Gut Microbiota in Alzheimer’s Disease, Depression, and Type 2 Diabetes Mellitus: The Role of Oxidative Stress

Abstract

Gut microbiota consists of over 100 trillion microorganisms including at least 1000 different species of bacteria and is crucially involved in physiological and pathophysiological processes occurring in the host. An imbalanced gastrointestinal ecosystem (dysbiosis) seems to be a contributor to the development and maintenance of several diseases, such as Alzheimer’s disease, depression, and type 2 diabetes mellitus. Interestingly, the three disorders are frequently associated as demonstrated by the high comorbidity rates. In this review, we introduce gut microbiota and its role in both normal and pathological processes; then, we discuss the importance of the gut-brain axis as well as the role of oxidative stress and inflammation as mediators of the pathological processes in which dysbiosis is involved. Specific sections pertain the role of the altered gut microbiota in the pathogenesis of Alzheimer’s disease, depression, and type 2 diabetes mellitus. The therapeutic implications of microbiota manipulation are briefly discussed. Finally, a conclusion comments on the possible role of dysbiosis as a common pathogenetic contributor (via oxidative stress and inflammation) shared by the three disorders.

The Role of Oxidative Stress in Common Risk Factors and Mechanisms of Cardio-Cerebrovascular Ischemia and Depression

“…The former involves factors like poor financial situation, marital status, and life events; the latter have genetic and gender predisposition and other health conditions like obesity [21] and diabetes [22]. Mechanism underlying depression includes the monoamine hypothesis, hypothalamic-pituitary-adrenal axis, inflammation, neuroplasticity, neurogenesis [20], and OS [23][24][25][26]. Recently, inflammation and neurogenesis hypotheses have gained more acceptances [27,28].…”

“…The brain is susceptible to glucose, and the risk of stroke increases by OS through complex mechanisms [49,50], and diabetes worsens results of acute coronary syndrome due to overactivation of OS [43]. Recent studies have proved that reducing OS response via antioxidant treatment is able to ease the depressive-like behavior caused by diabetes [51] and implicated gut microbiota as a common mechanism mediated by OS in diabetes and depression [23,52]. In conclusion, diabetes is an important risk factor for ischemic CVD and depression, and its pathogenesis is closely related to OS (Figure 1 B).…”

Oxidative Stress-Related Endothelial Damage in Vascular Depression and Vascular Cognitive Impairment: Beneficial Effects of Aerobic Physical Exercise

“…The most frequent depressive symptoms are sad mood, thoughts of guilt, lack of interest, sleep disorders, lack of appetite, psychomotor retardation or agitation, cognitive deficits, and suicidal ideation [17,18]. Among the different neurobiological mechanisms contributing to the occurrence of depression, it is possible to include the serotoninergic, norepinephrinergic, and dopaminergic deficits, the dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, the hyperproduction of proinflammatory mediators, and an altered gut-brain axis [19]. Despite the median age at depression onset typically being the early adulthood [20], depressive symptoms are common in the elderly and are associated with reduced quality of life and elevated mortality [21].…”

On elucidation of the role of mitochondria dysfunction and oxidative stress in multiple sclerosis

“…153 Research indicates a pro-inflammatory alteration in gut microbiome in MS, and microbiota transplants from MS patients into germ-free mice have been shown to result in increased severity in EAE symptoms and reduced proportions of anti-inflammatory IL-10+Tregs. 154 Notably, inflammation and OS play an important role in the pathological processes involving a disrupted gut microbiome 155 and several studies have shown that antioxidants can prevent or reverse dysbiosis. [156][157][158][159][160]…”