Emerging evidence indicates that the alterations in the gut microbiota-brain axis (GBA), which is the bilateral connection between the gut microbial communities and brain function, are involved in several mental illnesses, including depression. Certain probiotic strains have been revealed to improve depressive behaviours and the dysregulation of 5-hydroxytryptamine (5-HT) metabolism in depression. Here we evaluated the potential antidepressant effects of Lactobacillus helveticus strains using an in vitro enterochromaffin cell model (RIN14B). The L. helveticus strain WHH1889 was shown to significantly promote the level of 5-hydroxytryptamine (5-HTP, 5-HT precursor) and the gene expression of tryptophan hydroxylase 1 (Tph1), which is the key synthetase in the 5-HT biosynthesis in RIN14B cells. Ingestion of 0.2 ml WHH1889 (1´109 cfu/ml) in a chronic unpredictable mild stress (CUMS) mouse model of depression for five weeks normalised depressive and anxiety-like behaviours in the forced swim test, tail suspension test, sucrose preference test, and open field test. Meanwhile, the CUMS-induced elevated level of serum corticosterone and declined levels of hippocampal 5-HT and 5-HTP were reversed by WHH1889. Furthermore, the disturbances of the gut microbiome composition with reduced microbial diversity were also improved by WHH1889, accompanied by the increased colonic 5-HTP level and Tph1 gene expression. In summary, these findings indicate that WHH1889 exerts antidepressant-like effects on CUMS mice, which is associated with the modulations of the 5-HT/5-HTP metabolism and gut microbiome composition. Therefore, ingestion of the L. helveticus strain WHH1889 with antidepressant potentials may become an encouraging therapeutic option in the treatment of depression.
Purchase
Buy instant access (PDF download and unlimited online access):
Institutional Login
Log in with Open Athens, Shibboleth, or your institutional credentials
Personal login
Log in with your brill.com account
Aizawa, E., Tsuji, H., Asahara, T., Takahashi, T., Teraishi, T., Yoshida, S., Ota, M., Koga, N., Hattori, K. and Kunugi, H., 2016. Possible association of Bifidobacterium and Lactobacillus in the gut microbiota of patients with major depressive disorder. Journal of Affective Disorders 202: 254-257. https://doi.org/10.1016/j.jad.2016.05.038
Anagha, K., Shihabudheen, P. and Uvais, N.A., 2021. Side effect profiles of selective serotonin reuptake inhibitors: a cross-sectional study in a naturalistic setting. The Primary Care Companion for CNS Disorders 23: 35561. https://doi.org/10.4088/PCC.20m02747
Antoniuk, S., Bijata, M., Ponimaskin, E. and Wlodarczyk, J., 2019. Chronic unpredictable mild stress for modeling depression in rodents: meta-analysis of model reliability. Neuroscience and Biobehavioral Reviews 99: 101-116. https://doi/org/10.1016/j.neubiorev.2018.12.002
Benjamini, Y. and Hochberg, Y., 1995. Controlling the false discovery rate: a practical and powerful approach to multiple testing. Journal of the Royal Statistical Society Series B 57: 289-300. https://doi.org/10.1111/j.2517-6161.1995.tb02031.x
Bertollo, A.G., Grolli, R.E., Plissari, M.E., Gasparin, V.A., Quevedo, J., Reus, G.Z., Bagatini, M.D. and Ignacio, Z.M., 2020. Stress and serum cortisol levels in major depressive disorder: a cross-sectional study. AIMS Neuroscience 7: 459-469. https://doi.org/10.3934/Neuroscience.2020028
Capuco, A., Urits, I., Hasoon, J., Chun, R., Gerald, B., Wang, J.K., Kassem, H., Ngo, A.L., Abd-Elsayed, A., Simopoulos, T., Kaye, A.D. and Viswanath, O., 2020. Current perspectives on gut microbiome dysbiosis and depression. Advances in Therapy 37: 1328-1346. https://doi.org/10.1007/s12325-020-01272-7
Gao, K., Farzi, A., Ke, X., Yu, Y., Chen, C., Chen, S., Yu, T., Wang, H. and Li, Y., 2022. Oral administration of Lactococcus lactis WHH2078 alleviates depressive and anxiety symptoms in mice with induced chronic stress. Food and Function 13: 957-969. https://doi.org/10.1039/d1fo03723d
Gao, K., Mu, C.L., Farzi, A. and Zhu, W.Y., 2020. Tryptophan metabolism: a link between the gut microbiota and brain. Advances in Nutrition 11: 709-723. https://doi.org/10.1093/advances/nmz127
Gao, K., Pi, Y., Mu, C.L., Peng, Y., Huang, Z. and Zhu, W.Y., 2018a. Antibiotics-induced modulation of large intestinal microbiota altered aromatic amino acid profile and expression of neurotransmitters in the hypothalamus of piglets. Journal of Neurochemistry 146: 219-234. https://doi.org/10.1111/jnc.14333
Gao, K., Pi, Y., Peng, Y., Mu, C.L. and Zhu, W.Y., 2018b. Time-course responses of ileal and fecal microbiota and metabolite profiles to antibiotics in cannulated pigs. Applied Microbiology and Biotechnology 102: 2289-2299.https://doi.org/10.1007/s00253-018-8774-2
Giraffa, G., 2014. Lactobacillus helveticus: importance in food and health. Frontiers in Microbiology 5: 338. https://doi.org/10.3389/fmicb.2014.00338
Gu, F., Wu, Y., Liu, Y., Dou, M., Jiang, Y. and Liang, H., 2020. Lactobacillus casei improves depression-like behavior in chronic unpredictable mild stress-induced rats by the BDNF-TrkB signal pathway and the intestinal microbiota. Food and Function 11: 6148-6157. https://doi.org/10.1039/d0fo00373e
Ho, Y.T., Tsai, Y.C., Kuo, T.B.J. and Yang, C.C.H., 2021. Effects of Lactobacillus plantarum PS128 on depressive symptoms and sleep quality in self-reported insomniacs: a randomized, double-blind, placebo-controlled pilot trial. Nutrients 13: 2820. https://doi.org/10.3390/nu13082820
Huang, Y., Wang, Y., Wang, H., Liu, Z., Yu, X., Yan, J., Yu, Y., Kou, C., Xu, X., Lu, J., Wang, Z., He, S., Xu, Y., He, Y., Li, T., Guo, W., Tian, H., Xu, G., Xu, X., Ma, Y., Wang, L., Wang, L., Yan, Y., Wang, B., Xiao, S., Zhou, L., Li, L., Tan, L., Zhang, T., Ma, C., Li, Q., Ding, H., Geng, H., Jia, F., Shi, J., Wang, S., Zhang, N., Du, X., Du, X. and Wu, Y., 2019. Prevalence of mental disorders in China: a cross-sectional epidemiological study. The Lancet Psychiatry 6: 211-224. https://doi.org/10.1016/S2215-0366(18)30511-X
Jiang, H., Ling, Z., Zhang, Y., Mao, H., Ma, Z., Yin, Y., Wang, W., Tang, W., Tan, Z., Shi, J., Li, L. and Ruan, B., 2015. Altered fecal microbiota composition in patients with major depressive disorder. Brain, Behavior, and Immunity 48: 186-194. https://doi.org/10.1016/j.bbi.2015.03.016
Kawano, M., Miyoshi, M. and Miyazaki, T., 2019. Lactobacillus helveticus SBT2171 induces A20 expression via Toll-like receptor 2 signaling and inhibits the lipopolysaccharide-induced activation of nuclear factor-kappa B and mitogen-activated protein kinases in peritoneal macrophages. Frontiers in Immunology 10: 845. https://doi.org/10.3389/fimmu.2019.00845
Li, H., Wang, P., Huang, L., Li, P. and Zhang, D., 2019. Effects of regulating gut microbiota on the serotonin metabolism in the chronic unpredictable mild stress rat model. Neurogastroenterology and Motility 31: e13677. https://doi.org/10.1111/nmo.13677
Li, N., Liu, R.J., Dwyer, J.M., Banasr, M., Lee, B., Son, H., Li, X.Y., Aghajanian, G. and Duman, R.S., 2011. Glutamate N-methyl-D-aspartate receptor antagonists rapidly reverse behavioral and synaptic deficits caused by chronic stress exposure. Biological Psychiatry 69: 754-761. https://doi.org/10.1016/j.biopsych.2010.12.015
Liang, S., Wang, T., Hu, X., Luo, J., Li, W., Wu, X., Duan, Y. and Jin, F., 2015. Administration of Lactobacillus helveticus NS8 improves behavioral, cognitive, and biochemical aberrations caused by chronic restraint stress. Neuroscience 310: 561-577. https://doi.org/10.1016/j.neuroscience.2015.09.033
Livak, K.J. and Schmittgen, T.D., 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25: 402-408. https://doi.org/10.1006/meth.2001.1262
Maehata, H., Kobayashi, Y., Mitsuyama, E., Kawase, T., Kuhara, T., Xiao, J.Z., Tsukahara, T. and Toyoda, A., 2019. Heat-killed Lactobacillus helveticus strain MCC1848 confers resilience to anxiety or depression-like symptoms caused by subchronic social defeat stress in mice. Bioscience, Biotechnology, and Biochemistry 83: 1239-1247. https://doi.org/10.1080/09168451.2019.1591263
Mahar, I., Bambico, F.R., Mechawar, N. and Nobrega, J.N., 2014. Stress, serotonin, and hippocampal neurogenesis in relation to depression and antidepressant effects. Neuroscience and Biobehavioral Reviews 38: 173-192. https://doi.org/10.1016/j.neubiorev.2013.11.009
Mandic, A.D., Woting, A., Jaenicke, T., Sander, A., Sabrowski, W., Rolle-Kampcyk, U., von Bergen, M. and Blaut, M., 2019. Clostridium ramosum regulates enterochromaffin cell development and serotonin release. Scientific Reports 9: 1177. https://doi.org/10.1038/s41598-018-38018-z
Marasine, N.R., Sankhi, S., Lamichhane, R., Marasini, N.R. and Dangi, N.B., 2021. Use of antidepressants among patients diagnosed with depression: a scoping review. BioMed Research International 2021: 6699028. https://doi.org/10.1155/2021/6699028
Mayer, E.A., Tillisch, K. and Gupta, A., 2015. Gut/brain axis and the microbiota. Journal of Clinical Investigation 125: 926-938. https://doi.org/10.1172/JCI76304
Messaoudi, M., Lalonde, R., Violle, N., Javelot, H., Desor, D., Nejdi, A., Bisson, J.F., Rougeot, C., Pichelin, M., Cazaubiel, M. and Cazaubiel, J.M., 2011. Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. British Journal of Nutrition 105: 755-764. https://doi.org/10.1017/S0007114510004319
Mishra, P.K., Adusumilli, M., Deolal, P., Mason, G.F., Kumar, A. and Patel, A.B., 2020. Impaired neuronal and astroglial metabolic activity in chronic unpredictable mild stress model of depression: reversal of behavioral and metabolic deficit with lanicemine. Neurochemistry International 137: 104750. https://doi.org/10.1016/j.neuint.2020.104750
Misra, S. and Mohanty, D., 2019. Psychobiotics: a new approach for treating mental illness? Critical Reviews in Food Science and Nutrition 59: 1230-1236. https://doi.org/10.1080/10408398.2017.1399860
Noordzij, M., Dekker, F.W., Zoccali, C. and Jager, K.J., 2011. Sample size calculations. Nephron Clinical Practice 118: c319-323. https://doi.org/10.1159/000322830
Piwowarska, J., Chimiak, A., Matsumoto, H., Dziklinska, A., Radziwon-Zaleska, M., Szelenberger, W. and Pachecka, J., 2012. Serum cortisol concentration in patients with major depression after treatment with fluoxetine. Psychiatry Research 198: 407-411. https://doi.org/10.1016/j.psychres.2012.01.029
Sun, L., Zhang, H., Cao, Y., Wang, C., Zhao, C., Wang, H., Cui, G., Wang, M., Pan, Y., Shi, Y. and Nie, Y., 2019a. Fluoxetine ameliorates dysbiosis in a depression model induced by chronic unpredicted mild stress in mice. International Journal of Medical Sciences 16: 1260-1270. https://doi.org/10.7150/ijms.37322
Sun, Y., Geng, W., Pan, Y., Wang, J., Xiao, P. and Wang, Y., 2019b. Supplementation with Lactobacillus kefiranofaciens ZW3 from Tibetan kefir improves depression-like behavior in stressed mice by modulating the gut microbiota. Food and Function 10: 925-937. https://doi.org/10.1039/c8fo02096e
Taverniti, V. and Guglielmetti, S., 2012. Health-promoting properties of Lactobacillus helveticus. Frontiers in Microbiology 3: 392. https://doi.org/10.3389/fmicb.2012.00392
Tian, P., O’Riordan, K.J., Lee, Y.K., Wang, G., Zhao, J., Zhang, H., Cryan, J.F. and Chen, W., 2020. Towards a psychobiotic therapy for depression: Bifidobacterium breve CCFM1025 reverses chronic stress-induced depressive symptoms and gut microbial abnormalities in mice. Neurobiology of Stress 12: 100216. https://doi.org/10.1016/j.ynstr.2020.100216
Tian, P., Wang, G., Zhao, J., Zhang, H. and Chen, W., 2019a. Bifidobacterium with the role of 5-hydroxytryptophan synthesis regulation alleviates the symptom of depression and related microbiota dysbiosis. Journal of Nutritional Biochemistry 66: 43-51. https://doi.org/10.1016/j.jnutbio.2019.01.007
Tian, P., Zhu, H., Zou, R., Kong, Q., Xu, M., Zhao, J., Zhang, H., Chen, W. and Wang, G., 2021. An in vitro screening method for probiotics with antidepressant-like effect using the enterochromaffin cell model. Food and Function 12: 646-655. https://doi.org/10.1039/d0fo02307h
Tian, P., Zou, R., Song, L., Zhang, X., Jiang, B., Wang, G., Lee, Y.K., Zhao, J., Zhang, H. and Chen, W., 2019b. Ingestion of Bifidobacterium longum subspecies infantis strain CCFM687 regulated emotional behavior and the central BDNF pathway in chronic stress-induced depressive mice through reshaping the gut microbiota. Food and Function 10: 7588-7598. https://doi.org/10.1039/c9fo01630a
Vinderola, G., Matar, C. and Perdigon, G., 2007. Milk fermentation products of L. helveticus R389 activate calcineurin as a signal to promote gut mucosal immunity. BMC Immunology 8: 19. https://doi.org/10.1186/1471-2172-8-19
Wallace, C.J.K. and Milev, R.V., 2021. The efficacy, safety, and tolerability of probiotics on depression: clinical results from an open-label pilot study. Frontiers in Psychiatry 12: 618279. https://doi.org/10.3389/fpsyt.2021.618279
Wang, Q., Shen, L., Ma, S.Y., Chen, M.W., Lin, X., Hong, Y.L. and Feng, Y., 2016. Determination of the levels of two types of neurotransmitter and the anti-migraine effects of different dose-ratios of Ligusticum chuanxiong and Gastrodia elata. Journal of Food and Drug Analysis 24: 189-198. https://doi.org/10.1016/j.jfda.2015.08.005
Wang, S., Ishima, T., Zhang, J., Qu, Y., Chang, L., Pu, Y., Fujita, Y., Tan, Y., Wang, X. and Hashimoto, K., 2020. Ingestion of Lactobacillus intestinalis and Lactobacillus reuteri causes depression- and anhedonia-like phenotypes in antibiotic-treated mice via the vagus nerve. Journal of Neuroinflammation 17: 241.https://doi.org/10.1186/s12974-020-01916-z
Waters, P. and McCormick, C.M., 2011. Caveats of chronic exogenous corticosterone treatments in adolescent rats and effects on anxietylike and depressive behavior and hypothalamic-pituitary-adrenal (HPA) axis function. Biology of Mood and Anxiety Disorders 1: 4. https://doi.org/10.1186/2045-5380-1-4
Wei, C.L., Wang, S., Yen, J.T., Cheng, Y.F., Liao, C.L., Hsu, C.C., Wu, C.C. and Tsai, Y.C., 2019. Antidepressant-like activities of live and heat-killed Lactobacillus paracasei PS23 in chronic corticosterone-treated mice and possible mechanisms. Brain Research 1711: 202-213. https://doi.org/10.1016/j.brainres.2019.01.025
Wine, E., Gareau, M.G., Johnson-Henry, K. and Sherman, P.M., 2009. Strain-specific probiotic (Lactobacillus helveticus) inhibition of Campylobacter jejuni invasion of human intestinal epithelial cells. FEMS Microbiology Letters 300: 146-152. https://doi.org/10.1111/j.1574-6968.2009.01781.x
Xie, R., Jiang, P., Lin, L., Jiang, J., Yu, B., Rao, J., Liu, H., Wei, W. and Qiao, Y., 2020. Oral treatment with Lactobacillus reuteri attenuates depressive-like behaviors and serotonin metabolism alterations induced by chronic social defeat stress. Journal of Psychiatric Research 122: 70-78. https://doi.org/10.1016/j.jpsychires.2019.12.013
Yang, J., Zheng, P., Li, Y., Wu, J., Tan, X., Zhou, J., Sun, Z., Chen, X., Zhang, G., Zhang, H., Huang, Y., Chai, T., Duan, J., Liang, W., Yin, B., Lai, J., Huang, T., Du, Y., Zhang, P., Jiang, J., Xi, C., Wu, L., Lu, J., Mou, T., Xu, Y., Perry, S.W., Wong, M.L., Licinio, J., Hu, S., Wang, G. and Xie, P., 2020. Landscapes of bacterial and metabolic signatures and their interaction in major depressive disorders. Science Advances 6: eaba8555. https://doi.org/10.1126/sciadv.aba8555
Yano, J.M., Yu, K., Donaldson, G.P., Shastri, G.G., Ann, P., Ma, L., Nagler, C.R., Ismagilov, R.F., Mazmanian, S.K. and Hsiao, E.Y., 2015. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell 161: 264-276. 10.1016/j.cell.2015.02.047 Yohn, C.N., Gergues, M.M. and Samuels, B.A., 2017. The role of 5-HT receptors in depression. Molecular Brain 10: 28. https://doi.org/10.1186/s13041-017-0306-y
Zhang, M., Li, A., Yang, Q., Li, J., Wang, L., Liu, X., Huang, Y. and Liu, L., 2021. Beneficial effect of alkaloids from Sophora alopecuroides L. on CUMS-induced depression model mice via modulating gut microbiota. Frontiers in Cellular and Infection Microbiology 11: 665159. https://doi.org/10.3389/fcimb.2021.665159
| All Time | Past 365 days | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 1757 | 596 | 85 |
| Full Text Views | 55 | 20 | 1 |
| PDF Views & Downloads | 101 | 41 | 0 |
Emerging evidence indicates that the alterations in the gut microbiota-brain axis (GBA), which is the bilateral connection between the gut microbial communities and brain function, are involved in several mental illnesses, including depression. Certain probiotic strains have been revealed to improve depressive behaviours and the dysregulation of 5-hydroxytryptamine (5-HT) metabolism in depression. Here we evaluated the potential antidepressant effects of Lactobacillus helveticus strains using an in vitro enterochromaffin cell model (RIN14B). The L. helveticus strain WHH1889 was shown to significantly promote the level of 5-hydroxytryptamine (5-HTP, 5-HT precursor) and the gene expression of tryptophan hydroxylase 1 (Tph1), which is the key synthetase in the 5-HT biosynthesis in RIN14B cells. Ingestion of 0.2 ml WHH1889 (1´109 cfu/ml) in a chronic unpredictable mild stress (CUMS) mouse model of depression for five weeks normalised depressive and anxiety-like behaviours in the forced swim test, tail suspension test, sucrose preference test, and open field test. Meanwhile, the CUMS-induced elevated level of serum corticosterone and declined levels of hippocampal 5-HT and 5-HTP were reversed by WHH1889. Furthermore, the disturbances of the gut microbiome composition with reduced microbial diversity were also improved by WHH1889, accompanied by the increased colonic 5-HTP level and Tph1 gene expression. In summary, these findings indicate that WHH1889 exerts antidepressant-like effects on CUMS mice, which is associated with the modulations of the 5-HT/5-HTP metabolism and gut microbiome composition. Therefore, ingestion of the L. helveticus strain WHH1889 with antidepressant potentials may become an encouraging therapeutic option in the treatment of depression.
| All Time | Past 365 days | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 1757 | 596 | 85 |
| Full Text Views | 55 | 20 | 1 |
| PDF Views & Downloads | 101 | 41 | 0 |