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Nitrate ameliorates alcohol-induced cognitive impairment via oral microbiota.

Journal of neuroinflammation
April 15, 2025
Xiangxue Li et al. (19 authors)
Journal ArticleHuman StudyAnimal Study
Study Details

Study Goal

The researchers aimed to determine whether nitrate supplementation could mitigate alcohol-induced cognitive impairment and neuroinflammation, and whether the oral microbiota played a role in these effects.

Results Summary

Nitrate supplementation reduced cognitive impairment and neuroinflammation in alcohol-exposed mice, restored oral microbiota dysbiosis, and its benefits were lost when the oral microbiota was removed. Human microbiota transplants from nitrate-treated individuals improved cognition in germ-free mice, and lower nitrate-related bacteria correlated with worse cognitive impairment in drinkers.

Population

Mice chronically exposed to alcohol and germ-free mice; 63 human alcohol drinkers with varying cognitive impairment.

Effective Dosage

Not specified

Duration

Not specified

Interactions

None mentioned

Extracted Claims (8)
InterventionDirectionEndpointPopulationDosageImpactClaim #
nitrate supplementation
decrease
cognitive impairment induced by chronic alcohol exposure
mice
-
effectively mitigated
#1
nitrate supplementation
decrease
systemic and neuroinflammation
mice
-
reducing
#2
nitrate supplementation
neutral
dysbiosis of the oral microbiota caused by alcohol consumption
mice
-
restored
#3
removing the oral microbiota
decrease
beneficial effects of nitrate
-
-
led to a subsequent loss
#4
Oral microbiota from donor alcohol use disordered humans who had been taking the nitrate intervention
increase
cognitive function
germ-free mice
-
showed increased
#5
Oral microbiota from donor alcohol use disordered humans who had been taking the nitrate intervention
decrease
neuroinflammation
germ-free mice
-
showed reduced
#6
-
increase
higher cognitive impairment
63 alcohol drinkers with varying levels of cognitive impairment
-
associated with
#7
-
decrease
lower nitrate levels in plasma
63 alcohol drinkers with varying levels of cognitive impairment
-
associated with
#8
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".

Medical Subject Headings (MeSH)
NitratesCognitive DysfunctionAnimalsMiceMaleHumansMicrobiotaMice, Inbred C57BLEthanolMouthFemaleMiddle AgedAdult
Study Links
Quality Scores
SafetyNot Assessed
Efficacy85/10
Quality80/10
Research Impact Scores
APT Score0.05
Weight Score1.30
Normalized Score0.70
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