短链脂肪酸调控骨骼肌生理功能研究进展

doi:10.16431/j.cnki.1671-7236.2023.06.012

摘要/Abstract

摘要： 近年来，肠道菌群与宿主整个生命过程的相互作用受到越来越多的关注。肠道菌群可产生具有生物活性的可吸收代谢物，对维持宿主的健康起到了不可替代的作用。短链脂肪酸（short chain fatty acids，SCFAs）是肠道菌群发酵膳食纤维产生的主要代谢产物，主要包括乙酸、丙酸和丁酸，其作为介导肠道菌群与宿主各器官之间互作的媒介，广泛参与到宿主的生理活动中，其中也包括骨骼肌。骨骼肌作为机体最大和最重要的器官之一，维持其正常生理功能对于机体健康至关重要。目前关于SCFAs调控宿主的研究多集中在其他组织器官，调控骨骼肌的相关报道较少。鉴于SCFAs广泛的生理作用和骨骼肌自身的重要性，笔者就肠-肌轴理论、SCFAs的产生途径、转运及其对骨骼肌（质量、耐力、纤维特性）的调控作用进行综述，旨在加深对SCFAs调控骨骼肌这一生理过程的认识，为探索骨骼肌相关疾病的生物靶点提供新的思路。

关键词: 短链脂肪酸(SCFAs); 骨骼肌; 质量; 耐力; 纤维特性

Abstract: In recent years, more and more attention has been paid to the interaction between gut microbiota and the whole life process of the host.Gut microbiota plays an irreplaceable role in maintaining the health of the host mainly through the production of bioactive absorbable metabolites.Short chain fatty acids (SCFAs) are the main metabolites produced by gut microbiota fermentation of dietary fiber, mainly including acetate, propionate and butyrate.As a medium mediating the interaction between gut microbiota and various organs of the host, SCFAs are widely involved in the physiological activities of the host, including skeletal muscle.As one of the largest and most important organs of the body, skeletal muscle is very important for the health of the body to maintain its normal physiological function.At present, the studies on the regulation of host by SCFAs, mainly focus on other tissues and organs, while there are still few studies on the regulation of skeletal muscle.In view of the extensive physiological effects of SCFAs and the importance of skeletal muscle itself, the current research on the gut-muscle axis theory, the production pathway and transport of SCFAs, and the regulation of skeletal muscle (mass, endurance, fiber properties) as metabolites of intestinal flora were reviewed, and the current research status and future research directions were prospected.This study aims to deepen the understanding of the physiological process of SCFAs in regulating skeletal muscle, and provide new ideas for exploring biological targets of skeletal muscle-related diseases.

Key words: short-chain fatty acids (SCFAs); skeletal muscle; mass; endurance; fiber properties

中图分类号:

Q445

杨瑰桃, 马继登, 李学伟, 葛良鹏, 张进威. 短链脂肪酸调控骨骼肌生理功能研究进展[J]. 中国畜牧兽医, 2023, 50(6): 2286-2295.

YANG Guitao, MA Jideng, LI Xuewei, GE Liangpeng, ZHANG Jinwei. Research Advance on Regulation of Skeletal Muscle Physiology Function by Short Chain Fatty Acids[J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(6): 2286-2295.

参考文献

[1] HOOPER L V, GORDON J I.Commensal host-bacterial relationships in the gut[J].Science, 2001, 292(5519):1115-1118.
[2] 潘杰, 刘来浩, 牟建伟.肠道菌群与人类健康研究进展[J].山东师范大学学报, 2021, 36(4):337-365. PAN J, LIU L H, MU J W.Research progress of gut microbiota and human health[J].Journal of Shandong Normal University, 2021, 36(4):337-365.(in Chinese)
[3] CHO I, BLASER M J.The human microbiome:At the interface of health and disease[J].Nature Reviews Genetics, 2012, 13(4):260-270.
[4] KAU A L, AHERN P P, GRIFFIN N W, et al.Human nutrition, the gut microbiome and the immune system[J].Nature, 2011, 474(7351):327-336.
[5] LOZUPONE C A, STOMBAUGH J I, GORDON J I, et al.Diversity, stability and resilience of the human gut microbiota[J].Nature, 2012, 489(7415):220-230.
[6] TREMAROLI V, BÄCKHED F.Functional interactions between the gut microbiota and host metabolism[J].Nature, 2012, 489(7415):242-249.
[7] MORRISON D J, PRESTON T.Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism[J].Gut Microbes, 2016, 7(3):189-200.
[8] HERNANDEZ M A G, CANFORA E E, JOCKEN J W E, et al.The short-chain fatty acid acetate in body weight control and insulin sensitivity[J].Nutrients, 2019, 11(8):1943.
[9] DALILE B, VAN OUDENHOVE L, VERVLIET B, et al.The role of short-chain fatty acids in microbiota-gut-brain communication[J].Nature Reviews Gastroenterology and Hepatology, 2019, 16(8):461-478.
[10] MANDALIYA D K, SESHADRI S.Short chain fatty acids, pancreatic dysfunction and type 2 diabetes[J].Pancreatology, 2019, 19(2):280-284.
[11] NOGAL A, VALDES A M, MENNI C.The role of short-chain fatty acids in the interplay between gut microbiota and diet in cardio-metabolic health[J].Gut Microbes, 2021, 13(1):1-24.
[12] ZHOU D, FAN J G.Microbial metabolites in non-alcoholic fatty liver disease[J].World Journal of Gastroenterology, 2019, 25(17):2019-2028.
[13] FRONTERA W R, OCHALA J.Skeletal muscle:A brief review of structure and function[J]. Calcified Tissue International, 2015, 96(3):183-195.
[14] TICINESI A, NOUVENNE A, CERUNDOLO N, et al.Gut microbiota, muscle mass and function in aging:A focus on physical frailty and sarcopenia[J].Nutrients, 2019, 11(7):1633.
[15] MARGOLIS K G, CRYAN J F, MAYER E A.The microbiota-gut-brain axis:From motility to mood[J].Gastroenterology, 2021, 160(5):1486-1501.
[16] MORAIS L H, SCHREIBER Ⅳ H L, MAZMANIAN S K.The gut microbiota-brain axis in behaviour and brain disorders[J].Nature Reviews Microbiology, 2021, 19(4):241-255.
[17] ALBILLOS A, GOTTARDI A D, RESCIGNO M.The gut-liver axis in liver disease:Pathophysiological basis for therapy[J].Journal of Hepatology, 2020, 72(3):558-577.
[18] 蒋贤哲, 张博彦, 罗海玲, 等.肠肝轴在动物营养代谢和免疫中的作用[J].生物技术通报, 2022, 38(7):128-135. JIANG X Z, ZHANG B Y, LUO H L, et al.Role of gut-liver axis in animal nutritional metabolism and immunity[J].Biotechnology Bulletin, 2022, 38(7):128-135.(in Chinese)
[19] BUDDEN K F, GELLATLY S L, WOOD D L, et al.Emerging pathogenic links between microbiota and the gut-lung axis[J].Nature Reviews Microbiology, 2017, 15(1):55-63.
[20] LAHIRI S, KIM H, GARCIA-PEREZ I, et al.The gut microbiota influences skeletal muscle mass and function in mice[J].Science Translational Medicine, 2019, 11(502):eaan5662.
[21] QI R L, SUN J, QIU X Y, et al.The intestinal microbiota contributes to the growth and physiological state of muscle tissue in piglets[J].Scientific Reports, 2021, 11(1):11237.
[22] NAY K, JOLLET M, GOUSTARD B, et al.Gut bacteria are critical for optimal muscle function:A potential link with glucose homeostasis[J].American Journal of Physiology-Endocrinology and Metabolism, 2019, 317(1):E158-E171.
[23] CHEN Y M, WEI L, CHIU Y S, et al.Lactobacillus plantarum TWK10 supplementation improves exercise performance and increases muscle mass in mice[J].Nutrients, 2016, 8(4):205.
[24] NI Y, YANG X, ZHENG L, et al.Lactobacillus and Bifidobacterium improves physiological function and cognitive ability in aged mice by the regulation of gut microbiota[J].Molecular Nutrition and Food Research, 2019, 63(22):e1900603.
[25] CHEN L H, HUANG S Y, HUANG K C, et al.Lactobacillus paracasei PS23 decelerated age-related muscle loss by ensuring mitochondrial function in SAMP8 mice[J].Aging, 2019, 11(2):756-770.
[26] FIELDING R A, REEVES A R, JASUJA R, et al.Muscle strength is increased in mice that are colonized with microbiota from high-functioning older adults[J].Experimental Gerontology, 2019, 127:110722.
[27] KANG L, LI P, WANG D, et al.Alterations in intestinal microbiota diversity, composition, and function in patients with sarcopenia[J].Scientific Reports, 2021, 11(1):4628.
[28] TICINESI A, LAURETANI F, MILANI C, et al.Aging gut microbiota at the cross-road between nutrition, physical frailty, and sarcopenia:Is there a gut-muscle axis?[J].Nutrients, 2017, 9(12):1303.
[29] GROSICKI G J, FIELDING R A, LUSTGARTEN M S.Gut microbiota contribute to age-related changes in skeletal muscle size, composition, and function:Biological basis for a gut-muscle axis[J].Calcified Tissue International, 2018, 102(4):433-442.
[30] HAWLEY J A.Microbiota and muscle highway-two way traffic[J].Nature Reviews Endocrinology, 2020, 16(2):71-72.
[31] MASLOWSKI K M, VIEIRA A T, NG A, et al.Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43[J].Nature, 2009, 461(7268):1282-1286.
[32] MACFARLANE S, MACFARLANE G T.Regulation of short-chain fatty acid production[J].Proceedings of the Nutrition Society, 2003, 62(1):67-72.
[33] TOPPING DL, CLIFTON PM.Short-chain fatty acids and human colonic function:Roles of resistant starch and nonstarch polysaccharides[J].Physiological Reviews, 2001, 81(3):1031-1064.
[34] MILLER T L, WOLIN M J.Pathways of acetate, propionate, and butyrate formation by the human fecal microbial flora[J].Applied and Environmental Microbiology, 1996, 62(5):1589-1592.
[35] RAGSDALE S W, PIERCE E.Acetogenesis and the wood-ljungdahl pathway of CO₂ fixation[J].Biochimica et Biophysica Acta, 2008, 1784(12):1873-1898.
[36] REICHARDT N, DUNCAN S H, YOUNG P, et al.Phylogenetic distribution of three pathways for propionate production within the human gut microbiota[J].ISME Journal, 2014, 8(6):1323-1335.
[37] MACY J M, LJUNGDAHL L G, GOTTSCHALK G.Pathway of succinate and propionate formation in Bacteroides fragilis[J].Journal of Bacteriology, 1978, 134(1):84-91.
[38] SAXENA R K, ANAND P, SARAN S, et al.Microbial production and applications of 1, 2-propanediol[J].Indian Journal of Microbiology, 2010, 50(1):2-11.
[39] DUNCAN S H, LOUIS P, FLINT H J.Lactate-utilizing bacteria, isolated from human feces, that produce butyrate as a major fermentation product[J].Applied and Environmental Microbiology, 2004, 70(10):5810-5817.
[40] LOUIS P, FLINT H J.Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine[J].FEMS Microbiology Letters, 2009, 294(1):1-8.
[41] RAUF A, KHALIL A A, RAHMAN U U, et al.Recent advances in the therapeutic application of short-chain fatty acids (SCFAs):An updated review[J].Critical Reviews in Food Science and Nutrition, 2022, 62(22):6034-6054.
[42] GIRON M, THOMAS M, DARDEVET D, et al.Gut microbes and muscle function:Can probiotics make our muscles stronger?[J].Journal of Cachexia, Sarcopenia and Muscle, 2022, 13(3):1460-1476.
[43] WALSH M E, BHATTACHARYA A, SATARANATARAJAN K, et al.The histone deacetylase inhibitor butyrate improves metabolism and reduces muscle atrophy during aging[J].Aging Cell, 2015, 14(6):957-970.
[44] HAN D S, WU W K, LIU P Y, et al.Differences in the gut microbiome and reduced fecal butyrate in elders with low skeletal muscle mass[J].Clinical Nutrition, 2022, 41(7):1491-1500.
[45] TANG G, DU Y, GUAN H, et al.Butyrate ameliorates skeletal muscle atrophy in diabetic nephropathy by enhancing gut barrier function and FFA2-mediated PI3K/Akt/mTOR signals[J].British Journal of Pharmacology, 2022, 179(1):159-178.
[46] LV W Q, LIN X, SHEN H, et al.Human gut microbiome impacts skeletal muscle mass via gut microbial synthesis of the short-chain fatty acid butyrate among healthy menopausal women[J].Journal of Cachexia, Sarcopenia and Muscle, 2021, 12(6):1860-1870.
[47] JØRGENSEN H, LARSEN T, ZHAO X Q, et al.The energy value of short-chain fatty acids infused into the caecum of pigs[J].British Journal of Nutrition, 1997, 77(5):745-756.
[48] KONDO T, KISHI M, FUSHIMI T, et al.Acetic acid upregulates the expression of genes for fatty acid oxidation enzymes in liver to suppress body fat accumulation[J].Journal of Agricultural and Food Chemistry, 2009, 57(13):5982-5986.
[49] HENAGAN T M, STEFANSKA B, FANG Z, et al.Sodium butyrate epigenetically modulates high-fat diet-induced skeletal muscle mitochondrial adaptation, obesity and insulin resistance through nucleosome positioning[J].British Journal of Pharmacology, 2015, 172(11):2782-2798.
[50] 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].Nature Medicine, 2019, 25(7):1104-1109.
[51] ALLEN J M, MAILING L J, NIEMIRO G M, et al.Exercise alters gut microbiota composition and function in lean and obese humans[J].Medicine and Science in Sports and Exercise, 2018, 50(4):747-757.
[52] OKAMOTO T, MORINO K, UGI S, et al.Microbiome potentiates endurance exercise through intestinal acetate production[J].American Journal Physiology Endocrinology and Metablism, 2019, 316(5):E956-E966.
[53] GAO Z, YIN J, ZHANG J, et al.Butyrate improves insulin sensitivity and increases energy expenditure in mice[J].Diabetes, 2009, 58(7):1509-1517.
[54] FUSHIMI T, TAYAMA K, FUKAYA M, et al.Acetic acid feeding enhances glycogen repletion in liver and skeletal muscle of rats[J].Journal of Nutrition, 2001, 131(7):1973-1977.
[55] FUSHIMI T, SATO Y.Effect of acetic acid feeding on the circadian changes in glycogen and metabolites of glucose and lipid in liver and skeletal muscle of rats[J].British Journal of Nutrition, 2005, 94(5):714-719.
[56] SCHIAFFINO S, REGGIANI C.Fiber types in mammalian skeletal muscles[J].Physiological Reviews, 2011, 91(4):1447-1531.
[57] 周敏, 汪凯歌, 张濂, 等.微生物-肠-肌轴调节骨骼肌代谢和功能的研究进展[J].畜牧兽医学报, 2022, 53(9):2845-2857. ZHOU M, WANG K G, ZHANG L, et al.Advances in microbiota-gut-muscle axis regulating skeletal muscle metabolism and function[J].Acta Veterinaria et Zootechnica Sinica, 2022, 53(9):2845-2857.(in Chinese)
[58] MARUTA H, ABE R, YAMASHITA H.Effect of long-term supplementation with acetic acid on the skeletal muscle of aging sprague dawley rats[J].International Journal of Molecular Sciences, 2022, 23(9):4691.
[59] PAN J H, KIM J H, KIM H M, et al.Acetic acid enhances endurance capacity of exercise-trained mice by increasing skeletal muscle oxidative properties[J].Bioscience, Biotechnology, and Biochemistry, 2015, 79(9):1535-1541.
[60] HONG J, JIA Y, PAN S, et al.Butyrate alleviates high fat diet-induced obesity through activation of adiponectin-mediated pathway and stimulation of mitochondrial function in the skeletal muscle of mice[J].Oncotarget, 2016, 7(35):56071-56082.
[61] VAN DER HEE B, WELLS J M.Microbial regulation of host physiology by short-chain fatty acids[J].Trends in Microbiology, 2021, 29(8):700-712.
[62] HAN J H, KIM I S, JUNG S H, et al.The effects of propionate and valerate on insulin responsiveness for glucose uptake in 3T3-L1 adipocytes and C2C12 myotubes via G protein-coupled receptor 41[J].PLoS One, 2014, 9(4):e95268.
[63] WEIS W I, KOBILKA B K.The Molecular basis of G protein-coupled receptor activation[J].Annual Review of Biochemistry, 2018, 87:897-919.
[64] MARUTA H, YAMASHITA H.Acetic acid stimulates G-protein-coupled receptor GPR43 and induces intracellular calcium influx in L6 myotube cells[J].PLoS One, 2020, 15(9):e0239428.
[65] SHEN Y, WEI W, ZHOU D X.Histone acetylation enzymes coordinate metabolism and gene expression[J].Trends in Plant Science, 2015, 20(10):614-621.
[66] RENZINI A, D'ONGHIA M, COLETTI D, et al.Histone deacetylases as modulators of the crosstalk between skeletal muscle and other organs[J].Frontiers in Physiology, 2022, 13:706003.
[67] DAVIE J R.Inhibition of histone deacetylase activity by butyrate[J].Journal of Nutrition, 2003, 133(7 Suppl):2485S-2493S.
[68] CHRIETT S, ZERZAIHI O, VIDAL H, et al.The histone deacetylase inhibitor sodium butyrate improves insulin signalling in palmitate-induced insulin resistance in L6 rat muscle cells through epigenetically-mediated up-regulation of Irs1[J].Molecular and Cellular Endocrinology, 2017, 439:224-232.
[69] MIHAYLOVA M M, SHAW R J.The AMPK signalling pathway coordinates cell growth, autophagy and metabolism[J].Nature Cell Biology, 2011, 13(9):1016-1023.
[70] 赵俊星, 岳万福.表观遗传调控骨骼肌发育的研究进展[J].中国农业科技导报, 2014, 16(3):42-47. ZHAO J X, YUE W F.Control of skeletal muscle myogenesis by epigenetic regulations[J].Journal of Agricultural Science and Technology, 2014, 16(3):42-47.(in Chinese)
[71] DINGER M E, PANG K C, MERCER T R, et al.Differentiating protein-coding and noncoding RNA:Challenges and ambiguities[J].PLoS Computational Biology, 2008, 4(11):e1000176.
[72] CESANA M, CACCHIARELLI D, LEGNINI I, et al.A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA[J].Cell, 2011, 147(2):358-369.
[73] HAYES J, PERUZZI P P, LAWLER S.microRNAs in cancer:Biomarkers, functions and therapy[J].Trends in Molecular Medicine, 2014, 20(8):460-469.
[74] OUYANG H, CHEN X, WANG Z, et al.Circular RNAs are abundant and dynamically expressed during embryonic muscle development in chickens[J].DNA Research, 2018, 25(1):71-86.
[75] WU H, ZHANG Y.Reversing DNA methylation:Mechanisms, genomics, and biological functions[J].Cell, 2014, 156(1-2):45-68.
[76] YANG Y, FAN X, YAN J, et al.A comprehensive epigenome atlas reveals DNA methylation regulating skeletal muscle development[J].Nucleic Acids Research, 2021, 49(3):1313-1329.
[77] MBADHI M N, TANG J M, ZHANG J X.Histone lysine methylation and long non-coding RNA:The new target players in skeletal muscle cell regeneration[J].Frontiers in Cell and Developmental Biology, 2021, 9:759237.
[78] QI X, HU M, XIANG Y, et al.lncRNAs are regulated by chromatin states and affect the skeletal muscle cell differentiation[J].Cell Proliferation, 2020, 53(9):e12879.
[79] KRAUTKRAMER K A, KREZNAR J H, ROMANO K A, et al.Diet-microbiota interactions mediate global epigenetic programming in multiple host tissues[J].Molecular Cell, 2016, 64(5):982-992.
[80] 皮宇, 高侃, 朱伟云.动物宿主——肠道微生物代谢轴研究进展[J].微生物学报, 2017, 57(2):161-169. PI Y, GAO K, ZHU W Y.Advances in host-Microbe metabolic axis[J].Acta Microbiologica Sinica, 2017, 57(2):161-169.(in Chinese)