Microglial cells: Sensors for neuronal activity and microbiota-derived molecules

Abstract

Microglial cells play pleiotropic homeostatic activities in the brain, during development and in adulthood. Microglia regulate synaptic activity and maturation, and continuously patrol brain parenchyma monitoring for and reacting to eventual alterations or damages. In the last two decades microglia were given a central role as an indicator to monitor the inflammatory state of brain parenchyma. However, the recent introduction of single cell scRNA analyses in several studies on the functional role of microglia, revealed a not-negligible spatio-temporal heterogeneity of microglial cell populations in the brain, both during healthy and in pathological conditions. Furthermore, the recent advances in the knowledge of the mechanisms involved in the modulation of cerebral activity induced by gut microbe-derived molecules open new perspectives for deciphering the role of microglial cells as possible mediators of these interactions. The aim of this review is to summarize the most recent studies correlating gut-derived molecules and vagal stimulation, as well as dysbiotic events, to alteration of brain functioning, and the contribution of microglial cells.

Tissue-specific atlas of trans-models for gene regulation elucidates complex regulation patterns

“…The first example from the TF-Expression involves three genes, TYROBP (DAP12), IFIT3, and AIF1 (IBA1), which were discovered in the TF-Expression model across more than 37 shared tissues (Jaccard score > 0.8, p < 0.01). Interestingly, all three genes have increased expression in microglia [ 64 , 65 ] and are part of a gene signature in a mouse model of amyotrophic lateral sclerosis, where expression of IFIT3 and TYROBP increased during disease progression in the mice microglia, macrophages, neutrophils, and monocytes [ 66 ].

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Treatment of preterm brain injury via gut‐microbiota–metabolite–brain axis

“… 44 Dysbiosis can significantly affect the cell‐specific transcriptome, especially in microglia and their subtypes. 45 Moreover, changes in GM caused by diet, exercise, and antibiotics can act on microglia and then affect the recombination of neural networks, 46 and alter the neurophysiology of adolescence, including the expression of myelin‐related genes in the prefrontal cortex and the morphology of microglia in the basolateral amygdala. 47 In another CLP‐induced septicemia study in rats, the diversity and abundance of Bacteroides distasonis, Lactobacillus salivarius , and Clostridium cluster decreased, the activation of microglia increased, and the inflammatory factors in hippocampus and cortex increased.…”

Gut Microbiota to Microglia: Microbiome Influences Neurodevelopment in the CNS

“…Once the blood-brain barrier (BBB) was damaged, two separate studies found that IL-1, TNF-α, and IL-6 could diffuse across and cause increased expression of immune cell receptors, such as ICAM-1 and VCAM-1, in the brain parenchyma [44]. Subsequently, this resulted in recruitment of microglia and astrocytes, resulting in cytotoxicity [45,46]. Figure 2 is a diagram of how the gut and brain interact, and exemplifies the expanded pathway by which inflammatory markers have a direct impact on neuromodulation, often resulting in an inflammatory state in the brain.…”

“…More specifically to microglial cells, a recent review from 2022 described microglial cells as "sensors" for microbiotaderived molecules such as lipopolysaccharide (LPS), short chain fatty acids (SCFA), and tryptophan derivatives. As microglia serve in the role of patrolling brain parenchyma and surveying for signs of injury or infection, it is particularly the acute phase reactants from the microbiome that trigger inflammation [46].…”