The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Anxiogenic effect of subclinical bacterial infection in mice in the absence of overt immune activation
Abstract
Challenge of animals with infectious microorganisms is well documented to affect a number of behavioral measures through activation of immune-neural mechanisms. In the present study, the ability of an infectious microorganism to directly alter behavioral responses in the absence of an overt immunologic response was examined. Eight-week-old CF-1 male mice were infected orally with the Gram-negative pathogen Campylobacter jejuni in order to establish a subclinical infection that did not result in immune activation. Microbiological examination of cecal contents revealed the presence of C. jejuni in all infected, but not control, animals 1 and 2 days post-oral challenge. Measurement of interleukin-6 (IL-6) levels and peripheral blood leukocyte populations did not reveal the activation of an overt immune response in 1 or 2 day infected animals as compared to controls. Infected mice demonstrated altered levels of anxiety-like behaviors on the elevated plus-maze as compared to controls on Day 2, but not Day 1, as reflected by a significant decrease in exploratory and an increase in nonexploratory behaviors. The anxiogenic effect of a subclinical infection in the absence of an overt immunologic response suggests that the direct activation of neural pathways by microorganisms may play a role in behavior.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Landmark studies in the 1990s were the first and demonstrate that bacteria respond to host neuroendocrine signaling molecules (Lyte andErnst, 1992, 1993), including norepinephrine and epinephrine, and that the microbiota can affect host behavior via the gut-brain axis (Lyte et al., 1998).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Lyte et al., 1998
In the citing paper
“Campylobacter jejuni administration had previously been shown to induce anxiety-related behavior without initiating a systemic immune response (Lyte et al., 1998).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Lyte et al., 1998
In the citing paper
“These findings were also echoed in animal studies where low-level infections altered behavior even in the absence of immune activation (Lyte et al., 1998).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Lyte et al., 1998
Citations
Cites
Maier, S. F., & Watkins, L. R. (1998) · Psychological Review · doi:10.1037/0033-295x.105.1.83 · Cited by 1,130
Research works printed but not linked: 36
- Archer, 1973, Tests for emotionality in rats and mice: A review, Anim. Behav., 21, 205, 10.1016/S0003-3472(73)80065-X · DOI · Paper page
- Bradfield, 1992, Behavioral and physiologic effects of inapparent wound infection in rats, Lab. Anim. Sci., 42, 572
- Buck, 1994, Interleukin-6: a sensitive parameter for the early diagnosis of neonatal bacterial infection, Pediatrics, 93, 54, 10.1542/peds.93.1.54 · DOI
- Butzler, 1991, Campylobacter: Pathogenicity and significance in foods, Int. J. Food Microbiol., 12, 1, 10.1016/0168-1605(91)90043-O · DOI
- Cao, 1997, Anxiolytic-like profile of p-MPPI, a novel 5HT1A receptor antagonist, in the murine elevated plus-maze, Psychopharmacology, 129, 365, 10.1007/s002130050202 · DOI
- Cruz, 1994, Ethopharmacological analysis of rat behavior on the elevated plus-maze, Pharmacol. Biochem. Behav., 49, 171, 10.1016/0091-3057(94)90472-3 · DOI
- Donovick, 1987, The consequences of parasitic infection for the behavior of the mammalian host, Environ. Health Perspect., 73, 247, 10.1289/ehp.8773247 · DOI
- Ebadi, 1997, Neurotrophins and their receptors in nerve injury and repair, Neurochem. Int., 30, 347, 10.1016/S0197-0186(96)00071-X · DOI
- Fernandez Espejo, 1997, Structure of the mouse behaviour on the elevated plus-maze test of anxiety, Behav. Brain Res., 86, 105, 10.1016/S0166-4328(96)02245-0 · DOI
- Fiore, 1996, Schistosoma mansoni: Influence of infection on mouse behavior, Exp. Parasitol., 83, 46, 10.1006/expr.1996.0047 · DOI
- Gibertini, 1995, Spatial learning impairment in mice infected with Legionalla pneumophila or administered exogenous interleukin-1-beta, Brain Behav. Immun., 9, 113, 10.1006/brbi.1995.1012 · DOI
- Hotchin, 1977, Virus-induced behavioral alteration of mice, Science, 196, 671, 10.1126/science.854742 · DOI
- Hsu, 1986, The bacterial flora of the intestine of Ascaris suum and 5-hydroxytryptamine production, J. Parasit., 72, 545, 10.2307/3281505 · DOI
- Kavaliers, 1995, Decreased predator avoidance in parasitized mice: Neuromodulatory correlates, Parasitology, 111, 257, 10.1017/S0031182000081816 · DOI
- Kavaliers, 1995, Reduced spatial learning in mice infected with the nematode, Heligmosomoides polygyrus, Parasitology, 110, 591, 10.1017/S0031182000065318 · DOI
- Kulkarni, 1991, Elevated plus-maze: A novel psychobehavioral tool to measure anxiety in rodents, Methods Find. Exp. Clin. Pharmacol., 13, 573
- Lapin, 1995, Only controls: Effect of handling, sham injection, and intraperitoneal injection of saline on behavior of mice in an elevated plus-maze, J. Pharmacol. Toxicol. Methods., 34, 73, 10.1016/1056-8719(95)00025-D · DOI
- Lenard, 1992, Mammalian hormones in microbial cells, Trends Biochem. Sci., 17, 147, 10.1016/0968-0004(92)90323-2 · DOI
- Lister, 1987, The use of a plus-maze to measure anxiety in the mouse, Psychopharmacology, 92, 180, 10.1007/BF00177912 · DOI
- Lister, 1990, Ethologically-based animal models of anxiety disorders, Pharmacol. Ther., 46, 321, 10.1016/0163-7258(90)90021-S · DOI
- Lyte, 1990, Examination of the neuroendocrine basis for the social conflict-induced enhancement of immunity in mice, Physiol. Behav., 48, 685, 10.1016/0031-9384(90)90212-M · DOI
- McCardell, 1986, A mouse model for the measurement of virulence of species of Campylobacter, J. Infect. Dis., 153, 177, 10.1093/infdis/153.1.177 · DOI
- Minuk, 1986, Gamma-aminobutyric acid (GABA) production by eight common bacterial pathogens, Scand. J. Infect. Dis., 18, 465, 10.3109/00365548609032366 · DOI
- Moon, 1997, Comparative histopathology of intestinal infections, Adv. Exp. Med. Biol., 412, 1, 10.1007/978-1-4899-1828-4_1 · DOI
- Rodgers, 1993, Anxiety enhancement in the murine elevated plus-maze by immediate prior exposure to social stressors, Physiol. Behav., 53, 383, 10.1016/0031-9384(93)90222-2 · DOI
- Rodgers, 1995, Factor analysis of spatiotemporal and ethological measures in the murine elevated plus-maze test of anxiety, Pharmacol. Biochem. Behav., 52, 297, 10.1016/0091-3057(95)00138-M · DOI
- Savage, 1986, Gastrointestinal microflora in mammalian nutrition, Ann. Rev. Nutr, 6, 155, 10.1146/annurev.nu.06.070186.001103 · DOI
- Schrott, 1996, Increased anxiety behaviors in autoimmune mice, Behav. Neurosci., 110, 492, 10.1037/0735-7044.110.3.492 · DOI
- Sullivan, 1992, Correlation of plasma cytokine elevations with mortality rate in children with sepsis, J. Pediatr., 120, 510, 10.1016/S0022-3476(05)82476-X · DOI
- Swiergiel, 1997, Influenza virus infection of mice induces anorexia: Comparison with endotoxin and interleukin-1 and the effects of indomethacin, Pharmacol. Biochem. Behav., 57, 389, 10.1016/S0091-3057(96)00335-8 · DOI
- Tabor, 1985, Polyamines in microorganisms, Microbiol. Rev., 49, 81, 10.1128/MR.49.1.81-99.1985 · DOI
- Watkins, 1994, Blockade of interleukin-1 induced hypothermia by subdiaphragmatic vagotomy: Evidence for vagal mediation of immune-brain communication, Neurosci. Lett., 183, 1
- Watkins, 1995, Cytokine-to-brain communication: A review and analysis of alternative mechanisms, Life Sci., 57, 1011, 10.1016/0024-3205(95)02047-M · DOI · Paper page
- Winder, 1988, gamma-aminobutyric acid (GABA) and sepsis-related encephalopathy, Can. J. Neurol. Sci., 15, 23, 10.1017/S0317167100027128 · DOI
- Yirmiya, 1997, Intracerebral administration of Mycoplasma fermentans produces sickness behavior: Role of prostaglandins, Brain Res., 749, 71, 10.1016/S0006-8993(96)01295-4 · DOI
- Yurdaydin, 1995, Gut bacteria provide precursors of benzodiazepine receptor ligands in a rat model of hepatic encephalopathy, Brain Res., 679, 42, 10.1016/0006-8993(95)00241-H · DOI
Cited by
Sorted by citations
Cryan, J. F., O'Riordan, K. J., Cowan, C. S. M., Sandhu, K. V., Bastiaanssen, T. F. S., Boehme, M., Codagnone, M. G., Cussotto, S., Fulling, C., Golubeva, A. V., et al. (2019) · Physiological Reviews · doi:10.1152/physrev.00018.2018 · Cited by 5,286
Gut–brain axis: How the microbiome influences anxiety and depression
Foster, J. A., & McVey Neufeld, K.-A. (2013) · Trends in Neurosciences · doi:10.1016/j.tins.2013.01.005 · Cited by 2,460
Altered fecal microbiota composition in patients with major depressive disorder
Jiang, H., Ling, Z., Zhang, Y., Mao, H., Ma, Z., Yin, Y., Wang, W., Tang, W., Tan, Z., Shi, J., et al. (2015) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2015.03.016 · Cited by 2,275
“Moreover, previous studies have demonstrated that the presence of these pathogenic bacteria in the gastrointestinal tract can induce behavioral and psychological changes in animals and humans (Goehler et al., 2008; Lowe et al., 2014; Lyte et al., 1998, 2006).”
BackgroundThe gut microbiota–brain axis in behaviour and brain disorders
Morais, L. H., Schreiber, H. L., & Mazmanian, S. K. (2021) · Nature Reviews Microbiology · doi:10.1038/s41579-020-00460-0 · Cited by 2,149
Serotonin, tryptophan metabolism and the brain-gut-microbiome axis
O’Mahony, S. M., Clarke, G., Borre, Y. E., Dinan, T. G., & Cryan, J. F. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.07.027 · Cited by 2,012
Bercik, P., Denou, E., Collins, J., Jackson, W., Lu, J., Jury, J., Deng, Y., Blennerhassett, P., Macri, J., McCoy, K. D., et al. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.04.052 · Cited by 1,748
Psychobiotics: A novel class of psychotropic
Dinan, T. G., Stanton, C., & Cryan, J. F. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.05.001 · Cited by 1,287
“(48) have shown that oral administration of the pathogen Campylobacter jejuni, in”
BackgroundStress & the gut-brain axis: Regulation by the microbiome
Foster, J. A., Rinaman, L., & Cryan, J. F. (2017) · Neurobiology of Stress · doi:10.1016/j.ynstr.2017.03.001 · Cited by 1,150
“For example, the pathogenic bacteria Campylobacter jejuni, when administered to mice at subclinical doses, results in anxietylike behaviour (Lyte et al., 1998).”
Bercik, P., Park, A. J., Sinclair, D., Khoshdel, A., Lu, J., Huang, X., Deng, Y., Blennerhassett, P. A., Fahnestock, M., Moine, D., et al. (2011) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2011.01796.x · Cited by 1,018
Intestinal microbiota in functional bowel disorders: a Rome foundation report
Simrén, M., Barbara, G., Flint, H. J., Spiegel, B. M. R., Spiller, R. C., Vanner, S., Verdu, E. F., Whorwell, P. J., & Zoetendal, E. G. (2013) · Gut · doi:10.1136/gutjnl-2012-302167 · Cited by 939
Bercik, P., Verdu, E. F., Foster, J. A., Macri, J., Potter, M., Huang, X., Malinowski, P., Jackson, W., Blennerhassett, P., Neufeld, K. A., et al. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.06.063 · Cited by 674
Luczynski, P., McVey Neufeld, K.-A., Oriach, C. S., Clarke, G., Dinan, T. G., & Cryan, J. F. (2016) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyw020 · Cited by 632
Rao, A. V., Bested, A. C., Beaulne, T. M., Katzman, M. A., Iorio, C., Berardi, J. M., & Logan, A. C. (2009) · Gut Pathogens · doi:10.1186/1757-4749-1-6 · Cited by 577
“Recently it was discovered that gut pathogens in the GI tract can communicate with the central nervous system and influence behavior associated with emotion, anxiety in particular, even at extremely low levels and in the absence of an immune response [7,8].”
BackgroundMessaoudi, M., Violle, N., Bisson, J.-F., Desor, D., Javelot, H., & Rougeot, C. (2011) · Gut Microbes · doi:10.4161/gmic.2.4.16108 · Cited by 574
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
Gut Bacteria and Neurotransmitters
Dicks, L. M. T. (2022) · Microorganisms · doi:10.3390/microorganisms10091838 · Cited by 482
“This led to studies that investigated the relationship between gut microbiota and depression [176].”
BackgroundBonfili, L., Cecarini, V., Berardi, S., Scarpona, S., Suchodolski, J. S., Nasuti, C., Fiorini, D., Boarelli, M. C., Rossi, G., & Eleuteri, A. M. (2017) · Scientific Reports · doi:10.1038/s41598-017-02587-2 · Cited by 453
Goehler, L. E., Gaykema, R. P. A., Opitz, N., Reddaway, R., Badr, N., & Lyte, M. (2005) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2004.09.002 · Cited by 442
Self-citationThe microbiome: stress, health and disease
Moloney, R. D., Desbonnet, L., Clarke, G., Dinan, T. G., & Cryan, J. F. (2014) · Mammalian Genome · doi:10.1007/s00335-013-9488-5 · Cited by 430
“For example, the pathogenic bacteria Campylobacter jejuni, when administered to mice at subclinical doses, resulted in anxiety-like behaviour in mice (Lyte et al. 1998).”
BackgroundMicrobes and the gut‐brain axis
Bercik, P., Collins, S. M., & Verdu, E. F. (2012) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2012.01906.x · Cited by 417
Lyte, M. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003726 · Cited by 399
“jejuni [5] as described above and subsequent reports identifying the neural substrates both within the brain and vagalmediated gut-to-brain pathway [6].”
BackgroundSelf-citationMicrobes and mental health: A review
Rieder, R., Wisniewski, P. J., Alderman, B. L., & Campbell, S. C. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2017.01.016 · Cited by 446
“Animal studies have demonstrated increased anxiety and stress-induced memory dysfunction related to alterations in the pathogenic bacteria T. muris, C. rodentium, and C. jejuni (Goehler et al., 2008; Lyte et al., 1998, 2006; Bercik et al., 2010).”
BackgroundRelationship between the gut microbiome and brain function
Mohajeri, M. H., La Fata, G., Steinert, R. E., & Weber, P. (2018) · Nutrition Reviews · doi:10.1093/nutrit/nuy009 · Cited by 376
“was shown to induce anxiety-like behavior without inducing immune activation in mice.(81) As noted, in vivo models”
Cytokine, sickness behavior, and depression
Dantzer, R. (2006) · Neurologic Clinics · doi:10.1016/j.ncl.2006.03.003 · Cited by 340
The gut-brain axis: the missing link in depression
Evrensel, A., & Ceylan, M. E. (2015) · Clinical Psychopharmacology and Neuroscience · doi:10.9758/cpn.2015.13.3.239 · Cited by 338
LYTE, M., LI, W., OPITZ, N., GAYKEMA, R., & GOEHLER, L. (2006) · Physiology & Behavior · doi:10.1016/j.physbeh.2006.06.019 · Cited by 334
Self-citationThe Impact of Microbiota on Brain and Behavior: Mechanisms & Therapeutic Potential
Borre, Y. E., Moloney, R. D., Clarke, G., Dinan, T. G., & Cryan, J. F. (2014) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4939-0897-4_17 · Cited by 329
Brain-Gut-Microbiota Axis and Mental Health
Dinan, T. G., & Cryan, J. F. (2017) · Psychosomatic Medicine · doi:10.1097/psy.0000000000000519 · Cited by 325
Irritable bowel syndrome: A microbiome-gut-brain axis disorder?
Kennedy, P. J. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i39.14105 · Cited by 347
Anisman, H., Merali, Z., & Hayley, S. P. (2008) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2008.01.004 · Cited by 341
“Although cytokines may elicit effects pertinent to mood/ anxiety disorders (Anisman and Merali, 1999; Dantzer, 2001a; Dantzer et al., 2000; Hayley et al., 2005, 2002a; Kent et al., 1992; Lyte et al., 1998; Maier and Watkins, 1998; Musselman et al., 2001; Reichenberg et al., 2001), and appear to involve CNS mechanisms…”
Zheng, H., Jin, Q.-W., Wang, X.-X., Qi, Y.-L., Liu, W.-D., Ren, Y.-L., Zhao, D., Chen, F., Cheng, J.-D., Chen, X.-Z., et al. (n.d.) · doi:10.1007/13238.1674-8018 · Cited by 304
Microbiota regulation of the mammalian gut-brain axis
Burokas, A., Moloney, R. D., Dinan, T. G., & Cryan, J. F. (2015) · Advances in applied microbiology · doi:10.1016/bs.aambs.2015.02.001 · Cited by 300
Goehler, L. E., Park, S. M., Opitz, N., Lyte, M., & Gaykema, R. P. A. (2008) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2007.08.009 · Cited by 287
“Introduction Oral administration of certain bacteria, including the common food-borne bacterial pathogen Campylobacter jejuni (C. jejuni) enhances anxiety-like behavior in mice (Lyte et al. 1998; Lyte et al. 2006).”
BackgroundSelf-citationStress at the intestinal surface: catecholamines and mucosa–bacteria interactions
Lyte, M., Vulchanova, L., & Brown, D. R. (2011) · Cell and Tissue Research · doi:10.1007/s00441-010-1050-0 · Cited by 281
“…doses that were employed) resulted in the display of anxiety-like behaviors and the activation of neurons within specific brain regions associated with such behavior in the absence of any detectable immune response to the orally administered C. jejuni (Goehler et al. 2005, 2008; Lyte et al. 1998).”
BackgroundSelf-citationMajor depressive disorder: probiotics may be an adjuvant therapy.
Logan, A., & Katzman, M. (2005) · Medical Hypotheses · doi:10.1016/j.mehy.2004.08.019 · Cited by 277
“Orally administered Campylobacter jejuni, in subclinical doses too low to elicit immune activation, can result in anxiety provoking effects in mice [38].”
BackgroundFeeding gut microbes to nourish the brain: unravelling the diet–microbiota–gut–brain axis
Schneider, E., O’Riordan, K. J., Clarke, G. A., & Cryan, J. F. (2024) · Nature Metabolism · doi:10.1038/s42255-024-01108-6 · Cited by 317
“Landmark studies from the 1990s laid the groundwork by revealing that bacteria respond to host neuroendocrine signalling molecules, including noradrenaline and adrenaline, challenging prior beliefs about the gut–brain axis 162,163 .”
Yarandi, S., Peterson, D. A., Treisman, G. J., Moran, T. H., & Pasricha, P. J. (2016) · Journal of Neurogastroenterology and Motility · doi:10.5056/jnm15146 · Cited by 308
Microbes, immunity, and behavior: psychoneuroimmunology meets the microbiome
Dinan, T. G., & Cryan, J. F. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.103 · Cited by 246
The role of the gut microbiota in dietary interventions for depression and anxiety
Bear, T. L. K., Dalziel, J. E., Coad, J., Roy, N. C., Butts, C. A., & Gopal, P. K. (2020) · Advances in Nutrition · doi:10.1093/advances/nmaa016 · Cited by 229
“Some studies have shown no evidence of inflammation alongside behavioral changes (88, 108) or only a partial effect (98, 109, 110); however, even subclinical gut infection without overt inflammation caused behavioral changes in mice (87).”
BackgroundMicrobiome disturbances and autism spectrum disorders
Rosenfeld, C. S. (2015) · Drug Metabolism and Disposition · doi:10.1124/dmd.115.063826 · Cited by 229
“Infection of mice with the pathogenic gut bacteria Campylobacter jejuni results in a rapid increase in anxiety-like behaviors (Lyte et al., 1998).”
BackgroundEffect of Intestinal Microbial Ecology on the Developing Brain
Douglas‐Escobar, M., Elliott, E. C., & Neu, J. (2013) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/jamapediatrics.2013.497 · Cited by 211
Gur, T. L., Shay, L., Palkar, A. V., Fisher, S., Varaljay, V. A., Dowd, S., & Bailey, M. T. (2017) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2016.12.021 · Cited by 213
“While it is becoming increasingly clear that stress can alter the microbiome [9, 11], and the microbiome has the capability to influence behavior [12-14], direct evidence for prenatal stress altering intrauterine microbes, inflammation, and neurodevelopment has been elusive.”
BackgroundSelf-citationMicrobial Endocrinology: The Microbiota-Gut-Brain Axis in Health and Disease
Lyte, M., & Cryan, J. F. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-1-4939-0897-4 · Cited by 240
Self-citationMicrobiota-gut-brain signalling in Parkinson's disease: Implications for non-motor symptoms
Felice, V. D., Quigley, E. M., Sullivan, A. M., O'Keeffe, G. W., & O'Mahony, S. M. (2016) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2016.03.012 · Cited by 205
Frémont, M., Coomans, D. H., Massart, S., & Meirleir, K. D. (2013) · Anaerobe · doi:10.1016/j.anaerobe.2013.06.002 · Cited by 208
The role of the microbiota-gut-brain axis in neuropsychiatric disorders
Generoso, J. S., Giridharan, V. V., Lee, J., Macêdo, D. S., & Barichello, T. (2020) · Brazilian Journal of Psychiatry · doi:10.1590/1516-4446-2020-0987 · Cited by 250
Microbial Endocrinology and the Microbiota-Gut-Brain Axis
Lyte, M. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-1-4939-0897-4_1 · Cited by 231
“jejuni in mice [58].”
Self-citationLasselin, J., Schedlowski, M., Karshikoff, B., Engler, H., Lekander, M., & Konsman, J. P. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.05.001 · Cited by 165
“The first indications in animals that anxiety may be caused by inflammatory stimuli were that sick rodents spent less time in the open arms of an elevated plus maze and in the illuminated part of a lightdark box as well as in exploring a novel object in an open field (Lacosta et al., 1999; Lyte et al., 1998).”
Microbiota influence the development of the brain and behaviors in C57BL/6J mice
Lu, J., Synowiec, S., Lu, L., Yu, Y., Bretherick, T., Takada, S., Yarnykh, V., Caplan, J., Caplan, M., Claud, E. C., et al. (2018) · PLoS ONE · doi:10.1371/journal.pone.0201829 · Cited by 159
The microbiota-gut-brain axis in functional gastrointestinal disorders
De Palma, G., Collins, S. M., & Bercik, P. (2014) · Gut Microbes · doi:10.4161/gmic.29417 · Cited by 157
Cytokines, PGE2 and endotoxic fever: a re-assessment
Blatteis, C. M., Li, S., Li, Z., Feleder, C., & Perlík, V. (2005) · Prostaglandins & Other Lipid Mediators · doi:10.1016/j.prostaglandins.2005.01.001 · Cited by 153
Brain response to cecal infection with Campylobacter jejuni: analysis with Fos immunohistochemistry
Gaykema, R. P. A., Goehler, L. E., & Lyte, M. (2003) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2003.08.002 · Cited by 147
Self-citationDiet, gut microbiota and cognition
Proctor, C., Thiennimitr, P., Chattipakorn, N., & Chattipakorn, S. C. (2017) · Metabolic Brain Disease · doi:10.1007/s11011-016-9917-8 · Cited by 144
“Asymptomatic mice which had no overt immune response, were infected with the enteropathogen, Campylobacter jejuni, and were found to be more anxious than non-infected control mice (Lyte et al. 1998).”
BackgroundThe effects of gut microbiota on CNS function in humans
Tillisch, K. (2014) · Gut Microbes · doi:10.4161/gmic.29232 · Cited by 144
Gut inflammation in chronic fatigue syndrome
Lakhan, S. E., & Kirchgessner, A. (2010) · Nutrition & Metabolism · doi:10.1186/1743-7075-7-79 · Cited by 143
“Gut pathogens can communicate with the CNS and influence emotional behaviors such as anxiety and depression, even at extremely low levels and in the absence of an immune response [19,20].”
Influence of the microbiota-gut-brain axis on behavior and welfare in farm animals: A review
Kraïmi, N., Dawkins, M. S., Gebhardt‐Henrich, S. G., Velge, P., Rychlı́k, I., Volf, J., Créach, P., Smith, A. L., Colles, F. M., & Leterrier, C. (2019) · Physiology & Behavior · doi:10.1016/j.physbeh.2019.112658 · Cited by 161
Human Gut Microbiota: Toward an Ecology of Disease
Selber‐Hnatiw, S., Rukundo, B., Ahmadi, M., Akoubi, H., Al-Bizri, H., Aliu, A. F., Ambeaghen, T. U., Avetisyan, L., Bahar, I., Baird, A., et al. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.01265 · Cited by 151
Impact of Microbial Metabolites on Microbiota–Gut–Brain Axis in Inflammatory Bowel Disease
Banfi, D., Moro, E., Bosi, A., Bistoletti, M., Cerantola, S., Crema, F., Maggi, F., Giron, M. C., Giaroni, C., & Baj, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041623 · Cited by 160
“jejuni) [145] and was associated with changes in c-Fos expression in NVG cell bodies and the NTS, suggesting the occurrence of rapid afferent signals after exposure to potential pathogens [146].”
BackgroundFoley, K. A., Ossenkopp, K., Kavaliers, M., & MacFabe, D. F. (2014) · PLoS ONE · doi:10.1371/journal.pone.0087072 · Cited by 135
“An increase in anxiety is consistent with previous reports of prenatal VPA and enteric infection producing anxiety-like behavior in male and female adult rat offspring [50], [60].”
ResultGoehler, L. E., Lyte, M., & Gaykema, R. P. A. (2007) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2007.02.005 · Cited by 127
“We first became involved with these issues when one of us (ML) observed that mice treated per-orally with live bacteria (Campylobacter jejuni) seemed more anxious than saline-treated control mice (Lyte et al., 1998).”
BackgroundSelf-citationGut microbes in neurocognitive and mental health disorders
Halverson, T., & Alagiakrishnan, K. (2020) · Annals of Medicine · doi:10.1080/07853890.2020.1808239 · Cited by 125
“Rodents exposed to a subclinical dose of Campylobacter jejuni, exhibited anxiety-like behaviours [113].”
BackgroundReis, D. J., Ilardi, S. S., & Punt, S. E. W. (2018) · PLOS ONE · doi:10.1371/journal.pone.0199041 · Cited by 123
Bested, A. C., Logan, A. C., & Selhub, E. M. (2013) · Gut Pathogens · doi:10.1186/1757-4749-5-3 · Cited by 121
“Campylobacter jejuni), at quantities too low to produce a detectable immune response, could influence animal behavior indicative of human anxiety [6].”
BackgroundI.31, a new combination of probiotics, improves irritable bowel syndrome-related quality of life
Lorenzo‐Zúñiga, V. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i26.8709 · Cited by 120
Age Drives Distortion of Brain Metabolic, Vascular and Cognitive Functions, and the Gut Microbiome
Hoffman, J. D., Parikh, I. J., Green, S. J., Chlipala, G. E., Mohney, R. P., Keaton, M., Bauer, B., Hartz, A. M. S., & Lin, A. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00298 · Cited by 124
“jejuni increased anxiety-like behavioral measure in the EPM 2 days after infection (Lyte et al., 1998).”
BackgroundRole of Microbiota-Derived Extracellular Vesicles in Gut-Brain Communication
Cuesta, C. M., Guerri, C., Ureña, J., & Pascual, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22084235 · Cited by 142
“Conversely, the administration of antibiotics is able to induce mental disorders in patients [28] and treatment with specific bacterial strains can cause alterations to behavior and the nervous system with no immune response activation [29].”
BackgroundThe Microbiome-Gut-Brain Axis and Resilience to Developing Anxiety or Depression under Stress
Bear, T., Dalziel, J. E., Coad, J., Roy, N. C., Butts, C. A., & Gopal, P. K. (2021) · Microorganisms · doi:10.3390/microorganisms9040723 · Cited by 136
“In mice, gut infections or inflammation caused an increase in patterns of behavior thought to represent anxiety, including decreased exploration [27] and increased behavioral inhibition [28,29].”
BackgroundFurther evidence for the depressive effects of cytokines: Anhedonia and neurochemical changes
Anisman, H., Kokkinidis, L., & Merali, Z. (2002) · Brain Behavior and Immunity · doi:10.1016/s0889-1591(02)00011-9 · Cited by 112
Chronic fatigue syndrome: lactic acid bacteria may be of therapeutic value.
Logan, A., Rao, A., & Irani, D. (2003) · Medical Hypotheses · doi:10.1016/s0306-9877(03)00096-3 · Cited by 99
“the absence of an immune response, can directly activate neural pathways (134).”
BackgroundThe microbial organ in the gut as a driver of homeostasis and disease
Lyte, M. (2009) · Medical Hypotheses · doi:10.1016/j.mehy.2009.10.025 · Cited by 105
“As discussed above, it has been shown that bacteria within the gut, whether a novel introduced species [39,42] or increased microbial species diversity [45], can profoundly influence aspects of host homeostasis such as behavior.”
BackgroundSelf-citationFeeding melancholic microbes: MyNewGut recommendations on diet and mood
Dinan, T. G., Stanton, C., Long-Smith, C., Kennedy, P., Cryan, J. F., Cowan, C. S. M., Cenit, M. C., van der Kamp, J.-W., & Sanz, Y. (2019) · Clinical Nutrition · doi:10.1016/j.clnu.2018.11.010 · Cited by 95
“The maternal separation model of IBS supports the view of an altered gut microbiota in the condition together with a pro-inflammatory phenotype [25].”
BackgroundPinn, D. M., Aroniadis, O. C., & Brandt, L. J. (2014) · Neurogastroenterology & Motility · doi:10.1111/nmo.12479 · Cited by 93
Szyszkowicz, J. K., Wong, A., Anisman, H., Merali, Z., & Audet, M. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2017.06.009 · Cited by 97
The Effects of Inflammation, Infection and Antibiotics on the Microbiota-Gut-Brain Axis
Berčík, P., & Collins, S. M. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-1-4939-0897-4_13 · Cited by 98
Gut microbiota regulates key modulators of social behavior
Parashar, A., & Udayabanu, M. (2016) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2015.11.002 · Cited by 88
Chronic Toxoplasma Infection Modifies the Structure and the Risk of Host Behavior
Afonso, C., Paixão, V., & Costa, R. (2012) · PLoS ONE · doi:10.1371/journal.pone.0032489 · Cited by 87
“This is consistent with previous studies showing that asymptomatic Campylobacter jejuni-infected animals display an increase in closed arm entries in the elevated plus maze [23].”
Necrotizing Enterocolitis, Gut Microbiota, and Brain Development: Role of the Brain-Gut Axis
Niemarkt, H., de Meij, T., van Ganzewinkel, C., de Boer, N. D., Andriessen, P., Hütten, M., & Kramer, B. (2019) · Neonatology · doi:10.1159/000497420 · Cited by 85
Cowan, C. S. M., Callaghan, B. L., & Richardson, R. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.94 · Cited by 83
Vagal Interoceptive Modulation of Motivated Behavior
Maniscalco, J. W., & Rinaman, L. (2018) · Physiology · doi:10.1152/physiol.00036.2017 · Cited by 83
“Consistent with this idea, gut bacterial infections that are subthreshold to increase systemic proinflammatory cytokines can still promote anxiety-like behavior in rodents (145), concurrent with activation of cFos expression by vagal afferent neurons, cNTS neurons, and neurons within the BST and CeA (96).”
BackgroundThe microbiome as a novel paradigm in studying stress and mental health.
Liu, R. T. (2017) · American Psychologist · doi:10.1037/amp0000058 · Cited by 96
“…Increased anxiety symptoms/behavior Campylobacter jejuni, Citrobacter rodentium, Trichuris muris, high-fat microbiota Bruce-Keller et al. (2015); Lyte, Varcoe, and Bailey (1998); and Stilling, Dinan, and Cryan (2014) Decreased anxiety symptoms/behavior Bifidobacterium spp., Lactobacillus spp.…”
BackgroundGao, F., Guo, R., Ma, Q., Li, Y., Wang, W., Fan, Y., Ju, Y., Zhao, B., Gao, Y., Li, Q., et al. (2022) · Journal of Affective Disorders · doi:10.1016/j.jad.2022.02.024 · Cited by 92
“Members of [Ruminococcus] gnavus group could degrade gastrointestinal mucins, which may lead to the breakdown of mucus and thereby increased permeability of the gut (Lyte et al., 1998).”
Stevens, A. J., Purcell, R. V., Darling, K. A., Eggleston, M. J. F., Kennedy, M. A., & Rucklidge, J. J. (2019) · Scientific Reports · doi:10.1038/s41598-019-46146-3 · Cited by 88
Holder, M. K., Peters, N. V., Whylings, J., Fields, C. T., Gewirtz, A. T., Chassaing, B., & Vries, G. J. D. (2019) · Scientific Reports · doi:10.1038/s41598-018-36890-3 · Cited by 93
Neuromicrobiology: 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
Lyte, M., Chapel, A., Lyte, J. M., Ai, Y., Proctor, A., Jane, J.-L., & Phillips, G. J. (2016) · PLoS ONE · doi:10.1371/journal.pone.0146406 · Cited by 62
“For example, oral introduction of a novel bacterial species, Campylobacter jejuni, into mice resulted in the development of anxiety-like behavior in the absence of any detectable immune response [5, 6].”
BackgroundSelf-citationThe microbiota-gut-brain axis: Focus on the fundamental communication pathways
Bistoletti, M., Bosi, A., Banfi, D., Giaroni, C., & Baj, A. (2020) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2020.08.012 · Cited by 91
The microbiome and childhood diseases: Focus on brain‐gut axis
O’Mahony, S. M., Stilling, R. M., Dinan, T. G., & Cryan, J. F. (2015) · Birth Defects Research Part C Embryo Today Reviews · doi:10.1002/bdrc.21118 · Cited by 53
What’s bugging your teen?—The microbiota and adolescent mental health
McVey Neufeld, K.-A., Luczynski, P., Seira Oriach, C., Dinan, T. G., & Cryan, J. F. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.06.005 · Cited by 56
“…subclinical doses of pathogenic bacterial strains like Campylobacter jejuni and Citrobacter rodentium have shown induction of anxiety-like behavior and learning deficits in the absence of overt inflammatory responses (Lyte et al., 1998; Lyte et al., 2006; Goehler et al., 2008; Gareau et al., 2011).”
Gut Bacteria and Neuropsychiatric Disorders
Dicks, L. M. T., Hurn, D., & Hermanus, D. (2021) · Microorganisms · doi:10.3390/microorganisms9122583 · Cited by 63
“This may occur without changes in immune response, as animal studies have shown changes in behavior with low levels of microbial infections had little effect on immune activation [90].”
ResultGlioma induced alterations in fecal short-chain fatty acids and neurotransmitters
Dono, A., Patrizz, A., McCormack, R., Putluri, N., Ganesh, B. P., Kaur, B., McCullough, L. D., Ballester, L. Y., & Esquenazi, Y. (2020) · CNS Oncology · doi:10.2217/cns-2020-0007 · Cited by 60
“, serotonin [5-hydroxytryptamine], GABA, norepinephrine, epinephrine) which are involved in various host functions such as mood, behavior and cognition [6,17].”
BackgroundThe contribution of age-related changes in the gut-brain axis to neurological disorders
Khan, R., Gesù, C. M. D., Lee, J., & McCullough, L. D. (2024) · Gut Microbes · doi:10.1080/19490976.2024.2302801 · Cited by 62
“31 The interactions between the vagus nerve, the gut epithelium and the ENS are summarized in Figure 2.”
BackgroundMoshkin, M., Gerlinskaya, L., Morozova, O., Bakhvalova, V., & Evsikov, V. (2002) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(01)00096-8 · Cited by 54
“Viral or microbial infection can modifies host behaviour through direct activation of neural pathways (Lyte et al., 1998) or through the immune–neural mechanisms (Zalcman et al.”
BackgroundKrämer, P., & Bressan, P. (2015) · Perspectives on Psychological Science · doi:10.1177/1745691615583131 · Cited by 68
The Neuroprotective Effect of Tea Polyphenols on the Regulation of Intestinal Flora
Zhang, Z., Zhang, Y., Li, J., Fu, C., & Zhang, X. (2021) · Molecules · doi:10.3390/molecules26123692 · Cited by 55
“Previous studies have indicated that subclinical oral Campylobacter jejuni can induce anxiety-related behaviors without triggering a systemic immune response [27].”
BackgroundThe Matter of History: How Things Create the Past
Lecain, T. (2017) · doi:10.1017/9781316460252 · Cited by 47
5-HT7 receptor signaling: improved therapeutic strategy in gut disorders
Kim, J., & Khan, W. I. (2014) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2014.00396 · Cited by 51
“Sanitá, Italy”
BackgroundParasites and behavior: an ethopharmacological analysis and biomedical implications
Kavaliers, M., Colwell, D. D., & Choleris, E. (1999) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(99)00035-4 · Cited by 46
Gesù, C. M. D., Matz, L. M., & Buffington, S. A. (2021) · Neuroscience Research · doi:10.1016/j.neures.2021.05.003 · Cited by 47
Kaushik, M., Lamberton, P. H. L., & Webster, J. P. (2012) · Hormones and Behavior · doi:10.1016/j.yhbeh.2012.04.002 · Cited by 49
Lyte, M. (2013) · PharmaNutrition · doi:10.1016/j.phanu.2012.11.002 · Cited by 40
Self-citation
Metadata
- Authors
- Lyte, M., Varcoe, J. J., & Bailey, M. T.
- Affiliations
- Minnesota State University, Mankato (US)
- Corresponding author
- Lyte, Mark
- Venue
- Physiology & Behavior
- Publisher
- Elsevier BV
- Published
- 1998-08
- Volume
- 65
- Issue
- 1
- Pages
- 63-68
- ISSN
- 0031-9384 (ISSN-L)
- OpenAlex
- W2012109410
- Cited by
- 218
- References
- 0
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 14 · 2023: 9 · 2022: 17 · 2021: 12 · 2020: 17 · 2019: 11 · 2018: 12 · 2017: 20 · 2016: 19 · 2015: 13 · 2014: 14 · 2013: 14 · 2012: 6
- FWCI
- 0.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Physiology & Behavior (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5k02mh001371-02)
- National Institute of Mental Health (MH-50431, MH01371, R01MH050431)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- Campylobacter jejuni, anxiety-like behavior, anxiogenic effects, neuroimmune interactions, interleukin-6, peripheral blood leukocytes, elevated plus maze, exploratory behavior, oral infection, Gram-negative bacteria
- MeSH terms
- Animals, Anxiety, Behavior, Animal, Campylobacter Infections, Leukocyte Count, Male, Interleukin-6, Campylobacter jejuni, Lymphocyte Count, Mice, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
