Nitrate ameliorates alcohol-induced cognitive impairment via oral microbiota
Abstract 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 microbi...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-04-01
|
| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12974-025-03439-x |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849699290095550464 |
|---|---|
| author | Xiangxue Li Zhaojun Ni Weixiong Shi Kangqing Zhao Yanjie Zhang Lina Liu Zhong Wang Jie Chen Zhoulong Yu Xuejiao Gao Ying Qin Jingwen Zhao Wenjuan Peng Jie Shi Thomas R. Kosten Lin Lu Lei Su Yanxue Xue Hongqiang Sun |
| author_facet | Xiangxue Li Zhaojun Ni Weixiong Shi Kangqing Zhao Yanjie Zhang Lina Liu Zhong Wang Jie Chen Zhoulong Yu Xuejiao Gao Ying Qin Jingwen Zhao Wenjuan Peng Jie Shi Thomas R. Kosten Lin Lu Lei Su Yanxue Xue Hongqiang Sun |
| author_sort | Xiangxue Li |
| collection | DOAJ |
| description | Abstract 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”. |
| format | Article |
| id | doaj-art-e5bb4aea98bb4aa3a09da898bdbdf983 |
| institution | DOAJ |
| issn | 1742-2094 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj-art-e5bb4aea98bb4aa3a09da898bdbdf9832025-08-20T03:18:39ZengBMCJournal of Neuroinflammation1742-20942025-04-0122111610.1186/s12974-025-03439-xNitrate ameliorates alcohol-induced cognitive impairment via oral microbiotaXiangxue Li0Zhaojun Ni1Weixiong Shi2Kangqing Zhao3Yanjie Zhang4Lina Liu5Zhong Wang6Jie Chen7Zhoulong Yu8Xuejiao Gao9Ying Qin10Jingwen Zhao11Wenjuan Peng12Jie Shi13Thomas R. Kosten14Lin Lu15Lei Su16Yanxue Xue17Hongqiang Sun18Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital)Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital)NHC Key Laboratory of Human Disease Comparative Medicine, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Center, Peking Union Medical College (PUMC)Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital)Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital)Henan Collaborative Innovation Center of Prevention and Treatment of Mental Disorder, Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical UniversityPeking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital)Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital)Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital)Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital)Addiction Medicine Department, The Second People’s Hospital of Guizhou ProvinceAddiction Medicine Department, The Second People’s Hospital of Guizhou ProvinceAddiction Medicine Department, The Second People’s Hospital of Guizhou ProvinceNational Institute On Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking UniversityDepartment of Psychiatry, Pharmacology, Neuroscience, Immunology, Baylor College of MedicinePeking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital)NHC Key Laboratory of Human Disease Comparative Medicine, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Center, Peking Union Medical College (PUMC)National Institute On Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking UniversityPeking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital)Abstract 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”.https://doi.org/10.1186/s12974-025-03439-xAlcohol drinkersCognitive impairmentOral microbiotaNeuroinflammationNitrate |
| spellingShingle | Xiangxue Li Zhaojun Ni Weixiong Shi Kangqing Zhao Yanjie Zhang Lina Liu Zhong Wang Jie Chen Zhoulong Yu Xuejiao Gao Ying Qin Jingwen Zhao Wenjuan Peng Jie Shi Thomas R. Kosten Lin Lu Lei Su Yanxue Xue Hongqiang Sun Nitrate ameliorates alcohol-induced cognitive impairment via oral microbiota Journal of Neuroinflammation Alcohol drinkers Cognitive impairment Oral microbiota Neuroinflammation Nitrate |
| title | Nitrate ameliorates alcohol-induced cognitive impairment via oral microbiota |
| title_full | Nitrate ameliorates alcohol-induced cognitive impairment via oral microbiota |
| title_fullStr | Nitrate ameliorates alcohol-induced cognitive impairment via oral microbiota |
| title_full_unstemmed | Nitrate ameliorates alcohol-induced cognitive impairment via oral microbiota |
| title_short | Nitrate ameliorates alcohol-induced cognitive impairment via oral microbiota |
| title_sort | nitrate ameliorates alcohol induced cognitive impairment via oral microbiota |
| topic | Alcohol drinkers Cognitive impairment Oral microbiota Neuroinflammation Nitrate |
| url | https://doi.org/10.1186/s12974-025-03439-x |
| work_keys_str_mv | AT xiangxueli nitrateamelioratesalcoholinducedcognitiveimpairmentviaoralmicrobiota AT zhaojunni nitrateamelioratesalcoholinducedcognitiveimpairmentviaoralmicrobiota AT weixiongshi nitrateamelioratesalcoholinducedcognitiveimpairmentviaoralmicrobiota AT kangqingzhao nitrateamelioratesalcoholinducedcognitiveimpairmentviaoralmicrobiota AT yanjiezhang nitrateamelioratesalcoholinducedcognitiveimpairmentviaoralmicrobiota AT linaliu nitrateamelioratesalcoholinducedcognitiveimpairmentviaoralmicrobiota AT zhongwang nitrateamelioratesalcoholinducedcognitiveimpairmentviaoralmicrobiota AT jiechen nitrateamelioratesalcoholinducedcognitiveimpairmentviaoralmicrobiota AT zhoulongyu nitrateamelioratesalcoholinducedcognitiveimpairmentviaoralmicrobiota AT xuejiaogao nitrateamelioratesalcoholinducedcognitiveimpairmentviaoralmicrobiota AT yingqin nitrateamelioratesalcoholinducedcognitiveimpairmentviaoralmicrobiota AT jingwenzhao nitrateamelioratesalcoholinducedcognitiveimpairmentviaoralmicrobiota AT wenjuanpeng nitrateamelioratesalcoholinducedcognitiveimpairmentviaoralmicrobiota AT jieshi nitrateamelioratesalcoholinducedcognitiveimpairmentviaoralmicrobiota AT thomasrkosten nitrateamelioratesalcoholinducedcognitiveimpairmentviaoralmicrobiota AT linlu nitrateamelioratesalcoholinducedcognitiveimpairmentviaoralmicrobiota AT leisu nitrateamelioratesalcoholinducedcognitiveimpairmentviaoralmicrobiota AT yanxuexue nitrateamelioratesalcoholinducedcognitiveimpairmentviaoralmicrobiota AT hongqiangsun nitrateamelioratesalcoholinducedcognitiveimpairmentviaoralmicrobiota |