Gut microbiota and transcriptome dynamics in every-other-day fasting are associated with neuroprotection in rats with spinal cord injury

Junyu Wang; Xiaohua Zhao; Ruihan Zhou; Meiyu Wang; Wu Xiang; Zilong You; Min Li; Ruiling Tang; Jingqi Zheng; Jiayu Li; Li Zhu; Jiaxin Gao; Huaqiang Li; Rizhao Pang; Anren Zhang

doi:10.3389/fmicb.2023.1206909

Gut microbiota and transcriptome dynamics in every-other-day fasting are associated with neuroprotection in rats with spinal cord injury

Front Microbiol. 2023 Jul 28:14:1206909. doi: 10.3389/fmicb.2023.1206909. eCollection 2023.

Authors

Junyu Wang¹, Xiaohua Zhao^{2

3}, Ruihan Zhou², Meiyu Wang⁴, Wu Xiang², Zilong You⁵, Min Li⁶, Ruiling Tang², Jingqi Zheng², Jiayu Li⁷, Li Zhu⁶, Jiaxin Gao⁶, Huaqiang Li⁷, Rizhao Pang³, Anren Zhang⁷

Affiliations

¹ State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
² Department of Rehabilitation Medicine, General Hospital of Western Theater Command, Chengdu, China.
³ Department of Rehabilitation Medicine, The People's Hospital of Tongliang District, Chongqing, China.
⁴ Rehabilitation and Wellness Care Centre, Tian Fu College of Swufe, Chengdu, China.
⁵ Department of Biochemistry and Biophysics, School of Basic Medical Sciences, Peking University, Beijing, China.
⁶ Department of Rehabilitation Medicine, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai, China.
⁷ School of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Abstract

Introduction: Every-other-day fasting (EODF) is a classical intermittent fasting (IF) mode with neuroprotective effects that promotes motor function recovery after spinal cord injury (SCI) in rats. However, its dynamic effects on the gut microbiota and spinal cord transcriptome remain unknown.

Methods: In this study, 16S rRNA sequencing and RNA-seq analysis were used to investigate the effects of ad libitum (AL) and EODF dietary modes on the structural characteristics of rat gut microbiota in rats and the spinal cord transcriptome at various time points after SCI induction.

Results: Our results showed that both dietary modes affected the bacterial community composition in SCI rats, with EODF treatment inducing and suppressing dynamic changes in the abundances of potentially anti-inflammatory and pro-inflammatory bacteria. Furthermore, the differentially expressed genes (DEGs) enriched after EODF intervention in SCI rats were associated with various biological events, including immune inflammatory response, cell differentiation, protein modification, neural growth, and apoptosis. In particular, significant spatiotemporal differences were apparent in the DEGs associated with neuroprotection between the EODF and AL interventions. These DGEs were mainly focused on days 1, 3, and 7 after SCI. The relative abundance of certain genera was significantly correlated with DEGs associated with neuroprotective effects in the EODF-SCI group.

Discussion: Our results showed that EODF treatment may exert neuroprotective effects by modulating the transcriptome expression profile following SCI in rats. Furthermore, gut microbiota may be partially involved in mediating these effects.

Keywords: every-other-day fasting; gut microbiota; intermittent fasting; neuroprotection; spinal cord injury; transcriptome.