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      Lactobacilli and bifidobacteria ameliorate memory and learning deficits and oxidative stress in β-amyloid (1–42) injected rats

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          Abstract

          <p class="first" id="d1652341e156">The gastrointestinal microbiota affects brain function, including memory and learning. In this study we investigated the effects of probiotics on memory and oxidative stress biomarkers in an experimental model of Alzheimer's disease. Sixty rats were randomly divided into 5 groups: control; control-probiotics, which received probiotics for 8 weeks; sham operation, which received an intrahippocampal injection of phosphate-buffered saline; Alzheimer, which received an intrahippocampal injection of β-amyloid (Aβ1-42); and Alzheimer-probiotics, which in addition to being injected with Aβ1-42, received 2 g (1 × 1010 CFU/g) of probiotics (Lactobacillus acidophilus, L. fermentum, Bifidobacterium lactis, and B. longum) for 8 weeks. Memory and learning were measured using the Morris water maze, and oxidative stress biomarkers in the hippocampus were measured using ELISA kits. Morris water maze results indicated that compared with the Alzheimer group, the Alzheimer-probiotics group had significantly improved spatial memory, including shorter escape latency and travelled distance and greater time spent in the target quadrant. There was also improvement in oxidative stress biomarkers such as increased malondialdehyde levels and superoxide dismutase activity following the β-amyloid injection. Overall, it seems that probiotics play a role in improving memory deficit and inhibiting the pathological mechanisms of Alzheimer's disease by modifying microbiota. </p>

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          Most cited references30

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          Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression.

          The concept that intestinal microbial composition not only affects the health of the gut, but also influences centrally-mediated systems involved in mood, is supported by a growing body of literature. Despite the emergent interest in brain-gut communication and its possible role in the pathogenesis of psychiatric disorders such as depression, particularly subtypes with accompanying gastrointestinal (GI) symptoms, there are few studies dedicated to the search for therapeutic solutions that address both central and peripheral facets of these illnesses. This study aims to assess the potential benefits of the probiotic Bifidobacterium infantis in the rat maternal separation (MS) model, a paradigm that has proven to be of value in the study of stress-related GI and mood disorders. MS adult rat offsprings were chronically treated with bifidobacteria or citalopram and subjected to the forced swim test (FST) to assess motivational state. Cytokine concentrations in stimulated whole blood samples, monoamine levels in the brain, and central and peripheral hypothalamic-pituitary-adrenal (HPA) axis measures were also analysed. MS reduced swim behavior and increased immobility in the FST, decreased noradrenaline (NA) content in the brain, and enhanced peripheral interleukin (IL)-6 release and amygdala corticotrophin-releasing factor mRNA levels. Probiotic treatment resulted in normalization of the immune response, reversal of behavioral deficits, and restoration of basal NA concentrations in the brainstem. These findings point to a more influential role for bifidobacteria in neural function, and suggest that probiotics may have broader therapeutic applications than previously considered. Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.
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            Microorganisms with Claimed Probiotic Properties: An Overview of Recent Literature

            Probiotics are defined as live microorganisms, which when administered in adequate amounts, confer a health benefit on the host. Health benefits have mainly been demonstrated for specific probiotic strains of the following genera: Lactobacillus, Bifidobacterium, Saccharomyces, Enterococcus, Streptococcus, Pediococcus, Leuconostoc, Bacillus, Escherichia coli. The human microbiota is getting a lot of attention today and research has already demonstrated that alteration of this microbiota may have far-reaching consequences. One of the possible routes for correcting dysbiosis is by consuming probiotics. The credibility of specific health claims of probiotics and their safety must be established through science-based clinical studies. This overview summarizes the most commonly used probiotic microorganisms and their demonstrated health claims. As probiotic properties have been shown to be strain specific, accurate identification of particular strains is also very important. On the other hand, it is also demonstrated that the use of various probiotics for immunocompromised patients or patients with a leaky gut has also yielded infections, sepsis, fungemia, bacteraemia. Although the vast majority of probiotics that are used today are generally regarded as safe and beneficial for healthy individuals, caution in selecting and monitoring of probiotics for patients is needed and complete consideration of risk-benefit ratio before prescribing is recommended.
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              Regulation of the stress response by the gut microbiota: implications for psychoneuroendocrinology.

              There is now an expanding volume of evidence to support the view that commensal organisms within the gut play a role in early programming and later responsivity of the stress system. The gut is inhabited by 10¹³-10¹⁴ micro-organisms, which is ten times the number of cells in the human body and contains 150 times as many genes as our genome. It has long been recognised that gut pathogens such as Escherichia coli, if they enter the gut can activate the HPA. However, animals raised in a germ-free environment show exaggerated HPA responses to psychological stress, which normalises with monocolonisation by certain bacterial species including Bifidobacterium infantis. Moreover, increased evidence suggests that animals treated with probiotics have a blunted HPA response. Stress induces increased permeability of the gut allowing bacteria and bacterial antigens to cross the epithelial barrier and activate a mucosal immune response, which in turn alters the composition of the microbiome and leads to enhanced HPA drive. Increasing data from patients with irritable bowel syndrome and major depression indicate that in these syndromes alteration of the HPA may be induced by increased gut permeability. In the case of irritable bowel syndrome the increased permeability can respond to probiotic therapy. Detailed prospective studies in patients with mood disorders examining the gut microbiota, immune parameters and HPA activity are required to throw further light on this emerging area. It is however clear that the gut microbiota must be taken into account when considering the factors regulating the HPA. Copyright © 2012 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Applied Physiology, Nutrition, and Metabolism
                Appl. Physiol. Nutr. Metab.
                Canadian Science Publishing
                1715-5312
                1715-5320
                July 2018
                July 2018
                : 43
                : 7
                : 718-726
                Affiliations
                [1 ]Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
                [2 ]Cellular and Molecular Research Centre and Hematology Department, School of Allied Medical Science, Iran University of Medical Sciences, Tehran, Iran.
                [3 ]Pharmaceutical Science Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
                [4 ]Faculty of Veterinary Medicine, Islamic Azad University, Garmsar Branch, Garmsar, Iran.
                [5 ]Department of Anatomy, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
                [6 ]Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
                [7 ]Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran.
                Article
                10.1139/apnm-2017-0648
                29462572
                f11ade96-5aab-4a0a-8260-6f29757301e3
                © 2018

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