Neuroepithelial circuit formed by innervation of sensory enteroendocrine cells
Diego V. Bohórquez,Rafiq A. Shahid,Alan Erdmann,Alex M. Kreger,Yu Wang,Nicole Calakos,Fan Wang,Rodger A. Liddle +7 more
TLDR
It is determined that neuropods provide a direct connection between enteroendocrine cells and neurons innervating the small intestine and colon, and this neuroepithelial circuit can serve as both a sensory conduit for food and gut microbes to interact with the nervous system and a portal for viruses to enter the enteric and central nervous systems.Abstract:
Satiety and other core physiological functions are modulated by sensory signals arising from the surface of the gut. Luminal nutrients and bacteria stimulate epithelial biosensors called enteroendocrine cells. Despite being electrically excitable, enteroendocrine cells are generally thought to communicate indirectly with nerves through hormone secretion and not through direct cell-nerve contact. However, we recently uncovered in intestinal enteroendocrine cells a cytoplasmic process that we named neuropod. Here, we determined that neuropods provide a direct connection between enteroendocrine cells and neurons innervating the small intestine and colon. Using cell-specific transgenic mice to study neural circuits, we found that enteroendocrine cells have the necessary elements for neurotransmission, including expression of genes that encode pre-, post-, and transsynaptic proteins. This neuroepithelial circuit was reconstituted in vitro by coculturing single enteroendocrine cells with sensory neurons. We used a monosynaptic rabies virus to define the circuit’s functional connectivity in vivo and determined that delivery of this neurotropic virus into the colon lumen resulted in the infection of mucosal nerves through enteroendocrine cells. This neuroepithelial circuit can serve as both a sensory conduit for food and gut microbes to interact with the nervous system and a portal for viruses to enter the enteric and central nervous systems.read more
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BRIEF COMMUNICATION ARISING: Gut hormone PYY3-36 physiologically inhibits food intake
Rachel L. Batterham,Michael A. Cowley,Caroline J. Small,Herbert Herzog,Mark A Cohen,C. L. Dakin,Alison M. Wren,Audrey E. Brynes,Malcolm J. Low +8 more
TL;DR: The authors showed that post-prandial elevation of PYY3-36 may act through the arcuate nucleus Y2R to inhibit feeding in a gut-hypothalamic pathway.
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The Microbiota-Gut-Brain Axis
John F. Cryan,Kenneth J. O’Riordan,Caitlin S. M. Cowan,Kiran V. Sandhu,Thomaz F.S. Bastiaanssen,Marcus Boehme,Martín Gabriel Codagnone,Sofia Cussotto,Christine Fülling,Anna V. Golubeva,Katherine E. Guzzetta,Minal Jaggar,Caitriona M. Long-Smith,Joshua M. Lyte,Jason A. Martin,Alicia Molinero-Perez,Gerard M. Moloney,Emanuela Morelli,Enrique Morillas,Rory C. O'Connor,Joana S Cruz-Pereira,Veronica L. Peterson,Kieran Rea,Nathaniel L. Ritz,Eoin Sherwin,Simon Spichak,Emily M. Teichman,Marcel van de Wouw,Ana Paula Ventura-Silva,Shauna E. Wallace-Fitzsimons,Niall P. Hyland,Gerard Clarke,Timothy G. Dinan +32 more
TL;DR: Future studies will focus on understanding the mechanisms underlying the microbiota-gut-brain axis and attempt to elucidate microbial-based intervention and therapeutic strategies for neuropsychiatric disorders.
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Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders
TL;DR: This review will discuss the possible role played by the gut microbiota in maintaining intestinal barrier function and the CNS consequences when it becomes disrupted, and draw on both clinical and preclinical evidence to support this concept.
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Stress & the gut-brain axis: Regulation by the microbiome
TL;DR: This report summarizes and builds upon some of the key concepts in the symposium “The Microbiome: Development, Stress, and Disease” within the context of how microbiota might influence the neurobiology of stress.
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Enterochromaffin Cells Are Gut Chemosensors that Couple to Sensory Neural Pathways
Nicholas W. Bellono,James R. Bayrer,Duncan B. Leitch,Joel Castro,Joel Castro,Chuchu Zhang,Tracey A. O'Donnell,Tracey A. O'Donnell,Stuart M. Brierley,Stuart M. Brierley,Holly A. Ingraham,David Julius +11 more
TL;DR: C cultured intestinal organoids are exploited together with single-cell measurements to elucidate intrinsic biophysical, pharmacological, and genetic properties of EC cells, showing that EC cells express specific chemosensory receptors, are electrically excitable, and modulate serotonin-sensitive primary afferent nerve fibers via synaptic connections, enabling them to detect and transduce environmental, metabolic, and homeostatic information from the gut directly to the nervous system.
References
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Gut hormone PYY 3-36 physiologically inhibits food intake
Rachel L. Batterham,Michael A. Cowley,Caroline J. Small,Herbert Herzog,Mark Cohen,C. L. Dakin,Alison M. Wren,Audrey E. Brynes,Malcolm J. Low,Mohammad A. Ghatei,Roger D. Cone,Stephen R. Bloom +11 more
TL;DR: In this paper, the authors showed that post-prandial elevation of PYY3-36 may act through the arcuate nucleus Y2R to inhibit feeding in a gut-hypothalamic pathway.
Journal Article
BRIEF COMMUNICATION ARISING: Gut hormone PYY3-36 physiologically inhibits food intake
Rachel L. Batterham,Michael A. Cowley,Caroline J. Small,Herbert Herzog,Mark A Cohen,C. L. Dakin,Alison M. Wren,Audrey E. Brynes,Malcolm J. Low +8 more
TL;DR: The authors showed that post-prandial elevation of PYY3-36 may act through the arcuate nucleus Y2R to inhibit feeding in a gut-hypothalamic pathway.
Journal ArticleDOI
Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41
Buck S. Samuel,Abdullah Shaito,Toshiyuki Motoike,Federico E. Rey,Fredrik Bäckhed,Fredrik Bäckhed,Jill K. Manchester,Robert E. Hammer,S. Clay Williams,Jan R. Crowley,Masashi Yanagisawa,Jeffrey I. Gordon +11 more
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TL;DR: This Review summarizes current knowledge regarding the neuroendocrine regulation of food intake by the gastrointestinal system, focusing on gastric distention, intestinal and pancreatic satiation peptides, and the orexigenic gastric hormone ghrelin, and highlights mechanisms governing nutrient sensing and peptide secretion by enteroendocrine cells.
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