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      Clinical Interventions in Aging (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on prevention and treatment of diseases in people over 65 years of age. Sign up for email alerts here.

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      Gut microbiota, cognitive frailty and dementia in older individuals: a systematic review

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          Abstract

          Cognitive frailty, defined as the coexistence of mild cognitive impairment symptoms and physical frailty phenotype in older persons, is increasingly considered the main geriatric condition predisposing to dementia. Recent studies have demonstrated that gut microbiota may be involved in frailty physiopathology by promoting chronic inflammation and anabolic resistance. The contribution of gut microbiota to the development of cognitive impairment and dementia is less defined, even though the concept of “gut–brain axis” has been well demonstrated for other neuropsychiatric disorders. The aim of this systematic review was to summarize the current state-of-the-art literature on the gut microbiota alterations associated with cognitive frailty, mild cognitive impairment and dementia and elucidate the effects of pre- or probiotic administration on cognitive symptom modulation in animal models of aging and human beings. We identified 47 papers with original data (31 from animal studies and 16 from human studies) suitable for inclusion according to our aims. We concluded that several observational and intervention studies performed in animal models of dementia (mainly Alzheimer’s disease) support the concept of a gut–brain regulation of cognitive symptoms. Modulation of vagal activity and bacterial synthesis of substances active on host neural metabolism, inflammation and amyloid deposition are the main mechanisms involved in this physiopathologic link. Conversely, there is a substantial lack of human data, both from observational and intervention studies, preventing to formulate any clinical recommendation on this topic. Gut microbiota modulation of cognitive function represents, however, a promising area of research for identifying novel preventive and treatment strategies against dementia.

          Most cited references70

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          Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota

          Alzheimer’s disease is the most common form of dementia in the western world, however there is no cure available for this devastating neurodegenerative disorder. Despite clinical and experimental evidence implicating the intestinal microbiota in a number of brain disorders, its impact on Alzheimer’s disease is not known. To this end we sequenced bacterial 16S rRNA from fecal samples of Aβ precursor protein (APP) transgenic mouse model and found a remarkable shift in the gut microbiota as compared to non-transgenic wild-type mice. Subsequently we generated germ-free APP transgenic mice and found a drastic reduction of cerebral Aβ amyloid pathology when compared to control mice with intestinal microbiota. Importantly, colonization of germ-free APP transgenic mice with microbiota from conventionally-raised APP transgenic mice increased cerebral Aβ pathology, while colonization with microbiota from wild-type mice was less effective in increasing cerebral Aβ levels. Our results indicate a microbial involvement in the development of Abeta amyloid pathology, and suggest that microbiota may contribute to the development of neurodegenerative diseases.
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            The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates

            Geroscience, the new interdisciplinary field that aims to understand the relationship between aging and chronic age-related diseases (ARDs) and geriatric syndromes (GSs), is based on epidemiological evidence and experimental data that aging is the major risk factor for such pathologies and assumes that aging and ARDs/GSs share a common set of basic biological mechanisms. A consequence is that the primary target of medicine is to combat aging instead of any single ARD/GSs one by one, as favored by the fragmentation into hundreds of specialties and sub-specialties. If the same molecular and cellular mechanisms underpin both aging and ARDs/GSs, a major question emerges: which is the difference, if any, between aging and ARDs/GSs? The hypothesis that ARDs and GSs such as frailty can be conceptualized as accelerated aging will be discussed by analyzing in particular frailty, sarcopenia, chronic obstructive pulmonary disease, cancer, neurodegenerative diseases such as Alzheimer and Parkinson as well as Down syndrome as an example of progeroid syndrome. According to this integrated view, aging and ARDs/GSs become part of a continuum where precise boundaries do not exist and the two extremes are represented by centenarians, who largely avoided or postponed most ARDs/GSs and are characterized by decelerated aging, and patients who suffered one or more severe ARDs in their 60s, 70s, and 80s and show signs of accelerated aging, respectively. In between these two extremes, there is a continuum of intermediate trajectories representing a sort of gray area. Thus, clinically different, classical ARDs/GSs are, indeed, the result of peculiar combinations of alterations regarding the same, limited set of basic mechanisms shared with the aging process. Whether an individual will follow a trajectory of accelerated or decelerated aging will depend on his/her genetic background interacting lifelong with environmental and lifestyle factors. If ARDs and GSs are manifestations of accelerated aging, it is urgent to identify markers capable of distinguishing between biological and chronological age to identify subjects at higher risk of developing ARDs and GSs. To this aim, we propose the use of DNA methylation, N-glycans profiling, and gut microbiota composition to complement the available disease-specific markers.
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              Brain-gut interactions in inflammatory bowel disease.

              Psycho-neuro-endocrine-immune modulation through the brain-gut axis likely has a key role in the pathogenesis of inflammatory bowel disease (IBD). The brain-gut axis involves interactions among the neural components, including (1) the autonomic nervous system, (2) the central nervous system, (3) the stress system (hypothalamic-pituitary-adrenal axis), (4) the (gastrointestinal) corticotropin-releasing factor system, and (5) the intestinal response (including the intestinal barrier, the luminal microbiota, and the intestinal immune response). Animal models suggest that the cholinergic anti-inflammatory pathway through an anti-tumor necrosis factor effect of the efferent vagus nerve could be a therapeutic target in IBD through a pharmacologic, nutritional, or neurostimulation approach. In addition, the psychophysiological vulnerability of patients with IBD, secondary to the potential presence of any mood disorders, distress, increased perceived stress, or maladaptive coping strategies, underscores the psychological needs of patients with IBD. Clinicians need to address these issues with patients because there is emerging evidence that stress or other negative psychological attributes may have an effect on the disease course. Future research may include exploration of markers of brain-gut interactions, including serum/salivary cortisol (as a marker of the hypothalamic-pituitary-adrenal axis), heart rate variability (as a marker of the sympathovagal balance), or brain imaging studies. The widespread use and potential impact of complementary and alternative medicine and the positive response to placebo (in clinical trials) is further evidence that exploring other psycho-interventions may be important therapeutic adjuncts to the conventional therapeutic approach in IBD. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Clin Interv Aging
                Clin Interv Aging
                Clinical Interventions in Aging
                Clinical Interventions in Aging
                Dove Medical Press
                1176-9092
                1178-1998
                2018
                29 August 2018
                : 13
                : 1497-1511
                Affiliations
                [1 ]Department of Medicine and Surgery, University of Parma, Parma, Italy, andrea.ticinesi@ 123456unipr.it
                [2 ]Geriatric-Rehabilitation Department, Parma University Hospital, Parma, Italy, andrea.ticinesi@ 123456unipr.it
                [3 ]Microbiome Research Hub, University of Parma, Parma, Italy, andrea.ticinesi@ 123456unipr.it
                Author notes
                Correspondence: Andrea Ticinesi, Geriatric-Rehabilitation Department, Parma University Hospital, Parma, Italy; Via Antonio Gramsci 14, Parma 43126, Italy, Tel +39 347 184 5191, Email andrea.ticinesi@ 123456unipr.it
                Article
                cia-13-1497
                10.2147/CIA.S139163
                6120508
                30214170
                5a9d8450-a176-4405-81bd-73fe3bef088c
                © 2018 Ticinesi et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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                Categories
                Review

                Health & Social care
                microbiome,alzheimer’s disease,vascular dementia,mild cognitive impairment,dysbiosis

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