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The gut microbiome in human neurological disease: A review. Tremlett Helen,Bauer Kylynda C,Appel-Cresswell Silke,Finlay Brett B,Waubant Emmanuelle Annals of neurology Almost half the cells and 1% of the unique genes found in our bodies are human, the rest are from microbes, predominantly bacteria, archaea, fungi, and viruses. These microorganisms collectively form the human microbiota, with most colonizing the gut. Recent technological advances, open access data libraries, and application of high-throughput sequencing have allowed these microbes to be identified and their contribution to neurological health to be examined. Emerging evidence links perturbations in the gut microbiota to neurological disease, including disease risk, activity, and progression. This review provides an overview of the recent advances in microbiome research in relation to neuro(auto)immune and neurodegenerative conditions affecting humans, such as multiple sclerosis, neuromyelitis optica spectrum disorders, Parkinson disease, Alzheimer disease, Huntington disease, and amyotrophic lateral sclerosis. Study design and terminology used in this rapidly evolving, highly multidisciplinary field are summarized to empower and engage the neurology community in this "newly discovered organ." Ann Neurol 2017;81:369-382. 10.1002/ana.24901
Brain Structure and Response to Emotional Stimuli as Related to Gut Microbial Profiles in Healthy Women. Tillisch Kirsten,Mayer Emeran A,Gupta Arpana,Gill Zafar,Brazeilles Rémi,Le Nevé Boris,van Hylckama Vlieg Johan E T,Guyonnet Denis,Derrien Muriel,Labus Jennifer S Psychosomatic medicine OBJECTIVE:Brain-gut-microbiota interactions may play an important role in human health and behavior. Although rodent models have demonstrated effects of the gut microbiota on emotional, nociceptive, and social behaviors, there is little translational human evidence to date. In this study, we identify brain and behavioral characteristics of healthy women clustered by gut microbiota profiles. METHODS:Forty women supplied fecal samples for 16S rRNA profiling. Microbial clusters were identified using Partitioning Around Medoids. Functional magnetic resonance imaging was acquired. Microbiota-based group differences were analyzed in response to affective images. Structural and diffusion tensor imaging provided gray matter metrics (volume, cortical thickness, mean curvature, surface area) as well as fiber density between regions. A sparse Partial Least Square-Discrimination Analysis was applied to discriminate microbiota clusters using white and gray matter metrics. RESULTS:Two bacterial genus-based clusters were identified, one with greater Bacteroides abundance (n = 33) and one with greater Prevotella abundance (n = 7). The Prevotella group showed less hippocampal activity viewing negative valences images. White and gray matter imaging discriminated the two clusters, with accuracy of 66.7% and 87.2%, respectively. The Prevotella cluster was associated with differences in emotional, attentional, and sensory processing regions. For gray matter, the Bacteroides cluster showed greater prominence in the cerebellum, frontal regions, and the hippocampus. CONCLUSIONS:These results support the concept of brain-gut-microbiota interactions in healthy humans. Further examination of the interaction between gut microbes, brain, and affect in humans is needed to inform preclinical reports that microbial modulation may affect mood and behavior. 10.1097/PSY.0000000000000493
Refractory diet-dependent changes in neural microstructure: Implications for microstructural endophenotypes of neurologic and psychiatric disease. Magnetic resonance imaging Alterations in gut microbiome populations via dietary manipulation have been shown to induce diet-dependent changes in white matter microstructure. The purpose of this study is to examine the durability of these diet-induced microstructural alterations. We implemented a crossover experimental design where post-weaned male rats were assigned to one of four experimental diets. Following the administration of experimental diets and again following crossover and resumption of a normal diet, brains were imaged ex-vivo with diffusion tensor imaging. Following standard image preprocessing, tract-based spatial statistics and region-of-interest measurements were then calculated for all diffusion tensor indices. Voxel-wise differences in FA were identified in the high fat diet group when compared to animals receiving a control diet. Following crossover, there were new voxel-wise changes in both FA and TR that do not correspond to the regions previously identified. Animals crossed over from the high fiber diet demonstrate widespread and global changes in the diffusion tensor that stand in stark contrast to the minimal changes identified before crossover. While no significant differences between any of the diffusion metrics were identified in the high protein group before crossover, statistically significant decreased RD values were observed following resumption of a normal diet. Diet-induced changes in neural microstructure are durable changes that are unrecoverable following the resumption of a normal diet. We further show that in certain experimental diets, resumption of a normal diet can lead to further marked and unanticipated changes in white matter microstructure. 10.1016/j.mri.2019.02.006
The Gut Microbiome as a Component of the Gut-Brain Axis in Cognitive Health. Gao Wen,Baumgartel Kelley L,Alexander Sheila A Biological research for nursing INTRODUCTION:The human microbiome, the microorganisms living in and on the body, plays a vital role in brain physiology and pathophysiology. The gut microbiome (GMB) has been identified as a link in the gut-brain axis moderating cognitive development and health. OBJECTIVES:The objectives of this scoping review are to discuss mechanisms of the microbiome-gut-brain axis in cognition, review the existing literature on the GMB and cognition, and discuss implications for nursing research. METHODS:We searched Pubmed using the terms "gut microbiome," "brain," and "cognition" and the terms "gut brain axis," "microbiome," and "cognition"; removed duplicates, studies not published in English, and unrelated publications; and added additional articles identified through references. We retained the 85 most relevant publications for this review. RESULTS:Common themes in the current literature include GMB components; interactions on cognitive development; effects of GMB-gut-brain interactions on cognition, mild cognitive impairment and Alzheimer's disease; effects of GMB interactions with physiologic stress on cognition in critical care; and GMB modification for improved cognition. Review of the literature on each of these topics reveals multiple theoretical mechanisms of action for GMB-gut-brain interaction that modify cognitive development and function across the lifespan. DISCUSSION:GMB components and dysbiosis have been implicated in many cognitive states, and specific microbiota constituents contribute to cognitive development, stability, and impairment. The study of these interactions is relevant to nursing research as it addresses the holistic human experience and microbiome constituents are modifiable, facilitating translation into the clinical setting. 10.1177/1099800420941923
Recovery of brain structural abnormalities in morbidly obese patients after bariatric surgery. Zhang Y,Ji G,Xu M,Cai W,Zhu Q,Qian L,Zhang Y E,Yuan K,Liu J,Li Q,Cui G,Wang H,Zhao Q,Wu K,Fan D,Gold M S,Tian J,Tomasi D,Liu Y,Nie Y,Wang G-J International journal of obesity (2005) BACKGROUND/OBJECTIVES:Obesity-related brain structural abnormalities have been reported extensively, and bariatric surgery (BS) is currently the most effective intervention to produce sustained weight reduction in overtly obese (OB) people. It is unknown whether BS can repair the brain circuitry abnormalities concomitantly with long-term weight loss. SUBJECTS/METHODS:In order to investigate whether BS promotes neuroplastic structural recovery in morbidly OB patients, we quantified fractional anisotropy (FA), mean diffusivity (MD) and gray (GM) and white (WM) matter densities in 15 morbidly OB patients and in 18 normal weight (NW) individuals. OB patients were studied at baseline and also 1 month after laparoscopic sleeve gastrectomy surgery. RESULTS:Two-sample t-test between OB (baseline) and NW groups showed decreased FA values, GM/WM densities and increased MD value in brain regions associated with food intake control (that is, caudate, orbitofrontal cortex, body and genu of corpus callosum) and cognitive-emotion regulation (that is, inferior frontal gyrus, hippocampus, insula, external capsule) (P<0.05, family-wise error correction). Paired t-test in the OB group between before and after surgery showed that BS generated partial neuroplastic structural recovery in the OB group, but the differences had relative less strength and smaller volume (P<0.001). CONCLUSIONS:This study provides the first anatomical evidence for BS-induced acute neuroplastic recovery that might in part mediate the long-term benefit of BS in weight reduction. It also highlights the importance of this line of gut-brain axis research employing the combined BS and neuroimaging model for identifying longitudinal changes in brain structure that correlated with obesity status. 10.1038/ijo.2016.98
Vascular Cognitive Impairment and the Gut Microbiota. Li Sinian,Shao Yiming,Li Kanglan,HuangFu Changmei,Wang Wenjie,Liu Zhou,Cai Zhiyou,Zhao Bin Journal of Alzheimer's disease : JAD Vascular cognitive impairment (VCI), the second most common cause of dementia in elderly people, is a term that refers to all forms of cognitive disorders that can be attributed to cerebrovascular disease such as manifestations of discrete infarctions, brain hemorrhages, and white matter lesions. The gut microbiota (GM) has emerged recently as an essential player in the development of VCI. The GM may affect the brain's physiological, behavioral, and cognitive functions through the brain-gut axis via neural, immune, endocrine, and metabolic pathways. Therefore, microbiota dysbiosis may mediate or affect atherosclerosis, cerebrovascular disease, and endothelial dysfunction, which are the predominant risk factors for VCI. Moreover, the composition of the GM includes the bacterial component lipopolysaccharides and their metabolic products including trimethylamine-N-oxide and short-chain fatty acids. These products may increase the permeability of the intestinal epithelium, leading to systemic immune responses, low-grade inflammation, and altered signaling pathways that are associated with the pathogenesis of VCI. In this review, we discuss the proposed mechanisms of the GM in the maintenance of VCI and how it is implicated in acquired metabolic diseases, particularly in VCI regulation. 10.3233/JAD-171103
Understanding Neurogastroenterology From Neuroimaging Perspective: A Comprehensive Review of Functional and Structural Brain Imaging in Functional Gastrointestinal Disorders. Kano Michiko,Dupont Patrick,Aziz Qasim,Fukudo Shin Journal of neurogastroenterology and motility This review provides a comprehensive overview of brain imaging studies of the brain-gut interaction in functional gastrointestinal disorders (FGIDs). Functional neuroimaging studies during gut stimulation have shown enhanced brain responses in regions related to sensory processing of the homeostatic condition of the gut (homeostatic afferent) and responses to salience stimuli (salience network), as well as increased and decreased brain activity in the emotional response areas and reduced activation in areas associated with the top-down modulation of visceral afferent signals. Altered central regulation of the endocrine and autonomic nervous responses, the key mediators of the brain-gut axis, has been demonstrated. Studies using resting-state functional magnetic resonance imaging reported abnormal local and global connectivity in the areas related to pain processing and the default mode network (a physiological baseline of brain activity at rest associated with self-awareness and memory) in FGIDs. Structural imaging with brain morphometry and diffusion imaging demonstrated altered gray- and white-matter structures in areas that also showed changes in functional imaging studies, although this requires replication. Molecular imaging by magnetic resonance spectroscopy and positron emission tomography in FGIDs remains relatively sparse. Progress using analytical methods such as machine learning algorithms may shift neuroimaging studies from brain mapping to predicting clinical outcomes. Because several factors contribute to the pathophysiology of FGIDs and because its population is quite heterogeneous, a new model is needed in future studies to assess the importance of the factors and brain functions that are responsible for an optimal homeostatic state. 10.5056/jnm18072
Microbiome-derived carnitine mimics as previously unknown mediators of gut-brain axis communication. Science advances Alterations to the gut microbiome are associated with various neurological diseases, yet evidence of causality and identity of microbiome-derived compounds that mediate gut-brain axis interaction remain elusive. Here, we identify two previously unknown bacterial metabolites 3-methyl-4-(trimethylammonio)butanoate and 4-(trimethylammonio)pentanoate, structural analogs of carnitine that are present in both gut and brain of specific pathogen-free mice but absent in germ-free mice. We demonstrate that these compounds are produced by anaerobic commensal bacteria from the family Lachnospiraceae (Clostridiales) family, colocalize with carnitine in brain white matter, and inhibit carnitine-mediated fatty acid oxidation in a murine cell culture model of central nervous system white matter. This is the first description of direct molecular inter-kingdom exchange between gut prokaryotes and mammalian brain cells, leading to inhibition of brain cell function. 10.1126/sciadv.aax6328
Gut microbiome populations are associated with structure-specific changes in white matter architecture. Ong Irene M,Gonzalez Jose G,McIlwain Sean J,Sawin Emily A,Schoen Andrew J,Adluru Nagesh,Alexander Andrew L,Yu John-Paul J Translational psychiatry Altered gut microbiome populations are associated with a broad range of neurodevelopmental disorders including autism spectrum disorder and mood disorders. In animal models, modulation of gut microbiome populations via dietary manipulation influences brain function and behavior and has been shown to ameliorate behavioral symptoms. With striking differences in microbiome-driven behavior, we explored whether these behavioral changes are also accompanied by corresponding changes in neural tissue microstructure. Utilizing diffusion tensor imaging, we identified global changes in white matter structural integrity occurring in a diet-dependent manner. Analysis of 16S ribosomal RNA sequencing of gut bacteria also showed changes in bacterial populations as a function of diet. Changes in brain structure were found to be associated with diet-dependent changes in gut microbiome populations using a machine learning classifier for quantitative assessment of the strength of microbiome-brain region associations. These associations allow us to further test our understanding of the gut-brain-microbiota axis by revealing possible links between altered and dysbiotic gut microbiome populations and changes in brain structure, highlighting the potential impact of diet and metagenomic effects in neuroimaging. 10.1038/s41398-017-0022-5