实验动物肠道菌群特征分析及性别差异性的研究进展

doi:10.12300/j.issn.1674-5817.2024.124

摘要/Abstract

摘要：

实验动物是生命科学研究的基石，其作为人类生理、病理及疾病治疗的替代模型，在基础研究、药物开发和转化医学中具有不可替代的作用。肠道菌群是由细菌、真菌、病毒以及单细胞生物等构成的复杂微生物类群，其定植于宿主肠道内，与宿主正常生理代谢功能的维持和生命健康密切相关。有研究表明，肠道菌群组成结构的紊乱可引发肥胖、糖尿病、高血压、炎症性肠病以及阿尔茨海默病等多种疾病。因此，针对实验动物开展肠道菌群的特征性分析不仅有助于提升实验结果的可靠性，而且将有助于动物实验结果的转化应用。性别差异是生物学研究中的重要变量，其对实验动物的生理功能、代谢特征及肠道菌群组成均具有显著影响。然而，研究人员在较多生物学研究中存在明显的实验动物性别偏好性，这极大地限制了研究结果的普适性。本文对小鼠、大鼠、豚鼠、仓鼠、兔、犬、猫、非人灵长类动物、小型猪和鸡这10种生命科学实验中常用的实验动物的肠道菌群组成结构特征进行归纳总结，并对部分实验动物肠道菌群的性别差异进行分析。此外，针对实验动物与人类肠道菌群的对比分析，还为基于实验动物的比较医学研究提供了新视角。综上，相关研究成果在加深科研人员对不同实验动物肠道菌群特征及其性别差异性认识的同时，也将为科学研究中实验动物的选用、性别特异性疾病动物模型的构建和结果分析提供指导和借鉴。

关键词: 肠道菌群, 实验动物, 性别差异

Abstract:

Laboratory animals serve as the cornerstone in life science research, acting as surrogate models for human physiology, pathology, and disease treatment. They play an irreplaceable role in basic research, drug development, and translational medicine. Gut microbiota, a complex microbial community comprising bacteria, fungi, viruses, and unicellular organisms, colonizes the host's intestinal tract and is closely associated with the maintenance of normal physiological metabolism and overall health. Studies have shown that dysbiosis of the gut microbiota can lead to various diseases, including obesity, diabetes, hypertension, inflammatory bowel disease, and Alzheimer's disease. Therefore, conducting characteristic analyses of the gut microbial composition of laboratory animals can not only enhance the reliability of experimental outcomes but also facilitate their translational application. Sex differences represent a critical variable in biological research, significantly influencing the physiological functions, metabolic traits, and gut microbial composition of laboratory animals. However, a pronounced sex bias has been widely observed in many biological studies, thereby limiting the generalizability of results. This study focused on ten commonly used laboratory animals in life sciences, including mice, rats, guinea pigs, hamsters, rabbits, dogs, cats, non-human primates, miniature pigs, and chickens. Their gut microbial composition was summarized and related sex-specific differences of certain species were analyzed. Furthermore, by comparing the gut microbiota of laboratory animals with that of humans, this study offers novel perspectives for comparative medical research. In summary, this study not only deepens researchers' understanding of gut microbiota characteristics and sex-dependent variations across laboratory animal species but also provides practical guidance for selecting appropriate laboratory animals, constructing sex-specific disease models, and interpreting experimental results in scientific studies.

Key words: Gut microbiota, Laboratory animals, Sex difference

中图分类号:

R-332

沈黄奕,黄宇飞,杨云鹏. 实验动物肠道菌群特征分析及性别差异性的研究进展[J]. 实验动物与比较医学, 2025, 45(3): 349-359. DOI: 10.12300/j.issn.1674-5817.2024.124.

SHEN Huangyi,HUANG Yufei,YANG Yunpeng. Research Progress on Characteristics Analysis of Gut Microbiota and Its Sex Differences in Laboratory Animals[J]. Laboratory Animal and Comparative Medicine, 2025, 45(3): 349-359. DOI: 10.12300/j.issn.1674-5817.2024.124.

参考文献 59

[1]	IKEDA E, YAMAGUCHI M, KAWABATA S. Gut microbiota-mediated alleviation of dextran sulfate sodium-induced colitis in mice[J]. Gastro Hep Adv, 2024, 3(4):461-470. DOI:10.1016/j.gastha.2024.01.016 .
[2]	MOHAMMADHASANI K, VAHEDI FARD M, MOTTAGHI MOGHADDAM SHAHRI A, et al. Polyphenols improve non-alcoholic fatty liver disease via gut microbiota: a comprehensive review[J]. Food Sci Nutr, 2024, 12(8):5341-5356. DOI:10.1002/fsn3.4178 .
[3]	ZHAO J Q, ZHAO C Y, XUN T R, et al. Huang Gan formula alleviates systemic inflammation and uremia in adenine-induced chronic kidney disease rats may associate with modification of gut microbiota and colonic microenvironment[J]. Drug Des Devel Ther, 2024, 18:13-28. DOI:10.2147/DDDT.S421446 .
[4]	FEI S F, HOU C, JIA F. Effects of salidroside on atherosclerosis: potential contribution of gut microbiota[J]. Front Pharmacol, 2024, 15:1400981. DOI:10.3389/fphar. 2024. 1400981 .
[5]	POURAHMAD R, SALEKI K, ZARE GHOLINEJAD M, et al. Exploring the effect of gut microbiome on Alzheimer's disease[J]. Biochem Biophys Rep, 2024, 39:101776. DOI:10.1016/j.bbrep.2024.101776 .
[6]	LI Y Z, ZHANG R Z, FU C B, et al. Intratumoral microbiome promotes liver metastasis and dampens adjuvant imatinib treatment in gastrointestinal stromal tumor[J]. Cancer Lett, 2024, 601:217149. DOI:10.1016/j.canlet.2024.217149 .
[7]	BEERY A K, ZUCKER I. Sex bias in neuroscience and biomedical research[J]. Neurosci Biobehav Rev, 2011, 35(3):565-572. DOI:10.1016/j.neubiorev.2010.07.002 .
[8]	FALONY G, JOOSSENS M, VIEIRA-SILVA S, et al. Population-level analysis of gut microbiome variation[J]. Science, 2016, 352(6285):560-564. DOI:10.1126/science.aad3503 .
[9]	黄树武, 闵凡贵, 王静, 等. 常用小鼠、大鼠肠道菌群比较研究[J]. 中国实验动物学报, 2021, 29(6):777-784. DOI:10.3969/j.issn.1005-4847.2021.06.009 .
	HUANG S W, MIN F G, WANG J, et al. Comparative study of intestinal flora in common mice and rats[J]. Acta Lab Anim Sci Sin, 2021, 29(6):777-784. DOI:10.3969/j.issn.1005-4847.2021.06.009 .
[10]	LIANG X, BUSHMAN F D, FITZGERALD G A. Rhythmicity of the intestinal microbiota is regulated by gender and the host circadian clock[J]. Proc Natl Acad Sci USA, 2015, 112(33):10479-10484. DOI:10.1073/pnas.1501305112 .
[11]	CHEN S H, WANG C B, ZOU X, et al. Multi-omics insights implicate the remodeling of the intestinal structure and microbiome in aging[J]. Front Genet, 2024, 15:1450064. DOI:10.3389/fgene.2024.1450064 .
[12]	WU Y, PENG X X, LI X Y, et al. Sex hormones influence the intestinal microbiota composition in mice[J]. Front Microbiol, 2022, 13:964847. DOI:10.3389/fmicb.2022.964847 .
[13]	MAITE C B, ROY M, EMILIE V. The effect of sex-specific differences on IL-10^-/- mouse colitis phenotype and microbiota[J]. Int J Mol Sci, 2023, 24(12):10364. DOI:10.3390/ijms241210364 .
[14]	ELDERMAN M, HUGENHOLTZ F, BELZER C, et al. Sex and strain dependent differences in mucosal immunology and microbiota composition in mice[J]. Biol Sex Differ, 2018, 9(1):26. DOI:10.1186/s13293-018-0186-6 .
[15]	WANG L, TU Y X, CHEN L, et al. Male-biased gut microbiome and metabolites aggravate colorectal cancer development[J]. Adv Sci, 2023, 10(25): e2206238. DOI:10.1002/advs. 202206238 .
[16]	ZHU Q, QI N, SHEN L, et al. Sexual dimorphism in lipid metabolism and gut microbiota in mice fed a high-fat diet[J]. Nutrients, 2023, 15(9):2175. DOI:10.3390/nu15092175 .
[17]	SHI Y, WEI L, XING L, et al. Sex difference is a determinant of gut microbes and their metabolites SCFAs/MCFAs in high fat diet fed rats[J]. Curr Microbiol, 2022, 79(11):347. DOI:10.1007/s00284-022-03025-x .
[18]	CHANG Y M, KANG Y R, LEE Y G, et al. Sex differences in colonic gene expression and fecal microbiota composition in a mouse model of obesity-associated colorectal cancer[J]. Sci Rep, 2024, 14(1):3576. DOI:10.1038/s41598-024-53861-z .
[19]	EFRON P A, DARDEN D B, LI E C, et al. Sex differences associate with late microbiome alterations after murine surgical sepsis[J]. J Trauma Acute Care Surg, 2022, 93(2):137-146. DOI:10.1097/TA.0000000000003599 .
[20]	CHEN T L, YOU Y J, XIE G X, et al. Strategy for an association study of the intestinal microbiome and brain metabolome across the lifespan of rats[J]. Anal Chem, 2018, 90(4):2475-2483. DOI:10.1021/acs.analchem.7b02859 .
[21]	DUAN X Q, XIE X, ZHU C, et al. Sex difference of effect of Sophora flavescens on gut microbiota in rats[J]. Evid Based Complement Alternat Med, 2022, 2022:4552904. DOI:10.1155/2022/4552904 .
[22]	HILDEBRAND F, EBERSBACH T, NIELSEN H B, et al. A comparative analysis of the intestinal metagenomes present in guinea pigs (Cavia porcellus) and humans (Homo sapiens)[J]. BMC Genomics, 2012, 13:514. DOI:10.1186/1471-2164-13-514 .
[23]	FRIAS H, MURGA VALDERRAMA N L, FLORES DURAND G J, et al. Comparative analysis of fasting effects on the cecum microbiome in three guinea pig breeds: Andina, Inti, and Peru[J]. Front Microbiol, 2023, 14:1283738. DOI:10.3389/fmicb. 2023.1283738 .
[24]	AL K, SARR O, DUNLOP K, et al. Impact of birth weight and postnatal diet on the gut microbiota of young adult guinea pigs[J]. PeerJ, 2017, 5: e2840. DOI:10.7717/peerj.2840 .
[25]	WU Y J, FAN H, FENG Y L, et al. Unveiling the gut microbiota and metabolite profiles in guinea pigs with form deprivation myopia through 16S rRNA gene sequencing and untargeted metabolomics[J]. Heliyon, 2024, 10(9): e30491. DOI:10.1016/j.heliyon.2024.e30491 .
[26]	SYLVIA K E, JEWELL C P, RENDON N M, et al. Sex-specific modulation of the gut microbiome and behavior in Siberian hamsters[J]. Brain Behav Immun, 2017, 60:51-62. DOI:10.1016/j.bbi.2016.10.023 .
[27]	SENCIO V, MACHELART A, ROBIL C, et al. Alteration of the gut microbiota following SARS-CoV-2 infection correlates with disease severity in hamsters[J]. Gut Microbes, 2022, 14(1):2018900. DOI:10.1080/19490976.2021.2018900 .
[28]	FAN C, ZHENG Y J, XUE H L, et al. Different gut microbial types were found in captive striped hamsters[J]. PeerJ, 2023, 11: e16365. DOI:10.7717/peerj.16365 .
[29]	杨睿, 黎春秀, 付利芝, 等. 不同日龄家兔肠道微生物群落结构[J]. 中国兽医学报, 2017, 37(9):1693-1698. DOI: 10.16303/j.cnki.1005-4545.2017.09.10 .
	YANG R, LI C X, FU L Z, et al. Intestinal microbial community structure changes and analysis in the growth of weaning young rabbits[J]. Chin J Vet Sci, 2017, 37(9):1693-1698. DOI: 10.16303/j.cnki.1005-4545.2017.09.10 .
[30]	FU C, MA Y, XIA S Q, et al. Study on changes in gut microbiota and microbiability in rabbits at different developmental stages[J]. Animals, 2024, 14(12):1741. DOI:10.3390/ani14121741 .
[31]	ABDEL-KAFY E M, KAMEL K I, SEVERGNINI M, et al. Diversity and co-occurrence pattern analysis of cecal and jejunal microbiota in two rabbit breeds[J]. Animals, 2023, 13(14):2294. DOI:10.3390/ani13142294 .
[32]	LI K Y, ABDELSATTAR M M, GU M M, et al. The effects of temperature and humidity index on growth performance, colon microbiota, and serum metabolome of Ira rabbits[J]. Animals, 2023, 13(12):1971. DOI:10.3390/ani13121971 .
[33]	YOU I, KIM M J. Comparison of gut microbiota of 96 healthy dogs by individual traits: breed, age, and body condition score[J]. Animals, 2021, 11(8):2432. DOI:10.3390/ani11082432 .
[34]	FERNÁNDEZ-PINTEÑO A, PILLA R, MANTECA X, et al. Age-associated changes in intestinal health biomarkers in dogs[J]. Front Vet Sci, 2023, 10:1213287. DOI:10.3389/fvets.2023. 1213287 .
[35]	HU Q M, CHENG L G, CAO X T, et al. Comparative analysis of gut microbiota of Chinese Kunming dog, German Shepherd dog, and Belgian Malinois dog[J]. J Vet Sci, 2024, 25(6): e85. DOI:10.4142/jvs.24181 .
[36]	ROJAS C A, PARK B, SCARSELLA E, et al. Species-level characterization of the core microbiome in healthy dogs using full-length 16S rRNA gene sequencing[J]. Front Vet Sci, 2024, 11:1405470. DOI:10.3389/fvets.2024.1405470 .
[37]	LANGON X. Validation of method for faecal sampling in cats and dogs for faecal microbiome analysis[J]. BMC Vet Res, 2023, 19(1):274. DOI:10.1186/s12917-023-03842-7 .
[38]	KILBURN-KAPPELER L R, DOERKSEN T, LU A, et al. Evaluation of corn fermented protein on the fecal microbiome of cats[J]. J Anim Sci, 2024, 102: skae268. DOI:10.1093/jas/skae268 .
[39]	DRUT A, MKAOUAR H, KRIAA A, et al. Gut microbiota in cats with inflammatory bowel disease and low-grade intestinal T-cell lymphoma[J]. Front Microbiol, 2024, 15:1346639. DOI:10.3389/fmicb.2024.1346639 .
[40]	YANG Y P, LU Y, YU P J, et al. Characterization of gut microbial alterations in cynomolgus macaques during growth and maturation[J]. Zool Res, 2022, 43(2):176-179. DOI:10.24272/j.issn.2095-8137.2021.304 .
[41]	YANG Y P, XU N, YAO L L, et al. Characterizing bacterial and fungal communities along the longitudinal axis of the intestine in Cynomolgus monkeys[J]. Microbiol Spectr, 2023, 11(6): e0199623. DOI:10.1128/spectrum.01996-23 .
[42]	YANG Y P, YU M L, LU Y, et al. Characterizing the rhythmic oscillations of gut bacterial and fungal communities and their rhythmic interactions in male Cynomolgus monkeys[J]. Microbiol Spectr, 2024, 12(11): e0072224. DOI:10.1128/spectrum.00722-24 .
[43]	LI Y H, CHEN T, LI Y B, et al. Gut microbiota are associated with sex and age of host: Evidence from semi-provisioned Rhesus macaques in southwest Guangxi, China[J]. Ecol Evol, 2021, 11(12):8096-8122. DOI:10.1002/ece3.7643 .
[44]	田威龙, 司景磊, 刘笑笑, 等. 高脂高糖饮食对小型猪肠道微生物的影响[J]. 畜牧兽医学报, 2022, 53(4):1143-1153. DOI: 10.11843/j.issn.0366-6964.2022.04.014 .
	TIAN W L, SI J L, LIU X X, et al. Effects of high-fat and high-sugar diet on intestinal microbiota in mini-pigs[J]. Acta Vet Zootechnica Sin, 2022, 53(4):1143-1153. DOI: 10.11843/j.issn.0366-6964.2022.04.014 .
[45]	沈利叶, 潘永明, 徐雁云, 等. 高脂高糖饮食诱导五指山小型猪动脉粥样硬化模型肠道菌群的变化[J]. 中国实验动物学报, 2022, 30(3):299-308. DOI: 10.3969/j.issn.1005-4847.2022.03.001 .
	SHEN L Y, PAN Y M, XU Y Y, et al. Changes in intestinal flora in a Wuzhishan minipig atherosclerosis model induced by high-fat and high-sugar diet[J]. Acta Lab Anim Sci Sin, 2022, 30(3):299-308. DOI: 10.3969/j.issn.1005-4847.2022.03.001 .
[46]	JIANG X, CHEN B Z, GU D S, et al. Gut microbial compositions in four age groups of Tibetan minipigs[J]. Pol J Microbiol, 2018, 67(3):383-388. DOI:10.21307/pjm-2018-038 .
[47]	YOSI F, LERCH F, VÖTTERL J C, et al. Lactation-related dynamics of bacterial and fungal microbiomes in feces of sows and gut colonization in suckling and newly weaned piglets[J]. J Anim Sci, 2024, 102: skae321. DOI:10.1093/jas/skae321 .
[48]	WANG C, WEI S Y, CHEN N N, et al. Characteristics of gut microbiota in pigs with different breeds, growth periods and genders[J]. Microb Biotechnol, 2022, 15(3):793-804. DOI:10.1111/1751-7915.13755 .
[49]	YANG X, TAI Y R, MA Y H, et al. Cecum microbiome and metabolism characteristics of Silky Fowl and White Leghorn chicken in late laying stages[J]. Front Microbiol, 2022, 13:984654. DOI:10.3389/fmicb.2022.984654 .
[50]	WANG X Y, MENG J X, REN W X, et al. Amplicon-based metagenomic association analysis of gut microbiota in relation to egg-laying period and breeds of hens[J]. BMC Microbiol, 2023, 23(1):138. DOI:10.1186/s12866-023-02857-2 .
[51]	WANG Z J, LI S R, DING X Y, et al. Study on the differences in fecal metabolites and microbial diversity of Jiangshan black-bone chickens with different earlobe colors[J]. Animals, 2024, 14(21):3060. DOI:10.3390/ani14213060 .
[52]	WANG Y, YUAN Z J. Gut microbiota in two chickens' breeds: Characteristics and dynamic changes[J]. Microb Pathog, 2024, 197:107101. DOI:10.1016/j.micpath.2024.107101 .
[53]	BÖSWALD L F, POPPER B, MATZEK D, et al. Characterization of the gastrointestinal microbiome of the Syrian Hamster (Mesocricetus auratus) and comparison to data from mice[J]. FEBS Open Bio, 2024, 14(10):1701-1717. DOI:10.1002/2211-5463.13869 .
[54]	CROWLEY E J, KING J M, WILKINSON T, et al. Comparison of the microbial population in rabbits and guinea pigs by next generation sequencing[J]. PLoS One, 2017, 12(2): e0165779. DOI:10.1371/journal.pone.0165779 .
[55]	YANG Y P, ZHANG Z Y, WANG Y Q, et al. Colonization of microbiota derived from Macaca fascicularis, Bama miniature pigs, beagle dogs, and C57BL/6J mice alleviates DSS-induced colitis in germ-free mice[J]. Microbiol Spectr, 2024, 12(8): e0038824. DOI:10.1128/spectrum.00388-24 .
[56]	BAI X, ZHONG H, CUI X, et al. Metagenomic profiling uncovers microbiota and antibiotic resistance patterns across human, chicken, pig fecal, and soil environments[J]. Sci Total Environ, 2024, 947:174734. DOI:10.1016/j.scitotenv. 2024.174734 .
[57]	BERETTA S, APPARICIO M, TONIOLLO G H, et al. The importance of the intestinal microbiota in humans and dogs in the neonatal period[J]. Anim Reprod, 2023, 20(3): e20230082. DOI:10.1590/1984-3143-AR2023-0082 .
[58]	ITO Y, NAGASAWA M, KOYAMA K, et al. Comparative analysis based on shared amplicon sequence variants reveals that cohabitation influences gut microbiota sharing between humans and dogs[J]. Front Vet Sci, 2024, 11:1417461. DOI:10.3389/fvets.2024.1417461 .
[59]	DU G K, HUANG H R, ZHU Q W, et al. Effects of cat ownership on the gut microbiota of owners[J]. PLoS One, 2021, 16(6): e0253133. DOI:10.1371/journal.pone.0253133 .