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Effect of gut microbiome modulation on muscle function and cognition: the PROMOTe randomised controlled trial.
Ni Lochlainn, M, Bowyer, RCE, Moll, JM, García, MP, Wadge, S, Baleanu, AF, Nessa, A, Sheedy, A, Akdag, G, Hart, D, et al
Nature communications. 2024;15(1):1859
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Humans lose skeletal muscle with advancing age, and this can progress to sarcopenia. Dietary protein is crucial for maintaining skeletal muscle health; however, several factors can lead to reduced protein intake in older age. The aim of this study was to test whether the addition of gut microbiome modulation could augment established muscle function improvements from combined protein (branched chain amino acids [BCAA]) and resistance exercise. This study was based on the PROMOTe (effect of PRebiotic and prOtein on Muscle in Older Twins) trial which was a randomised controlled trial in which twin pairs (n= 72) were randomised, one twin to each study arm. Results showed that prebiotics improved cognition but did not impact muscle strength and function, compared with placebo. Furthermore, gut microbiome modulation via prebiotic supplementation in the context of ageing-muscle research is feasible and well tolerated, with clear responses noted in the gut microbiota composition and function. Authors concluded that cheap and readily available gut microbiome interventions hold promise for improving cognitive frailty in our ageing population.
Abstract
Studies suggest that inducing gut microbiota changes may alter both muscle physiology and cognitive behaviour. Gut microbiota may play a role in both anabolic resistance of older muscle, and cognition. In this placebo controlled double blinded randomised controlled trial of 36 twin pairs (72 individuals), aged ≥60, each twin pair are block randomised to receive either placebo or prebiotic daily for 12 weeks. Resistance exercise and branched chain amino acid (BCAA) supplementation is prescribed to all participants. Outcomes are physical function and cognition. The trial is carried out remotely using video visits, online questionnaires and cognitive testing, and posting of equipment and biological samples. The prebiotic supplement is well tolerated and results in a changed gut microbiome [e.g., increased relative Bifidobacterium abundance]. There is no significant difference between prebiotic and placebo for the primary outcome of chair rise time (β = 0.579; 95% CI -1.080-2.239 p = 0.494). The prebiotic improves cognition (factor score versus placebo (β = -0.482; 95% CI,-0.813, -0.141; p = 0.014)). Our results demonstrate that cheap and readily available gut microbiome interventions may improve cognition in our ageing population. We illustrate the feasibility of remotely delivered trials for older people, which could reduce under-representation of older people in clinical trials. ClinicalTrials.gov registration: NCT04309292.
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Probiotic intervention benefits multiple neural behaviors in older adults with mild cognitive impairment.
Fei, Y, Wang, R, Lu, J, Peng, S, Yang, S, Wang, Y, Zheng, K, Li, R, Lin, L, Li, M
Geriatric nursing (New York, N.Y.). 2023;51:167-175
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Mild cognitive impairment (MCI) is an intermediate stage between the normal cognitive changes associated with aging and dementia. Recent research shows that probiotic supplementation can regulate the balance of the intestinal flora and improve self-care ability and cognition in older adults. The aim of this study was to explore the effects and the underlying mechanisms of probiotic supplementation on MCI older adults. This study was a pilot randomised controlled trial (RCT) to investigate the effects of 12 weeks of probiotic supplementation in patients with MCI. Participants were randomly assigned to the probiotic group or control group. Results demonstrated the beneficial effects of probiotic supplementation intervention on multiple neural behaviours by regulating the homeostasis of the gut microbiota in older MCI patients. Authors conclude that this study provided new insights into nutrition interventions in older MCI patients. However, further trials with larger cohorts should be conducted to confirm the effects of probiotic intervention in MCI patients and provide more clinical evidence for its preventive and therapeutic effects.
Abstract
Probiotic supplements were shown to improve cognitive function in Alzheimer's disease (AD) patients. However, it is still unclear whether this applies to older individuals with mild cognitive impairment (MCI). We aimed to explore the effects of probiotic supplementation on multiple neural behaviors in older adults with MCI. Forty-two MCI patients (age > 60 years) were randomly divided into two groups and consumed either probiotics (n=21) or placebo (n=21) for 12 weeks. Various scale scores, gut microbiota measures and serological indicators were recorded pre- and posttreatment. After 12 weeks of intervention, cognitive function and sleep quality were improved in the probiotic group compared with those in the control group, and the underlying mechanisms were associated with changes in the intestinal microbiota. In conclusion, our study demonstrated that probiotic treatment enhanced cognitive function and sleep quality in older MCI patients, thus providing important insights into the clinical prevention and treatment of MCI.
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A Randomized, Double-Blind, Placebo-Controlled Study of an Anthocyanin-Rich Functional Ingredient on Cognitive Function and Eye Dryness in Late Adulthood Volunteers: Roles of Epigenetic and Gut Microbiome Modulations.
Wattanathorn, J, Tong-Un, T, Thukham-Mee, W, Paholpak, P, Rangseekhajee, P
Nutrients. 2023;15(16)
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The global market of functional foods targeting wellness promotion, disease risk reduction, and quality of life promotion has been increasing. Due to this demand, the development of novel functional ingredients is essential when producing new fortified foods and beverages. The aim of this study was to determine the effect of the eight-week consumption of a functional soup containing “Anthaplex” [a novel functional ingredient consisting of the extracts of purple waxy corn (Zea mays) and coloured sticky rice (Oryza sativa)] on cognitive function and eye dryness in healthy volunteers in late adulthood. This study was an 8-week, 3-arm, randomised, double-blind, placebo-controlled study. A total of 69 participants were randomly assigned to placebo, D2 (2g of Anthaplex), or D4 (4g of Anthaplex) treatment group. Results showed that “Anthaplex” can improve cognitive function and working memory together with eye dryness. Authors concluded that “Anthaplex” could be a new functional ingredient for supplements aiming to improve cognitive function and eye dryness.
Abstract
Due to the rising demand for supplements targeting cognitive enhancement and dry eye together with the health benefits of anthocyanins, we have developed a functional soup containing an anthocyanin-rich functional ingredient, or "Anthaplex," and assessed the effects on cognitive function and eye dryness together with the possible mechanisms. A total of 69 male and female health volunteers were randomized and divided into placebo, D2, and D4 groups. All subjects consumed 120 mL of placebo or functional soup containing "Anthaplex" either at 2 or 4 g per serving per day within 5 min in the morning for eight weeks. The cognitive function, working memory, dry eye, AChE, MAO, MAO-A, MAO-B, and GABA-T activities, BDNF, HAC, HDAC, and DNMT activities, pH, and amount of lactic acid-producing bacteria, particularly Lactobacillus and Bifidobacterium spp. in feces, were determined before intervention and after eight weeks of consumption. Subjects who consumed the "Anthaplex" soup had improved cognitive function, working memory, eye dryness, histone acetylation, ACh E suppression, and BDNF with increased Bifidobacterium spp. but decreased pH in feces. These data suggest that "Anthaplex" improves cognitive function and eye dryness via the modulations of the histone acetylation process, gut microbiome, and cholinergic function.
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Modulating the Gut Microbiome in Multiple Sclerosis Management: A Systematic Review of Current Interventions.
Tsogka, A, Kitsos, DK, Stavrogianni, K, Giannopapas, V, Chasiotis, A, Christouli, N, Tsivgoulis, G, Tzartos, JS, Giannopoulos, S
Journal of clinical medicine. 2023;12(24)
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Multiple sclerosis (MS) is an autoimmune disease caused by the altered immune system mistakenly attacking the central nervous system. While genetics play a leading causative role in the manifestation of this disease, other contributing environmental factors can also exist, such as a disruption in the intestinal microbial composition. Previous research has shown that the bidirectional communication between the brain's and gut's health, also known as the gut-brain axis, may contribute to the prognosis of MS. Modulating gut microbial composition can be a therapeutic strategy in MS patients to manage symptoms and prevent disease progression. This systematic review assessed different protocols for modulating gut microbial composition, including dietary modifications, probiotic use, intermittent fasting, and faecal microbial transplantation. The review included thirteen studies that compared the effects of the above gut microbial modulation intervention protocols in MS patients with healthy participants. While different dietary modification strategies improved MS symptoms, probiotic supplementations and intermittent fasting reduced inflammation, and faecal microbial transplantation showed promising positive effects in a few reports. Due to the methodological limitations of the included studies, further robust studies are required to evaluate the beneficial effects of gut microbial modulation strategies in reducing the symptoms of MS patients. However, healthcare professionals can use the results of this study to understand the benefits of gut microbial modulation in MS patients.
Abstract
This review attempted to explore all recent clinical studies that have investigated the clinical and autoimmune impact of gut microbiota interventions in multiple sclerosis (MS), including dietary protocols, probiotics, fecal microbiota transplantation (FMT), and intermittent fasting (IF). Methods: Thirteen studies were held between 2011 and 2023 this demonstrated interventions in gut microbiome among patients with MS and their impact the clinical parameters of the disease. These included specialized dietary interventions, the supply of probiotic mixtures, FMT, and IF. Results: Dietary interventions positively affected various aspects of MS, including relapse rates, EDSS disability scores, MS-related fatigue, and metabolic features. Probiotic mixtures showed promising results on MS-related fatigue, EDSS parameters, inflammation; meanwhile, FMT-though a limited number of studies was included-indicated some clinical improvement in similar variables. IF showed reductions in EDSS scores and significant improvement in patients' emotional statuses. Conclusions: In dietary protocols, clinical MS parameters, including relapse rate, EDSS, MFIS, FSS, and MSQoL54 scales, were significantly improved through the application of a specific diet each time. Probiotic nutritional mixtures promote a shift in inflammation towards an anti-inflammatory cytokine profile in patients with MS. The administration of such mixtures affected disability, mood levels, and quality of life among patients with MS. FMT protocols possibly demonstrate a therapeutic effect in some case reports. IF protocols were found to ameliorate EDSS and FAMS scores. All interventional means of gut microbiome modulation provided significant conclusions on several clinical aspects of MS and highlight the complexity in the relationship between MS and the gut microbiome.
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Clinical, gut microbial and neural effects of a probiotic add-on therapy in depressed patients: a randomized controlled trial.
Schaub, AC, Schneider, E, Vazquez-Castellanos, JF, Schweinfurth, N, Kettelhack, C, Doll, JPK, Yamanbaeva, G, Mählmann, L, Brand, S, Beglinger, C, et al
Translational psychiatry. 2022;12(1):227
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Major depressive disorder (MDD) is one of the most prevalent and burdensome psychiatric disorders. Compelling preclinical data indicate that the gut microbiota affects brain functions and depressive behaviour, providing a promising novel target for the treatment of depression. The aims of this study were to (i) examine the effect of a short-term, high-dose probiotic add-on therapy on depressive symptoms in MDD patients, and (ii) explore the effects of a probiotic supplementation on gut microbiota composition as well as brain structure and function. This study was a double-blind randomised controlled trial of a probiotic add-on therapy for four weeks in depressed patients. Patients (n=60) were randomly allocated to the two study groups and tested at three different time points. Results showed that an add-on probiotic treatment improves depressive symptoms and maintains healthy enterotypes, species richness and increases specific health related bacterial taxa. Furthermore, on a neural level, probiotics altered negative biases and emotional valence additionally to treatment-as-usual for depression. Authors conclude that their findings highlight the role of the microbiota-gut-brain axis in MDD and emphasises the potential of microbiota-related treatment approaches as therapies to improve the effectiveness of current treatments in depression.
Abstract
A promising new treatment approach for major depressive disorder (MDD) targets the microbiota-gut-brain (MGB) axis, which is linked to physiological and behavioral functions affected in MDD. This is the first randomized controlled trial to determine whether short-term, high-dose probiotic supplementation reduces depressive symptoms along with gut microbial and neural changes in depressed patients. Patients with current depressive episodes took either a multi-strain probiotic supplement or placebo over 31 days additionally to treatment-as-usual. Assessments took place before, immediately after and again four weeks after the intervention. The Hamilton Depression Rating Sale (HAM-D) was assessed as primary outcome. Quantitative microbiome profiling and neuroimaging was used to detect changes along the MGB axis. In the sample that completed the intervention (probiotics N = 21, placebo N = 26), HAM-D scores decreased over time and interactions between time and group indicated a stronger decrease in the probiotics relative to the placebo group. Probiotics maintained microbial diversity and increased the abundance of the genus Lactobacillus, indicating the effectivity of the probiotics to increase specific taxa. The increase of the Lactobacillus was associated with decreased depressive symptoms in the probiotics group. Finally, putamen activation in response to neutral faces was significantly decreased after the probiotic intervention. Our data imply that an add-on probiotic treatment ameliorates depressive symptoms (HAM-D) along with changes in the gut microbiota and brain, which highlights the role of the MGB axis in MDD and emphasizes the potential of microbiota-related treatment approaches as accessible, pragmatic, and non-stigmatizing therapies in MDD. Trial Registration: www.clinicaltrials.gov , identifier: NCT02957591.
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Serotonin Reuptake Inhibitors and the Gut Microbiome: Significance of the Gut Microbiome in Relation to Mechanism of Action, Treatment Response, Side Effects, and Tachyphylaxis.
Sjöstedt, P, Enander, J, Isung, J
Frontiers in psychiatry. 2021;12:682868
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In preceding centuries common thought was that psychiatric disorders originated from the gut. In later years this concept was replaced by the idea of it being a disorder of the brain and that an imbalance of neurotransmitters is the cause of depression and other psychiatric conditions (monoamine hypothesis). This theory has been dominating psychiatric research for the past decades, and selective serotonin reuptake inhibitors (SSRIs) have become a widespread treatment option for psychological disorders. Despite their benefits, their use also presents clinical challenges such as treatment resistance, side effects or loss of effect. Consequently, the monoamine hypothesis has become disputed with other pathophysiological mechanisms having been proposed in recent years. With an appreciation of the pathophysiological complexities, this opinion-based article sought to present alternate views and to suggest areas for future research regarding psychiatric disorders, SSRIs and the gut-brain axis. The gut-brain axis has complex communication and signalling pathways in essence, the gut microbiome can exert significant effects on emotions, behaviours, metabolic risks, and the metabolism of drugs. Nerve cells of the gut also generate substantial amounts of serotonin for use within the gut. Equally, the gut microbiome produces and uses serotonin. It appears that some of the side effects associated with SSRIs, such as weight gain, are mediated via the gut microbiome. Further evidence suggests that SSRIs and several other psychotropic drugs exert antimicrobial action, which can alter the balance and integrity of the gut microbiome. Therefore, it would be valuable to further investigate the impact of long-term SSRI use on the microbial constellation in the gut and whether certain microbiome patterns could help predict treatment responsiveness or side effects, that may be manageable via microbiome manipulation. The authors believe that an advanced understanding of the dynamics of the gut microbiome could provide better and personalized treatment options for mental health conditions. This article provides a brief insight into current thoughts and theories of psychiatric disorders, SSRIs and the gut.
Abstract
The monoamine hypothesis of psychopharmacology has been dominating the biological psychiatric research field for decades. Currently psychiatric research has increasingly appreciated psychiatric disorders and suicidal behavior as being highly complex and multi-etiological. In this pathway the gut microbiome and its interrelationship with the brain is gaining traction. The usage of selective serotonin reuptake inhibitors (SSRIs) is increasing in the general population. This is due to their effect on a broad range of psychiatric disorders, and their favorable side effect profile. Still, there are enigmatic aspects about SSRIs, such as the difficulty to predict effect in individual patients, inter-individual differences in side effect, tachyphylaxis (a sudden loss of response to a certain drug), and to date, uncertainties on how they exert their clinical effect. A majority of the serotonin in the human body is produced within the gut, and SSRIs affect enteric neurons. They also exhibit antimicrobial properties that comes with the potential of disrupting microbial hemostasis. We propose that the role of the gut-brain axis and the gut microbiome in relation to psychopharmacology should be more highlighted. With this article, together with similar articles, we would like to provide a hypothetical framework for future studies within this field. We believe that this would have the potential to provide a paradigm shift within the field of psychopharmacology, and result in findings that potentially could contribute to the development of a more personalized and tailored treatment.
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Exploring the Role and Potential of Probiotics in the Field of Mental Health: Major Depressive Disorder.
Johnson, D, Thurairajasingam, S, Letchumanan, V, Chan, KG, Lee, LH
Nutrients. 2021;13(5)
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A bi-directional communication between the brain and the microbiome of the gut may exist, known as the microbiome-gut-brain axis (MGBA). The role of this and the use of probiotics in relation to many psychiatric and neurological disorders is being increasingly researched. This review aimed to summarise the research on the use of probiotics for the treatment of mental health disorders and major depressive disorder (MDD). Probiotics and their use were summarised concluding that they have a diverse range of health benefits due to their anti-inflammatory, antipathogenic and antimicrobial actions. Imbalances in the four major phyla of gut bacteria; Bacteroidetes, Firmicutes, Proteobacteria and Actinobacteria may have a major role in the development of MDD. Probiotics may have several mechanisms through which they benefit MDD and decreased inflammation in the brain, increased production of chemicals involved in brain signalling and decreased stress hormones, were all implicated. It was concluded that probiotics have mental health benefits, however gaps in the evidence from studies needs to be addressed. This study could be used by healthcare professionals to understand the role of probiotics in the treatment of mental health disorders and in particular MDD.
Abstract
The field of probiotic has been exponentially expanding over the recent decades with a more therapeutic-centered research. Probiotics mediated microbiota modulation within the microbiota-gut-brain axis (MGBA) have been proven to be beneficial in various health domains through pre-clinical and clinical studies. In the context of mental health, although probiotic research is still in its infancy stage, the promising role and potential of probiotics in various mental disorders demonstrated via in-vivo and in-vitro studies have laid a strong foundation for translating preclinical models to humans. The exploration of the therapeutic role and potential of probiotics in major depressive disorder (MDD) is an extremely noteworthy field of research. The possible etio-pathological mechanisms of depression involving inflammation, neurotransmitters, the hypothalamic-pituitary-adrenal (HPA) axis and epigenetic mechanisms potentially benefit from probiotic intervention. Probiotics, both as an adjunct to antidepressants or a stand-alone intervention, have a beneficial role and potential in mitigating anti-depressive effects, and confers some advantages compared to conventional treatments of depression using anti-depressants.
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Effects of Probiotics on Anxiety, Stress, Mood and Fitness of Badminton Players.
Salleh, RM, Kuan, G, Aziz, MNA, Rahim, MRA, Rahayu, T, Sulaiman, S, Kusuma, DWY, Adikari, AMGCP, Razam, MSM, Radhakrishnan, AK, et al
Nutrients. 2021;13(6)
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Exercise has been shown to improve fitness, wellbeing, and health. However, strenuous exercise may be detrimental physiologically, as well as affecting psychological health. The aim of this study was to determine the effects of daily probiotic supplementation on anxiety, stress, mood and fitness levels among competitive badminton players. This study was a randomised, placebo-controlled study. Recruited participants (n=30) were randomly divided into the probiotic group and the control group. The participants were given treatments for six weeks without altering the training schedule of the athletes. Results showed that stress and anxiety in badminton players could be alleviated with the daily consumption of probiotics for six weeks. Additionally, probiotics supplementation increased aerobic capacity. Authors conclude that probiotic supplements could be beneficial for athletes to enhance their mental state and physical performance. Thus, probiotic supplementation that may influence the regulation of pathways (neuro-endocrine) and mechanism of action in response to physical and psychological stressors encountered by badminton players should further studied.
Abstract
BACKGROUND Reports of probiotic consumption on athletes' performance are debatable due to their equivocal results. There is a need for more evidence on the effects of probiotic intake on psychological state and fitness level. Thus, this study determined the effects of daily probiotic consumption on competitive anxiety, perceived stress and mood among university badminton players, besides their fitness like aerobic capacity, strength, speed, leg power and agility. METHODS Thirty university badminton players aged from 19 to 22 years old were randomly divided equally into two groups, where the probiotic group (PG; n = 15) received a drink that contained Lactobacillus casei Shirota (3 × 1010 CFU) and placebo group (CG; n = 15) a placebo drink for six weeks. Anxiety, stress and mood levels were determined using the CSAI-2R, PSS and BRUMS questionnaires, respectively. Fitness levels were measured using by subjecting the players to 20-m shuttle runs (aerobic capacity), handgrips (muscular strength), vertical jumps (leg power), 40-m dash (speed) and T-test (agility). The Student's t-test (p < 0.05) was used to determine the differences between PG and CG players. RESULTS After six weeks, the anxiety and stress levels of PG players significantly decreased by 16% (p < 0.001) and 20% (p < 0.001), respectively, but there were no significant changes detected in CG players. Supplementation of probiotics also improved aerobic capacity in PG players by 5.9% (p < 0.001) but did not influence the speed, strength, leg power and agility. CONCLUSIONS Probiotics supplementation showed improved aerobic capacity and relieve anxiety and stress. However, further studies need to be carried out to determine the mechanisms through which probiotic intake produces these effects.
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Harnessing the Power of Microbiome Assessment Tools as Part of Neuroprotective Nutrition and Lifestyle Medicine Interventions.
Toribio-Mateas, M
Microorganisms. 2018;6(2)
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This is a practical review written by a clinician for other clinicians. It draws from an extensive body of evidence on the links between the gut microbes (bacteria amongst them), called the microbiota, both in health and in a variety of human diseases. The author, who is also a researcher in the communication between the gut and the brain (the gut-brain axis), focuses on the translation of science into simple clinical applications that result in measurable health outcomes, and in particular in neurodegenerative conditions such as Alzheimer's and Parkinson's, but also other less well studied such as Chronic Fatigue Syndrome (CFS). The paper also covers mental health / mood conditions such as anxiety, and depression. Practitioners who work in the area of gut health and use stool tests to assess various imbalances their patients may be experiencing will get the most out this paper. The author takes a look at the physiological processes that influence gastrointestinal as well as brain health and discusses how tools such as the characterisation or "mapping" of commensal bacteria (the bacteria that lives inside our guts normally), along with the identification of potential opportunistic and pathogenic bacteria and parasites, together with knowledge of molecules such as short chain fatty acids or zonulin can enable better clinical decision making by nutrition and lifestyle medicine practitioners. The paper also includes a valuable discussion on patient-reported outcome measures (PROMs), and particularly on the use of MYMOP by practitioners as a validated tool to collect insight from exposure to real world data in clinical practice.
Abstract
An extensive body of evidence documents the importance of the gut microbiome both in health and in a variety of human diseases. Cell and animal studies describing this relationship abound, whilst clinical studies exploring the associations between changes in gut microbiota and the corresponding metabolites with neurodegeneration in the human brain have only begun to emerge more recently. Further, the findings of such studies are often difficult to translate into simple clinical applications that result in measurable health outcomes. The purpose of this paper is to appraise the literature on a select set of faecal biomarkers from a clinician’s perspective. This practical review aims to examine key physiological processes that influence both gastrointestinal, as well as brain health, and to discuss how tools such as the characterisation of commensal bacteria, the identification of potential opportunistic, pathogenic and parasitic organisms and the quantification of gut microbiome biomarkers and metabolites can help inform clinical decisions of nutrition and lifestyle medicine practitioners.
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Gut microbiome alterations in Alzheimer's disease.
Vogt, NM, Kerby, RL, Dill-McFarland, KA, Harding, SJ, Merluzzi, AP, Johnson, SC, Carlsson, CM, Asthana, S, Zetterberg, H, Blennow, K, et al
Scientific reports. 2017;7(1):13537
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Research into what causes Alzheimer’s Disease (AD) is on-going, including a proposal for a potential role of human bacterial profiles. This cross-sectional study of 25 patients diagnosed with AD and 25 individuals with no AD diagnosis (matched for age, sex, ethnicity, BMI and diabetes status) aimed to compare the gut microbiome between AD and non-AD states using faecal samples. The researchers found that the gut microbiome of the AD patients was less diverse and compositionally distinct from the age-matched control group. In particular, the AD group had decreased Firmicutes and Bifidobacterium and increased Bacteriodetes compared with control. This small study suggests therefore that the gut microbiome may be a target for therapeutic manipulation when working with patients with AD.
Abstract
Alzheimer's disease (AD) is the most common form of dementia. However, the etiopathogenesis of this devastating disease is not fully understood. Recent studies in rodents suggest that alterations in the gut microbiome may contribute to amyloid deposition, yet the microbial communities associated with AD have not been characterized in humans. Towards this end, we characterized the bacterial taxonomic composition of fecal samples from participants with and without a diagnosis of dementia due to AD. Our analyses revealed that the gut microbiome of AD participants has decreased microbial diversity and is compositionally distinct from control age- and sex-matched individuals. We identified phylum- through genus-wide differences in bacterial abundance including decreased Firmicutes, increased Bacteroidetes, and decreased Bifidobacterium in the microbiome of AD participants. Furthermore, we observed correlations between levels of differentially abundant genera and cerebrospinal fluid (CSF) biomarkers of AD. These findings add AD to the growing list of diseases associated with gut microbial alterations, as well as suggest that gut bacterial communities may be a target for therapeutic intervention.