Microbiome meets microglia in neuroinflammation and neurological disorders

Abstract

One of the emerging hot topics in biosciences is the intriguing link between gut microbial communities and its influences outside the gastrointestinal tract, such as the central nervous system (CNS), including its cognitive activities and immune responses. Beyond its neuroprotective properties, microglia are also critical for neuronal synaptic pruning and neural remodeling during CNS development. Prolonged microglia activation and neuroinflammation are considered key contributors to neurological disorders. In this regard, it is becoming increasingly important to consider the potential influences underlying the crosstalk between the intestinal microbiota ecosystem and host when determining biomarkers of disease and treatment efficacy. The commensal microbiota is critical for immune development and continuous function through the recognition of bacteriaproduced and regulated metabolites. In cases of microbial dysbiosis and microglial dysfunction, chronic neuroinflammation may persist, leading to the propagation of neurological disorders. To address potential mechanisms, this review focuses on the microbiota-gut-brain axis as it relates to communication pathways that have been linked to aberrant CNS immune activity and pathology. We also address anti-inflammatory and neuroprotective mediators which may counteract these detrimental activities. Finally, we explore the potential benefits of current and novel microbiome-targeted approaches to treat neuroinflammation and consequential neurological disease.

The Microbiota/Microbiome and the Gut–Brain Axis: How Much Do They Matter in Psychiatry?

“…The immune system appears to be at the heart of the gut–microbiota–brain relationship. Indeed, an altered composition of the gut microbiota might compromise the epithelial intestinal integrity and lead to a defective defence against pathogenic microorganisms, with consequent inflammatory reactions and, ultimately, neuro-inflammation [ 30 ]. Moreover, dysbiosis causes an increase in the amount of short-chain fatty acids (SCFAs), such as acetate, propionate and butyrate, that might activate microglia cells, i.e., the immune cells of the CNS, leading to an increase in cytokines that may eventually alter brain connections and the blood–brain barrier (BBB) [ 31 , 32 ].…”

Induction of distinct neuroinflammatory markers and gut dysbiosis by differential pyridostigmine bromide dosing in a chronic mouse model of GWI showing persistent exercise fatigue and cognitive impairment

“…Members of family Lachnospiraceae are important producers of the SCFA butyrate [ 108 , 109 ], and are associated with maintenance of gut barrier function [ 110 , 111 ]. Since butyrate has been shown to ameliorate intestinal and inflammatory processes in GWI mice [ 25 ] and neuroinflammation [ 112 ], the microbiome structure changes we observed in GW mice suggest a compromised gut barrier and possible route leading to neuroinflammation in GW mice. Interestingly, Alhasson and colleagues [ 26 ] reported a decrease in abundance of family-level OTU S24–7 (Bacteroidales family) and greater abundance of two unclassified/unnamed families from the order Clostridiales and in their GW chemical exposed relative to unexposed group [ 26 ].…”

Stressor-Specific Microbiota Intervention

“…Postbiotics are defined as inactivated microbiota with or without metabolites or cell components ( 63 ). Rifaximin, an intestinally acting antibiotic with low systemic absorption and minimal risk for provoking antibiotic resistance ( 64 ), exerts anti-inflammatory effects and enriches the beneficial microbiota ( 5 ). An increase in Bifidobacterium and Lactobacillus has been reported after rifaximin treatment ( 65 ).…”

“…Third, chronic inflammation and microbiota dysbiosis related to various stressors might be associated with neuropsychiatric disorders, such as depression ( 4 ). Possible mechanisms linking inflammation to neuropsychiatric disorders include cytokine-mediated stimulation of indoleamine 2,3-dioxygenase to retard serotonin production; cytokine-mediated oxidative stress and glial cell damage in the prefrontal cortex and amygdala; cytokine-mediated glutamate dysregulation and excitotoxicity, leading to reduced brain-derived neurotrophic factor (BDNF) production; inflammation-induced glucocorticoid resistance and decreased inhibitory feedback of corticotropin-releasing hormone (CRH); and cytokine-mediated intensification of the stress response ( 5 ). Finally, microglia and the gut microbiota might communicate via signal transduction through the vagus nerve ( 6 ) and circulation ( 7 ).…”