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

Yanbo Liu; Zhen Li; Tianning Sun; Zhigang He; Hongbing Xiang; Jun Xiong

doi:10.3389/fmicb.2022.1028913

Frontiers in Microbiology (Nov 2022)

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

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

Affiliations

Yanbo Liu: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Zhen Li: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Tianning Sun: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Zhigang He: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Hongbing Xiang: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Jun Xiong: Hepatobiliary Surgery Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

DOI: https://doi.org/10.3389/fmicb.2022.1028913
Journal volume & issue: Vol. 13

Abstract

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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.

Published in Frontiers in Microbiology

ISSN: 1664-302X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Science: Microbiology
Website: http://www.frontiersin.org/journals/microbiology

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