Administration of pre/probiotics with conventional drug treatment in Alzheimer's disease

The most important are: (1) a direct microbial infection inducing a neuroinflammatory state in the brain of AD patients; (2) an age-related dysbiosis”, which hypothesizes that AD arises during the process of aging of the immune system; (3) an antimicrobial protection hypothesis, which suggests that the accumulation of Aβ in the brain represents an immune response to the accumulation of harmful bacteria; and (4) the hygiene hypothesis of AD, which indicates in an excessive sanitation in early life the cause of late impaired function of the immune system. From these data two conclusions can be drawn: (1) AD drugs that have negative effects on gut microbiota could lead to a worsening of the disease in the long term, although temporarily alleviating the symptoms; (2) it is possible that an adjuvant treatment with pre/probiotics can prevent and/or cure gut dysbiosis and, therefore, allow the therapeutic effects of AD drugs to be exploited more completely. The concept of making the neurotransmitter acetylcholine available, or limiting the neuronal excitability with NMDA receptor antagonist, certainly has an important scientific rationale and it is supported by robust preclinical and clinical evidence. In in vitro pharmacological studies performed to characterize these and new therapeutic compounds, neuronal cell lines are normally used in absence of other cellular elements potentially influenced by gut microbiota, such as glial cells, cells of the immune response, and immune and endocrine molecules, such as cytokines and hormones.