高脂饮食对结肠慢传输型便秘影响的研究进展

摘要

结肠慢传输型便秘（STC）是功能性便秘的亚型之一，近年来临床发病率逐渐提高。该病病因复杂、症状迁延不愈，给患者的生活质量和临床诊疗带来沉重负担。随着我国饮食结构西方化趋势的加剧，高脂饮食的摄入与STC发病之间的关联日益受到关注。高脂饮食不仅可直接改变结肠运动节律，更可通过干扰肠神经系统功能、扰乱肠道菌群稳态、诱发肠道慢性炎症、干扰肠-脑轴通讯等多重途径，参与STC的发生与发展。结合近年来的研究成果，对高脂饮食在STC中的作用机制及其潜在治疗靶点进行综述，以期为临床干预提供新思路。

关键词

高脂饮食 / 慢传输型便秘 / 肠道菌群 / 肠神经系统 / 肠脑轴

参考文献

[1] Vriesman MH , Koppen IJN , Camilleri M , et al. Management of functional constipation in children and adults [J]. Nat Rev Gastroenterol Hepatol, 2020, 17（1）: 21-39. DOI: 10.1038/s41575—019—0222—y.

[2] Vlismas LJ , Wu W , Ho V . Idiopathic slow transit constipation: pathophysiology, diagnosis, and management[J]. Medicina (Kaunas), 2024, 60（1）: 108. DOI: 10. 3390/medicina60010108.

[3] Mushref MA , Srinivasan S . Effect of high fat—diet and obesity on gastrointestinal motility[J]. Ann Transl Med, 2013, 1（2）: 14. DOI: 10.3978/j.issn.2305—5839. 2012. 11.01.

[4] Cingolani F , Balasubramaniam A , Srinivasan S . Molecular mechanisms of enteric neuropathies in high—fat diet feeding and diabetes[J]. Neurogastroenterol Motil, 2025, 37（8）: e14897. DOI: 10.1111/nmo.14897.

[5] Taba Taba Vakili S , Nezami BG , Shetty A , et al. Association of high dietary saturated fat intake and uncontrolled diabetes with constipation: evidence from the national health and nutrition examination survey[J]. Neurogastroenterol Motil, 2015, 27（10）: 1389-1397. DOI: 10.1111/nmo.12630.

[6] Mukai R , Handa O , Naito Y , et al. High—fat diet causes constipation in mice via decreasing colonic mucus[J]. Dig Dis Sci, 2020, 65（8）: 2246-2253. DOI: 10.1007/ s10620—019—05954—3.

[7] Kim JE , Seol A , Choi YJ , et al. Similarities and differences in constipation phenotypes between Lep knockout mice and high fat diet—induced obesity mice[J]. PLoS One, 2022, 17（12）: e0276445. DOI: 10.1371/journal.pone.0276445.

[8] Furness JB , Callaghan BP , Rivera LR , et al. The enteric nervous system and gastrointestinal innervation: integrated local and central control[J]. Adv Exp Med Biol, 2014, 817: 39-71. DOI: 10.1007/978—1—4939—0897—4_3.

[9] Nguyen TT , Baumann P , Tüscher O , et al. The aging enteric nervous system[J]. Int J Mol Sci, 2023, 24（11）: 9471. DOI: 10.3390/ijms24119471.

[10] Zhang YC , Chen BX , Xie XY , et al. Role of Tenascin—X in regulating TGF—β/Smad signaling pathway in pathogenesis of slow transit constipation[J]. World J Gastroenterol, 2020, 26（7）: 717-724. DOI: 10.3748/wjg.v26.i7.717.

[11] Nyavor Y , Estill R , Edwards H , et al. Intestinal nerve cell injury occurs prior to insulin resistance in female mice ingesting a high—fat diet[J]. Cell Tissue Res, 2019, 376（3）: 325-340. DOI: 10.1007/s00441—019—03002—0.

[12] Nezami BG , Mwangi SM , Lee JE , et al. MicroRNA 375 mediates palmitate—induced enteric neuronal damage and high—fat diet—induced delayed intestinal transit in mice[J]. Gastroenterology, 2014, 146（2）: 473-483.e3. DOI: 10.1053/j. gastro.2013.10.053.

[13] Bhattarai Y , Fried D , Gulbransen B , et al. High—fat diet—induced obesity alters nitric oxide—mediated neuromuscular transmission and smooth muscle excitability in the mouse distal colon[J]. Am J Physiol Gastrointest Liver Physiol, 2016, 311（2）: G210-220. DOI: 10.1152/ajpgi.00085.2016.

[14] Goldstein AM , Hofstra RM , Burns AJ . Building a brain in the gut: development of the enteric nervous system[J]. Clin Genet, 2013, 83（4）: 307-316. DOI: 10.1111/ cge.12054.

[15] Sharkey KA . Emerging roles for enteric glia in gastrointestinal disorders[J]. J Clin Invest, 2015, 125（3）: 918-925. DOI: 10.1172/jci76303.

[16] Gulbransen BD , Christofi FL . Are we close to targeting enteric glia in gastrointestinal diseases and motility disorders[J]. Gastroenterology, 2018, 155（2）: 245-251. DOI: 10.1053/j.gastro.2018.06.050.

[17] Cirillo C , Sarnelli G , Esposito G , et al. S100B protein in the gut: the evidence for enteroglial—sustained intestinal inflammation[J]. World J Gastroenterol, 2011, 17（10）: 1261-1266. DOI: 10.3748/wjg.v17.i10.1261.

[18] Antonioli L , D'Antongiovanni V , Pellegrini C , et al. Colonic dysmotility associated with high—fat diet—induced obesity: role of enteric glia[J]. FASEB J, 2020, 34（4）: 5512-5524. DOI: 10.1096/fj.201901844R.

[19] Antonioli L , Caputi V , Fornai M , et al. Interplay between colonic inflammation and tachykininergic pathways in the onset of colonic dysmotility in a mouse model of diet—induced obesity[J]. Int J Obes （Lond）, 2019, 43（2）: 331-343. DOI: 10.1038/s41366—018—0166—2.

[20] 梁青山， 刘沙， 庄卓男 . 高原缺氧环境下肠道菌群紊乱与肠道疾病的研究进展[J]. 中国现代普通外科进展， 2024， 27（3）： 242-244. DOI: 10.3969/j.issn.1009—9905.2024.03.020.

[21] Johnson AJ , Vangay P , Al—Ghalith GA , et al. Daily sampling reveals personalized diet—microbiome associations in humans[J]. Cell Host Microbe, 2019, 25（6）: 789-802.e5. DOI: 10.1016/j.chom.2019.05.005.

[22] Zhang C , Zhang M , Wang S , et al. Interactions between gut microbiota, host genetics and diet relevant to development of metabolic syndromes in mice[J]. ISME J, 2010, 4（2）: 232-241. DOI: 10.1038/ismej.2009.112.

[23] Tan R , Dong H , Chen Z , et al. Intestinal microbiota mediates high—fructose and high—fat diets to induce chronic intestinal inflammation[J]. Front Cell Infect Microbiol, 2021, 11: 654074. DOI: 10.3389/fcimb.2021.654074.

[24] Hildebrandt MA , Hoffmann C , Sherrill—Mix SA , et al. High—fat diet determines the composition of the murine gut microbiome independently of obesity[J]. Gastroenterology, 2009, 137（5）: 1716-1724.e1—2. DOI: 10.1053/j.gastro. 2009. 08.042.

[25] Reichardt F , Chassaing B , Nezami BG , et al. Western diet induces colonic nitrergic myenteric neuropathy and dysmotility in mice via saturated fatty acid— and lipopolysaccharide—induced TLR4 signalling[J]. J Physiol, 2017, 595（5）: 1831-1846. DOI: 10.1113/jp273269.

[26] Mukhopadhya I , Louis P . Gut microbiota—derived short—chain fatty acids and their role in human health and disease[J]. Nat Rev Microbiol, 2025, 23（10）: 635-651. DOI: 10.1038/s41579—025—01183—w.

[27] Liu TH , Chen GL , Lin CH , et al. Lactobacillus plantarum TWK10 relieves loperamide—induced constipation in rats fed a high—fat diet via modulating enteric neurotransmitters, short—chain fatty acids and gut microbiota[J]. Food Funct, 2025, 16（1）: 181-194. DOI: 10.1039/d4fo02270j.

[28] Das R , Wille L , Zhang L , et al. A quantitative systems pharmacology model of colonic motility with applications in drug development[J]. J Pharmacokinet Pharmacodyn, 2019, 46（5）: 485-498. DOI: 10.1007/s10928—019—09651—6.

[29] Cao H , Liu X , An Y , et al. Dysbiosis contributes to chronic constipation development via regulation of serotonin transporter in the intestine[J]. Sci Rep, 2017, 7（1）: 10322. DOI: 10.1038/s41598—017—10835—8.

[30] van der Schoot A , Helander C , Whelan K , et al. Probiotics and synbiotics in chronic constipation in adults: a systematic review and meta—analysis of randomized controlled trials[J]. Clin Nutr, 2022, 41（12）: 2759-2777. DOI: 10.1016/j.clnu.2022.10.015.

[31] Ye L , Li G , Goebel A , et al. Caspase—11—mediated enteric neuronal pyroptosis underlies western diet—induced colonic dysmotility[J]. J Clin Invest, 2020, 130（7）: 3621-3636. DOI: 10.1172/jci130176.

[32] Faggin S , Cerantola S , Bosi A , et al. Small intestine neuromuscular dysfunctions and neurogliopathy in a mouse model of high—fat diet—induced obesity: involvement of toll—like receptor 4[J]. Int J Mol Sci, 2025, 26（21）: 10710. DOI: 10.3390/ ijms262110710.

[33] Ramírez—Maldonado LM , Guerrero—Castro J , Rodríguez—Mejía JL , et al. Obesogenic cafeteria diet induces dynamic changes in gut microbiota, reduces myenteric neuron excitability, and impairs gut contraction in mice[J]. Am J Physiol Gastrointest Liver Physiol, 2025, 328（1）: G32-G48. DOI: 10.1152/ ajpgi. 00198.2024.

[34] de La Serre CB , Ellis CL , Lee J , et al. Propensity to high—fat diet—induced obesity in rats is associated with changes in the gut microbiota and gut inflammation[J]. Am J Physiol Gastrointest Liver Physiol, 2010, 299（2）: G440-G448. DOI: 10.1152/ ajpgi.00098. 2010.

[35] Sampath C , Wilus D , Tabatabai M , et al. Mechanistic role of antioxidants in rescuing delayed gastric emptying in high fat diet induced diabetic female mice[J]. Biomed Pharmacother, 2021, 137: 111370. DOI: 10.1016/j. biopha. 2021. 111370.

[36] Neuman MG . Immune dysfunction in inflammatory bowel disease[J]. Transl Res, 2007, 149（4）: 173-186. DOI: 10.1016/j.trsl.2006.11.009.

[37] Vianna CR , Donato J Jr , Rossi J , et al. Cannabinoid receptor 1 in the vagus nerve is dispensable for body weight homeostasis but required for normal gastrointestinal motility[J]. J Neurosci, 2012, 32（30）: 10331-10337. DOI: 10.1523/ jneurosci.4507—11. 2012.