The Experts below are selected from a list of 114486 Experts worldwide ranked by ideXlab platform
John F. Cryan - One of the best experts on this subject based on the ideXlab platform.
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Growing up in a Bubble: Using Germ-Free Animals to Assess the Influence of the Gut Microbiota on Brain and Behavior
International Journal of Neuropsychopharmacology, 2016Co-Authors: Pauline Luczynski, Gerard Clarke, Timothy G. Dinan, Karen-anne Mcvey Neufeld, Clara Seira Oriach, John F. CryanAbstract:There is a growing recognition of the importance of the commensal intestinal microbiota in the development and later function of the central nervous system. Research using Germ-Free mice (mice raised without any exposure to microorganisms) has provided some of the most persuasive evidence for a role of these bacteria in gut-brain signalling. Key findings show that the microbiota is necessary for normal stress responsivity, anxiety-like behaviors, sociability, and cognition. Furthermore, the microbiota maintains central nervous system homeostasis by regulating immune function and blood brain barrier integrity. Studies have also found that the gut microbiota influences neurotransmitter, synaptic, and neurotrophic signalling systems and neurogenesis. The principle advantage of the Germ-Free mouse model is in proof-of-principle studies and that a complete microbiota or defined consortiums of bacteria can be introduced at various developmental time points. However, a Germ-Free upbringing can induce permanent neurodevelopmental deficits that may deem the model unsuitable for specific scientific queries that do not involve early-life microbial deficiency. As such, alternatives and complementary strategies to the Germ-Free model are warranted and include antibiotic treatment to create microbiota-deficient Animals at distinct time points across the lifespan. Increasing our understanding of the impact of the gut microbiota on brain and behavior has the potential to inform novel management strategies for stress-related gastrointestinal and neuropsychiatric disorders.
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Germ-Free Animals
The Gut-Brain Axis, 2016Co-Authors: Pauline Luczynski, K.a. Mcvey Neufeld, Gerard Clarke, Timothy G. Dinan, John F. CryanAbstract:A rapidly growing body of evidence demonstrates that the commensal microorganisms living within the gut influence brain and behavior. Germ-Free (GF) mice (microbiota deficient from birth) have been a key tool in realizing much of this knowledge. The gut microbiota is required for normal stress responsivity, sociability, and cognition. Underlying the behavioral and physiological profile of GF mice are alterations in microglial activation, blood–brain barrier permeability, and neurogenesis. Evidence also suggests that the absence of microbiota impacts neuronal communication and synaptic plasticity. One of the advantages of the GF model is that it offers the opportunity for the introduction of select bacteria, or bacterial populations, at different developmental periods. However, developmental effects arising from a GF upbringing may confound some of the conclusions drawn from this model. An increasing understanding of the impact of the microbiota on brain function and structure has the potential to inform novel treatments for the often co-morbid neuropsychiatric and gastrointestinal disorders.
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mind altering microorganisms the impact of the gut microbiota on brain and behaviour
Nature Reviews Neuroscience, 2012Co-Authors: John F. Cryan, Timothy G. DinanAbstract:Recent years have witnessed the rise of the gut microbiota as a major topic of research interest in biology. Studies are revealing how variations and changes in the composition of the gut microbiota influence normal physiology and contribute to diseases ranging from inflammation to obesity. Accumulating data now indicate that the gut microbiota also communicates with the CNS — possibly through neural, endocrine and immune pathways — and thereby influences brain function and behaviour. Studies in Germ-Free Animals and in Animals exposed to pathogenic bacterial infections, probiotic bacteria or antibiotic drugs suggest a role for the gut microbiota in the regulation of anxiety, mood, cognition and pain. Thus, the emerging concept of a microbiota-gut-brain axis suggests that modulation of the gut microbiota may be a tractable strategy for developing novel therapeutics for complex CNS disorders.
Philippe Gerard - One of the best experts on this subject based on the ideXlab platform.
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Gut microbiome and obesity. How to prove causality?
Annals of the American Thoracic Society, 2017Co-Authors: Philippe GerardAbstract:In recent years, the gut microbiota (the microorganisms that live in our digestive tract) has become an area of great interest. Indeed, this intestinal microbial community performs essential functions in maintaining our health, and has been proven to influence host physiology and metabolism. Thereby, dysregulation of this gut microbiota may be implicated in the development of various diseases, including obesity. However, studies rarely assess causality, which requires the use of Germ-Free Animals and microbiota transplant. Using these strategies, some gut microbiota were shown to confer obesity and associated metabolic disorders to mice, suggesting a causative link between gut bacteria and metabolic diseases.
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Gut microbiota and obesity.
Cellular and Molecular Life Sciences, 2015Co-Authors: Philippe GerardAbstract:The human intestine harbors a complex bacterial community called the gut microbiota. This microbiota is specific to each individual despite the existence of several bacterial species shared by the majority of adults. The influence of the gut microbiota in human health and disease has been revealed in the recent years. Particularly, the use of Germ-Free Animals and microbiota transplant showed that the gut microbiota may play a causal role in the development of obesity and associated metabolic disorders, and lead to identification of several mechanisms. In humans, differences in microbiota composition, functional genes and metabolic activities are observed between obese and lean individuals suggesting a contribution of the gut microbiota to these phenotypes. Finally, the evidence linking gut bacteria to host metabolism could allow the development of new therapeutic strategies based on gut microbiota modulation to treat or prevent obesity.
Timothy G. Dinan - One of the best experts on this subject based on the ideXlab platform.
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Growing up in a Bubble: Using Germ-Free Animals to Assess the Influence of the Gut Microbiota on Brain and Behavior
International Journal of Neuropsychopharmacology, 2016Co-Authors: Pauline Luczynski, Gerard Clarke, Timothy G. Dinan, Karen-anne Mcvey Neufeld, Clara Seira Oriach, John F. CryanAbstract:There is a growing recognition of the importance of the commensal intestinal microbiota in the development and later function of the central nervous system. Research using Germ-Free mice (mice raised without any exposure to microorganisms) has provided some of the most persuasive evidence for a role of these bacteria in gut-brain signalling. Key findings show that the microbiota is necessary for normal stress responsivity, anxiety-like behaviors, sociability, and cognition. Furthermore, the microbiota maintains central nervous system homeostasis by regulating immune function and blood brain barrier integrity. Studies have also found that the gut microbiota influences neurotransmitter, synaptic, and neurotrophic signalling systems and neurogenesis. The principle advantage of the Germ-Free mouse model is in proof-of-principle studies and that a complete microbiota or defined consortiums of bacteria can be introduced at various developmental time points. However, a Germ-Free upbringing can induce permanent neurodevelopmental deficits that may deem the model unsuitable for specific scientific queries that do not involve early-life microbial deficiency. As such, alternatives and complementary strategies to the Germ-Free model are warranted and include antibiotic treatment to create microbiota-deficient Animals at distinct time points across the lifespan. Increasing our understanding of the impact of the gut microbiota on brain and behavior has the potential to inform novel management strategies for stress-related gastrointestinal and neuropsychiatric disorders.
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Germ-Free Animals
The Gut-Brain Axis, 2016Co-Authors: Pauline Luczynski, K.a. Mcvey Neufeld, Gerard Clarke, Timothy G. Dinan, John F. CryanAbstract:A rapidly growing body of evidence demonstrates that the commensal microorganisms living within the gut influence brain and behavior. Germ-Free (GF) mice (microbiota deficient from birth) have been a key tool in realizing much of this knowledge. The gut microbiota is required for normal stress responsivity, sociability, and cognition. Underlying the behavioral and physiological profile of GF mice are alterations in microglial activation, blood–brain barrier permeability, and neurogenesis. Evidence also suggests that the absence of microbiota impacts neuronal communication and synaptic plasticity. One of the advantages of the GF model is that it offers the opportunity for the introduction of select bacteria, or bacterial populations, at different developmental periods. However, developmental effects arising from a GF upbringing may confound some of the conclusions drawn from this model. An increasing understanding of the impact of the microbiota on brain function and structure has the potential to inform novel treatments for the often co-morbid neuropsychiatric and gastrointestinal disorders.
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mind altering microorganisms the impact of the gut microbiota on brain and behaviour
Nature Reviews Neuroscience, 2012Co-Authors: John F. Cryan, Timothy G. DinanAbstract:Recent years have witnessed the rise of the gut microbiota as a major topic of research interest in biology. Studies are revealing how variations and changes in the composition of the gut microbiota influence normal physiology and contribute to diseases ranging from inflammation to obesity. Accumulating data now indicate that the gut microbiota also communicates with the CNS — possibly through neural, endocrine and immune pathways — and thereby influences brain function and behaviour. Studies in Germ-Free Animals and in Animals exposed to pathogenic bacterial infections, probiotic bacteria or antibiotic drugs suggest a role for the gut microbiota in the regulation of anxiety, mood, cognition and pain. Thus, the emerging concept of a microbiota-gut-brain axis suggests that modulation of the gut microbiota may be a tractable strategy for developing novel therapeutics for complex CNS disorders.
Sarkis K Mazmanian - One of the best experts on this subject based on the ideXlab platform.
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proinflammatory t cell responses to gut microbiota promote experimental autoimmune encephalomyelitis
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Juscilene S Menezes, Yoshinori Umesaki, Sarkis K MazmanianAbstract:Although the effects of commensal bacteria on intestinal immune development seem to be profound, it remains speculative whether the gut microbiota influences extraintestinal biological functions. Multiple sclerosis (MS) is a devastating autoimmune disease leading to progressive deterioration of neurological function. Although the cause of MS is unknown, microorganisms seem to be important for the onset and/or progression of disease. However, it is unclear how microbial colonization, either symbiotic or infectious, affects autoimmunity. Herein, we investigate a role for the microbiota during the induction of experimental autoimmune encephalomyelitis (EAE), an animal model for MS. Mice maintained under Germ-Free conditions develop significantly attenuated EAE compared with conventionally colonized mice. Germ-Free Animals, induced for EAE, produce lower levels of the proinflammatory cytokines IFN-γ and IL-17A in both the intestine and spinal cord but display a reciprocal increase in CD4+CD25+Foxp3+ regulatory T cells (Tregs). Mechanistically, we show that gut dendritic cells from Germ-Free Animals are reduced in the ability to stimulate proinflammatory T cell responses. Intestinal colonization with segmented filamentous bacteria (SFB) is known to promote IL-17 production in the gut; here, we show that SFBs also induced IL-17A–producing CD4+ T cells (Th17) in the CNS. Remarkably, Germ-Free Animals harboring SFBs alone developed EAE, showing that gut bacteria can affect neurologic inflammation. These findings reveal that the intestinal microbiota profoundly impacts the balance between pro- and antiinflammatory immune responses during EAE and suggest that modulation of gut bacteria may provide therapeutic targets for extraintestinal inflammatory diseases such as MS.
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an immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system
Cell, 2005Co-Authors: Sarkis K Mazmanian, Arthur O Tzianabos, Dennis L KasperAbstract:Summary The mammalian gastrointestinal tract harbors a complex ecosystem consisting of countless bacteria in homeostasis with the host immune system. Shaped by evolution, this partnership has potential for symbiotic benefit. However, the identities of bacterial molecules mediating symbiosis remain undefined. Here we show that, during colonization of Animals with the ubiquitous gut microorganism Bacteroides fragilis , a bacterial polysaccharide (PSA) directs the cellular and physical maturation of the developing immune system. Comparison with Germ-Free Animals reveals that the immunomodulatory activities of PSA during B. fragilis colonization include correcting systemic T cell deficiencies and T H 1/T H 2 imbalances and directing lymphoid organogenesis. A PSA mutant of B. fragilis does not restore these immunologic functions. PSA presented by intestinal dendritic cells activates CD4 + T cells and elicits appropriate cytokine production. These findings provide a molecular basis for host-bacterial symbiosis and reveal the archetypal molecule of commensal bacteria that mediates development of the host immune system.
Jerjang Chang - One of the best experts on this subject based on the ideXlab platform.
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role of the intestinal microbiota in the activation of the promutagen 2 6 dinitrotoluene to mutagenic urine metabolites and comparison of gi enzyme activities in germ free and conventionalized male fischer 344 rats
Cancer Letters, 1994Co-Authors: Elizabeth S George, Robert W Chadwick, Michael J Kohan, Joyce C Allison, Ronald Williams, Jerjang ChangAbstract:Abstract After male Germ-Free and conventionalized Fischer 344 rats were administered per os (p.o.) 75 mg/kg 2,6-DNT, intestinal nitroreductase, β-glucuronidase, and azo reductase activities were lower in the cecum and large intestine of Germ-Free Animals. However, there was no significant difference in the small intestinal nitroreductase and azo reductase compared to the conventionalized counterparts. This indicated a potential mucosal source for the enzymes. Urines from Germ-Free rats (1144 ± 64 revertants/ml) were less mutagenic than those from conventionalized Animals (1467 ± 171 revertants/ml) in Salmonella typhimurium strain TA98 without S9. In the presence of S9, urine from conventionalized Animals (894 ± 56 revertants/ml) was more mutagenic than that from Germ-Free rats (686 ± 60 revertants/ml). The presence of the intestinal flora plays an important role in the activation of 2,6-DNT but other metabolic pathways, such as the small intestinal mucosal and/or hepatic enzymes, are present that can generate excreted genotoxicants.