Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Nov 7:13:1028913.
doi: 10.3389/fmicb.2022.1028913. eCollection 2022.

Gut microbiota-generated short-chain fatty acids are involved in para-chlorophenylalanine-induced cognitive disorders

Yanbo Liu  1 , Zhen Li  1 , Tianning Sun  1 , Zhigang He  1 , Hongbing Xiang  1 , Jun Xiong  2
Affiliations

Gut microbiota-generated short-chain fatty acids are involved in para-chlorophenylalanine-induced cognitive disorders

Yanbo Liu et al. Front Microbiol. .

Abstract

Neurocognitive disorders (NCDs) include complex and multifactorial diseases that affect many patients. The 5-hydroxytryptamine (5-HT) neuron system plays an important role in NCDs. Existing studies have reported that para-chlorophenylalanine (PCPA), a 5-HT scavenger, has a negative effect on cognitive function. However, we believe that PCPA may result in NCDs through other pathways. To explore this possibility, behavioral tests were performed to evaluate the cognitive function of PCPA-treated mice, suggesting the appearance of cognitive dysfunction and depression-like behavior. Furthermore, 16S rRNA and metabolomic analyses revealed that dysbiosis and acetate alternation could be related to PCPA-induced NCDs. Our results suggest that not only 5-HT depletion but also dysbiosis and acetate alternation contributed to PCPA-related NCDs. Specifically, the latter promotes NCDs by reducing short-chain fatty acid levels. Together, these findings provide an alternative perspective on PCPA-induced NCDs.

Keywords: cognitive disorders; dysbiosis; gut microbiota; para-chlorophenylalanine (PCPA); short-chain fatty acids (SCFAs).

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Para-chlorophenylalanine (PCPA) treatment induced cognitive dysfunction and depression-like behavior in mice. (A) Concentration. (B) Total travel distance of open field test (OFT). (C) Time spent in the central area of OFT. (D) Time spent in the novel arm of the Y-maze test. (E) Recognition index of novel object recognition test (NORT). Data are presented as the mean ± SEM. *P < 0.05; ****P < 0.0001; ns, not significant.
FIGURE 2
FIGURE 2
Para-chlorophenylalanine (PCPA) treatment induced gut microbiota alternation in mice. (A) α-diversity Chao1 index. (B) α-diversity PD Whole Tree Index. (C) Boxplot of principal component analysis (PCA). (D,E) Linear discriminant analysis Effect Size (LEfSe) analysis. (F) Relative abundance of the species g_Parabacteroides. (G) Relative abundance of the species g_Lactobacillus. (H) Relative abundance of the species g_Escherichia-Shigella. (I) Relative abundance of the family Enterobacteriaceae. (J) Relative abundance of the family Peptostreptococcaceae. (K) Relative abundance of the family Enterococcaceae. (L–N) KEGG analysis. Data are presented as the mean ± SEM. *P < 0.05; *P < 0.01; ****P < 0.0001; ns, not significant.
FIGURE 3
FIGURE 3
The levels of short-chain fatty acids (SCFAs) in the blood and hippocampus. (A–L) Comparison of the SCFA levels in the hippocampus and the blood between two groups. (M,N) OPLS-DA plot. Data are presented as the mean ± SEM. *P < 0.05; **P < 0.01; ns, not significant.
FIGURE 4
FIGURE 4
Correlation of short-chain fatty acids (SCFAs) levels with dysbiosis and cognitive impairment. (A) Correlations between the SCFAs and gut microbiota. (B) Heatmap of corrections between SCFAs and behavioral tests of the para-chlorophenylalanine (PCPA) group. (C) Heatmap of corrections between SCFAs and behavioral tests of the Control group.
See this image and copyright information in PMC

References

    1. American Psychiatric Publication (2013). Diagnostic and statistical manual of mental disorders: Dsm-5™ (5th ed.). Codas 25:191. 10.1176/appi.books.9780890425596 - DOI - PubMed
    1. Antunes M., Biala G. (2012). The novel object recognition memory: Neurobiology, test procedure, and its modifications. Cogn. Process. 13 93–110. 10.1007/s10339-011-0430-z - DOI - PMC - PubMed
    1. Arnoriaga-Rodríguez M., Fernández-Real J. M. (2019). Microbiota impacts on chronic inflammation and metabolic syndrome - related cognitive dysfunction. Rev. Endocr. Metab. Disord. 20 473–480. 10.1007/s11154-019-09537-5 - DOI - PubMed
    1. Baba T., Takeda A., Murakami A., Koga T., Isomura T., Mori E. (2022). Effect of donepezil for dementia prevention in Parkinson’s disease with severe hyposmia (The Dash-Pd study): A randomized long-term placebo-controlled trial. EClinicalMedicine 51:101571. 10.1016/j.eclinm.2022.101571 - DOI - PMC - PubMed
    1. Bacqué-Cazenave J., Bharatiya R., Barrière G., Delbecque J. P., Bouguiyoud N., Di Giovanni G., et al. (2020). Serotonin in Animal Cognition and Behavior. Int. J. Mol. Sci. 21:1649. 10.3390/ijms21051649 - DOI - PMC - PubMed

LinkOut - more resources