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Targeting the microbiome-gut-brain axis for improving cognition in schizophrenia and major mood disorders: A narrative review.
Bioque, M, González-Rodríguez, A, Garcia-Rizo, C, Cobo, J, Monreal, JA, Usall, J, Soria, V, , , Labad, J
Progress in neuro-psychopharmacology & biological psychiatry. 2021;:110130
Abstract
Cognitive impairment has been consistently found to be a core feature of serious mental illnesses such as schizophrenia and major mood disorders (major depression and bipolar disorder). In recent years, a great effort has been made in elucidating the biological causes of cognitive deficits and the search for new biomarkers of cognition. Microbiome and gut-brain axis (MGB) hormones have been postulated to be potential biomarkers of cognition in serious mental illnesses. The main aim of this review was to synthesize current evidence on the association of microbiome and gut-brain hormones on cognitive processes in schizophrenia and major mood disorders and the association of MGB hormones with stress and the immune system. Our review underscores the role of the MGB axis on cognitive aspects of serious mental illnesses with the potential use of agents targeting the gut microbiota as cognitive enhancers. However, the current evidence for clinical trials focused on the MGB axis as cognitive enhancers in these clinical populations is scarce. Future clinical trials using probiotics, prebiotics, antibiotics, or faecal microbiota transplantation need to consider potential mechanistic pathways such as the HPA axis, the immune system, or gut-brain axis hormones involved in appetite control and energy homeostasis.
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Going with the grain: Fiber, cognition, and the microbiota-gut-brain-axis.
Berding, K, Carbia, C, Cryan, JF
Experimental biology and medicine (Maywood, N.J.). 2021;(7):796-811
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Abstract
Healthy dietary intake has been acknowledged for decades as one of the main contributors to health. More recently, the field of nutritional psychiatry has progressed our understanding regarding the importance of nutrition in supporting mental health and cognitive function. Thereby, individual nutrients, including omega-3 fatty acids and polyphenols, have been recognized to be key drivers in this relationship. With the progress in appreciating the influence of dietary fiber on health, increasingly research is focusing on deciphering its role in brain processes. However, while the importance of dietary fiber in gastrointestinal and metabolic health is well established, leading to the development of associated health claims, the evidence is not conclusive enough to support similar claims regarding cognitive function. Albeit the increasing knowledge of the impact of dietary fiber on mental health, only a few human studies have begun to shed light onto the underexplored connection between dietary fiber and cognition. Moreover, the microbiota-gut-brain axis has emerged as a key conduit for the effects of nutrition on the brain, especially fibers, that are acted on by specific bacteria to produce a variety of health-promoting metabolites. These metabolites (including short chain fatty acids) as well as the vagus nerve, the immune system, gut hormones, or the kynurenine pathway have been proposed as underlying mechanisms of the microbiota-brain crosstalk. In this minireview, we summarize the evidence available from human studies on the association between dietary fiber intake and cognitive function. We provide an overview of potential underlying mechanisms and discuss remaining questions that need to be answered in future studies. While this field is moving at a fast pace and holds promise for future important discoveries, especially data from human cohorts are required to further our understanding and drive the development of public health recommendations regarding dietary fiber in brain health.
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A systematic review of existing peripheral biomarkers of cognitive aging: Is there enough evidence for biomarker proxies in behavioral modification interventions?: An initiative in association with the nutrition, exercise and lifestyle team of the Canadian Consortium on Neurodegeneration in Aging.
Fiocco, AJ, Krieger, L, D'Amico, D, Parrott, MD, Laurin, D, Gaudreau, P, Greenwood, C, Ferland, G
Ageing research reviews. 2019;:72-119
Abstract
Peripheral biomarkers have shown significant value in predicting brain health and may serve as a useful proxy measurement in the assessment of evidence-based lifestyle behavior modification programs, including physical activity and nutrition programs, that aim to maintain cognitive function in late life. The aim of this systematic review was to elucidate which peripheral biomarkers are robustly associated with cognitive function among relatively healthy non-demented older adults. Following the standards for systematic reviews (PICO, PRIMSA), and employing MEDLINE and Scopus search engines, 222 articles were included in the review. Based on the review of biomarker proxies of cognitive health, it is recommended that a comprehensive biomarker panel, or biomarker signature, be developed as a clinical end point for behavior modification trials aimed at enhancing cognitive function in late life. The biomarker signature should take a multisystemic approach, including lipid, immune/inflammatory, and metabolic biomarkers in the biological signature index of cognitive health.
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Effect of High-Fat Diets on Oxidative Stress, Cellular Inflammatory Response and Cognitive Function.
Tan, BL, Norhaizan, ME
Nutrients. 2019;(11)
Abstract
Cognitive dysfunction is linked to chronic low-grade inflammatory stress that contributes to cell-mediated immunity in creating an oxidative environment. Food is a vitally important energy source; it affects brain function and provides direct energy. Several studies have indicated that high-fat consumption causes overproduction of circulating free fatty acids and systemic inflammation. Immune cells, free fatty acids, and circulating cytokines reach the hypothalamus and initiate local inflammation through processes such as microglial proliferation. Therefore, the role of high-fat diet (HFD) in promoting oxidative stress and neurodegeneration is worthy of further discussion. Of particular interest in this article, we highlight the associations and molecular mechanisms of HFD in the modulation of inflammation and cognitive deficits. Taken together, a better understanding of the role of oxidative stress in cognitive impairment following HFD consumption would provide a useful approach for the prevention of cognitive dysfunction.
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Cognitive Function and the Microbiome.
Gareau, MG
International review of neurobiology. 2016;:227-246
Abstract
There is increasing evidence that the composition of the resident bacteria within the gastrointestinal tract can influence the brain and behavior, particularly with respect to cognitive function. Cognitive function encompasses the life-long process of learning, both long- and short-term processes. Cognition was originally thought to be exclusively regulated by the central nervous system, with long-term potentiation and neurogenesis contributing to the creation and storage of memories, but now other systems, including, for example, the immune system and the intestinal microbiome may also be involved. Cognitive impairment has been identified in numerous disease states, both gastrointestinal and extraintestinal in nature, many of which have also been characterized as having a role for dysbiosis in disease pathogenesis. This includes, but is not limited to, inflammatory bowel diseases, irritable bowel syndrome, type 1 diabetes, obesity, major depressive disorder, and autism spectrum disorder. The role of cognition and the microbiome will be discussed in this chapter for all these diseases, as well as evidence for a role in maintaining overall human health and well being. Finally, evidence for a role for probiotics in beneficially modulating the microbiota and leading to improved cognition will be discussed.
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A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood.
Steenbergen, L, Sellaro, R, van Hemert, S, Bosch, JA, Colzato, LS
Brain, behavior, and immunity. 2015;:258-64
Abstract
BACKGROUND Recent insights into the role of the human microbiota in cognitive and affective functioning have led to the hypothesis that probiotic supplementation may act as an adjuvant strategy to ameliorate or prevent depression. OBJECTIVE Heightened cognitive reactivity to normal, transient changes in sad mood is an established marker of vulnerability to depression and is considered an important target for interventions. The present study aimed to test if a multispecies probiotic containing Bifidobacterium bifidum W23, Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Lactobacillus brevis W63, Lactobacillus casei W56, Lactobacillus salivarius W24, and Lactococcus lactis (W19 and W58) may reduce cognitive reactivity in non-depressed individuals. DESIGN In a triple-blind, placebo-controlled, randomized, pre- and post-intervention assessment design, 20 healthy participants without current mood disorder received a 4-week probiotic food-supplement intervention with the multispecies probiotics, while 20 control participants received an inert placebo for the same period. In the pre- and post-intervention assessment, cognitive reactivity to sad mood was assessed using the revised Leiden index of depression sensitivity scale. RESULTS Compared to participants who received the placebo intervention, participants who received the 4-week multispecies probiotics intervention showed a significantly reduced overall cognitive reactivity to sad mood, which was largely accounted for by reduced rumination and aggressive thoughts. CONCLUSION These results provide the first evidence that the intake of probiotics may help reduce negative thoughts associated with sad mood. Probiotics supplementation warrants further research as a potential preventive strategy for depression.
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Two strategies for response to 14 °C cold-water immersion: is there a difference in the response of motor, cognitive, immune and stress markers?
Brazaitis, M, Eimantas, N, Daniuseviciute, L, Mickeviciene, D, Steponaviciute, R, Skurvydas, A
PloS one. 2014;(9):e109020
Abstract
Here, we address the question of why some people have a greater chance of surviving and/or better resistance to cold-related-injuries in prolonged exposure to acute cold environments than do others, despite similar physical characteristics. The main aim of this study was to compare physiological and psychological reactions between people who exhibited fast cooling (FC; n = 20) or slow cooling (SC; n = 20) responses to cold water immersion. Individuals in whom the T(re) decreased to a set point of 35.5 °C before the end of the 170-min cooling time were indicated as the FC group; individuals in whom the T(re) did not decrease to the set point of 35.5 °C before the end of the 170-min cooling time were classified as the SC group. Cold stress was induced using intermittent immersion in bath water at 14 °C. Motor (spinal and supraspinal reflexes, voluntary and electrically induced skeletal muscle contraction force) and cognitive (executive function, short term memory, short term spatial recognition) performance, immune variables (neutrophils, leucocytes, lymphocytes, monocytes, IL-6, TNF-α), markers of hypothalamic-pituitary-adrenal axis activity (cortisol, corticosterone) and autonomic nervous system activity (epinephrine, norepinephrine) were monitored. The data obtained in this study suggest that the response of the FC group to cooling vs the SC group response was more likely an insulative-hypothermic response and that the SC vs the FC group displayed a metabolic-insulative response. The observations that an exposure time to 14 °C cold water--which was nearly twice as short (96-min vs 170-min) with a greater rectal temperature decrease (35.5 °C vs 36.2 °C) in the FC group compared with the SC group--induces similar responses of motor, cognitive, and blood stress markers were novel. The most important finding is that subjects with a lower cold-strain-index (SC group) showed stimulation of some markers of innate immunity and suppression of markers of specific immunity.
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The role of extended-release niacin on immune activation and neurocognition in HIV-infected patients treated with antiretroviral therapy - CTN PT006: study protocol for a randomized controlled trial.
Lebouché, B, Jenabian, MA, Singer, J, Graziani, GM, Engler, K, Trottier, B, Thomas, R, Brouillette, MJ, Routy, JP
Trials. 2014;:390
Abstract
BACKGROUND Approximately 30% of HIV-1-infected patients receiving antiretroviral therapy who achieve virologic control have unsatisfactory immune reconstitution, with CD4+ T-cell counts persistently below 350 cells/μL. These patients are at elevated risk for clinical progression to AIDS and non-AIDS events. CD4+ T-cell depletion following infection and persistent immune activation can partially explain this low CD4+ T-cell recovery. Recent data suggest a link between the tryptophan oxidation pathway, immune activation and HIV disease progression based on overstimulation of the tryptophan oxidation pathway by HIV antigens and by interferon-gamma. This overstimulation reduces levels of circulating tryptophan, resulting in inflammation which has been implicated in the development of neurocognitive dysfunction. Niacin (vitamin B3) is able to control the excess tryptophan oxidation, correcting tryptophan depletion, and therefore represents an interesting strategy to improve CD4 recovery.We aim to design a crossover proof-of-concept study to assess supplementation with an extended-release form of niacin (Niaspan FCT™) in combination with antiretroviral therapy, compared to antiretroviral therapy alone, on T-cell immune activation as defined by changes in the percentage of CD8+ CD38+ HLA-DR+ T-cells. METHODS/DESIGN This randomized, open-label, interventional crossover study with an immediate versus deferred use of Niaspan FCT for 24 weeks will assess its ability to reduce immune activation and thus increase CD4 recovery in 20 HIV-infected individuals with suboptimal immune responses despite sustained virologic suppression. A substudy evaluating neurocognitive function will also be conducted. DISCUSSION This randomized trial will provide an opportunity to evaluate the potential benefit of oral extended-release niacin, a drug that can indirectly increase tryptophan, to reduce immune activation and in turn increase CD4+ T-cell recovery. The study will also allow for the evaluation of the impact of Niaspan FCT on neurocognitive function in HIV-infected individuals with suboptimal immune responses despite sustained virologic suppression. TRIAL REGISTRATION This study was registered with ClinicalTrials.gov on 17 December 2013 (registration number: NCT02018965).
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Oral zinc supplementation may improve cognitive function in schoolchildren.
de Moura, JE, de Moura, EN, Alves, CX, Vale, SH, Dantas, MM, Silva, Ade A, Almeida, Md, Leite, LD, Brandão-Neto, J
Biological trace element research. 2013;(1):23-8
Abstract
Zinc is an important micronutrient for humans, and zinc deficiency among schoolchildren is deleterious to growth and development, immune competence, and cognitive function. However, the effect of zinc supplementation on cognitive function remains poorly understood. The purpose of our study was to evaluate the effect of oral zinc supplementation (5 mg Zn/day for 3 months) on the Full Scale Intelligence Quotient (FSIQ), Verbal Intelligence Quotient (VIQ), and Performance Intelligence Quotient (PIQ) using a Wechsler Intelligence Scale for Children (WISC-III). We studied 36 schoolchildren aged 6 to 9 years (7.8 ± 1.1) using a nonprobability sampling method. The baseline serum zinc concentrations increased significantly after zinc supplementation (p < 0.0001), with no difference between sexes. Tests were administered under basal conditions before and after zinc supplementation, and there was no difference in FSIQ according to gender or age. The results demonstrated that zinc improved the VIQ only in the Information Subtest (p = 0.009), although the supplementation effects were more significant in relation to the PIQ, as these scores improved for the Picture Completion, Picture Arrangement, Block Design, and Object Assembly Subtests (p = 0.0001, for all subtests). In conclusion, zinc supplementation improved specific cognitive abilities, thereby positively influencing the academic performance of schoolchildren, even those without marginal zinc deficiency.
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The impact of inflammation on cognitive function in older adults: implications for healthcare practice and research.
Sartori, AC, Vance, DE, Slater, LZ, Crowe, M
The Journal of neuroscience nursing : journal of the American Association of Neuroscience Nurses. 2012;(4):206-17
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Accumulating evidence suggests that levels of inflammation, an immune response, increase with age throughout the body and the brain. The effects of inflammation on the brain, both acute and chronic, have been associated with cognitive decline and risk of dementia in older adults. Factors believed to increase inflammation include certain health-related behaviors, such as smoking, poor diet, and inactivity as well as health conditions like diabetes, hypertension, and chronic obstructive pulmonary disease, most of which require medical intervention and monitoring. As such, nurses and healthcare professionals are likely to encounter patients who are at a high risk for future development of inflammation-related cognitive decline. A review of inflammatory processes and their relation to cognitive function in older adults is provided, along with factors that may increase or reduce inflammation. Implications for practice and research are discussed.