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Microbiota-gut-brain axis dysregulation in Alzheimer's disease and its modulation through probiotic supplementation
Moira Marizzoni1, Elisa Mombelli1, Silvia Alboni2
1Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
Background:
The microbiota-gut-brain axis (MGBA) has been implicated in the pathophysiology of Alzheimer's Disease (AD).Probiotics reduced the progression of ADin different mouse models, possibly through MGBA modulation, but human data are still limited.
Objective:
Here, we evaluated whether differences in the gut microbiome (GM), pro-inflammatory markers and other MGBA mediators were associated with probable AD (pAD). We also assessed the impact of a 12-week probiotic treatment on MGBA.
Methods:
Forty-five pAD patients and 47 healthy subjects (HC) were recruited at IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli of Brescia (Italy). An uncontrolled clinical investigation was performed to test the effects of 12-week probiotic supplementation in the pAD group. Fecal microbiota composition, intestinal and blood inflammatory markers, and microbiota-related metabolites were assessed before supplementation in all participants and after only in pAD.
Results:
pAD patients showed intestinal inflammation, an altered GM profile, blood changes in the tryptophan metabolism, and reduced glutamate levels compared with HC (p-value < 0.049). Probiotic supplementation partially modulated these alterations, determining a reduction in several pro-inflammatory mediators, and an increase of GM-related protective factors, such as butyrate (p-value < 0.040) in pAD.
Conclusions:
These findings confirmed the presence of MGBA alterations in AD and suggested a potential beneficial effect of probiotic supplementation through modulation of GM functionality rather than composition. Further research is required to confirm these results and their clinical relevance.
Insights
Alzheimer's Disease (AD) patients show gut microbiome alterations. Probiotic treatment partially improved gut health and reduced inflammation, suggesting potential benefits for AD management.
Area of Science:
- Neuroscience
- Microbiology
- Gastroenterology
Background:
- The microbiota-gut-brain axis (MGBA) is increasingly linked to Alzheimer's Disease (AD) pathophysiology.
- Probiotics show promise in preclinical AD models, but human studies are limited.
Purpose of the Study:
- To investigate gut microbiome (GM) differences, inflammation, and MGBA mediators in probable AD (pAD).
- To assess the impact of 12-week probiotic treatment on MGBA in pAD patients.
Main Methods:
- Recruited 45 pAD patients and 47 healthy controls (HC).
- Assessed fecal microbiota, intestinal/blood inflammatory markers, and metabolites before and after probiotic supplementation in pAD patients.
Main Results:
- pAD patients exhibited intestinal inflammation, altered GM, and changes in tryptophan metabolism and glutamate levels compared to HC.
- Probiotic supplementation reduced pro-inflammatory mediators and increased protective factors like butyrate in pAD patients.
Conclusions:
- Confirmed MGBA alterations in AD patients.
- Probiotics may benefit AD by modulating GM functionality, not just composition.
- Further research is needed to validate clinical relevance.
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