The DOI matches its Crossref record; 69 of the 71 references it cites were found in a registry or an index.
Bacterial infection causes stress-induced memory dysfunction in mice
Open accessAbstract
BACKGROUND: The brain-gut axis is a key regulator of normal intestinal physiology; for example, psychological stress is linked to altered gut barrier function, development of food allergies and changes in behaviour. Whether intestinal events, such as enteric bacterial infections and bacterial colonisation, exert a reciprocal effect on stress-associated behaviour is not well established. OBJECTIVE: To determine the effects of either acute enteric infection or absence of gut microbiota on behaviour, including anxiety and non-spatial memory formation. METHODS: Behaviour was assessed following infection with the non-invasive enteric pathogen, Citrobacter rodentium in both C57BL/6 mice and germ-free Swiss-Webster mice, in the presence or absence of acute water avoidance stress. Whether daily treatment with probiotics normalised behaviour was assessed, and potential mechanisms of action evaluated. RESULTS: No behavioural abnormalities were observed, either at the height of infection (10 days) or following bacterial clearance (30 days), in C rodentium-infected C57BL/6 mice. When infected mice were exposed to acute stress, however, memory dysfunction was apparent after infection (10 days and 30 days). Memory dysfunction was prevented by daily treatment of infected mice with probiotics. Memory was impaired in germ-free mice, with or without exposure to stress, in contrast to conventionally reared, control Swiss-Webster mice with an intact intestinal microbiota. CONCLUSIONS: The intestinal microbiota influences the ability to form memory. Memory dysfunction occurs in infected mice exposed to acute stress, while in the germ-free setting memory is altered at baseline.
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“Firstly, studies in germ-free (GF) animals showed that the brain is affected in the absence of microbiota (see Table 2) (Clarke et al., 2013;Diaz Heijtz et al., 2011;Gareau et al., 2011;Hegstrand and Hine, 1986;Neufeld et al., 2011;Sudo et al., 2004).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Gareau et al., 2011
In the citing paper
“In addition, these animals exhibit altered BDNF expression in the hippocampus (Bercik et al., 2011a;Diaz Heijtz et al., 2011;Gareau et al., 2011), which as stated earlier has an important role in synaptic plasticity and cognition (Baj et al., 2013;Lu et al., 2014;Neufeld et al., 2011), suggesting a crucial involvement of microbes in regulating hippocampal-dependent memory function.”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Gareau et al., 2011
In the citing paper
“In addition, these animals exhibit altered BDNF expression in the hippocampus (Bercik et al., 2011a;Diaz Heijtz et al., 2011;Gareau et al., 2011), which as stated earlier has an important role in synaptic plasticity and cognition (Baj et al., 2013;Lu et al., 2014;Neufeld et al., 2011), suggesting a crucial involvement of microbes in regulating hippocampal-dependent memory function.”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Gareau et al., 2011
In the citing paper
“It has been shown that GF mice exhibit an impaired ability to remember a familiar object when presented with a novel object (Gareau et al., 2011;Luk et al., 2018), as well as impaired working memory in remembering a familiar environment in the spontaneous alternation task (Gareau et al., 2011).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Gareau et al., 2011
In the citing paper
“It has been shown that GF mice exhibit an impaired ability to remember a familiar object when presented with a novel object (Gareau et al., 2011;Luk et al., 2018), as well as impaired working memory in remembering a familiar environment in the spontaneous alternation task (Gareau et al., 2011).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Gareau et al., 2011
In the citing paper
“Indeed, different Lactobacillus strains were capable of restoring deficits in object recognition memory induced by chronic restraint stress (Liang et al., 2015a), as well as preventing these deficits in GF mice (Gareau et al., 2011), in a mouse model of colitis (Emge et al., 2016), and in immunodeficient mice (Smith et al., 2014).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Gareau et al., 2011
In the citing paper
“BDNF expression as measured by immunohistochemistry was decreased in the CA1 hippocampal brain area in GF stressed mice compared to stressed controls (Gareau et al., 2011).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Gareau et al., 2011
In the citing paper
“An increasing body of preclinical and human evidence demonstrates that the MGB axis plays important roles in the development and maintenance of various components of cognition (191, 362, 375).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [362]
In the citing paper
“The introduction of pathogenic bacteria reduced cognitive abilities and heightened anxiety-like behaviors (362, 363).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [362]
In the citing paper
“This deficit was prevented by daily administration of a Lactobacillus sp. probiotic combination before infection.”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [362]
In the citing paper
“Gareau et al. demonstrated impaired short-term recognition and working memory in 5 to 6-week-old germ-free mice when compared to conventionally reared counterparts (362).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [362]
In the citing paper
“Studies in germ-free mice have shown that, in the absence of microbes, the brain is markedly affected, exhibiting deficits in learning, memory formation and recognition, and social and emotional behaviors (58, 123, 124, 362).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [362]
In the citing paper
“Germ-free mice present with social cognitive deficits, which may be associated with biochemical changes, such as decreased hippocampal BDNF and c-FOS expression, important in memory (124, 362, 376, 377).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [362]
In the citing paper
“Administration of C. rodentium, combined with acute stress, led to memory dysfunction in young adult germ-free mice (362).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [362]
In the citing paper
“For example, Gareau et al. demonstrated a lack of memory in germ-free mice in the T-maze test and novel object test in situations with or without stress (362).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [362]
In the citing paper
“These studies show that rodents lacking all gut bacteria from birth (germ-free animals) have memory deficits28 and behavioral abnormalities29, 30 when compared to animals with normal gut microbiota.”
From The relation between cesarean birth and child cognitive development (2017) · cites this paper as [28]
In the citing paper
“Interestingly, these cognitive deficits in rodents can be corrected through the colonization of the intestine via a fecal transplant from the control group, but only if it occurs early in life.”
From The relation between cesarean birth and child cognitive development (2017) · cites this paper as [28]
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“ROLE OF THE INTESTINAL MICROBIOTA IN LEARNING AND MEMORY In this issue of Gut, Gareau et al (see page 307) extend the possible interactions between the intestinal microbiota and the CNS by investigating the effect of Citrobacter rodentium infection on learning and memory.(11) Previous studies have shown that C rodenti…”
InfluentialThe Microbiota–Gut–Brain Axis and Neurological Disorders: A Comprehensive Review
Nakhal, M. M., Yassin, L. K., Alyaqoubi, R., Saeed, S., Alderei, A., Alhammadi, A., Alshehhi, M., Almehairbi, A., Houqani, S. A., BaniYas, S., et al. (2024) · Life · doi:10.3390/life14101234 · Cited by 136
The Influence of Nutrition on Intestinal Permeability and the Microbiome in Health and Disease
Inczefi, O., Bacsúr, P., Resál, T., Keresztes, C., & Molnár, T. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.718710 · Cited by 90
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“GTM dysbiosis is often associated with metabolic [11,12], autoimmune [13] and neurological disorders [10,14] and can also increase the risk of pathogen invasion [7,8].”
BackgroundAccelerated Amyloid Beta Pathogenesis by Bacterial Amyloid FapC
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The gut microbiome and Alzheimer’s disease: Complex and bidirectional interactions
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“rhamnosus and Lactobacillus helveticus strains) prevents both the increase in intestinal permeability(87) and the memory dysfunction.(90) Up to 65% of patients suffering from myocardial infarction experience depressive symptoms and 20% of them develop major depression.”
BackgroundRodrigues, D. M., Sousa, A. J., Johnson‐Henry, K. C., Sherman, P. M., & Gareau, M. G. (2012) · The Journal of Infectious Diseases · doi:10.1093/infdis/jis177 · Cited by 83
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Damiani, F., Cornuti, S., & Tognini, P. (2023) · Neuropharmacology · doi:10.1016/j.neuropharm.2023.109491 · Cited by 95
“Also, GF animals exhibited altered spatial working memory and reference memory (Gareau et al., 2011),”
Su, A., Yang, W., Zhao, L., Pei, F., Yuan, B., Zhong, L., Ma, G., & Hu, Q. (2018) · Food & Function · doi:10.1039/c7fo01991b · Cited by 80
Hu, L., Zhu, S., Peng, X., Li, K., Peng, W., Zhong, Y., Kang, C., Cao, X., Liu, Z., & Zhao, B. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-200035 · Cited by 80
“Coin-cidentally, studies using animal models have shown that probiotics, such as Lactobacillus and Bifidobac-teria , restore the memory impairments induced by stress [34, 35].”
Wu, M., Yang, X., Li, X., Duan, W., & Du, J. (2021) · Behavioural Brain Research · doi:10.1016/j.bbr.2021.113125 · Cited by 86
The microbiome-gut-brain axis: implications for schizophrenia and antipsychotic induced weight gain
Kanji, S., Fonseka, T. M., Marshe, V. S., Sriretnakumar, V., Hahn, M. K., & Müller, D. J. (2018) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-017-0820-z · Cited by 79
“Further studies examining this axis have found use of probiotics to mitigate the behaviors associated with stress [21] and attenuate corticosterone levels due to stress [22].”
BackgroundGut-brain axis: A matter of concern in neuropsychiatric disorders…!
Naveed, M., Zhou, Q.-G., Chu, X., Taleb, A., Meng, F. J., Ahmed, B., Zhang, Y., Fukunaga, K., & Han, F. (2020) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2020.110051 · Cited by 82
Foster, L., Tompkins, T. A., & Dahl, W. J. (2011) · Beneficial Microbes · doi:10.3920/bm2011.0032 · Cited by 77
Absence of gut microbiota influences lipopolysaccharide-induced behavioral changes in mice
Campos, A. C., Rocha, N. P., Nicoli, J. R., Vieira, L. Q., Teixeira, M. M., & Teixeira, A. L. (2016) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.06.027 · Cited by 78
“Memory deficits were associated with decrease in hippocampus brain-derived neurotrophic factor (BDNF) and c-Fos (Gareau et al, 2011).”
Chen, J., He, S., Fang, L., Wang, B., Bai, S., Xie, J., Zhou, C., Wang, W., & Xie, P. (2020) · Aging · doi:10.18632/aging.102775 · Cited by 82
“Many previous studies focused on the effects of gut microbiota on brain functions [21, 22].”
BackgroundLiu, P., Gao, M., Liu, Z., Zhang, Y., Tu, H., Lei, L., Wu, P., Zhang, A., Yang, C., Li, G., et al. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.800764 · Cited by 79
Role of Brain-Gut-Microbiota Axis in Depression: Emerging Therapeutic Avenues
Bhatt, S., Kanoujia, J., Lakshmi, S. M., Patil, C., Gupta, G., Chellappan, D. K., & Dua, K. (2022) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527321666220329140804 · Cited by 83
Sun, N., Hu, H., Wang, F., Li, L., Zhu, W., Shen, Y., Xiu, J., & Xu, Q. (2021) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2020.11.032 · Cited by 75
Matisz, C. E., & Gruber, A. J. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.12.020 · Cited by 71
The new link between gut–brain axis and neuropsychiatric disorders
Fetissov, S. O., & Déchelotte, P. (2011) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0b013e32834936e7 · Cited by 78
Ceylani, T., Jakubowska-Doğru, E., Gurbanov, R., Teker, H. T., & Gozen, A. G. (2018) · Heliyon · doi:10.1016/j.heliyon.2018.e00644 · Cited by 77
“Hyperreactivity to stress followed by stress-induced memory impairment was also reported after enteric infections in animal models [11, 12].”
Microbiota and Neurodevelopmental Trajectories: Role of Maternal and Early-Life Nutrition
Codagnone, M. G., Stanton, C., O’Mahony, S. M., Dinan, T. G., & Cryan, J. F. (2019) · Annals of Nutrition and Metabolism · doi:10.1159/000499144 · Cited by 74
Jones, J. D., Rahmani, E., Garcia, E., & Jacobs, J. P. (2020) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2020.01.009 · Cited by 79
“Additionally, mice infected with an enteric pathogen then exposed to acute stress developed memory dysfunction [17].”
BackgroundSlyepchenko, A., Carvalho, A. F., Cha, D. S., Kasper, S. F., & McIntyre, R. S. (2015) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527313666141130205242 · Cited by 73
Salmonella Typhimurium and Multidirectional Communication in the Gut
Gart, E. V., Suchodolski, J. S., Welsh, T. H., Alaniz, R. C., Randel, R. D., & Lawhon, S. D. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.01827 · Cited by 73
“Thus, neuroendocrine-immune intercommunication of the gut–brain axis is important in both the healthy and disease state of animals and humans.”
BackgroundHu, H., Zhang, S., Liu, F., Zhang, P., Muhammad, Z., & Pan, S. (2019) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.9b03731 · Cited by 71
Mohammadi, G., Dargahi, L., Peymani, A., Mirzanejad, Y., Alizadeh, S. A., Naserpour, T., & Nassiri‐Asl, M. (2018) · Journal of the American College of Nutrition · doi:10.1080/07315724.2018.1487346 · Cited by 76
“helveticus R0052 in both stress-exposed and Western diet-fed mice (44,45).”
BackgroundKuijer, E. J., & Steenbergen, L. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105296 · Cited by 76
“hippocampus, and disrupts non-spatial hippocampal-dependent memory, all of which could be rescued by probiotics (Gareau et al., 2011).”
The Gut-Heart Axis: Updated Review for The Roles of Microbiome in Cardiovascular Health
Bui, T. V. A., Hwangbo, H., Lai, Y., Hong, S. B., Choi, Y.-J., Park, H., & Ban, K. (2023) · Korean Circulation Journal · doi:10.4070/kcj.2023.0048 · Cited by 70
Nod-like receptors are critical for gut-brain axis signalling in mice
Pusceddu, M. M., Barboza, M., Keogh, C. E., Schneider, M., Stokes, P., Sladek, J. A., Kim, H. J. D., Torres‐Fuentes, C., Goldfild, L. R., Gillis, S. E., et al. (2019) · The Journal of Physiology · doi:10.1113/jp278640 · Cited by 69
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Microbiome and Cognitive Impairment: Can Any Diets Influence Learning Processes in a Positive Way?
Novotný, M., Klímová, B., & Vališ, M. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00170 · Cited by 68
“Interestingly, in control mice, this dysfunction was prevented by the prophylactic administration of probiotics prior to the infection itself (Gareau et al., 2011; Liang et al., 2015).”
BackgroundLei, W., Cheng, Y., Liu, X., Gao, J., Zhu, Z., Ding, W., Xu, X., Li, Y., Ling, Z., Jiang, R., et al. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1582119 · Cited by 68
“Additionally, probiotics can modulate the hypothalamic-pituitary-adrenal (HPA) axis and restore neuronal activation under stress, as seen in increased c-Fos and BDNF expression in the hippocampus (148).”
Zeraati, M., Enayati, M., Kafami, L., Shahidi, S. H., & Salari, A. (2019) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.107685 · Cited by 65
Ketogenic Diet: An Effective Treatment Approach for Neurodegenerative Diseases
Zhang, H., Tao, Y., & Leng, S. X. (2022) · Current Neuropharmacology · doi:10.2174/1570159x20666220830102628 · Cited by 80
Marques, T. M., Cryan, J. F., Shanahan, F., Fitzgerald, G. F., Ross, R. P., Dinan, T. G., & Stanton, C. (2013) · Innovative Food Science & Emerging Technologies · doi:10.1016/j.ifset.2013.10.016 · Cited by 68
Bonfrate, L., Tack, J. F., Grattagliano, I., Cuomo, R., & Portincasa, P. (2013) · Scandinavian Journal of Gastroenterology · doi:10.3109/00365521.2013.799220 · Cited by 69
“[62] Gareau MG, Wine E, Rodrigues DM, Cho JH, Whary MT, Philpott DJ, et al.”
BackgroundNeuromicrobiology: How Microbes Influence the Brain
de la Fuente‐Núñez, C., Meneguetti, B. T., Franco, O. L., & Lu, T. K. (2017) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.7b00373 · Cited by 75
Gut microbiota in dementia. Critical review of novel findings and their potential application
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Lv, T., Ye, M., Luo, F., Hu, B., Wang, A., Chen, J., Yan, J., He, Z., Chen, F., Qian, C., et al. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.10.027 · Cited by 67
Salami, M. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.613120 · Cited by 67
Inflammation Theories in Psychotic Disorders: A Critical Review
Suvisaari, J., & Mantere, O. (2013) · Infectious Disorders - Drug Targets · doi:10.2174/18715265112129990032 · Cited by 68
“Furthermore, some enteric pathogens may cause memory impairment [78].”
BackgroundThe Impact of Microbiota-Gut-Brain Axis on Diabetic Cognition Impairment
Xu, Y., Zhou, H., & Zhu, Q. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00106 · Cited by 67
“Another research conducted in animals also observed that germ-free can impair memory function (Gareau et al., 2011).”
BackgroundNikolova, V. L., Zaidi, S. Y., Young, A. H., Cleare, A. J., & Stone, J. M. (2019) · Therapeutic Advances in Psychopharmacology · doi:10.1177/2045125319859963 · Cited by 66
“groups differ only according to treatment allocation, but no other factors that may influence outcome); (7) use of standardized measures, (8) use of intention-to-treat (ITT) analysis; and (9) differences between study sites.”
Disrupted Neurogenesis in Germ-Free Mice: Effects of Age and Sex
Scott, G. A., Terstege, D. J., Vu, A. P., Law, S., Evans, A., & Epp, J. R. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00407 · Cited by 61
“Previous research in rodents has shown that, generally, learning and memory is impaired following disruption of the gut microbiome (Gareau et al., 2011; Wang et al., 2015; Fröhlich et al., 2016; Möhle et al., 2016).”
BackgroundNagu, P., Parashar, A., Behl, T., & Mehta, V. (2021) · Journal of Molecular Neuroscience · doi:10.1007/s12031-021-01829-3 · Cited by 68
“anxiolytic effects and increasing motor activity (Gareau et al. 2011; Diaz Heijtz et al. 2011).”
Ohnmacht, C., Marques, R., Presley, L. L., Sawa, S., Lochner, M., & Eberl, G. (2011) · Cellular Microbiology · doi:10.1111/j.1462-5822.2011.01577.x · Cited by 67
“, 2009), and altering behaviour (Gareau et al., 2011; Neufeld et al., 2011).”
BackgroundMicrobiome to Brain: Unravelling the Multidirectional Axes of Communication
Aidy, S. E., Stilling, R. M., Dinan, T. G., & Cryan, J. F. (2016) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-20215-0_15 · Cited by 65
“…an altered expression of genes involved in neuropeptide production, N -methyl- D -aspartate (NMDA) receptor sub-units (Neufeld et al. 2011 ) and genes involved in brain development and behaviour including altered expression of BDNF in the hippocampus (Diaz Heijtz et al. 2011 ; Gareau et al. 2011 ).”
Background
Metadata
- Authors
- Gareau, M. G., Wine, E., Rodrigues, D. M., Cho, J. H., Whary, M. T., Philpott, D. J., MacQueen, G., & Sherman, P. M.
- Affiliations
- Hospital for Sick Children (CA)
- University of Alberta (CA)
- University of Toronto (CA)
- Massachusetts Institute of Technology (US)
- University of Calgary (CA)
- Corresponding author
- Sherman, Philip M
- ORCID
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2010-10-21
- Volume
- 60
- Issue
- 3
- Pages
- 307-317
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- OpenAlex
- W2170856053
- Cited by
- 909
- References
- 71
- Citations by year
- 2026: 19 · 2025: 53 · 2024: 72 · 2023: 60 · 2022: 94 · 2021: 91 · 2020: 113 · 2019: 79 · 2018: 73 · 2017: 62 · 2016: 60 · 2015: 36 · 2014: 41 · 2013: 22 · 2012: 17
- FWCI
- 7.17
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- cc-by-nc
- Locations
- Gut (publishedVersion)
- PubMed (publishedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Keywords
- enteric bacterial infection, Citrobacter rodentium, gut microbiota, germ-free mice, non-spatial memory, anxiety, water avoidance stress, probiotics, gut-brain axis, acute stress
- MeSH terms
- Animals, Anxiety, Behavior, Animal, Colon, Corticosterone, Enterobacteriaceae Infections, Feces, Female, Germ-Free Life, Hippocampus, Hyperplasia, Memory Disorders, Mice, Inbred C57BL, Stress, Psychological, Cytokines, Proto-Oncogene Proteins c-fos, Inflammation Mediators, Brain-Derived Neurotrophic Factor, Probiotics, Citrobacter rodentium, Mice
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