中文｜English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 42 Issue 5
May  2026
Turn off MathJax
Article Contents
Article Navigation >  Journal of Clinical Hepatology  > 2026  >  42(5): 1160-1165

Protective effect of short-chain fatty acids against liver fibrosis and analogical application of its mechanism to pancreatic fibrosis

DOI: 10.12449/JCH260523
  • 1.

    The First Clinical Medical School of Lanzhou University，Lanzhou 730000，China

  • 2.

    Department of General Surgery，The First Hospital of Lanzhou University，Lanzhou 730000，China

  • 3.

    Gansu Province Key Laboratory of Biotherapy and Regenerative Medicine，Lanzhou 730000，China

  • 4.

    National Clinical Key Specialty of General Surgery，The First Hospital of Lanzhou University，Lanzhou 730000，China

  • 5.

    Gansu Clinical Research Center for General Surgery，The First Hospital of Lanzhou University，Lanzhou 730000，China

Research funding:

Gansu Province Science and Technology Major Special Plan Project (24ZDFA005);

Outstanding Young Talents and Key Talents in Health Industry in Gansu Province (GSWSQN2023-01)

More Information
  • Corresponding author: ZHANG Lei， ldyy_lzhang@lzu.edu.cn （ORCID： 0009-0009-5562-2951）
  • Received Date: 2025-09-17
  • Accepted Date: 2025-10-29
  • Published Date: 2026-05-25
    Abstract
  • Short-chain fatty acids （SCFA） are the main metabolic products generated by the fermentation of dietary fiber by gut microbiota. Studies have shown that SCFA not only play a role in energy metabolism， but also act as important signaling molecules， exhibiting a significant potential in alleviating liver and pancreatic fibrosis. The core mechanism of SCFA mainly involves the regulation of various key signaling pathways by activating G protein-coupled receptors and inhibiting the activity of histone deacetylase， thereby suppressing the activation and proliferation of hepatic stellate cell （HSC） and pancreatic stellate cell （PSC）， which is a key link in fibrosis formation. In addition， SCFA can effectively alleviate tissue inflammation response， improve intestinal barrier function， and regulate gut microbiota balance， thus indirectly preventing the process of fibrosis mediated by the “gut-liver/pancreas axis”. Compared with the research on SCFA in liver fibrosis， studies on their role in pancreatic fibrosis are limited. Given that HSC and PSC are highly homologous， the transcription factors and proteins that have been confirmed in liver fibrosis-related studies are also similarly expressed in PSC， suggesting that they may also influence the activation of PSC. This article systematically summarizes the recent advances in the research on SCFA in alleviating liver and pancreatic fibrosis， in order to provide new perspectives for exploring the mechanism of pancreatic fibrosis and developing related interventional strategies.

     

    • FullText(HTML)
  • loading
    • References(42)
  • [1]
    KONG FY, LI ZS. Research progress on pancreatic diseases[J]. Chin J Pancreatol, 2021, 21( 1): 6- 15. DOI: 10.3760/cma.j.cn115667-20201125-00191.

    孔凡扬, 李兆申. 胰腺疾病的研究进展[J]. 中华胰腺病杂志, 2021, 21( 1): 6- 15. DOI: 10.3760/cma.j.cn115667-20201125-00191.
    [2]
    ZHANG XQ, XIE XY, WANG YZ, et al. Interleukin-26 promotes the proliferation and activation of hepatic stellate cells to exacerbate liver fibrosis by the TGF-β1/Smad2 signaling pathway[J]. Int J Clin Exp Pathol, 2019, 12( 12): 4271- 4279.
    [3]
    VALDES AM, WALTER J, SEGAL E, et al. Role of the gut microbiota in nutrition and health[J]. BMJ, 2018, 361: k2179. DOI: 10.1136/bmj.k2179.
    [4]
    ZOU FG, QIU Y, HUANG YL, et al. Effects of short-chain fatty acids in inhibiting HDAC and activating p38 MAPK are critical for promoting B10 cell generation and function[J]. Cell Death Dis, 2021, 12( 6): 582. DOI: 10.1038/s41419-021-03880-9.
    [5]
    GAO ZT, CHEN Y, HE HD, et al. Short-chain fatty acids modulate the role of NLRP3 inflammatory ves-icle pathway in CKD and the progress of traditional Chinese medicine intervention[J]. Chin J Clin Pharmacol Ther, 2025, 30( 6): 812- 819. DOI: 10.12092/j.issn.1009-2501.2025.06.011.

    高子恬, 陈彧, 贺海东, 等. 短链脂肪酸调控NLRP3炎症小体通路在慢性肾脏病中的作用及中药干预的研究进展[J]. 中国临床药理学与治疗学, 2025, 30( 6): 812- 819. DOI: 10.12092/j.issn.1009-2501.2025.06.011.
    [6]
    LONGO S, RIZZA S, FEDERICI M. Microbiota-gut-brain axis: Relationships among the vagus nerve, gut microbiota, obesity, and diabetes[J]. Acta Diabetol, 2023, 60( 8): 1007- 1017. DOI: 10.1007/s00592-023-02088-x.
    [7]
    FOCK E, PARNOVA R. Mechanisms of blood-brain barrier protection by microbiota-derived short-chain fatty acids[J]. Cells, 2023, 12( 4): 657. DOI: 10.3390/cells12040657.
    [8]
    JAVID H, SHARBAF MASHHAD A, YAZDANI S, et al. The role of viruses in cancer development versus cancer therapy: An oncological perspective[J]. Cancer Med, 2023, 12( 10): 11127- 11148. DOI: 10.1002/cam4.5694.
    [9]
    DENG H, CHEN YM, WANG L, et al. PI3K/mTOR inhibitors promote G6PD autophagic degradation and exacerbate oxidative stress damage to radiosensitize small cell lung cancer[J]. Cell Death Dis, 2023, 14( 10): 652. DOI: 10.1038/s41419-023-06171-7.
    [10]
    GANESAN R, YOON SJ, SUK KT. Microbiome and metabolomics in liver cancer: Scientific technology[J]. Int J Mol Sci, 2023, 24( 1): 537. DOI: 10.3390/ijms24010537.
    [11]
    HONG Q, KIM H, CAI GY, et al. Modulation of TGF-β signaling new approaches toward kidney disease and fibrosis therapy[J]. Int J Biol Sci, 2025, 21( 4): 1649- 1665. DOI: 10.7150/ijbs.101548.
    [12]
    SAMADDAR A, VAN NISPEN J, ARMSTRONG A, et al. Lower systemic inflammation is associated with gut firmicutes dominance and reduced liver injury in a novel ambulatory model of parenteral nutrition[J]. Ann Med, 2022, 54( 1): 1701- 1713. DOI: 10.1080/07853890.2022.2081871.
    [13]
    SONG XP, LAO J, WANG LL, et al. Research advances on short-chain fatty acids in gastrointestinal acute graft-versus-host disease[J]. Ther Adv Hematol, 2024, 15: 20406207241237602. DOI: 10.1177/20406207241237602.
    [14]
    YING ZH, MAO CL, XIE W, et al. Postbiotics in rheumatoid arthritis: Emerging mechanisms and intervention perspectives[J]. Front Microbiol, 2023, 14: 1290015. DOI: 10.3389/fmicb.2023.1290015.
    [15]
    RASTOGI S, MOHANTY S, SHARMA S, et al. Possible role of gut microbes and host's immune response in gut-lung homeostasis[J]. Front Immunol, 2022, 13: 954339. DOI: 10.3389/fimmu.2022.954339.
    [16]
    CAENGPRASATH N, GONZALEZ-ABUIN N, SHCHEPINOVA M, et al. Internalization-dependent free fatty acid receptor 2 signaling is essential for propionate-induced anorectic gut hormone release[J]. iScience, 2020, 23( 9): 101449. DOI: 10.1016/j.isci.2020.101449.
    [17]
    LV Y, YANG XT, SUN XW, et al. Immune-microbiota dysregulation in maintenance hemodialysis: A 16S rRNA sequencing-based analysis of gut flora and T cell profiles[J]. Ren Fail, 2025, 47( 1): 2498630. DOI: 10.1080/0886022X.2025.2498630.
    [18]
    ZHANG ZL, ZHANG H, CHEN T, et al. Regulatory role of short-chain fatty acids in inflammatory bowel disease[J]. Cell Commun Signal, 2022, 20( 1): 64. DOI: 10.1186/s12964-022-00869-5.
    [19]
    LI XJ, SHAN QY, WU X, et al. Gut microbiota regulates oxidative stress and inflammation: A double-edged sword in renal fibrosis[J]. Cell Mol Life Sci, 2024, 81( 1): 480. DOI: 10.1007/s00018-024-05532-5.
    [20]
    SINGH N, GURAV A, SIVAPRAKASAM S, et al. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis[J]. Immunity, 2014, 40( 1): 128- 139. DOI: 10.1016/j.immuni.2013.12.007.
    [21]
    ELHAG DA, KUMAR M, KHODOR S AL. Exploring the triple interaction between the host genome, the epigenome, and the gut microbiome in type 1 diabetes[J]. Int J Mol Sci, 2021, 22( 1): 125. DOI: 10.3390/ijms22010125.
    [22]
    WEN S, LIU M, PAN CY, et al. Research progress on immunometabolism and gut microbiota in cryptococcal meningitis: Mechanisms and therapeutic implications[J]. Front Neurosci, 2025, 19: 1622349. DOI: 10.3389/fnins.2025.1622349.
    [23]
    CHEN JL, LIU X, BAI YX, et al. Tonsillar microbiota alterations contribute to immune responses in psoriasis by skewing aged neutrophils[J]. Br J Dermatol, 2025, 193( 2): 310- 321. DOI: 10.1093/bjd/ljaf134.
    [24]
    SHIN Y, HAN S, KWON J, et al. Roles of short-chain fatty acids in inflammatory bowel disease[J]. Nutrients, 2023, 15( 20): 4466. DOI: 10.3390/nu15204466.
    [25]
    YANG B, LI XH, WANG JH, et al. The efficacy and safety of fecal microbiota transplantation in the treatment of sarcopenia: A retrospective study[J]. J Transl Med, 2025, 23( 1): 645. DOI: 10.1186/s12967-025-06557-5.
    [26]
    YE JZ, LV LX, WU WR, et al. Butyrate protects mice against methionine-choline-deficient diet-induced non-alcoholic steatohepatitis by improving gut barrier function, attenuating inflammation and reducing endotoxin levels[J]. Front Microbiol, 2018, 9: 1967. DOI: 10.3389/fmicb.2018.01967.
    [27]
    XU YX, ZHENG SY, JIANG S, et al. The effect of Chinese herbal formulas combined with metformin on modulating the gut microbiota in the amelioration of type 2 diabetes mellitus: A systematic review and meta-analysis[J]. Front Endocrinol, 2022, 13: 927959. DOI: 10.3389/fendo.2022.927959.
    [28]
    LU H, ZHANG MM, HU YN, et al. Short-chain fatty acids alleviate cholestatic liver injury by improving gut microbiota and bile acid metabolism[J]. Int Immunopharmacol, 2025, 154: 114564. DOI: 10.1016/j.intimp.2025.114564.
    [29]
    SUN YY, LU YY, JING DD. Research progress on gut microecology in the occurrence and development of chronic pancreatitis and pancreatic cancer[J]. Int J Digest Dis, 2021, 41( 4): 240- 243. DOI: 10.3969/j.issn.1673-534X.2021.04.003.

    孙莹莹, 陆颖影, 靖大道. 慢性胰腺炎和胰腺癌发生及发展中肠道微生态的研究进展[J]. 国际消化病杂志, 2021, 41( 4): 240- 243. DOI: 10.3969/j.issn.1673-534X.2021.04.003.
    [30]
    PAN LL, REN ZN, YANG J, et al. Gut microbiota controls the development of chronic pancreatitis: A critical role of short-chain fatty acids-producing Gram-positive bacteria[J]. Acta Pharm Sin B, 2023, 13( 10): 4202- 4216. DOI: 10.1016/j.apsb.2023.08.002.
    [31]
    PAN YY, LI JN, FAN ZY, et al. New insights into chronic pancreatitis: Potential mechanisms related to probiotics[J]. Microorganisms, 2024, 12( 9): 1760. DOI: 10.3390/microorganisms12091760.
    [32]
    KANIKA G, KHAN S, JENA G. Sodium butyrate ameliorates L-arginine-induced pancreatitis and associated fibrosis in wistar rat: Role of inflammation and nitrosative stress[J]. J Biochem Mol Toxicol, 2015, 29( 8): 349- 359. DOI: 10.1002/jbt.21698.
    [33]
    HEGAZY RA. Unraveling liver cirrhosis: Bridging pathophysiology to innovative therapeutics[J]. J Gastroenterol Hepatol, 2025, 40( 10): 2449- 2462. DOI: 10.1111/jgh.70037.
    [34]
    WANG XY, LI MM, LIU XJ, et al. Isolation of murine pancreatic stellate cells and the establishment of a new ex-vivo activation model[J]. Clin Exp Gastroenterol, 2025, 18: 79- 89. DOI: 10.2147/ceg.s507384.
    [35]
    CANDELLI M, FRANCESCHI F. New advances in gastroenterology: The crucial role of molecular medicine[J]. Int J Mol Sci, 2023, 24( 19): 14907. DOI: 10.3390/ijms241914907.
    [36]
    ZHENG MF, LI HY, SUN L, et al. Interleukin-6 participates in human pancreatic stellate cell activation and collagen I production via TGF-β1/Smad pathway[J]. Cytokine, 2021, 143: 155536. DOI: 10.1016/j.cyto.2021.155536.
    [37]
    KOMAR HM, SERPA G, KERSCHER C, et al. Inhibition of Jak/STAT signaling reduces the activation of pancreatic stellate cells in vitro and limits caerulein-induced chronic pancreatitis in vivo[J]. Sci Rep, 2017, 7( 1): 1787. DOI: 10.1038/s41598-017-01973-0.
    [38]
    MANOHAR M, KANDIKATTU HK, VERMA AK, et al. IL-15 regulates fibrosis and inflammation in a mouse model of chronic pancreatitis[J]. Am J Physiol Gastrointest Liver Physiol, 2018, 315( 6): G954- G965. DOI: 10.1152/ajpgi.00139.2018.
    [39]
    YU SY, LUAN Y, TANG SY, et al. Uncovering tumor-promoting roles of activin a in pancreatic ductal adenocarcinoma[J]. Adv Sci, 2023, 10( 16): 2207010. DOI: 10.1002/advs.202207010.
    [40]
    LI KK, REN KW, DU S, et al. Development of liver cancer organoids: Reproducing tumor microenvironment and advancing research for liver cancer treatment[J]. Technol Cancer Res Treat, 2024, 23: 15330338241285097. DOI: 10.1177/15330338241285097.
    [41]
    ZHENG MF, GAO RP. Vitamin D: A potential star for treating chronic pancreatitis[J]. Front Pharmacol, 2022, 13: 902639. DOI: 10.3389/fphar.2022.902639.
    [42]
    SENDLER M, BEYER G, MAHAJAN UM, et al. Complement component 5 mediates development of fibrosis, via activation of stellate cells, in 2 mouse models of chronic pancreatitis[J]. Gastroenterology, 2015, 149( 3): 765- 776. e 10. DOI: 10.1053/j.gastro.2015.05.012.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(1)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (22) PDF downloads(9) Cited by()
    Proportional views
    Related
        

    The first journal specializing in hepatobiliary and pancreatic diseases in China

    Supervisor：Ministry of Education of the People's Republic of China

    Sponsor：Jilin University

    Academic Support: Chinese Society of Hepatology，Chinese Medical Association

    Address: 461 Xinjiang Road, Changchun

    Submit：0431-88782044

    Peer review：0431-88783542

    Email：lcgdb@vip.163.com

    About Journal

    Submission Guideline

    Journal Online

    Hepatobiliary College

    Guidelines

    YesterdayIP[]YesterdayPV[]TodayIP[]TodayPV[]Online[]

    Website Design © 2020 Editorial Board of Journal of Clinical Hepatology 吉ICP备10000617号-1 Supported by: Beijing Renhe Information Technology Co. Ltd  

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return