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Author

Min GuFollow

Document Type

Campus-Only Access for One (1) Year

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Food Science

Year Degree Awarded

2018

Month Degree Awarded

September

First Advisor

Hang Xiao

Subject Categories

Food Science

Abstract

The microbial cells that colonize the human body, including mucosal and skin environments, are at least as abundant as our somatic cells and certainly contain far more genes than our human genome. Gut microbiota dysbiosis is associated with the onset and progress of several diseases, like diabetes, obesity, inflammatory bowel disease. One of the environmental factor-diet intervention can modulate the compositions of gut microbiota, which in turn may contribute to altered health outcomes such as changes in the risks of chronic diseases. Orange peel has been a traditional herb in China, and some of its compounds has shown health benefits. However, to our knowledge, limited information is available about the interaction between bioactive dietary compounds in

orange peel and gut microbiota. Firstly, we aim to study the metabolic fate of limonin and how it will modify the gut microbiota in mice.

Unchallenged mice were fed a diet containing limonin (0.05% w/w) for 9 weeks. Limonin distribution analysis revealed that most limonin was unabsorbed and persisted to colon. During the 9-week feeding time, mice gut microbiota profile was altered continuously. After 9 weeks’ dietary intervention, diversity of the mouse gut microbiota was significantly enhanced compared with control group. In the meantime, the gut microbiota community structures were markedly distinct between the two groups. Limonin treatment significantly unregulated the abundance of 27 genera and downregulated the level of 5 genera. Based on the analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) database, 11 functional pathways were predicted to be upregulated while 9 functional pathways were downregulated dramatically. Specifically, the functional pathways related to the production of bacterial toxin and the Staphylococcus aureus infection were suppressed dramatically with limonin treatment.

Here we observed that gut microbiota was changed by limonin supplementation. We hypothesized that nobiletin, another major compound from orange peel, could alter mice gut microbiota, which might contribute to host health benefits of nobiletin. In this study, we determined the effects of dietary nobiletin intervention dextran sodium sulfate (DSS)-induced colitis as well as the composition of gut microbiota in mice. The results revealed that nobiletin treatment significantly decreased the severity of colonic inflammation in DSS-treated mice, evidenced by the reduced production of pro- inflammatory cytokines (i.e., GM-CSF, INF-𝛾, IL-1𝛽, IL-2, IL-6, KC/GRO, and TNF-𝛼) in the colonic mucosa, increased colon length, and decreased disease activity index and

histologic score of inflammation (p

Besides, we found that gut microbiota in the colon involved the metabolism of nobiletin and contributed to the anti-inflammation effect of nobiletin. Therefore, we isolated and identified the bacteria with nobiletin metabolizing capacity. Bacteria Isolate G7 was the potential one belong to species Bifidobacterium pseudocatenulatum, which is commonly regarded as probiotic. Except the metabolizing ability, its secretion has strong anti-inflammation effect by blocking the NF-𝑘B pathway in Raw 264.7 cells. Isolate G7 secretion performed strong anti-cancer effect on human colon cancer cell HCT116 by promoting cell apoptosis, arrest cell cycle at G2/M phase and downregulate the gene expression of wnt signaling pathway.

The oral delivery of probiotics to the colon is often difficult because they lose viability when exposed to the harsh conditions in the upper gastrointestinal tract, such as the highly acidic gastric fluids. Properly designed encapsulation technologies can be used

to protect probiotics during their transit through the human gut. In this study, an anaerobic probiotic (Bifidobacterium pseudocatenulatum G7 or BPG7) was encapsulated within alginate microgels that also contained antacid agents to control their internal pH within the stomach. Probiotic-loaded microgels were exposed to a simulated gastrointestinal tract (GIT) model to establish the impact of gastric and small intestinal conditions on their physicochemical properties and cell viability. In the absence of antacid, no live probiotic cells were detected in the microgels after exposure to gastrointestinal conditions. Conversely, in the presence of antacid, there was only a 1.5 log CFU decrease in cell viability after incubation in simulated gastric fluids for 2 h. After the antacid microgels were then incubated in simulated intestinal fluids, viable probiotic cells were still detected when CaCO3 was used as an antacid but not when Mg(OH)2 was used. Overall, these results indicate that alginate microgels containing CaCO3 as an antacid were the most efficient at protecting the probiotic during passage through the upper GIT. This novel encapsulation technology may be useful for the oral delivery of probiotics to the gut in the form of functional foods or supplements.

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