Date of Award

Summer 8-16-2024

Level of Access Assigned by Author

Open-Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical Sciences

Advisor

Suzanne Ishaq

Second Committee Member

Yanyan Li

Third Committee Member

Melody Neely

Additional Committee Members

Tao Zhang

Abigail Johnson

Abstract

Inflammatory bowel disease is a chronic intestinal condition characterized by severe inflammation, oxidative stress, microbial dysbiosis, and cellular structure and barrier damage. The complex mechanism of pathologies makes it challenging to manage the disease effectively. Most current treatments target only inflammation using steroids and antibiotics with side effects. Therefore, recent research has focused on safe and effective nutritional options. Broccoli sprouts, Brassica oleracea variety italica, is a member of the Brassicaceae family and has documented antioxidant, anti-inflammatory, and gut protective benefits against inflammatory bowel diseases. These benefits have been associated mainly with sulforaphane from dietary glucosinolates present in broccoli sprouts. However, many other dietary and microbially derived metabolites are present in broccoli sprouts that are yet to be identified and explored against inflammatory bowel diseases. Commensal bacteria such as Bifidobacterium and Bacteroides have been reported to participate in hydrolyzing dietary metabolites for gut benefits. However, there is a need for more studies on the differential effects of broccoli sprouts on metabolite concentration and microbial communities in diverse patients with these gut conditions. Additionally, the interactions of these metabolites with

microbial communities in specific gut regions still need to be clarified. Therefore, this project utilized dietary assessments, computational analyses, and a global metabolomics approach to identify beneficial metabolites and microbial interactions across different age groups and genders associated with broccoli sprouts diet as a potential nutritional intervention against inflammatory bowel diseases.

First, I assessed the role of high consumption of dark green vegetables diets such as Brassicas, fruits, and fiber on the healthy eating index using dietary history surveys and the effect of steamed broccoli sprouts intervention on the microbial response of Bacteroides thetaiotaomicron genes for benefit in healthy individuals with self-reported gut problems. Bacteroides thetaiotaomicron genes are associated with increased conversion of glucosinolates from broccoli sprouts into isothiocyanates, such as sulforaphane, for anti-inflammatory and antioxidant effects against inflammatory bowel disease. The data showed a healthy eating index of >70 in individuals who consumed at least twice daily dark green vegetables may have a high expression of Bacteroides thetaiotaomicron genes. This result was particularly evident before, at the end, and seven days after the broccoli sprout diet in young and middle-aged persons with gut conditions who consumed high amounts of dark green vegetables, fiber, and fruits above the daily values recommended by the dietary guidelines for Americans. These vital results provide information for future research to explore personalized approaches for dietary recommendations for individuals with gut conditions in compliance with dietary guidelines for Americans and its beneficial effect on diet-microbial responsiveness, particularly in young adults.

Second, I utilized untargeted metabolomics and computational tools to examine the effects of steamed broccoli sprouts intervention on the concentrations of beneficial dietary and microbial- derived metabolites. Also, I investigated the association between the metabolites, commensal

bacteria, and Bacteroides thetaiotaomicron genes in ulcerative colitis mice. Metabolites annotated in fecal samples after broccoli sprouts diet includes sulforaphane, short-chain fatty acids, tryptophan, indoles, glutamic, and polyphenols with antioxidant, anti-inflammatory, and gut- protective effects against mouse models of inflammatory bowel diseases. These metabolites positively correlate with commensal bacteria, Bacteroides, Intestinimonas, Oscillibacter, and Lachnospiraceae species in the colon, cecal and jejunum regions. These findings open up exciting avenues for future research, particularly in targeting region-specific benefits of broccoli sprouts intervention against inflammatory bowel diseases.

Lastly, I examined the differential effect of two different preparations, steamed and mildly heated broccoli sprouts diets, as interventions for ulcerative colitis in female and male, young and adult mice. Metabolic profiles of plasma samples revealed increased concentrations of glucoraphanin and glucoerucin, iso-ferulic acid, flavanone-4-glucuronide, and denticulaflavonol are which may be associated with decreased disease activity and recovery from colitis observed in adult female mice. Adult male and younger mice may benefit more from mildly heated broccoli sprouts with increased concentrations of catechin, proanthocyanidins, short-chain fatty acids, and glutathione metabolites. Novel information generated from this study could guide the targeted application of broccoli intervention as nutritional management for specific age and gender groups with inflammatory bowel condition

Comments

Alaba, T.E., Holman, J.M., Ishaq, S.L., Li, Y. 2024. Current knowledge on the preparation and benefits of cruciferous vegetables as relates to in vitro, in vivo, and clinical models of Inflammatory Bowel Disease. Current Developments in Nutrition: 102160.

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