Integrated Label-Free and 10-Plex DiLeu Isobaric Tag Quantitative Methods for Profiling Changes in the Mouse Hypothalamic Neuropeptidome and Proteome: Assessment of the Impact of the Gut Microbiome (original) (raw)
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Recent findings within the microbiota–gut–brain–endocrine metabolic interactome
Pathology and Laboratory Medicine International, 2017
Purpose of review: We have established that many metabolic biomes exist within the complex mammalian gut. Substantial metabolism occurs within these biomes and is called co-metabolism of the host and resident microorganisms. This gut-brain-endocrine metabolic interaction emphasizes how bacteria can affect the brain and the hormonal axes in the process of co-metabolism. This review highlights new findings in this regard. Recent findings: In this review, we explore how the gut microbiota affect the development and regulation of the hypothalamic-pituitary-adrenal axis and neurochemistry from mental health and behavioral health to memory, depression, mood, anxiety, obesity, and the development of the blood-brain barrier. Summary: This review describes the implications of the findings for clinical practice or research. Interaction of small molecules within these biomes is now described collectively as a "metabolic interactome". Metabolites of the gut-brain-endocrine axis and our overall gut health constantly shape the host phenotype in ways previously unimagined, and this niche represents potential targets for treatment and drug design, since the interaction or biochemical interplay results in net metabolite production and/or end products to exercise either positive or negative effects on human health.
Journal of neurogastroenterology and motility, 2016
Gut microbiome is an integral part of the Gut-Brain axis. It is becoming increasingly recognized that the presence of a healthy and diverse gut microbiota is important to normal cognitive and emotional processing. It was known that altered emotional state and chronic stress can change the composition of gut microbiome, but it is becoming more evident that interaction between gut microbiome and central nervous system is bidirectional. Alteration in the composition of the gut microbiome can potentially lead to increased intestinal permeability and impair the function of the intestinal barrier. Subsequently, neuro-active compounds and metabolites can gain access to the areas within the central nervous system that regulate cognition and emotional responses. Deregulated inflammatory response, promoted by harmful microbiota, can activate the vagal system and impact neuropsychological functions. Some bacteria can produce peptides or short chain fatty acids that can affect gene expression a...
Gut microbiome and brain: scope and perspectives
International Journal of Psychological Research
©2022. International Journal of Psychological Research provides open access to all its contents under the terms of the license creative commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) Declaration of data availability: All relevant data are within the article, as well as the information support files.
Impact of the gut microbiota on the neuroendocrine and behavioural responses to stress in rodents
OCL, 2015
The gastro-intestinal tract hosts a complex microbial ecosystem, the gut microbiota, whose collective genome coding capacity exceeds that of the host genome. The gut microbiota is nowadays regarded as a full organ, likely to contribute to the development of pathologies when its dynamic balance is disrupted (dysbiosis). In the last decade, evidence emerged that the gut microbiota influences brain development and function. In particular, comparisons between germ-free and conventional laboratory rodents showed that the absence of the gut microbiota exacerbates the hypothalamic pituitary adrenal (HPA) system reactivity to stress and alters the anxiety-like behaviour. Furthermore, the dysfunctions observed in germ-free animals can be corrected if the gut microbiota is restored in early life but not in adulthood, suggesting a critical period for microbiota imprinting on the responsiveness to stress. The modes of action are still to be deciphered. They may involve transport of neuroactive bacterial metabolites to the brain through the bloodstream, stimulation of the vagus nerve or of entero-endocrine cells, or modulation of the immune system and, consequently, of the inflammatory status. The discovery that the gut microbiota regulates the neuroendocrine and behavioural responses to stress paves the way for the hypothesis that gut microbiota dysbioses could contribute to the pathophysiology of anxiety-related disorders. In this regard, treatments of anxiety-prone rodent strains with probiotics or antibiotics aimed at modifying their gut microbiota have shown an anxiolytic-like activity. Clinical trials are now needed to know if results obtained in preclinical studies can translate to humans. Keywords: Gut-brain axis / germ-free / probiotic / hypothalamic pituitary adrenal axis / anxiety Résumé-Effet du microbiote intestinal sur les réponses neuroendocrinienne et comportementale au stress. Le tractus gastro-intestinal héberge une communauté microbienne complexe appelée microbiote, dont le potentiel génétique excède celui de l'hôte en richesse et diversité. Le microbiote intestinal est considéré aujourd'hui comme un véritable organe, susceptible de contribuer au développement de pathologies si son équilibre est rompu (on parle alors de dysbiose). Au cours de la dernière décennie, des travaux ont commencé à mettre en évidence que le microbiote intestinal influençait le développement et le fonctionnement du cerveau. En particulier, des comparaisons entre rongeurs axéniques et conventionnels ont montré que l'absence de microbiote intestinal intensifiait la réponse au stress de l'axe corticotrope et modifiait le niveau d'anxiété. Ces anomalies ne peuvent être corrigées que si la restauration du microbiote chez les animaux axéniques intervient avant l'âge adulte. Ceci suggère l'existence d'une période critique du développement au cours de laquelle le microbiote influence la maturation des structures cérébrales impliquées dans la réponse au stress. Les mécanismes d'action ne sont pas encore complètement élucidés. Pourraient intervenir des métabolites microbiens neuro-actifs, atteignant le cerveau par voie sanguine, une stimulation des afférences intestinales du nerf vague, une stimulation des cellules endocrines de la paroi intestinale, ou une modulation du système immunitaire et, par conséquent, du statut inflammatoire de l'organisme. La découverte que le microbiote intestinal régule les réponses neuroendocrinienne et comportementale au stress conduit à l'hypothèse que des dysbioses du microbiote pourraient contribuer à la physiopathologie des troubles anxieux ou des troubles de l'humeur ayant une composante anxieuse. À cet égard, la modulation du microbiote intestinal avec des probiotiques ou des antibiotiques chez des lignées de rongeurs prédisposées à l'anxiété a un effet de type anxiolytique. Des essais cliniques sont maintenant nécessaires pour déterminer si ces résultats précliniques sont transposables à l'Homme.
Gut Microbiome-Brain Communications Regulate Host Physiology and Behavior
Journal of Nutritional Health & Food Science, 2015
cell injury [6], metabolic regulation [7], GI tract development [8], innate and adaptive immune responses, and absorption of nutrients [9,10]. Alterations in microbiota composition and dysregulation of the intestinal mucosa homeostasis have been implicated in the development and progression of pathologies. This compositional change in the microbiota and/ or an abnormality in the interactions between the host and the commensal microbiota is referred to as dysbiosis. Gut microbiota dysbiosis has been linked to chronic low-grade intestinal inflammation and acute intestinal autoimmunity diseases such as Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD) [11,12]. Abnormal microbiota composition is associated with a wide range of metabolic and behavioral disorders, such as anxiety/depression [13-15], autism spectrum disorders [16-18], hepatic encephalopathy [19], multiple sclerosis [20, 21], allergies [22], visceral pain [23,24], atherosclerosis [25] and cardiovascular risks [26]. GI microbiota dysbiosis might also be involved in the development and persistence of systemic disorders [27]. For example, obesity has been characterized by a decrease in overall diversity [28] and an increase in Proteobacteria abundance and in the Firmicutes to Bacteroidetes ratio [28,29] and microbiota composition is believed to influence energy balance and glucose homeostasis [30-32]. Evidence that changes in microbiota composition are correlated with metabolic and behavioral disorders has drawn attention to a potential causal role for the microbiota in pathologies and has led to the emergence of the 'microbiota-gutbrain axis' concept [33-35]. The gut-brain axis is a bidirectional communication system between the GI tract and the brain [36] via hormonal, immunological, and neural signaling. Information from the GI tract and the intestinal microbiota can reach the peripheral and Central Nervous System (CNS), concurrently the brain is able to influence GI functions such as motility and secretion but also immune responses and cytokine production [36,37]. The Microbiota-Gut-Brain Axis The gut microbiota can modulate gut-brain axis signaling via direct and indirect mechanisms. The microbiota acts via endocrine, metabolic (bacterial components and metabolites),
The Gut Microbiome and the Brain
Journal of Medicinal Food, 2014
The human gut microbiome impacts human brain health in numerous ways: (1) Structural bacterial components such as lipopolysaccharides provide low-grade tonic stimulation of the innate immune system. Excessive stimulation due to bacterial dysbiosis, small intestinal bacterial overgrowth, or increased intestinal permeability may produce systemic and/or central nervous system inflammation. (2) Bacterial proteins may cross-react with human antigens to stimulate dysfunctional responses of the adaptive immune system. (3) Bacterial enzymes may produce neurotoxic metabolites such as Dlactic acid and ammonia. Even beneficial metabolites such as short-chain fatty acids may exert neurotoxicity. (4) Gut microbes can produce hormones and neurotransmitters that are identical to those produced by humans. Bacterial receptors for these hormones influence microbial growth and virulence. (5) Gut bacteria directly stimulate afferent neurons of the enteric nervous system to send signals to the brain via the vagus nerve. Through these varied mechanisms, gut microbes shape the architecture of sleep and stress reactivity of the hypothalamic-pituitary-adrenal axis. They influence memory, mood, and cognition and are clinically and therapeutically relevant to a range of disorders, including alcoholism, chronic fatigue syndrome, fibromyalgia, and restless legs syndrome. Their role in multiple sclerosis and the neurologic manifestations of celiac disease is being studied. Nutritional tools for altering the gut microbiome therapeutically include changes in diet, probiotics, and prebiotics. KEY WORDS: D-lactic acid endotoxin microbial endocrinology microbiome prebiotics probiotics short-chain fatty acids trimethylamine oxide (TMAO)
Journal of Clinical Medicine, 2018
The central nervous system (CNS) and the human gastrointestinal (GI) tract communicate through the gut-brain axis (GBA). Such communication is bi-directional and involves neuronal, endocrine, and immunological mechanisms. There is mounting data that gut microbiota is the source of a number of neuroactive and immunocompetent substances, which shape the structure and function of brain regions involved in the control of emotions, cognition, and physical activity. Most GI diseases are associated with altered transmission within the GBA that are influenced by both genetic and environmental factors. Current treatment protocols for GI and non-GI disorders may positively or adversely affect the composition of intestinal microbiota with a diverse impact on therapeutic outcome(s). Alterations of gut microbiota have been associated with mood and depressive disorders. Moreover, mental health is frequently affected in GI and non-GI diseases. Deregulation of the GBA may constitute a grip point fo...
Gut, Microbiome, and Brain Regulatory Axis: Relevance to Neurodegenerative and Psychiatric Disorders
Cellular and molecular neurobiology, 2018
It has become apparent that the molecular and biochemical integrity of interactive families, genera, and species of human gut microflora is critically linked to maintaining complex metabolic and behavioral processes mediated by peripheral organ systems and central nervous system neuronal groupings. Relatively recent studies have established intrinsic ratios of enterotypes contained within the human microbiome across demographic subpopulations and have empirically linked significant alterations in the expression of bacterial enterotypes with the initiation and persistence of several major metabolic and psychiatric disorders. Accordingly, the goal of our review is to highlight potential thematic/functional linkages of pathophysiological alterations in gut microbiota and bidirectional gut-brain signaling pathways with special emphasis on the potential roles of gut dysbiosis on the pathophysiology of psychiatric illnesses. We provide critical discussion of putative thematic linkages of ...