Uts2b is a microbiota-regulated gene expressed in vagal afferent neurons connected to enteroendocrine cells producing cholecystokinin

Yoshioka, Y.; Tachibana, Yoshihisa; Uesaka, Toshihiro; Hioki, Hiroyuki; Sato, Yuya; Fukumoto, Takumi; Enomoto, Hideki

doi:10.1016/j.bbrc.2022.03.117

Cited by 5 publications

(5 citation statements)

References 22 publications

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“…2,49 Additionally, a few prior studies have reported that the gut microbiota and various microbial products regulate the transcriptome and excitability of vagal neurons. 58 For instance, nodose neurons from mice reared GF exhibited altered gene expression profiles when compared to those from SPF mice, 61 suggesting that the microbiome modulates the cellular state of vagal afferent neurons. In addition, bacterial supernatants from a cultured microbial community increased the intrinsic excitability of nodose neurons in vitro , through a mechanism that implicated a role for bacterial cysteine proteases.…”

Section: Discussionmentioning

confidence: 99%

“…37 As such, it is possible that the reductions in vagal tone seen in GF mice could be mediated by changes in both intestinal and non-intestinal vagal afferents and/or the presence of residual microbes or microbial products in the intestine of SPF mice treated twice daily with ABX by oral gavage. Moreover, the reported alterations in nodose gene expression in GF mice relative to SPF mice 61 raise the question of whether there are early influences of microbiota status on vagal neuronal development, which are not captured by oral ABX treatment during adulthood. Further studies are needed to uncover the relative contributions of different vagal neuronal subtypes in mediating microbiome-induced alterations in vagal tone, as well as to what degree microbes endogenous to different parts of the gastrointestinal tract contribute to these alterations.…”

Section: Discussionmentioning

confidence: 99%

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Vagal interoception of microbial metabolites from the small intestinal lumen

Jameson,

Kazmi,

Son

et al. 2023

Preprint

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SUMMARYThe vagus nerve is proposed to enable communication between the gut microbiome and brain, but activity-based evidence is lacking. Herein, we assess the extent of gut microbial influences on afferent vagal activity and metabolite signaling mechanisms involved. We find that mice reared without microbiota (germ-free, GF) exhibit decreased vagal afferent tone relative to conventionally colonized mice (specific pathogen-free, SPF), which is reversed by colonization with SPF microbiota. Perfusing non-absorbable antibiotics (ABX) into the small intestine of SPF mice, but not GF mice, acutely decreases vagal activity, which is restored upon re-perfusion with bulk lumenal contents or sterile filtrates from the small intestine and cecum of SPF, but not GF, mice. Of several candidates identified by metabolomic profiling, microbiome-dependent short-chain fatty acids, bile acids, and 3-indoxyl sulfate stimulate vagal activity with varied response kinetics, which is blocked by co-perfusion of pharmacological antagonists of FFAR2, TGR5, and TRPA1, respectively, into the small intestine. At the single-unit level, serial perfusion of each metabolite class elicits more singly responsive neurons than dually responsive neurons, suggesting distinct neuronal detection of different microbiome- and macronutrient-dependent metabolites. Finally, microbial metabolite-induced increases in vagal activity correspond with activation of neurons in the nucleus of the solitary tract, which is also blocked by co-administration of their respective receptor antagonists. Results from this study reveal that the gut microbiome regulates select metabolites in the intestinal lumen that differentially activate chemosensory vagal afferent neurons, thereby enabling microbial modulation of interoceptive signals for gut-brain communication.HIGHLIGHTSMicrobiota colonization status modulates afferent vagal nerve activityGut microbes differentially regulate metabolites in the small intestine and cecumSelect microbial metabolites stimulate vagal afferents with varied response kineticsSelect microbial metabolites activate vagal afferent neurons and brainstem neurons via receptor-dependent signaling

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Vagal interoception of microbial metabolites from the small intestinal lumen

Jameson,

Kazmi,

Son

et al. 2023

Preprint

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“…Based on previous study (Yoshioka et al, 2022), in situ hybridization (ISH) was performed on a 16 μm section of E13.5 embryos. Pcgf1 digoxigenin (DIG)‐labeled cRNA probe was synthesized from a DNA fragment of the Pcgf1 cDNA (nucleotide 33–382) using the DIG RNA Labeling Kit (11175025910, Roche, Basel, Switzerland).…”

Section: Methodsmentioning

confidence: 99%

“…Based on previous study (Yoshioka et al, 2022), in situ hybridization (ISH) was performed on a 16 μm section of E13.5 embryos.…”

Section: In Situ Hybridizationmentioning

confidence: 99%

Pcgf1 gene disruption reveals primary involvement of epigenetic mechanism in neuronal subtype specification in the enteric nervous system

et al. 2023

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The enteric nervous system (ENS) regulates gut functions independently from the central nervous system (CNS) by its highly autonomic neural circuit that integrates diverse neuronal subtypes. Although several transcription factors are shown to be necessary for the generation of some enteric neuron subtypes, the mechanisms underlying neuronal subtype specification in the ENS remain elusive. In this study, we examined the biological function of Polycomb group RING finger protein 1 (PCGF1), one of the epigenetic modifiers, in the development and differentiation of the ENS by disrupting the Pcgf1 gene selectively in the autonomic‐lineage cells. Although ENS precursor migration and enteric neurogenesis were largely unaffected, neuronal differentiation was impaired in the Pcgf1‐deficient mice, with the numbers of neurons expressing somatostatin (Sst+) decreased in multiple gut regions. Notably, the decrease in Sst+ neurons was associated with the corresponding increase in calbindin+ neurons in the proximal colon. These findings suggest that neuronal subtype conversion may occur in the absence of PCGF1 and that epigenetic mechanism is primarily involved in specification of some enteric neuron subtypes.This article is protected by copyright. All rights reserved.

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“…The ENS can secrete neurotransmitters and neuropeptides, such as acetycholine (Ach), noradrenaline (NE), nitric oxide (NO), and vasoactive intestinal peptide (VIP), which are important mediators affecting the gut barrier [6] . Evidence has shown that the gut microbiota-regulated gene Uts2b or its metabolites such as SCFAs can stimulate enteroendocrine cells (EECs) to secrete cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), peptide YY (PYY) and other hormones [71] , [72] , [73] . GLP-1 is normally secreted by EECs and released into the bloodstream, where they regulate the rumen barrier once they reach the rumen wall [74] .…”

Section: “Gut/rumen Leakage” Is the Pathological Basis Of The Migrati...mentioning

confidence: 99%

Gut/rumen-mammary gland axis in mastitis: Gut/rumen microbiota–mediated “gastroenterogenic mastitis”

Zhao

et al. 2024

Journal of Advanced Research

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Uts2b is a microbiota-regulated gene expressed in vagal afferent neurons connected to enteroendocrine cells producing cholecystokinin

Cited by 5 publications

References 22 publications

Vagal interoception of microbial metabolites from the small intestinal lumen

Vagal interoception of microbial metabolites from the small intestinal lumen

Pcgf1 gene disruption reveals primary involvement of epigenetic mechanism in neuronal subtype specification in the enteric nervous system

Gut/rumen-mammary gland axis in mastitis: Gut/rumen microbiota–mediated “gastroenterogenic mastitis”

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