Microbiota-gut-brain axis dysregulation in Alzheimer’s disease and its modulation through probiotic supplementation

Oct 15, 2025Brain, behavior, and immunity

Disruption of the Gut Microbe-Brain Link in Alzheimer's Disease and Its Improvement with Probiotics

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Gut-Brain Axis on OpenScience ↗PubMed ↗DOI ↗

Abstract

Probable Alzheimer's Disease patients showed significant differences in gut microbiome and inflammatory markers compared to healthy subjects (p-value < 0.049).

Intestinal inflammation and an altered gut microbiome profile were observed in probable Alzheimer's Disease patients.
Blood changes in tryptophan metabolism and reduced levels of glutamate were linked to the altered gut microbiome.
Probiotic supplementation for 12 weeks partially modulated intestinal inflammation and reduced several pro-inflammatory markers in patients.
An increase in microbiota-related protective factors, such as butyrate, was noted following probiotic treatment (p-value < 0.040).
The findings suggest that alterations in the microbiota-gut-brain axis may be associated with Alzheimer's Disease.

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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.