Latest Advances in the Effects of Caloric Restriction on Gut Microbiota in Healthy，Aged and Diseased Populations

doi:10.12114/j.issn.1007-9572.2020.00.472

Abstract

Abstract: Caloric restriction（CR） plays a part in promoting health and longevity，delaying aging，and preventing the development of metabolic disorders and age-related diseases. Recent studies have found that gut microbiota play a key role in healthy，aged and diseased hosts，and changes in diet can significantly affect the balance of beneficial and pathogenic bacteria in the gut. CR is one of the most commonly used dietary interventions，whose benefits may be produced via the modification of gut microbiota. This article reviews the latest advances in the effects of CR on gut microbiota in healthy，aged and diseased populations，providing microbiological evidence for clinical application and promotion of CR.

Key words: Caloric restriction, Gut microbiota, Health, Aging, Diseases, Review

摘要： 基金项目：国家自然科学基金面上项目（81973927；81873356）
热量限制可以促进机体健康、延长寿命、延缓衰老、防止代谢紊乱和与年龄相关疾病的发生发展。近年来，研究发现肠道菌群在宿主的健康、衰老和疾病中均发挥了关键作用，饮食的改变可显著影响肠道有益菌和致病菌的平衡。热量限制是最常采用的饮食干预疗法之一，其有益作用可能是通过肠道菌群介导的。本文通过综述热量限制对健康、衰老和疾病状态下机体肠道菌群影响的相关研究进展，以期为热量限制的临床应用和推广提供微生物学证据。

关键词: 热量限制, 肠道菌群, 健康, 衰老, 疾病, 综述

YE Jiamei,ZHONG Dongling,LI Juan, et al. Latest Advances in the Effects of Caloric Restriction on Gut Microbiota in Healthy，Aged and Diseased Populations　[J]. Chinese General Practice, 2021, 24(7): 895-900. DOI: 10.12114/j.issn.1007-9572.2020.00.472.
叶佳美,钟冬灵,李涓等. 热量限制对健康、衰老和疾病机体肠道菌群影响的研究进展[J]. 中国全科医学, 2021, 24(7): 895-900. DOI: 10.12114/j.issn.1007-9572.2020.00.472.

References

［1］FONTANA L，PARTRIDGE L，LONGO V D．Extending healthy life span：from yeast to humans［J］．Science，2010，328（5976）：321-326．DOI：10.1126/science.1172539.
［2］VASCONCELOS A R，YSHII L M，VIEL T A，et al．Intermittent fasting attenuates lipopolysaccharide-induced neuroinflammation and memory impairment［J］．J Neuroinflammation，2014，11：85．DOI：10.1186/1742-2094-11-85.
［3］LER R E，PETERSON D A，GORDON J I．Ecological and evolutionary forces shaping microbial diversity in the human intestine［J］．Cell，2006，124（4）：837-848．DOI：10.1016/j.cell.2006.02.017.
［4］CATTERSON J H，KHEROCHA M，DYSON M C，et al．Short-term，intermittent fasting induces long-lasting gut health and TOR-independent lifespan extension［J］．Curr Biol，2018，28（11）：1714-1724．DOI：10.1016/j.cub.2018.04.015.
［5］OTT B，SKURK T，HASTREITER L，et al．Effect of caloric restriction on gut permeability，inflammation markers，and fecal microbiota in obese women［J］．Sci Rep，2017，7（1）：11955．DOI：10.1038/s41598-017-12109-9.
［6］刘宝祥，王风芹．对高血压患者采用热量限制干预的临床效果［J］．临床医药文献电子杂志，2017，4（17）：3198-3199．DOI：10.16281/j.cnki.jocml.2017.17.017.
［7］MULLER H，DE TOLEDO F W，RESCH K L．Fasting followed by vegetarian diet in patients with rheumatoid arthritis：a systematic review［J］．Scand J Rheumatol，2001，30（1）：1-10．
［8］金钗，徐明智．肠道菌群与高尿酸血症及痛风的相关性研究［J］．中国微生态学杂志，2019，31（8）：980-984．
［9］HENNEBELLE M，ROY M，ST-PIERRE V，et al．Energy restriction does not prevent insulin resistance but does prevent liver steatosis in aging rats on a western-style diet［J］．Nutrition，2015，31（3）：523-530．DOI：10.1016/j.nut.2014.09.009.
［10］WANG S，HUANG M，YOU X，et al．Gut microbiota mediates the anti-obesity effect of calorie restriction in mice［J］．Sci Rep，2018，8（1）：13037．DOI：10.1038/s41598-018-31353-1.
［11］KOHL K D，AMAYA J，PASSEMENT C A，et al．Unique and shared responses of the gut microbiota to prolonged fasting：a comparative study across five classes of vertebrate hosts［J］．FEMS Microbiol Ecol，2014，90（3）：883-894．DOI：10.1111/1574-6941.12442.
［12］LI T，QI M，GATESOUPE F J，et al．Adaptation to fasting in crucian carp（carassius auratus）：gut microbiota and its correlative relationship with immune function［J］．Microb Ecol，2019，78（1）：6-19．DOI：10.1007/s00248-018-1275-0.
［13］BIAN X，YANG L，WU W，et al．Pediococcus pentosaceus LI05 alleviates DSS-induced colitis by modulating immunological profiles，the gut microbiota and short-chain fatty acid levels in a mouse model［J］．Microb Biotechnol，2020，13（4）：1228-1244．DOI：10.1111/1751-7915.13583.
［14］OZKUL C，YALINAY M，KARAKAN T．Islamic fasting leads to an increased abundance of Akkermansia muciniphila and Bacteroides fragilis group：a preliminary study on intermittent fasting［J］．Turk J Gastroenterol，2019，30（12）：1030-1035．DOI：10.5152/tjg.2019.19185.
［15］DING Y H，QIAN L Y，PANG J，et al．The regulation of immune cells by Lactobacilli：a potential therapeutic target for anti-atherosclerosis therapy［J］．Oncotarget，2017，8（35）：59915-59928．DOI：10.18632/oncotarget.18346.
［16］FRAUMENE C，MANGHINA V，CADONI E，et al．Caloric restriction promotes rapid expansion and long-lasting increase of Lactobacillus in the rat fecal microbiota［J］．Gut Microbes，2018，9（2）：104-114．DOI：10.1080/19490976.2017.1371894.
［17］TURNBAUGH P J，LEY R E，MAHOWALD M A，et al．An obesity-associated gut microbiome with increased capacity for energy harvest［J］．Nature，2006，444（7122）：1027-1031．DOI：10.1038/nature05414.
［18］MORENO-NAVARRETE J M，SERINO M，BLASCO-BAQUE V，et al．Gut microbiota interacts with markers of adipose tissue browning，insulin action and plasma acetate in morbid obesity［J］．Mol Nutr Food Res，2018，62（3）：1700721．
［19］TANCA A，ABBONDIO M，PALOMBA A，et al．Caloric restriction promotes functional changes involving short-chain fatty acid biosynthesis in the rat gut microbiota［J］．Sci Rep，2018，8（1）：14778．DOI：10.1038/s41598-018-33100-y.
［20］GENTILE C L，WEIR T L．The gut microbiota at the intersection of diet and human health［J］．Science，2018，362（6416）：776-780．DOI：10.1126/science.aau5812.
［21］WANG H，HOU L，KWAK D，et al．Increasing regulatory T cells with interleukin-2 and interleukin-2 antibody complexes attenuates lung inflammation and heart failure progression［J］．Hypertension，2016，68（1）：114-122．
［22］CHEN J，VITETTA L．Inflammation-modulating effect of butyrate in the prevention of colon cancer by dietary fiber［J］．Clin Colorectal Cancer，2018，17（3）：e541-544．DOI：10.1016/j.clcc.2018.05.001.
［23］KIM M，FRIESEN L，PARK J，et al．Microbial metabolites，short-chain fatty acids，restrain tissue bacterial load，chronic inflammation，and associated cancer in the colon of mice［J］．Eur J Immunol，2018，48（7）：1235-1247．DOI：10.1002/eji.201747122.
［24］DAMMS-MACHADO A，MITRA S，SCHOLLENBERGER A E，et al．Effects of surgical and dietary weight loss therapy for obesity on gut microbiota composition and nutrient absorption［J］．Biomed Res Int，2015，2015：806248．DOI：10.1155/2015/806248.
［25］ZENG T，CUI H，TANG D，et al．Short-term dietary restriction in old mice rejuvenates the aging-induced structural imbalance of gut microbiota［J］．Biogerontology，2019，20（6）：837-848．DOI：10.1007/s10522-019-09830-5.
［26］BIRAGYN A，FERRUCCI L．Gut dysbiosis：a potential link between increased cancer risk in ageing and inflammaging［J］．Lancet Oncol，2018，19（6）：e295-304．DOI：10.1016/S1470-2045(18)30095-0.
［27］ZHANG C，LI S，YANG L，et al．Structural modulation of gut microbiota in life-long calorie-restricted mice［J］．Nat Commun，2013，4：2163．DOI：10.1038/ncomms3163.
［28］KOK D，RUSLI F，VAN DER LUGT B，et al．Lifelong calorie restriction affects indicators of colonic health in aging C57Bl/6J mice［J］．J Nutr Biochem，2018，56：152-164．DOI：10.1016/j.jnutbio.2018.01.001.
［29］ZWEIGNER J，SCHUMANN R R，WEBER J R．The role of lipopolysaccharide-binding protein in modulating the innate immune response［J］．Microbes Infect，2006，8（3）：946-952．DOI：10.1016/j.micinf.2005.10.006.
［30］PAN F，ZHANG L，LI M，et al．Predominant gut Lactobacillus murinus strain mediates anti-inflammaging effects in calorie-restricted mice［J］．Microbiome，2018，6（1）：54．
［31］AMABEBE E，ROBERT F O，AGBALALAH T，et al．Microbial dysbiosis-induced obesity：role of gut microbiota in homoeostasis of energy metabolism［J］．Br J Nutr，2020，123（10）：1127-1137．DOI：10.1017/S0007114520000380.
［32］YU E W，GAO L，STASTKA P，et al．Fecal microbiota transplantation for the improvement of metabolism in obesity：the FMT-TRIM double-blind placebo-controlled pilot trial［J］．PLoS Med，2020，17（3）：e1003051．DOI：10.1371/journal.pmed.1003051.
［33］LEY R E，TURNBAUGH P J，KLEIN S，et al．Microbial ecology：human gut microbes associated with obesity［J］．Nature，2006，444（7122）：1022-1023．DOI：10.1038/4441022a.
［34］BRACHE L K，ASTRUP A，LARSEN L H．Is butyrate the link between diet，intestinal microbiota and obesity-related metabolic diseases?［J］．Obes Rev，2013，14（12）：950-959．DOI：10.1111/obr.12068.
［35］RUIZ A，CERDO T，JAUREGUI R，et al．One-year calorie restriction impacts gut microbial composition but not its metabolic performance in obese adolescents［J］．Environ Microbiol，2017，19（4）：1536-1551．DOI：10.1111/1462-2920.13713.
［36］ZHENG X，ZHOU K，ZHANG Y，et al．Food withdrawal alters the gut microbiota and metabolome in mice［J］．FASEB J，2018，32（9）：4878-4888．DOI：10.1096/fj.201700614R.
［37］MORENO-NAVARRETE J M，FERNANDEZ-REAL J M．The gut microbiota modulates both browning of white adipose tissue and the activity of brown adipose tissue［J］．Rev Endocr Metab Disord，2019，20（4）：387-397．
［38］FABBIANO S，SUAREZ-ZAMORANO N，CHEVALIER C，et al．
Functional gut microbiota remodeling contributes to the caloric restriction-induced metabolic improvements［J］．Cell Metab，2018，28（6）：907-921．DOI：10.1016/j.cmet.2018.08.005.
［39］WANG X，QUINN P J．Lipopolysaccharide：biosynthetic pathway and structure modification［J］．Prog Lipid Res，2010，49（2）：97-107．DOI：10.1016/j.plipres.2009.06.002.
［40］EMIOLA A，GEORGE J，ANDREWS S S．A complete pathway model for lipid a biosynthesis in escherichia coli［J］．PLoS One，2014，10（4）：e121216．DOI：10.1371/journal.pone.0121216.
［41］LI G，XIE C，LU S，et al．Intermittent fasting promotes white adipose browning and decreases obesity by shaping the gut microbiota［J］．Cell Metab，2017，26（5）：801．DOI：10.1016/j.cmet.2017.10.007.
［42］李亚楠，鲁燕，祁小飞，等．2型糖尿病患者肠道菌群特征及其与胰岛素抵抗间的关系［J］．中国临床研究，2019，32（12）：1682-1685．DOI：10.13429/j.cnki.cjcr.2019.12.018.
［43］BELI E，YAN Y，MOLDOVAN L，et al．Restructuring of the gut microbiome by intermittent fasting prevents retinopathy and prolongs survival in db/db mice［J］．Diabetes，2018，67（9）：1867-1879．DOI：10.2337/db18-0158.
［44］CHENG C W，VILLANI V，BUONO R，et al．Fasting-mimicking diet promotes Ngn3-driven beta-cell regeneration to reverse diabetes［J］．Cell，2017，168（5）：775-788．
［45］WEI S，HAN R，ZHAO J，et al．Intermittent administration of a fasting-mimicking diet intervenes in diabetes progression，restores beta cells and reconstructs gut microbiota in mice［J］．Nutr Metab （Lond），2018，15：80．DOI：10.1186/s12986-018-0318-3.
［46］王保安，汤敏．2型糖尿病患者血清胆红素、胆汁酸水平与糖尿病视网膜病变的关系研究［J］．河北医药，2017，39（7）：1041-1043．DOI：10.3969/j.issn.1002-7386.2017.07.024.
［47］LIU Z，DAI X，ZHANG H，et al．Gut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairment［J］．Nat Commun，2020，11（1）：855．DOI：10.1038/s41467-020-14676-4.
［48］CHEN J，CHIA N，KALARI K R，et al．Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls［J］．Sci Rep，2016，6：28484．
［49］CHOI I Y，PICCIO L，CHILDRESS P，et al．A diet mimicking fasting promotes regeneration and reduces autoimmunity and multiple sclerosis symptoms［J］．Cell Rep，2016，15（10）：2136-2146．DOI：10.1016/j.celrep.2016.05.009.
［50］CIGNARELLA F，CANTONI C，GHEZZI L，et al．Intermittent fasting confers protection in CNS autoimmunity by altering the gut microbiota［J］．Cell Metab，2018，27（6）：1222-1235．
［51］CELIBERTO L S，GRAEF F A，HEALEY G R，et al．Inflammatory bowel disease and immunonutrition：novel therapeutic approaches through modulation of diet and the gut microbiome［J］．Immunology，2018，155（1）：36-52．
［52］LI H，CHRISTMAN L M，LI R，et al．Synergic interactions between polyphenols and gut microbiota in mitigating inflammatory bowel diseases［J］．Food Funct，2020．［Epub ahead of print］．DOI：10.1039/d0fo00713g.
［53］HUDA-FAUJAN N，ABDULAMIR A S，FATIMAH A B，et al．The impact of the level of the intestinal short chain fatty acids in inflammatory bowel disease patients versus healthy subjects［J］．Open Biochem J，2010，4：53-58．
［54］RANGAN P，CHOI I，WEI M，et al．Fasting-mimicking diet modulates microbiota and promotes intestinal regeneration to reduce inflammatory bowel disease pathology［J］．Cell Rep，2019，26（10）：2704-2719．DOI：10.1016/j.celrep.2019.02.019.
［55］ZHOU B，XIA X，WANG P，et al．Induction and amelioration of methotrexate-induced gastrointestinal toxicity are related to immune response and gut microbiota［J］．EBioMedicine，2018，33：122-133．DOI：10.1016/j.ebiom.2018.06.029.
［56］TANG D，ZENG T，WANG Y，et al．Dietary restriction increases protective gut bacteria to rescue lethal methotrexate-induced intestinal toxicity［J］．Gut Microbes，2020．［Epub ahead of print］．DOI：10.1080/19490976.2020.1714401.
［57］曾凡娟，周一鸣，曹文娟，等．益生菌对血液肿瘤化疗儿童腹泻发生率及肠黏膜屏障功能指标水平的影响探究［J］．中国合理用药探索，2019，16（12）：75-77．
［58］LIU T，WU Y，WANG L，et al．A more robust gut microbiota in calorie-restricted mice is associated with attenuated intestinal injury caused by the chemotherapy drug cyclophosphamide［J］．mBio，2019，10（2）：e02903-18．DOI：10.1128/mBio.02903-18.

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