Off-campus UNL users: To download campus access dissertations, please use the following link to log into our proxy server with your NU ID and password. When you are done browsing please remember to return to this page and log out.

Non-UNL users: Please talk to your librarian about requesting this dissertation through interlibrary loan.

Milk Exosomes and MicroRNAs Alter the Gut Microbiota and Affect Gut Health and Spatial Memory in Mice

Fang Zhou, University of Nebraska - Lincoln


Exosomes are nano-sized particles that play essential roles in cell-to-cell communication, facilitated by the transfer of exosome cargos such as RNAs, proteins and lipids from donor cells to adjacent or distant recipient cells. Evidence demonstrated maternal milk exosomes were absorbed and accumulated primarily in intestinal mucosa, liver, kidneys and brain in mouse pups. In addition, quantities of dietary milk exosomes and exosome microRNAs escaped absorption and reached the large intestine. However, the roles of milk exosomes and microRNA cargos in intestine and brain are now unclear. The first two chapters of this dissertation are to assess the effects of dietary bovine milk exosomes on the bacterial community in murine gut. We have shown that dietary intake of exosomes (and age), but not sex, had significant effects on the microbial communities in the colon in C57BL/J mice. Besides, bovine milk exosomes selected polymorphisms and mutations in gut bacteria, and these selections altered to the synthesis of microbial metabolites. The third chapter focus on the roles of maternal milk exosomes and microRNAs on growth and gut health in neonate pups. We have created two transgenic mouse models by temporally and spatially controlling the synthesis of exosome and mature microRNAs, respectively. The results demonstrated the loss of maternal exosomes and microRNAs biogenesis had no effect on the content of main macronutrients and water in milk. Milk exosomes and microRNAs promoted growth and gut health of newborn pups during lactation. The fourth chapter of this dissertation focuses on the role of dietary exosomes and their cargos on learning and memory in C57BL/6 mice. We identified that dietary milk exosomes and their cargos had effects on the cognitive behavior in C57BL/6. More than 100 transcripts were identified differentially expressed in pups brain ages 7 weeks fed exosome-defined diets. Top two enriched pathways, axon guidance and calcium signaling, suggested dietary exosomes played role on neuronal growth. Dendritic morphology analysis was consistent with the conclusion above.

Subject Area

Nutrition|Molecular biology|Bioinformatics|Physiological psychology

Recommended Citation

Zhou, Fang, "Milk Exosomes and MicroRNAs Alter the Gut Microbiota and Affect Gut Health and Spatial Memory in Mice" (2020). ETD collection for University of Nebraska - Lincoln. AAI28259111.