Table 1.
Animal studies about Microbiota and ASD-like phenotypes
| Study | Country | Subject | Behavior | Group | Description |
|---|---|---|---|---|---|
| Sudo et al. [158] | Japan | Mice | Stress response | Germ free/Specific pathogen free/Gnotobiotic mice | Germfree mice have elevated stress response, reduced BDNF in cortex and hippocampus. Germfree colonization with Bifidobacterium infantis reversed hypothalamic-pituitary-adrenal stress response |
| Verdú et al. [159] | Canada | Mice | Visceral hypersensitivity | Groups treated with Antibiotic and Lactobacillus paracasei, Antibiotic or Placebo (saline water) | L. paracasei NCC2461 normalized visceral sensitivity |
| Desbonnet et al. [141] | Ireland | Rats | Depression-like behavior | Groups treated with Bifidobacteria infantis or not | Probiotic B. infantis treatment did not change swimming, climbing, and immobility but decreased IFNγ, TNFα and IL-6 cytokines |
| Desbonnet et al. [142] | Ireland | Rats | Depression-like behavior | Maternal separation stress models treated with B. infantis, citalopram or not | Probiotic Bifidobacterium infantis treatment in a maternal separation stress model normalized IL-6 levels, increased swim behavior and reduced immobility in forced swim test, and restored basal noradrenaline levels in brainstem |
| McKernan et al. [160] | Ireland | Rats | Visceral hypersensitivity | Visceral normosensitive (Sprague-Dawley) and visceral hypersensitive (Wistar-Kyoto) rat | Probiotic Bifidobacterium infantis 35624 reduces visceral pain |
| Bercik et al. [161] | Canada | Mice | Anxiety-like behavior | Uninfected control and T muris-infected mice, treated with placebo, etanercept, budesonide, and probiotics | Colonic inflammation induced anxiety like behavior, decreased hippocampal BDNF mRNA, and increased circulating TNF-α and IFNγ Probiotic Bifidobacterium longum restored behavior and BDNF |
| Messaoudi et al. [145] | France | Rats and adults | Anxiety, depression, and stress | Groups treated with probiotic preparation, placebo (0.5% methylcellulose solution) and diazepam | Probiotic (Lactobacillus helveticus and Bifidobacterium longum) reduced anxiety-like behavior in rats and reduced psychological stress inpatients |
| Diaz Heijtz et al. [63] | Sweden | Mice | Motor activity and anxiety-like behavior | Germ free/Specific pathogen free | Germ-free mice have increased motor activity and decreased anxiety Changes in PSD-95 and synaptophysin expression in striatum |
| Bravo et al. [162] | Canada | Mice | Anxiety-and depression-related behaviors | Lactobacillus rhamnosus (JB-1)-fed mice Broth-fed mice (control) | Probiotic L. rhamnosus treatment of mice in a stress model reduced stress and increased GABA receptor expression in prefrontal cortex. L. rhamnosus increased cortical GABA (B1b) receptor expression, decreased GABA (Aα2) expression in prefrontal cortex and amygdala, but increased in hippocampus. L.rhamnosus reduced stress, anxiety and depression behavior |
| Bercik et al. [163] | Canada | Mice | Anxiety-like behavior | Dextran sodium sulfate colitis with Bifidobacterium longum or control medium | Chemical colitis mouse model treated with probiotic (B. longum) had normalized anxiety like behavior. Chronic colitis model has increased anxiety. B. longum normali zed behavior, but no change in BDNF expression |
| Hsiao et al. [37] | USA | Mice | ASD-like behaviors | MIA offspring treated with vehicle or Bacteroides fragilis | MIA mice have decreased GI barrier, increased IL-6, decreased cytokine/ chemokine, and gut microbial dysbiosis, and autism-related behaviors that were restored following colonization with B.fragilis |
| Desbonnet et al. [66] | Ireland | Mice | Social preference and repetitive behaviors | Germ free rearing and germ-free bacterial colonization mice groups | Germ free mice had deficits in social avoidance, social novelty, social investigation and also had increased repetitive self-grooming |
| Buffington et al. [67] | USA | Mice | Social behavior | Maternal high fat diet treated with Lactobacillus reuteri or not | Maternal high fat diet induced social deficits in offspring are restored following colonization with Lactobacillus reuteri |
| Sharon et al. [68] | USA | Mice | Social behavior and repetitive behaviors | Mice colonized by feces of human donors with ASD or TD donor | Mice with human ASD, but not TD displayed ASD-like behaviors Extensive alternative splicing of risk genes are observed in brains of mice with ASD. Metabolome analysis showed significant differences between the two groups |
ASD: autism spectrum disorder, BDNF: brain derived neurotrophic factor, TNF-α: tumor necrosis factor-α, IL: interleukin , GABA: gamma-amino-butyric acid, MIA: maternal immune activation, GI: gastrointestinal, TD: typically developed