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Advanced Neurology Inflammation and gut microbiota in depression

with anxiety and depression have a higher abundance of techniques for different diseases (e.g., anxiety, depression,
pro-inflammatory bacteria species, such as Desulfovibrio bipolar disorder, and autism spectrum disorders) need to
and Enterobacteriaceae, but lower SCFA-producing be further investigated.
Faecalibacterium compared to controls . Stilling et al. have FMT is considered a promising therapy; for example,
[12]
suggested that butyrate and other SCFAs in the systemic FMT has been recommended in clinical guidelines for the
circulation may reduce depression-like behavior in animal treatment of recurrent Clostridioides difficile infection .
[90]
models by elevating the levels of histone acetylation and However, FMT has been considered investigational
BDNF in specific brain regions, such as the prefrontal by most regulatory agencies and has not obtained
cortex . Moreover, sodium butyrate has been shown to marketing approval from the United State Food and Drug
[82]
ameliorate LPS-induced depression-like behaviors as well Administration (FDA) for any indication . Although the
[91]
as hippocampal microglial inflammation and activation in described risks range from mild gastrointestinal symptoms
mice . to severe infection, FMT is largely considered a safe
[83]
5. Potential intervention strategies for procedure [90,92] . The fact that the variability and uncertainty
in the source and donor of fecal microbiota may affect
depression the health risk profile of recipients has been highlighted
5.1. Fecal microbiota transplantation (FMT) by recent reports of rare cases of multidrug-resistant
organisms, including Shiga toxin-producing Escherichia
Restoring gut homeostasis through FMT may be an effective coli and enteropathogenic E. coli, where these organisms
intervention for depression. Sudo et al. have compared GF were not additionally screened [93,94] . While information on
and specific pathogen-free mice to investigate HPA reaction the long-term effects of FMT in humans is sparse, several
to stress. GF mice had elevated plasma adrenocorticotropic animal studies have shown that disease phenotypes such as
hormone and corticosterone with reduced BDNF obesity and metabolic disorders can be transferred through
expression in the cortex and hippocampus in response FMT [95-97] . In the absence of biochemical markers to screen
to restraint stress relative to specific pathogen-free (SPF) donor stools, there is concern about which phenotypes
mice. Interestingly, the exaggerated HPA response in GF may escape detection and subsequently be transmitted
mice could be reversed by B. infantis or fecal microbes from via FMT. Gupta et al. have examined the evolving risk
SPF mice . Recently, Rao et al. have demonstrated that of FMT and affirmed that screening for such organisms
[57]
FMT increased serotonin expression and decreased the or markers has been a standard practice since 2016 [90,98] .
production of IL-1β and TNF-α in a chronic unpredictable Therefore, much work remains to be done before FMT can
stress (CUS) rat model, suppressing the activation of glial be applied to the clinical management of depression. One
cells, and NLRP3 inflammasome in the prefrontal cortex alternative to FMT is dietary therapy, such as increasing
and hippocampus, and thus ameliorating depression- the abundance of probiotics in the gut through consistent
like behaviors . Similarly, our group has found that the consumption of probiotics, which will be further discussed
[84]
transplantation of fecal microbiota into GF mice from in the next section.
NLRP3 KO mice alleviated CUS-induced depression-like
behaviors. Moreover, the gut microbiota compositions 5.2. Dietary interventions for depression
of NLRP3 KO and wild-type mice differed in the relative There is a growing interest in the relationship between
abundance of Firmicutes, Proteobacteria, and Bacteroidetes dietary patterns and depression. Emerging evidence has
spp. . Importantly, Bercik et al. have demonstrated that suggested that diet has a strong influence on neurological
[34]
the gut-brain axis is regulated by FMT. GF BALB/c mice processes and emotional behavior because it strongly affects
that were subjected to microbiota transplantation from the the gut microbiota [99,100] . Long-term anti-inflammatory
National Institutes of Health (NIH) Swiss mice showed dietary patterns may prevent depression, whereas pro-
increased exploratory behavior and BDNF levels in the inflammatory patterns may promote depression-related
hippocampus. In contrast, GF NIH Swiss mice that were conditions [100,101] . However, the mechanisms underlying
subjected to microbiota transplantation from BALB/c this relationship are currently unclear. A “Western” dietary
mice had reduced exploratory behavior . Case reports, pattern, which is characterized by high consumption of
[85]
systematic reviews, and meta-analyses have suggested that sweet and fatty food, fried and processed food, refined
FMT can improve depressive symptoms in patients with grains, red meat, and high-fat dairy products, with low
mental depression [86-89] . These findings strongly suggest consumption of fruits and vegetables, is associated with
that disease or health phenotypes can be transferred a higher incidence of depression [102-104] . In a randomized
from the host to transplanted individuals through the controlled trial, a Mediterranean-style dietary pattern
gut microbiota. However, precise and personalized FMT supplemented with fish oil has shown to improve the mental

Volume 1 Issue 3 (2022) 6 https://doi.org/10.36922/an.v1i3.272