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Abstract: The gut microbiota is an indispensable symbiotic entity within the human holobiont, serving as a critical regulator of host lipid metabolism homeostasis. Therefore, it has emerged as a central subject of research in the pathophysiology of metabolic disorders. This microbial consortium orchestrates key aspects of host lipid dynamics—including absorption, metabolism, and storage—through multifaceted mechanisms such as the enzymatic processing of dietary polysaccharides, the facilitation of long-chain fatty acid uptake by intestinal epithelial cells (IECs), and the bidirectional modulation of adipose tissue functionality. Mounting evidence underscores that gut microbiota-derived metabolites not only directly mediate canonical lipid metabolic pathways but also interface with host immune pathways, epigenetic machinery, and circadian regulatory systems, thereby establishing an intricate crosstalk that coordinates systemic metabolic outputs. Perturbations in microbial composition (dysbiosis) drive pathological disruptions to lipid homeostasis, serving as a pathogenic driver for conditions such as obesity, hyperlipidemia, and non-alcoholic fatty liver disease (NAFLD). This review systematically examines the emerging mechanistic insights into the gut microbiota-mediated regulation of intestinal lipid metabolism, while it elucidates its translational implications for understanding metabolic disease pathogenesis and developing targeted therapies.

肠道微生物群与肠道脂质代谢间的相互作用：机制和影响

[1]AbumradNA, CabodevillaAG, SamovskiD, et al., 2021. Endothelial cell receptors in tissue lipid uptake and metabolism. Circ Res, 128(3):433-450.

[2]AgusA, ClémentK, SokolH, 2021. Gut microbiota-derived metabolites as central regulators in metabolic disorders. Gut, 70(6):1174-1182.

[3]AhmedH, LeyrolleQ, KoistinenV, et al., 2022. Microbiota-derived metabolites as drivers of gut‒brain communication. Gut Microbes, 14(1):2102878.

[4]Arnoriaga-RodríguezM, Mayneris-PerxachsJ, BurokasA, et al., 2020. Obesity impairs short-term and working memory through gut microbial metabolism of aromatic amino acids. Cell Metab, 32(4):548-560.e7.

[5]AronssonL, HuangY, PariniP, et al., 2010. Decreased fat storage by Lactobacillus paracasei is associated with increased levels of angiopoietin-like 4 protein (ANGPTL4). PLoS ONE, 5(9):e13087.

[6]ArpaiaN, CampbellC, FanXY, et al., 2013. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature, 504(7480):451-455.

[7]BäckhedF, DingH, WangT, et al., 2004. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci USA, 101(44):15718-15723.

[8]BäckhedF, CrawfordPA, O'DonnellD, et al., 2007a. Postnatal lymphatic partitioning from the blood vasculature in the small intestine requires fasting-induced adipose factor. Proc Natl Acad Sci USA, 104(2):606-611.

[9]BäckhedF, ManchesterJK, SemenkovichCF, et al., 2007b. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci USA, 104(3):979-984.

[10]BrownEM, ClardyJ, XavierRJ, 2023. Gut microbiome lipid metabolism and its impact on host physiology. Cell Host Microbe, 31(2):173-186.

[11]CareyRA, MontagD, 2021. Exploring the relationship between gut microbiota and exercise: short-chain fatty acids and their role in metabolism. BMJ Open Sport Exerc Med, 7(2):e000930.

[12]ChambersES, PrestonT, FrostG, et al., 2018. Role of gut microbiota-generated short-chain fatty acids in metabolic and cardiovascular health. Curr Nutr Rep, 7(4):198-206.

[13]Dávalos-SalasM, MontgomeryMK, ReehorstCM, et al., 2019. Deletion of intestinal Hdac3 remodels the lipidome of enterocytes and protects mice from diet-induced obesity. Nat Commun, 10:5291.

[14]DeehanEC, MocanuV, MadsenKL, 2024. Effects of dietary fibre on metabolic health and obesity. Nat Rev Gastroenterol Hepatol, 21(5):301-318.

[15]DepommierC, EverardA, DruartC, et al., 2021. Serum metabolite profiling yields insights into health promoting effect of A. muciniphila in human volunteers with a metabolic syndrome. Gut Microbes, 13(1):1994270.

[16]DoddD, SpitzerMH, van TreurenW, et al., 2017. A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites. Nature, 551(7682):648-652.

[17]DuanCH, WuJH, WangZ, et al., 2023. Fucose promotes intestinal stem cell-mediated intestinal epithelial development through promoting Akkermansia-related propanoate metabolism. Gut Microbes, 15(1):2233149.

[18]DuschaA, GiseviusB, HirschbergS, et al., 2020. Propionic acid shapes the multiple sclerosis disease course by an immunomodulatory mechanism. Cell, 180(6):1067-1080.e16.

[19]EshlemanEM, RiceT, PotterC, et al., 2024. Microbiota-derived butyrate restricts tuft cell differentiation via histone deacetylase 3 to modulate intestinal type 2 immunity. Immunity, 57(2):319-332.e6.

[20]EverardA, BelzerC, GeurtsL, et al., 2013. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci USA, 110(22):9066-9071.

[21]FanY, PedersenO, 2021. Gut microbiota in human metabolic health and disease. Nat Rev Microbiol, 19:55-71.

[22]FramptonJ, MurphyKG, FrostG, et al., 2020. Short-chain fatty acids as potential regulators of skeletal muscle metabolism and function. Nat Metab, 2(9):840-848.

[23]FrazierK, ManzoorS, CarrollK, et al., 2023. Gut microbes and the liver circadian clock partition glucose and lipid metabolism. J Clin Invest, 133(18):e162515.

[24]FuchsCD, SimbrunnerB, BaumgartnerM, et al., 2025. Bile acid metabolism and signalling in liver disease. J Hepatol, 82(1):134-153.

[25]GilijamsePW, HartstraAV, LevinE, et al., 2020. Treatment with Anaerobutyricum soehngenii: a pilot study of safety and dose-response effects on glucose metabolism in human subjects with metabolic syndrome. npj Biofilms Microbiomes, 6:16.

[26]GraySM, MossAD, HerzogJW, et al., 2024. Mouse adaptation of human inflammatory bowel diseases microbiota enhances colonization efficiency and alters microbiome aggressiveness depending on the recipient colonic inflammatory environment. Microbiome, 12:147.

[27]GuoX, LiJH, XuJ, et al., 2025. Gut microbiota and epigenetic inheritance: implications for the development of IBD. Gut Microbes, 17(1):2490207.

[28]HeZG, LiuYB, LiZ, et al., 2023. Gut microbiota regulates circadian oscillation in hepatic ischemia-reperfusion injury-induced cognitive impairment by interfering with hippocampal lipid metabolism in mice. Hepatol Int, 17(6):1645-1658.

[29]HondaA, MiyazakiT, IwamotoJ, et al., 2020. Regulation of bile acid metabolism in mouse models with hydrophobic bile acid composition. J Lipid Res, 61(1):54-69.

[30]HooperLV, GordonJI, 2001. Commensal host-bacterial relationships in the gut. Science, 292(5519):1115-1118.

[31]HooperLV, MidtvedtT, GordonJI, 2002. How host-microbial interactions shape the nutrient environment of the mammalian intestine. Annu Rev Nutr, 22:283-307.

[32]HooperLV, LittmanDR, MacphersonAJ, 2012. Interactions between the microbiota and the immune system. Science, 336(6086):1268-1273.

[33]HuangFJ, ZhengXJ, MaXH, et al., 2019. Theabrownin from Pu-erh tea attenuates hypercholesterolemia via modulation of gut microbiota and bile acid metabolism. Nat Commun, 10:4971.

[34]JangJW, CapaldiE, SmithT, et al., 2024. Trimethylamine N-oxide: a meta-organismal axis linking the gut and fibrosis. Mol Med, 30:128.

[35]JiaL, JiangYY, WuLL, et al., 2024. Porphyromonas gingivalis aggravates colitis via a gut microbiota-linoleic acid metabolism-Th17/Treg cell balance axis. Nat Commun, 15:1617.

[36]JiaW, WeiML, RajaniC, et al., 2021. Targeting the alternative bile acid synthetic pathway for metabolic diseases. Protein Cell, 12(5):411-425.

[37]JinJ, HuangfuBX, XingFG, et al., 2023. Combined exposure to deoxynivalenol facilitates lipid metabolism disorder in high-fat-diet-induced obesity mice. Environ Int, 182:108345.

[38]KawanoY, EdwardsM, HuangYM, et al., 2022. Microbiota imbalance induced by dietary sugar disrupts immune-mediated protection from metabolic syndrome. Cell, 185(19):3501-3519.e20.

[39]KorbeliusM, KuentzelKB, BradićI, et al., 2023. Recent insights into lysosomal acid lipase deficiency. Trends Mol Med, 29(6):425-438.

[40]KoremT, ZeeviD, SuezJ, et al., 2015. Growth dynamics of gut microbiota in health and disease inferred from single metagenomic samples. Science, 349(6252):1101-1106.

[41]KuangZ, WangYH, LiY, et al., 2019. The intestinal microbiota programs diurnal rhythms in host metabolism through histone deacetylase 3. Science, 365(6460):1428-1434.

[42]LiNH, LiJ, WangH, et al., 2023. Aromatic amino acids and their interactions with gut microbiota-related metabolites for risk of gestational diabetes: a prospective nested case-control study in a Chinese cohort. Ann Nutr Metab, 79(3):291-300.

[43]LiSJ, ZhugeAX, ChenH, et al., 2025. Sedanolide alleviates DSS-induced colitis by modulating the intestinal FXR-SMPD3 pathway in mice. J Adv Res, 69:413-426.

[44]LiXL, YangYY, ZhangB, et al., 2022. Lactate metabolism in human health and disease. Signal Transduct Target Ther, 7:305.

[45]LiXX, LauHCH, YuJ, 2020. Microbiota-mediated phytate metabolism activates HDAC3 to contribute intestinal homeostasis. Signal Transduct Target Ther, 5:211.

[46]LiYY, MaJ, YaoK, et al., 2020. Circadian rhythms and obesity: timekeeping governs lipid metabolism. J Pineal Res, 69(3):e12682.

[47]LiuYL, HouYL, WangGJ, et al., 2020. Gut microbial metabolites of aromatic amino acids as signals in host-microbe interplay. Trends Endocrinol Metab, 31(11):818-834.

[48]LuYJ, YangWL, QiZY, et al., 2023. Gut microbe-derived metabolite indole-3-carboxaldehyde alleviates atherosclerosis. Signal Transduct Target Ther, 8:378.

[49]MaiuoloJ, CarresiC, GliozziM, et al., 2022. The contribution of gut microbiota and endothelial dysfunction in the development of arterial hypertension in animal models and in humans. Int J Mol Sci, 23(7):3698.

[50]MakkiK, DeehanEC, WalterJ, et al., 2018. The impact of dietary fiber on gut microbiota in host health and disease. Cell Host Microbe, 23(6):705-715.

[51]MinBH, DeviS, KwonGH, et al., 2024. Gut microbiota-derived indole compounds attenuate metabolic dysfunction-associated steatotic liver disease by improving fat metabolism and inflammation. Gut Microbes, 16(1):2307568.

[52]NgI, LukIY, NightingaleR, et al., 2023. Intestinal-specific Hdac3 deletion increases susceptibility to colitis and small intestinal tumor development in mice fed a high-fat diet. Am J Physiol Gastrointest Liver Physiol, 325(6):G508-G517.

[53]NogalA, ValdesAM, MenniC, 2021. The role of short-chain fatty acids in the interplay between gut microbiota and diet in cardio-metabolic health. Gut Microbes, 13(1):1897212.

[54]PlovierH, EverardA, DruartC, et al., 2017. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat Med, 23:107-113.

[55]QinN, YangFL, LiA, et al., 2014. Alterations of the human gut microbiome in liver cirrhosis. Nature, 513(7516):59-64.

[56]RothschildD, WeissbrodO, BarkanE, et al., 2018. Environment dominates over host genetics in shaping human gut microbiota. Nature, 555(7695):210-215.

[57]SchoelerM, CaesarR, 2019. Dietary lipids, gut microbiota and lipid metabolism. Rev Endocr Metab Disord, 20(4):461-472.

[58]StähliBE, ScharlM, MatterCM, 2023. A roadmap for gut microbiome-derived aromatic amino acids for improved cardiovascular risk stratification. Eur Heart J, 44(32):3097-3099.

[59]SuXM, GaoYH, YangRC, 2022. Gut microbiota-derived tryptophan metabolites maintain gut and systemic homeostasis. Cells, 11(15):2296.

[60]ThingholmLB, RühlemannMC, KochM, et al., 2019. Obese individuals with and without type 2 diabetes show different gut microbial functional capacity and composition. Cell Host Microbe, 26(2):252-264.e10.

[61]TurnbaughPJ, LeyRE, MahowaldMA, et al., 2006. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature, 444(7122):1027-1031.

[62]VieujeanS, JairathV, Peyrin-BirouletL, et al., 2025. Understanding the therapeutic toolkit for inflammatory bowel disease. Nat Rev Gastroenterol Hepatol, 22(6):371-394.

[63]WagnerA, WangC, FesslerJ, et al., 2021. Metabolic modeling of single Th17 cells reveals regulators of autoimmunity. Cell, 184(16):4168-4185.e21.

[64]WangJJ, ZhuNN, SuXM, et al., 2023. Gut-microbiota-derived metabolites maintain gut and systemic immune homeostasis. Cells, 12(5):793.

[65]WangYH, HooperLV, 2019. Immune control of the microbiota prevents obesity. Science, 365(6451):316-317.

[66]WangYH, KuangZ, YuXF, et al., 2017. The intestinal microbiota regulates body composition through NFIL3 and the circadian clock. Science, 357(6354):912-916.

[67]WangYH, WangM, ChenJX, et al., 2023. The gut microbiota reprograms intestinal lipid metabolism through long noncoding RNA Snhg9. Science, 381(6660):851-857.

[68]WangZN, SunY, HanYW, et al., 2023. Eucommia bark/leaf extract improves HFD-induced lipid metabolism disorders via targeting gut microbiota to activate the Fiaf-LPL gut-liver axis and SCFAs-GPR43 gut-fat axis. Phytomedicine, 110:154652.

[69]WenST, HeL, ZhongZT, et al., 2021. Stigmasterol restores the balance of Treg/Th17 cells by activating the butyrate-PPARγ axis in colitis. Front Immunol, 12:741934.

[70]WuHQ, MuCL, LiX, et al., 2024a. Breed-driven microbiome heterogeneity regulates intestinal stem cell proliferation via Lactobacillus-lactate-GPR81 signaling. Adv Sci, 11(33):2400058.

[71]WuHQ, MuCL, XuLP, et al., 2024b. Host-microbiota interaction in intestinal stem cell homeostasis. Gut Microbes, 16(1):2353399.

[72]WuSE, Hashimoto-HillS, WooV, et al., 2020. Microbiota-derived metabolite promotes HDAC3 activity in the gut. Nature, 586(7827):108-112.

[73]WuWR, LvLX, ShiD, et al., 2017. Protective effect of Akkermansia muciniphila against immune-mediated liver injury in a mouse model. Front Microbiol, 8:1804.

[74]XuHT, FangF, WuKZ, et al., 2023. Gut microbiota-bile acid crosstalk regulates murine lipid metabolism via the intestinal FXR-FGF19 axis in diet-induced humanized dyslipidemia. Microbiome, 11:262.

[75]YadavJ, LiangT, QinTR, et al., 2023. Gut microbiome modified by bariatric surgery improves insulin sensitivity and correlates with increased brown fat activity and energy expenditure. Cell Rep Med, 4(5):101051.

[76]YinYH, SichlerA, EckerJ, et al., 2023. Gut microbiota promote liver regeneration through hepatic membrane phospholipid biosynthesis. J Hepatol, 78(4):820-835.

[77]YounossiZM, KoenigAB, AbdelatifD, et al., 2016. Global epidemiology of nonalcoholic fatty liver disease‒meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology, 64(1):73-84.

[78]ZhangD, JianYP, ZhangYN, et al., 2023. Short-chain fatty acids in diseases. Cell Commun Signal, 21:212.

[79]ZhangSW, GangXK, YangS, et al., 2021. The alterations in and the role of the Th17/Treg balance in metabolic diseases. Front Immunol, 12:678355.

[80]ZhaoLP, ZhangF, DingXY, et al., 2018. Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science, 359(6380):1151-1156.

[81]ZhaoRQ, JiY, ChenX, et al., 2023. Flammulina velutipes polysaccharides regulate lipid metabolism disorders in HFD-fed mice via bile acids metabolism. Int J Biol Macromol, 253:127308.

[82]ZhuBL, WangX, LiLJ, 2010. Human gut microbiome: the second genome of human body. Protein Cell, 1(8):718-725.