Synaptic and neural circuitry dysfunction found in postmortem brain tissue from individuals with ASD. Increased Clostridium and Lactobacillus and decreased Bacteroidetes and Bifidobacterium found in fecal samples collected from children with ASD.

Mice lacking microglia during early stages of postnatal development demonstrate cognitive and behavioral hallmarks reminiscent of ASD, in addition to abnormal neuronal signaling. Decreased SCFA levels in ASD patients compared to healthy controls.

Monocolonization of GF mice with Bacteroides fragilis attenuates cognitive and GI defects in mice.

Elevated pro-inflammatory cytokine release (IL-2, IL-6, IL-8, and TNF-α) and neuroinflammation in the CNS. High levels of colitis and GI dysfunction in schizophrenic patients.

Elevated microglial density in temporal cortex of schizophrenic patients. GF and MIA mice display schizophrenic-like behaviors (e.g., decreased sociability and anhedonia).

Microglia-mediated disruptions in white matter structure and volume in the prefrontal cortex. Oropharyngeal microbiota of schizophrenic patients is less diverse than controls and enriched in Lactobacilli, Bifidobacterium, and Eubacterium and depleted in Neisseria and Haemophilus.

Abnormal synaptic remodeling by microglia disrupts neural circuitry in schizophrenic patients due to increased expression of complement proteins C3 and C4. Schizophrenic patients demonstrate dysregulation of several metabolic pathways regulated by the gut microbiota.

Increased microglial secretion of exosomes carrying pro-inflammatory cytokines in individuals with MDD. Probiotic supplementation of Lactobacillus casei improved mood in patients with depression.

Chronic stress, a partial contributor to/risk factor for depression, is attributed to increased microglia-driven neuroinflammation. Mouse model of MDD exhibiting high levels of stress has increased levels of Clostridium and reduced levels of Lactobacillus and Bacteroides.

Precise role of heightened neuroinflammation in the brain in MDD remains poorly understood.

PET scans from 11 PD patients reveal widespread microglial activation in the basal ganglia and the temporal and frontal cortex that exceeds the level of activation found in healthy controls. Microbiota of PD patients demonstrate increased levels of Enterobacteriaceae and decreased levels of Bacteroidetes and Prevotellaceae.

α-Synuclein aggregates trigger microglial activation in the substantia nigra. Concentrations of SCFAs (acetate, propionate, and butyrate) were lower in fecal samples collected from PD patients.

Microglial release of pro-inflammatory cytokines and neurotoxic factors is a contributing factor to dopaminergic cell death. SIBO was observed in 25–54.5% of patients.

Heightened microglial activation observed in several Parkinsonian-like transgenic mice (α-synuclein overexpression) and toxin-induced mouse models (MPTP, 6-OHDA, and rotenone). Misfolding and aggregation of α-synuclein may begin in enteric neurons that innervate the gut.

GF mice overexpressing α-synuclein demonstrate attenuated motor and GI symptoms compared to their SPF counterparts.

Microglia were found to drive propagation of tau protein. Reduction of microbial diversity following antibiotic administration reduced amyloid beta pathology and microglial activation in AD mice.

Microglia aggregation surrounds amyloid beta plaques. Microbiota of APPPS1 transgenic mice have a higher Bacteroidetes/Firmicutes ratio compared to WT mice along with reduced levels of Verrucomicrobia.

Neurodegeneration occurs partially in response to microglia-driven chronic inflammation. In vitro administration of several SCFAs (valeric acid, propionic acid, and butyric acid) obstructs aggregation of amyloid beta protein.

Neuroprotective microglia subtype recently identified operating through a TREM2-mediated signaling pathway.

Complement protein (C1q), involved in mediating microglial synaptic remodeling, is upregulated in AD mouse models.

Microglial release of pro-inflammatory cytokines and neurotoxic factors (TNF-α and IL-1β) increases as disease progresses. G93 ALS mice expressing mutant SOD1 protein have lower expression of intestinal epithelial tight junction proteins and subsequent disruption to the intestinal barrier.

Microglia expressing mutated Cu,Zn superoxide dismutase (SOD1), a familial ALS gene, accelerates loss of motor neurons and disease progression, while WT microglia conferred neuroprotective effects. G93 mice have a varying gut microbiota composition compared to healthy control mice with reduced levels of Escherichia coli, Fermicus, and butyrate-producing bacteria.

The neuroprotective role of anti-inflammatory microglia found in early stages of ALS is lost as increased levels of pro-inflammatory microglial activity drive neurodegeneration. Drinking water supplemented with the SCFA butyrate improved intestinal barrier function and life expectancy in a G93 ALS mouse model.

Secretion of mutated SOD1 protein into extracellular space triggers microglial dysfunction and activation.

Activated microglia produce reactive oxygen species that contribute to oxidative stress and heightened neuronal injury, neurodegeneration, and demyelination. High concurrence of inflammatory bowel disease and MS.

Inhibiting microglial activation prevented the onset of EAE in mice and decreased the presence of CNS lesions. Dysbiosis found in MS patients (n = 20) characterized by depleted levels of Bacteroides and Prevotella and enriched levels of Bifidobacterium and Streptococcus compared to healthy controls.

Microglia-mediated remyelination is impaired in MS patients. Patients (n = 31) with MS have an altered microbiota composition compared to age- and gender-matched controls, with increased levels of Pseudomonas and Mycoplana.

Activation of microglia during the early stage of disease facilitates recruitment of T cells from the periphery. Monocolonization of GF mice with different species enriched in MS patients (Akkermansia muciniphila and Parabacteroides distasonis) influenced differentiation of regulatory T cells and lymphocytes.

Subsets of microglia with activated TNFR2 and TREM2 signaling demonstrate a neuroprotective role in EAE mice. Development and severity of EAE is lower in GF mice and antibiotic-treated mice compared to SPF mice, as shown by an attenuated release of pro-inflammatory cytokines.