REFERENCES
1. Zheng D, Liwinski T, Elinav E. Interaction between microbiota and immunity in health and disease. Cell Res. 2020;30:492-506.
2. Wu J, Wang K, Wang X, Pang Y, Jiang C. The role of the gut microbiome and its metabolites in metabolic diseases. Protein Cell. 2020;12:360-73.
4. Michaudel C, Sokol H. The gut microbiota at the service of immunometabolism. Cell Metab. 2020;32:514-23.
5. Isenring J, Bircher L, Geirnaert A, Lacroix C. In vitro human gut microbiota fermentation models: opportunities, challenges, and pitfalls. Microbiome Res Rep. 2023;2:2.
6. Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R. Diversity, stability and resilience of the human gut microbiota. Nature. 2012;489:220-30.
7. Ni J, Wu GD, Albenberg L, Tomov VT. Gut microbiota and IBD: causation or correlation? Nat Rev Gastroenterol Hepatol. 2017;14:573-84.
8. Norman JM, Handley SA, Baldridge MT, et al. Disease-specific alterations in the enteric virome in inflammatory bowel disease. Cell. 2015;160:447-60.
9. Tripathi A, Debelius J, Brenner DA, et al. The gut-liver axis and the intersection with the microbiome. Nat Rev Gastroenterol Hepatol. 2018;15:397-411.
10. Vich Vila A, Collij V, Sanna S, et al. Impact of commonly used drugs on the composition and metabolic function of the gut microbiota. Nat Commun. 2020;11:362.
11. Wong SH, Yu J. Gut microbiota in colorectal cancer: mechanisms of action and clinical applications. Nat Rev Gastroenterol Hepatol. 2019;16:690-704.
12. Young VB. The role of the microbiome in human health and disease: an introduction for clinicians. BMJ. 2017:j831.
13. Vilà-quintana L, Fort E, Pardo L, et al. Metagenomic study reveals phage-bacterial interactome dynamics in gut and oral microbiota in pancreatic diseases. Int J Mol Sci. 2024;25:10988.
14. Chu H, Duan Y, Lang S, et al. The Candida albicans exotoxin candidalysin promotes alcohol-associated liver disease. J Hepatol. 2020;72:391-400.
15. Lang S, Duan Y, Liu J, et al. Intestinal fungal dysbiosis and systemic immune response to fungi in patients with alcoholic hepatitis. Hepatology. 2019;71:522-38.
16. Clooney AG, Sutton TD, Shkoporov AN, et al. Whole-virome analysis sheds light on viral dark matter in inflammatory bowel disease. Cell Host Microbe. 2019;26:764-778.e5.
17. Lang S, Demir M, Martin A, et al. Intestinal virome signature associated with severity of nonalcoholic fatty liver disease. Gastroenterology. 2020;159:1839-52.
18. Stockdale SR, Shkoporov AN, Khokhlova EV, et al. Interpersonal variability of the human gut virome confounds disease signal detection in IBD. Commun Biol. 2023;6:221.
19. Tun HM, Peng Y, Massimino L, et al. Gut virome in inflammatory bowel disease and beyond. Gut. 2024;73:350-60.
20. Zuo T, Lu XJ, Zhang Y, et al. Gut mucosal virome alterations in ulcerative colitis. Gut. 2019;68:1169-79.
21. Liang G, Bushman FD. The human virome: assembly, composition and host interactions. Nat Rev Microbiol. 2021;19:514-27.
22. Ackermann HW, Prangishvili D. Prokaryote viruses studied by electron microscopy. Arch Virol. 2012;157:1843-9.
23. Twort FW. Further investigations on the nature of ultra-microscopic viruses and their cultivation. J Hyg (Lond). 2009;36:204-35.
24. Knowles B, Silveira CB, Bailey BA, et al. Lytic to temperate switching of viral communities. Nature. 2016;531:466-70.
25. Davies EV, Winstanley C, Fothergill JL, James CE, Millard A. The role of temperate bacteriophages in bacterial infection. FEMS Microbiol Lett. 2016;363:fnw015.
26. Olszak T, Latka A, Roszniowski B, Valvano MA, Drulis-kawa Z. Phage life cycles behind bacterial biodiversity. Curr Med Chem. 2017;24:LiveAll1.
27. Dion MB, Oechslin F, Moineau S. Phage diversity, genomics and phylogeny. Nat Rev Microbiol. 2020;18:125-38.
28. Gan L, Feng Y, Du B, et al. Bacteriophage targeting microbiota alleviates non-alcoholic fatty liver disease induced by high alcohol-producing Klebsiella pneumoniae. Nat Commun. 2023;14:3215.
29. Duan Y, Llorente C, Lang S, et al. Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease. Nature. 2019;575:505-11.
30. Cao Z, Fan D, Sun Y, et al. The gut ileal mucosal virome is disturbed in patients with Crohn’s disease and exacerbates intestinal inflammation in mice. Nat Commun. 2024;15:1638.
31. Salmond GPC, Fineran PC. A century of the phage: past, present and future. Nat Rev Microbiol. 2015;13:777-86.
32. Aminov R. History of antimicrobial drug discovery: major classes and health impact. Biochem Pharmacol. 2017;133:4-19.
33. Becattini S, Taur Y, Pamer EG. Antibiotic-Induced changes in the Intestinal Microbiota and Disease. Trends Mol Med. 2016;22:458-78.
34. Goossens H, Ferech M, Vander Stichele R, Elseviers M. Outpatient antibiotic use in Europe and association with resistance: a cross-national database study. Lancet. 2005;365:579-87.
35. Spellberg B, Bartlett JG, Gilbert DN. The future of antibiotics and resistance. N Engl J Med. 2013;368:299-302.
36. Aranaga C, Pantoja LD, Martínez EA, Falco A. Phage therapy in the era of multidrug resistance in bacteria: a systematic review. Int J Mol Sci. 2022;23:4577.
37. Hatfull GF, Dedrick RM, Schooley RT. Phage therapy for antibiotic-resistant bacterial infections. Annu Rev Med. 2022;73:197-211.
38. Uchechukwu CF, Shonekan A. Current status of clinical trials for phage therapy. J Med Microbiol. 2024;73:001895.
40. Jiang L, Lang S, Duan Y, et al. Intestinal virome in patients with alcoholic hepatitis. Hepatology. 2020;72:2182-96.
41. Alkhalil SS. The role of bacteriophages in shaping bacterial composition and diversity in the human gut. Front Microbiol. 2023;14:1232413.
42. Rybicka I, Kaźmierczak Z, Vives M. The human phageome: niche-specific distribution of bacteriophages and their clinical implications. Appl Environ Microbiol. 2025;91:e01788-24.
43. Shuwen H, Kefeng D. Intestinal phages interact with bacteria and are involved in human diseases. Gut Microbes. 2022;14:2113717.
47. Turner JR. Intestinal mucosal barrier function in health and disease. Nat Rev Immunol. 2009;9:799-809.
48. Clayburgh DR, Shen L, Turner JR. A porous defense: the leaky epithelial barrier in intestinal disease. Lab Invest. 2004;84:282-91.
49. Tian X, Li S, Wang C, et al. Gut virome-wide association analysis identifies cross-population viral signatures for inflammatory bowel disease. Microbiome. 2024;12:130.
50. Majzoub ME, Paramsothy S, Haifer C, et al. The phageome of patients with ulcerative colitis treated with donor fecal microbiota reveals markers associated with disease remission. Nat Commun. 2024;15:8979.
51. Fernandes MA, Verstraete SG, Phan TG, et al. Enteric virome and bacterial microbiota in children with ulcerative colitis and Crohn disease. J Pediatr Gastroenterol Nutr. 2019;68:30-6.
52. Wagner J, Maksimovic J, Farries G, et al. Bacteriophages in gut samples from pediatric Crohn’s disease patients: metagenomic analysis using 454 pyrosequencing. Inflamm Bowel Dis. 2013;19:1598-608.
53. Sinha A, Li Y, Mirzaei MK, et al. Transplantation of bacteriophages from ulcerative colitis patients shifts the gut bacteriome and exacerbates the severity of DSS colitis. Microbiome. 2022;10:105.
54. Carasso S, Zaatry R, Hajjo H, et al. Inflammation and bacteriophages affect DNA inversion states and functionality of the gut microbiota. Cell Host Microbe. 2024;32:322-334.e9.
55. Federici S, Kredo-russo S, Valdés-mas R, et al. Targeted suppression of human IBD-associated gut microbiota commensals by phage consortia for treatment of intestinal inflammation. Cell. 2022;185:2879-2898.e24.
56. Gogokhia L, Buhrke K, Bell R, et al. Expansion of bacteriophages is linked to aggravated intestinal inflammation and colitis. Cell Host Microbe. 2019;25:285-299.e8.
57. Obermeier F, Dunger N, Strauch UG, et al. CpG motifs of bacterial DNA essentially contribute to the perpetuation of chronic intestinal inflammation. Gastroenterology. 2005;129:913-27.
59. Younossi Z, Anstee QM, Marietti M, et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2017;15:11-20.
60. Hagström H, Shang Y, Hegmar H, Nasr P. Natural history and progression of metabolic dysfunction-associated steatotic liver disease. Lancet Gastroenterol Hepatol. 2024;9:944-56.
61. Hsu CL, Lang S, Demir M, Fouts DE, Stärkel P, Schnabl B. Any alcohol use in NAFLD patients is associated with significant changes to the intestinal virome. Hepatology. 2023;77:2073-83.
62. Kwan SY, Sabotta CM, Cruz LR, et al. Gut phageome in Mexican Americans: a population at high risk for metabolic dysfunction-associated steatotic liver disease and diabetes. mSystems. 2024;9:e0043424.
63. Jew MH, Hsu CL. Alcohol, the gut microbiome, and liver disease. J Gastroenterol Hepatol. 2023;38:1205-10.
64. Hsu CL, Zhang X, Jiang L, et al. Intestinal virome in patients with alcohol use disorder and after abstinence. Hepatol Commun. 2022;6:2058-69.
65. Llorente C, Jepsen P, Inamine T, et al. Gastric acid suppression promotes alcoholic liver disease by inducing overgrowth of intestinal Enterococcus. Nat Commun. 2017;8:837.
66. Liwinski T, Heinemann M, Schramm C. The intestinal and biliary microbiome in autoimmune liver disease - current evidence and concepts. Semin Immunopathol. 2022;44:485-507.
67. Shah A, Macdonald GA, Morrison M, Holtmann G. Targeting the gut microbiome as a treatment for primary sclerosing cholangitis: a conceptional framework. Am J Gastroenterol. 2020;115:814-22.
68. Hov JR, Karlsen TH. The microbiota and the gut-liver axis in primary sclerosing cholangitis. Nat Rev Gastroenterol Hepatol. 2022;20:135-54.
69. Karlsen TH, Folseraas T, Thorburn D, Vesterhus M. Primary sclerosing cholangitis - a comprehensive review. J Hepatol. 2017;67:1298-323.
70. Ichikawa M, Nakamoto N, Kredo-russo S, et al. Bacteriophage therapy against pathological Klebsiella pneumoniae ameliorates the course of primary sclerosing cholangitis. Nat Commun. 2023;14:3261.
71. Nakamoto N, Sasaki N, Aoki R, et al. Gut pathobionts underlie intestinal barrier dysfunction and liver T helper 17 cell immune response in primary sclerosing cholangitis. Nat Microbiol. 2019;4:492-503.
72. Webb G, Siminovitch K, Hirschfield G. The immunogenetics of primary biliary cirrhosis: a comprehensive review. J Autoimmun. 2015;64:42-52.
73. Sarcognato S, Sacchi D, Grillo F, et al. Autoimmune biliary diseases: primary biliary cholangitis and primary sclerosing cholangitis. Pathologica. 2021;113:170-84.
74. Xiang X, Yang X, Shen M, et al. Ursodeoxycholic acid at 18-22 mg/kg/d showed a promising capacity for treating refractory primary biliary cholangitis. Can J Gastroenterol Hepatol. 2021;2021:6691425.
75. Barba Bernal R, Ferrigno B, Morales EM, et al. Beth Israel Deaconess Medical Center, Boston, MA, USA. Management of primary biliary cholangitis: current treatment and future perspectives. Turk J Gastroenterol. 2023;34:89-100.
76. Tang R, Wei Y, Li Y, et al. Gut microbial profile is altered in primary biliary cholangitis and partially restored after UDCA therapy. Gut. 2018;67:534-41.
77. Trivedi PJ, Hirschfield GM, Adams DH, Vierling JM. Immunopathogenesis of primary biliary cholangitis, primary sclerosing cholangitis and autoimmune hepatitis: themes and concepts. Gastroenterology. 2024;166:995-1019.
78. Guo Z, He K, Pang K, et al. Exploring advanced therapies for primary biliary cholangitis: insights from the gut microbiota-bile acid-immunity network. Int J Mol Sci. 2024;25:4321.
80. Banks PA, Bollen TL, Dervenis C, et al. Classification of acute pancreatitis - 2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013;62:102-11.
81. Beyer G, Habtezion A, Werner J, Lerch MM, Mayerle J. Chronic pancreatitis. Lancet. 2020;396:499-512.
82. Campion EW, Forsmark CE, Swaroop Vege S, Wilcox CM. Acute pancreatitis. N Engl J Med. 2016;375:1972-81.
83. Tan C, Ling Z, Huang Y, et al. Dysbiosis of intestinal microbiota associated with inflammation involved in the progression of acute pancreatitis. Pancreas. 2015;44:868-75.
84. Frost F, Weiss FU, Sendler M, et al. The gut microbiome in patients with chronic pancreatitis is characterized by significant dysbiosis and overgrowth by opportunistic pathogens. Clin Transl Gastroenterol. 2020;11:e00232.
85. Zhang C, Li G, Lu T, et al. The interaction of microbiome and pancreas in acute pancreatitis. Biomolecules. 2023;14:59.
86. Zhu Y, Mei Q, Fu Y, Zeng Y. Alteration of gut microbiota in acute pancreatitis and associated therapeutic strategies. Biomed Pharmacother. 2021;141:111850.
87. Shareefdeen H, Hill C. The gut virome in health and disease: new insights and associations. Curr Opin Gastroenterol. 2022;38:549-54.
88. Schepis T, De Lucia SS, Nista EC, et al. Microbiota in pancreatic diseases: a review of the literature. J Clin Med. 2021;10:5920.
89. Patel BK, Patel KH, Bhatia M, Iyer SG, Madhavan K, Moochhala SM. Gut microbiome in acute pancreatitis: a review based on current literature. World J Gastroenterol. 2021;27:5019-36.
90. Li J, Pan X, Yang J, et al. Enteral virus depletion modulates experimental acute pancreatitis via toll-like receptor 9 signaling. Biochem Pharmacol. 2020;171:113710.
91. Sinha A, Maurice CF. Bacteriophages: uncharacterized and dynamic regulators of the immune system. Mediators Inflamm. 2019;2019:1-14.
92. Sulakvelidze A, Alavidze Z, Morris JG Jr. Bacteriophage therapy. Antimicrob Agents Chemother. 2001;45:649-59.
93. Asheshov IN, Khan S, Lahiri MN. The treatment of cholera with bacteriophage. Ind Med Gaz. 1931;66:179-84.
94. Titécat M, Rousseaux C, Dubuquoy C, et al. Safety and efficacy of an AIEC-targeted bacteriophage cocktail in a mice colitis model. J Crohns Colitis. 2022;16:1617-27.
95. Sangster W, Hegarty JP, Stewart DB Sr. Phage tail-like particles kill Clostridium difficile and represent an alternative to conventional antibiotics. Surgery. 2015;157:96-103.
96. Corbellino M, Kieffer N, Kutateladze M, et al. Eradication of a multidrug-resistant, carbapenemase-producing Klebsiella pneumoniae isolate following oral and intra-rectal therapy with a custom made, lytic bacteriophage preparation. Clin Infect Dis. 2020;70:1998-2001.
97. Sarker SA, Sultana S, Reuteler G, et al. Oral phage therapy of acute bacterial diarrhea with two coliphage preparations: a randomized trial in children from Bangladesh. EBioMedicine. 2016;4:124-37.
98. Schooley RT, Biswas B, Gill JJ, et al. Development and use of personalized bacteriophage-based therapeutic cocktails to treat a patient with a disseminated resistant Acinetobacter baumannii infection. Antimicrob Agents Chemother. 2017;61:e00954-17.
99. Mah C, Jayawardana T, Leong G, et al. Assessing the relationship between the gut microbiota and inflammatory bowel disease therapeutics: a systematic review. Pathogens. 2023;12:262.
100. Taylor VL, Fitzpatrick AD, Islam Z, Maxwell KL. The diverse impacts of phage morons on bacterial fitness and virulence. Adv Virus Res. 2019;103:1-31.
101. Guerrero-Bustamante CA, Hatfull GF, Ehrt S. Bacteriophage tRNA-dependent lysogeny: requirement of phage-encoded tRNA genes for establishment of lysogeny. mBio. 2024;15:e03260-23.
102. Manrique P, Montero I, Fernandez-gosende M, Martinez N, Cantabrana CH, Rios-covian D. Past, present, and future of microbiome-based therapies. Microbiome Res Rep. 2024;3:23.
103. Wang Q, Euler CW, Delaune A, Fischetti VA. Using a novel lysin to help control Clostridium difficile infections. Antimicrob Agents Chemother. 2015;59:7447-57.
104. Mao X, Larsen SB, Zachariassen LSF, et al. Transfer of modified gut viromes improves symptoms associated with metabolic syndrome in obese male mice. Nat Commun. 2024;15:4704.
105. Mendes BG, Duan Y, Schnabl B. Immune response of an oral Enterococcus faecalis phage cocktail in a mouse model of ethanol-induced liver disease. Viruses. 2022;14:490.
106. Chen Q, Dong Z, Ding T, et al. Isolation and characterization of a novel Enterococcus phage Phi_Eg_SY1. Virus Res. 2023;332:199132.
107. Badia JM, Amador S, González-sánchez C, et al. Appropriate use of antibiotics in acute pancreatitis: a scoping review. Antibiotics (Basel). 2024;13:894.
108. Lu J, Ding Y, Qu Y, et al. Risk factors and outcomes of multidrug-resistant bacteria infection in infected pancreatic necrosis patients. Infect Drug Resist. 2022;Volume 15:7095-106.
109. Hao H, Liu Y, Cao J, et al. Genomic new insights into emergence and clinical therapy of multidrug-resistant Klebsiella pneumoniae in infected pancreatic necrosis. Front Microbiol. 2021;12:669230.
110. Bruttin A, Brüssow H. Human volunteers receiving phage T4 orally: a safety test of phage therapy. Antimicrob Agents Chemother. 2005;49:2874-8.
111. Grubb DS, Wrigley SD, Freedman KE, et al. PHAGE-2 study: supplemental bacteriophages extend bifidobacterium animalis subsp. lactis BL04 benefits on gut health and microbiota in healthy adults. Nutrients. 2020;12:2474.
112. Liu M, Hernandez-morales A, Clark J, et al. Comparative genomics of Acinetobacter baumannii and therapeutic bacteriophages from a patient undergoing phage therapy. Nat Commun. 2022;13:3776.
113. Jansen D, Matthijnssens J. The emerging role of the gut virome in health and inflammatory bowel disease: challenges, covariates and a viral imbalance. Viruses. 2023;15:173.
114. Glassner KL, Abraham BP, Quigley EM. The microbiome and inflammatory bowel disease. J Allergy Clin Immunol. 2020;145:16-27.
115. Koncz M, Stirling T, Hadj Mehdi H, et al. Genomic surveillance as a scalable framework for precision phage therapy against antibiotic-resistant pathogens. Cell. 2024;187:5901-5918.e28.
116. Yehl K, Lemire S, Yang AC, et al. Engineering phage host-range and suppressing bacterial resistance through phage tail fiber mutagenesis. Cell. 2019;179:459-469.e9.
117. Oechslin F. Resistance development to bacteriophages occurring during bacteriophage therapy. Viruses. 2018;10:351.
118. Bikard D, Euler CW, Jiang W, et al. Exploiting CRISPR-Cas nucleases to produce sequence-specific antimicrobials. Nat Biotechnol. 2014;32:1146-50.
119. Gencay YE, Jasinskytė D, Robert C, et al. Engineered phage with antibacterial CRISPR-Cas selectively reduce E. coli burden in mice. Nat Biotechnol. 2023;42:265-74.
120. Chen J, Quiles-puchalt N, Chiang YN, et al. Genome hypermobility by lateral transduction. Science. 2018;362:207-12.
121. Penadés JR, Chen J, Quiles-puchalt N, Carpena N, Novick RP. Bacteriophage-mediated spread of bacterial virulence genes. Curr Opin Microbiol. 2015;23:171-8.
122. Berkson JD, Wate CE, Allen GB, et al. Phage-specific immunity impairs efficacy of bacteriophage targeting Vancomycin resistant Enterococcus in a murine model. Nat Commun. 2024;15:2993.
123. Łusiak-szelachowska M, Międzybrodzki R, Rogóż P, Weber-dąbrowska B, Żaczek M, Górski A. Do anti-phage antibodies persist after phage therapy? A preliminary report. Antibiotics (Basel). 2022;11:1358.
124. Liu D, Van Belleghem JD, De Vries CR, et al. The safety and toxicity of phage therapy: a review of animal and clinical studies. Viruses. 2021;13:1268.
125. Champagne-jorgensen K, Luong T, Darby T, Roach DR. Immunogenicity of bacteriophages. Trends Microbiol. 2023;31:1058-71.
126. Colom J, Cano-sarabia M, Otero J, et al. Microencapsulation with alginate/CaCO3: a strategy for improved phage therapy. Sci Rep. 2017;7:41441.
127. Moghtader F, Solakoglu S, Piskin E. Alginate- and chitosan-modified gelatin hydrogel microbeads for delivery of E. coli phages. Gels. 2024;10:244.
128. Yang Q, Le S, Zhu T, Wu N. Regulations of phage therapy across the world. Front Microbiol. 2023;14:1250848.
129. Strathdee SA, Hatfull GF, Mutalik VK, Schooley RT. Phage therapy: from biological mechanisms to future directions. Cell. 2023;186:17-31.
130. Intralytix Inc. Intralytix Receives FDA Clearance to Initiate Phase I / IIa Clinical Trials. Available from: https://www.prnewswire.com/news-releases/intralytix-receives-fda-clearance-to-initiate-phase-i--iia-clinical-trials-300599772.html [accessed on 2025-10-21].
131. BiomX Inc. BiomX Announces Positive Results of a Phase 1a Pharmacokinetic Study for Inflammatory Bowel Disease/Primary Sclerosing Cholangitis (IBD/PSC) Evaluating Delivery of Oral BX002 Phage Therapy. Available from: https://www.businesswire.com/news/home/20210202005228/en/BiomX-Announces-Positive-Results-of-a-Phase-1a-Pharmacokinetic-Study-for-Inflammatory-Bowel-DiseasePrimary-Sclerosing-Cholangitis-IBDPSC-Evaluating-Delivery-of-Oral-BX002-Phage-Therapy [accessed on 2025-10-21].
132. BiomX Inc. BiomX Announces Closing of the Acquisition of Adaptive Phage Therapeutics and Concurrent $50 Million Financing. Available from: https://www.thepharmaletter.com/biotechnology/biomx-announces-adaptive-merger-and-financing [accessed on 2025-10-21].






