Microbiota-gut-brain axis and probiotic supplementation in AD patients

The microbiota-gut-brain axis (MGBA) has been implicated in the pathophysiology of Alzheimer's Disease (AD). Probiotics reduced the progression of AD in different mouse models, possibly through MGBA modulation, but human data are still limited. Here, we evaluated whether the presence of a gut microbiota (GM) community was associated to probable AD (pAD), to a pro-inflammatory status and to a specific MGBA profile. We also assessed the impact of a 12-week probiotic treatment on MGBA. 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. 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 modulated GM composition and several blood features, determining a reduction in several pro-inflammatory mediators, and an increase of protective factors, such as butyrate (p-value< 0.040) in pAD. These findings confirmed the presence of MGBA alterations in AD and suggest a potential beneficial effect of probiotic supplementation in counteracting such changes. Further research is required to confirm these findings and their clinical relevance.