Dysbiosis and Alzheimer’s Disease: A Role for Chronic Stress?

Abstract

Alzheimer’s disease (AD) is an incurable, neuropsychiatric, pathological condition that deteriorates the worth of geriatric lives. AD is characterized by aggregated senile amyloid plaques, neurofibrillary tangles, neuronal loss, gliosis, oxidative stress, neurotransmitter dysfunction, and bioenergetic deficits. The changes in GIT composition and harmony have been recognized as a decisive and interesting player in neuronal pathologies including AD. Microbiota control and influence the oxidoreductase status, inflammation, immune system, and the endocrine system through which it may have an impact on the cognitive domain. The altered and malfunctioned state of microbiota is associated with minor infections to complicated illnesses that include psychosis and neurodegeneration, and several studies show that microbiota regulates neuronal plasticity and neuronal development. The altered state of microbiota (dysbiosis) may affect behavior, stress response, and cognitive functions. Chronic stress-mediated pathological progression also has a well-defined role that intermingles at various physiological levels and directly impacts the pathological advancement of AD. Chronic stress-modulated alterations affect the well-established pathological markers of AD but also affect the gut–brain axis through the mediation of various downstream signaling mechanisms that modulate the microbial commensals of GIT. The extensive literature reports that chronic stressors affect the composition, metabolic activities, and physiological role of microbiota in various capacities. The present manuscript aims to elucidate mechanistic pathways through which stress induces dysbiosis, which in turn escalates the neuropathological cascade of AD. The stress–dysbiosis axis appears a feasible zone of work in the direction of treatment of AD.

The Microbiota–Gut–Brain Axis and Alzheimer Disease. From Dysbiosis to Neurodegeneration: Focus on the Central Nervous System Glial Cells

“…Dysbiosis is a condition characterized by quantitative and qualitative changes in the microbiota composition, of which the results are possibly noxious to the host. The quantitative changes consist in the presence of fewer beneficial microbiota, and the qualitative in a lower variety of microbiota species [ 24 ]. The main genera of hostile bacteria are the Enterobacteriacee , a family including the gut commensals Escherichia, Shigella, Proteus , and Klebsiella .…”

“…Dysbiosis is constantly associated with insulin resistance and type 2 diabetes, dyslipidemia, hypertension, obesity and, because of the significant association found between metabolic diseases and AD, the formers are considered as possible etiological factors for AD [ 24 , 34 , 49 , 60 ]. Among the taxa present in the microbiota, it has been shown that, in dysbiosis, the imbalance between Proteobacteria and Bifidobacteria in favor of the former is associated with a decrease in the synthesis of SCFAs and the appearance of dyslipidemia.…”

“…Bifidobacteria owns lipid-lowering and hypocholesterolemic activity, facilitating the fecal elimination of cholesterol and reducing its absorption. This taxon also promotes an increase in the serum levels of leptin, an anti-obesity hormone [ 24 , 61 ]. The observation that statin treatment for hypercholesterolemia was associated with a lower risk of developing AD, and the high frequency of elevated plasma level of this lipid in AD patients, has moved the attention to the implication of cholesterol and its metabolites in the pathogenesis of AD [ 62 ].…”

“…Studies in AD patients have demonstrated a significant association between an altered BA profile in the blood and cognitive impairment [ 63 ]. Thus, dysbiosis triggers several changes in the organ functions, all conducible to an inflammatory status powered by the guest hostile bacterial strains [ 14 , 24 , 35 , 50 , 54 ].…”

Microbiota and epigenetics: promising therapeutic approaches?

“…Meanwhile, the term psychobiotics was used recently to describe certain pre/probiotics which have the potential to improve the neurological signs related to certain disorders such as autism, Alzheimer’s, and Parkinson’s (Doenyas 2018 ; Sampson et al 2016 ; Sarkar et al 2016 ; Sharma et al 2021 ; Skonieczna-Żydecka et al 2018 ).…”