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A Neural Circuit for Gut-Induced Reward
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“Furthermore, a recent study in mice has shown that activation of GI vagal afferents influence reward behavior in mice (Han et al., 2018)”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Han et al., 2018
In the citing paper
“a recent report show that optogenetic stimulation of the vagal gut-to-brain axis modulates reward related behavior (Han et al., 2018), indicating that the vagus nerve connects the gut to the brain reward system.”
From Mechanisms underlying microbial-mediated changes in social behavior in mouse models of autism spectrum disorder (2019) · cites this paper as Han et al., 2018
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“Vagal stimulation has also been shown to induce dopamine release in the substantia nigra (Han et al., 2018).”
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“Some of these hormones (e.g., CCK) stimulate vagus nerves, implying that rapid feed-forward signals are mediated by neurons in the nodose ganglia (Alhadeff et al., 2019; Bai et al., 2019; Han et al., 2018; Kaelberer et al., 2018; Williams et al., 2016).”
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Vagus nerve stimulation drives selective circuit modulation through cholinergic reinforcement
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The gut-to-brain axis for toxin-induced defensive responses
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Enteric neurons increase maternal food intake during reproduction
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Gut microbes participate in food preference alterations during obesity
d’Oplinter, A. D. W., Rastelli, M., Hul, M. V., Delzenne, N. M., Cani, P. D., & Everard, A. (2021) · Gut Microbes · doi:10.1080/19490976.2021.1959242 · Cited by 112
“demonstrated that fat uses a PPARαdependent pathway and the vagus nerve to inform the striatum and induce dopamine release.(27) On the other hand, sugar-induced striatal dopamine release is mainly due to the metabolism of the sugar in the gut, completed with the information from a portal vein sensor.”
BackgroundThe Microbiota–Gut–Brain Axis: Psychoneuroimmunological Insights
Marano, G., Mazza, M., Lisci, F. M., Ciliberto, M., Traversi, G., Kotzalidis, G. D., Berardis, D. D., Laterza, L., Sani, G., Gasbarrini, A., et al. (2023) · Nutrients · doi:10.3390/nu15061496 · Cited by 116
“What makes it possible is the contribution of the HPA axis [117], the immune system [118] and the vagus nerve [22,119]: the latter, when stimulated, increases the levels of dopamine in the brain [120].”
Koutzoumis, D. N., Vergara, M., Pino, J. A., Buddendorff, J., Khoshbouei, H., Mandel, R. J., & Torres, G. E. (2019) · Experimental Neurology · doi:10.1016/j.expneurol.2019.113159 · Cited by 103
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Livneh, Y., & Andermann, M. L. (2021) · Neuron · doi:10.1016/j.neuron.2021.08.036 · Cited by 105
The critical role of CCK in the regulation of food intake and diet-induced obesity
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Skeletal interoception in bone homeostasis and pain
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Interactions between central nervous system and peripheral metabolic organs
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“LCN2, an osteoblasts-derived protein, activates the appetite-suppressing signal in the brain to influence energy metabolism (Flower, 1996; Mosialou et al., 2017; Ste. Marie et al., 2000).”
BackgroundResultInfluentialModulation of Short-Chain Fatty Acids as Potential Therapy Method for Type 2 Diabetes Mellitus
Tang, R., & Li, L. (2021) · Canadian Journal of Infectious Diseases and Medical Microbiology · doi:10.1155/2021/6632266 · Cited by 96
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Identification of lung innervating sensory neurons and their target specificity
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Schiller, M., Azulay‐Debby, H., Boshnak, N., Elyahu, Y., Korin, B., Ben-Shaanan, T. L., Koren, T., Krot, M., Hakim, F., & Rolls, A. (2021) · Immunity · doi:10.1016/j.immuni.2021.04.007 · Cited by 73
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Huang, D., Grady, F. S., Peltekian, L., & Geerling, J. C. (2020) · The Journal of Comparative Neurology · doi:10.1002/cne.24975 · Cited by 69
“…short-latency inhibition of midbrain dopaminergic neurons in response to noxious stimuli (Coizet, Dommett, Klop, Redgrave, & Overton, 2010), which appears to operate in parallel with PB projections that relay viscerosensory signals and directly excite dopaminergic neurons (Han et al., 2018).”
BackgroundThe role of the gut microbiome in opioid use
Ren, M., & Lotfipour, S. (2019) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000538 · Cited by 69
“A vagal gut-to-brain circuit has been established to play a critical role in reward and motivation (Han et al., 2018), and gut bacteria influence how animals respond to various rewards, such as food and drugs (Korner and Leibel, 2003; Duca et al., 2012; Alcock et al., 2014; Kiraly et al., 2016; van…”
BackgroundInfluentialEnteroendocrine cell types that drive food reward and aversion
Bai, L., Sivakumar, N., Yu, S., Mesgarzadeh, S., Ding, T., Ly, T., Corpuz, T. V., Grove, J. C. R., Jarvie, B. C., & Knight, Z. A. (2022) · eLife · doi:10.7554/elife.74964 · Cited by 73
“It is less clear which vagal cells mediate CCK’s effects on flavor preference, although stimulation of all gut-innervating vagal afferents is reinforcing (Han et al., 2018).”
BackgroundNon-invasive stimulation of vagal afferents reduces gastric frequency
Teckentrup, V., Neubert, S., Santiago, J. C. P., Hallschmid, M., Walter, M., & Kroemer, N. B. (2020) · Brain Stimulation · doi:10.1016/j.brs.2019.12.018 · Cited by 64
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Self-citationGut microbiota and neuropsychiatric disorders: Implications for neuroendocrine-immune regulation
Ge, T., Yao, X., Zhao, H., Yang, W., Zou, X., Peng, F., Li, B., & Cui, R. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105909 · Cited by 62
Vagus nerve stimulation increases stomach-brain coupling via a vagal afferent pathway
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Jameson, K. G., Kazmi, S. A., Ohara, T. E., Son, C., Yu, K. B., Mazdeyasnan, D., Leshan, E., Vuong, H. E., Paramo, J., Lopez-Romero, A., et al. (2024) · iScience · doi:10.1016/j.isci.2024.111699 · Cited by 88
“…tracing studies have uncovered polysynaptic connections from gut-innervating vagal afferent neurons to higher order brain regions such as substantia nigra and hippocampus, 109 suggesting the potential for microbial metabolites to impact complex behavioral responses beyond those involved in feeding.”
Gut microbes and food reward: From the gut to the brain
d’Oplinter, A. D. W., Huwart, S. J. P., Cani, P. D., & Everard, A. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.947240 · Cited by 57
Role of gut microbiota in brain function and stress-related pathology
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“[30] demonstrated that gutinnervating vagal sensory neurons are an essential component of the neuronal reward pathway, linking sensory neurons in the upper gut to striatal dopamine release.”
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“In line with this anatomical distribution, some recent papers have found that the right branch of the vagus nerve affects preferentially the SN pars compacta [44, 45].”
Bharwani, A., West, C. L., Champagne-Jorgensen, K., Neufeld, K. M., Ruberto, J., Kunze, W., Bienenstock, J., & Forsythe, P. (2019) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.108067 · Cited by 46
Orellana, E. R., Covașă, M., & Hajnal, A. S. (2019) · Biochemical Pharmacology · doi:10.1016/j.bcp.2019.04.004 · Cited by 43
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Self-citationMapping of Extrinsic Innervation of the Gastrointestinal Tract in the Mouse Embryo
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“In contrast to considerable advances in mapping neural circuitry along the gut-brain axis (GBA) within adult animals (Han et al., 2018; Kaelberer et al., 2018), relatively little is known about the mechanisms underlying visceral nerve assembly to integrate visceral sensory afferent and motor…”
BackgroundMicrobiome and substances of abuse
Salavrakos, M., Leclercq, S., de Timary, P., & Dom, G. (2020) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2020.110113 · Cited by 45
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Innate gut microbiota predisposes to high alcohol consumption
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Peripheral effects of vagus nerve stimulation on anxiety and extinction of conditioned fear in ratsPreprint
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“…a recent study, optical stimulation of the right vagal sensory ganglion in mice promoted self-stimulation behavior, drove a conditioned place and flavor preference, and increased dopamine release from the substantia nigra in mice, implicating the vagus nerve in gut-induce reward (Han et al. 2018).”
Clarke, G. S., Page, A. J., & Eldeghaidy, S. (2024) · Pharmacology Research & Perspectives · doi:10.1002/prp2.70027 · Cited by 51
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“The vagal afferents carry information that is incredibly important for interoceptive sensations, including mood and food reward value [149–151].”
Neuroendocrine gut–brain signaling in obesity
Gruber, T., Lechner, F., Krieger, J.-P., & García‐Cáceres, C. (2024) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2024.05.002 · Cited by 41
“…of vagal afferent neurons) exhibit a profound left – right asymmetry in the types of signal that they detect: as such, it appears that the left nodose ganglion conveys distension-induced satiety, whereas the right nodose ganglion signals food reward and nutritional preference to the brain [31,32].”
Wang, L., Li, S., Hao, Y., Liu, X., Liu, Y., Zuo, L., Tai, F., Yin, L., Young, L. J., & Li, D. (2024) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2024.174026 · Cited by 38
The gut-brain axis mediates bacterial driven modulation of reward signaling
Kim, J. S., Williams, K., Kirkland, R. A., Schade, R., Freeman, K. G., Cawthon, C. R., Rautmann, A. W., Smith, J. M., Edwards, G. L., Glenn, T. C., et al. (2023) · Molecular Metabolism · doi:10.1016/j.molmet.2023.101764 · Cited by 32
“The mesocortical (ventral tegmental area (VTA) projecting to NAc) DA system has been implicated in motivational drive and food seeking [7e9] while the nigrostriatal DA (projections from the substantia nigra (SN) to the dorsal striatum) pathway plays a role in both food anticipatory behavior [10] and reinforcement [4].”
InfluentialSelf-citationBrain signaling dynamics after vagus nerve stimulation
Teckentrup, V., Krylova, M., Jamalabadi, H., Neubert, S., Neuser, M. P., Hartig, R., Fallgatter, A. J., Walter, M., & Kroemer, N. B. (2021) · NeuroImage · doi:10.1016/j.neuroimage.2021.118679 · Cited by 30
Blackie, L., Gaspar, P., Mosleh, S., Lushchak, O. V., Kong, L., Jin, Y., Zielinska, A. P., Cao, B., Mineo, A., Silva, B., et al. (2024) · Nature · doi:10.1038/s41586-024-07463-4 · Cited by 32
An analysis of sensory-specific satiation: Food liking, food wanting, and the effects of distraction
Rogers, P. J., Drumgoole, F. D. Y., Quinlan, E., & Thompson, Y. (2020) · Learning and Motivation · doi:10.1016/j.lmot.2020.101688 · Cited by 32
Brain–stomach coupling: Anatomy, functions, and future avenues of research
Rebollo, I., Wolpert, N., & Tallon‐Baudry, C. (2021) · Current Opinion in Biomedical Engineering · doi:10.1016/j.cobme.2021.100270 · Cited by 30
Microbes and Parkinson’s disease: from associations to mechanisms
Cannon, T., & Gruenheid, S. (2022) · Trends in Microbiology · doi:10.1016/j.tim.2022.01.004 · Cited by 33
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“Alterations of carboxylic acids were associated with pathophysiologic mechanisms of depression.(10,11) For instance, the metabolites, which were particularly involved in tryptophan–kynurenine and fatty acid metabolic pathways, were reported to be related to depression.”
BackgroundNeuronal Regulation of Feeding and Energy Metabolism: A Focus on the Hypothalamus and Brainstem
Chen, J. W., Cai, M., & Zhan, C. (2024) · Neuroscience Bulletin · doi:10.1007/s12264-024-01335-7 · Cited by 37
“Another study revealed that the nodose ganglion-NTS-PBN-substantia nigra (SNc) pathway mediates satiety-induced reward signals [90].”
Gruber, T., Lechner, F., Murat, C., Contreras, R. E., Sanchez-Quant, E., Miok, V., Makris, K., Thuc, O. L., González‐García, I., García-Clavé, E., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.113305 · Cited by 28
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“…nutrients versus satiety is the demonstration of separate gut-to-brain signalling of nutrient reward and satiation (e.g., Dockray, 2014; Han et al., 2018; Li et al., 2022; Myers, 2018; Sclafani, 2013; Woods, 2004), and evidence that satiety per se is not rewarding (Sclafani & Ackroff,…”
Vagus Nerve and Gut-Brain Communication
Wang, Y., Duan, C., Du, X., Zhu, Y. J., Wang, L., Hu, J., & Sun, Y. (2024) · The Neuroscientist · doi:10.1177/10738584241259702 · Cited by 33
“This overlap could explain the occurrence of binge-eating behavior (Han and others 2018; Rossi and others 2021).”
Transcutaneous vagus nerve stimulation improves emotional processing
Zhao, T., Schiweck, C., Jamalambadi, H., Meyer, K., Brandt, E. S. L., Schneider, M., Aichholzer, M., Qubad, M., Bouzouina, A., Schillo, S., et al. (2024) · Journal of Affective Disorders · doi:10.1016/j.jad.2024.11.077 · Cited by 26
The gut–organ axis: Clinical aspects and immune mechanisms
Fukasawa, N., Tsunoda, J., Sunaga, S., Kiyohara, H., Nakamoto, N., Teratani, T., Mikami, Y., & Kanai∥, T. (2025) · Allergology International · doi:10.1016/j.alit.2025.01.004 · Cited by 34
On the roles of the Duodenum and the Vagus nerve in learned nutrient preferences
Qu, T., Han, W., Niu, J., et al. (2019) · Appetite · doi:10.1016/j.appet.2019.04.014 · Cited by 26
Self-citationKim, H. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00281 · Cited by 28
Acute Vagus Nerve Stimulation Facilitates Short Term Memory and Cognitive Flexibility in Rats
Driskill, C. M., Childs, J. E., Itmer, B., Rajput, J. S., & Kroener, S. (2022) · Brain Sciences · doi:10.3390/brainsci12091137 · Cited by 28
“There is no evidence that stimulation of the left vagus nerve alone is rewarding or reinforcing [23,36] (but see [45]), suggesting that VNS’ effects on cognitive flexibility in the current study were not due to changes in appetitive or motivational properties of the stimuli used in the task.”
Ma, S., Liu, X., & Cai, W. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.116344 · Cited by 24
Gut-brain communication: Functional anatomy of vagal afferents
Berthoud, H., Münzberg, H., Morrison, C. D., & Neuhuber, W. (2025) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2025.103058 · Cited by 26
Lynch, C. M. K., Nagpal, J. K., Clarke, G. A., & Cryan, J. F. (2021) · Current Opinion in Physiology · doi:10.1016/j.cophys.2021.100468 · Cited by 25
Mechanisms and Functions of Sweet Reception in Oral and Extraoral Organs
Yoshida, R., & Ninomiya, Y. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25137398 · Cited by 26
“…to the vagal nerve, then to nodose ganglion neurons, neurons in the nucleus of the solitary tract, and eventually to the parabrachial region and dopaminergic neurons in the substantia nigra [112], thereby establishing the neural reward pathway crucial for the development of sugar preference.”
BackgroundThe (dys)regulation of energy storage in obesity
Levin, B. E., Geary, N., & Lutz, T. A. (2025) · Physiological Reviews · doi:10.1152/physrev.00002.2024 · Cited by 27
Lewis, N., Villani, A., & Lagopoulos, J. (2025) · Neuroscience · doi:10.1016/j.neuroscience.2025.01.031 · Cited by 25
“The vagal-brain pathway has been identified as integral in both the dopaminergic reward pathway (Han et al., 2018) and the HPA axis (Bull-Larsen and Mohajeri, 2019), which are processes altered in ADHD (Plichta and Scheres, 2014; Chang et al., 2020), and dysbiosis may play a role in this.”
From gut microbiota to brain: implications on binge eating disorders
Guo, W., & Xiong, W. (2024) · Gut Microbes · doi:10.1080/19490976.2024.2357177 · Cited by 27
“89 In a model of mice experiencing an excessive bout of overeating, the c-fos expression in the NTS, PVT, ARC, the dorsal medial hypothalamus and other nuclei associated with feeding or stress exhibited a significant elevation.”
James, D. M., Davidson, E. A., Yanes, J. A., Moshiree, B., & Dallman, J. E. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.662916 · Cited by 25
“Consistent with functions established in mammals, the zebrafish AP has been shown to be responsive to the pain-inducing Trp1A agonist AITC (Haney et al., 2020).”
BackgroundHuwart, S. J. P., d’Oplinter, A. D. W., Rastelli, M., Hul, M. V., de Vos, W. M., Luquet, S. H., Cani, P. D., & Everard, A. (2022) · Cells · doi:10.3390/cells11162534 · Cited by 24
“also evoked asymmetry when they reported that motivation and dopamine activity in the brain are mediated by right, but not left, vagal sensory ganglion activation [56].”
Brain-Gut and Microbiota-Gut-Brain Communication in Type-2 Diabetes Linked Alzheimer’s Disease
Momen, Y. S., Mishra, J., & Kumar, N. (2024) · Nutrients · doi:10.3390/nu16152558 · Cited by 26
“…either by the activation of mechanoreceptors that can sense the luminal volume or by the activation of chemoreceptors that can be triggered by chemical stimuli produced by enteroendocrine cells (EECs) such as hormones and neurotransmitters upon detecting the gut microbiota’s metabolites [116–118].”
Intestinal distension orchestrates neuronal activity in the enteric nervous system of adult mice
Cavin, J., Wongkrasant, P., Glover, J., Balemba, O. B., MacNaughton, W. K., & Sharkey, K. A. (2023) · The Journal of Physiology · doi:10.1113/jp284171 · Cited by 21
“…et al., 2020; Williams et al., 2016) and spinal afferent (Lai et al., 2020) pathways react to a variety of stimuli including stretch, nutrients and bacterial products to control both gut functions (Obata et al., 2020; Williams et al., 2016) and behaviour (Han et al., 2018; Suarez et al., 2018).”
BackgroundGarcía-Luna, C., Sanchez‐Watts, G., Arnold, M., de Lartigue, G., DeWalt, N., Langhans, W., & Watts, A. G. (2021) · eNeuro · doi:10.1523/eneuro.0419-20.2021 · Cited by 23
Self-citationRegulation of Cardiac Function by the Autonomic Nervous System
Hafez, O. A., & Chang, R. B. (2024) · Physiology · doi:10.1152/physiol.00018.2024 · Cited by 29
Food, microbes, sex and old age: on the plasticity of gastrointestinal innervation
Ameku, T., Beckwith, H., Blackie, L., & Miguel‐Aliaga, I. (2020) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2019.12.004 · Cited by 20
“The net effect of vagal activation was thought to be negative on food reward, but a recent study challenged this view by revealing that vagal afferents can also transmit reward signals to the brain [34].”
Metadata
- Authors
- Han, W., Tellez, L. A., Perkins, M. H., Perez, I. O., Qu, T., Ferreira, J., Ferreira, T. L., Quinn, D., Liu, Z.-W., Gao, X.-B., Kaelberer, M. M., Bohórquez, D. V., Shammah-Lagnado, S. J., de Lartigue, G., & de Araujo, I. E.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-10
- Volume
- 175
- Issue
- 3
- Pages
- 887-888
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W4233569565
- Cited by
- 204
- References
- 0
- Citations by year
- 2026: 9 · 2025: 25 · 2024: 34 · 2023: 21 · 2022: 29 · 2021: 33 · 2020: 29 · 2019: 22 · 2018: 2
- FWCI
- 9.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- Funders
- National Institute on Deafness and Other Communication Disorders (R01DC014859)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- gut-brain axis, vagal afferent neurons, lateral parabrachial nucleus, striatal dopamine release, dopaminergic neurons, rabies virus tracing
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