1.
Microbiota-gut-brain axis in the Alzheimer's disease pathology - an overview.
Giridharan, VV, Barichello De Quevedo, CE, Petronilho, F
Neuroscience research. 2022;:17-21
Abstract
Alzheimer's disease (AD) and related dementias (ADRD) are still a serious global public health concern more than a century after the German neuropathologist and psychiatrist Dr. Aloysius Alzheimer described the first case. The World Health Organization (WHO) estimates that over 50 million people worldwide suffer from dementia, with AD accounting for 60-70% of all cases. In addition, the global dementia epidemic is estimated to affect 82 million individuals by 2030 and 152 million by 2050. Along with genetic factors, environmental factors, and aging also increase the risks of developing neurodegenerative disorders. For example, gut microbiota can serve as non-genetic factors that define a threshold for maintaining a homeostatic balance or developing illnesses. The scientific community has explored and identified that patients with AD often present with dysbiosis of the bowel and dysregulated gastrointestinal (GI) tract. Research describes it as a bidirectional relationship by which the brain communicates with the gut's microbiome through the vagus nerve, immune and neuroimmune systems, enteroendocrine system, neurotransmitters, branched-chain amino acids, short-chain fatty acids (SCFAs), agonists of aryl hydrocarbon receptors (AHRs), bile acids, and the hypothalamic-pituitary-adrenal (HPA) axis. In this narrative review, we explore and clarify the involvement of the microbiota-gut-brain axis in AD pathology.
2.
Clinical significance and potential role of trimethylamine N-oxide in neurological and neuropsychiatric disorders.
Mudimela, S, Vishwanath, NK, Pillai, A, Morales, R, Marrelli, SP, Barichello, T, Giridharan, VV
Drug discovery today. 2022;(11):103334
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Abstract
In the past three decades, research on the gut microbiome and its metabolites, such as trimethylamines (TMA), trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), branched-chain amino acids (BCAAs), bile acids, tryptophan and indole derivatives, has attracted the attention of many scientists and industrialists. Among these metabolites, TMAO is produced from dietary choline, phosphatidylcholine, carnitine,andbetaine. TMAO and other gut metabolites, such as TMA and SCFAs, reach the brain by crossing the blood-brain barrier (BBB) and are involved in brain development, neurogenesis, and behavior. Gut-microbiota composition is influenced by diet, lifestyle, antibiotics, and age. Several studies have confirmed that altered TMAO levels contribute to metabolic, vascular, psychiatric, and neurodegenerative disorders. This review focuses on how altered TMAO levels impact oxidative stress, microglial activation, and the apoptosis of neurons, and may lead to neuroinflammation, which can subsequently result in the development of psychiatric, cognitive, and behavioral disorders.
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The role of the microbiota-gut-brain axis in neuropsychiatric disorders.
Generoso, JS, Giridharan, VV, Lee, J, Macedo, D, Barichello, T
Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999). 2021;43(3):293-305
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Plain language summary
Metabolites produced by the gut microbiota have been shown to influence mood and behaviour via the microbiota-gut-brain axis, and there is increased interest in better understanding this interaction in the context of mental health. This review summarises the evidence around the influence of gut microbiota in various neuropsychiatric disorders, primarily focusing on the metabolic pathways that originate in the gut microbiota. Current research highlights an association between gut microbiota metabolites with neuropsychiatric disorders and that probiotics demonstrate a significant therapeutic role in many of these disorders. Based on the current literature, the authors conclude it is crucial to better understand the complex microbiota-host interaction in health and disease, leading to more targeted and improved therapeutic interventions.
Abstract
The microbiota-gut-brain axis is a bidirectional signaling mechanism between the gastrointestinal tract and the central nervous system. The complexity of the intestinal ecosystem is extraordinary; it comprises more than 100 trillion microbial cells that inhabit the small and large intestine, and this interaction between microbiota and intestinal epithelium can cause physiological changes in the brain and influence mood and behavior. Currently, there has been an emphasis on how such interactions affect mental health. Evidence indicates that intestinal microbiota are involved in neurological and psychiatric disorders. This review covers evidence for the influence of gut microbiota on the brain and behavior in Alzheimer disease, dementia, anxiety, autism spectrum disorder, bipolar disorder, major depressive disorder, Parkinson's disease, and schizophrenia. The primary focus is on the pathways involved in intestinal metabolites of microbial origin, including short-chain fatty acids, tryptophan metabolites, and bacterial components that can activate the host's immune system. We also list clinical evidence regarding prebiotics, probiotics, and fecal microbiota transplantation as adjuvant therapies for neuropsychiatric disorders.