Table 2.
Neurotoxicity mechanisms associated with pharmaceuticals- and bacteria-mediated disruption of gut–brain axis in zebrafish.
| Model | Experiment | Biochemical assay | Main results | References |
|---|---|---|---|---|
| Adult zebrafish | Exposure of adult zebrafish to 6 and 60 μg/L enrofloxacin for 28 days | 16S rRNA gene sequence. neuroinflammatory and neurotransmission systems | Elevated Bacteroidetes proportion, but reduced Firmicutes/Bacteroidetes ratio. Increased intestinal TNF-α, IL-6, GLP1 and 5-HT but decreased plasma cortisol and ACTH concentrations. Increased brain NPY, brain-derived neurotrophic factor and CRH | Tian et al. (2023) |
| Adult zebrafish | Exposure of adult zebrafish to cyclophosphamide at 0.05, 0.5, 5 and 50 μg/L for 2 months | 16S rRNA gene sequence. Neurobehavior-related genes, dopamine-related genes, GABAergic- and serotonergic-related genes | Increased Fusobacteriales, Patescibateria, Rhodobacterals, Reyanellales and Staphylococcales proportions. Down-regulated neurobehavior-related genes (olig2 and lgals8), dopamine-related genes (th2 and drd2b) and GABAergic pathway (dlg4, grin2aa, grin2ab, opn3, opn5, tmtops, valopa and bdnf), whereas serotonergic-related genes (mao and tph1a) were up-regulated | Li et al. (2022) |
| Adult zebrafish | Exposure of zebrafish to flunitrazepam at 0, 0.2, and 5 μg/L for 30 days | 16S rRNA gene sequence. ROCK, Rho A, and inflammatory genes expression | Increased Proteobacteria and Actinobacteria but decreased Fusobacteriota and Firmicutes populations. Intestinal expression of pro-inflammatory mediators, up-regulated ROCK and Rho A, down-regulated anti-inflammatory cytokine expression, Occludin and zonula occludens 1 proteins | Lin et al. (2023a, b) |
| Adult zebrafish | Exposure of zebrafish to morphine (40 mg/kg) and sinomenine (80 mg/kg) with or without antibiotic (vancomycin, 100 mg/L; gentamicin, 10 mg/L, and kanamycin, 5 mg/L) | Identification of 16S rRNA gene sequence. Expression of occludins, drd2a and htr2a genes | Morphine increased Fusobacteria but decreased Actinobacteria proportion leading to up-regulated Bacteroidetes/Firmicutes ratio. Downregulated occludin a and occludin b but up-regulated drd2a and htr2a gene expression | Chen et al. (2020) |
| Adult zebrafish | Exposure of zebrafish to morphine (40 mg/kg) and isorhynchophylline (100 mg/kg) with or without antibiotic (vancomycin, 100 mg/L; gentamicin, 10 mg/L, and kanamycin, 5 mg/L) | Expression of dopaminergic, serotonergic, glutamatergic and opioid system genes | Isorhynchophylline inhibited morphine-mediated down-regulation of Oprms and Oprds genes expression as well as the up-regulation of drd2a, htr2a, gad1 and gad2 genes expression | Chen et al. (2021) |
| Juvenile and adult zebrafish | Exposure of zebrafish to 250 μg/L triclosan from 30 dpf (juvenile zebrafish) to 90 dpf (adult zebrafish) | 16S rRNA gene sequence. Biomarkers of inflammation, neurotransmission and apoptosis Histopathological examination | Increased Actinobacteria, Fusobacteria and Planctomycetacia proportion, with decreased Proteobacteria and Firmicutes. Elevated proinflammatory cytokines (IL6, IL1β, and IL21). Altered neurotransmission with gut and brain injuries | Wang et al. (2022a, b, c) |
| Adult zebrafish | Exposure of adult female zebrafish to L. casei, L. delbrueckii, and L. paracasei at a final concentration of 1.6 × 106 CFU/mL per aquarium and 200 mg/L of piracetam (a reference nootropic drug that reduces anxiety in humans) for 2 weeks | Identification of 16S rRNA gene sequence. Expression of glutamertagic genes | L. delbrueckii treatment increased Lactobacillus sp., Verrucomicrobium sp., Kaistia sp., Methylobacterium sp., Singulispira sp., Gordonia sp., and Mycobacterium sp. but decreased Legionella, Planctomyces, Flavobacterium, and Prevotella. L. delbrueckii treatment increased gad gene expression | Olorocisimo et al. (2023) |
| Adult zebrafish | Oral LGG supplementation at 106 CFUs/gram body weight to adult wild-type zebrafish chronically exposed to waterborne ethanol (0.01% v/v) for seven consecutive days | Histopathological examination of the zebrafish brain | Mitigation of ethanol-induced aberrant neurobehavior and brain injury in zebrafish | Aparna and Patri (2023) |
| Adult zebrafish | Exposure of adult wild-type zebrafish to Paraburkholderia sabiae (1.0 × 109 cell/L) in the rearing water twice a day at feeding times for 1 month | Identification of 16S rRNA gene sequence. GABAergic and serotogenic genes expression. Evaluation of neurotransmitter (taurine) concentration | Increased Rhizobiales populations namely Bradyrhizobiaceae, Pirellulaceae, Rhodospirillaceae and Xanthobacteraceae; decreased Actinomycetales populations namely Aeromonadaceae, Gordoniaceae, Gordonia, Nakamurellaceae, Nocardiaceae and Nocardia. Brain tph2 gene expression was increased | Ichikawa et al. (2023) |