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Advanced Neurology Inflammation and gut microbiota in depression

signaling in astrocytes and mitigate CNS inflammation 4. Short-chain fatty acids as key products of
in multiple sclerosis patients as well as improve gut gut-brain communication
[53]
permeability by targeting AhR in a mouse colitis model .
[54]
Endogenous SCFAs are mainly the products of fermentation
Dysregulation of the HPA axis is strongly associated with of non-digestible carbohydrates by gut microbiota. The
depressive episodes [55,56] . A direct example of microbiota principal SCFAs in the gut are acetate, propionate, and
modulation of HPA responsiveness is the reversibility of the butyrate, accounting for more than 95% of total SCFAs in
exaggerated HPA stress response in GF mice in response the host . SCFAs affect the pathophysiological conditions
[65]
to restraint stress by transplantation of Bifidobacterium of the host through a variety of mechanisms, including
infantis . GF mice have an underdeveloped immune system the regulation of histone acetylation and methylation,
[57]
due to the absence of commensal microbiota [13,58] . Increased activation of G-protein coupled receptors, promotion of
stress reactivity and weakened intestinal barrier have been hormone (e.g., glucagon-like peptide 1) and neurochemical
observed in GF mice [57,59] . Stress is known to induce leaky (e.g., serotonin) secretion, and regulation of vagus nerve
gut and BBB impairment, thus allowing pathogens and local circuit [65-67] . Butyrate has been shown to improve cognitive
inflammatory mediators to translocate across the intestinal dysfunction in a high-fat diet-induced obese model and
mucosa and directly affect both immune and neuronal a vascular dementia model, while propionate has been
cells in the CNS [19-21,23] . Interestingly, supplementation with reported to reduce the reward response to high-energy food
Lactobacillus farciminis can reduce intestinal permeability in the human striatum [68-70] . As shown in a study, a mixture
and prevent HPA hyperreactivity, induced by restraint of acetate, propionate, and butyrate alleviated alterations
stress, in rats . Gut microbiota may regulate brain function in anhedonia and heightened stress responsiveness as well
[24]
through vagus nerve signaling. A study has shown that as inhibited increased intestinal permeability induced by
subdiaphragmatic vagotomy can block depression-like psychosocial stress in mice .
[71]
behaviors and reduce the expression of synaptic proteins.
This is linked to the increased relative abundance of several Receptors (FFARs) that sense and transmit free fatty
[72]
beneficial microbiota, including Lactobacillus sp. BL302, acid signals have been found in the peripheral and CNSs .
Lactobacillus hominis, and Lactobacillus reuteri . Activation of FFARs by SCFAs appears to have a direct and
[60]
local anti-inflammatory effect on microglia activation as
[73]
3.2. Cellular immune pathway well as a systemic anti-inflammatory effect on neutrophils
[74]
Intestinal immune cells can directly regulate the and dendritic cells that also express FFARs . The ability of
neuroimmune balance and neuroinflammatory response. SCFAs to cross the BBB and their presence in the brain has
14
Intestinal B cells differentiate into IgA-secreting plasma been confirmed by injecting radiolabeled C-SCFAs into
[75]
cells to regulate the gut microbiota. Gut-derived IgA the carotid artery of rats . Neurons and the immune cell
plasma cells have been found in the CNS of mice with crosstalk that contributes to brain function and behavior
[76,77]
experimental autoimmune encephalomyelitis and to are affected by SCFAs . In addition, SCFAs are important
attenuate neuroinflammation in an IL-10-dependent for maintaining the integrity and function of the BBB. It
[61]
manner . The brain appears to recruit immune cells from has been shown that propionate, an SCFA, protects the
the gut to protect the CNS from the entry of peripheral BBB from deleterious inflammatory and oxidative stimuli
pathogens [61,62] . On the other hand, neuroimmune cells are via transcription factor nuclear factor erythroid 2-related
[78]
also modulated by intestinal cells. Subpopulations of IFN- factor 2 (Nrf2) signaling . In a study, the increased BBB
γ-producing meningeal natural killer (NK) cells from the permeability in GF mice after birth and during adulthood
gut can modulate the neuroimmune function and promote was found to be related to lower expression of BBB tight
astrocyte development; this effect is also regulated by junction proteins claudin-5 and occludin, which can be
the gut microbiome . Moreover, the depletion of gut mitigated by the exposure of these mice to SCFA-producing
[63]
[79]
microbiome by antibiotics leads to a substantial reduction bacteria . Reduced SCFA production in autistic patients
in IFN-γ-producing meningeal NK cells, downregulating may lead to gut barrier dysfunction, which could impair
the anti-inflammatory effects of astrocytes, and thus immune responses and BBB integrity, contributing to
[80]
presumably limiting their protective potential [63,64] . brain dysfunction .
Although there is increasing evidence of communication A comparison study has demonstrated a decrease in
between the gut and the brain, the specific mechanisms are butyrate production (anti-inflammatory properties) by
poorly understood. Further studies are needed to reveal Faecalibacterium and an increase in LPS production (pro-
the mechanisms by which the gut microbiota and immune inflammatory properties) by Flavonifractor in depressed
responses modulate CNS inflammation in the context of patients compared to healthy controls . A recent
[81]
depression. systematic review of 26 studies has revealed that patients

Volume 1 Issue 3 (2022) 5 https://doi.org/10.36922/an.v1i3.272