The role of the microbiome in cancer development and therapy

CA A Cancer Journal for Clinicians, Journal Year: 2017, Volume and Issue: 67(4), P. 326 - 344

Published: May 8, 2017

Answer questions and earn CME/CNE The human body harbors enormous numbers of microbiota that influence cancer susceptibility, in part through their prodigious metabolic capacity profound on immune cell function. Microbial pathogens drive tumorigenesis 15% to 20% cases. Even larger malignancies are associated with an altered composition commensal (dysbiosis) based microbiome studies using metagenomic sequencing. Although association cannot distinguish whether changes causes or effects cancer, a causative role is supported by rigorously controlled preclinical gnotobiotic mouse models colonized one more specific bacteria. These demonstrate can alter susceptibility progression diverse mechanisms, such as modulating inflammation, inducing DNA damage, producing metabolites involved oncogenesis tumor suppression. Evidence emerging be manipulated for improving treatment. By incorporating probiotics adjuvants checkpoint immunotherapy designing small molecules target microbial enzymes, harnessed improve care. CA Cancer J Clin 2017;67:326-344. © 2017 American Society.

Language: Английский

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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

The International Journal of Neuropsychopharmacology, Journal Year: 2016, Volume and Issue: 19(8), P. pyw020 - pyw020

Published: Feb. 23, 2016

There is a growing recognition of the importance commensal intestinal microbiota in development and later function central nervous system. Research using germ-free mice (mice raised without any exposure to microorganisms) has provided some most persuasive evidence for role these bacteria gut-brain signalling. Key findings show that necessary normal stress responsivity, anxiety-like behaviors, sociability, cognition. Furthermore, maintains system homeostasis by regulating immune blood brain barrier integrity. Studies have also found gut influences neurotransmitter, synaptic, neurotrophic signalling systems neurogenesis. The principle advantage mouse model proof-of-principle studies complete or defined consortiums can be introduced at various developmental time points. However, upbringing induce permanent neurodevelopmental deficits may deem unsuitable specific scientific queries do not involve early-life microbial deficiency. As such, alternatives complementary strategies are warranted include antibiotic treatment create microbiota-deficient animals distinct points across lifespan. Increasing our understanding impact on behavior potential inform novel management stress-related gastrointestinal neuropsychiatric disorders.

Language: Английский

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Anxiety, Depression, and the Microbiome: A Role for Gut Peptides

Neurotherapeutics, Journal Year: 2017, Volume and Issue: 15(1), P. 36 - 59

Published: Nov. 13, 2017

Language: Английский

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Altered microbiomes distinguish Alzheimer’s disease from amnestic mild cognitive impairment and health in a Chinese cohort

Brain Behavior and Immunity, Journal Year: 2019, Volume and Issue: 80, P. 633 - 643

Published: May 8, 2019

(Background): Alzheimer's disease (AD), clinically characterized by the progressive neurodegenerative condition and cognitive impairment, is one of main causes disability in elder people worldwide. Recently, several animal studies indicated that 'gut-brain' axis might contribute to amyloid deposition AD. However, data about gut dysbiosis human AD remains scarce literature, especially including whole process In this prospective cross-sectional study, we aimed at identifying differences microbiome between patients with (Pre-onset stage amnestic mild aMCI; AD) normal cognition healthy controls (HC). Additionally, potential association IM clinical characteristics was evaluated. A total 97 subjects (33 AD, 32 aMCI, HC) were recruited study. The composition bacterial communities determined 16S ribosomal RNA Miseq sequencing. addition, Phylogenetic Investigation Communities Reconstruction Unobserved States (PICRUSt) used predict function shift intestinal microbiota. Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) or Clinical Dementia Rating (CDR) scores evaluate severity impairment patients. fecal microbial diversity decreased compared aMCI HC. And distinct among control groups. Among taxa, proportion phylum Firmicutes significantly reduced (P = 0.008), whereas Proteobacteria 0.024) highly enriched similar alterations observed order, class family levels these two phyla. Gammaproteobacteria, Enterobacteriales Enterobacteriaceae showed a prevalence from HC Further, significant correlation abundance altered microbiomes. Moreover, KEGG results increased modules related glycan biosynthesis metabolism pathways immune system Importantly, discriminating models based on predominant microbiota could effectively distinguish (AUC 0.890, 0.940, respectively), also 0.925). Notably, both 0.688) 0.698). Distinct communities, Enterobacteriaceae, associated when predementia subjects. These novel findings will give new clues understand provide therapeutic target for intervention marker disease.

Language: Английский

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The gut microbiome in human neurological disease: A review

Annals of Neurology, Journal Year: 2017, Volume and Issue: 81(3), P. 369 - 382

Published: Feb. 21, 2017

Almost half the cells and 1% of unique genes found in our bodies are human, rest from microbes, predominantly bacteria, archaea, fungi, viruses. These microorganisms collectively form human microbiota, with most colonizing gut. Recent technological advances, open access data libraries, application high‐throughput sequencing have allowed these microbes to be identified their contribution neurological health examined. Emerging evidence links perturbations gut microbiota disease, including disease risk, activity, progression. This review provides an overview recent advances microbiome research relation neuro(auto)immune neurodegenerative conditions affecting humans, such as multiple sclerosis, neuromyelitis optica spectrum disorders, Parkinson Alzheimer Huntington amyotrophic lateral sclerosis. Study design terminology used this rapidly evolving, highly multidisciplinary field summarized empower engage neurology community “newly discovered organ.” Ann Neurol 2017;81:369–382

Language: Английский

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The microbiome: A key regulator of stress and neuroinflammation

Neurobiology of Stress, Journal Year: 2016, Volume and Issue: 4, P. 23 - 33

Published: March 5, 2016

There is a growing emphasis on the relationship between complexity and diversity of microorganisms that inhabit our gut (human gastrointestinal microbiota) health/disease, including brain health disorders central nervous system. The microbiota-gut-brain axis dynamic matrix tissues organs brain, glands, gut, immune cells microbiota communicate in complex multidirectional manner to maintain homeostasis. Changes this environment can lead broad spectrum physiological behavioural effects hypothalamic-pituitary-adrenal (HPA) activation, altered activity neurotransmitter systems function. While an appropriate, co-ordinated response, such as or stress response are necessary for survival, dysfunctional be detrimental host contributing development number CNS disorders. In review, involvement stress-mediated immune-mediated modulation neuroendocrine, consequential behaviour considered. We also focus mechanisms by which commensal regulate neuroinflammation further aim exploit understanding their role stress-related consequence neuroinflammatory processes.

Language: Английский

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The Gut–Brain Axis

Annual Review of Medicine, Journal Year: 2021, Volume and Issue: 73(1), P. 439 - 453

Published: Oct. 20, 2021

Preclinical evidence has firmly established bidirectional interactions among the brain, gut, and gut microbiome. Candidate signaling molecules at least three communication channels have been identified. Communication within this system is nonlinear, with multiple feedback loops, likely involves between different channels. Alterations in gut-brain-microbiome identified rodent models of several digestive, psychiatric, neurological disorders. While alterations gut-brain clearly irritable bowel syndrome, a causative role microbiome syndrome remains to be determined. In absence specific microbial targets for more effective therapies, current approaches are limited dietary interventions centrally targeted pharmacological behavioral approaches. A comprehensive understanding influences well-designed randomized controlled trials needed translate these exciting preclinical findings into therapies.

Language: Английский

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Brain–Heart Interaction

Circulation Research, Journal Year: 2017, Volume and Issue: 121(4), P. 451 - 468

Published: Aug. 3, 2017

Neurocardiology is an emerging specialty that addresses the interaction between brain and heart, is, effects of cardiac injury on heart. This review article focuses dysfunction in setting stroke such as ischemic stroke, hemorrhage, subarachnoid hemorrhage. The majority post-stroke deaths are attributed to neurological damage, cardiovascular complications second leading cause mortality. Accumulating clinical experimental evidence suggests a causal relationship damage heart dysfunction. Thus, it important determine whether triggered by unrelated complication, or underlying stroke. Stroke-induced may lead fatality potentially lifelong problems (such failure), mild recoverable neurogenic stress cardiomyopathy Takotsubo cardiomyopathy. role location lateralization lesions after brain-heart interaction; biomarkers manifestations complications; mechanisms hypothalamic-pituitary-adrenal axis; catecholamine surge; sympathetic parasympathetic regulation; microvesicles; microRNAs; gut microbiome, immunoresponse, systemic inflammation, discussed.

Language: Английский

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Effects of Psychological, Environmental and Physical Stressors on the Gut Microbiota

Frontiers in Microbiology, Journal Year: 2018, Volume and Issue: 9

Published: Sept. 11, 2018

Stress, a ubiquitous part of daily human life, has varied biological effects which are increasingly recognized as including modulation commensal microorganisms residing in the gastrointestinal tract, gut microbiota. In turn, microbiota influences host stress response and associated sequelae, thereby implicating an important mediator health. This narrative review aims to synthesize evidence concerning impact psychological, environmental, physical stressors on composition activity. The reviewed include psychological stress, circadian disruption, sleep deprivation, environmental extremes (high altitude, heat, cold), pathogens, toxicants pollutants, activity, diet (nutrient food restriction). Stressors were selected for their direct relevance military personnel, population that is commonly exposed these stressors, often at extremes, combination. However, also common, alone or combination, some civilian populations. Evidence from preclinical studies collectively indicates alter but vary across can may be beneficial detrimental Translation findings humans largely lacking present. gap precludes concluding with certainty transient cumulative exposures have any consistent, meaningful provocative highlights need translational research aiming elucidate microbiota, how manipulated, example by using nutrition, mitigate adverse responses.

Language: Английский

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The Gut–Brain Axis and the Microbiome: Mechanisms and Clinical Implications

Clinical Gastroenterology and Hepatology, Journal Year: 2018, Volume and Issue: 17(2), P. 322 - 332

Published: Oct. 4, 2018

Language: Английский

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