosis. As gut dysbiosis has been seen to be sufficient cause metabolic and neurologic disorders, the interaction between an unhealthy diet, exercise, and the gut microbiome was investigated. From these studies using C57Bl/6J mice, it was determined that while diet had the most significant influence, exercise impacted cecal metabolism most.

Another approach that is commonly used to combat the negative affect of unhealthy diets is there dietary supplements. One of these supplements is fenugreek seeds (Trigonella foenum-graecum), which has been used in traditional herbal remedies to treat Type 2 diabetes and obesity. A proposed method by which fenugreek provides benefit is through gut microbiome alterations, which then alters the metabolome. Investigations of the metabolome of C57Bl/6J mice given ground fenugreek seeds (2% [percent] w/w) revealed that the large intestinal and liver metabolite profiles were significantly impacted by fenugreek.

The significant impact of nutrients on the metabolism is not limited to multicellular organisms. Using a unique one-host-two-temperate phage model system from the environmentally relevant Roseobacter clade, the influence of nutrients and phages were evaluated. The effects of a complex growth substrate were compared to glutamate and acetate on the metabolism and lipid regulation of two Sulfitobacter lysogens. From these analyses it was discovered that while there were small differences in the metabolome between strains, the lipids display dramatic differences based on growth substrate. Additionally, it was determined that phages impact the metabolite and lipid profiles in a nutrient dependent way.

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