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Advanced Neurologyurology
Advanced Ne Inflammation and gut microbiota in depression

reuptake inhibitors and serotonin-norepinephrine Overall, depression is characterized by low-grade
reuptake inhibitors. Non-pharmacological therapy, such systemic and neurological inflammation, leakage of the BBB
as cognitive therapy, is also used when medications and intestinal mucosal barrier, a high relative abundance
[4]
fail to meet the treatment outcome . Unfortunately, of the pro-inflammatory species of gut microbiota, and a
our knowledge of depression and our ability to treat it low abundance of SCFA-producing probiotics (Figure 1).
effectively is lacking; for example, despite temporary To meet the current requirements for depression/MDD-
remission with antidepressant medication, patients either targeted treatment strategies, the present review provides a
have a high risk of relapse or do not adequately respond to necessary update to the expanding literature describing the
pharmacological treatment . Therefore, new insights into characterization and interaction between gut microbiota
[4]
the underlying pathophysiology of depression are urgently and neuroinflammation in depression. This review also
required to develop more effective therapeutic strategies. aims to integrate information and explore the potential
mechanisms for modulating gut microbiota homeostasis
Neuroinflammation is known to be associated with
a variety of neurological diseases, such as Alzheimer’s in the treatment of depression.
disease and Parkinson’s disease . Inflammatory processes 2. Changes in gut homeostasis as a
[6]
[5]
are implicated in the pathophysiology of depression. component of depression
Numerous studies have suggested a strong association
between depression and pro-inflammatory mediators in 2.1. Leaky gut and inflammation
peripheral blood and cerebrospinal fluid (CSF) as well
[7]
as an association between the therapeutic application The intestinal barrier is a dynamic dense entity that
of interferon (IFN)-α and depression in 30 – 50% of provides a strong physical barrier. It interacts with and
patients [8,9] . According to a meta-analysis, patients with responds to various stimuli, such as inhibiting pathogen
colonization through the production of antimicrobial
MDD have higher levels of interleukin (IL)-6 and C-reactive substances and preventing bacterial adhesion through
protein (CRP) compared to non-depressed subjects .
[10]
Another meta-analysis based on clinical trials has shown the secretion of immunoglobulin A (Ig A) as well as
[19]
that pro-inflammatory cytokine inhibitors (adalimumab, glycocalyx and mucus . However, an increased intestinal
permeability may underlie the persistent low-grade
etanercept, infliximab, and tocilizumab) can alleviate inflammation observed in neurological disorders, such
depressive symptoms in patients . In addition, the leakage as depression . In a study, there was increased intestinal
[11]
[20]
of the blood-brain barrier (BBB) observed in depression
is partly due to the persistent low-grade inflammation fatty acid binding protein (FABP), a marker of enterocyte
damage, in the blood of recent suicidal patients. The high
present in depressive states. Inflammation is likely a critical level of intestinal FABP was found to be related to the
disease modifier that promotes susceptibility to depression. severity of depressive symptoms and suicidal symptoms.
However, the exact mechanism of the interaction between Moreover, the level of IL-6 was also increased in the blood
[7]
inflammation and depression remains unclear .
of recent suicidal patients and found to be correlated
The gut-brain axis is a potential area of research as there with two gut permeability markers: zonulin and FABP .
[20]
is mounting evidence showing that the gut microbiota has Psychological stress has been shown to increase small
a strong influence on emotional behavior and neurological intestinal permeability in humans . Camilleri and Clark
[21]
processes . The human gut is home to nearly 100 trillion et al. have pointed out that there is a strong correlation
[12]
bacteria that are essential for maintaining health . In the between stress and changes in gut microbiota composition,
[13]
last decades, a growing number of evidence has suggested including a decrease in the composition of commensal
that the gut-brain axis is involved in the pathophysiology bacteria and an increase in the level of inflammation,
of neurodevelopmental and neurological disorders, disrupting the integrity and permeability of the intestine
where the gut microbiota is a key regulator in the gut- and causing leaky gut [19,22] . Specifically, the increased
brain axis [14,15] . Alterations in gut microbiota composition translocation of bacterial toxins and food particles due
and subsequent metabolites of short-chain fatty acids to a compromised gut barrier has been associated with
(SCFAs) have been increasingly observed in patients with the activation of the immune system and the production
depression . Similarly, an imbalance of gut microbiota has of inflammatory mediators . A leaky gut allows the
[16]
[19]
also been discovered in animal models with depression- translocation of lipopolysaccharide (LPS) from the gut
like behavior . Interestingly, probiotic formulations have into the circulation, activating immune cells and leading
[17]
shown anxiolytic-like activity in a rat model and led to to an increased release of pro-inflammatory mediators and
the remission of psychological distress in volunteers of a systemic hypo-inflammation . It has been shown that
[23]
clinical trial . stress increased paracellular permeability in the colon,
[18]
Volume 1 Issue 3 (2022) 2 https://doi.org/10.36922/an.v1i3.272