Abstract
The microbiota–gut–brain axis plays an important role in the development of neurodegenerative diseases. Commensal and pathogenic enteric bacteria can influence brain and immune system function by the production of lipopolysaccharides and amyloid. Dysbiosis of the intestinal microbiome induces local and consecutively systemic immune-mediated inflammation. Proinflammatory cytokines then trigger neuroinflammation and finally neurodegeneration. Immune-mediated oxidative stress can lead to a deficiency of vitamins and essential micronutrients. Furthermore, the wrong composition of gut microbiota might impair the intake and metabolization of nutrients. In patients with Alzheimer’s disease (AD) significant alterations of the gut microbiota have been demonstrated. Standard Western diet, infections, decreased physical activity and chronic stress impact the composition and diversity of gut microbiota. A higher abundancy of “pro-inflammatory” gut microbiota goes along with enhanced systemic inflammation and neuroinflammatory processes. Thus, AD beginning in the gut is closely related to the imbalance of gut microbiota. Modulation of gut microbiota by Mediterranean diet, probiotics and curcumin can slow down cognitive decline and alter the gut microbiome significantly. A multi-domain intervention approach addressing underlying causes of AD (inflammation, infections, metabolic alterations like insulin resistance and nutrient deficiency, stress) appears very promising to reduce or even reverse cognitive decline by exerting positive effects on the gut microbiota.
Highlights
Alzheimer’s disease (AD) is the most common form of dementia in older aged populations worldwide
Recent studies show that lifestyle appears to play an underestimated role in the development of AD and may attenuate genetic risk factors: a recent study investigating the role of a healthy lifestyle and of genetic risk in nearly 200,000 patients without cognitive impairment at the age of 60 years could show that both, an unfavorable lifestyle and high genetic risk were linked with a higher risk to get dementia [211]
AD has been regarded as a disease which only derives from the central nervous system (CNS) without influence of the periphery for many decades
Summary
Alzheimer’s disease (AD) is the most common form of dementia in older aged populations worldwide. Aβ can activate the microglia— the brain’s innate immune cells to induce a neuroinflammatory response. This initially beneficial response in the central nervous system (CNS) can have detrimental effects, if it continues for longer periods, as it triggers the chronic release of pro-inflammatory cytokines [8]. These cytokines nourish chronic neuroinflammatory cascades, which over the course of years lead to irreversible neurodegeneration, especially in the hippocampus. Recent data indicate that neuro-inflammatory cascades, and alterations of gut microbiota play a crucial role in the development of neurodegeneration: data investigating gut microbiota in humans strongly suggest that neuroinflammation is related strongly to gut dysbiosis (as reviewed in the following chapters)
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