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The Neuroendocrinology of the Microbiota-Gut-Brain Axis: A Behavioural Perspective
Open accessAbstract
The human gut harbours trillions of symbiotic bacteria that play a key role in programming different aspects of host physiology in health and disease. These intestinal microbes are also key components of the gut-brain axis, the bidirectional communication pathway between the gut and the central nervous system (CNS). In addition, the CNS is closely interconnected with the endocrine system to regulate many physiological processes. An expanding body of evidence is supporting the notion that gut microbiota modifications and/or manipulations may also play a crucial role in the manifestation of specific behavioural responses regulated by neuroendocrine pathways. In this review, we will focus on how the intestinal microorganisms interact with elements of the host neuroendocrine system to modify behaviours relevant to stress, eating behaviour, sexual behaviour, social behaviour, cognition and addiction.
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“This relationship, like the microbiota-gut-brain axis itself, is bidirectional -the microbiota can modulate stress-induced alterations in anxiety, memory, cognition and neuroinflammation (for reviews, see Cussotto et al., 2018;Farzi et al., 2018;Foster et al., 2017;Rea et al., 2016;Sherwin et al., 2016a).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Cussotto et al., 2018
In the citing paper
“The development of the blood-brain barrier is now well established to be contingent upon the presence of commensal gut flora (10, 11).”
From Association Between Gut Microbiota and Autism Spectrum Disorder: A Systematic Review and Meta-Analysis (2019) · cites this paper as [10]
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1 retracted
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Alterations of gut microbiota composition in post-finasteride patients: a pilot study
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Opioid Use, Gut Dysbiosis, Inflammation, and the Nervous System
Jalodia, R., Abu, Y. F., Oppenheimer, M. R., Truitt, B., Meng, J., Chupikova, I., Tao, J., Ghosh, N., Dutta, R. K., Kolli, U., et al. (2022) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-021-10046-z · Cited by 40
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BackgroundGut-Brain Axis and Neurological Disorders-How Microbiomes Affect our Mental Health
Bhatia, N. Y., Jalgaonkar, M. P., Hargude, A. B., Sherje, A. P., Oza, M. J., & Doshi, G. (2022) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527321666220822172039 · Cited by 38
Enactive Pragmatism and Ecological Psychology
Crippen, M. (2020) · Frontiers in Psychology · doi:10.3389/fpsyg.2020.538644 · Cited by 40
“This is more so since gut problems have body-wide ramifications with bacteria imbalances predicting conditions, such as anxiety, depression, autism, schizophrenia, Alzheimer’s, and eating disorders (Burrus, 2012; Foster and McVey Neufeld, 2013; Severance et al., 2016; van de Wouw et al., 2017; Wong et al., 2017; Cusso…”
BackgroundZhang, J., Deji, C., Fan, J., Chang, L., Miao, X., Xiao, Y., Zhu, Y., & Li, S. (2020) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2020.110058 · Cited by 34
Birmann, P. T., Casaril, A. M., Pesarico, A. P., Caballero, P. S., Smaniotto, T. Â., Rodrigues, R. R., Moreira, Â. N., Conceição, F. R., Sousa, F. S. S., Collares, T. V., et al. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105740 · Cited by 35
The gut microbiota and microbial metabolites are associated with tail biting in pigs
Verbeek, E., Keeling, L. J., Landberg, R., Lindberg, J. E., & Dicksved, J. (2021) · Scientific Reports · doi:10.1038/s41598-021-99741-8 · Cited by 39
Brown-Algae Polysaccharides as Active Constituents against Nonalcoholic Fatty Liver Disease
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“Moreover, different strains of gut bacteria are also able to produce neurotransmitters and neuropeptides that can interfere with the mechanism regulating energy homeostasis and food intake [15].”
BackgroundZolfaghari, S. I., Khorasgani, M. R., & Noorbakhshnia, M. (2020) · Physiology & Behavior · doi:10.1016/j.physbeh.2020.113224 · Cited by 32
Bhuiyan, P., Chen, Y., Karim, M., Dong, H., & Qian, Y. (2021) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2021.04.010 · Cited by 33
Yang, Y. H., Ishima, T., Wan, X., Wei, Y., Chang, L., Zhang, J., Qu, Y., & Hashimoto, K. (2021) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-021-01325-0 · Cited by 32
Adrenomedullin: Not Just Another Gastrointestinal Peptide
Martínez-Herrero, S., & Martı́nez, A. (2022) · Biomolecules · doi:10.3390/biom12020156 · Cited by 33
“the gut microbiota, whose interaction with GI hormones seems to have a key role in the effects of diets and improving the treatment of some intestinal disorders [7,8].”
BackgroundImmune-Mediated Diseases from the Point of View of Psychoneuroimmunoendocrinology
Ortega, M. A., Montero, C. G., Fraile‐Μartinez, O., Álvarez-Mon, M. Á., Gomez-Lahoz, A. M., Lahera, G., Monserrat, J., Rodríguez–Jiménez, R., Quintero, J., & Álvarez‐Mon, M. (2022) · Biology · doi:10.3390/biology11070973 · Cited by 33
“These substances have important neuroimmunoendocrine effects, driving to an enhanced inflammation, gonadal axis disruption, and defects in neuroplasticity and neurogenesis, negatively influencing mood and aggravating psychiatric conditions [64].”
BackgroundThe microbiota–gut–brain axis: A promising avenue to foster healthy developmental outcomes
Brett, B. E., & de Weerth, C. (2019) · Developmental Psychobiology · doi:10.1002/dev.21824 · Cited by 31
Gut Microbiome: A New Organ System in Body
Anwar, H., Irfan, S., Hussain, G., Faisal, M. N., Muzaffar, H., Mustafa, I., Mukhtar, I., Malik, S., & Ullah, M. I. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.89634 · Cited by 33
The Microbiome and Its Implications in Cancer Immunotherapy
Choudhry, H. (2021) · Molecules · doi:10.3390/molecules26010206 · Cited by 31
Potential effects of the most prescribed drugs on the microbiota-gut-brain-axis: A review
Garg, K., & Mohajeri, M. H. (2024) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2024.110883 · Cited by 33
“GM may influence the brain via bacterial production of neurotransmitters and metabolites (so-called chemical signalling), the vagal nerve, the immune system, or the neuroendocrine system including the hypothalamic-pituitary-adrenal axis (HPAA) (Chakrabarti et al., 2022; Cussotto et al., 2018).”
The Role of the Gut Microbiota in Neurodegenerative Diseases
Mani, A. P., Balasubramanian, B., Mali, L. A., Joseph, K. S., Meyyazhagan, A., Pappuswamy, M., & Joseph, B. V. (2024) · Microbiology Research · doi:10.3390/microbiolres15020033 · Cited by 37
Li, X., Chen, L.-M., Kumar, G., Zhang, S.-J., Zhong, Q.-H., Zhang, H., Gui, G., Wu, L.-L., Fan, H., & Sheng, J.-W. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.820106 · Cited by 29
Sardá, F. A. H., Giuntini, E. B., de Oliveira, A. F., de Souza, G. S. F., do Prado, S. B. R., Taddei, C. R., TADINI, C. C., Bittinger, K. L., Bushman, F. D., de Menezes, E. W., et al. (2025) · npj Biofilms and Microbiomes · doi:10.1038/s41522-025-00817-4 · Cited by 30
Gut Steroids and Microbiota: Effect of Gonadectomy and Sex
Diviccaro, S., FitzGerald, J. A., Cioffi, L., Falvo, E., Crispie, F., Cotter, P. D., O’Mahony, S. M., Giatti, S., Caruso, D., & Melcangi, R. C. (2022) · Biomolecules · doi:10.3390/biom12060767 · Cited by 28
The Intervention of Prebiotics on Depression via the Gut–Brain Axis
He, Q., Si, C., Sun, Z., Chen, Y., & Zhang, X. (2022) · Molecules · doi:10.3390/molecules27123671 · Cited by 29
Leão, L. L., Miri, S., & Hammami, R. (2024) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2024.101173 · Cited by 29
“Thus, there is a strong bidirectional relationship between endogenous sex hormones and the gut microbiome, which may impact neurobiological and neuroendocrine functions in the host through the gut-brain axis (Cussotto et al., 2018).”
Complex Gastrointestinal and Endocrine Sources of Inflammation in Schizophrenia
Severance, E. G., Dickerson, F., & Yolken, R. H. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.00549 · Cited by 29
Exploring the Impact of the Microbiome on Neuroactive Steroid Levels in Germ-Free Animals
Diviccaro, S., Caputi, V., Cioffi, L., Giatti, S., Lyte, J. M., Caruso, D., O’Mahony, S. M., & Melcangi, R. C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222212551 · Cited by 27
“utilize neurotransmitters and steroid hormones to exchange information among the different brain regions and with the peripheral organs [4].”
BackgroundTherapeutic applications of gut microbes in cardiometabolic diseases: current state and perspectives
Yuan, L., Li, Y., Chen, M., Xue, L., Wang, J., Ding, Y., Gu, Q., Zhang, J., Zhao, H., Xie, X., et al. (2024) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-024-13007-7 · Cited by 28
“Intestinal microorganisms can also interact with elements of the host neuroendocrine system to modify behaviors relevant to social behavior, eating behavior, cognition, addiction, and sexual behavior (Cussotto et al. 2018).”
Sgro, M., Kodila, Z. N., Brady, R. D., Reichelt, A. C., Mychasiuk, R., & Yamakawa, G. R. (2021) · SLEEP · doi:10.1093/sleep/zsab268 · Cited by 25
Role of the gut-microbiota-metabolite-brain axis in the pathogenesis of preterm brain injury
Li, L., Yang, J., Liu, T., & Shi, Y. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115243 · Cited by 28
Lassmann, Ł., Pollis, M., Żółtowska, A., & Manfredini, D. (2022) · Biomedicines · doi:10.3390/biomedicines10071528 · Cited by 26
“Moreover, sleep disorders increase susceptibility to stress [20] and have a negative effect on the intestines [21], which, in turn, enhances the stress response [22].”
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Bellot, M., Carrillo, M. P., Bedrossiantz, J., Zheng, J., Mandal, R., Wishart, D. S., Gómez‐Canela, C., Vila‐Costa, M., Prats, E., Piña, B., et al. (2023) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2023.115888 · Cited by 26
Gut-brain relationship in dementia and Alzheimer's disease: Impact on stress and immunity
Mukherjee, U., & Reddy, P. H. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102843 · Cited by 25
Kiełbik, P., & Witkowska‐Piłaszewicz, O. (2024) · Animals · doi:10.3390/ani14142048 · Cited by 27
“The microbiome can influence the animal central nervous system via the vagus nerve [49], neurotransmitter level regulation [50], the hypothalamic–pituitary–adrenal (HPA) axis [51], influence on the immune system [52], and production of metabolites [53] (Figure 1).”
BackgroundMolecular Mechanisms behind Obesity and Their Potential Exploitation in Current and Future Therapy
Nicze, M., Dec, A., Borówka, M., Krzyżak, D., Bołdys, A., Bułdak, Ł., & Okopień, B. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25158202 · Cited by 30
Siegel, M. P., & Conklin, S. M. (2020) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2019.100029 · Cited by 27
Oral Microbiota Changes Contribute to Autism Spectrum Disorder in Mice
Qiao, Y., Gong, W., Li, B., Xu, R., Wang, M., Shen, L., Shi, H. Y., & Li, Y. (2022) · Journal of Dental Research · doi:10.1177/00220345211070470 · Cited by 23
“Decades of studies have demonstrated that the gut microbiota contributes to the pathogenesis of ASD and modulates brain function and behaviors via the microbiota-gut-brain axis (MacFabe 2015; Dinan et al. 2017; Cussotto et al. 2018).”
BackgroundGut-Brain Axis Deregulation and Its Possible Contribution to Neurodegenerative Disorders
Villavicencio-Tejo, F., Olesen, M. A., Navarro, L., Calisto, N., Iribarren, C., GARCÍA, K. P., Corsini, G., & Quintanilla, R. A. (2023) · Neurotoxicity Research · doi:10.1007/s12640-023-00681-0 · Cited by 24
“Furthermore, alterations in the GI, CNS, autonomic nervous system, and immune system by microbiota may lead to changes in fat storage and energy balance, gastrointestinal barrier function, low-grade inflammation, and increased stress reactivity (Cussotto et al. 2018; Salim 2017).”
Stress and the Gut-Brain Axis: Implications for Cancer, Inflammation and Sepsis
Moughnyeh, M., Brawner, K. M., Kennedy, B. A., Yeramilli, V. A., Udayakumar, N., Graham, J. A., & Martin, C. A. (2021) · Journal of Surgical Research · doi:10.1016/j.jss.2021.02.055 · Cited by 24
Decoding the Role of Gut-Microbiome in the Food Addiction Paradigm
Novelle, M. G. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18136825 · Cited by 24
Making migraine easier to stomach: the role of the gut−brain−immune axis in headache disorders
Sgro, M., Ray, J. C., Foster, E., & Mychasiuk, R. (2023) · European Journal of Neurology · doi:10.1111/ene.15934 · Cited by 21
“However, given that the GBI axis regulates stress reactivity, anxiety and emotional behaviour via the HPA axis [55], it may play a role in triggering migraine and TTH attacks.”
BackgroundInfluentialThe gut microbiome: an important role in neurodegenerative diseases and their therapeutic advances
Li, S., Zhao, L., Xiao, J., Guo, Y., Fu, R., Zhang, Y., & Xu, S. (2023) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-023-04853-6 · Cited by 23
“Gut microbes can transmit signals or regulate intestinal motility through the neuroendocrine system with the central nervous system [24, 25].”
Awe, T., Fasawe, A. S., Sawe, C., Ogunware, A. E., Jamiu, A. T., & Allen, M. O. (2024) · AIMS neuroscience · doi:10.3934/neuroscience.2024004 · Cited by 24
Tenets in Microbial Endocrinology: A New Vista in Teleost Reproduction
Haque, R., Das, I. I., Sawant, P. B., Chadha, N. K., Sahoo, L., Kumar, R., & Sundaray, J. K. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.871045 · Cited by 22
Chronic Stress as a Risk Factor for Type 2 Diabetes: Endocrine, Metabolic, and Immune Implications
Lisco, G., Giagulli, V. A., Pergola, G. D., Guastamacchia, E., Jirillo, E., Vitale, E., & Triggiani, V. (2023) · Endocrine Metabolic & Immune Disorders - Drug Targets · doi:10.2174/1871530323666230803095118 · Cited by 25
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Xu, J., Wu, Z., Zhang, M., Liu, S., Zhou, L., Yang, C., & Liu, C. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.694446 · Cited by 22
“There is mutual communication between the intestinal and central nervous systems through various pathways (Cussotto et al., 2018).”
BackgroundPatricio-Martínez, A., Patricio, F., Macuil-Chapuli, E., Martínez-Juárez, E. Á., Flores-Díaz, S., Cedillo-Ramirez, M. L., & Limón, I. D. (2025) · Frontiers in Neuroscience · doi:10.3389/fnins.2025.1598011 · Cited by 23
“…system (GIS) and the central nervous system (CNS), integrating the autonomic nervous system (ANS), the enteric nervous system (Carabotti et al., 2015; Hulme et al., 2022), endocrine pathways (Cussotto et al., 2018; Wachsmuth et al., 2022), and immune responses (Fung, 2020; Powell et al., 2017).”
ALZHEIMER’S DISEASE AND ITS RELATIONSHIP WITH THE MICROBIOTA-GUT-BRAIN AXIS
Faulin, T. D. E. S., & Estadella, D. (2023) · Arquivos de Gastroenterologia · doi:10.1590/s0004-2803.202301000-17 · Cited by 25
“The composition of the gut microbiota influences the CNS, resulting in changes in host behavior (68,69) .”
BackgroundShi, J., Zhang, X., Chen, J., Shen, R.-S., Cui, H., & Wu, H. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1275860 · Cited by 22
Prospects for Leveraging the Microbiota as Medicine for Hypertension
Durgan, D. J., Zubcevic, J. A., Vijay–Kumar, M., Yang, T., Manandhar, I., Aryal, S., Muralitharan, R. R., Li, H., Li, Y., Abais‐Battad, J. M., et al. (2024) · Hypertension · doi:10.1161/hypertensionaha.124.21721 · Cited by 21
The gut microbiome and adult hippocampal neurogenesis: A new focal point for epilepsy?
Dohm-Hansen, S., Donoso, F., Lucassen, P. J., Clarke, G. A., & Nolan, Y. M. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105746 · Cited by 21
“, 2019) and through hormonal regulation (Cussotto et al., 2018; Martin et al., 2019), which may have implications for the regulation of neuroinflammation,”
BackgroundXu, Z., Lu, H., Hu, C., Wen, Y., Shang, D., Gan, T., Guo, Z., Dai, L., & Luo, Y. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.139503 · Cited by 19
Peng, Z., Hou, T., Yang, K., Zhang, J., Mao, Y.-H., & Hou, X. (2025) · Nutrients · doi:10.3390/nu17111769 · Cited by 21
“The GM can regulate the CNS by secreting a variety of metabolites and synthesizing neurotransmitters and neuromodulators [90,105].”
Gut Microbiome as a Mediator of Stress Resilience: A Reactive Scope Model Framework
Houtz, J. L., Taff, C. C., & Vitousek, M. N. (2022) · Integrative and Comparative Biology · doi:10.1093/icb/icac030 · Cited by 19
Yamaoka, K., Uotsu, N., & Hoshino, E. (2022) · Neurobiology of Stress · doi:10.1016/j.ynstr.2022.100479 · Cited by 18
Koller, A. M., Săsăran, M. O., & Mărginean, C. O. (2025) · Nutrients · doi:10.3390/nu17111883 · Cited by 23
“Furthermore, gut microbes modulate host responses via SCFAs and neurotransmitters like GABA and serotonin, affecting central appetite regulation [63–65].”
Wang, Y., Zhang, J., Deji, C., Fan, J., Miao, X., Li, S. C., Zeng, X., & Guan, F. (2021) · Journal of Neuroscience Research · doi:10.1002/jnr.24963 · Cited by 18
“The neuroactive effect of METH could also influence the gut microbiome via the neuroendocrine system, such as the hypothalamic– pituitary– adrenalaxis (Cussotto et al., 2018).”
BackgroundLeigh, S., Lynch, C. M. K., Bird, B., Griffin, B. T., Cryan, J. F., & Clarke, G. A. (2022) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2022.2043849 · Cited by 19
Lou, H., Liu, X., & Liu, P. (2023) · Frontiers in Psychology · doi:10.3389/fpsyg.2023.1143827 · Cited by 20
“Therefore, the MGBA is a bidirectional channel through which the gut microbiota can influence brain function through neural, endocrine, and immune pathways, while the brain can also influence the gut microbiota through neural, endocrine, and immune pathways (Cussotto et al., 2018).”
BackgroundYe, H., Ghosh, T. S., Hueston, C. M., Vlčková, K., Golubeva, A. V., Hyland, N. P., & O’Toole, P. W. (2023) · Gut Microbes · doi:10.1080/19490976.2023.2282796 · Cited by 19
“58,59 B. intestinihominis has been reported to be more abundant in high-functioning older adults (aged above 70) compared with low-functioning adults, and the transfer of high-functioning donor microbiota into GF mice improved their grip strength 60 .”
BackgroundMicrobiota modulates the steroid response to acute immune stress in male mice
Vagnerová, K., Gazárková, T., Vodička, M., Ergang, P., Klusoňová, P., Hudcovic, T., Šrůtková, D., Hermanová, P. P., Nováková, L., & Pácha, J. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1330094 · Cited by 18
“The interaction between microbiota and brain is bidirectional using several different mechanisms of communication (20).”
BackgroundThe zebrafish gut microbiome influences benzo[a]pyrene developmental neurobehavioral toxicity
Stagaman, K., Alexiev, A., Sieler, M. J., Hammer, A. J., Kasschau, K. D., Truong, L., Tanguay, R. L., & Sharpton, T. J. (2024) · Scientific Reports · doi:10.1038/s41598-024-65610-3 · Cited by 22
Cheng, R., Xu, T. C., Zhang, Y., Wang, F., Zhao, L., Jiang, Y., & He, F. (2019) · Probiotics and Antimicrobial Proteins · doi:10.1007/s12602-019-09571-4 · Cited by 18
Cheng, H.-W., Jiang, S., & Hu, J. (2019) · Oral Health by Using Probiotic Products · doi:10.5772/intechopen.86775 · Cited by 17
Supplementation of Lactobacillus early in life alters attention bias to threat in piglets
Verbeek, E., Dicksved, J., & Keeling, L. J. (2021) · Scientific Reports · doi:10.1038/s41598-021-89560-2 · Cited by 19
Gut microbiota-metabolite interactions meditate the effect of dietary patterns on precocious puberty
Wang, Y., Jin, C., Li, H., Liang, X., Zhao, C., Wu, N., Yue, M., Zhao, L., Han, Y., Wang, Q., et al. (2024) · iScience · doi:10.1016/j.isci.2024.109887 · Cited by 16
The Functions of Major Gut Microbiota in Obesity and Type 2 Diabetes
Liu, S., Tao, Z., Qiao, M., & Shi, L. (2025) · Metabolites · doi:10.3390/metabo15030167 · Cited by 16
“…contributes through regulating the neuroendocrine system of the brain and through the production of hormone-like metabolites by the gut microbiome [83,84], which are associated with various behavioral aspects, including sexual, stress-related, learning, memory, eating, and obesity behaviors [83].”
High-fat-diet-induced gut microbiome changes in mice
Tang, W., Pan, L., Cheng, J., Wang, X., Zheng, L., Wang, S., Zhou, Y., & Wang, H. (2022) · Stress and Brain · doi:10.26599/sab.2022.9060012 · Cited by 15
Han, W., Zheng, Y., Wang, L., & An, C. (2023) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2023.578172 · Cited by 17
Bao, C., Wei, M., Pan, H., Wen, M., Liu, Z., Xu, Y., & Jiang, H. (2023) · Frontiers in Nutrition · doi:10.3389/fnut.2023.1184311 · Cited by 16
Brain signatures of chronic gut inflammation
Hall, C. V., Radford‐Smith, G. L., Savage, E., Robinson, C., Cocchi, L., & Moran, R. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.1250268 · Cited by 15
He, J., Liu, F., Xu, P., Xu, T., Yu, H., Wu, B., Wang, H., Chen, J., Zhang, K., Zhang, J., et al. (2024) · Depression and Anxiety · doi:10.1155/da/6651804 · Cited by 18
“The gut microbiota in fl uences the HPA axis through microbial antigens, cytokines, and prostaglandins, with stressors such as maternal separation affecting microbial composition [170 – 172].”
Rendina, D. N., Lubach, G. R., Phillips, G. J., Lyte, M., & Coe, C. L. (2019) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/mpg.0000000000002394 · Cited by 16
“In addition to influencing host metabolism, gut bacteria can sustain infant health by providing protection against pathogens (3,4).”
BackgroundPinacho‐Guendulain, B., Montiel-Castro, A. J., Ramos‐Fernández, G., & Pacheco‐López, G. (2022) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2022.876849 · Cited by 13
“These findings strongly suggest that gut microbes can interact with the neuroendocrine system, via the microbiota-gut-brain axis, to affect host behavior (Cussotto et al., 2018).”
BackgroundInfluentialInvestigating the gut-brain axis in a neurodevelopmental rodent model of schizophrenia
Katz-Barber, M. W., Hollins, S. L., Cuskelly, A., Leong, A. J. W., Dunn, A. L., Harms, L. R., & Hodgson, D. M. (2020) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2020.100048 · Cited by 13
“As previous research suggests, a decrease in this bacteria could possibly account for the increased levels of circulating corticosterone and IL6 and CRHR1mRNA found in the adolescent female MIA-ACE offspring in this study (Cussotto et al., 2018; Hollins et al., 2018; Neuman et al., 2015).”
BackgroundZhang, M., Song, S., Zhao, D., Shi, J., Xu, X., Zhou, G., & Li, C. (2020) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2020.108487 · Cited by 14
Zafari, R., Goudarzi, N., Kamroo, A., Tafti, M. F., Ghorbani, A., Talebian, N., Najafi, S., Shahbazian, S., Rahmanian, M., Parvardeh, S., et al. (2025) · Nutrition & Metabolism · doi:10.1186/s12986-025-01022-y · Cited by 14
“It has been demonstrated that inflammatory markers, including TNF-α, IL-1β, and IL-6, which are produced through the gut microbiome, can significantly influence the development of the hypothalamic-pituitary-adrenal (HPA) axis [65].”
Potential Role of Host Microbiome in Areca Nut-Associated Carcinogenesis and Addiction
Chen, L., Yuan, F., Chen, S., Li, X., Kong, L., & Zhang, W. (2022) · Molecules · doi:10.3390/molecules27238171 · Cited by 13
Gut Microbiota: A Modulator and Therapeutic Target for Chronic Pain
Lou, L., Zhou, L., & Wang, Y. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04663-x · Cited by 13
“In addition to their potential role in migraines through immune responses, such as the activation of inflammatory processes, gut microbes may also play a part through neuroendocrine and vagal mechanisms [86, 87].”
Wang, J., Lei, M., Liu, Y., Wang, Z., Fan, J., & Wang, Y. (2025) · Aquaculture · doi:10.1016/j.aquaculture.2025.742157 · Cited by 11
Liu, M., Han, M., Fu, Y., Zhang, D., Zhao, Y., Li, Q., Hu, H., Guo, H., Huang, L., Tan, C., et al. (2025) · Food & Function · doi:10.1039/d5fo01041a · Cited by 14
Kheloui, S., Smith, A., & Ismail, N. (2022) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2022.101041 · Cited by 15
Cellular and Molecular Roles of Immune Cells in the Gut-Brain Axis in Migraine
Zhou, Y., Pang, M., Ma, Y., Lu, L., Zhang, J., Wang, P., Li, Q., & Yang, F. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03623-1 · Cited by 12
“The terminals of these usually possess neuropeptides like CGRP or SP [86].”
Micic, D. (2023) · Acta Endocrinologica (Bucharest) · doi:10.4183/aeb.2023.234 · Cited by 13
The interplay between the microbiota and opioid in the treatment of neuropathic pain
Gong, Z., Xue, Q., Luo, Y., Yu, B., Hua, B., & Liu, Z. (2024) · Frontiers in Microbiology · doi:10.3389/fmicb.2024.1390046 · Cited by 11
“The gut-brain axis constitutes a complex bidirectional communication network (Cussotto et al., 2018; Russo et al., 2018).”
BackgroundMicrobiome-Gut-Brain Axis: AI Insights
Amaan, A., Garg, P., & Prachi, S. (2024) · Insights in Biology and Medicine · doi:10.29328/journal.ibm.1001027 · Cited by 13
Transepithelial Effect of Probiotics in a Novel Model of Gut Lumen to Nerve Signaling
Piletz, J. E., Cooper, J., Chidester, K., Erson, K., Melton, S., Osemeka, A., Patterson, M., Strickland, K., Wan, J. X., & Williams, K. (2022) · Nutrients · doi:10.3390/nu14224856 · Cited by 11
“Yang, X.; Yu, D.; Xue, L.; Li, H.; Du, J. Probiotics Modulate the Microbiota–Gut–Brain Axis and Improve Memory Deficits in Aged SAMP8 Mice.”
BackgroundInfluentialAlmheiri, R. T., Hajjar, B. M., Alkhaaldi, S. M. I., Rabeh, N., Aljoudi, S., Abd‐Elrahman, K. S., & Hamdan, H. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-06201-2 · Cited by 12
“Some studies have shown that injecting oxytocin into patients can reduce stress levels [97].”
InfluentialMora, S., Martín-González, E., Prados-Pardo, Á., Moreno, J., López, M. J., Pilar-Cuéllar, F., Castro, E., Díaz, Á., Flores, P., & Moreno, M. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.08.010 · Cited by 10
Immune Homeostasis: A Novel Example of Teamwork
Kumar, V., & Stewart, J. H. (2024) · Methods in molecular biology · doi:10.1007/978-1-0716-3754-8_1 · Cited by 11
Probiotics in autism spectrum disorder: Recent insights from animal models
Golbaghi, N., Naeimi, S., Darvishi, A., Najari, N., & Cussotto, S. (2024) · Autism · doi:10.1177/13623613241246911 · Cited by 11
“The HPA axis, as a part of the neuroendocrine system involved in emotion and mood, is considered one pathway playing a role in the gut–brain axis of ASD patients (Cussotto et al., 2018).”
SIGNALLING THROUGH THE MICROBIOTA-GUT-BRAIN TRIADE
AMZĂR, A. I. (2022) · FARMACIA · doi:10.31925/farmacia.2022.3.4 · Cited by 10
Li, N., Liu, T., Wang, Y.-Y., Xu, T., Shi, H., Chang, L., & Zhu, L. (2024) · Neuroscience · doi:10.1016/j.neuroscience.2024.08.010 · Cited by 11
Shen, C., Deshmukh, H., Santos, J. M., Elmassry, M. M., Presto, P., Driver, Z., Bhakta, V., Yakhnitsa, V., Kiritoshi, T., Ji, G., et al. (2024) · The Journal of Frailty & Aging · doi:10.14283/jfa.2024.65 · Cited by 9
Lee, Y., Park, K., Lee, N., & Paik, H. (2025) · Brain Research · doi:10.1016/j.brainres.2025.149925 · Cited by 9
Prenatal Isoflurane Exposure Induces Developmental Neurotoxicity in Rats: the Role of Gut Microbiota
Wang, L., Yang, X., Zhou, D., Cheng, T., Zhang, X., & Wu, H. (2022) · Neurotoxicity Research · doi:10.1007/s12640-022-00487-6 · Cited by 10
“This process parallels neurodevelopment, which begins early in embryonic life and lasts through post-adolescence (O’Mahony et al. 2015; Thaiss et al. 2016; Cussotto et al. 2018; Tilg et al. 2020).”
BackgroundIntroducing sexual dysfunction in mental care
Gombert, M., Ballester, P., Segura, A., & Peiró, A. M. (2020) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2020.1849135 · Cited by 9
“control the response to social stimuli [13].”
Guo, W., Wan, X., Ma, L., Zhang, J., & Hashimoto, K. (2021) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2021.05.012 · Cited by 9
Harshaw, C., Kojima, S., Wellman, C. L., Demas, G. E., Morrow, A. L., Taft, D. H., Kenkel, W. M., Leffel, J. K., & Alberts, J. R. (2022) · Developmental Psychobiology · doi:10.1002/dev.22289 · Cited by 9
“…microbiome–brain interactions, both as a construct (Boem et al., 2021; Martin et al., 2018; Sarkar et al., 2018) and as a constellation of phenomena (Cusick et al., 2021; Cussotto et al., 2018; Nagpal & Cryan, 2021), have stimulated vigorous activity in basic, translational, and clinical research.”
BackgroundMicrobiome: A Key Regulator of Body-Brain Interactions
O’Riordan, K. J., Aburto, M. R., Nagpal, J. K., Clarke, G. A., & Cryan, J. F. (2025) · Advances in experimental medicine and biology · doi:10.1007/978-3-031-89525-8_6 · Cited by 9
Analysis of Hindgut Microbiome of Sheep and Effect of Different Husbandry Conditions
Minozzi, G., Biscarini, F., Costa, E. D., Chincarini, M., Ferri, N., Palestrini, C., Minero, M., Mazzola, S., Piccinini, R., Vignola, G., et al. (2020) · Animals · doi:10.3390/ani11010004 · Cited by 9
Metadata
- Authors
- Cussotto, S., Sandhu, K. V., Dinan, T. G., & Cryan, J. F.
- Affiliations
- University College Cork (IE)
- Corresponding author
- Cryan, John F.
- Venue
- Frontiers in Neuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2018-10
- Volume
- 51
- Pages
- 80-101
- ISSN
- 0091-3022 (ISSN-L)
- OpenAlex
- W2804326576
- Cited by
- 326
- References
- 407
- Citations by year
- 2026: 17 · 2025: 43 · 2024: 53 · 2023: 43 · 2022: 54 · 2021: 36 · 2020: 43 · 2019: 32 · 2018: 5
- FWCI
- 2.84
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Frontiers in Neuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Arrow@dit (Dublin Institute of Technology) (submittedVersion, cc-by-nc-nd)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- gut microbiota, gut-brain axis, neuroendocrine system, behavioral responses, stress, eating behaviour, sexual behavior, social behavior, cognition, addiction, host-microbe interactions
- MeSH terms
- Gastrointestinal Microbiome, Animals, Brain, Feeding Behavior, Humans, Learning, Neurosecretory Systems, Sexual Behavior, Social Behavior, Stress, Psychological, Behavior, Addictive
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