The enteric nervous system

Physiological Reviews, Journal Year: 2022, Volume and Issue: 103(2), P. 1487 - 1564

Published: Dec. 15, 2022

Of all the organ systems in body, gastrointestinal tract is most complicated terms of numbers structures involved, each with different functions, and types signaling molecules utilized. The digestion food absorption nutrients, electrolytes, water occurs a hostile luminal environment that contains large diverse microbiota. At core regulatory control digestive defensive functions enteric nervous system (ENS), complex neurons glia gut wall. In this review, we discuss 1) intrinsic neural involved 2) how ENS interacts immune system, microbiota, epithelium to maintain mucosal defense barrier function. We highlight developments have revolutionized our understanding physiology pathophysiology control. These include new molecular architecture ENS, organization function motor circuits, roles glia. explore transduction stimuli by enteroendocrine cells, regulation intestinal glia, local role microbiota regulating structure ENS. Multifunctional work together glial macrophages, interstitial cells integrating an array signals initiate outputs are precisely regulated space time homeostasis.

Language: Английский

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The preference for sugar over sweetener depends on a gut sensor cell

Nature Neuroscience, Journal Year: 2022, Volume and Issue: 25(2), P. 191 - 200

Published: Jan. 13, 2022

Guided by gut sensory cues, humans and animals prefer nutritive sugars over non-caloric sweeteners, but how the steers such preferences remains unknown. In intestine, neuropod cells synapse with vagal neurons to convey sugar stimuli brain within seconds. Here, we found that cholecystokinin (CCK)-labeled duodenal differentiate transduce luminal from sweeteners vagus nerve using sweet taste receptors sodium glucose transporters. The two stimulus types elicited distinct neural pathways: while sweetener stimulated purinergic neurotransmission, glutamatergic neurotransmission. To probe contribution of these behavior, developed optogenetics for lumen engineering a flexible fiberoptic. We showed preference in mice depends on cell signaling. By swiftly discerning precise identity nutrient stimuli, serve as entry point guide choices.

Language: Английский

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The intestine as an endocrine organ and the role of gut hormones in metabolic regulation

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2023, Volume and Issue: 20(12), P. 784 - 796

Published: Aug. 25, 2023

Language: Английский

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Gut microbiota dysbiosis in functional gastrointestinal disorders: Underpinning the symptoms and pathophysiology

JGH Open, Journal Year: 2021, Volume and Issue: 5(9), P. 976 - 987

Published: March 23, 2021

Functional gastrointestinal disorders (FGIDs), currently known as of gut-brain interaction, are emerging microbiota-gut-brain abnormalities that prevalent worldwide. The pathogenesis FGIDs is heterogeneous and intertwined with gut microbiota its derived molecule-modulated mechanisms, including dysmotility, visceral hypersensitivity, immune abnormalities, abnormal secretion, impaired barrier function. There has been phenomenal progress in understanding the role by underpinning species alternations between healthy pathological conditions such FGIDs. However, precise microbiota-directed cellular molecular pathogeneses yet enigmatic. Determining mechanistic link (GI) diseases difficult due to (i) lack robust animal models imitating various aspects human FGID pathophysiology; (ii) absence longitudinal and/or studies unveil interaction FGID-relevant pathogenesis; (iii) uncertainty about connections studies; (iv) insufficient data supporting a holistic view disease-specific pathophysiological changes patients. These unidentified gaps open possibilities explore mechanisms directed through dysbiosis current treatment options for dysbiotic limited; dietary interventions, antibiotics, probiotics, fecal transplantation front-line clinical options. Here, we review contribution molecules homeostasis possible involved leading potential therapeutics

Language: Английский

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Specialized Mechanosensory Epithelial Cells in Mouse Gut Intrinsic Tactile Sensitivity

Gastroenterology, Journal Year: 2021, Volume and Issue: 162(2), P. 535 - 547.e13

Published: Oct. 22, 2021

Language: Английский

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Current Treatment Options and Therapeutic Insights for Gastrointestinal Dysmotility and Functional Gastrointestinal Disorders

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Jan. 25, 2022

Functional gastrointestinal disorders (FGIDs) have been re-named as of gut-brain interactions. These conditions are not only common in clinical practice, but also the community. In reference to Rome IV criteria, most FGIDs, include functional dyspepsia (FD) and irritable bowel syndrome (IBS). Additionally, there is substantial overlap these other specific motility disorders, such gastroparesis. heterogeneous intertwined with several proposed pathophysiological mechanisms, altered gut motility, intestinal barrier dysfunction, immune visceral hypersensitivity, GI secretion, presence degree bile acid malabsorption, microbial dysbiosis, alterations axis. The treatment options currently available lifestyle modifications, dietary microbiota manipulation interventions including fecal transplantation, prokinetics, antispasmodics, laxatives, centrally peripherally acting neuromodulators. However, that targets mechanisms underlying symptoms scanty. Pharmacological agents developed based on cellular molecular pathologies might provide best avenue for future pharmaceutical development. therapies lack long-term effectiveness safety their use treat FGIDs. Furthermore, fundamental challenges treating should be defined; instance, 1. Cause effect cannot disentangled between due current entail off-label medications symptoms. 2. Despite knowledge our plays an essential part maintaining health, exact functions homeostasis still unclear. What constitutes a healthy microbiome further, precise definition dysbiosis lacking. More comprehensive, large-scale, longitudinal studies utilizing multi-omics data needed dissect contribution disease pathogenesis. Accordingly, we review options, insight pathophysiology, therapeutic modalities, challenges, clues care management dyspepsia, gastroparesis, syndrome, constipation, diarrhea.

Language: Английский

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Xiao Cheng Qi Decoction, an Ancient Chinese Herbal Mixture, Relieves Loperamide-Induced Slow-Transit Constipation in Mice: An Action Mediated by Gut Microbiota

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(2), P. 153 - 153

Published: Jan. 24, 2024

Xiao Cheng Qi (XCQ) decoction, an ancient Chinese herbal mixture, has been used in treating slow-transit constipation (STC) for years. The underlying action mechanism relieving the clinical symptoms is unclear. Several lines of evidence point to a strong link between and gut microbiota. Short-chain fatty acids (SCFAs) microbial metabolites have shown affect 5-HT synthesis by activating GPR43 receptor localized on intestinal enterochromaffin cells, since receptors are known influence colonic peristalsis. objective this study was evaluate efficacy XCQ alleviating mouse model STC induced loperamide. application loperamide leads decrease transport fecal water, which establish animal STC. In addition, relationship microbiota determined. materials, composed Rhei Radix et Rhizoma (Rhizomes Rheum palmatum L., Polygonaceae) 55.2 g, Magnoliae Officinalis Cortex (Barks Magnolia officinalis Rehd. Wils, Magnoliaceae) 27.6 Aurantii Fructus Immaturus (Fruitlet Citrus aurantium Rutaceae) 36.0 were extracted with water prepare decoction. constipated mice (10 mg/kg/day), then treated oral dose extract (2.0, 4.0, 8.0 g/kg/day) two times day. Mosapride administered as positive drug. loperamide-induced mice, therapeutic parameters XCQ-treated determined, i.e., (i) constipation, composition microbiota, amount short-chain feces; (ii) plasma level 5-HT; (iii) expressions 5-HT4 colon. ameliorated mice. treatment increased relative abundances Lactobacillus, Prevotellaceae_UCG_001, Prevotellaceae_NK3B31_group, Muribaculaceae, Roseburia feces decreased Desulfovibrio, Tuzzerella, Lachnospiraceae_ NK4A136_group. levels SCFAs stools from group significantly lower than those control group, greatly elevated via XCQ. Compared receptor, significantly. anti-constipation could be related modulation increase SCFAs, 5-HT, receptor. Our results indicate that potent natural product strategy constipation.

Language: Английский

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The gut-brain axis: spatial relationship between spinal afferent nerves and 5-HT-containing enterochromaffin cells in mucosa of mouse colon

AJP Gastrointestinal and Liver Physiology, Journal Year: 2022, Volume and Issue: 322(5), P. G523 - G533

Published: March 16, 2022

Cross talk between the gastrointestinal tract and brain is of significant relevance for human health disease. However, our understanding how gut communicate has been limited by a lack techniques to identify precise spatial relationship extrinsic nerve endings their proximity specific cell types that line inner surface tract. We used an in vivo anterograde tracing technique, previously developed laboratory, selectively label single spinal afferent axons mouse colonic mucosa. The closest three-dimensional distances axonal varicosities enterochromaffin (EC) cells, which contain serotonin (5-hydroxytryptamine; 5-HT), were then measured. mean (± standard deviation) any varicosity along axon or its ending, nearest EC cell, 5.7 ± 6.0 μm (median: 3.6 μm) 26.9 18.6 24.1 μm), respectively. Randomization location cells revealed similar results this actual data. These are ∼200-1,000 times greater than those pre- postsynaptic membranes (15-25 nm) underlie synaptic transmission vertebrate nervous system. Our findings suggest 5-HT-containing release substances activate centrally projecting nerves likely via diffusion, as such signaling unlikely occur with fidelity synapse.NEW & NOTEWORTHY show absence close physical contact Similar relative observed randomized afferents compared This suggests released from act neighboring relay sensory information lumen brain.

Language: Английский

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A Dual-Biomineralized Yeast Micro-/Nanorobot with Self-Driving Penetration for Gastritis Therapy and Motility Recovery

ACS Nano, Journal Year: 2023, Volume and Issue: 17(7), P. 6410 - 6422

Published: March 29, 2023

Micro-/nanorobots have attracted great interest in the field of drug delivery and treatment, while preparations for biocompatible robots are extremely challenging. Here, a self-driving yeast micro-/nanorobot (Cur@CaY-robot) is designed via dual biomineralization acid catalysis calcium carbonate (CaCO3). Inner nano-CaCO3 inside cells (CaY) biomineralized through cell respiration provides nanoscaffolds highly encapsulating curcumin (Cur). Meanwhile, CaCO3 crystals outside (outer-CaCO3) uniaxial growth offer an asymmetric power source self-propelled motility. The Cur@CaY-robot displays efficient motion gastric acid, with potential deep penetration to thick mucus, which significantly improves accumulation agents stomach wall tissue robust gastritis therapy. More importantly, Ca2+ cations released from also synergistically repair motility mice. Such micro-/nanorobots exhibit desirable biocompatibility biodegradability good loading capacity drugs. This work idea design environmentally friendly biosynthesis strategy active precise

Language: Английский

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Identification of vagal afferent nerve endings in the mouse colon and their spatial relationship with enterochromaffin cells

Cell and Tissue Research, Journal Year: 2024, Volume and Issue: 396(3), P. 313 - 327

Published: Feb. 22, 2024

Abstract Understanding how the gut communicates with brain, via sensory nerves, is of significant interest to medical science. Enteroendocrine cells (EEC) that line mucosa gastrointestinal tract release neurochemicals, including largest quantity 5-hydroxytryptamine (5-HT). How substances, like 5-HT, from enterochromaffin (EC) activates vagal afferent nerve endings unresolved. We performed anterograde labelling nodose ganglia in vivo and identified axons whole-mount full-length preparations mouse colon. then determined spatial relationship between mucosal-projecting EC situ using 3D imaging. The mean distances mucosa, or nearest varicosities along axon branches, cell were 29.6 ± 19.2 μm ( n = 107, N 6) 25.7 15.2 119, 6), respectively. No made close contacts cells. are many hundreds times greater than known pre- post-synaptic membranes (typically 10–20 nm) underlie synaptic transmission vertebrates. absence any physical 5-HT-containing leads inescapable conclusion mechanism by which 5-HT ECs colonic occurs a paracrine fashion, activate afferents.

Language: Английский

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