Emerging roles of gut microbiota and the immune system in the development of the enteric nervous system

Kabouridis, Panagiotis S.; Pachnis, Vassilis

doi:10.1172/jci76308

Cited by 90 publications

(70 citation statements)

References 136 publications

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“…Through a significant degree of coevolution, gut microbiota thrive in a mutually beneficial, symbiotic relationship with the host. Gut commensals exert a battery of functions for the optimal health of an organism, including the processing of nutrients, degradation of xenobiotics, protection from pathogenic microbes, regulation of intestinal barrier homeostasis, and maturation of the immune and enteric nervous systems (Eberl, 2010;Kabouridis and Pachnis, 2015). In turn, the intestine provides a warm, nutrient-rich, and protective environment for the many species of gut-resident microbes.…”

Section: Background Chronic Infectionsmentioning

confidence: 99%

Resistance Mechanisms to Immune-Checkpoint Blockade in Cancer: Tumor-Intrinsic and -Extrinsic Factors

Pitt¹,

Vétizou²,

Daillère³

et al. 2016

Immunity

802

594

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Inhibition of immune regulatory checkpoints, such as CTLA-4 and the PD-1-PD-L1 axis, is at the forefront of immunotherapy for cancers of various histological types. However, such immunotherapies fail to control neoplasia in a significant proportion of patients. Here, we review how a range of cancer-cell-autonomous cues, tumor-microenvironmental factors, and host-related influences might account for the heterogeneous responses and failures often encountered during therapies using immune-checkpoint blockade. Furthermore, we describe the emerging evidence of how the strong interrelationship between the immune system and the host microbiota can determine responses to cancer therapies, and we introduce a concept by which prior or concomitant modulation of the gut microbiome could optimize therapeutic outcomes upon immune-checkpoint blockade.

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Section: Background Chronic Infectionsmentioning

confidence: 99%

Resistance Mechanisms to Immune-Checkpoint Blockade in Cancer: Tumor-Intrinsic and -Extrinsic Factors

Pitt¹,

Vétizou²,

Daillère³

et al. 2016

Immunity

802

594

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“…Moreover, the intestine of germ-free mice suffers from several defects. Particularly, their gastrointestinal nervous and immune systems are very immature, and accordingly conventionalization partially corrects these defects [17,18]. More importantly, the gut barrier permeability is markedly altered in germ-free mice, which makes their intestine leaky and especially permeable to a variety of compounds, such as inflammatory lipopolysaccharides [19].…”

Section: Outcomes Of Changing Microbiotamentioning

confidence: 99%

Gut Microbiota and Host Metabolism: What Relationship

Mithieux

2017

Neuroendocrinology

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A large number of genomic studies have reported associations between the gut microbiota composition and metabolic diseases such as obesity or type 2 diabetes. This led to the widespread idea that a causal relationship could exist between intestinal microbiota and metabolic diseases. At odds with this idea, some compelling studies reported that global changes in microbiota composition have no effect on the host metabolism in obese mice or humans. However, specific bacteria are able to confer host metabolic benefits, such as Akkermansia muciniphila or Prevotella copri, when they are given by gavage in obese mice. A crucial link by which gut bacteria communicate with the host mucosa is based on metabolites or low-molecular-weight compounds. Among them, short-chain fatty acids produced from the fermentation of dietary fibers initiate beneficial effects on the host metabolism via the activation of intestinal gluconeogenesis (a mucosal function exerting antidiabetic and antiobesity effects through the activation of gut-brain neural circuits). However, fermentation of short-chain fatty acids is a function that is widespread among the main bacterial phyla and thus weakly depends on microbiota composition. Therefore, even if some bacteria may confer on the host metabolic benefits, the causal role of microbiota in metabolic diseases is not established.

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“…Th e type of diet could modify the intestinal microbiota and infl uence the brain and cardiovascular function in an integrated manner in which autonomic and endocrine systems participate. All this falls within the scope of the neurovisceral integration, in which the nervous system, whose development can be infl uenced by the intestinal microbiota (Kabouridis and Pachnis 2015), and the enteric endocrine system, including the classical APUD (amine precursor uptake and decarboxilation) system, could play a major role. Pearse and Polak (1971) proposed that APUD cells, where classic neurotransmitters and neuropeptides coexist, are originated from neural crest and interact with both autonomous and endocrine systems (Baylis et al 1993).…”

Section: Th E Gut In the Neuroendocrine Integration For The Cardiovasmentioning

confidence: 99%

Bidirectional asymmetry in the neurovisceral communication for the cardiovascular control: New insights

Prieto

Segarra

Martı́nez-Cañamero

et al. 2017

Endocrine Regulations

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Th e cardiovascular control involves a bidirectional functional connection between the brain and heart. We hypothesize that this connection could be extended to other organs using endocrine and autonomic nervous systems (ANS) as communication pathways. Th is implies a neuroendocrine interaction controlling particularly the cardiovascular function where the enzymatic cascade of the renin-angiotensin system (RAS) plays an essential role. It acts not only through its classic endocrine connection but also the ANS. In addition, the brain is functionally, anatomically, and neurochemically asymmetric. Moreover, this asymmetry goes even beyond the brain and it includes both sides of the peripheral nervous and neuroendocrine systems. We revised the available information and analyze the asymmetrical neuroendocrine bidirectional interaction for the cardiovascular control. Negative and positive correlations involving the RAS have been observed between brain, heart, kidney, gut, and plasma in physiologic and pathologic conditions. Th e central role of the peptides and enzymes of the RAS within this neurovisceral communication, as well as the importance of the asymmetrical distribution of the various RAS components in the pathologies involving this connection, are particularly discussed. In conclusion, there are numerous evidences supporting the existence of a neurovisceral connection with multiorgan involvement that controls, among others, the cardiovascular function. Th is connection is asymmetrically organized.

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Emerging roles of gut microbiota and the immune system in the development of the enteric nervous system

Cited by 90 publications

References 136 publications

Resistance Mechanisms to Immune-Checkpoint Blockade in Cancer: Tumor-Intrinsic and -Extrinsic Factors

Resistance Mechanisms to Immune-Checkpoint Blockade in Cancer: Tumor-Intrinsic and -Extrinsic Factors

Gut Microbiota and Host Metabolism: What Relationship

Bidirectional asymmetry in the neurovisceral communication for the cardiovascular control: New insights

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