Human-derived fecal microbiota transplantation alleviates social deficits of the BTBR mouse model of autism through a potential mechanism involving vitamin B6 metabolism

Zheng，Lifeng1,2; Jiao，Yinming3; Zhong，Haolin1; Tan，Yan2; Yin，Yiming2; Liu，Yanhong2; Liu，Ding2; Wu，Manli2; Wang，Guoyun3; Huang，Jinqun2; Wang，Ping4; Qin，Meirong4; Wang，Mingbang5,6; Xiao，Yang7; Lv，Tiying8; Luo，Yangzi9; Hu，Han2; Hou，Sheng Tao1; Kui，Ling3

2024-06-18

10.1128/msystems.00257-24

mSystems   影响因子和分区

2379-5077

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by social communication deficiencies and stereotypic behaviors influenced by hereditary and/or environmental risk factors. There are currently no approved medications for treating the core symptoms of ASD. Human fecal microbiota transplantation (FMT) has emerged as a potential intervention to improve autistic symptoms, but the underlying mechanisms are not fully understood. In this study, we evaluated the effects of human-derived FMT on behavioral and multi-omics profiles of the BTBR mice, an established model for ASD. FMT effectively alleviated the social deficits in the BTBR mice and normalized their distinct plasma metabolic profile, notably reducing the elevated long-chain acylcarnitines. Integrative analysis linked these phenotypic changes to specific Bacteroides species and vitamin B6 metabolism. Indeed, vitamin B6 supplementation improved the social behaviors in BTBR mice. Collectively, these findings shed new light on the interplay between FMT and vitamin B6 metabolism and revealed a potential mechanism underlying the therapeutic role of FMT in ASD.IMPORTANCEAccumulating evidence supports the beneficial effects of human fecal microbiota transplantation (FMT) on symptoms associated with autism spectrum disorder (ASD). However, the precise mechanism by which FMT induces a shift in the microbiota and leads to symptom improvement remains incompletely understood. This study integrated data from colon-content metagenomics, colon-content metabolomics, and plasma metabolomics to investigate the effects of FMT treatment on the BTBR mouse model for ASD. The analysis linked the amelioration of social deficits following FMT treatment to the restoration of mitochondrial function and the modulation of vitamin B6 metabolism. Bacterial species and compounds with beneficial roles in vitamin B6 metabolism and mitochondrial function may further contribute to improving FMT products and designing novel therapies for ASD treatment.

autism spectrum disorder (ASD) Bacteroides BTBR fatty acid metabolism fecal microbiota transplantation (FMT) pyridoxal 5′-phosphate (PLP) social deficit vitamin B6 metabolism

SCI

英语

第一

2-s2.0-85196582256

Scopus

1.Brain Research Centre and Department of Neuroscience,Southern University of Science and Technology,Shenzhen,China
2.Xbiome Co. Ltd.,Shenzhen,China
3.Shenzhen Qianhai Shekou Free Trade Zone Hospital,Shenzhen,China
4.Shenzhen Institute for Drug Control,Shenzhen,China
5.Microbiome Therapy Center,Medical School,Shenzhen University,Shenzhen,South China Hospital,China
6.Shanghai Key Laboratory of Birth Defects,Division of Neonatology,Children's Hospital of Fudan University,National Center for Children's Health,China
7.Department of Hematology,Shenzhen Qianhai Shekou Free Trade Zone Hospital,Shenzhen,China
8.Guangzhou University of Chinese Medicine,Guangzhou,China
9.Faculty of Biology,Medicine and Health,University of Manchester,United Kingdom

Zheng，Lifeng,Jiao，Yinming,Zhong，Haolin,et al. Human-derived fecal microbiota transplantation alleviates social deficits of the BTBR mouse model of autism through a potential mechanism involving vitamin B6 metabolism[J]. mSystems,2024,9(6).

Zheng，Lifeng.,Jiao，Yinming.,Zhong，Haolin.,Tan，Yan.,Yin，Yiming.,...&Kui，Ling.(2024).Human-derived fecal microbiota transplantation alleviates social deficits of the BTBR mouse model of autism through a potential mechanism involving vitamin B6 metabolism.mSystems,9(6).

Zheng，Lifeng,et al."Human-derived fecal microbiota transplantation alleviates social deficits of the BTBR mouse model of autism through a potential mechanism involving vitamin B6 metabolism".mSystems 9.6(2024).