Nitrate ameliorates alcohol-induced cognitive impairment via oral microbiota
Alcohol use is associated with cognitive impairment and dysregulated inflammation. Oral nitrate may benefit cognitive impairment in aging through altering the oral microbiota. Similarly, the beneficial effects of nitrate on alcohol-induced cognitive decline and the roles of the oral microbiota merit investigation. Here we found that nitrate supplementation effectively mitigated cognitive impairment induced by chronic alcohol exposure in mice, reducing both systemic and neuroinflammation. Furthermore, nitrate restored the dysbiosis of the oral microbiota caused by alcohol consumption. Notably, removing the oral microbiota led to a subsequent loss of the beneficial effects of nitrate. Oral microbiota from donor alcohol use disordered humans who had been taking the nitrate intervention were transplanted into germ-free mice which then showed increased cognitive function and reduced neuroinflammation. Finally, we examined 63 alcohol drinkers with varying levels of cognitive impairment and found that lower concentrations of nitrate metabolism-related bacteria were associated with higher cognitive impairment and lower nitrate levels in plasma. These findings highlight the protective role of nitrate against alcohol-induced cognition impairment and neuroinflammation and suggest that the oral microbiota associated with nitrate metabolism and brain function may form part of a "microbiota-mouth-brain axis".
Authors
- Lin Lü (ORCID: https://orcid.org/0000-0001-5881-892X)
- Zhoulong Yu
- Jie Shi (ORCID: https://orcid.org/0000-0001-6567-8160)
- Zhaojun Ni (ORCID: https://orcid.org/0000-0001-6778-5760)
- Weixiong Shi
- Xiangxue Li (ORCID: https://orcid.org/0000-0002-1779-6178)
- Jingwen Zhao (ORCID: https://orcid.org/0000-0002-2192-4320)
- Yan-Xue Xue (ORCID: https://orcid.org/0000-0003-2979-0045)
- Hongqiang Sun (ORCID: https://orcid.org/0000-0002-8434-4462)
- Guanghua Su (ORCID: https://orcid.org/0000-0003-1473-3814)
- Thomas R. Kosten (ORCID: https://orcid.org/0000-0003-1505-555X)
- Ying Qin (ORCID: https://orcid.org/0000-0002-6099-2190)
- Kangqing Zhao (ORCID: https://orcid.org/0000-0001-7366-5669)
- Xuejiao Gao (ORCID: https://orcid.org/0000-0002-2323-8180)
- Yanjie Zhang (ORCID: https://orcid.org/0000-0002-7964-2326)
- Jie Chen (ORCID: https://orcid.org/0000-0002-6808-1076)
- Zhong Wang (ORCID: https://orcid.org/0000-0002-7342-0845)
- Wenjuan Peng
- Lina Liu (ORCID: https://orcid.org/0009-0006-0436-8031)
Institutions
- Baylor College of Medicine (US)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Peking University (CN)
- Henan Psychiatric Hospital (CN)
- Institute of Laboratory Animal Science (CN)
- National Institutes for Food and Drug Control (CN)
- Guizhou Provincial People's Hospital (CN)
- Peking University Sixth Hospital (CN)
Publication Details
- Journal
- Journal of Neuroinflammation
- Published
- 2025-04-15
- DOI
- https://doi.org/10.1186/s12974-025-03439-x
- Citations
- 9
- Primary Topic
- Alcoholism and Thiamine Deficiency
- Type
- article
- Field-Weighted Citation Impact
- 12.50
Funders
- National Children's Research Centre
- National Natural Science Foundation of China
- Ministry of Science and Technology of the People's Republic of China
- Peking University
- National Key Research and Development Program of China