Modulation of Glial Cell Functions by the Gut–Brain Axis: A Role in Neurodegenerative Disorders and Pain Transmission

Abstract

Studies on host microbiota and their interactions with the central nervous system (CNS) have grown considerably in the last decade. Indeed, it has been widely demonstrated that dysregulations of the bidirectional gut–brain crosstalk are involved in the development of several pathological conditions, including chronic pain. In addition, the activation of central and peripheral glial cells is also implicated in the pathogenesis and progression of pain and other neurodegenerative disorders. Recent preclinical findings suggest that the gut microbiota plays a pivotal role in regulating glial maturation, morphology and function, possibly through the action of different microbial metabolites, including the most studied short-chain fatty acids (SCFAs). Moreover, altered microbiota composition has been reported in CNS disorders characterized by glial cell activation. In this review, we discuss recent studies showing the role of the gut microbiota and the effects of its depletion in modulating the morphology and function of glial cells (microglia and astrocytes), and we hypothesize a possible role for glia–microbiota interactions in the development and maintenance of chronic pain.

Association between hippocampal microglia, AD and LATE‐NC, and cognitive decline in older adults

“…Additional lifestyle factors, including poor or fragmented sleep and dietary habits, 29 , 30 have also been shown to influence microglia inflammation. More recent work implicates other biological mechanisms, including dysbiosis of the gut 31 , 32 and the role of the inflammasome, innate immune sensors that regulate inflammation in response to harmful stimuli. 33 Together, these studies solidify the fact that cognitive aging is a complex disease process and that much work remains to understand the relationship between lifestyle stressors/factors, microglia inflammation, and cognition.…”

Practice of Peritoneal Adhesions in Osteopathic Medicine: Part 2

“…This alteration of movement could generate intestinal dysbiosis [ 14 ]. Intestinal dysbiosis alters the function of the microbiota, which dysfunction alerts spinal and central glial cells, as well as astrocytes in the brain [ 15 , 16 ]. The intestine can produce different molecules (microbe-derived neurotransmitters) able to pass the various intestinal and peritoneal barriers and reach the medulla and/or the central nervous system (brain-intestine axis) [ 15 ].…”

“…Intestinal dysbiosis alters the function of the microbiota, which dysfunction alerts spinal and central glial cells, as well as astrocytes in the brain [ 15 , 16 ]. The intestine can produce different molecules (microbe-derived neurotransmitters) able to pass the various intestinal and peritoneal barriers and reach the medulla and/or the central nervous system (brain-intestine axis) [ 15 ]. These neurotransmitters stimulate glial cells, astrocytes (and oligodendrocytes) to produce pro-inflammatory substances and alter myelin, disturbing the correct neural transmission, and generating a pain and inflammation loop [ 15 , 16 ].…”

“…The intestine can produce different molecules (microbe-derived neurotransmitters) able to pass the various intestinal and peritoneal barriers and reach the medulla and/or the central nervous system (brain-intestine axis) [ 15 ]. These neurotransmitters stimulate glial cells, astrocytes (and oligodendrocytes) to produce pro-inflammatory substances and alter myelin, disturbing the correct neural transmission, and generating a pain and inflammation loop [ 15 , 16 ]. If the pain or dysfunction is chronic there will be a structural and functional change of the nervous system [ 17 ].…”