5 GUT MICROBIOTA-MEDIATED DRUG NEUROTOXICITY
The intestinal microbiota produces vast amounts of metabolites some of
which exert neurotoxicity, such as D-lactic acid and ammonia (Galland,
2014). Ammonia is a key factor contributing to hepatic encephalopathy
which is accumulated in the brain when the liver undergoes dysfunction
(Wijdicks, 2016), and modulation of gut microbiota has been demonstrated
effective in decreasing ammonia production and subsequently alleviating
encephalopathy (Shen et al., 2015). Moreover, the intestinal microbiota
is also indirectly engaged in neurotoxicity of xenobiotics including
environmental neurotoxicants, metals, drugs, and pesticides (Dempsey et
al., 2019) of which neurotoxicity is the most frequently encountered
adverse effect in antibiotic exposure representing in multiple ways
including headache, delirium, psychosis, and seizure (Bangert and
Hasbun, 2019; Champagne-Jorgensen et al., 2019) (Fig.5). While some
absorbable antibiotics enter the brain through blood brain barrier (BBB)
and cause direct damage, most non-absorbable antibiotics such as
neomycin and vancomycin also induce impairments in nervous system and
behavior, suggesting a pivotal of the gut-brain axis plays therein
(Fröhlich et al., 2016). With antibiotic treatment proven efficient in a
variety of microbiota-implicated diseases, tackling antibiotics-induced
neurotoxicity seems more troublesome, especially with its mechanisms
remaining ambiguous. Besides antibiotics, anesthetics and psychotropic
drugs are also found to exert neurotoxicity with intestinal microbiome
involved and they will also be discussed afterward.