Ingestion of Lactobacillus strain reduces anxiety and improves cognitive function in the hyperammonemia rat
Open accessAbstract
Evidence suggests that the hyperammonemia (HA)-induced neuroinflammation and alterations in the serotonin (5-HT) system may contribute to cognitive decline and anxiety disorder during hepatic encephalopathy (HE). Probiotics that maintain immune system homeostasis and regulate the 5-HT system may be potential treatment for HA-mediated neurological disorders in HE. In this study, we tested the efficacy of probiotic Lactobacillus helveticus strain NS8 in preventing cognitive decline and anxiety-like behavior in HA rats. Chronic HA was induced by intraperitoneal injection of ammonium acetate for four weeks in male Sprague-Dawley rats. HA rats were then given Lactobacillus helveticus strain NS8 (10(9) CFU mL(-1)) in drinking water as a daily supplementation. The Morris water maze task assessed cognitive function, and the elevated plus maze test evaluated anxiety-like behavior. Neuroinflammation was assessed by measuring the inflammatory markers: inducible nitric oxide synthase, prostaglandin E2, and interleukin-1 β in the brain. 5-HT system activity was evaluated by measuring 5-HT and its metabolite, 5-HIAA, and the 5-HT precursor, tryptophan. Probiotic treatment of HA rats significantly reduced the level of inflammatory markers, decreased 5-HT metabolism, restored cognitive function and improved anxiety-like behavior. These results indicate that probiotic L. helveticus strain NS8 is beneficial for the treatment of cognitive decline and anxiety-like behavior in HA rats.
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Lactobacillus strains restore spatial memory impairments induced by diet in immunodeficient mice, age, hyperammonemia, and gut microbiota depletion after chronic antibiotic treatment.
“These strains also proved effective in restoring spatial memory impairments induced by diet in immunodeficient mice (Ohland et al., 2013), age (Jeong et al., 2015), hyperammonemia (Luo et al., 2014), and by gut microbiota depletion after chronic antibiotic treatment (Wang et al., 2015).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Luo et al., 2014
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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
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 · see citing works
Ohland, C. L., Kish, L., Bell, H., Thiesen, A., Hotte, N., Pankiv, E., & Madsen, K. L. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.02.008 · Cited by 273 · see citing works
Anti-inflammatory effects of bifidobacteria by inhibition of LPS-induced NF-κB activation
Riedel, C. U. (2006) · World Journal of Gastroenterology · doi:10.3748/wjg.v12.i23.3729 · Cited by 210 · see citing works
Flagged first, then by citations
Research works printed but not linked: 44
- Rodrigo R, Cauli O, Gomez-Pinedo U, Agusti A, Hernandez-Rabaza V, Garcia-Verdugo JM, Felipo V. Hyperammonemia induces neuro- inflammation that contributes to cognitive impairment in rats with hepatic encephalopathy. Gastroenterology, 2010, 139: 675-684
- Saul WSWB. Hyperammonemic encephalopathy. Medicine (Abing- don), 2002, 81: 240-249
- Felipo V, Butterworth RF. Neurobiology of ammonia. Prog Neurobiol, 2002, 67: 259-279
- Lajtha A, Reith MEA, eds. Handbook of Neurochemistry and Molecular Neurobiology. 3rd ed. New York: Springer, 2008
- Basile AS, Jones EA. Ammonia and GABA-ergic neurotransmission: Interrelated factors in the pathogenesis of hepatic encephalopathy. Hepatology, 1997, 25: 1303-1305
- Montoliu C, Piedrafita B, Serra MA, del Olmo JA, Urios A, Rodrigo JM, Felipo V. IL-6 and IL-18 in blood may discriminate cirrhotic patients with and without minimal hepatic encephalopathy. J Clin Gastroenterol, 2009, 43: 272-279
- Gibertini M, Newton C, Friedman H, Klein TW. Spatial learning impairment in mice infected with legionella pneumophila or administered exogenous interleukin-1β. Brain Behav Immun, 1995, 9: 113-128
- Wiltfang J, Nolte W, Weißenborn K, Komhuber J, Rüther E. Psychiatric aspects of portal-systemic encephalopathy. Metab Brain Dis, 1998, 13: 379-389
- Erecinska M, Pastuszko A, Wilson DF, Nelson D. Ammonia-induced release of neurotransmitters from rat brain synaptosomes: differences between the effects on amines and amino acids. J Neurochem, 1987, 49: 1258-1265 10
- Rössle M, Luft M, Herz R, Klein B, Lehmann M, Gerok W. Amino acid, ammonia and neurotransmitter concentrations in hepatic encephalopathy: serial analysis in plasma and cerebrospinal fluid during treatment with an adapted amino acid solution. Klin Wochenschr, 1984, 62: 867-875
- Bergqvist PBF, Hjorth S, Audet RM, Apelqvist G, Bengtsson F, Butterworth RF. Ammonium acetate challenge in experimental chronic hepatic encephalopathy induces a transient increase of brain 5-HT release in vivo. Eur Neuropsychopharm, 1996, 6: 317-322
- Miura H, Ozaki N, Sawada M, Isobe K, Ohta T, Nagatsu T. A link between stress and depression: shifts in the balance between the kynurenine and serotonin pathways of tryptophan metabolism and the etiology and pathophysiology of depression. Stress, 2008, 11: 198-209
- Vignau J, Costisella O, Canva V, Imbenotte M, Duhamel A, Lhermitte M. Impact of interferon alpha immunotherapy on tryptophan metabolism in patients with chronic hepatitis C. Results of a pilot studies on ten patients. Encephale, 2009, 35: 477-483
- Laugeray A, Launay JM, Callebert J, Surget A, Belzung C, Barone PR. Peripheral and cerebral metabolic abnormalities of the trypto- phan-kynurenine pathway in a murine model of major depression. Behav Brain Res, 2010, 210: 84-91 16
- Butterworth RF, Norenberg MD, Felipo V, Ferenci P, Albrecht J, Blei AT, Members of the ICoEMoHE. Experimental models of hepatic encephalopathy: ISHEN guidelines. Liver Int, 2009, 29: 783-788
- Lena PJ, Subramanian P. Effects of melatonin on the levels of antioxidants and lipid peroxidation products in rats treated with ammonium acetate. Pharmazie, 2004, 59: 636-639
- Moroni F, Lombardi G, Moneti G, Cortesini C. The release and neosynthesis of glutamic acid are increased in experimental models of hepatic encephalopathy. J Neurochem, 1983, 40: 850-854
- Subash S, Subramanian P. Morin a flavonoid exerts antioxidant potential in chronic hyperammonemic rats: a biochemical and histopathological study. Mol Cell Biochem, 2009, 327: 153-161
- Bajaj JS, Sanyal AJ, Bell D, Gilles H, Heuman DM. Predictors of the recurrence of hepatic encephalopathy in lactulose-treated patients. Aliment Pharm Therap, 2010, 31: 1012-1017
- Flamm SL. Rifaximin treatment for reduction of risk of overt hepatic encephalopathy recurrence. Therap Adv Gastroenterol, 2011, 4: 199-206
- Nicaise C, Prozzi D, Viaene E, Moreno C, Gustot T, Quertinmont E, Demetter P, Suain V, Goffin P, Devière J, Hols P. Control of acute, chronic, and constitutive hyperammonemia by wild-type and genetically engineered Lactobacillus plantarum in rodents. Hepato- logy, 2008, 48: 1184-1192
- Steidler L, Hans W, Schotte L, Neirynck S, Obermeier F, Falk W, Fiers W, Remaut E. Treatment of murine colitis by Lactococcus lactis secreting interleukin-10. Science, 2000, 289: 1352-1355
- Desbonnet L, Garrett L, Clarke G, Bienenstock J, Dinan TG. The probiotic Bifidobacteria infantis: an assessment of potential antidepressant properties in the rat. J Psychiat Res, 2008, 43: 164-174 26
- Benton D, Williams C, Brown A. Impact of consuming a milk drink containing a probiotic on mood and cognition. Eur J Clin Nutr, 2007, 61: 355-361
- Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, Dinan TG, Bienenstock J, Cryan JF. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci USA, 2011, 108: 16050-16055
- Joo HM, Kim KA, Myoung KS, Ahn YT, Lee JH, Huh CS, Han MJ, Kim DH. Lactobacillus helveticus HY7801 ameliorates vulvovaginal candidiasis in mice by inhibiting fungal growth and NF-κB activation. Int Immunopharmacol, 2012, 14: 39-46 31
- Gokcimen A, Kocak A, Gulle K, Sutcu R, Elmas O, Caliskan S, Ozguner F. The effects of allopurinol on rat liver and spleen tissues in a chronic hyperammonemia animal model. Saudi Med J, 2007, 28: 1648-1653
- Sgouras D, Maragkoudakis P, Petraki K, Martinez-Gonzalez B, Eriotou E, Michopoulos S, Kalantzopoulos G, Tsakalidou E, Mentis A. In vitro and in vivo inhibition of helicobacter pylori by lactobacillus casei strain shirota. Appl Environ Microb, 2004, 70: 518-526
- Walf AA, Frye CA. The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nat Protocols, 2007, 2: 322-328
- Wolfer DP, Stagljar-Bozicevic M, Errington ML, Lipp HP. Spatial memory and learning in transgenic mice: fact or artifact? Physiology, 1998, 13: 118-123
- Monfort P, Cauli O, Montoliu C, Rodrigo R, Llansola M, Piedrafita B, el Mlili N, Boix J, Agustí A, Felipo V. Mechanisms of cognitive alterations in hyperammonemia and hepatic encephalopathy: therapeutical implications. Neurochem Int, 2009, 55: 106-112
- Cauli O, Rodrigo R, Piedrafita B, Boix J, Felipo V. Inflammation and hepatic encephalopathy: Ibuprofen restores learning ability in rats with portacaval shunts. Hepatology, 2007, 46: 514-519
- Khasnavis S, Jana A, Roy A, Wood T, Ghosh S, Watson R, Pahan K. Suppression of nuclear factor-B activation and inflammation in microglia by a physically-modified saline. J Biol Chem, 2012, 287: 29529-29542
- Enck P, Klosterhalfen S, Martens U. Probiotic therapy for irritable bowel syndrome. Dtsch Med Wochenschr, 2011, 136: 371-375
- Laugeray A, Launay JM, Callebert J, Surget A, Belzung C, Barone PR. Evidence for a key role of the peripheral kynurenine pathway in the modulation of anxiety-and depression-like behaviours in mice: focus on individual differences. Pharmacol Biochem Be, 2011, 98: 161-168 43
- Iversen SD. 5-HT and anxiety. Neuropharmacology 1984, 23: 1553- 1560 44
- Jennings KA, Loder MK, Sheward WJ, Pei Q, Deacon RMJ, Benson MA, Olverman HJ, Hastie ND, Harmar AJ, Shen S, Sharp T. Increased expression of the 5-HT transporter confers a low-anxiety phenotype linked to decreased 5-HT transmission. J Neurosci, 2006, 26: 8955-8964
- O'Connor JC, André C, Wang Y, Lawson MA, Szegedi SS, Lestage J, Castanon N, Kelley KW, Dantzer R. Interferon-γ and tumor necrosis factor-α mediate the upregulation of indoleamine 2,3-dioxygenase and the induction of depressive-like behavior in mice in response to bacillus calmette-guérin. J Neurosci, 2009, 29: 4200-4209
- Däubener W, Schmidt SK, Heseler K, Spekker KH, MacKenzie CR. Antimicrobial and immunoregulatory effector mechanisms in human endothelial cells. Indoleamine 2,3-dioxygenase versus inducible nitric oxide synthase. Thromb Haemost, 2009, 102: 1110-1116
- Gurtner GJ, Newberry RD, Schloemann SR, McDonald KG, Stenson WF. Inhibition of indoleamine 2,3-dioxygenase augments trinitroben- zene sulfonic acid colitis in mice. Gastroenterology, 2003, 125: 1762-1773 49
- Forsythe P, Inman MD, Bienenstock J. Oral treatment with live Lactobacillus reuteri inhibits the allergic airway response in mice. Am J Respir Crit Care Med, 2007, 15: 561-569
- Valladares R, Bojilova L, Potts AH, Cameron E, Gardner C, Lorca G, Gonzalez CF. Lactobacillus johnsonii inhibits indoleamine 2,3- dioxygenase and alters tryptophan metabolite levels in BioBreeding rats. FASEB J, 2013, 27: 1711-1720
- Wu HQ, Pereira ER, Bruno J, Pellicciari R, Albuquerque E, Schwarcz R. The astrocyte-derived α7 nicotinic receptor antagonist kynurenic acid controls extracellular glutamate levels in the prefrontal cortex. J Mol Neurosci, 2010, 40: 204-210
- Cortese BM, Mitchell TR, Galloway MP, Prevost KE, Fang J, Moore GJ, Uhde TW. Region-specific alteration in brain glutamate: possible relationship to risk-taking behavior. Physiol Behav, 2010, 99: 445-450
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- Authors
- Luo, J., Wang, T., Liang, S., Hu, X., Li, W., & Jin, F.
- Affiliations
- Chinese Academy of Sciences (CN)
- Corresponding author
- Jin, Feng
- Venue
- Science China Life Sciences
- Published
- 2014-02-19
- Volume
- 57
- Issue
- 3
- Pages
- 327-335
- ISSN
- 1674-7305 (ISSN-L)
- 1869-1889
- OpenAlex
- W2063894277
- Cited by
- 187
- References
- 4
- Citations by year
- 2026: 11 · 2025: 12 · 2024: 12 · 2023: 12 · 2022: 29 · 2021: 19 · 2020: 29 · 2019: 13 · 2018: 22 · 2017: 9 · 2016: 11 · 2015: 7 · 2014: 1
- FWCI
- 13.37
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Science China Life Sciences (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- hyperammonemia, probiotics, hepatic encephalopathy, anxiety-like behavior, cognitive function, neuroinflammation, serotonergic system, 5-hydroxyindoleacetic acid, tryptophan, indoleamine 2,3-dioxygenase, IL-1β, prostaglandin E2, inducible nitric oxide synthase, cognitive decline
- MeSH terms
- Animals, Anxiety, Brain, Cognition Disorders, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Hepatic Encephalopathy, Humans, Hydroxyindoleacetic Acid, Lactobacillus, Male, Serotonin, Dinoprostone, Rats, Sprague-Dawley, Inflammation Mediators, Probiotics, Hyperammonemia, Rats, Nitric Oxide Synthase Type II, Interleukin-1beta
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