Marine fungal metabolite butyrolactone I improves Aβ<sub>1-42</sub>-induced cognitive impairment in mice via gut-brain axial microbiota remodeling, anti-inflammation, and antioxidation

Fuyan YANG; Longjian ZHOU; Jiahang DENG; Yuan WANG; Zhiyou YANG; Yongping ZHANG; Yayue LIU; Yi ZHANG

doi:10.1007/s00343-025-4317-8

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Marine fungal metabolite butyrolactone I improves Aβ_1-42-induced cognitive impairment in mice via gut-brain axial microbiota remodeling, anti-inflammation, and antioxidation

Biology | Updated：2026-03-26

- Marine fungal metabolite butyrolactone I improves Aβ_1-42-induced cognitive impairment in mice via gut-brain axial microbiota remodeling, anti-inflammation, and antioxidation
- Journal of Oceanology and Limnology Vol. 44, Issue 1, Pages: 386-405(2026)
- Affiliations：
  
  1.Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Provincial Engineering Laboratory for Marine Biological Products, Marine Biomedicine R&D Center at Shenzhen Institute of Guangdong Ocean University, Zhanjiang Municipal Key Laboratory of Marine Drugs and Nutrition for Brain Health, Research Institute for Marine Drugs and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China
  2.Southern Marine Science and Engineering Guangdong Laboratory (Zhanjiang), Zhanjiang 524088, China
  3.Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian 116034, China
- Author bio：
  
  yang_zhiyou@sina.com
  hubeizhangyi@163.com
- Funds：
- DOI：10.1007/s00343-025-4317-8
  CLC：
- Received：27 November 2024，
  
  Accepted：14 March 2025，
  
  Online First：07 April 2025，
  
  Published：01 January 2026
- Accepted：
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YANG Fuyan,ZHOU Longjian,DENG Jiahang,et al.Marine fungal metabolite butyrolactone I improves Aβ_1-42-induced cognitive impairment in mice via gut-brain axial microbiota remodeling, anti-inflammation, and antioxidation[J].Journal of Oceanology and Limnology,2026,44(01):386-405.
DOI：

YANG Fuyan,ZHOU Longjian,DENG Jiahang,et al.Marine fungal metabolite butyrolactone I improves Aβ_1-42-induced cognitive impairment in mice via gut-brain axial microbiota remodeling, anti-inflammation, and antioxidation[J].Journal of Oceanology and Limnology,2026,44(01):386-405. DOI： 10.1007/s00343-025-4317-8.

摘要

Abstract

Alzheimer’s disease (AD) is a complex neurodegenerative disorder associated with changes in inflammation

oxidative stress

and gut microbiota composition. Butyrolactone I (BTL-I)

a fungal metabolite

has shown anti-inflammatory

microbiota regulating

and memory-improving potentials in previous in vitro and AlCl

-induced zebrafish studies. However

its effects of memory-improving and gut-brain axis regulating on Aβ-induced mammalian AD models have not been explored. In this study

intragastric administrated BTL-I ameliorated cognitive deficits related to recognition and spatial memory impaired by Aβ

1-42

intracerebroventricular injection in mice. BTL-I maintained gut microbiota balance by increasing the abundance of

Blautia

Muribaculaceae

Bacteroides

Akkermansia

etc.

and decreasing CAG-352

Clostridia UCG-014

different Lachnospiraceae groups

etc.

and Firmicutes/Bacteroidota ratio and elevated the levels of short-chain fatty acids. Additionally

it alleviated intestinal oxidative stress

inflammatory responses

and pathological damage. Furthermore

BTL-I reversed Aβ

1-42

-induced activation of microglia and astrocytes in the hippocampus and inhibited the elevated oxidative stress and pro-inflammatory cytokines in both plasma and brain. The correlation analysis between the regulated taxa and biomarkers supports the role of gut microbiota in adjusting inflammation

oxidative stress

and memory. In conclusion

BTL-I may serve as a valuable drug lead for treating Alzheimer’s disease by systematically inhibiting microbiota imbalance

inflammation

and oxidative stress along the gut-brain axis.

关键词

Keywords

references

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Marine fungal metabolite butyrolactone I improves Aβ1-42-induced cognitive impairment in mice via gut-brain axial microbiota remodeling, anti-inflammation, and antioxidation

DOI：10.1007/s00343-025-4317-8

摘要

Abstract

关键词

Keywords

references

Marine fungal metabolite butyrolactone I improves Aβ_1-42-induced cognitive impairment in mice via gut-brain axial microbiota remodeling, anti-inflammation, and antioxidation