Enhanced intestinal protein fermentation in schizophrenia

Ying Liang; Xing Shi; Yang Shen; Zhuoran Huang; Jian Wang; Changjun Shao; Yanan Chu; Jing Chen; Jun Yu; Yu Kang

doi:10.1186/s12916-022-02261-z

Enhanced intestinal protein fermentation in schizophrenia

BMC Med. 2022 Feb 9;20(1):67. doi: 10.1186/s12916-022-02261-z.

Authors

Ying Liang^#¹, Xing Shi^#^{2

3}, Yang Shen^#¹, Zhuoran Huang⁴, Jian Wang^{2

5}, Changjun Shao^{2

5}, Yanan Chu^{2

5}, Jing Chen^{2

5}, Jun Yu^{2

5

6}, Yu Kang^{7

8}

Affiliations

¹ National Clinical Research Center for Mental Disorders, Peking University Sixth Hospital, Institute of Mental Health, Key Laboratory of Mental Health, Ministry of Health, Peking University, Beijing, China.
² CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.
³ The First Affiliated Hospital (Shenzhen People's Hospital), Southern University of Science and Technology, Shenzhen, 518055, China.
⁴ School of Life Sciences, Huaibei Normal University, Huaibei, ,235000, Anhui, China.
⁵ China National Center for Bioinformation, Beijing, 100101, China.
⁶ University of Chinese Academy of Sciences, No.19 Yuquan Road, Shijingshan District, Beijing, 100049, China.
⁷ CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China. kangy@big.ac.cn.
⁸ China National Center for Bioinformation, Beijing, 100101, China. kangy@big.ac.cn.

^# Contributed equally.

Abstract

Background: Emerging findings highlighted the associations of mental illness to nutrition and dysbiosis in the intestinal microbiota, but the underlying mechanisms, especially in schizophrenia (SZ), remain unclarified.

Methods: We conducted a case-control study of SZ patients (case to control=100:52) by performing sequencing of the gut metagenome; measurement of fecal and plasma non-targeted metabolome; including short-, medium-, and long-chain fatty acids; and targeted metabolites, along with recorded details of daily intakes of food.

Results: The metagenome analysis uncovered enrichment of asaccharolytic species and reduced abundance of carbohydrate catabolism pathways and enzymes in the gut of SZ patients, but increased abundance of peptidases in contrast to their significantly reduced protein intake. Fecal metabolome analysis identified increased concentrations of many protein catabolism products, including amino acids (AAs), urea, branched short-chain fatty acids, and various nitrogenous derivates of aromatic AAs in SZ patients. Protein synthesis, represented by the abundance of AA-biosynthesis pathways and aminoacyl-tRNA transferases in metagenome, was significantly decreased. The AUCs (area under the curve) of the diagnostic random forest models based on their abundance achieved 85% and 91%, respectively. The fecal levels of AA-fermentative enzymes and products uniformly showed positive correlations with the severity of psychiatric symptoms.

Conclusions: Our findings revealed apparent dysbiosis in the intestinal microbiome of SZ patients, where microbial metabolism is dominated by protein fermentation and shift from carbohydrate fermentation and protein synthesis in healthy conditions. The aberrant macronutrient metabolism by gut microbes highlights the importance of nutrition care and the potential for developing microbiota-targeted therapeutics in SZ.

Keywords: Dysbiosis; Gut microbiota; Macronutrient metabolism; Metabolome; Metagenome; Nutrition care; Protein fermentation; Schizophrenia.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Case-Control Studies
Dysbiosis
Feces / chemistry
Fermentation
Humans
Metagenome
Schizophrenia*