Probiotics decrease depressive behaviors induced by constipation via activating the AKT signaling pathway
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Chronic constipation is often accompanied by emotional disorders such as depression and anxiety. The aim of this study was to determine whether administration of a multispecies probiotic can decrease depressive behaviors through the gut-brain axis and identify any underlying mechanisms. A mouse model of constipation induced by loperamide (5 mg·kg−1,i.p.) was used. For that purpose, 36 ICR male mice were divided into three groups: control, constipation and probiotic groups. The probiotic group received treatment with a probiotic once per day for 14 days via a gavage. All other groups were given an equal volume of normal saline. The fecal parameters and intestinal transit ratio were recorded. The forced swimming test and tail suspension test were used to detect changes in depressive behaviors. Total superoxide dismutase (T-SOD) activity and malondialdehyde (MDA) levels were measured by assay kits. We also detected neuronal survival, as well as phosphorylated Ser/Thr protein kinase (p-AKT), Bcl-2, Bcl-2 associated X protein (Bax) and cleaved caspase-3 levels in the hippocampus. The results showed that administration of a probiotic could ameliorate depressive behaviors and relieve neuronal cell injury in the hippocampal CA3 regions. Moreover, probiotic treatment decreased MDA levels and increased SOD activity. Furthermore, probiotic administration increased p-AKT and Bcl-2 levels in the hippocampus of the constipated mice, while decreasing the concentrations of Bax and cleaved caspase-3, so as to inhibit the neural apoptosis. In the present study, we confirm that probiotics can alleviate depression induced by constipation through protecting neuronal health via activation of the AKT signaling pathway.
KeywordsOxidative stress AKT Depression Probiotic Constipation Microbiota-gut-brain axis
This research was supported by the National Natural Science Foundation of China (81471994), Jiangsu Privincial Natural Science Foundation (BK20151154), Jiangsu Privincial Medical Talent (ZDRCA2016053), Six talent peaks project of Jiangsu Province (WSN-135), Advanced health talent of six-one project of Jiangsu Province (LGY2016042), and Jiangsu Provincial Commission of Health and Family Planning Research Project (H201631). The authors thank Renxian Tang, Xiaomei Liu, Feng Zhou, Xiaotian Wang of Department of Pathogen Biology and Immunology, Laboratory of Infection and Immunity of Xuzhou Medical University for their support and help during the experiments.
Compliance with ethical standards
Conflict of interest
All authors state that there is no conflict of interest.
- Arseneault-Breard J, Rondeau I, Gilbert K, Girard SA, Tompkins TA, Godbout R, Rousseau G (2012) Combination of lactobacillus helveticus R0052 and Bifidobacterium longum R0175 reduces post-myocardial infarction depression symptoms and restores intestinal permeability in a rat model. Br J Nutr 107:1793–1799CrossRefGoogle Scholar
- Food and Agriculture Organization of the United Nations and WHO Working Group (2002) Guidelines for the evaluation of probiotic in food. FAO/WHO, GenevaGoogle Scholar
- Messaoudi M, Lalonde R, Violle N, Javelot H, Desor D, Nejdi A, Bisson JF, Rougeot C, Pichelin M, Cazaubiel M, Cazaubiel JM (2011) Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br J Nutr 105:755–764CrossRefGoogle Scholar
- Moraga-Amaro R, Gonzalez H, Ugalde V, Donoso-Ramos JP, Quintana-Donoso D, Lara M, Morales B, Rojas P, Pacheco R (2016) Dopamine receptor D5 deficiency results in a selective reduction of hippocampal NMDA receptor subunit NR2B expression and impaired memory. Neuropharmacology 103:222–235CrossRefGoogle Scholar
- Samad N, Saleem A (2017) Administration of Allium cepa L. bulb attenuates stress-produced anxiety and depression and improves memory in male mice. Metab Brain Dis 2017Google Scholar
- Slyepchenko A, Maes M, Jacka FN, Köhler CA, Barichello T, McIntyre RS, Berk M, Grande I, Foster JA, Vieta E, Carvalho AF (2017) Gut microbiota, bacterial translocation, and interactions with diet: pathophysiological links between major depressive disorder and non-communicable medical comorbidities. Psychother Psychosom 86:31–46CrossRefGoogle Scholar
- Staller K, Barshop K, Kuo B (2017) Depression but not symptom severity is associated with work and school absenteeism in refractory chronic constipation. J Clin Gastroenterol 00Google Scholar
- Yang N, Ren Z, Zheng J, Feng L, Li D, Gao K, Zhang L, Liu Y, Zuo P (2016) 5-(4-hydroxy-3-dimethoxybenzylidene)-rhodanine(RD-1)-improved mitochondrial function prevents anxiety- and depressive-like states induced by chronic corticosterone injections in mice. Neuropharmacology 105:587–593CrossRefGoogle Scholar