肠道菌群紊乱和自闭症3

肠道菌群紊乱和自闭症3•1Faculty of Life Sciences, The University of Manchester , Manchester , UK.AbstractAutism spectrum disorder (ASD) is a heterogeneous condition affecting an individual's ability tocommunicate and socialize and often presents with repetitive movements or behaviors. It tends to be severe with less than 10% achieving independent living with a marked variation in the progression of the condition. To date, the literature supports a multifactorial model with the largest, most detailed twin study demonstrating strong environmental contribution to the development of the condition. Here, we present a brief review of the neurological, immunological, and autonomic abnormalities in ASD focusing on the causative roles of environmental agents and abnormal gut microbiota. We present a working hypothesis attempting to bring together the influence of environment on the abnormal neurological, immunological, and neuroimmunological functions and we explain in brief how such pathophysiology can lead to, and/or exacerbate ASD symptomatology. At present, there is a lack of consistent findings relating to theneurobiology of autism. Whilst we postulate such variable findings may reflect the marked heterogeneity in clinical presentation and as such the variable findings may be of pathophysiological relevance, more research into the neurobiology of autism is necessary before establishing a working hypothesis. Both the literature review and hypothesis presented here explore possible neurobiological explanations with an emphasis of environmental etiologies and are presented with this bias.Ann Pharm Fr. 2014 Jan;72(1):15-21. doi: 10.1016/j.pharma.2013.09.001. Epub 2013 Oct 16.[Current view on gut microbiota].[Article in French]Bourlioux P1.Author information•111, avenue de la République, 94400 Vitry-sur-Seine, France. Electronic address: pierre.bourlioux@u-psud.fr.AbstractGut microbiota is more and more important since metagenomic research have brought new knowledge on this topic especially for human health. Firstly, gut microbiota is a key element for our organism he lives in symbiosis with. Secondly, it interacts favorably with many physiological functions of our organism. Thirdly, at the opposite, it can be an active participant in intestinal pathologies linked to a dysbiosis mainly in chronic inflammatory bowel diseases like Crohn disease or ulcerative colitis but also in obesity, metabolic syndrome, and more prudently in autism and behavioral disorders. In order to keep a good health, it is essential to protect our gut microbiota as soon as our young age and maintain it healthy. Face to a more and more important number of publications for treating certain digestive diseases with fecal microbial transplantation, it needs to be very careful and recommend further studies in order to assess risks and define standardized protocols. Gut microbiota metabolic capacities towards xenobiotics need to bedeveloped, and we must take an interest in the modifications they induce on medicinal molecules. On theother hand, it is essential to study the potent effects of pesticides and other pollutantson microbiota functions.•1Department of Microbiology and Immunology, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA; Department of Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA.•2Department of Microbiology and Immunology, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA; Department of Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA. Electronic address: Lloyd.H.Kasper@.AbstractMammals live in a co-evolutionary association with the plethora of microorganisms that reside at a variety of tissue microenvironments. The microbiome represents the collective genomes of these co-existing microorganisms, which is shaped by host factors such as genetics and nutrients but in turn is able to influence host biology in health and disease. Niche-specific microbiome, prominently the gut microbiome, has the capacity to effect both local and distal sites within the host. The gut microbiome has played a crucial role in the bidirectional gut-brain axis that integrates the gutand central nervous system (CNS) activities, and thus the concept of microbiome-gut-brain axis is emerging. Studies are revealing how diverse forms of neuro-immune and neuro-psychiatric disorders are correlated with or modulated by variations of microbiome, microbiota-derived products and exogenous antibiotics and probiotics. The microbiome poises the peripheral immune homeostasis and predisposes host susceptibility to CNS autoimmune diseases such as multiple sclerosis. Neural, endocrine and metabolic mechanisms are also critical mediators of the microbiome-CNS signaling, which are more involved in neuro-psychiatricdisorders such as autism, depression, anxiety, stress. Research on the role of microbiome in CNSdisorders deepens our academic knowledge about host-microbiome commensalism in central regulation and in practicality, holds conceivable promise for developing novel prognostic and therapeutic avenues for CNS disorders.Nat Rev Neurol. 2014 Feb;10(2):60. doi: 10.1038/nrneurol.2013.267. Epub 2013 Dec 24.Neurodevelopmental disorders: human gut microbiota alleviate behavioural symptoms in a mouse modelofautism spectrum disorder.Malkki H.Comment on•1Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.•2Nutricia Research, Utrecht, The Netherlands; Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.•3Nutricia Research, Utrecht, The Netherlands; Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.•4Nutricia Research, Utrecht, The Netherlands.•5Nutricia Research, Utrecht, The Netherlands. Electronic address: raish.oozeer@.AbstractAutism spectrum disorder (ASD) is a heterogeneous group of complex neurodevelopmental disorders with evidence of genetic predisposition. Intestinal disturbances are reported in ASD patients andcompositional changes in gut microbiota are described. However, the role of microbiota in brain disorders is poorly documented. Here, we used a murine model of ASD to investigate the relationbetween gut microbiota and autism-like behaviour. Using next generation sequencingtechnology, microbiota composition was investigated in mice in utero exposed to valproic acid (VPA).Moreover, levels of short chain fatty acids (SCFA) and lactic acid in caecal content were determined. Our data demonstrate a transgenerational impact of in utero VPA exposure on gut microbiota in the offspring.Prenatal VPA exposure affected operational taxonomic units (OTUs) assigned to genera within the main phyla of Bacteroidetes and Firmicutes and the order of Desulfovibrionales, corroborating human ASD studies. In addition, OTUs assigned to genera of Alistipes, Enterorhabdus, Mollicutes andErysipelotrichalis were especially associated with male VPA-exposed offspring. The microbial differences of VPA in utero-exposed males deviated from those observed in females and was (i) positively associated with increased levels of caecal butyrate as well as ileal neutrophil infiltration and (ii) inversely associated with intestinal levels of serotonin and social behaviour scores. These findings show that autism-likebehaviour and its intestinal phenotype is associated with altered microbial colonization and activity in a murine model for ASD, with preponderance in male offspring. These results open new avenues in the scientific trajectory of managing neurodevelopmental disorders by gut microbiome modulation.•1Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA; Division of Chemistry and Chemical Engineering, California Institute of Technology,Pasadena, CA 91125, USA. Electronic address: ehsiao@.•2Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.•3Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, TX 77030, USA.•4Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.•5Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: php@.•6Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: sarkis@.AbstractNeurodevelopmental disorders, including autism spectrum disorder (ASD), are defined by core behavioral impairments; however, subsets of individuals display a spectrum of gastrointestinal (GI) abnormalities.We demonstrate GI barrier defects and microbiota alterations in the maternal immune activation (MIA) mouse model that is known to display features of ASD. Oral treatment of MIA offspring with the human commensal Bacteroides fragilis corrects gut permeability, alters microbial composition, and ameliorates defects in communicative, stereotypic, anxiety-like and sensorimotor behaviors. MIA offspring display an altered serum metabolomic profile, and B. fragilis modulates levels of several metabolites. Treating naive mice with a metabolite that is increased by MIA and restored by B. fragilis causes certain behavioral abnormalities, suggesting that gut bacterial effects on the host metabolome impact behavior. Taken together, these findings support a gut-microbiome-brain connection in a mouse model of ASD and identifya potential probiotic therapy for GI and particular behavioral symptoms in human neurodevelopmentaldisorders.•1Alimentary Pharmabiotic Center.AbstractTo date, there is rapidly increasing evidence for host-microbe interaction at virtually all levels ofcomplexity, ranging from direct cell-to-cell communication to extensive systemic signalling, and involving various organs and organ systems, including the central nervous system. As such, the discovery that differential microbial composition is associated with alterations in behaviour and cognition hassignificantly contributed to establishing the microbiota-gut-brain axis as an extension of the well-accepted gut-brain axis concept. Many efforts have been focused on delineating a role for this axis in health and disease, ranging from stress-related disorders such as depression, anxiety and irritable bowel syndrome to neurodevelopmental disorders such as autism. There is also a growing appreciation of the role of epigenetic mechanisms in shaping brain and behaviour. However, the role of epigenetics ininforming host-microbe interactions has received little attention to date. This is despite the fact that there are many plausible routes of interaction between epigenetic mechanisms and the host-microbiota dialogue. From this new perspective we put forward novel, yet testable, hypotheses. Firstly, we suggest that gut-microbial products can affect chromatin plasticity within their host's brain that in turn leads to changes in neuronal transcription and eventually alters host behaviour. Secondly, we argue that the microbiota is an important mediator of gene-environment interactions. Finally, we reason thatthe microbiota itself may be viewed as an epigenetic entity. In conclusion, the fields of (neuro)epigenetics and microbiology are converging at many levels and more interdisciplinary studies are necessary to unravel the full range of this interaction.•1Preventative Health National Research Flagship, CSIRO Animal, Food and Health Sciences, Gate 13, Kintore Avenue, Adelaide, South Australia 5001, Australia. michael.conlon@csiro.au.AbstractBACKGROUND:A recent report indicated that numbers of Sutterella spp. are elevated in gastrointestinal biopsies takenfrom children with autismspectrum disorder (ASD). We have recently reported changes in the numbers of some bacteria within the stool of ASD children, and now examine whether numbers of Sutterella spp. and some other mucosa-associated bacteria linked with gastrointestinal disease (Ruminococcus gnavus and Ruminococcus torques) are also altered in the stool of these children.FINDINGS:We show that numbers of Sutterella spp. are elevated in feces of ASD children relative to controls, and that numbers of R. torques are higher in the children with ASD with a reported functionalgastrointestinal disorder than those without such a disorder.CONCLUSIONS:We show further evidence of changes in the gut microbiota of children with ASD and confirm that the abundance of Sutterella spp. is altered in stool.•1Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.AbstractAutism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) areneurodevelopmental disorders which occur in childhood and may persist into adulthood. Although the etiology of these disorders is largely unknown, genetic and environmental factors are thought to play a role in the development of ASD and ADHD. Allergic immune reactions, in prenatal and postnatal phases, are examples of these environmental factors, and adverse reactions to foods are reported in thesechildren. In this review, we address the clinical and preclinical findings of (food) allergy in ASD and ADHD and suggest possible underlying mechanisms. Furthermore, opportunities for nutritional interventions in neurodevelopmental disorders are provided.•1Department of Soil, Plant and Food Sciences, University of Bari Aldo Moro, Bari, Italy.AbstractThis study aimed at investigating the fecal microbiota and metabolome of children with PervasiveDevelopmental Disorder Not Otherwise Specified (PDD-NOS) and autism (AD) in comparison to healthy children (HC). Bacterial tag-encoded FLX-titanium amplicon pyrosequencing (bTEFAP) of the 16S rDNA and 16S rRNA analyses were carried out to determine total bacteria (16S rDNA) and metabolically active bacteria (16S rRNA), respectively. The main bacterial phyla (Firmicutes, Bacteroidetes, Fusobacteria and Verrucomicrobia) significantly (P<0.05) changed among the three groups of children. As estimated by rarefaction, Chao and Shannon diversity index, the highest microbial diversity was found in AD children.Based on 16S-rRNA and culture-dependent data, Faecalibacterium and Ruminococcus were present at the highest level in fecal samples of PDD-NOS and HC children. Caloramator, Sarcina and Clostridium genera were the highest in AD children. Compared to HC, the composition of Lachnospiraceae family also differed in PDD-NOS and, especially, AD children. Except for Eubacterium siraeum, the lowest level of Eubacteriaceae was found on fecal samples of AD children. The level of Bacteroidetes genera and some Alistipes and Akkermansia species were almost the highest in PDD-NOS or AD children as well as almost all the identified Sutterellaceae and Enterobacteriaceae were the highest in AD. Compared to HC children, Bifidobacterium species decreased in AD. As shown by Canonical Discriminant Analysis of Principal Coordinates, the levels of free amino acids and volatile organic compounds of fecal samples were markedly affected in PDD-NOS and, especially, AD children. If the gut microbiota differences among AD and PDD-NOS and HC children are one of the concomitant causes or the consequence of autism, they may have implications regarding specific diagnostic test, and/or for treatment and prevention.。