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image of Gut Microbiota in the Hepato-Cardiorenal Axis: Microbial Metabolites, Inflammation, and Emerging Therapeutic Targets

Abstract

Introduction

To sustain systemic homeostasis, the gut microbiota manages immunological, metabolic, and inflammatory processes. Multiorgan diseases, especially those impacting the liver, kidney, and cardiovascular system through the hepato-cardiorenal axis, have been strongly associated with dysbiosis.

Methods

A comprehensive literature search was conducted using PubMed, Scopus, Web of Science, Science Direct, and Google Scholar, with the focus on articles till 2025. Eligible sources included clinical trials, systematic reviews, and peer-reviewed academic publications that discussed metabolites, gut microbiota, and treatment approaches for diseases of the liver, kidney, and heart. A qualitative synthesis of the data indicated important mechanisms and potential treatments.

Results

SCFAs have anti-inflammatory and intestinal barrier integrity-enhancing qualities, whereas uremic toxins and TMAO promote oxidative stress, fibrosis, and vascular dysfunction. Hepatic steatosis, insulin resistance, and systemic inflammation are all affected by the dysbiosis-induced bile acid imbalance. Microbiota-targeted therapies include fecal microbiota transplantation, fiber- or polyphenol-rich diets, probiotics, prebiotics, synbiotics, and pharmacological modification of bile acid or TMAO pathways, which have potential but need more comprehensive validation.

Discussion

The findings show that, among other factors, gut metabolites—such as uremic toxins, bile acids, TMAO, and SCFAs — are key players in mediating inflammation and metabolic dysregulation across the hepato-cardiorenal axis. However, the lack of consistent treatment protocols and differences in microbiome composition limit the practical application of preclinical research that has clearly demonstrated the existence of mechanistic links. Future research should focus on long-term clinical outcomes, biomarker identification, and precise microbiome modifications to establish causation and improve therapy effectiveness.

Conclusion

The gut microbiota significantly influences the hepato-cardiorenal axis through metabolite-mediated signalling. While therapeutic modulation shows promise, precision medicine approaches and high-quality randomized trials are essential to tackle multi-organ metabolic and inflammatory diseases.

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2026-01-14
2026-02-24

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References

  1. Afzaal M. Saeed F. Shah Y.A. Hussain M. Rabail R. Socol C.T. Hassoun A. Pateiro M. Lorenzo J.M. Rusu A.V. Aadil R.M. Human gut microbiota in health and disease: Unveiling the relationship. Front. Microbiol. 2022 13 999001 10.3389/fmicb.2022.999001 36225386
    [Google Scholar]
  2. Valencia S. Zuluaga M. Florian Pérez M.C. Montoya-Quintero K.F. Candamil-Cortés M.S. Robledo S. Human gut microbiome: A connecting organ between nutrition, metabolism, and health. Int. J. Mol. Sci. 2025 26 9 4112 10.3390/ijms26094112 40362352
    [Google Scholar]
  3. de Vos W.M. Tilg H. Van Hul M. Cani P.D. Gut microbiome and health: mechanistic insights. Gut 2022 71 5 1020 1032 10.1136/gutjnl‑2021‑326789 35105664
    [Google Scholar]
  4. Tilg H. Adolph T.E. Trauner M. Gut-liver axis: Pathophysiological concepts and clinical implications. Cell Metab. 2022 34 11 1700 1718 10.1016/j.cmet.2022.09.017 36208625
    [Google Scholar]
  5. Abdalla M.M.I. Gut-liver axis in diabetes: Mechanisms and therapeutic opportunities. World J. Gastroenterol. 2025 31 29 109090 10.3748/wjg.v31.i29.109090 40809928
    [Google Scholar]
  6. Olofsson L.E. Bäckhed F. The metabolic role and therapeutic potential of the microbiome. Endocr. Rev. 2022 43 5 907 926 10.1210/endrev/bnac004 35094076
    [Google Scholar]
  7. Buchynskyi M. Kamyshna I. Halabitska I. Petakh P. Kunduzova O. Oksenych V. Kamyshnyi O. Unlocking the gut-liver axis: Microbial contributions to the pathogenesis of metabolic-associated fatty liver disease. Front. Microbiol. 2025 16 1577724 10.3389/fmicb.2025.1577724 40351307
    [Google Scholar]
  8. Yoo J.Y. Groer M. Dutra S.V.O. Sarkar A. McSkimming D.I. Correction: Gut microbiota and immune system interactions. Microorganisms 2020 8 12 2046 10.3390/microorganisms8122046 33371530
    [Google Scholar]
  9. Magne F. Gotteland M. Gauthier L. Zazueta A. Pesoa S. Navarrete P. Balamurugan R. The Firmicutes/Bacteroidetes ratio: A relevant marker of gut dysbiosis in obese patients? Nutrients 2020 12 5 1474 10.3390/nu12051474 32438689
    [Google Scholar]
  10. Isiaka AB Anakwenze VN Uzoka UH Ilodinso CR Oso MO Ekwealor CC Exploring the role of gut microbiota in human health. GSC Biol Pharm Sci. 2024 27 1 051 59 10.30574/gscbps
    [Google Scholar]
  11. Van Hul M. Cani P.D. Petitfils C. De Vos W.M. Tilg H. El-Omar E.M. What defines a healthy gut microbiome? Gut 2024 73 11 1893 1908 10.1136/gutjnl‑2024‑333378 39322314
    [Google Scholar]
  12. Yan S. Zhang X. Jia X. Zhang J. Han X. Su C. Zhao J. Gou W. Xu J. Zhang B. Characterization of the composition variation of healthy human gut microbiome in correlation with antibiotic usage and yogurt consumption. Antibiotics 2022 11 12 1827 10.3390/antibiotics11121827 36551483
    [Google Scholar]
  13. García-Gamboa R. Díaz-Torres O. Senés-Guerrero C. Gradilla-Hernández M.S. Moya A. Pérez-Brocal V. Garcia-Gonzalez A. González-Avila M. Associations between bacterial and fungal communities in the human gut microbiota and their implications for nutritional status and body weigh t. Sci. Rep. 2024 14 1 5703 10.1038/s41598‑024‑54782‑7 38459054
    [Google Scholar]
  14. Chen C. Chen S. Wang B. A glance at the gut microbiota and the functional roles of the microbes based on marmot fecal samples. Front. Microbiol. 2023 14 1035944 10.3389/fmicb.2023.1035944 37125200
    [Google Scholar]
  15. Guillén N. Pathogenicity and virulence of Entamoeba histolytica, the agent of amoebiasis. Virulence 2023 14 1 2158656 10.1080/21505594.2022.2158656 36519347
    [Google Scholar]
  16. Horrocks V. King O.G. Yip A.Y.G. Marques I.M. McDonald J.A.K. Role of the gut microbiota in nutrient competition and protection against intestinal pathogen colonization. Microbiology 2023 169 001377 10.1099/mic.0.001377
    [Google Scholar]
  17. Chen Y. Zhou J. Wang L. Role and mechanism of gut microbiota in human disease. Front. Cell. Infect. Microbiol. 2021 11 625913 10.3389/fcimb.2021.625913 33816335
    [Google Scholar]
  18. Zhao L.Y. Mei J.X. Yu G. Lei L. Zhang W.H. Liu K. Chen X.L. Kołat D. Yang K. Hu J.K. Role of the gut microbiota in anticancer therapy: from molecular mechanisms to clinical applications. Signal Transduct. Target. Ther. 2023 8 1 201 10.1038/s41392‑023‑01406‑7 37179402
    [Google Scholar]
  19. Poll B.G. Cheema M.U. Pluznick J.L. Gut microbial metabolites and blood pressure regulation: Focus on SCFAs and TMAO. Physiology (Bethesda) 2020 35 4 275 284 10.1152/physiol.00004.2020 32490748
    [Google Scholar]
  20. Qi L. Chen Y. Circulating bile acids as biomarkers for disease diagnosis and prevention. J. Clin. Endocrinol. Metab. 2023 108 2 251 270 10.1210/clinem/dgac659 36374935
    [Google Scholar]
  21. Pei T. Li W. Zhou Z. Zhang Q. Yu G. Yin S. Chen H. Tang J. The relationship between tryptophan metabolism and gut microbiota: Interaction mechanism and potential effects in infection treatment. Microbiol. Res. 2025 298 128211 10.1016/j.micres.2025.128211 40393170
    [Google Scholar]
  22. Swallah M.S. Sun H. Affoh R. Fu H. Yu H. Antioxidant potential overviews of secondary metabolites (polyphenols) in fruits. Int. J. Food Sci. 2020 2020 1 8 10.1155/2020/9081686 32455130
    [Google Scholar]
  23. Miyajima M. Amino acids: Key sources for immunometabolites and immunotransmitters. Int. Immunol. 2020 32 7 435 446 10.1093/intimm/dxaa019 32383454
    [Google Scholar]
  24. Ademosun A.O. Ajeigbe O.F. Ademosun M.T. Ogunruku O.O. Oboh G. Improving gut microbiome through diet rich in dietary fibre and polyphenols: The case for orange peels. Hum. Nutr. Metab. 2025 39 200295 10.1016/j.hnm.2024.200295
    [Google Scholar]
  25. Pham N.H.T. Joglekar M.V. Wong W.K.M. Nassif N.T. Simpson A.M. Hardikar A.A. Short-chain fatty acids and insulin sensitivity: A systematic review and meta-analysis. Nutr. Rev. 2024 82 2 193 209 10.1093/nutrit/nuad042 37290429
    [Google Scholar]
  26. Facchin S. Bertin L. Bonazzi E. Lorenzon G. De Barba C. Barberio B. Zingone F. Maniero D. Scarpa M. Ruffolo C. Angriman I. Savarino E.V. Short-chain fatty acids and human health: From metabolic pathways to current therapeutic implications. Life 2024 14 5 559 10.3390/life14050559 38792581
    [Google Scholar]
  27. Fusco W. Lorenzo M.B. Cintoni M. Porcari S. Rinninella E. Kaitsas F. Lener E. Mele M.C. Gasbarrini A. Collado M.C. Cammarota G. Ianiro G. Short-chain fatty-acid-producing bacteria: Key components of the human gut microbiota. Nutrients 2023 15 9 2211 10.3390/nu15092211 37432351
    [Google Scholar]
  28. He J. Zhang P. Shen L. Niu L. Tan Y. Chen L. Zhao Y. Bai L. Hao X. Li X. Zhang S. Zhu L. Short-chain fatty acids and their association with signalling pathways in inflammation, glucose and lipid metabolism. Int. J. Mol. Sci. 2020 21 17 6356 10.3390/ijms21176356 32887215
    [Google Scholar]
  29. Recharla N. Geesala R. Shi X.Z. Gut microbial metabolite butyrate and its therapeutic role in inflammatory bowel disease: A literature review. Nutrients 2023 15 10 2275 10.3390/nu15102275 37242159
    [Google Scholar]
  30. Ney L.M. Wipplinger M. Grossmann M. Engert N. Wegner V.D. Mosig A.S. Short chain fatty acids: Key regulators of the local and systemic immune response in inflammatory diseases and infections. Open Biol. 2023 13 3 230014 10.1098/rsob.230014 36977462
    [Google Scholar]
  31. Feng Y. Xu D. Short-chain fatty acids are potential goalkeepers of atherosclerosis. Front. Pharmacol. 2023 14 1271001 10.3389/fphar.2023.1271001 38027009
    [Google Scholar]
  32. Stubbs J.R. House J.A. Ocque A.J. Zhang S. Johnson C. Kimber C. Schmidt K. Gupta A. Wetmore J.B. Nolin T.D. Spertus J.A. Yu A.S. Serum trimethylamine-N-oxide is elevated in CKD and correlates with coronary atherosclerosis burden. J. Am. Soc. Nephrol. 2016 27 1 305 313 10.1681/ASN.2014111063 26229137
    [Google Scholar]
  33. Zhou Y. Zhang Y. Jin S. Lv J. Li M. Feng N. The gut microbiota derived metabolite trimethylamine N-oxide: Its important role in cancer and other diseases. Biomed. Pharmacother. 2024 177 117031 10.1016/j.biopha.2024.117031 38925016
    [Google Scholar]
  34. Heinrich-Sanchez Y. Vital M. Trimethylamine- N -oxide formation, the bacterial taxa involved and intervention strategies to reduce its concentration in the human body. Ann. Med. 2025 57 1 2525403 10.1080/07853890.2025.2525403 40598778
    [Google Scholar]
  35. Wastyk H.C. Fragiadakis G.K. Perelman D. Dahan D. Merrill B.D. Yu F.B. Topf M. Gonzalez C.G. Van Treuren W. Han S. Robinson J.L. Elias J.E. Sonnenburg E.D. Gardner C.D. Sonnenburg J.L. Gut-microbiota-targeted diets modulate human immune status. Cell 2021 184 16 4137 4153.e14 10.1016/j.cell.2021.06.019 34256014
    [Google Scholar]
  36. Fan X. McCullough R.L. Huang E. Bellar A. Kim A. Poulsen K.L. McClain C.J. Mitchell M. McCullough A.J. Radaeva S. Barton B. Szabo G. Dasarathy S. Rotroff D.M. Nagy L.E. Diagnostic and prognostic significance of complement in patients with alcohol-associated hepatitis. Hepatology 2021 73 3 983 997 10.1002/hep.31419 32557728
    [Google Scholar]
  37. Jing L. Zhang H. Xiang Q. Shen L. Guo X. Zhai C. Hu H. Targeting trimethylamine N-oxide: A new therapeutic strategy for alleviating atherosclerosis. Front. Cardiovasc. Med. 2022 9 864600 10.3389/fcvm.2022.864600 35770223
    [Google Scholar]
  38. Valenbreder I.M.E. Balăn S. Breuer M. Adriaens M.E. Mapping out the gut microbiota-dependent trimethylamine N-oxide super pathway for systems biology applications. Front. Syst. Biol. 2023 3 1074749 10.3389/fsysb.2023.1074749 40809486
    [Google Scholar]
  39. Huang R. Yan L. Lei Y. The gut microbial-derived metabolite trimethylamine N-oxide and atrial fibrillation: Relationships, mechanisms, and therapeutic strategies. Clin. Interv. Aging 2021 16 1975 1986 10.2147/CIA.S339590 34876810
    [Google Scholar]
  40. Shao J.W. Ge T.T. Chen S.Z. Wang G. Yang Q. Huang C.H. Xu L.C. Chen Z. Role of bile acids in liver diseases mediated by the gut microbiome. World J. Gastroenterol. 2021 27 22 3010 3021 10.3748/wjg.v27.i22.3010 34168404
    [Google Scholar]
  41. Majait S. Nieuwdorp M. Kemper M. Soeters M. The black box orchestra of gut bacteria and bile acids: Who is the conductor? Int. J. Mol. Sci. 2023 24 3 1816 10.3390/ijms24031816 36768140
    [Google Scholar]
  42. Zerem E. Kunosic S. Kurtcehajic A. Zerem D. Zerem O. Bile acids in metabolic dysfunction-associated steatotic liver disease. World J. Hepatol. 2025 17 8 108606 10.4254/wjh.v17.i8.108606 40901599
    [Google Scholar]
  43. Jin W. Zheng M. Chen Y. Xiong H. Update on the development of TGR5 agonists for human diseases. Eur. J. Med. Chem. 2024 271 116462 10.1016/j.ejmech.2024.116462 38691888
    [Google Scholar]
  44. Cui C. Gao S. Shi J. Wang K. Gut-liver axis: The role of intestinal microbiota and their metabolites in the progression of metabolic dysfunction-associated steatotic liver disease. Gut Liver 2025 19 4 479 507 10.5009/gnl240539 40336226
    [Google Scholar]
  45. Wang X. Peng J. Cai P. Xia Y. Yi C. Shang A. Akanyibah F.A. Mao F. The emerging role of the gut microbiota and its application in inflammatory bowel disease. Biomed. Pharmacother. 2024 179 117302 10.1016/j.biopha.2024.117302 39163678
    [Google Scholar]
  46. Liu P. Jin M. Hu P. Sun W. Tang Y. Wu J. Zhang D. Yang L. He H. Xu X. Gut microbiota and bile acids: Metabolic interactions and impacts on diabetic kidney disease. Curr. Res. Microb. Sci. 2024 7 100315 10.1016/j.crmicr.2024.100315 39726973
    [Google Scholar]
  47. Li Y. Wang L. Yi Q. Luo L. Xiong Y. Regulation of bile acids and their receptor FXR in metabolic diseases. Front. Nutr. 2024 11 1447878 10.3389/fnut.2024.1447878 39726876
    [Google Scholar]
  48. Amini Khiabani S. Asgharzadeh M. Samadi Kafil H. Chronic kidney disease and gut microbiota. Heliyon 2023 9 8 e18991 10.1016/j.heliyon.2023.e18991 37609403
    [Google Scholar]
  49. Wang M. ApoC3 fires up monocytes to promote tissue damage. Nat. Rev. Nephrol. 2020 16 3 131 10.1038/s41581‑019‑0246‑0 31853009
    [Google Scholar]
  50. Bas M. Daglilar S. Kuskonmaz N. Kalkandelen C. Erdemir G. Kuruca S.E. Tulyaganov D. Yoshioka T. Gunduz O. Ficai D. Ficai A. Mechanical and biocompatibility properties of calcium phosphate bioceramics derived from salmon fish bone wastes. Int. J. Mol. Sci. 2020 21 21 8082 10.3390/ijms21218082 33138182
    [Google Scholar]
  51. Gut E Soulage O Popkov VA Zharikova AA Demchenko EA Andrianova NV Gut microbiota as a source of uremic toxins. Toxins 2022 23 1 483 10.3390/ijms23010483.
    [Google Scholar]
  52. Xu Y. Bi W.D. Shi Y.X. Liang X.R. Wang H.Y. Lai X.L. Bian X.L. Guo Z.Y. Derivation and elimination of uremic toxins from kidney-gut axis. Front. Physiol. 2023 14 1123182 10.3389/fphys.2023.1123182 37650112
    [Google Scholar]
  53. Cozzolino M. Magagnoli L. Ciceri P. From physicochemical classification to multidimensional insights: A comprehensive review of uremic toxin research. Toxins 2025 17 6 295 10.3390/toxins17060295 40559873
    [Google Scholar]
  54. Lin X. Liang W. Li L. Xiong Q. He S. Zhao J. Guo X. Xiang S. Zhang P. Wang H. Ying C. Yao Y. Zuo X. The accumulation of gut microbiome–derived indoxyl sulfate and p-cresyl sulfate in patients with end-stage renal disease. J. Ren. Nutr. 2022 32 5 578 586 10.1053/j.jrn.2021.09.007 34736844
    [Google Scholar]
  55. Xu X. Zhou J. Xie H. Zhang R. Gu B. Liu L. Liu M. Chang X. Immunomodulatory mechanisms of the gut microbiota and metabolites on regulatory T cells in rheumatoid arthritis. Front. Immunol. 2025 16 1610254 10.3389/fimmu.2025.1610254 40692793
    [Google Scholar]
  56. Xu Z. Wang T. Wang Y. Li Y. Sun Y. Qiu H.J. Short-chain fatty acids: Key antiviral mediators of gut microbiota. Front. Immunol. 2025 16 1614879 10.3389/fimmu.2025.1614879 40787446
    [Google Scholar]
  57. Qin N. Xie X. Deng R. Gao S. Zhu T. The role of the tryptophan metabolites in gut microbiota-brain axis and potential treatments: a focus on ischemic stroke. Front. Pharmacol. 2025 16 1578018 10.3389/fphar.2025.1578018 40556758
    [Google Scholar]
  58. Kuo W.T. Zuo L. Odenwald M.A. Madha S. Singh G. Gurniak C.B. Abraham C. Turner J.R. The tight junction protein ZO-1 is dispensable for barrier function but critical for effective mucosal repair. Gastroenterology 2021 161 6 1924 1939 10.1053/j.gastro.2021.08.047 34478742
    [Google Scholar]
  59. Eom J.Y. Choi S.H. Kim H.J. Kim D. Bae J.H. Kwon G.S. Lee D. Hwang J.H. Kim D.K. Baek M.C. Cho Y.E. Hemp-derived nanovesicles protect leaky gut and liver injury in dextran sodium sulfate-induced colitis. Int. J. Mol. Sci. 2022 23 17 9955 10.3390/ijms23179955 36077356
    [Google Scholar]
  60. Moonwiriyakit A. Pathomthongtaweechai N. Steinhagen P.R. Chantawichitwong P. Satianrapapong W. Pongkorpsakol P. Tight junctions: From molecules to gastrointestinal diseases. Tissue Barriers 2023 11 2 2077620 10.1080/21688370.2022.2077620 35621376
    [Google Scholar]
  61. Audo R. Sanchez P. Rivière B. Mielle J. Tan J. Lukas C. Macia L. Morel J. Immediato Daien C. Rheumatoid arthritis is associated with increased gut permeability and bacterial translocation that are reversed by inflammation control. Rheumatology (Oxford) 2023 62 3 1264 1271 10.1093/rheumatology/keac454
    [Google Scholar]
  62. Kaminsky L.W. Al-Sadi R. Ma T.Y. IL-1β and the intestinal epithelial tight junction barrier. Front. Immunol. 2021 12 767456 10.3389/fimmu.2021.767456 34759934
    [Google Scholar]
  63. Hussain Z. Park H. Inflammation and impaired gut physiology in post-operative ileus: Mechanisms and treatment options. J. Neurogastroenterol. Motil. 2022 28 4 517 530 10.5056/jnm22100 36250359
    [Google Scholar]
  64. Kim C.H. Complex regulatory effects of gut microbial short-chain fatty acids on immune tolerance and autoimmunity. Cell. Mol. Immunol. 2023 20 4 341 350 10.1038/s41423‑023‑00987‑1 36854801
    [Google Scholar]
  65. Meyer F. Wendling D. Demougeot C. Prati C. Verhoeven F. Cytokines and intestinal epithelial permeability: A systematic review. Autoimmun. Rev. 2023 22 6 103331 10.1016/j.autrev.2023.103331 37030338
    [Google Scholar]
  66. Han B. Lv X. Liu G. Li S. Fan J. Chen L. Huang Z. Lin G. Xu X. Huang Z. Zhan L. Lv X. Gut microbiota-related bile acid metabolism-FXR/TGR5 axis impacts the response to anti-α4β7-integrin therapy in humanized mice with colitis. Gut Microbes 2023 15 1 2232143 10.1080/19490976.2023.2232143
    [Google Scholar]
  67. Fujisaka S. Watanabe Y. Tobe K. The gut microbiome: A core regulator of metabolism. J. Endocrinol. 2023 256 3 256 10.1530/JOE‑22‑0111 36458804
    [Google Scholar]
  68. Gao P. Rinott E. Dong D. Mei Z. Wang F. Liu Y. Kamer O. Yaskolka Meir A. Tuohy K.M. Blüher M. Stumvoll M. Stampfer M.J. Shai I. Wang D.D. Gut microbial metabolism of bile acids modifies the effect of Mediterranean diet interventions on cardiometabolic risk in a randomized controlled trial. Gut Microbes 2024 16 1 2426610 10.1080/19490976.2024.2426610 39535126
    [Google Scholar]
  69. Peng Y.L. Wang S.H. Zhang Y.L. Chen M.Y. He K. Li Q. Huang W.H. Zhang W. Effects of bile acids on the growth, composition and metabolism of gut bacteria. NPJ Biofilms Microbiomes 2024 10 1 112 10.1038/s41522‑024‑00566‑w 39438471
    [Google Scholar]
  70. Antwi M.B. Jennings A. Lefere S. Clarisse D. Geerts A. Devisscher L. De Bosscher K. Unlocking therapeutic potential: exploring cross-talk among emerging nuclear receptors to combat metabolic dysfunction in steatotic liver disease. npj Metabolic Health and Disease 2024 2 1 13 10.1038/s44324‑024‑00013‑6 40603501
    [Google Scholar]
  71. Bertolini A. Fiorotto R. Strazzabosco M. Bile acids and their receptors: modulators and therapeutic targets in liver inflammation. Semin. Immunopathol. 2022 44 4 547 564 10.1007/s00281‑022‑00935‑7 35415765
    [Google Scholar]
  72. Ding C. Wang Z. Dou X. Yang Q. Ning Y. Kao S. Sang X. Hao M. Wang K. Peng M. Zhang S. Han X. Cao G. Farnesoid X receptor: From structure to function and its pharmacology in liver fibrosis. Aging Dis. 2023 0 10.14336/AD.2023.0830 37815898
    [Google Scholar]
  73. Panzitt K. Wagner M. FXR in liver physiology: Multiple faces to regulate liver metabolism. Biochim. Biophys. Acta Mol. Basis Dis. 2021 1867 7 166133 10.1016/j.bbadis.2021.166133 33771667
    [Google Scholar]
  74. Thibaut M.M. Bindels L.B. Crosstalk between bile acid-activated receptors and microbiome in entero-hepatic inflammation. Trends Mol. Med. 2022 28 3 223 236 10.1016/j.molmed.2021.12.006 35074252
    [Google Scholar]
  75. Kadasah S.F. Radwan M.O. Overview of ursolic acid potential for the treatment of metabolic disorders, autoimmune diseases, and cancers via nuclear receptor pathways. Biomedicines 2023 11 10 2845 10.3390/biomedicines11102845 37893218
    [Google Scholar]
  76. Azizsoltani A. Niknam B. Taghizadeh-Teymorloei M. Ghoodjani E. Dianat-Moghadam H. Alizadeh E. Therapeutic implications of obeticholic acid, a farnesoid X receptor agonist, in the treatment of liver fibrosis. Biomed. Pharmacother. 2025 189 118249 10.1016/j.biopha.2025.118249 40527040
    [Google Scholar]
  77. Almeqdadi M. Gordon F.D. Farnesoid X receptor agonists: A promising therapeutic strategy for gastrointestinal diseases. Gastro Hep Adv. 2024 3 3 344 352 10.1016/j.gastha.2023.09.013 39131134
    [Google Scholar]
  78. Duan Y. Gong K. Xu S. Zhang F. Meng X. Han J. Regulation of cholesterol homeostasis in health and diseases: from mechanisms to targeted therapeutics. Signal Transduct. Target. Ther. 2022 7 1 265 10.1038/s41392‑022‑01125‑5 35918332
    [Google Scholar]
  79. Aron-Wisnewsky J. Vigliotti C. Witjes J. Le P. Holleboom A.G. Verheij J. Nieuwdorp M. Clément K. Gut microbiota and human NAFLD: disentangling microbial signatures from metabolic disorders. Nat. Rev. Gastroenterol. Hepatol. 2020 17 5 279 297 10.1038/s41575‑020‑0269‑9 32152478
    [Google Scholar]
  80. Albillos A. de Gottardi A. Rescigno M. The gut-liver axis in liver disease: Pathophysiological basis for therapy. J. Hepatol. 2020 72 3 558 577 10.1016/j.jhep.2019.10.003 31622696
    [Google Scholar]
  81. Arab J.P. Arrese M. Shah V.H. Gut microbiota in non‐alcoholic fatty liver disease and alcohol‐related liver disease: Current concepts and perspectives. Hepatol. Res. 2020 50 4 407 418 10.1111/hepr.13473 31840358
    [Google Scholar]
  82. Cani P.D. Moens de Hase E. Van Hul M. Gut microbiota and host metabolism: From proof of concept to therapeutic intervention. Microorganisms 2021 9 6 1302 10.3390/microorganisms9061302 34203876
    [Google Scholar]
  83. Kordy K. Li F. Lee D.J. Kinchen J.M. Jew M.H. La Rocque M.E. Zabih S. Saavedra M. Woodward C. Cunningham N.J. Tobin N.H. Aldrovandi G.M. Metabolomic predictors of non-alcoholic steatohepatitis and advanced fibrosis in children. Front. Microbiol. 2021 12 713234 10.3389/fmicb.2021.713234 34475864
    [Google Scholar]
  84. Han D. Wu Y. Lu D. Pang J. Hu J. Zhang X. Wang Z. Zhang G. Wang J. Polyphenol-rich diet mediates interplay between macrophage-neutrophil and gut microbiota to alleviate intestinal inflammation. Cell Death Dis. 2023 14 10 656 10.1038/s41419‑023‑06190‑4 37813835
    [Google Scholar]
  85. Yang M. Khoukaz L. Qi X. Kimchi E.T. Staveley-O’Carroll K.F. Li G. Diet and gut microbiota interaction-derived metabolites and intrahepatic immune response in NAFLD development and treatment. Biomedicines 2021 9 12 1893 10.3390/biomedicines9121893 34944709
    [Google Scholar]
  86. An L. Wirth U. Koch D. Schirren M. Drefs M. Koliogiannis D. Nieß H. Andrassy J. Guba M. Bazhin A.V. Werner J. Kühn F. The role of gut-derived lipopolysaccharides and the intestinal barrier in fatty liver diseases. J. Gastrointest. Surg. 2022 26 3 671 683 10.1007/s11605‑021‑05188‑7 34734369
    [Google Scholar]
  87. Kessoku T. Kobayashi T. Imajo K. Tanaka K. Yamamoto A. Takahashi K. Kasai Y. Ozaki A. Iwaki M. Nogami A. Honda Y. Ogawa Y. Kato S. Higurashi T. Hosono K. Yoneda M. Okamoto T. Usuda H. Wada K. Kobayashi N. Saito S. Nakajima A. Endotoxins and non-alcoholic fatty liver disease. Front. Endocrinol. (Lausanne) 2021 12 770986 10.3389/fendo.2021.770986 34777261
    [Google Scholar]
  88. Wang J. Wang X. Zhuo E. Chen B. Chan S. Gut‑liver axis in liver disease: From basic science to clinical treatment (Review). Mol. Med. Rep. 2024 31 1 10 10.3892/mmr.2024.13375 39450549
    [Google Scholar]
  89. Jarmukhanov Z. Mukhanbetzhanov N. Kozhakhmetov S. Nurgaziyev M. Sailybayeva A. Bekbossynova M. Kushugulova A. The association between the gut microbiota metabolite trimethylamine N-oxide and heart failure. Front. Microbiol. 2024 15 1440241 10.3389/fmicb.2024.1440241 39391607
    [Google Scholar]
  90. Canyelles M. Borràs C. Rotllan N. Tondo M. Escolà-Gil J.C. Blanco-Vaca F. Gut microbiota-derived TMAO: A causal factor promoting atherosclerotic cardiovascular disease? Int. J. Mol. Sci. 2023 24 3 1940 10.3390/ijms24031940 36768264
    [Google Scholar]
  91. Yu X. Wang Y. Yang R. Wang Z. Wang X. Wang S. Zhang W. Dong J. Chen W. Ji F. Gao W. Trimethylamine N-oxide predicts cardiovascular events in coronary artery disease patients with diabetes mellitus: A prospective cohort study. Front. Endocrinol. (Lausanne) 2024 15 1360861 10.3389/fendo.2024.1360861 39092284
    [Google Scholar]
  92. Zhang Y. Huang L. Ou S. Research progress on the association between TMAO and vascular calcification in patients with chronic kidney disease. Ren. Fail. 2024 46 2 2435485 10.1080/0886022X.2024.2435485 39627031
    [Google Scholar]
  93. Chulenbayeva L. Issilbayeva A. Sailybayeva A. Bekbossynova M. Kozhakhmetov S. Kushugulova A. Short-chain fatty acids and their metabolic interactions in heart failure. Biomedicines 2025 13 2 343 10.3390/biomedicines13020343 40002756
    [Google Scholar]
  94. Li X.S. Obeid S. Klingenberg R. Gencer B. Mach F. Räber L. Gut microbiota-dependent trimethylamine N-oxide in acute coronary syndromes: a prognostic marker beyond traditional risk factors. Eur. Heart J. 2017 38 11 814 824 10.1093/eurheartj/ehw582 28077467
    [Google Scholar]
  95. Zhang Y. Wang Y. Ke B. Du J. TMAO: how gut microbiota contributes to heart failure. Transl. Res. 2021 228 109 125 10.1016/j.trsl.2020.08.007 32841736
    [Google Scholar]
  96. Berding K. Vlckova K. Marx W. Schellekens H. Stanton C. Clarke G. Jacka F. Dinan T.G. Cryan J.F. Diet and the microbiota–gut–brain axis: sowing the seeds of good mental health. Adv. Nutr. 2021 12 4 1239 1285 10.1093/advances/nmaa181 33693453
    [Google Scholar]
  97. Xu J. Moore B.N. Pluznick J.L. Short-chain fatty acid receptors and blood pressure regulation. Hypertension 2022 79 10 2127 2137 10.1161/HYPERTENSIONAHA.122.18558 35912645
    [Google Scholar]
  98. Tsuji K. Uchida N. Nakanoh H. Fukushima K. Haraguchi S. Kitamura S. Wada J. The gut–kidney axis in chronic kidney diseases. Diagnostics 2024 15 1 21 10.3390/diagnostics15010021 39795549
    [Google Scholar]
  99. Lim X. Ooi L. Ding U. Wu H.H.L. Chinnadurai R. Gut microbiota in patients receiving dialysis: A review. Pathogens 2024 13 9 801 10.3390/pathogens13090801 39338992
    [Google Scholar]
  100. McIntyre C.W. Harrison L.E.A. Eldehni M.T. Jefferies H.J. Szeto C.C. John S.G. Sigrist M.K. Burton J.O. Hothi D. Korsheed S. Owen P.J. Lai K-B. Li P.K.T. Circulating endotoxemia. Clin. J. Am. Soc. Nephrol. 2011 6 1 133 141 10.2215/CJN.04610510 20876680
    [Google Scholar]
  101. Cheng T.H. Ma M.C. Liao M.T. Zheng C.M. Lu K.C. Liao C.H. Hou Y.C. Liu W.C. Lu C.L. Indoxyl sulfate, a tubular toxin, contributes to the development of chronic kidney disease. Toxins 2020 12 11 684 10.3390/toxins12110684 33138205
    [Google Scholar]
  102. Lim Y.J. Sidor N.A. Tonial N.C. Che A. Urquhart B.L. Uremic toxins in the progression of CKD and CVD: Mechanisms and therapeutic targets. Toxins 2021 13 2 142 10.3390/toxins13020142
    [Google Scholar]
  103. Peris-Fernández M. Roca-Marugán M. Amengual J.L. Balaguer-Timor Á. Viejo-Boyano I. Soldevila-Orient A. Uremic toxins and inflammation in stage 5 CKD. Biomedicines 2024 12 3 38540220
    [Google Scholar]
  104. Noels H. van der Vorst E.P.C. Rubin S. Emmett A. Marx N. Tomaszewski M. Renal–cardiac crosstalk in heart failure. Circ. Res. 2025 136 9 1306 1334 10.1161/CIRCRESAHA.124.325488 40403103
    [Google Scholar]
  105. Yan X. Shi L. Zhu X. Zhao J. Zhao Y. Luo J. From microbial homeostasis to systemic pathogenesis: Gut flora in neuropsychiatric, metabolic, and cancer disorders. J. Inflamm. Res. 2025 18 8851 8873 10.2147/JIR.S531671 40635765
    [Google Scholar]
  106. Palm C.L. Nijholt K.T. Bakker B.M. Westenbrink B.D. Short-chain fatty acids in the metabolism of heart failure. Front. Cardiovasc. Med. 2022 9 915102 10.3389/fcvm.2022.915102 35898266
    [Google Scholar]
  107. Koratala A. Verbrugge F. Kazory A. Hepato-cardio-renal syndrome. Adv. Kidney Dis. Health 2024 31 2 127 132 10.1053/j.akdh.2023.07.002 38649216
    [Google Scholar]
  108. Wang Q. Lu X. Hu W. Zhang C. Liu K. Tong K. Gut–liver axis mechanism of prenatal caffeine exposure and NAFLD susceptibility. Food Sci. Hum. Wellness 2024 13 6 3522 3535 10.26599/FSHW.2023.9250035
    [Google Scholar]
  109. Wang S. Zhang K. Huang Q. Meng F. Deng S. TLR4 signalling in ischemia/reperfusion injury: a promising target for linking inflammation, oxidative stress and programmed cell death to improve organ transplantation outcomes. Front. Immunol. 2024 15 1447060 10.3389/fimmu.2024.1447060 39091500
    [Google Scholar]
  110. Sandireddy R. Sakthivel S. Gupta P. Behari J. Tripathi M. Singh B.K. ystemic impacts of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) on heart, muscle, and kidney related diseases. Front. Cell Dev. Biol. 2024 12 1433857 39086662 10.3389/fcell.2024.1433857
    [Google Scholar]
  111. Bingyu W. Jun Q. Bingyang L. Xi Y. Jianqing Z. Jiangfang L. Trimethylamine N-oxide promotes endothelial–mesenchymal transition. Int. Immunopharmacol. 2024 142 113209 10.1016/j.intimp.2024.113209 39340998
    [Google Scholar]
  112. Chiuariu T. Șalaru D. Ureche C. Vasiliu L. Lupu A. Lupu V.V. Șerban A.M. Zăvoi A. Benchea L.C. Clement A. Tudurachi B.S. Sascău R.A. Stătescu C. Cardiac and renal fibrosis: The silent killer in the cardiovascular continuum. J. Cardiovasc. Dev. Dis. 2024 11 2 62 10.3390/jcdd11020062 38392276
    [Google Scholar]
  113. Camargo L.L. Wang Y. Rios F.J. McBride M. Montezano A.C. Touyz R.M. Oxidative and ER stress in hypertension vasculopathy. Can. J. Cardiol. 2023 39 12 1874 1887 10.1016/j.cjca.2023.10.012 37875177
    [Google Scholar]
  114. Li Y. Liu Q. Pan C.Y. Lan X.Y. Free fatty acid receptor 2: mechanisms and clinical prospects. Pharmacol. Ther. 2025 272 108878 10.1016/j.pharmthera.2025.108878 40383399
    [Google Scholar]
  115. Lee D.H. Kim M.T. Han J.H. GPR41 and GPR43: From development to metabolic regulation. Biomed. Pharmacother. 2024 175 116735 10.1016/j.biopha.2024.116735 38744220
    [Google Scholar]
  116. Gao J. Mang Q. Sun Y. Xu G. SCFAs modulate hepatic glucose and lipid metabolism via FFAR/AMPK signaling. Int. J. Mol. Sci. 2025 26 8 3654 10.3390/ijms26083654 40332278
    [Google Scholar]
  117. R Muralitharan R. Zheng T. Dinakis E. Xie L. Barbaro-Wahl A. Jama H.A. Nakai M. Paterson M. Leung K.C. McArdle Z. Mirabito Colafella K. Johnson C. Qin W. Salimova E. Bitto N.J. Kaparakis-Liaskos M. Kaye D.M. O’Donnell J.A. Mackay C.R. Marques F.Z. Gut microbiota metabolites sensed by GPR41/43 protect against hypertension. Circ. Res. 2025 136 4 e20 e33 10.1161/CIRCRESAHA.124.325770 39840468
    [Google Scholar]
  118. Wang H. Kang T. Li W. Reduced maternal SCFAs in GDM diminish GPR43 signaling and induce offspring CAKUT. Commun. Biol. 2025 8 1 1063 10.1038/s42003‑025‑08469‑y 40676152
    [Google Scholar]
  119. HuangW.ManY.GaoC.ZhouL.GuJ.XuH. f Short-chain fatty acids ameliorate diabetic nephropathy via GPR43-mediated inhibition of oxidative stress and NF-κB signaling. Oxid. Med. Cell. Longev. 2020 2020 1 21 10.1155/2020/8706898
    [Google Scholar]
  120. Wang Y. Dou W. Qian X. Chen H. Zhang Y. Yang L. Wu Y. Xu X. Advancements in the study of short-chain fatty acids and their therapeutic effects on atherosclerosis. Life Sci. 2025 369 123528 10.1016/j.lfs.2025.123528 40049368
    [Google Scholar]
  121. Abudureheman D. Janaerbieke S. Song Y. Han S. Yimaer W. Wang H. Mechanisms and intervention strategies of TMAO in abdominal aortic aneurysm. Cardiology 2025 1 32 10.1159/000546190 40349700
    [Google Scholar]
  122. Mazziotta C. Tognon M. Martini F. Torreggiani E. Rotondo J.C. Probiotics mechanism of action on immune cells and beneficial effects on human health. Cells 2023 12 1 184 10.3390/cells12010184 36611977
    [Google Scholar]
  123. Teichmann J. Cockburn D.W. In vitro fermentation reveals changes in butyrate production dependent on resistant starch source and microbiome composition. Front. Microbiol. 2021 12 640253 10.3389/fmicb.2021.640253 33995299
    [Google Scholar]
  124. Latif A. Shehzad A. Niazi S. Zahid A. Ashraf W. Iqbal M.W. Rehman A. Riaz T. Aadil R.M. Khan I.M. Özogul F. Rocha J.M. Esatbeyoglu T. Korma S.A. Probiotics: Mechanism of action, health benefits and their application in food industries. Front. Microbiol. 2023 14 1216674 10.3389/fmicb.2023.1216674 37664108
    [Google Scholar]
  125. Fu J. Zheng Y. Gao Y. Xu W. Dietary fiber intake and gut microbiota in human health. Microorganisms 2022 10 12 2507 10.3390/microorganisms10122507 36557760
    [Google Scholar]
  126. Oliver A. Chase A.B. Weihe C. Orchanian S.B. Riedel S.F. Hendrickson C.L. Lay M. Sewall J.M. Martiny J.B.H. Whiteson K. High-fiber, whole-food dietary intervention alters the human gut microbiome but not fecal short-chain fatty acids. mSystems 2021 6 2 10.1128/msystems.00115‑21 33727392
    [Google Scholar]
  127. Bian J. Liebert A. Bicknell B. Chen X.M. Huang C. Pollock C.A. Faecal microbiota transplantation and chronic kidney disease. Nutrients 2022 14 12 2528 10.3390/nu14122528 35745257
    [Google Scholar]
  128. Li D. Lu Y. Yuan S. Cai X. He Y. Chen J. Wu Q. He D. Fang A. Bo Y. Song P. Bogaert D. Tsilidis K. Larsson S.C. Yu H. Zhu H. Theodoratou E. Zhu Y. Li X. Gut microbiota–derived metabolite trimethylamine-N-oxide and multiple health outcomes: An umbrella review and updated meta-analysis. Am. J. Clin. Nutr. 2022 116 1 230 243 10.1093/ajcn/nqac074 35348578
    [Google Scholar]
  129. Silva Y.P. Bernardi A. Frozza R.L. Short-chain fatty acids from gut microbiota in gut–brain communication. Front. Endocrinol. (Lausanne) 2020 11 25 10.3389/fendo.2020.00025 32082260
    [Google Scholar]
  130. Boonma P. Shapiro J.M. Hollister E.B. Badu S. Wu Q. Weidler E.M. Probiotic VSL#3 reduces colonic permeability and pain in IBS patients. Front. Pain Res. (Lausanne) 2021 ••• 2
    [Google Scholar]
  131. Grimaldi R. Swann J.R. Vulevic J. Gibson G.R. Costabile A. Fermentation properties and prebiotic activity of Bimuno® galacto-oligosaccharide in vitro. Br. J. Nutr. 2016 116 3 480 486 10.1017/S0007114516002269 27267934
    [Google Scholar]
  132. Kotzampassi K. Giamarellos-Bourboulis E.J. Voudouris A. Kazamias P. Eleftheriadis E. Synbiotic 2000Forte® in critically ill trauma patients: a randomized controlled trial. World J. Surg. 2006 30 10 1848 1855 10.1007/s00268‑005‑0653‑1 16983476
    [Google Scholar]
  133. Chen J.P. Chen G.C. Wang X.P. Qin L. Bai Y. Dietary fiber and metabolic syndrome: meta-analysis and mechanisms. Nutrients 2017 10 1 24 10.3390/nu10010024 29278406
    [Google Scholar]
  134. Guasch-Ferré M. Salas-Salvadó J. Ros E. Estruch R. Corella D. Fitó M. Martínez-González M.A. Arós F. Gómez-Gracia E. Fiol M. Lapetra J. Lamuela-Raventos R.M. Tur J. Martinez J.A. Serra-Majem L. Pintó X. PREDIMED Investigators The PREDIMED trial, Mediterranean diet and health outcomes: How strong is the evidence? Nutr. Metab. Cardiovasc. Dis. 2017 27 7 624 632 10.1016/j.numecd.2017.05.004 28684083
    [Google Scholar]
  135. Doosetty S. Umeh C. Eastwood W. Samreen I. Penchala A. Kaur H. Chilinga C. Kaur G. Mohta T. Nakka S. Tangirala P. Nakka S. Efficacy of fecal microbiota (Rebyota) in recurrent Clostridium difficile infections: systematic review and meta-analysis. Cureus 2024 16 4 e58862 10.7759/cureus.58862 38800285
    [Google Scholar]
  136. Annunziata G. Ciampaglia R. Maisto M. D’Avino M. Caruso D. Tenore G.C. Taurisolo® reduces biomarkers associated with atherosclerosis. Front. Cardiovasc. Med. 2021 ••• 8
    [Google Scholar]
  137. Smith S.M. Pegram A.H. Obeticholic Acid. J. Pharm. Technol. 2017 33 2 66 71 10.1177/8755122516687122
    [Google Scholar]
  138. Roda A. Oral formulation for ileo-cecal sodium butyrate delivery. World J. Gastroenterol. 2007 13 7 1079 1084 10.3748/wjg.v13.i7.1079 17373743
    [Google Scholar]
  139. Krupa KN Nguyen H Parmar M Obeticholic acid. StatPearls StatPearls Publishing 2025 33620812
    [Google Scholar]
  140. Shirley M. Maralixibat: First approval. Drugs 2022 82 1 71 76 10.1007/s40265‑021‑01649‑0 34813049
    [Google Scholar]
  141. YiS.KimI.HagerR.StrazzeriM.M.GarrardL.MatsubayashiT. f FDA approval summary: Odevixibat for pruritus in PFIC. Gastro Hep Adv. 2025 4 4 100596 10.1016/j.gastha.2024.100596 40454003
    [Google Scholar]
  142. Deeks E.D. Odevixibat: First Approval. Drugs 2021 81 15 1781 1786 10.1007/s40265‑021‑01594‑y 34499340
    [Google Scholar]
  143. RinellaM.E.LieuH.D.KowdleyK.V.GoodmanZ.D.AlkhouriN.LawitzE. f Aldafermin in NASH with compensated cirrhosis: randomized trial. Hepatology 2024 79 3 674 689 10.1097/HEP.0000000000000607 37732990
    [Google Scholar]
  144. Ali M.H. Rehman O.U. Talha M. Fatima E. Fatima L. Zain A. Safety of FGF19 analog aldafermin in NASH: meta-analysis. Ann. Med. Surg. (Lond.) 2024 86 12 7072 7081 10.1097/MS9.0000000000002649 39649867
    [Google Scholar]
  145. Patel PH Can AS Colesevelam. StatPearls Treasure Island 2025
    [Google Scholar]
  146. Gąsiorowska A. Romanowski M. Walecka-Kapica E. Kaczka A. Chojnacki C. Padysz M. Microencapsulated sodium butyrate + pre/probiotics in IBS: randomized trial. J. Clin. Med. 2024 14 1 39797089
    [Google Scholar]
  147. Chambers E.S. Viardot A. Psichas A. Morrison D.J. Murphy K.G. Zac-Varghese S.E.K. Targeted propionate delivery reduces appetite and adiposity. Gut 2015 64 11 1744 1754 10.1136/gutjnl‑2014‑307913 25500202
    [Google Scholar]
  148. Turck D. Bohn T. de la Montaña Cámara Hurtado M. Castenmiller J. De Henauw S. Jos Á. Maciuk A. Mangelsdorf I. Mcnulty B. Naska A. Pentieva K. Siani A. Thies F. Aguilera Gómez M. Frenzel T. McArdle H.J. Moldeus P. Neuhäuser-Berthold M. Schlatter J.R. van Loveren H. Matijević L. Hirsch-Ernst K.I. EFSA Panel on Nutrition; Novel Foods and Food Allergens (NDA) Safety of inulin-propionate ester as a novel food pursuant to Regulation (EU) 2015/2283. EFSA J. 2025 23 7 e9534 40708711
    [Google Scholar]
  149. Gupta N. Buffa J.A. Roberts A.B. Sangwan N. Skye S.M. Li L. Ho K.J. Varga J. DiDonato J.A. Tang W.H.W. Hazen S.L. Targeted inhibition of gut microbial trimethylamine N-oxide production reduces renal tubulointerstitial fibrosis and functional impairment in a murine model of chronic kidney disease. Arterioscler. Thromb. Vasc. Biol. 2020 40 5 1239 1255 10.1161/ATVBAHA.120.314139 32212854
    [Google Scholar]
  150. Organ C.L. Li Z. Sharp T.E. III Polhemus D.J. Gupta N. Goodchild T.T. Tang W.H.W. Hazen S.L. Lefer D.J. Nonlethal inhibition of gut microbial trimethylamine-N-oxide production improves cardiac function and remodeling in a murine model of heart failure. J. Am. Heart Assoc. 2020 9 10 e016223 10.1161/JAHA.119.016223 32390485
    [Google Scholar]
  151. Schugar R.C. Gliniak C.M. Osborn L.J. Massey W. Sangwan N. Horak A. Banerjee R. Orabi D. Helsley R.N. Brown A.L. Burrows A. Finney C. Fung K.K. Allen F.M. Ferguson D. Gromovsky A.D. Neumann C. Cook K. McMillan A. Buffa J.A. Anderson J.T. Mehrabian M. Goudarzi M. Willard B. Mak T.D. Armstrong A.R. Swanson G. Keshavarzian A. Garcia-Garcia J.C. Wang Z. Lusis A.J. Hazen S.L. Brown J.M. Gut microbe-targeted choline trimethylamine lyase inhibition improves obesity via rewiring of host circadian rhythms. eLife 2022 11 e63998 10.7554/eLife.63998 35072627
    [Google Scholar]
  152. Health benefits of whole grain oats in population at risk of cardio metabolic disease. NCT01925365. 2013 Available from: https://clinicaltrials.gov/ct2/show/NCT01925365
  153. Effect of the Synbiotic Probinul-Neutro® on gastrointestinal symptoms and plasma p-Cresol level in chronic renal failur. NCT02008331. Available from: https://clinicaltrials.gov/ct2/show/NCT02008331
  154. Prebiotics, gut microbiota, and cardiometabolic health. NCT02346838 2025 Available from: https://clinicaltrials.gov/ct2/show/NCT02346838
  155. Transplantation of microbes for treatment of metabolic syndrome & NAFLD (FMT). NCT02496390 2025 Available from: https://clinicaltrials.gov/ct2/show/NCT02496390
  156. Prebiotics fibre supplementation and gut microbiotas in nonalcoholic fatty liver disease. NCT02568605 Available from: https://clinicaltrials.gov/ct2/show/NCT02568605
  157. Prebiotics in patients with nonalcoholic liver disease. NCT02642172 2025 Available from: https://clinicaltrials.gov/ct2/show/NCT02642172
  158. Trial of faecal microbiota transplantation in cirrhosis (PROFIT). NCT02862249 2024 Available from: https://clinicaltrials.gov/ct2/show/NCT02862249
  159. Oral fecal transplant in cirrhosis. NCT03152188. Available from: https://clinicaltrials.gov/ct2/show/NCT03152188
  160. Histological improvement of NASH with prebiotic. NCT03184376 2017 Available from: https://clinicaltrials.gov/ct2/show/NCT03184376
  161. The effect of probiotics on chronic kidney disease. NCT03228563 2025 Available from: https://clinicaltrials.gov/ct2/show/NCT03228563
  162. effects upon gut flora and plasma levels of trimethyla mine-N-oxide (TMAO) - wineflora study. NCT03232099 2021 Available from: https://clinicaltrials.gov/ct2/show/NCT03232099
  163. Blueberries for improving vascular endothelial function in post menopausal women with elevated blood pressure. NCT03370991, 2025 Available from: https://clinicaltrials.gov/ct2/show/NCT03370991
  164. Effect of probiotic consumption on chronic kidney disease. NCT03400228 2018 Available from: https://clinicaltrials.gov/ct2/show/NCT03400228
  165. FMT in cirrhosis and hepatic encephalopathy. NCT03796598, 20205 Available from: https://clinicaltrials.gov/ct2/show/NCT03796598
  166. Dietary modulation of intestinal microbiota as trigger of liver health: role of bile acids - "A diet for liver health" (ADLH). NCT03897218, 2023 Available from: https://clinicaltrials.gov/ct2/show/NCT03897218
  167. Cardiovascular health arterial stiffness raspberry and microbiome (CHARM) (CHARM). NCT04087278. 2023 Available from: https://clinicaltrials.gov/ct2/show/NCT04087278
  168. A pilot study to investigate the effect of water-soluble tTomato extract on TMAO. NCT04160481. 2020 Available from: https://clinicaltrials.gov/ct2/show/NCT04160481
  169. The role of gut microbiome on cardiovascular health benefits of dietary lignans (CardioFlax Study). NCT04179136 2020 Available from: https://clinicaltrials.gov/ct2/show/NCT04179136
  170. Probiotics and low protein diet in advanced chronic kidney disease (ProLowCKD). NCT04204005 2022 Available from: https://clinicaltrials.gov/ct2/show/NCT04204005
  171. Dietary intervention and gut mic robiotai in hepatocellular carcinoma (HCC).NCT07143955, 2025 Available from: https://clinicaltrials.gov/ct2/show/NCT07143955
  172. Yang S.Y. Han S.M. Lee J.Y. Kim K.S. Lee J.E. Lee D.W. Advancing gut microbiome research: The shift from metagenomics to multi-omics and future perspectives. J. Microbiol. Biotechnol. 2025 35 e2412001 10.4014/jmb.2412.12001 40223273
    [Google Scholar]
  173. Philips C.A. Schnabl B. Bajaj J.S. Gut microbiome and alcohol-associated liver disease. J. Clin. Exp. Hepatol. 2022 12 5 1349 1359 10.1016/j.jceh.2021.12.016 36157139
    [Google Scholar]
  174. McGuinness A.J. Stinson L.F. Snelson M. Loughman A. Stringer A. Hannan A.J. Cowan C.S.M. Jama H.A. Caparros-Martin J.A. West M.L. Wardill H.R. Australasian Human Microbiome Research Network (AHMRN) Committee From hype to hope: Considerations in conducting robust microbiome science. Brain Behav. Immun. 2024 115 120 130 10.1016/j.bbi.2023.09.022 37806533
    [Google Scholar]
  175. Roume H. Mondot S. Saliou A. Le Fresne-Languille S. Doré J. Multicenter evaluation of gut microbiome profiling by next-generation sequencing reveals major biases in partial-length metabarcoding approach. Sci. Rep. 2023 13 1 22593 10.1038/s41598‑023‑46062‑7 38114587
    [Google Scholar]
  176. Forry S.P. Servetas S.L. Kralj J.G. Soh K. Hadjithomas M. Cano R. Carlin M. Amorim M.G. Auch B. Bakker M.G. Bartelli T.F. Bustamante J.P. Cassol I. Chalita M. Dias-Neto E. Duca A.D. Gohl D.M. Kazantseva J. Haruna M.T. Menzel P. Moda B.S. Neuberger-Castillo L. Nunes D.N. Patel I.R. Peralta R.D. Saliou A. Schwarzer R. Sevilla S. Takenaka I.K.T.M. Wang J.R. Knight R. Gevers D. Jackson S.A. Variability and bias in microbiome metagenomic sequencing: an interlaboratory study comparing experimental protocols. Sci. Rep. 2024 14 1 9785 10.1038/s41598‑024‑57981‑4 38684791
    [Google Scholar]
  177. Han Y. He J. Li M. Peng Y. Jiang H. Zhao J. Li Y. Deng F. Unlocking the potential of metagenomics with the PacBio high-fidelity sequencing technology. Microorganisms 2024 12 12 2482 10.3390/microorganisms12122482 39770685
    [Google Scholar]
  178. Martínez Arbas S. Busi S.B. Queirós P. de Nies L. Herold M. May P. Wilmes P. Muller E.E.L. Narayanasamy S. Challenges, strategies, and perspectives for reference-independent longitudinal multi-omic microbiome studies. Front. Genet. 2021 12 666244 10.3389/fgene.2021.666244 34194470
    [Google Scholar]
  179. Kool J. Tymchenko L. Shetty S.A. Fuentes S. Reducing bias in microbiome research: Comparing methods from sample collection to sequencing. Front. Microbiol. 2023 14 1094800 10.3389/fmicb.2023.1094800 37065158
    [Google Scholar]
  180. Wu Y. Wang X. Wu W. Yang J. Mendelian randomization analysis reveals an independent causal relationship between four gut microbes and acne vulgaris. Front. Microbiol. 2024 15 1326339 10.3389/fmicb.2024.1326339 38371936
    [Google Scholar]
  181. Han D. Gao P. Li R. Tan P. Xie J. Zhang R. Li J. Multicenter assessment of microbial community profiling using 16S rRNA gene sequencing and shotgun metagenomic sequencing. J. Adv. Res. 2020 26 111 121 10.1016/j.jare.2020.07.010 33133687
    [Google Scholar]
  182. Turnbaugh P.J. Gordon J.I. An invitation to the marriage of metagenomics and metabolomics. Cell 2008 134 5 708 713 10.1016/j.cell.2008.08.025 18775300
    [Google Scholar]
  183. Boicean A. Birlutiu V. Ichim C. Brusnic O. Onișor D.M. Fecal microbiota transplantation in liver cirrhosis. Biomedicines 2023 11 11 2930 10.3390/biomedicines11112930 38001930
    [Google Scholar]
  184. Blandino G. Fazio D. Di Marco R. Probiotics: Overview of microbiological and immunological characteristics. Expert Rev. Anti Infect. Ther. 2008 6 4 497 508 10.1586/14787210.6.4.497 18662116
    [Google Scholar]
  185. Sorboni S.G. Moghaddam H.S. Jafarzadeh-Esfehani R. Soleimanpour S. A comprehensive review on the role of the gut microbiome in human neurological disorders. Clin. Microbiol. Rev. 2022 35 1 e00338-20 10.1128/CMR.00338‑20 34985325
    [Google Scholar]
  186. Brown E.M. Clardy J. Xavier R.J. Gut microbiome lipid metabolism and its impact on host physiology. Cell Host Microbe 2023 31 2 173 186 10.1016/j.chom.2023.01.009 36758518
    [Google Scholar]
/content/journals/cpd/10.2174/0113816128413464251209115653
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Gut Microbiota in the Hepato-Cardiorenal Axis: Microbial Metabolites, Inflammation, and Emerging Therapeutic Targets
Bentham Science Publishers ; https://doi.org/10.2174/0113816128413464251209115653
/content/journals/cpd/10.2174/0113816128413464251209115653
/content/journals/cpd/10.2174/0113816128413464251209115653
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  • Article Type:     Review Article
Keywords: uremic toxins ; Trimethyline-N-Dioxide ; insulin ; Gut microbiota ; dysbiosis ; short-chain fatty acids

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