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      Gut Microbiota: Implications in Alzheimer’s Disease

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          Abstract

          Alzheimer’s disease (AD), the most common cause of dementia, is a neurodegenerative disease that seriously threatens human health and life quality. The main pathological features of AD include the widespread deposition of amyloid-beta and neurofibrillary tangles in the brain. So far, the pathogenesis of AD remains elusive, and no radical treatment has been developed. In recent years, mounting evidence has shown that there is a bidirectional interaction between the gut and brain, known as the brain–gut axis, and that the intestinal microbiota are closely related to the occurrence and development of neurodegenerative diseases. In this review, we will summarize the laboratory and clinical evidence of the correlation between intestinal flora and AD, discuss its possible role in the pathogenesis, and prospect its applications in the diagnosis and treatment of AD.

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          Dementia in China: epidemiology, clinical management, and research advances

          Longfei Jia, Meina Quan, Yue Fu … (2019)
          China has the largest population of patients with dementia in the world, imposing a heavy burden on the public and health care systems. More than 100 epidemiological studies on dementia have been done in China, but the estimates of the prevalence and incidence remain inconsistent because of the use of different sampling methods. Despite improved access to health services, inadequate diagnosis and management for dementia is still common, particularly in rural areas. The Chinese Government issued a new policy to increase care facilities for citizens older than 65 years, but most patients with dementia still receive care at home. Western medicines for dementia symptoms are widely used in China, but many patients choose Chinese medicines even though they have little evidence supporting efficacy. The number of clinical trials of Chinese and western medicines has substantially increased as a result of progress in research on new antidementia drugs but international multicentre studies are few in number. Efforts are needed to establish a national system of dementia care enhance training in dementia for health professionals, and develop global collaborations to prevent and cure this disease.
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            Altered microbiomes distinguish Alzheimer’s disease from amnestic mild cognitive impairment and health in a Chinese cohort

            Ping Liu, Li WU, Guoping Peng … (2019)
            (Background): Alzheimer's disease (AD), clinically characterized by the progressive neurodegenerative condition and cognitive impairment, is one of the main causes of disability in elder people worldwide. Recently, several animal studies indicated that the 'gut-brain' axis might contribute to the amyloid deposition of AD. However, data about gut dysbiosis in human AD remains scarce in the literature, especially including the whole process of AD. In this prospective and cross-sectional study, we aimed at identifying differences in microbiome between patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD) and the normal cognition healthy controls (HC). Additionally, the potential association between IM and clinical characteristics of AD was evaluated.
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              Modified Mediterranean-ketogenic diet modulates gut microbiome and short-chain fatty acids in association with Alzheimer's disease markers in subjects with mild cognitive impairment

              Ravinder Nagpal, Bryan J. Neth, Shaohua WANG … (2019)
              Background Alzheimer's disease (AD) prevalence is increasing, but its etiology remains elusive. Gut microbes can contribute to AD pathology and may help identifying novel markers and therapies against AD. Herein, we examine how the gut microbiome differs in older adults with mild cognitive impairment compared to cognitively normal counterparts, and whether and how a modified Mediterranean-ketogenic diet (MMKD) alters the gut microbiome signature in association with cerebrospinal fluid (CSF) AD biomarkers. Methods A randomized, double-blind, cross-over, single-center pilot study of MMKD versus American Heart Association Diet (AHAD) intervention is performed on 17 subjects (age: 64.6 ± 6.4 yr), of which 11 have mild cognitive impairment, while 6 are cognitively normal. Subjects undergo MMKD and AHAD intervention for 6-weeks separated by 6-weeks washout periods. Gut microbiome, fecal short-chain fatty acids (SCFAs), and markers of AD in CSF including amyloid β (Aβ)-40 and Aß-42, total tau, and phosphorylated tau-181 (tau-p181) are measured at before and after diet interventions. Findings At baseline, subjects with normal vs. impaired cognition show no notable difference in microbiome diversity but several unique microbial signatures are detected in subjects with mild cognitive impairment. Proteobacteria correlate positively with Aβ-42: Aβ-40 while fecal propionate and butyrate correlates negatively with Aβ-42 in subjects with mild cognitive impairment. Several bacteria are differently affected by the two diets with distinct patterns between cognitively normal and impaired subjects. Notably, the abundance of Enterobacteriaceae, Akkermansia, Slackia, Christensenellaceae and Erysipelotriaceae increases while that of Bifidobacterium and Lachnobacterium reduces on MMKD, while AHAD increases Mollicutes. MMKD slightly reduces fecal lactate and acetate while increasing propionate and butyrate. Conversely, AHAD increases acetate and propionate while reducing butyrate. Interpretation The data suggest that specific gut microbial signatures may depict the mild cognitive impairment and that the MMKD can modulate the gut microbiome and metabolites in association with improved AD biomarkers in CSF.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Clin Med
                Journal ID (iso-abbrev): J Clin Med
                Journal ID (publisher-id): jcm
                Title: Journal of Clinical Medicine
                Publisher: MDPI
                ISSN (Electronic): 2077-0383
                Publication date (Electronic): 29 June 2020
                Publication date Collection: July 2020
                Volume: 9
                Issue: 7
                Electronic Location Identifier: 2042
                Affiliations
                [1 ]Department of Neurology and Institute of Neurology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; heyixiheyixi@ 123456163.com (Y.H.); libinyin@ 123456126.com (B.L.)
                [2 ]Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of the Ministry of Education, Second Military Medical University, Shanghai 200433, China; dingyasun@ 123456163.com
                Author notes
                [* ]Correspondence: chensd@ 123456rjh.com.cn
                Author information
                https://orcid.org/0000-0003-1953-382X
                Article
                Publisher ID: jcm-09-02042
                DOI: 10.3390/jcm9072042
                PMC ID: 7409059
                PubMed ID: 32610630
                SO-VID: f1cbaa59-3e3a-444d-b729-5c10337cf4dd
                Copyright © © 2020 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 30 March 2020
                Date accepted : 15 June 2020
                Categories
                Subject: Review

                Keywords: alzheimer’s disease,gut microbiota,microbiota–gut–brain axis,neurodegenerative disease,intestinal flora
                Data availability:
                Keywords: alzheimer’s disease, gut microbiota, microbiota–gut–brain axis, neurodegenerative disease, intestinal flora

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