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Article ; Online: In Memoriam-Helen J. Cooke (1943-2021).

Carey, Hannah V / Raybould, Helen E

2022 Volume 163, Issue 6, Page(s) 1475–1476

Language	English
Publishing date	2022-08-13
Publishing country	United States
Document type	Editorial
ZDB-ID	80112-4
ISSN	1528-0012 ; 0016-5085
ISSN (online)	1528-0012
ISSN	0016-5085
DOI	10.1053/j.gastro.2022.08.026
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Article ; Online: Microfluidic compartmentalization of rat vagal afferent neurons to model gut-brain axis.

Girardi, Gregory / Zumpano, Danielle / Raybould, Helen / Seker, Erkin

Bioelectronic medicine

2024 Volume 10, Issue 1, Page(s) 3

Abstract: ... the course of 24 h. Additionally, mechanical perturbation (e.g., rinsing) of the neurite terminals ...

Abstract	Background: Vagal afferent neurons represent the key neurosensory branch of the gut-brain axis, which describes the bidirectional communication between the gastrointestinal system and the brain. These neurons are important for detecting and relaying sensory information from the periphery to the central nervous system to modulate feeding behavior, metabolism, and inflammation. Confounding variables complicate the process of isolating the role of the vagal afferents in mediating these physiological processes. Therefore, we developed a microfluidic model of the sensory branch of the gut-brain axis. We show that this microfluidic model successfully compartmentalizes the cell body and neurite terminals of the neurons, thereby simulates the anatomical layout of these neurons to more accurately study physiologically-relevant processes. Methods: We implemented a primary rat vagal afferent neuron culture into a microfluidic platform consisting of two concentric chambers interconnected with radial microchannels. The microfluidic platform separated cell bodies from neurite terminals of vagal afferent neurons. We then introduced physiologically-relevant gastrointestinal effector molecules at the nerve terminals and assessed their retrograde transport along the neurite or capacity to elicit an electrophysiological response using live cell calcium imaging. Results: The angle of microchannel outlets dictated the probability of neurites growing into a chamber versus tracking along chamber walls. When the neurite terminals were exposed to fluorescently-labeled cholera toxin subunit B, the proteins were taken up and retrogradely transported along the neurites over the course of 24 h. Additionally, mechanical perturbation (e.g., rinsing) of the neurite terminals significantly increased intracellular calcium concentration in the distal soma. Finally, membrane-displayed receptor for capsaicin was expressed and trafficked along newly projected neurites, as revealed by confocal microscopy. Conclusions: In this work, we developed a microfluidic device that can recapitulate the anatomical layout of vagal afferent neurons in vitro. We demonstrated two physiologically-relevant applications of the platforms: retrograde transport and electrophysiological response. We expect this tool to enable controlled studies on the role of vagal afferent neurons in the gut-brain axis.
Language	English
Publishing date	2024-02-21
Publishing country	England
Document type	Journal Article
ZDB-ID	2929561-0
ISSN	2332-8886 ; 2332-8886
ISSN (online)	2332-8886
ISSN	2332-8886
DOI	10.1186/s42234-023-00140-3
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Article ; Online: Microbial metabolites and the vagal afferent pathway in the control of food intake.

Raybould, Helen E / Zumpano, Danielle L

Physiology & behavior

2021 Volume 240, Page(s) 113555

Abstract: The gut microbiota is able to influence overall energy balance via effects on both energy intake and expenditure, and is a peripheral target for potential obesity therapies. However, the precise mechanism by which the gut microbiota influences energy ... ...

Abstract	The gut microbiota is able to influence overall energy balance via effects on both energy intake and expenditure, and is a peripheral target for potential obesity therapies. However, the precise mechanism by which the gut microbiota influences energy intake and body weight regulation is not clear. Microbes use small molecules to communicate with each other; some of these molecules are ligands at mammalian receptors and this may be a mechanism by which microbes communicate with the host. Here we briefly review the literature showing beneficial effects of microbial metabolites on food intake regulation and examine the potential role for vagal afferent neurons, the gut-brain axis.
MeSH term(s)	Afferent Pathways ; Animals ; Eating ; Energy Metabolism ; Gastrointestinal Microbiome ; Neurons, Afferent ; Vagus Nerve
Language	English
Publishing date	2021-08-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3907-x
ISSN	1873-507X ; 0031-9384
ISSN (online)	1873-507X
ISSN	0031-9384
DOI	10.1016/j.physbeh.2021.113555
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Article ; Online: Estrogen and gut satiety hormones in vagus-hindbrain axis.

Huang, Kuei-Pin / Raybould, Helen E

Peptides

2020 Volume 133, Page(s) 170389

Abstract: Estrogens modulate different physiological functions, including reproduction, inflammation, bone formation, energy expenditure, and food intake. In this review, we highlight the effect of estrogens on food intake regulation and the latest literature on ... ...

Abstract	Estrogens modulate different physiological functions, including reproduction, inflammation, bone formation, energy expenditure, and food intake. In this review, we highlight the effect of estrogens on food intake regulation and the latest literature on intracellular estrogen signaling. In addition, gut satiety hormones, such as cholecystokinin, glucagon-like peptide 1 and leptin are essential to regulate ingestive behaviors in the postprandial period. These peripheral signals are sensed by vagal afferent terminals in the gut wall and transmitted to the hindbrain axis. Here we 1. review the role of the vagus-hindbrain axis in response to gut satiety signals and 2. consider the potential synergistic effects of estrogens on gut satiety signals at the level of vagal afferent neurons and nuclei located in the hindbrain. Understanding the action of estrogens in gut-brain axis provides a potential strategy to develop estrogen-based therapies for metabolic diseases and emphasizes the importance of sex difference in the treatment of obesity.
MeSH term(s)	Animals ; Cholecystokinin/metabolism ; Eating ; Energy Metabolism ; Estrogens ; Female ; Gastrointestinal Hormones/physiology ; Glucagon-Like Peptide 1/metabolism ; Humans ; Leptin/metabolism ; Male ; Neurons, Afferent/metabolism ; Receptors, Estrogen/metabolism ; Rhombencephalon/physiology ; Satiety Response/physiology ; Vagus Nerve/physiology
Chemical Substances	Estrogens ; Gastrointestinal Hormones ; Leptin ; Receptors, Estrogen ; Glucagon-Like Peptide 1 (89750-14-1) ; Cholecystokinin (9011-97-6)
Language	English
Publishing date	2020-08-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	769028-9
ISSN	1873-5169 ; 0196-9781
ISSN (online)	1873-5169
ISSN	0196-9781
DOI	10.1016/j.peptides.2020.170389
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Article: Microbial metabolites and the vagal afferent pathway in the control of food intake

Raybould, Helen E / Zumpano, Danielle L

Physiology & behavior. 2021 Oct. 15, v. 240

2021

Abstract	The gut microbiota is able to influence overall energy balance via effects on both energy intake and expenditure, and is a peripheral target for potential obesity therapies. However, the precise mechanism by which the gut microbiota influences energy intake and body weight regulation is not clear. Microbes use small molecules to communicate with each other; some of these molecules are ligands at mammalian receptors and this may be a mechanism by which microbes communicate with the host. Here we briefly review the literature showing beneficial effects of microbial metabolites on food intake regulation and examine the potential role for vagal afferent neurons, the gut-brain axis.
Keywords	behavior ; body weight changes ; energy intake ; food intake ; intestinal microorganisms ; ligands ; mammals ; metabolites ; obesity ; physiology
Language	English
Dates of publication	2021-1015
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	3907-x
ISSN	1873-507X ; 0031-9384
ISSN (online)	1873-507X
ISSN	0031-9384
DOI	10.1016/j.physbeh.2021.113555
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Article ; Online: The heat is on: does direct application of capsaicin to autonomic nerves produce a specific deafferentation?

Raybould, Helen E

The Journal of physiology

2013 Volume 591, Issue 6, Page(s) 1405

MeSH term(s)	Animals ; Capsaicin/pharmacology ; Vagus Nerve/drug effects
Chemical Substances	Capsaicin (S07O44R1ZM)
Language	English
Publishing date	2013-03-14
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/jphysiol.2013.251868
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Article ; Online: Cultured Vagal Afferent Neurons as Sensors for Intestinal Effector Molecules.

Girardi, Gregory / Zumpano, Danielle / Goshi, Noah / Raybould, Helen / Seker, Erkin

Biosensors

2023 Volume 13, Issue 6

Abstract: The gut-brain axis embodies the bi-directional communication between the gastrointestinal tract and the central nervous system (CNS), where vagal afferent neurons (VANs) serve as sensors for a variety of gut-derived signals. The gut is colonized by a ... ...

Abstract	The gut-brain axis embodies the bi-directional communication between the gastrointestinal tract and the central nervous system (CNS), where vagal afferent neurons (VANs) serve as sensors for a variety of gut-derived signals. The gut is colonized by a large and diverse population of microorganisms that communicate via small (effector) molecules, which also act on the VAN terminals situated in the gut viscera and consequently influence many CNS processes. However, the convoluted in vivo environment makes it difficult to study the causative impact of the effector molecules on VAN activation or desensitization. Here, we report on a VAN culture and its proof-of-principle demonstration as a cell-based sensor to monitor the influence of gastrointestinal effector molecules on neuronal behavior. We initially compared the effect of surface coatings (poly-L-lysine vs. Matrigel) and culture media composition (serum vs. growth factor supplement) on neurite growth as a surrogate of VAN regeneration following tissue harvesting, where the Matrigel coating, but not the media composition, played a significant role in the increased neurite growth. We then used both live-cell calcium imaging and extracellular electrophysiological recordings to show that the VANs responded to classical effector molecules of endogenous and exogenous origin (cholecystokinin serotonin and capsaicin) in a complex fashion. We expect this study to enable platforms for screening various effector molecules and their influence on VAN activity, assessed by their information-rich electrophysiological fingerprints.
MeSH term(s)	Neurons, Afferent/metabolism ; Vagus Nerve/physiology ; Cholecystokinin/metabolism ; Cholecystokinin/pharmacology ; Neurons/metabolism ; Central Nervous System/metabolism
Chemical Substances	Cholecystokinin (9011-97-6)
Language	English
Publishing date	2023-05-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662125-3
ISSN	2079-6374 ; 2079-6374
ISSN (online)	2079-6374
ISSN	2079-6374
DOI	10.3390/bios13060601
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Article ; Online: Milk oligosaccharide-driven persistence of Bifidobacterium pseudocatenulatum modulates local and systemic microbial metabolites upon synbiotic treatment in conventionally colonized mice.

Larke, Jules A / Heiss, Britta E / Ehrlich, Amy M / Taft, Diana H / Raybould, Helen E / Mills, David A / Slupsky, Carolyn M

Microbiome

2023 Volume 11, Issue 1, Page(s) 194

Abstract: Background: Bifidobacteria represent an important gut commensal in humans, particularly during initial microbiome assembly in the first year of life. Enrichment of Bifidobacterium is mediated though the utilization of human milk oligosaccharides (HMOs), ...

Abstract	Background: Bifidobacteria represent an important gut commensal in humans, particularly during initial microbiome assembly in the first year of life. Enrichment of Bifidobacterium is mediated though the utilization of human milk oligosaccharides (HMOs), as several human-adapted species have dedicated genomic loci for transport and metabolism of these glycans. This results in the release of fermentation products into the gut lumen which may offer physiological benefits to the host. Synbiotic pairing of probiotic species with a cognate prebiotic delivers a competitive advantage, as the prebiotic provides a nutrient niche. Methods: To determine the fitness advantage and metabolic characteristics of an HMO-catabolizing Bifidobacterium strain in the presence or absence of 2'-fucosyllactose (2'-FL), conventionally colonized mice were gavaged with either Bifidobacterium pseudocatenulatum MP80 (B.p. MP80) (as the probiotic) or saline during the first 3 days of the experiment and received water or water containing 2'-FL (as the prebiotic) throughout the study. Results: 16S rRNA gene sequencing revealed that mice provided only B.p. MP80 were observed to have a similar microbiota composition as control mice throughout the experiment with a consistently low proportion of Bifidobacteriaceae present. Using Conclusions: This study reinforces that the colonization of the gut with a commensal microorganism does not guarantee a specific functional output. Video Abstract.
MeSH term(s)	Humans ; Animals ; Mice ; Bifidobacterium pseudocatenulatum ; Synbiotics ; RNA, Ribosomal, 16S/genetics ; Milk, Human ; Oligosaccharides ; Bifidobacterium ; Prebiotics ; Actinobacteria
Chemical Substances	RNA, Ribosomal, 16S ; Oligosaccharides ; Prebiotics
Language	English
Publishing date	2023-08-28
Publishing country	England
Document type	Video-Audio Media ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2697425-3
ISSN	2049-2618 ; 2049-2618
ISSN (online)	2049-2618
ISSN	2049-2618
DOI	10.1186/s40168-023-01624-9
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Article ; Online: Quantifying Gut Microbial Short-Chain Fatty Acids and Their Isotopomers in Mechanistic Studies Using a Rapid, Readily Expandable LC-MS Platform.

Weng, Cheng-Yu Charlie / Suarez, Christopher / Cheang, Shawn Ehlers / Couture, Garret / Goodson, Michael L / Barboza, Mariana / Kalanetra, Karen M / Masarweh, Chad F / Mills, David A / Raybould, Helen E / Lebrilla, Carlito B

Analytical chemistry

2024 Volume 96, Issue 6, Page(s) 2415–2424

Abstract: Short-chain fatty acids (SCFAs) comprise the largest group of gut microbial fermentation products. While absorption of most nutrients occurs in the small intestine, indigestible dietary components, such as fiber, reach the colon and are processed by the ... ...

Abstract	Short-chain fatty acids (SCFAs) comprise the largest group of gut microbial fermentation products. While absorption of most nutrients occurs in the small intestine, indigestible dietary components, such as fiber, reach the colon and are processed by the gut microbiome to produce a wide array of metabolites that influence host physiology. Numerous studies have implicated SCFAs as key modulators of host health, such as in regulating irritable bowel syndrome (IBS). However, robust methods are still required for their detection and quantitation to meet the demands of biological studies probing the complex interplay of the gut-host-health paradigm. In this study, a sensitive, rapid-throughput, and readily expandible UHPLC-QqQ-MS platform using 2-PA derivatization was developed for the quantitation of gut-microbially derived SCFAs, related metabolites, and isotopically labeled homologues. The utility of this platform was then demonstrated by investigating the production of SCFAs in cecal contents from mice feeding studies, human fecal bioreactors, and fecal/bacterial fermentations of isotopically labeled dietary carbohydrates. Overall, the workflow proposed in this study serves as an invaluable tool for the rapidly expanding gut-microbiome and precision nutrition research field.
MeSH term(s)	Humans ; Mice ; Animals ; Liquid Chromatography-Mass Spectrometry ; Chromatography, Liquid ; Gastrointestinal Microbiome/physiology ; Tandem Mass Spectrometry ; Fatty Acids, Volatile/metabolism
Chemical Substances	Fatty Acids, Volatile
Language	English
Publishing date	2024-01-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021/acs.analchem.3c04352
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Article ; Online: Gut microbiota, epithelial function and derangements in obesity.

Raybould, Helen E

The Journal of physiology

2011 Volume 590, Issue 3, Page(s) 441–446

Abstract: The gut epithelium is a barrier between the 'outside' and 'inside' world. The major function of the epithelium is to absorb nutrients, ions and water, yet it must balance these functions with that of protecting the 'inside' world from potentially harmful ...

Abstract	The gut epithelium is a barrier between the 'outside' and 'inside' world. The major function of the epithelium is to absorb nutrients, ions and water, yet it must balance these functions with that of protecting the 'inside' world from potentially harmful toxins, irritants, bacteria and other pathogens that also exist in the gut lumen. The health of an individual depends upon the efficient digestion and absorption of all required nutrients from the diet. This requires sensing of meal components by gut enteroendocrine cells, activation of neural and humoral pathways to regulate gastrointestinal motor, secretory and absorptive functions, and also to regulate food intake and plasma levels of glucose. In this way, there is a balance between the delivery of food and the digestive and absorptive capacity of the intestine. Maintenance of the mucosal barrier likewise requires sensory detection of pathogens, toxins and irritants; breakdown of the epithelial barrier is associated with gut inflammation and may ultimately lead to inflammatory bowel disease. However, disruption of the barrier alone is not sufficient to cause frank inflammatory bowel disease. Several recent studies have provided compelling new evidence to suggest that changes in epithelial barrier function and inflammation are associated with and may even lead to altered regulation of body weight and glucose homeostasis. This article provides a brief review of some recent evidence to support the hypothesis that changes in the gut microbiota and alteration of gut epithelial function will perturb the homeostatic humoral and neural pathways controlling food intake and body weight.
MeSH term(s)	Animals ; Humans ; Inflammation/complications ; Inflammation/microbiology ; Intestinal Mucosa/microbiology ; Intestinal Mucosa/pathology ; Intestinal Mucosa/physiology ; Obesity/microbiology
Language	English
Publishing date	2011-12-19
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/jphysiol.2011.222133
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