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Advanced Neurology Inflammation and gut microbiota in depression

systemic inflammation in patients with Parkinson’s ultimately leading to cognitive impairment . Indeed,
[40]
disease , while Blautia species may be associated with the levels of serum lgA and IgM against the LPS of
[30]
good cognition and decreased inflammation in hepatic enterobacteria have been found to be significantly higher
encephalopathy . In a study, the transplantation of in MDD patients than in control subjects . In addition,
[23]
[31]
gut microbiota from patients with rheumatoid arthritis a study has found elevated expressions of gut microbial
activated an abnormal differentiation of T cells in 16S rRNA subunit in the blood plasma of MDD patients
germ-free (GF) mice, thereby inducing depression-like compared to healthy controls .
[25]
behavior . Moreover, two animal studies have shown that Despite the conflicting results, there is a general
[32]
fecal microbiota transplantation from MDD patients to GF consensus that MDD patients have abnormal levels of pro-
mice or microbiota-depleted rats can induce depression- inflammatory cytokines in the peripheral circulation .
[41]
like behaviors, thus elucidating the role of the pro- Alvarez-Mon et al. have reported that MDD patients
inflammatory species of gut microbiota in the pathology have abnormally functioning CD4 T lymphocytes with
+
of depression [28,33] . Consistently, the transplantation of fecal increased levels of circulating IL-17 and TNF-α . Pro-
[42]
microbiota from NOD-like receptor protein 3 (NLRP3) inflammatory cytokines can activate the hypothalamic-
knock-out (KO) mice reduced the depression-like behavior pituitary-adrenal (HPA) axis in MDD, leading to elevated
induced by chronic unpredictable stress in recipient mice cortisol levels and glucocorticoid receptor resistance .
[43]
in our previous study, which was found to be related Furthermore, the pro-inflammatory cytokines released
to the changes in the relative abundance of Firmicutes, from microglia (e.g., TNF-α) can reduce the levels of
Proteobacteria, and Bacteroidetes phyla . However, due to neurotransmitters such as serotonin, dopamine, and
[34]
large individual variability, methodological heterogeneity, norepinephrine in MDD patients via several ways, one
and dietary diversity, we are only beginning to fully [44]
understand the implications of the gut microbiome on of which includes reducing their synthesis . Different
types of immune cells, such as T cells, produce, store,
human mental health and neuropsychiatric disorders .
[35]
and respond to serotonin, which is associated with mood
3. Inflammatory pathways across the gut- disorders [45,46] . In MDD patients, the persistence of pro-
brain axis inflammatory cytokines (e.g., TNF-α and IL-1β) can
impair the BBB function . Under stress conditions, BBB
[47]
3.1. Systemic circulation pathway impairments may lead to the infiltration of immune cells.
It has been shown that T cells and monocytes infiltrate the
Inflammation has been widely discussed in reviews of brain under stress. In depressed mice models, T helper
brain diseases involving the gut-brain axis, such as the 17 cells accumulate in different brain regions, such as the
interaction of central nervous system (CNS)-resident hippocampus, promoting depression-like behaviors [48,49] .
and peripheral immune pathways , the relationship
[36]
between inflammasome and gut microbiota , as Byproducts of the gut microbiota can play a
[37]
well as the crosstalk between neuroinflammation and neuroimmunomodulatory role in neurological
peripheral inflammatory mediators . The cytokine disorders . For example, in a study, the gut microbiome
[14]
[38]
hypothesis suggests that physiological pathways involved from an aged donor was found to be sufficient to reduce
in inflammation and stress responses may play a key role the host SCFAs and induce cognitive decline . SCFAs
[50]
in the pathology of depression. The stress-induced chronic (primarily acetate, propionate, and butyrate), derived
low-grade cytokine release in depression drives the overall from gut bacterial fermentation of non-digestible
immune response toward proinflammation rather than carbohydrates, have been reported to be present in human
[51]
anti-inflammation. The pro-inflammatory mediators in CSF and blood . It is believed that systemic SCFAs
the circulation disrupt both epithelial and endothelial can cross the BBB and regulate BBB permeability and
tight junctions, compromising the integrity of the gut- microglia functions. For example, a study has found that
vascular barrier and the BBB . This leads to an increase oral SCFAs can ameliorate depression-like behaviors in
[39]
in intestinal permeability (leaky gut) and a disrupted CNS mice exposed to chronic stress, which is associated with
barrier, providing a gateway for food antigens, toxins, and the inhibition of hippocampal neurogenesis decline, BBB
pathogens from the gut to reach the brain, followed by the damage, microglia activation, and neuroinflammation by
activation of neuroimmune cells, which in turn triggers SCFAs . Tryptophan metabolites that are derived from
[52]
neuroinflammation . For example, the increased systemic gut microbiota represent another example of the gut-brain
[39]
inflammation and subsequent neuroinflammation caused axis in the regulation of host inflammatory responses.
by the intraperitoneal injection of bacterial endotoxin A study has shown that tryptophan, metabolized by the gut
LPS mediate microglia activation and neuronal cell death, microbiota, can activate aryl hydrocarbon receptor (AhR)

Volume 1 Issue 3 (2022) 4 https://doi.org/10.36922/an.v1i3.272