The gut microbiota in neurodegenerative diseases: revisiting possible therapeutic targets for cannabidiol

Understanding the pathophysiology of Alzheimer's disease (AD) is essential to improve the efficacy of treatments and, consequently, patients' lives. Unfortunately, traditional therapeutic strategies have not been effective. There is therefore an urgent need to discover or develop alternative treatment strategies. Recently, some pieces of the puzzle appear to emerge: on a hand, the gut microbiota (GM) has gained attention since intestinal dysbiosis aggravates and generates some of the pathological processes of AD; on the other hand, cannabidiol (CBD), a phytocannabinoid, attenuates intestinal inflammation and possesses neuroprotective properties. Intestinal dysbiosis (increased population of proinflammatory bacteria) in AD increases plasma lipopolysaccharide and Aβ peptide levels, both responsible for increasing the permeability of the blood-brain barrier (BBB). A leaky BBB may facilitate the entry of peripheral inflammatory mediators into the central nervous system and ultimately aggravate neuroinflammation and neuronal death due to chronic activation of glial cells. Studies investigating the GM reported a strong relationship between intestinal dysbiosis and AD. In this review we conjecture that the GM is a promising therapeutic target for CBD in the context of AD.