Ketogenic Diet Alleviates Hypoglycemia-Induced Neuroinflammation via Modulation the Gut Microbiota in Mice.

Abstract

SCOPE:

This study aims to investigate the role of gut microbiota regulation with ketogenic diet (KD) in hypoglycemia-induced neuroinflammation.

METHODS AND RESULTS:

Immunofluorescence staining and western blotting show that KD alleviates blood-brain barrier injury induced by hypoglycemia by increasing Podxl and zonula occludens-1 (ZO-1) levels. KD-fed mice show reduced brain edema by decreasing aquaporin-4 (AQP4) content and maintaining its polarized expression. 16S rRNA gene amplicon sequencing results show that KD reduces the Chao 1 index of gut microbiota α-diversity, and significant separation is detected in the β-diversity analysis between the control and KD-fed mice. KD increases the relative abundance of Firmicutes and Proteobacteria and decreases that of Bacteroidetes. Hypoglycemia can reduce SOD and GSH-PX levels while increasing TNF-α, IL-1β, and IL-6 mRNA levels in the brain tissues of mice. KD alleviates hypoglycemia-induced neuroinflammation by inhibiting microglia activation and TLR4/p38MAPK/NF-κB signaling pathway. Importantly, antibiotic cocktail depletion of the gut microbiota weakens anti-inflammatory and antioxidation responses in KD-fed mice.

CONCLUSION:

Collectively, these findings suggest that KD alleviates hypoglycemia-induced brain injury via gut microbiota modulation, which may provide novel insights into the therapy for hypoglycemia.

• Authors: Cixia Li, Jiarong Pan, Penghao Sun, Shuai Wang, Songlin Wang, Wenyu Feng, Shulin Chen, Xuejun Chai, Shanting Zhao, Xiaoyan Zhu
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 67 Issue 11 Pg. e2200711 (06 2023) ISSN: 1613-4133 [Electronic] Germany
• PMID: 37052374 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023 Wiley-VCH GmbH.

Chemical References

• RNA, Ribosomal, 16S

Topics

• Mice
• Animals
• Diet, Ketogenic
• Gastrointestinal Microbiome
• Neuroinflammatory Diseases
• RNA, Ribosomal, 16S
• Hypoglycemia