bims-metalz Biomed News
on Metabolic causes of Alzheimer’s disease
Issue of 2023‒08‒27
five papers selected by
Mikaila Chetty, Goa University

  1. Int J Mol Sci. 2023 Aug 15. pii: 12819. [Epub ahead of print]24(16):
      Alzheimer's Disease (AD) is a progressively debilitating form of dementia that affects millions of individuals worldwide. Although a vast amount of research has investigated the complex interplay between gut microbiota and neurodegeneration, the metaproteomic effects of microbiota on AD pathogenesis remain largely uncharted territory. This study aims to reveal the role of gut microbiota in AD pathogenesis, particularly regarding changes in the proteome and molecular pathways that are intricately linked to disease progression. We operated state-of-the-art Nano-Liquid Chromatography Mass Spectrometry (nLC-MS/MS) to compare the metaproteomic shifts of 3-month-old transgenic (3M-ALZ) and control (3M-ALM, Alzheimer's Littermate) mice, depicting the early onset of AD with those of 12-month-old ALZ and ALM mice displaying the late stage of AD. Combined with computational analysis, the outcomes of the gut-brain axis-focused inquiry furnish priceless knowledge regarding the intersection of gut microbiota and AD. Accordingly, our data indicate that the microbiota, proteome, and molecular changes in the intestine arise long before the manifestation of disease symptoms. Moreover, disparities exist between the normal-aged flora and the gut microbiota of late-stage AD mice, underscoring that the identified vital phyla, proteins, and pathways hold immense potential as markers for the early and late stages of AD. Our research endeavors to offer a comprehensive inquiry into the intricate interplay between gut microbiota and Alzheimer's Disease utilizing metaproteomic approaches, which have not been widely adopted in this domain. This highlights the exigency for further scientific exploration to elucidate the underlying mechanisms that govern this complex and multifaceted linkage.
    Keywords:  5xFAD mice; Alzheimer’s Disease; gut microbiota; metaproteomics; neurodegeneration; proteomics
  2. Semin Neurol. 2023 Aug 22.
      Increasing research links the gut microbiome to neurodegenerative disorders. The gut microbiome communicates with the central nervous system via the gut-brain axis and affects behavioral and cognitive phenotypes. Dysbiosis (a dysfunctional microbiome) drives increased intestinal permeability and inflammation that can negatively affect the brain via the gut-brain axis. Healthier metabolic and lipid profiles and cognitive phenotypes are observed in individuals with more distinct microbiomes. In this review, we discuss the role of the gut microbiome and gut-brain axis in neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease and related animal models, in cancer and cancer treatments, and in metabolic syndrome. We also discuss strategies to improve the gut microbiome and ultimately brain function. Because healthier cognitive phenotypes are observed in individuals with more distinct microbiomes, increased efforts are warranted to develop therapeutic strategies for those at increased risk of developing neurological disorders and patients diagnosed with those disorders.
  3. Front Neurosci. 2023 ;17 1241418
      Extracellular vesicles (EVs) serve as cell-to-cell and inter-organ communicators by conveying proteins and nucleic acids with regulatory functions. Emerging evidence shows that gut microbial-released EVs play a pivotal role in the gut-brain axis, bidirectional communication, and crosstalk between the gut and the brain. Increasing pre-clinical and clinical evidence suggests that gut bacteria-released EVs are capable of eliciting distinct signaling to the brain with the ability to cross the blood-brain barrier, exerting regulatory function on brain cells such as neurons, astrocytes, and microglia, via their abundant and diversified protein and nucleic acid cargo. Conversely, EVs derived from certain species of bacteria, particularly from gut commensals with probiotic properties, have recently been shown to confer distinct therapeutic effects on various neurological disorders. Thus, gut bacterial EVs may be both a cause of and therapy for neuropathological complications. This review marshals the basic, clinical, and translational studies that significantly contributed to our up-to-date knowledge of the therapeutic potential of gut microbial-derived EVs in treating neurological disorders, including strokes, Alzheimer's and Parkinson's disease, and dementia. The review also discusses the newer insights in recent studies focused on developing superior therapeutic microbial EVs via genetic manipulation and/or dietary intervention.
    Keywords:  extracellular vesicle; gut bacteria; gut-brain axis; microbiota; neurological disorder
  4. Biomedicines. 2023 Aug 14. pii: 2267. [Epub ahead of print]11(8):
      Physical activity has been demonstrated to have a significant impact on gut microbial diversity and function. Emerging research has revealed certain aspects of the complex interactions between the gut, exercise, microbiota, and neurodegenerative diseases, suggesting that changes in gut microbial diversity and metabolic function may have an impact on the onset and progression of neurological conditions. This study aimed to review the current literature from several databases until 1 June 2023 (PubMed/MEDLINE, Web of Science, and Google Scholar) on the interplay between the gut, physical exercise, microbiota, and neurodegeneration. We summarized the roles of exercise and gut microbiota on neurodegeneration and identified the ways in which these are all connected. The gut-brain axis is a complex and multifaceted network that has gained considerable attention in recent years. Research indicates that gut microbiota plays vital roles in metabolic shifts during physiological or pathophysiological conditions in neurodegenerative diseases; therefore, they are closely related to maintaining overall health and well-being. Similarly, exercise has shown positive effects on brain health and cognitive function, which may reduce/delay the onset of severe neurological disorders. Exercise has been associated with various neurochemical changes, including alterations in cortisol levels, increased production of endorphins, endocannabinoids like anandamide, as well as higher levels of serotonin and dopamine. These changes have been linked to mood improvements, enhanced sleep quality, better motor control, and cognitive enhancements resulting from exercise-induced effects. However, further clinical research is necessary to evaluate changes in bacteria taxa along with age- and sex-based differences.
    Keywords:  exercise interventions; gut–brain axis; immune system; inflammation; lactate; metabolic function; microbial diversity; neurodegenerative disease
  5. Front Neurosci. 2023 ;17 1225875
      The gut microbiota (GM) plays an important role in the physiology and pathology of the host. Microbiota communicate with different organs of the organism by synthesizing hormones and regulating body activity. The interaction of the central nervous system (CNS) and gut signaling pathways includes chemical, neural immune and endocrine routes. Alteration or dysbiosis in the gut microbiota leads to different gastrointestinal tract disorders that ultimately impact host physiology because of the abnormal microbial metabolites that stimulate and trigger different physiologic reactions in the host body. Intestinal dysbiosis leads to a change in the bidirectional relationship between the CNS and GM, which is linked to the pathogenesis of neurodevelopmental and neurological disorders. Increasing preclinical and clinical studies/evidence indicate that gut microbes are a possible susceptibility factor for the progression of neurological disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS) and autism spectrum disorder (ASD). In this review, we discuss the crucial connection between the gut microbiota and the central nervous system, the signaling pathways of multiple biological systems and the contribution of gut microbiota-related neurological disorders.
    Keywords:  gut dysbiosis; gut-brain axis; microbiota; neurological disorders; signaling pathways