Fecal Microbiota Transplantation from Healthy Donors Reduced Alcohol-induced Anxiety and Depression in an Animal Model of Chronic Alcohol Exposure

Zheng Xu ； Zengxun Liu ； Xiaoguang Dong ； Tao Hu ； Lingling Wang ； Junwei Li ； Xiaoyu Liu ； Jinhao Sun

《The Chinese Journal of Physiology》 61卷6期 (2018/12) Pp. 360-371

https://doi.org/10.4077/CJP.2018.BAH633

摘要

Alcohol addiction can cause brain dysfunction and threatens both individuals and society. Recently, emerging studies have suggested the dysbiosis of gut microbiota induced by alcohol exposure contributed to the reward-seeking behaviors as well as anxiety, depression. In the current study, animal model of chronic alcohol exposure was established by providing mice with gradient concentrations of alcohol from 2%, 4%, and 6% to 8% for 21 days. Moreover, three fecal microbiota transplantation (FMT) plans were innovatively designed to explore the potential effects of FMT from 3 healthy donors on alcohol-induced neuropsychic behaviors. To our knowledge, for the first time, we found that anxiety and depression after alcohol intake were gradually relieved with the extension of transplantation. Although the two-week FMT starting at the end of alcohol treatment had few effects, the transplantation started at 8% ethanol exposure alleviated alcohol-induced depression in tail suspension test. More importantly, accompanied by three-week exposure, the five-week FMT significantly decreased anxiety-like behaviors in open field test and depression in tail suspension test. These data validated the role of gut microbiota in alcohol addiction and indicated the modulation of healthy donor FMT on alcohol-related anxiety and depression, providing a new target for treating alcohol addiction by targeting microbiota.

關鍵字

alcohol addiction ； anxiety ； depression ； fecal microbiota transplantation ； gut microbiota

參考文獻

Leclercq, S., Starkel, P., Delzenne, N.M. and de Timary, P. The gut microbiota: A new target in the management of alcohol dependence? Alcohol Doi: 10.1016/j.alcohol.2018.03.005, 2018 (In Press).

Zheng, P., Zeng, B., Zhou, C., Liu, M., Fang, Z., Xu, X., Zeng, L., Chen, J., Fan, S., Du, X., Zhang, X., Yang, D., Yang, Y., Meng, H., Li, W., Melgiri, N.D., Licinio, J., Wei, H., and Xie, P. Gut micro-biome remodeling induces depressive-like behaviors through a pathway mediated by the host's metabolism. Mol. Psychiatry 21: 786-796, 2016.

Zuo, Z., Fan, H., Tang, X.D., Chen, Y.M., Xun, L.T., Li, Y., Song, Z.J. and Zhai, H.Q. Effect of different treatments and alcohol addiction on gut microbiota in minimal hepatic encephalopathy patients. Exp. Ther. Med. 14: 4887-4895, 2017

Burokas, A., Arboleya, S., Moloney, R.D., Peterson, V.L., Murphy, K., Clarke, G., Stanton, C., Dinan, T.G. and Cryan, J.F. Targeting the microbiota-gut-brain axis: prebiotics have anxiolytic and antidepressant-like effects and reverse the impact of chronic stress in mice. Biol. Psychiatry 82: 472-487, 2017.

Crumeyrolle-Arias, M., Jaglin, M., Bruneau, A., Vancassel, S., Cardona, A., Daugé, V., Naudon, L. and Rabot, S. Absence of the gut microbiota enhances anxiety-like behavior and neuro-endocrine response to acute stress in rats. Psychoneuroendocrinology 42: 207-217, 2014.