Neonatal maternal separation causes colonic dysfunction in rat pups including impaired host resistance
Abstract
Previous studies have shown that early life stress in the form of intermittent maternal separation (MS) predisposes adult rats to develop stress-induced intestinal mucosal dysfunction and visceral hypersensitivity. However, the mechanism involved in the functional abnormalities is unclear. Our aim was to study immature animals during or shortly after exposure to MS to determine whether there are early pathophysiological changes in the gut. Sprague-Dawley rat pups were individually separated from the dam for 3 h/d from 4 to 21 d of age; nonseparated (NS) control pups remained in the home cage with the dam. On d 19-20, d 24-25, and d 29-30, blood was collected for corticosterone measurement, and colonic tissues were removed for functional and morphologic assessment. Corticosteroid levels were elevated in MS pups compared with NS, indicating that MS was indeed stressful. The distal colon demonstrated significantly enhanced ion secretion and macromolecular permeability at d 19-20 and d 24-25, returning to normal by d 29-30. Electron microscopy and bacterial culture studies indicated bacteria adhering to and penetrating into the colonic epithelium of the MS pups at all time points, while such events were rare in NS pups. The pathophysiological changes were inhibited by injecting pups sc with a corticotropin-releasing hormone (CRH) receptor antagonist daily during MS. Our studies indicate that early psychological trauma predisposes neonatal rats to develop persistent mucosal barrier dysfunction, including impaired host defense to luminal bacteria, by a mechanism involving peripheral CRH receptors.
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Neonatal stress can lead to short- and long-term alterations in the diversity and composition of the gut microbiota.
“Several studies have demonstrated that neonatal stress can lead to short- and long-term alterations in the diversity and composition of the GM (345–347).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [345]
Cites
Measurement of Cutaneous Inflammation: Estimation of Neutrophil Content with an Enzyme Marker
Bradley, P. P., Priebat, D. A., Christensen, R. D., & Rothstein, G. (1982) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12506462 · Cited by 3,628 · see citing works
Plotsky, P. M., & Meaney, M. J. (1993) · Molecular Brain Research · doi:10.1016/0169-328x(93)90189-v · Cited by 1,638 · see citing works
SÁNCHEZ, M. M., LADD, C. O., & PLOTSKY, P. M. (2001) · Development and Psychopathology · doi:10.1017/s0954579401003029 · Cited by 1,003 · see citing works
Huot, R. L., Thrivikraman, K. V., Meaney, M. J., & Plotsky, P. M. (2001) · Psychopharmacology · doi:10.1007/s002130100701 · Cited by 506 · see citing works
Childhood sexual abuse, stressful life events and risk for major depression in women
KENDLER, K. S., KUHN, J. W., & PRESCOTT, C. A. (2004) · Psychological Medicine · doi:10.1017/s003329170400265x · Cited by 475 · see citing works
Coutinho, S. V., Plotsky, P. M., Sablad, M., Miller, J. C., Zhou, H., Bayati, A. I., McRoberts, J. A., & Mayer, E. A. (2002) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00240.2001 · Cited by 456 · see citing works
Levine, S. (2001) · Physiology & Behavior · doi:10.1016/s0031-9384(01)00496-6 · Cited by 428 · see citing works
Plasma concentrations of total and free corticosterone during development in the rat.
Henning, S. (1978) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1978.235.5.e451 · Cited by 414 · see citing works
Fukudo, S., Nomura, T., & Hongo, M. (1998) · Gut · doi:10.1136/gut.42.6.845 · Cited by 387 · see citing works
Söderholm, J. D., Yang, P., Ceponis, P., Vohra, A., Riddell, R., Sherman, P. M., & Perdue, M. H. (2002) · Gastroenterology · doi:10.1053/gast.2002.36019 · Cited by 362 · see citing works
Self-citationThe temporal dynamics of the stress response
Koolhaas, J. M., Meerlo, P., de Boer, S. F., STRUBBE, J. H., & Bohus, B. (1997) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(96)00057-7 · Cited by 331 · see citing works
Responses to maternal separation : mechanisms and mediators
Kuhn, C. M., & Schanberg, S. M. (1998) · International Journal of Developmental Neuroscience · doi:10.1016/s0736-5748(98)00034-3 · Cited by 287 · see citing works
Stress and the developing limbic-hypothalamic-pituitary-adrenal axis
M. Vázquez, D. (1998) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(98)00029-8 · Cited by 274 · see citing works
Castagliuolo, I., LaMont, J. T., Qiu, B., Fleming, S. M., Bhaskar, K. R., Nikulásson, S. Þ., Kornetsky, C. H., & Pothoulakis, C. (1996) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1996.271.5.g884 · Cited by 251 · see citing works
Corticotropin-releasing hormone mimics stress-induced colonic epithelial pathophysiology in the rat
Santos, J., Saunders, P. R., Hanssen, N. P. M., Yang, P., Yates, D. A., Groot, J. A., & Perdue, M. H. (1999) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1999.277.2.g391 · Cited by 251 · see citing works
Self-citationSöderholm, J. D., Yates, D. A., Gareau, M. G., Yang, P.-C., MacQueen, G., & Perdue, M. H. (2002) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00314.2002 · Cited by 243 · see citing works
Self-citationSanderson, I. R., & Walker, W. A. (1993) · Gastroenterology · doi:10.1016/0016-5085(93)90436-g · Cited by 241 · see citing works
Barreau, F., Ferrier, L., Fioramonti, J., & Bueno, L. P. (2004) · Gut · doi:10.1136/gut.2003.024174 · Cited by 240 · see citing works
Taché, Y., Martı́nez, V., Wang, L., & Million, M. (2004) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0705760 · Cited by 228 · see citing works
Stress stimulates transepithelial macromolecular uptake in rat jejunum
Kiliaan, A. J., Saunders, P. R., Bijlsma, P. B., Berin, M. C., Taminiau, J. A., Groot, J. A., & Perdue, M. H. (1998) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1998.275.5.g1037 · Cited by 223 · see citing works
Self-citationChronic stress impairs rat growth and jejunal epithelial barrier function: role of mast cells
Santos, J., Benjamin, M. A., Yang, P., Prior, T., & Perdue, M. H. (2000) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.2000.278.6.g847 · Cited by 205 · see citing works
Self-citationUdall, J. N., Pang, K. Y., Fritze, L. M. S., Kleinman, R. E., & Walker, W. A. (1981) · Pediatric Research · doi:10.1203/00006450-198103000-00008 · Cited by 175 · see citing works
Barreau, F., Cartier, C., Ferrier, L., Fioramonti, J., & Bueno, L. P. (2004) · Gastroenterology · doi:10.1053/j.gastro.2004.05.019 · Cited by 171 · see citing works
Maternally separated rats show deficits in maternal care in adulthood
Lovic, V., González, A., & Fleming, A. S. (2001) · Developmental Psychobiology · doi:10.1002/dev.1024 · Cited by 149 · see citing works
Recollection of Childhood Events in Adults with Irritable Bowel Syndrome
Lowman, B., Drossman, D. A., Cramer, E. M., & McKee, D. C. (1987) · Journal of Clinical Gastroenterology · doi:10.1097/00004836-198706000-00017 · Cited by 146 · see citing works
Relation of peroxidase activity in gut mucosa to inflammation
Smith, J. W., & Castro, G. A. (1978) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1978.234.1.r72 · Cited by 118 · see citing works
Rosztoczy, A. I., Fioramonti, J., Jármay, K., Barreau, F., Wittmann, T., & Bueno, L. P. (2003) · Neurogastroenterology & Motility · doi:10.1046/j.1350-1925.2003.00451.x · Cited by 91 · see citing works
Yang, P., Berin, M. C., Yu, L. C., & Perdue, M. H. (2001) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64010-2 · Cited by 78 · see citing works
Self-citationThompson, F. M., Mayrhofer, G., & Cummins, A. (1996) · Gastroenterology · doi:10.1053/gast.1996.v111.pm8698223 · Cited by 50 · see citing works
Epithelial Growth of the Small Intestine in Human Infants
Thompson, F. M., Catto‐Smith, A. G., Moore, D., Davidson, G. P., & Cummins, A. G. (1998) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/00005176-199805000-00004 · Cited by 48 · see citing works
Kim, J. W., Jeon, W. K., & Kim, E. J. (2005) · Clinical Nutrition · doi:10.1016/j.clnu.2005.04.004 · Cited by 41 · see citing works
Baram, T. Z., Mitchell, W. G., Brunson, K. L., & Haden, E. (1999) · Developmental Neuroscience · doi:10.1159/000017407 · Cited by 35 · see citing works
Wenzl, H., Schimpl, G., Feierl, G., & Steinwender, G. (2001) · Digestive Diseases and Sciences · doi:10.1023/a:1010734717218 · Cited by 34 · see citing works
Differences in control of descending inhibition in the proximal and distal regions of rat colon
Hata, F., Kataoka, T., Takeuchi, T., Yagasaki, O., & Yamano, N. (1990) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1990.tb14198.x · Cited by 27 · see citing works
Structural and enzymatic changes during colonic maturation in the fetal and suckling rat
Colony, P. C., Kois, J. M., & Peiffer, L. P. (1989) · Gastroenterology · doi:10.1016/0016-5085(89)90069-3 · Cited by 26 · see citing works
Pathophysiologic glucocorticoid elevations promote bacterial translocation after thermal injury
Jones, W. G., Minei, J. P., Richardson, R. P., Fahey, T. J., Calvano, S. E., Antonacci, A. C., Shires, G. T., & Shires, G. T. (1990) · Infection and Immunity · doi:10.1128/iai.58.10.3257-3261.1990 · Cited by 22 · see citing works
Development of Colonic Fluid and Electrolyte Transport
Finkel, Y., Aperia, A. C., & Eklöf, A. (1985) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/00005176-198506000-00023 · Cited by 13 · see citing works
Flagged first, then by citations
1 of the 38 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Bacterial infection causes stress-induced memory dysfunction in mice
Gareau, M. G., Wine, E., Rodrigues, D. M., Cho, J. H., Whary, M. T., Philpott, D. J., MacQueen, G., & Sherman, P. M. (2011) · Gut · doi:10.1136/gut.2009.202515 · Cited by 909 · see citing works
“In rodents, neonatal maternal separation is associated with hypothalamic-pituitary-adrenal (HPA) axis alterations, colonic dysfunction and altered intestinal microbiota in neonates, and stress-induced colonic dysfunction and behavioural changes later during adulthood.”
BackgroundSelf-citationBrain–Gut Interactions in Inflammatory Bowel Disease
Bonaz, B. L., & Bernstein, C. N. (2013) · Gastroenterology · doi:10.1053/j.gastro.2012.10.003 · Cited by 667 · see citing works
5-Hydroxytryptamine (serotonin) in the gastrointestinal tract
Gershon, M. D. (2013) · Current Opinion in Endocrinology, Diabetes & Obesity · doi:10.1097/med.0b013e32835bc703 · Cited by 617 · see citing works
Malnutrition as an enteric infectious disease with long-term effects on child development
Guerrant, R. L., Oriá, R. B., Moore, S. R., Oriá, M. O. B., & Lima, A. Â. M. (2008) · Nutrition Reviews · doi:10.1111/j.1753-4887.2008.00082.x · Cited by 544 · see citing works
Microbiota and host determinants of behavioural phenotype in maternally separated mice
De Palma, G., Blennerhassett, P., Lu, J., Deng, Y., Park, A. J., Green, W., Denou, E., Silva, M. A., Santacruz, A., Sanz, Y., et al. (2015) · Nature Communications · doi:10.1038/ncomms8735 · Cited by 517 · see citing works
Gareau, M. G., Jury, J., MacQueen, G., Sherman, P. M., & Perdue, M. H. (2007) · Gut · doi:10.1136/gut.2006.117176 · Cited by 472 · see citing works
Self-citationMaternal separation as a model of brain-gut axis dysfunction
O’Mahony, S. M., Hyland, N. P., Dinan, T. G., & Cryan, J. F. (2011) · Psychopharmacology · doi:10.1007/s00213-010-2010-9 · Cited by 415 · see citing works
Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis
Rusch, J. A., Layden, B. T., & Dugas, L. R. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1130689 · Cited by 415 · see citing works
Le Huërou-Luron, I., Blat, S., & Boudry, G. (2010) · Nutrition Research Reviews · doi:10.1017/s0954422410000065 · Cited by 407 · see citing works
Stress and the Microbiota–Gut–Brain Axis in Visceral Pain: Relevance to Irritable Bowel Syndrome
Moloney, R. D., Johnson, A. C., O’Mahony, S. M., Dinan, T. G., Meerveld, B. G., & Cryan, J. F. (2015) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12490 · Cited by 396 · see citing works
Association Between Early Adverse Life Events and Irritable Bowel Syndrome
Bradford, K., Shih, W., Videlock, E. J., Presson, A. P., Naliboff, B. D., Mayer, E. A., & Chang, L. (2011) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2011.12.018 · Cited by 322 · see citing works
Stress signaling pathways activated by weaning mediate intestinal dysfunction in the pig
Moeser, A. J., Klok, C. V., Ryan, K. A., Wooten, J. G., Little, D., Cook, V. L., & Blikslager, A. T. (2006) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00197.2006 · Cited by 320 · see citing works
The microbiota–gut–brain axis in gastrointestinal disorders: stressed bugs, stressed brain or both?
Palma, G. D., Collins, S. M., Berčík, P., & Verdu, E. F. (2014) · The Journal of Physiology · doi:10.1113/jphysiol.2014.273995 · Cited by 293 · see citing works
The Role of Stress on Physiologic Responses and Clinical Symptoms in Irritable Bowel Syndrome
Chang, L. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.01.032 · Cited by 268 · see citing works
Diseases, Disorders, and Comorbidities of Interoception
Bonaz, B., Lane, R. D., Oshinsky, M. L., Kenny, P. J., Sinha, R., Mayer, E. A., & Critchley, H. D. (2021) · Trends in Neurosciences · doi:10.1016/j.tins.2020.09.009 · Cited by 260 · see citing works
The Spectrum of Achalasia: Lessons From Studies of Pathophysiology and High-Resolution Manometry
Kahrilas, P. J., & Boeckxstaens, G. E. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.08.038 · Cited by 234 · see citing works
CRF induces intestinal epithelial barrier injury via the release of mast cell proteases and TNF-α
Overman, E. L., Rivier, J. E., & Moeser, A. J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0039935 · Cited by 207 · see citing works
Enteric nervous system development: what could possibly go wrong?
Rao, M., & Gershon, M. D. (2018) · Nature reviews. Neuroscience · doi:10.1038/s41583-018-0041-0 · Cited by 201 · see citing works
Videlock, E. J., Adeyemo, M. A., Licudine, A., Hirano, M., Ohning, G., Mayer, M., Mayer, E. A., & Chang, L. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.08.058 · Cited by 198 · see citing works
Visceral Pain: The Neurophysiological Mechanism
Sengupta, J. N. (2009) · Handbook of experimental pharmacology · doi:10.1007/978-3-540-79090-7_2 · Cited by 201 · see citing works
Microbiota-gut-brain axis and cognitive function
Gareau, M. G. (2014) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4939-0897-4_16 · Cited by 189 · see citing works
Self-citationMoya-Pérez, Á., Pérez‐Villalba, A., Benítez‐Páez, A., Campillo, I., & Sanz, Y. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2017.05.011 · Cited by 177 · see citing works
Leigh, S., Uhlig, F., Wilmes, L., Sánchez-Díaz, P., Gheorghe, C. E., Goodson, M. S., Kelley‐Loughnane, N., Hyland, N. P., Cryan, J. F., & Clarke, G. A. (2023) · The Journal of Physiology · doi:10.1113/jp281951 · Cited by 193 · see citing works
Barreau, F., Ferrier, L., Fioramonti, J., & Bueno, L. P. (2007) · Pediatric Research · doi:10.1203/pdr.0b013e3180db2949 · Cited by 156 · see citing works
Welch, M. G., Margolis, K. G., Li, Z., & Gershon, M. D. (2014) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00176.2014 · Cited by 152 · see citing works
Gareau, M. G., Jury, J., & Perdue, M. H. (2007) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00392.2006 · Cited by 147 · see citing works
Self-citationIntestinal permeability and irritable bowel syndrome
Camilleri, M., & Gorman, H. (2007) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2007.00925.x · Cited by 144 · see citing works
Probiotics normalize the gut-brain-microbiota axis in immunodeficient mice
Smith, C. J., Emge, J. R., Berzins, K., Lung, L., Khamishon, R., Shah, P., Rodrigues, D. M., Sousa, A. J., Reardon, C., Sherman, P. M., et al. (2014) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00238.2014 · Cited by 143 · see citing works
Self-citationWelch, M. G., Tamir, H., Gross, K. J., Chen, J. C., Anwar, M., & Gershon, M. D. (2008) · The Journal of Comparative Neurology · doi:10.1002/cne.21872 · Cited by 132 · see citing works
Cognitive Function and the Microbiome
Gareau, M. G. (2016) · International review of neurobiology · doi:10.1016/bs.irn.2016.08.001 · Cited by 131 · see citing works
Self-citationCowan, C. S. M., Callaghan, B. L., Kan, J. M., & Richardson, R. (2015) · Genes Brain & Behavior · doi:10.1111/gbb.12263 · Cited by 127 · see citing works
Understanding the Connection between Gut Homeostasis and Psychological Stress
Zhang, H., Wang, Z., Wang, G., Song, X., Qian, Y., Liao, Z., Sui, L., Ai, L., & Xia, Y. (2023) · Journal of Nutrition · doi:10.1016/j.tjnut.2023.01.026 · Cited by 127 · see citing works
Man, S. M., Kaakoush, N. O., Leach, S. T., Nahidi, L., Lu, H. K., Norman, J. M., Day, A. S., Zhang, L., & Mitchell, H. M. (2010) · The Journal of Infectious Diseases · doi:10.1086/657316 · Cited by 117 · see citing works
Role of Corticotropin-releasing Factor in Gastrointestinal Permeability
Rodiño‐Janeiro, B. K., Alonso, C., Pigrau, M., Lobo, B., Vicario, M., & Santos, J. (2014) · Journal of Neurogastroenterology and Motility · doi:10.5056/jnm14084 · Cited by 119 · see citing works
The Role of Psychological Stress in Inflammatory Bowel Disease
Mawdsley, J. E. D., & Rampton, D. S. (2006) · NeuroImmunoModulation · doi:10.1159/000104861 · Cited by 116 · see citing works
Teitelbaum, A. A., Gareau, M. G., Jury, J., Yang, P. C., & Perdue, M. H. (2008) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.90210.2008 · Cited by 116 · see citing works
Self-citationDistrutti, E., Cipriani, S., Mencarelli, A., Renga, B., & Fiorucci, S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0063893 · Cited by 107 · see citing works
Neurons and Glia in the Enteric Nervous System and Epithelial Barrier Function
Vergnolle, N., & Cirillo, C. (2018) · Physiology · doi:10.1152/physiol.00009.2018 · Cited by 106 · see citing works
The Brain-Gut Axis in Health and Disease
Omran, Y. A., & Aziz, Q. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-1-4939-0897-4_6 · Cited by 106 · see citing works
Childhood functional abdominal pain: mechanisms and management
Korterink, J., Devanarayana, N. M., Rajindrajith, S., Vlieger, A. M., & Benninga, M. A. (2015) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2015.21 · Cited by 106 · see citing works
Visceral pain: gut microbiota, a new hope?
Pusceddu, M. M., & Gareau, M. G. (2018) · Journal of Biomedical Science · doi:10.1186/s12929-018-0476-7 · Cited by 100 · see citing works
Self-citationBarouei, J., Moussavi, M., & Hodgson, D. M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0046051 · Cited by 99 · see citing works
Sun, Q., Cheng, L., Zeng, X., Zhang, X., Wu, Z., & Weng, P. (2020) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2020.07.208 · Cited by 98 · see citing works
Pohl, C. S., Medland, J. E., & Moeser, A. J. (2015) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00206.2015 · Cited by 94 · see citing works
Neonatal maternal separation enhances central sensitivity to noxious colorectal distention in rat
Chung, E. K. Y., Zhang, X., Li, Z., Zhang, H., Xu, H., & Bian, Z. (2007) · Brain Research · doi:10.1016/j.brainres.2007.03.047 · Cited by 86 · see citing works
Faturi, C. D. B., Tiba, P. A., Kawakami, S. E., Catallani, B., Kerstens, M., & Suchecki, D. (2009) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2009.09.002 · Cited by 77 · see citing works
Cytokines and irritable bowel syndrome: Where do we stand?
Bashashati, M., Rezaei, N., Andrews, C. N., Chen, C., Daryani, N. E., Sharkey, K. A., & Storr, M. (2011) · Cytokine · doi:10.1016/j.cyto.2011.11.019 · Cited by 73 · see citing works
Early life stress disrupts intestinal homeostasis via NGF-TrkA signaling
Wong, H. L. X., Qin, H., Tsang, S. W., Zuo, X., Che, S., Chow, C. F. W., Li, X., Xiao, H., Zhao, L., Huang, T., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09744-3 · Cited by 71 · see citing works
Stress and the Commensal Microbiota: Importance in Parturition and Infant Neurodevelopment
Gur, T., Worly, B. L., & Bailey, M. T. (2015) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2015.00005 · Cited by 69 · see citing works
Øines, E., Murison, R., Mrdalj, J., Grønli, J., & Milde, A. M. (2012) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.11.024 · Cited by 66 · see citing works
Gut permeability and depressive symptom severity in unmedicated adolescents
Calarge, C. A., Devaraj, S., & Shulman, R. J. (2018) · Journal of Affective Disorders · doi:10.1016/j.jad.2018.12.077 · Cited by 65 · see citing works
O’Mahony, S. M., Chua, A., Quigley, E. M. M., Clarke, G. A., Shanahan, F., Keeling, P. W. N., & Dinan, T. G. (2008) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2007.01065.x · Cited by 64 · see citing works
Modulation of intestinal barrier function by glucocorticoids: Lessons from preclinical models
Tena‐Garitaonaindia, M., Arredondo‐Amador, M., Mascaraque, C., Asensio, M., Marı́n, J. J. G., Martínez‐Augustin, O., & de Medina, F. S. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106056 · Cited by 63 · see citing works
Probiotics Prevent Death Caused byCitrobacter rodentiumInfection in Neonatal Mice
Gareau, M. G., Wine, E., Reardon, C., & Sherman, P. M. (2009) · The Journal of Infectious Diseases · doi:10.1086/648614 · Cited by 59 · see citing works
Self-citationLong term effects of pre- and early postnatal nutrition and environment on the gut1
Lallès, J. P. (2012) · Journal of Animal Science · doi:10.2527/jas.53904 · Cited by 58 · see citing works
Rincel, M., Lépinay, A. L., Janthakhin, Y., Soudain, G., Yvon, S., Silva, S. D., Joffre, C., Aubert, A., Séré, A., Layé, S., et al. (2017) · Brain Structure and Function · doi:10.1007/s00429-017-1526-8 · Cited by 56 · see citing works
Cowan, C. S. M., Callaghan, B. L., & Richardson, R. (2013) · Behavioral Neuroscience · doi:10.1037/a0034118 · Cited by 55 · see citing works
Chung, E. K. Y., Zhang, X.-J., Xu, H., Sung, J. J. �., & Bian, Z. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.07.055 · Cited by 53 · see citing works
Vargas-Martínez, F., Uvnás-Moberg, K., Petersson, M., Olausson, H., & Jiménez-Estrada, I. (2014) · Progress in neurobiology · doi:10.1016/j.pneurobio.2014.10.001 · Cited by 49 · see citing works
Dysbiosis and Alzheimer’s Disease: Cause or Treatment Opportunity?
Janeiro, M. H., Ramírez, M. J., & Solas, M. (2021) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-020-01024-9 · Cited by 50 · see citing works
Estienne, M., Claustre, J., Clain-Gardechaux, G., Paquet, A., Taché, Y., Fioramonti, J., & Plaisancié, P. (2010) · Gut · doi:10.1136/gut.2009.190728 · Cited by 50 · see citing works
van den Wijngaard, R. M., Stanisor, O. I., van Diest, S. A., Welting, O., Wouters, M. M., de Jonge, W. J., & Boeckxstaens, G. E. (2011) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2011.01840.x · Cited by 49 · see citing works
Effects of Stress on Commensal Microbes and Immune System Activity
Gur, T., & Bailey, M. T. (2016) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-20215-0_14 · Cited by 49 · see citing works
A spectrum of intestinal injury models in neonatal mice
Zani, A., Zani‐Ruttenstock, E., Peyvandi, F., Lee, C., Li, B., & Pierro, A. (2015) · Pediatric Surgery International · doi:10.1007/s00383-015-3813-x · Cited by 49 · see citing works
Maternal separation in rodents: a journey from gut to brain and nutritional perspectives
Rincel, M., & Darnaudéry, M. (2019) · Proceedings of The Nutrition Society · doi:10.1017/s0029665119000958 · Cited by 50 · see citing works
Boyer, P. E., D’Costa, S., Edwards, L., Milloway, M. C., Susick, E., Borst, L. B., Thakur, S., Campbell, J. M., Crenshaw, J., Polo, J., et al. (2015) · British Journal Of Nutrition · doi:10.1017/s000711451400422x · Cited by 47 · see citing works
Maghami, S., Zardooz, H., Khodagholi, F., Binayi, F., Saber, R. R., Hedayati, M., Sahraei, M., & Ansari, M. A. (2018) · PLoS ONE · doi:10.1371/journal.pone.0204731 · Cited by 47 · see citing works
Association Between Child Maltreatment and Constipation
Rajindrajith, S., Devanarayana, N. M., Lakmini, C., Subasinghe, V., de Silva, D. G. H., & Benninga, M. A. (2013) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/mpg.0000000000000249 · Cited by 45 · see citing works
Rajindrajith, S., Devanarayana, N. M., & Benninga, M. A. (2015) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/mpg.0000000000001006 · Cited by 42 · see citing works
Kerschaver, C. V., Turpin, D. L., Michiels, J., & Pluske, J. R. (2023) · Animals · doi:10.3390/ani13101644 · Cited by 41 · see citing works
Hu, S., Xiao, Y., Zhu, L., Li, L., Hu, C.-Y., Jiang, X., & Xu, G.-Y. (2012) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00338.2012 · Cited by 41 · see citing works
Yu, Z., Cen, Y.-X., Wu, B.-H., Cheng, W., Xiong, F., Li, D., Liu, T.-T., Luo, M., Guo, L., Li, Y., et al. (2019) · World Journal of Gastroenterology · doi:10.3748/wjg.v25.i29.3956 · Cited by 41 · see citing works
Luo, J., Qin, H., Wong, C.-K., Tsang, S. Y., Huang, Y., & Bian, Z. (2011) · Journal of Pain · doi:10.1016/j.jpain.2010.11.005 · Cited by 40 · see citing works
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 35 · see citing works
Zhang, X.-J., Li, Z., Chung, E. K. Y., Zhang, H.-Q., Xu, H., Sung, J. J. �., & Bian, Z. (2008) · Journal of Molecular Neuroscience · doi:10.1007/s12031-008-9134-y · Cited by 34 · see citing works
Early life experience shapes the functional organization of stress-responsive visceral circuits
Rinaman, L., Banihashemi, L., & Koehnle, T. J. (2011) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.04.008 · Cited by 33 · see citing works
Molecular basis of the irritable bowel syndrome
Vaiopoulou, A. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i2.376 · Cited by 33 · see citing works
Li, L., Xie, R., Hu, S., Wang, Y., Yu, T., Xiao, Y., Jiang, X., Gu, J., Hu, C.-Y., & Xu, G.-Y. (2012) · Molecular Pain · doi:10.1186/1744-8069-8-89 · Cited by 31 · see citing works
Li, B., Zani, A., Lee, C. M., Zani-Ruttenstock, E., Zhang, Z., Li, X., Ip, W., Gonska, T., & Pierro, A. (2016) · Journal of Pediatric Surgery · doi:10.1016/j.jpedsurg.2016.02.073 · Cited by 23 · see citing works
Peripheral relays in stress-induced activation of visceral afferents in the gut
van den Wijngaard, R. M., Klooker, T. K., de Jonge, W. J., & Boeckxstaens, G. E. (2009) · Autonomic Neuroscience · doi:10.1016/j.autneu.2009.07.004 · Cited by 30 · see citing works
Zhu, L., Zhao, L., Qu, R., Zhu, H., Wang, Y., Jiang, X., & Xu, G. (2015) · Scientific Reports · doi:10.1038/srep16109 · Cited by 25 · see citing works
Katiraei, P., & Bultron, G. (2011) · PubMed Central · doi:10.3748/wjg.v17.i23.2791 · Cited by 26 · see citing works
Collins, J. M., Caputi, V., Manurung, S., Gross, G., Fitzgerald, P., Golubeva, A. V., Popov, J., Deady, C., Dinan, T. G., Cryan, J. F., et al. (2022) · Neuropharmacology · doi:10.1016/j.neuropharm.2022.109026 · Cited by 22 · see citing works
The impact of voluntary exercise on relative telomere length in a rat model of developmental stress
Botha, M., Grace, L. K., Bugarith, K., Russell, V. A., Kidd, M., Seedat, S., & Hemmings, S. M. J. (2012) · BMC Research Notes · doi:10.1186/1756-0500-5-697 · Cited by 21 · see citing works
Woloszynek, S., Pastor, S. J., Mell, J. C., Nandi, N., Sokhansanj, B. A., & ROSEN, G. L. (2016) · International review of cytology · doi:10.1016/bs.ircmb.2016.01.003 · Cited by 19 · see citing works
Early maternal separation induces alterations of colonic epithelial permeability and morphology
Li, B., Lee, C., Zani, A., Zani‐Ruttenstock, E., Ip, W., Chi, L., Delgado-Olguı́n, P., Gonska, T. Y., & Pierro, A. (2014) · Pediatric Surgery International · doi:10.1007/s00383-014-3611-x · Cited by 19 · see citing works
Chaloner, A., Rao, A., Al–Chaer, E. D., & Meerveld, B. G. (2009) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2009.09.001 · Cited by 18 · see citing works
Challenges and prospects for pharmacotherapy in functional gastrointestinal disorders
Sanger, G. J., Chang, L., Bountra, C., & Houghton, L. A. (2010) · Therapeutic Advances in Gastroenterology · doi:10.1177/1756283x10369922 · Cited by 17 · see citing works
Tan, X., Pei, W., Xie, C., Wang, Z., Liu, J., Cheng, Y., Mao, T., Shi, L., Zhao, X., Lu, Q., et al. (2021) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2021/6679348 · Cited by 16 · see citing works
Early maternal separation promotes alterations in the thermoregulatory profile of adult Wistar rats
Melo, C., Vizin, R. C. L., Silva, N. U., Ishikawa, D. T., Echeverry, M. B., Carrettiero, D. C., & Almeida, M. C. (2018) · Journal of Thermal Biology · doi:10.1016/j.jtherbio.2018.09.013 · Cited by 16 · see citing works
Stress and food allergy: mechanistic considerations
Schreier, H. M. C., & Wright, R. J. (2013) · Annals of Allergy Asthma & Immunology · doi:10.1016/j.anai.2013.08.002 · Cited by 15 · see citing works
Kłak, K., Maciuszek, M., Michalik, A., Mazur, M., Zawisza, M., Pecio, A., Nowak, B. F., & Chadzińska, M. (2025) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2025.110301 · Cited by 17 · see citing works
Extracellular Hsp 72: A Double-Edged Sword for Host Defense
Fleshner, M., Johnson, J. D., & Friedman, J. (2007) · Springer eBooks · doi:10.1007/978-1-4020-5585-0_15 · Cited by 15 · see citing works
Alanyl-glutamine restores maternal deprivation-induced TLR4 levels in a rat neonatal model
Mbodji, K., Torre, S., Haas, V. K., Déchelotte, P., & Marion‐Letellier, R. (2011) · Clinical Nutrition · doi:10.1016/j.clnu.2011.04.002 · Cited by 14 · see citing works
Early Life Stress Induces Both Acute and Chronic Colonic Barrier Dysfunction
Gareau, M. G., Wine, E., & Sherman, P. M. (2009) · NeoReviews · doi:10.1542/neo.10-4-e191 · Cited by 13 · see citing works
Self-citationSancho‐Alonso, M., Sarriés-Serrano, U., Miquel-Rio, L., Yanes-Castilla, C., Paz, V., Meana, J. J., Perelló, M., & Bortolozzi, A. A. (2024) · Revista de Psiquiatría y Salud Mental · doi:10.1016/j.sjpmh.2024.07.002 · Cited by 12 · see citing works
Włodarczyk, M., Sobolewska-Włodarczyk, A., Stec-Michalska, K., Fichna, J., & Wiśniewska-Jarosińska, M. (2016) · Pharmacological Reports · doi:10.1016/j.pharep.2016.04.008 · Cited by 11 · see citing works
Hasegawa, R., Saito‐Nakaya, K., Gu, L., Kanazawa, M., & Fukudo, S. (2023) · BioPsychoSocial Medicine · doi:10.1186/s13030-022-00258-x · Cited by 11 · see citing works
Elizabeth, M., & Zabielski, R. (2013) · InTech eBooks · doi:10.5772/55425 · Cited by 11 · see citing works
Yang, D. C., Bai, R., Li, C., Sun, Y., Jing, H., Wang, Z., Chen, Y., & Dong, Y. (2024) · Journal of Inflammation Research · doi:10.2147/jir.s488290 · Cited by 9 · see citing works
- Authors
- Gareau, M. G., Jury, J., Yang, P. C., MacQueen, G., & Perdue, M. H.
- Affiliations
- McMaster University (CA)
- Corresponding author
- Gareau, Mélanie G
- Venue
- Pediatric Research
- Published
- 2006-01
- Volume
- 59
- Issue
- 1
- Pages
- 83-88
- ISSN
- 0031-3998 (ISSN-L)
- 1530-0447
- OpenAlex
- W1970620887
- Cited by
- 139
- References
- 38
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 8 · 2022: 4 · 2021: 6 · 2020: 4 · 2019: 4 · 2018: 8 · 2017: 4 · 2016: 7 · 2015: 14 · 2014: 13 · 2013: 9 · 2012: 9
- FWCI
- 4.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pediatric Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- AstraZeneca
- Crohn's and Colitis Foundation
- Crohn's and Colitis Foundation of Canada
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Health Professions › Pharmacy › Infant Health and Development
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- maternal separation, early life stress, neonatal rats, corticosterone, macromolecule permeability, corticotropin-releasing factor receptor, CRH receptor antagonist, visceral hypersensitivity, host resistance
- MeSH terms
- Animals, Animals, Newborn, Bacterial Adhesion, Body Weight, Colon, Colonic Diseases, Corticosterone, Female, Intestinal Mucosa, Maternal Deprivation, Rats, Sprague-Dawley, Receptors, Corticotropin-Releasing Hormone, Rats
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