Gut Microbiota as a Therapeutic Target

The gut microbiome plays a significant role in myriad biological processes, including health maintenance, digestion, immune system development, diseases, brain function, metabolism and aging. The intricate network of interactions between the gut, gut microbiome and the central nervous system (CNS) is called the microbiota gut-brain axis. The microbiota-gut-brain axis regulates glial functions and therefore is a phenomenal target to manipulate the progression of neurodegenerative diseases.

The Villapol laboratory’s efforts are heavily focused on TBI. Any brain injury caused by an external force , such as falls, car accidents, gunshot wounds or contact sports, are referred to as TBIs. According to the Centers for Disease Control and Prevention, there are about 190 TBI-related deaths daily on average in the United States. Using a preclinical TBI model, Villapol concluded that TBI can cause disturbances in the gut microbiota and lipid metabolism in the liver.

Villapol believes that the brain can be protected from the adverse effects of TBI by modifying the composition of the gut microbiome.

“By understanding and intervening in the gut-brain-liver axis, researchers and medical practitioners could develop strategies to improve outcomes for individuals affected by TBI,” commented Villapol.

According to Villapol, “Our results underscore the potential of probiotic interventions as a viable therapeutic strategy to address TBI-induced impairments, emphasizing the need for gender-specific treatment approaches.” Gut dysbiosis is strongly correlated with neuroinflammatory diseases. Specific neuroinflammatory diseases associated with the gut microbiome include multiple sclerosis, AD, and Parkinson’s disease. A hallmark of several neurological diseases is impairment of the blood-brain barrier that is critical for brain homeostasis. This causes harmful proteins such as beta amyloid plaques and tau tangles to accumulate in the brain while also preventing effective treatment using the blood stream. Under these circumstances, nanomedicine becomes a promising approach. Villapol developed a novel delivery system that uses biomimetic nanoparticles for drug delivery as well as diagnostics for AD and brain injury. According to Villapol, “Biomimetic nanoparticles are a promising tool that can accelerate a therapy's translation more efficiently than cellular or exosome‐based techniques due to the ease of fabrication, purification, and similarity between the different nanoparticle batches. Relevant differences in nanoparticle biodistribution after brain trauma in filtering organs suggest a potential local and systemic future targeting strategy. Biomimetic nanoparticles could be strong candidates for acute pharmacologic treatment in TBI patients.” “By observing the infiltration of nanoparticles into inflamed tissues, we can design how to overcome the therapeutic challenges of TBI using pharmacological therapy targeting specific inflammatory mechanisms,” Villapol added.

Additionally, Villapol and her team performed gut microbiome profiling on samples from 124 hospitalized COVID-19 patients using full-length 16S rRNA gene sequencing and found significant associations between mental health status, systemic inflammation and gut dysbiosis. “The relationship between the gut-brain axis, gut microbiota, and psychiatric disorders, such as depression and anxiety, remains an area of active research and debate within the psychiatric community. While recent studies suggest that gut microbiota alterations may influence brain function and contribute to depressive and anxiety symptoms, the underlying mechanisms are not yet fully understood. Randomized controlled trials are necessary to assess the effectiveness of microbiome-targeted therapies, such as probiotics and dietary interventions,” Villapol commented.