Skip to content
2000
Volume 25, Issue 5
  • ISSN: 1566-5232
  • E-ISSN: 1875-5631

Abstract

Background

Fibrosis refers to abnormal deposition of extracellular matrix, which leads to organ dysfunction. Metabolic alterations, especially enhanced glycolysis and suppressed fatty acid oxidation, are recognized as an essential pathogenic process of fibrosis. Recently, several reports indicate that the changes in microbiota composition are associated with metabolic disorders, suggesting microbes may contribute to organ fibrosis by regulating metabolic processes.

Methods

In this study, microbial reannotation was carried out on the RNA-seq data of fibrotic organs. Then, the microbial composition differences among healthy and fibrotic organ samples were determined by alpha and beta diversity analysis. Common and specific microbial markers of fibrosis were also identified by LEfSe. After that, the correlation analysis of the characteristic microbe- gene-functional pathway was conducted to confirm the effects of microbes on host metabolism.

Results

The results showed that the microbial composition significantly differed between healthy and diseased organs. Besides, the common characteristic microbes interacted closely with each other and contributed to fibrosis through symbiosis or inhibition. The largest proportion in fibrosis organs was which was the main source of pathogenic microbes.

Conclusion

Further study found that the metabolic alteration driven by common and special characteristic microbes in fibrotic organs focused on the processes related to glycolysis and fatty acid metabolism.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cgt/10.2174/0115665232257596231011110813
2025-01-03
2025-10-04

  • From This Site

    /content/journals/cgt/10.2174/0115665232257596231011110813
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. ZeisbergM. KalluriR. Cellular Mechanisms of Tissue Fibrosis. 1. Common and organ-specific mechanisms associated with tissue fibrosis.Am. J. Physiol. Cell Physiol.20133043C216C22510.1152/ajpcell.00328.201223255577
     [Google Scholar]
  2. RockeyD.C. BellP.D. HillJ.A. Fibrosis-a common pathway to organ injury and failure.N. Engl. J. Med.2015372121138114910.1056/NEJMra130057525785971
     [Google Scholar]
  3. MicallefL. VedrenneN. BilletF. CoulombB. DarbyI.A. DesmoulièreA. The myofibroblast, multiple origins for major roles in normal and pathological tissue repair.Fibrogenesis Tissue Repair20125S1Suppl. 1S510.1186/1755‑1536‑5‑S1‑S523259712
     [Google Scholar]
  4. DeesC. ChakrabortyD. DistlerJ.H.W. Cellular and molecular mechanisms in fibrosis.Exp. Dermatol.202130112113110.1111/exd.1419332931037
     [Google Scholar]
  5. WeiskirchenR. WeiskirchenS. TackeF. Organ and tissue fibrosis: Molecular signals, cellular mechanisms and translational implications.Mol. Aspects Med.20196521510.1016/j.mam.2018.06.00329958900
     [Google Scholar]
  6. KangY.P. LeeS.B. LeeJ. KimH.M. HongJ.Y. LeeW.J. ChoiC.W. ShinH.K. KimD.J. KohE.S. ParkC.S. KwonS.W. ParkS.W. Metabolic profiling regarding pathogenesis of idiopathic pulmonary fibrosis.J. Proteome Res.20161551717172410.1021/acs.jproteome.6b0015627052453
     [Google Scholar]
  7. XieN. TanZ. BanerjeeS. CuiH. GeJ. LiuR.M. BernardK. ThannickalV.J. LiuG. Glycolytic reprogramming in myofibroblast differentiation and lung fibrosis.Am. J. Respir. Crit. Care Med.2015192121462147410.1164/rccm.201504‑0780OC26284610
     [Google Scholar]
  8. Rodríguez-GarcíaA. SamsóP. FontovaP. Simon-MolasH. ManzanoA. CastañoE. RosaJ.L. Martinez-OutshoornU. VenturaF. Navarro-SabatéÀ. BartronsR. TGF-β1 targets Smad, p38 MAPK, and PI3K/Akt signaling pathways to induce PFKFB3 gene expression and glycolysis in glioblastoma cells.FEBS J.2017284203437345410.1111/febs.1420128834297
     [Google Scholar]
  9. YinX. ChoudhuryM. KangJ.H. SchaefbauerK.J. JungM.Y. AndrianifahananaM. HernandezD.M. LeofE.B. Hexokinase 2 couples glycolysis with the profibrotic actions of TGF-β.Sci. Signal.201912612eaax406710.1126/scisignal.aax406731848318
     [Google Scholar]
  10. AndrianifahananaM. HernandezD.M. YinX. KangJ.H. JungM.Y. WangY. YiE.S. RodenA.C. LimperA.H. LeofE.B. Profibrotic up-regulation of glucose transporter 1 by TGF-β involves activation of MEK and mammalian target of rapamycin complex 2 pathways.FASEB J.201630113733374410.1096/fj.201600428R27480571
     [Google Scholar]
  11. de Paz-LugoP. LupiáñezJ.A. Meléndez-HeviaE. High glycine concentration increases collagen synthesis by articular chondrocytes in vitro: acute glycine deficiency could be an important cause of osteoarthritis.Amino Acids201850101357136510.1007/s00726‑018‑2611‑x30006659
     [Google Scholar]
  12. MichaelJ.C. FreshwaterM.F. HoopesJ.E. Enzyme activities in granulation tissue: Energy for collagen synthesis.J. Surg. Res.197620212112510.1016/0022‑4804(76)90108‑6130515
     [Google Scholar]
  13. KepplerD.O.R. HübnerG. Liver injury induced by 2-deoxy-d-galactose.Exp. Mol. Pathol.197319336537710.1016/0014‑4800(73)90067‑14763635
     [Google Scholar]
  14. HendersonJ. DuffyL. StrattonR. FordD. O’ReillyS. Metabolic reprogramming of glycolysis and glutamine metabolism are key events in myofibroblast transition in systemic sclerosis pathogenesis.J. Cell. Mol. Med.20202423140261403810.1111/jcmm.1601333140521
     [Google Scholar]
  15. KangH.M. AhnS.H. ChoiP. KoY.A. HanS.H. ChingaF. ParkA.S.D. TaoJ. SharmaK. PullmanJ. BottingerE.P. GoldbergI.J. SusztakK. Defective fatty acid oxidation in renal tubular epithelial cells has a key role in kidney fibrosis development.Nat. Med.2015211374610.1038/nm.376225419705
     [Google Scholar]
  16. LakshmiS.P. ReddyA.T. ReddyR.C. Transforming growth factor β suppresses peroxisome proliferator-activated receptor γ expression via both SMAD binding and novel TGF-β inhibitory elements.Biochem. J.201747491531154610.1042/BCJ2016094328100650
     [Google Scholar]
  17. QianJ. NiuM. ZhaiX. ZhouQ. ZhouY. β-Catenin pathway is required for TGF-β1 inhibition of PPARγ expression in cultured hepatic stellate cells.Pharmacol. Res.201266321922510.1016/j.phrs.2012.06.00322706027
     [Google Scholar]
  18. ZhengF. FornoniA. ElliotS.J. GuanY. BreyerM.D. StrikerL.J. StrikerG.E. Upregulation of type I collagen by TGF-β in mesangial cells is blocked by PPARγ activation.Am. J. Physiol. Renal Physiol.20022824F639F64810.1152/ajprenal.00189.200111880325
     [Google Scholar]
  19. WeiJ. GhoshA.K. SargentJ.L. KomuraK. WuM. HuangQ.Q. JainM. WhitfieldM.L. Feghali-BostwickC. VargaJ. PPARγ downregulation by TGFß in fibroblast and impaired expression and function in systemic sclerosis: a novel mechanism for progressive fibrogenesis.PLoS One2010511e1377810.1371/journal.pone.001377821072170
     [Google Scholar]
  20. ZhaoX. PsarianosP. GhoraieL.S. YipK. GoldsteinD. GilbertR. WitterickI. PangH. HussainA. LeeJ.H. WilliamsJ. BratmanS.V. AillesL. Haibe-KainsB. LiuF.F. Metabolic regulation of dermal fibroblasts contributes to skin extracellular matrix homeostasis and fibrosis.Nat. Metab.20191114715710.1038/s42255‑018‑0008‑532694814
     [Google Scholar]
  21. FanY. PedersenO. Gut microbiota in human metabolic health and disease.Nat. Rev. Microbiol.2021191557110.1038/s41579‑020‑0433‑932887946
     [Google Scholar]
  22. ValdesA.M. WalterJ. SegalE. SpectorT.D. Role of the gut microbiota in nutrition and health.BMJ2018361k217910.1136/bmj.k217929899036
     [Google Scholar]
  23. PooreG.D. KopylovaE. ZhuQ. CarpenterC. FraraccioS. WandroS. KosciolekT. JanssenS. MetcalfJ. SongS.J. KanbarJ. Miller-MontgomeryS. HeatonR. MckayR. PatelS.P. SwaffordA.D. KnightR. Microbiome analyses of blood and tissues suggest cancer diagnostic approach.Nature2020579780056757410.1038/s41586‑020‑2095‑132214244
     [Google Scholar]
  24. ZhangX. CokerO.O. ChuE.S.H. FuK. LauH.C.H. WangY.X. ChanA.W.H. WeiH. YangX. SungJ.J.Y. YuJ. Dietary cholesterol drives fatty liver-associated liver cancer by modulating gut microbiota and metabolites.Gut202170476177410.1136/gutjnl‑2019‑31966432694178
     [Google Scholar]
  25. MarquesF.Z. NelsonE. ChuP.Y. HorlockD. FiedlerA. ZiemannM. TanJ.K. KuruppuS. RajapakseN.W. El-OstaA. MackayC.R. KayeD.M. High-fiber diet and acetate supplementation change the gut microbiota and prevent the development of hypertension and heart failure in hypertensive mice.Circulation20171351096497710.1161/CIRCULATIONAHA.116.02454527927713
     [Google Scholar]
  26. ZhangD. LiS. WangN. TanH.Y. ZhangZ. FengY. The cross-talk between gut microbiota and lungs in common lung diseases.Front. Microbiol.20201130110.3389/fmicb.2020.0030132158441
     [Google Scholar]
  27. MalhotraS. HayesD.Jr WozniakD.J. Cystic fibrosis and pseudomonas aeruginosa: The host-microbe interface.Clin. Microbiol. Rev.2019323e00138-1810.1128/CMR.00138‑1831142499
     [Google Scholar]
  28. WatersE.M. NeillD.R. KamanB. SahotaJ.S. ClokieM.R.J. WinstanleyC. KadiogluA. Phage therapy is highly effective against chronic lung infections with Pseudomonas aeruginosa.Thorax201772766666710.1136/thoraxjnl‑2016‑20926528265031
     [Google Scholar]
  29. BeyoğluD. IdleJ.R. The metabolomic window into hepatobiliary disease.J. Hepatol.201359484285810.1016/j.jhep.2013.05.03023714158
     [Google Scholar]
  30. BernasconiE. PattaroniC. KoutsokeraA. PisonC. KesslerR. BendenC. SoccalP.M. MagnanA. AubertJ.D. MarslandB.J. NicodL.P. Airway microbiota determines innate cell inflammatory or tissue remodeling profiles in lung transplantation.Am. J. Respir. Crit. Care Med.2016194101252126310.1164/rccm.201512‑2424OC27248293
     [Google Scholar]
  31. SuzukiM. IkariJ. AnazawaR. TanakaN. KatsumataY. ShimadaA. SuzukiE. TatsumiK. PAD4 deficiency improves bleomycin-induced neutrophil extracellular traps and fibrosis in mouse lung.Am. J. Respir. Cell Mol. Biol.202063680681810.1165/rcmb.2019‑0433OC32915635
     [Google Scholar]
  32. KornbergM.D. BhargavaP. KimP.M. PutluriV. SnowmanA.M. PutluriN. CalabresiP.A. SnyderS.H. Dimethyl fumarate targets GAPDH and aerobic glycolysis to modulate immunity.Science2018360638744945310.1126/science.aan466529599194
     [Google Scholar]
  33. TulicM.K. PicheT. VerhasseltV. Lung-gut cross-talk: evidence, mechanisms and implications for the mucosal inflammatory diseases.Clin. Exp. Allergy201646451952810.1111/cea.1272326892389
     [Google Scholar]
  34. MadanJ.C. KoestlerD.C. StantonB.A. DavidsonL. MoultonL.A. HousmanM.L. MooreJ.H. GuillM.F. MorrisonH.G. SoginM.L. HamptonT.H. KaragasM.R. PalumboP.E. FosterJ.A. HibberdP.L. O’TooleG.A. Serial analysis of the gut and respiratory microbiome in cystic fibrosis in infancy: Interaction between intestinal and respiratory tracts and impact of nutritional exposures.MBio201234e00251-1210.1128/mBio.00251‑1222911969
     [Google Scholar]
  35. GengJ. LiuY. DaiH. WangC. Fatty acid metabolism and idiopathic pulmonary fibrosis.Front. Physiol.20221279462910.3389/fphys.2021.79462935095559
     [Google Scholar]
  36. ChengD. XuQ. WangY. LiG. SunW. MaD. ZhouS. LiuY. HanL. NiC. Metformin attenuates silica-induced pulmonary fibrosis via AMPK signaling.J. Transl. Med.202119134910.1186/s12967‑021‑03036‑534399790
     [Google Scholar]
  37. MaronB.A. OldhamW.M. ChanS.Y. VargasS.O. AronsE. ZhangY.Y. LoscalzoJ. LeopoldJ.A. Upregulation of steroidogenic acute regulatory protein by hypoxia stimulates aldosterone synthesis in pulmonary artery endothelial cells to promote pulmonary vascular fibrosis.Circulation2014130216817910.1161/CIRCULATIONAHA.113.00769025001622
     [Google Scholar]
  38. AlbillosA. de GottardiA. RescignoM. The gut-liver axis in liver disease: Pathophysiological basis for therapy.J. Hepatol.202072355857710.1016/j.jhep.2019.10.00331622696
     [Google Scholar]
  39. LianN. JinH. ZhangF. WuL. ShaoJ. LuY. ZhengS. Curcumin inhibits aerobic glycolysis in hepatic stellate cells associated with activation of adenosine monophosphate-activated protein kinase.IUBMB Life201668758959610.1002/iub.151827278959
     [Google Scholar]
  40. StienstraR. Lichtenauer-KaligisE. MüllerM. Stress- (and diet-) related regulation of hepatic nuclear receptors and its relevance for ABC-transporter functions.Drug Metab. Rev.200436239140610.1081/DMR‑12003757315237861
     [Google Scholar]
  41. IncecikF. HergunerO. WillemsP. MunganN. Spinocerebellar ataxia-21 in a Turkish child.Ann. Indian Acad. Neurol.2018211687010.4103/aian.AIAN_415_1729720801
     [Google Scholar]
  42. KimE. ParkS. ChoiN. LeeJ. YoeJ. KimS. JungH.Y. KimK.T. KangH. FryerJ.D. ZoghbiH.Y. HwangD. LeeY. Deficiency of Capicua disrupts bile acid homeostasis.Sci. Rep.201551827210.1038/srep0827225653040
     [Google Scholar]
  43. MooreE.S. DaugherityE.K. KarambiziD.I. CummingsB.P. Behling-KellyE. SchaeferD.M.W. SouthardT.L. McFaddenJ.W. WeissR.S. Sex-specific hepatic lipid and bile acid metabolism alterations in Fancd2-deficient mice following dietary challenge.J. Biol. Chem.201929443156231563710.1074/jbc.RA118.00572931434739
     [Google Scholar]
  44. WuY. ChenS. WenP. WuM. WuY. MaiM. HuangJ. PGAM1 deficiency ameliorates myocardial infarction remodeling by targeting TGF-β via the suppression of inflammation, apoptosis and fibrosis.Biochem. Biophys. Res. Commun.202153493394010.1016/j.bbrc.2020.10.07033168191
     [Google Scholar]
  45. AhamedJ. TerryH. ChoiM.E. LaurenceJ. Transforming growth factor-β1-mediated cardiac fibrosis.AIDS201630453554210.1097/QAD.000000000000098226605511
     [Google Scholar]
/content/journals/cgt/10.2174/0115665232257596231011110813
Loading
Identification of the Metabolic Characteristic of Organ Fibrosis Using Microbial Analysis on RNA-seq Data
Curr. Gene Ther. 25, 761 (2025); https://doi.org/10.2174/0115665232257596231011110813
/content/journals/cgt/10.2174/0115665232257596231011110813
/content/journals/cgt/10.2174/0115665232257596231011110813
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher’s website along with the published article.

file format download Download

  • Article Type:     Research Article
Keyword(s): fatty acid metabolism; fibrosis; glycolysis; metabolic reprogramming; Microbes; Proteobacteria

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test