Influence of gut microbiota on neuropsychiatric disorders

Table 1 Preclinical evidences of the role of gut microbiota on behavior

Germ-free (GF) mice have shown impaired social behavior[39]

GF mice have displayed exaggerated stress response[21] and differences in anxiety-like behavior[22,23]

GF mice have showed crucial changes in multiple neurotransmitters and their receptors in different brain regions[23]

GF animals have exhibited an impaired neurogenesis[25] and structural and functional changes in the amygdala[26]

GF mice have shown prefrontal cortical hypermyelination[27]

Microglial function impaired in GF animals is rescued by the oral treatment with short chain fatty acids[11]

Gut microbiota has been shown to modulate brain-derived neurotrophic factor, oxytocin and vasopressin brain levels[20]

Different probiotic preparations for administration to rats and mice have shown to achieve a reduction in anxiety-like and depressive-like behaviors[6,58]

Table 2 Current evidences linking gut microbiota to neuropsychiatric disorders

Autism

Increase in microbiota diversity is associated with autism[43]

Abundance of Bacteroidetes has found to be linked with severe autistic cases[43]

Increase in short chain fatty acids has been found in fecal samples from autistic children[44]

A specific strain of the species Lactobacillus reuteri has shown to modulate oxytocin levels and reverse autism-related behavior[41]

Schizophrenia

Dopamine, the key neurotransmitter associated with schizophrenia pathophysiology, is produced by components of the microbiota[53]

Increased gastrointestinal inflammation is associated with schizophrenia[53]

Intake of antibiotics is associated with the risk of schizophrenia[54]

Attention deficit hyperactivity disorder

The risk of developing ADHD has been suggested to be associated with many perinatal risk factors, including delivery mode, gestational age, type of feeding, maternal health and early life stressors, all of them linked to gut microbiota alterations[56]

Dietary components modulating gut microbiota may influence ADHD development or symptoms[56]

Depression

Increase in gut microbiota alpha diversity is associated with depression[59,63]

Lower numbers of Bifidobacterium and Lactobacillus have been found in individuals with depression[60]

Increases in the genus Eggerthella, Holdemania, Gelria, Turicibacter, Paraprevotella and Anaerofilm, and reductions in Prevotella and Dialister have been found in individuals with depression[61]

A negative correlation between Faecalibacterium spp. and severity of depressive symptoms has been reported[61]

Role of diet on depression onset is suggested (Mediterranean diet seems to protect, whereas Western diet seems to be associated with an increased risk)[64]

Different strains of Lactobacillus rhamnosus, Lactobacillus helveticus, Bifidobacterium longum, Bifidobacterium breve and Bifidobacterium infantis have been shown to attenuate depression and anxiety-related behavior in rodents[58]

A probiotic combination (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) has proven effective in increasing the subject’s resilience to stress in humans[57]

Parkinson’s disease

Alterations in bowel function, mainly constipation, often precede the onset of motor symptoms associated with PD[76]

Reduction in the levels of Prevotellaceae has been found in PD patients[80]

Positive correlation between levels of Enterobacteriaceae and the severity of postural instability and gait difficulty was proven in PD patients[80]

Reduction in short chain fatty acids[78] and butyrate-producing bacteria (Blautia, Coprococcus, Faecalibacterium spp and Roseburia)[79] were found in fecal samples from PD patients

GF mice overexpressing human α-synuclein (αSyn) display reduced microglia activation, αSyn aggregates and motor deficits (treatment with short chain fatty acids restored all major features of PD in GF mice)[77]

Gut microbiota transfer from PD patients into GF mice overexpressing human α-synuclein (αSyn) enhances physical impairments whereas gut microbiota transfer from healthy human donor does not enhances those deficiencies[77]

Alzheimer’s disease

Risk factors for AD such as metabolic syndrome, type 2 diabetes and obesity are associated with gut microbiota alterations[86,87]

Gut microbiota seems to be involved in the accumulation of amyloid plaques according to the results of a study using a mouse model of AD[88]

AD: Alzheimer’s disease; PD: Parkinson’s disease; ADHD: Attention deficit hyperactivity disorder.