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Abstract
Acquired brain injury, such as stroke and traumatic brain injury, are devastating injuries that result in long-term disability and death. Recently, inter-organ communication has gained attention due to its pivotal role in homeostasis and disease pathophysiology. Particularly, the microbiome-gut-brain axis is the major inter-organ communication for maintaining homeostasis in brain injuries. The microbiome is the genetic material of all the microorganisms that live on and inside the body and is essential for nutrition, human development, and immunity. In particular, the gut microbiome is a key regulator of the gut-brain axis and is closely related to neurological function and mental health of the host. The microbiome is also present in other parts of the human body, including oral cavity, skin, and hair, etc. This dissertation aims to evaluate the effect of acquired brain injury on microbiome and homeostasis in gut and oral cavity. In manuscript #1, gut microbiome changes were characterized during the acute stage of stroke in a pig model. Ischemic stroke significantly induced shifts in microbial diversity, increased levels of opportunistic pathogens, and reduced beneficial microbes, which were associated with the stroke severity. In manuscript #2, changes in gut inflammation and gut membrane integrity was investigated following the intracisternal administration of Tanshinone IIA-loaded nanoparticles (Tan IIA-NPs) and induced pluripotent stem cell-derived neural stem cell (iNSCs) transplantation therapy during the long-term ischemic stroke in a pig model. Tan IIA-NP+iNSC treatment increased fecal SCFAs levels, reduced protein levels of TNF-α and TNF-α receptor 1 and increased expression of gut tight junction proteins occludin, claudin1, and ZO-1. In manuscript #3, we investigated whether the traumatic brain injury (TBI) alters oral microbiota composition, which is the second largest microbial community in body. TBI reduced Faith’s Phylogenetic Diversity and altered beta-diversity of the oral microbiome compared to the sham surgery without altering the taxonomical composition. Findings from these studies suggest that acquired brain injury such as stroke and TBI modulate microbial composition in gut and oral cavity and the crosstalk between the microbiome and the host may be a potential therapeutic target for conditions involving neurological disorders.