Possible Mechanism of Chronic Constipation Improvement via Exercise-induced Changes in Gut Microbiota Composition and Metabolites

doi:10.12114/j.issn.1007-9572.2021.00.044

Abstract

Abstract: As a common health problem and an inducing factor for many diseases with high mortality rate，chronic constipation seriously affects human health and quality of life，bringing heavy mental and economic burden on families and society.However，due to limited efficacy of available treatments for chronic constipation，it is necessary to find a new，convenient，inexpensive and effective treatment.Exercise plays an important role in the prevention and treatment of chronic constipation.In addition，exercise can regulate the composition of gut microbiota，and some studies have shown that gut microbiota disorder after constipation reduces the content of gut microbiota metabolites（such as SCFA and 5-HT），inhibits intestinal movement and accelerates the development of chronic constipation，so there must be a close relationship between exercise，gut flora and constipation.This paper reviews the regulatory effect of exercise on constipation，the mechanism of gut microbiota in regulating constipation and the influence of exercise on gut microbiota，so as to explore the possibility of improving chronic constipation by exercise-induced changes in gut microbiota composition，and to further improve the mechanism of exercise in the remission of constipation.

Key words: Chronic constipation, Exercise, Gut microbiota, Short chain fatty acids, Review

摘要： 慢性便秘是常见的健康问题，也是许多高死亡率疾病的诱发因素，严重影响人类的健康和生存质量，给家庭和社会带来沉重的精神和经济负担，而目前针对慢性便秘的治疗方法疗效有限，故需寻找一种便捷、经济、有效的方法。运动在慢性便秘的预防和治疗中发挥着重要作用，并且运动可调节肠道菌群的组成，而有研究表明便秘后发生的肠道菌群紊乱使肠腔内菌群代谢物〔如短链脂肪酸（SCFA）、5-羟色胺（5-HT）〕含量降低，抑制肠道运动，加速慢性便秘的发展，提示运动、菌群与便秘三者间存在密切联系。本文就运动对便秘的调节作用、肠道菌群在便秘中的调控机制和运动对肠道菌群的影响进行综述，以此探索运动通过调节肠道菌群的组成改善慢性便秘的可能性，希望能进一步完善运动缓解便秘的作用机制。

关键词: 慢性便秘, 运动, 肠道菌群, 短链脂肪酸, 综述

HU Xiaomin,YE Jiamei,WANG Liqun, et al. Possible Mechanism of Chronic Constipation Improvement via Exercise-induced Changes in Gut Microbiota Composition and Metabolites　[J]. Chinese General Practice, 2021, 24(15): 1984-1988. DOI: 10.12114/j.issn.1007-9572.2021.00.044.
胡晓敏,叶佳美,王丽群等. 基于肠道菌群探讨运动改善慢性便秘的可能机制[J]. 中国全科医学, 2021, 24(15): 1984-1988. DOI: 10.12114/j.issn.1007-9572.2021.00.044.

References

［1］LACY B E，MEARIN F，CHANG L，et al．Bowel disorders［J］．Gastroenterology，2016，150（6）：1393-1407．DOI：10.1053/j.gastro.2016.02.031.
［2］中华医学会消化病学分会胃肠动力学组，功能性胃肠病协作组．中国慢性便秘专家共识意见（2019，广州）［J］．中华消化杂志，2019，39（9）：577-598．DOI：10.3760/cma.j.issn.0254-1432.2019.09.001.
Neurogastroenterology and Motility Committee，Chinese Society of Gastroenterolog．Chinese expert consensus on chronic constipation （2019，Guangzhou）［J］．Chin J Dig，2019，39（9）：577-598．DOI：10.3760/cma.j.issn.0254-1432.2019.09.001.
［3］JOHANSON J F，KRALSTEIN J．Chronic constipation：a survey of the patient perspective［J］．Aliment Pharmacol Ther，2007，25（5）：599-608．DOI：10.1111/j.1365-2036.2006.03238.x.
［4］DE MEIJ T G，DE GROOT E F，ECK A，et al．Characterization of microbiota in children with chronic functional constipation［J］．PLoS One，2016，11（10）：e0164731．DOI：10.1371/journal.pone.0164731.
［5］DE VADDER F，GRASSET E，MANNERAS H L，et al．Gut microbiota regulates maturation of the adult enteric nervous system via enteric serotonin networks［J］．Proc Natl Acad Sci U S A，2018，115（25）：6458-6463．DOI：10.1073/pnas.1720017115.
［6］MADEMPUDI R S，NEELAMRAJU J，AHIRE J J，et al．Bacillus coagulans unique IS2 in constipation：a double-blind，placebo-controlled study［J］．Probiotics Antimicrob Proteins，2019，12（2）：335-342．DOI：10.1007/s12602-019-09542-9.
［7］TIAN H，DING C，GONG J，et al．Treatment of slow transit constipation with fecal microbiota transplantation：a pilot study［J］．J Clin Gastroenterol，2016，50（10）：865-870．DOI：10.1097/MCG.0000000000000472.
［8］CHRYSOSTOMOU V，GALIC S，VANWIJNGAARDEN P，et al．Exercise reverses age-related vulnerability of the retina to injury by preventing complement-mediated synapse elimination via a BDNF-dependent pathway［J］．Aging Cell，2016，15（6）：1082-1091．DOI：10.1111/acel.12512.
［9］PEDERSEN L，IDORN M，OLOFSSON G H，et al．Voluntary running suppresses tumor growth through epinephrine- and IL-6-dependent NK cell mobilization and redistribution［J］．Cell Metab，2016，23（3）：554-562．DOI：10.1016/j.cmet.2016.01.011.
［10］ASAKURA K，MASAYASU S，SASAKI S．Dietary intake，physical activity，and time management are associated with constipation in preschool children in Japan［J］．Asia Pac J Clin Nutr，2017，26（1）：118-129．DOI：10.6133/apjcn.112015.02.
［11］HUANG R，HO S Y，LO W S，et al．Physical activity and constipation in Hong Kong adolescents［J］．PLoS One，2014，9（2）：e90193．DOI：10.1371/journal.pone.0090193.
［12］SONG B K，KIM Y S，KIM H S，et al．Combined exercise improves gastrointestinal motility in psychiatric in patients［J］．World J Clin Cases，2018，6（8）：51-57．DOI：10.12998/wjcc.v6.i8.207.
［13］DAVIS J，CAMILLERI M，ECKERT D，et al．Physical activity is associated with accelerated gastric emptying and increased ghrelin in obesity［J］．Neurogastroenterol Motil，2020．DOI：10.1111/nmo.13879.
［14］乔德才，时晓昀，刘晓莉．不同强度运动对体育专业女大学生胃肠激素和免疫物质的影响［J］．中国运动医学杂志，2008，27（6）：735-736，751．DOI：10.16038/j.1000-6710.2008.06.018.
［15］BILSKI J，MAZURBIALY A I，MAGIEROWSKI M，et al．Exploiting significance of physical exercise in prevention of gastrointestinal disorders［J］．Current Pharmaceutical Design，2018，24（18）：1916-1925．DOI：10.2174/1381612824666180522103759.
［16］KHALIF I，QUIGLEY E M，KONOVITEH E A，et al．Alterations in the colonic flora and intestinal permeability and evidence of immune activation in chronic constipation［J］．Dig Liver Dis，2005，37（11）：838-849．DOI：10.1016/j.dld.2005.06.008.
［17］田宏亮．菌群移植治疗慢传输型便秘的临床机制研究及治疗策略优化［D］．南京：南京大学，2017.
［18］GE X，ZHAO W，DING C，et al．Potential role of fecal microbiota from patients with slow transit constipation in the regulation of gastrointestinal motility［J］．Sci Rep，2017，7（1）：441．DOI：10.1038/s41598-017-00612-y.
［19］WANG L，HU L，XU Q，et al．Bifidobacterium adolescentis exerts strain-specific effects on constipation induced by Loperamide in BALB/c mice［J］．Int J Mol Sci，2017，18（2）：318．DOI：10.3390/ijms18020318.
［20］WANG L，HU L，YAN S，et al．Effects of different oligosaccharides at various dosages on the composition of gut microbiota and short-chain fatty acids in mice with constipation［J］．Food Funct，2017，8（5）：1966-1978．DOI：10.1039/c7fo00031f.
［21］ZHAO L，HUANG Y，LU L，et al．Saturated long-chain fatty acid-producing bacteria contribute to enhanced colonic motility in rats［J］．Mbio，2018，6（1）：107．DOI：10.1186/s40168-018-0492-6.
［22］DRRHAN E C，YANG C，PEREZ-MUNOZ M E，et al．Precision microbiome modulation with discrete dietary fiber structures directs short-chain fatty acid production［J］．Cell Host Microbe，2020，27（3）：389-404．DOI：10.1016/j.chom.2020.01.006.
［23］WILLIAMS E K，CHANG R B，STROCHLIE D E，et al．Sensory neurons that detect stretch and nutrients in the digestive system［J］．Cell，2016，166（1）：209-221．DOI：10.1016/j.cell.2016.05.011.
［24］MARTIN A M，YABUT J M，CHOO J M，et al．The gut microbiome regulates host glucose homeostasis via peripheral serotonin［J］．Proc Natl Acad Sci U S A，2019，116（40）：19802-19804．DOI：10.1073/pnas.1909311116.
［25］CAO H，LIU X，AN Y，et al．Dysbiosis contributes to chronic constipation development via regulation of serotonin transporter in the intestine［J］．Scientific Reports，2017，7（1）：10322．DOI：10.1038/s41598-017-10835-8.
［26］ISRAELYAN N，DEL COLLE A，LI Z，et al．Effects of serotonin and slow-release 5-hydroxytryptophan on gastrointestinal motility in a mouse model of depression［J］．Gastroenterology，2019，157（2）：507-521．DOI：10.1053/j.gastro.2019.04.022.
［27］SIOPI E，CHEVALIER G，KATSIMPARDI L，et al．Changes in gut microbiota by chronic stress impair the efficacy of fluoxetine［J］．Cell Rep，2020，30（11）：3682-3690．DOI：10.1016/j.celrep.2020.02.099.
［28］OBATA Y，CSATANO á，BOEING S，et al．Neuronal programming by microbiota regulates intestinal physiology［J］．Nature，2020，578（7794）：284-289．DOI：10.1038/s41586-020-1975-8.
［29］JANKIPERSADSING S A，HADIZADEH F，BONDER M J，et al．A GWAS meta-analysis suggests roles for xenobiotic metabolism and ion channel activity in the biology of stool frequency［J］．Gut，2017，66（4）：756-758．DOI：10.1136/gutjnl-2016-312398.
［30］CHANDRASEKHARAN B，SAEEDI B J，ALAM A，et al．Interactions between commensal bacteria and enteric neurons，via FPR1 induction of ROS，increase gastrointestinal motility in mice［J］．Gastroenterology，2019，157（1）：179-192．DOI：10.1053/j.gastro.2019.03.045.
［31］ALLEN J M，MAILING L J，COHRS J，et al．Exercise training-induced modification of the gut microbiota persists after microbiota colonization and attenuates the response to chemically-induced colitis in gnotobiotic mice［J］．Gut Microbes，2018，9（2）：115-130．DOI：10.1080/19490976.2017.1372077.
［32］CAMPBELL S C，WISNIEWSKI P J，NOJI M，et al．The effect of diet and exercise on intestinal integrity and microbial diversity in mice［J］．PLoS One，2016，11（3）：e0150502．DOI：10.1371/journal.pone.0150502.
［33］QUEIPO-ORTUNO M I，SEOANE L M，MURRI M，et al．Gut microbiota composition in male rat models under different nutritional status and physical activity and its association with serum leptin and ghrelin levels［J］．PLoS One，2013，8（5）：e65465．DOI：10.1371/journal.pone.0065465.
［34］ YU J C，HALE V L，KHODADADI H，et al．Whole body vibration-induced omental macrophage polarization and fecal microbiome modification in a murine model［J］．Int J Mol Sci，2019，20（13）：3125．DOI：10.3390/ijms20133125.
［35］ALLEN J M，MAILING L J，NIEMIRO G M，et al．Exercise alters gut microbiota composition and function in lean and obese humans［J］．Med Sci Sports Exerc，2018，50（4）：747-757．DOI：10.1249/MSS.0000000000001495.
［36］CRONIN O，BARTON W，SKUSE P，et al．A prospective metagenomic and metabolomic analysis of the impact of exercise and/or whey protein supplementation on the gut microbiome of sedentary adults［J］．mSystems，2018，3（3）：e00044-18．DOI：10.1128/mSystems.00044-18.
［37］BARTON W，PENNEY N C，CRONIN O，et al．The microbiome of professional athletes differs from that of more sedentary subjects in composition and particularly at the functional metabolic level［J］．Gut，2018，67（4）：625-633．DOI：10.1136/gutjnl-2016-313627.
［38］PETERSEN L M，BAUTISTA E J，NGUYEN H，et al．Community characteristics of the gut microbiomes of competitive cyclists［J］．Microbiome，2017，5（1）：98．DOI：10.1186/s40168-017-0320-4.
［39］SCHEIMAN J，LUBER J M，CHAVKIN T A，et al．Meta-omics analysis of elite athletes identifies a performance-enhancing microbe that functions via lactate metabolism［J］．Nat Med，2019，25（7）：1104-1109．DOI：10.1038/s41591-019-0485-4.
［40］蒋兴宇，赵霞，邹凌云，等．适度运动对人体肠道菌群结构的影响［J］．第三军医大学学报，2017，39（18）：1824-1831．DOI：10.16016/j.1000-5404.201703049.
［41］YANO J M，YU K，DONALDSON G P，et al．Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis［J］．Cell，2015，161（2）：264-276．DOI：10.1016/j.cell.2015.02.047.
［42］KORECKA A，DONA A，LAHIRI S，et al．Bidirectional communication between the Aryl hydrocarbon Receptor（AhR） and the microbiome tunes host metabolism［J］．NPJ Biofilms Microbiomes，2016，2：16014．DOI：10.1038/npjbiofilms.2016.14.
［43］ZHANG T，LI Q，CHENG L，et al．Akkermansia muciniphila is a promising probiotic［J］．Microb Biotechnol，2019，12（6）：1109-1125．DOI：10.1111/1751-7915.13410.
［44］LIU Y，WANG Y，NI Y，et al．Gut microbiome fermentation determines the efficacy of exercise for diabetes prevention［J］．Cell Metab，2020，31（1）：77-91．DOI：10.1016/j.cmet.2019.11.001.

[1]	WANG Xu, WEI Xu, ZHU Liguo, FENG Tianxiao, WANG Zhipeng, SHI Bin. Research Ideas of the Efficacy Mechanism and Prospect Analysis of Traditional Chinese Manipulative Therapy on Treating Spinal Degenerative Diseases with Combination of Medicine and Industry [J]. Chinese General Practice, 2023, 26(33): 4118-4124.
[2]	XIN Gongkai, CONG Xin, YUAN Lei, CHENG Yuetong, NI Cuiping, ZHANG Weiwei, ZHANG Pingping, LIU Yu. Research Progress on Comprehensive Assessment Tools for the Elderly with Dementia [J]. Chinese General Practice, 2023, 26(33): 4103-4109.
[3]	ZHANG Siyu, ZHOU Yuqiu, DU Xiaohui, WANG Zhengjun. Advances in Duration of Untreated Psychosis and Its Early Intervention [J]. Chinese General Practice, 2023, 26(33): 4110-4117.
[4]	MENG Jiangtao, YANG Siyu, SUN Lei, LEI Ruining, ZHAO Xiaoxia. Advances in the Prognostic Value of Diffusion Tensor Imaging with Motor Evoked Potential for Motor Function in Cerebral Infarction Patients with Hemiplegia [J]. Chinese General Practice, 2023, 26(32): 4098-4102.
[5]	WANG Jiaxin, ZHAO Yali. Domestic and International Assessment Tools for Medical Teamwork: a Systematic Review [J]. Chinese General Practice, 2023, 26(31): 3951-3962.
[6]	WEI Mengyu, WANG Jiajia, ZHANG Yingying, LI Chunyang, LI Jiansheng. Research Status of Patient-reported Outcome Assessment Tools for Obstructive Sleep Apnea [J]. Chinese General Practice, 2023, 26(30): 3725-3733.
[7]	YUAN Xiwei, NAN Yuemin. Research Progress of Structure, Function and Mechanism of Action of Mitofusin 2 in Liver Diseases [J]. Chinese General Practice, 2023, 26(30): 3841-3846.
[8]	CHENG Jingwei, QIAO Junjun, YIN Zhen, HU Junpeng, WANG Qinghe, LIU Yangqing, WANG Yanfang. Interpretation of ISPAD Clinical Practice Consensus Guidelines 2022: Exercise in Children and Adolescents with Diabetes [J]. Chinese General Practice, 2023, 26(30): 3719-3724.
[9]	XIAO Yuqian, BAI Yanjie, WANG Yan, CHEN Shuying, CHEN Limin, SUN Kexin, WAN Jun. Research Progress of Mitochondrial Transfer in Post-stroke Cognitive Impairment [J]. Chinese General Practice, 2023, 26(30): 3833-3840.
[10]	LIU Yu, YUE Ting, YANG Dongyu, ZHAO Zhongting, YANG Jibo, ZHU Tiantian. Research Progress on Mechanism of Autophagy in the Pathogenesis of Rheumatoid Arthritis [J]. Chinese General Practice, 2023, 26(29): 3710-3714.
[11]	PU Yu, ZHANG Jixiang, DONG Weiguo. Advances in Ferroptosis and Inflammatory Bowel Disease [J]. Chinese General Practice, 2023, 26(29): 3698-3703.
[12]	XIAO Liqi, YANG Li, CUI Saixian, ZHANG Yayuan, WANG Yulu, HE Yan. Advances in the Association of High Salt-induced Gut Microbiota Disturbances with Salt-sensitive Blood Pressure [J]. Chinese General Practice, 2023, 26(29): 3704-3709.
[13]	WANG Qianqian, WANG Xiaohang, ZHOU Xiaoying, QIU Shanhu, SUN Zilin. Exercise is the Foundation of Weight Loss [J]. Chinese General Practice, 2023, 26(28): 3471-3476.
[14]	JIANG Qiuhui, LI Xuejun. Exercise is Not the Foundation of Weight Loss [J]. Chinese General Practice, 2023, 26(28): 3477-3481.
[15]	REN Yanfeng, LIU Shimeng, TAO Ying, CHEN Yingyao. A Systematic Review of Medication Preferences for Patients with Depression Based on Discrete Choice Experiment and Best-worst Scaling [J]. Chinese General Practice, 2023, 26(28): 3559-3564.