Gut microbiota and its importance in the management of inflammatory bowel disease: A promising pathway to better health
DOI:
https://doi.org/10.61882/jcbior.4.3.248Keywords:
Microbiota, Inflammatory bowel disease, Dysbiosis, ProbioticsAbstract
Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract. The gut microbiota plays a crucial role in the development and progression of IBD. In IBD patients, the composition of the gut microbiota is significantly different from that of healthy individuals. Dysbiosis, an imbalance of beneficial and harmful bacteria, is a hallmark of IBD. The development of microbiota-targeted treatments requires a comprehensive understanding of the gut microbiota composition, its interaction with the host immune system, and its role in the pathogenesis of IBD. This review discusses the prospects for microbiome-based therapies in IBD. Pre- and probiotics, as well as faecal microbiota transplant (FMT), are examples of microbiome-targeted treatments. These approaches are predicated on the idea that reestablishing a healthy gut microbiome might reduce mucosal inflammation. The fundamental components of commensal gut bacteria's metabolism are known as prebiotics. Probiotics are supplements that artificially introduce gut microorganisms that are believed to have positive effects on the surrounding microenvironment and may even help with IBD symptom relief. FMT is a more direct way of introducing bacteria than probiotics, yet the same bacteria are present in the bodies of healthy people at larger concentrations. Current evidence suggests that microbiome-targeted therapeutics may have some benefit for IBD. With advancements in technology and research, microbiota-targeted treatments have the potential to revolutionize the management of IBD and improve clinical outcomes for patients.
References
1. Ng SC, Shi HY, Hamidi N, Underwood FE, Tang W, Benchimol EI, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet. 2017;390(10114):2769-78. DOI: 10.1016/S0140-6736(17)32448-0 PMID: 29050646
2. Haneishi Y, Furuya Y, Hasegawa M, Picarelli A, Rossi M, Miyamoto J. Inflammatory Bowel Diseases and Gut Microbiota. Int J Mol Sci. 2023;24(4). DOI: 10.3390/ijms24043817 PMID: 36835245
3. Manor O, Dai CL, Kornilov SA, Smith B, Price ND, Lovejoy JC, et al. Health and disease markers correlate with gut microbiome composition across thousands of people. Nat Commun. 2020;11(1):5206. DOI: 10.1038/s41467-020-18871-1 PMID: 33060586
4. Oligschlaeger Y, Yadati T, Houben T, Condello Olivan CM, Shiri-Sverdlov R. Inflammatory Bowel Disease: A Stressed "Gut/Feeling". Cells. 2019;8(7). DOI: 10.3390/cells8070659 PMID: 31262067
5. Pant A, Maiti TK, Mahajan D, Das B. Human Gut Microbiota and Drug Metabolism. Microb Ecol. 2023;86(1):97-111. DOI: 10.1007/s00248-022-02081-x PMID: 35869999
6. Halfvarson J, Brislawn CJ, Lamendella R, Vazquez-Baeza Y, Walters WA, Bramer LM, et al. Dynamics of the human gut microbiome in inflammatory bowel disease. Nat Microbiol. 2017;2:17004. DOI: 10.1038/nmicrobiol.2017.4 PMID: 28191884
7. Belizario JE, Faintuch J. Microbiome and Gut Dysbiosis. Exp Suppl. 2018;109:459-76. DOI: 10.1007/978-3-319-74932-7_13 PMID: 30535609
8. Martinez JE, Kahana DD, Ghuman S, Wilson HP, Wilson J, Kim SCJ, et al. Unhealthy Lifestyle and Gut Dysbiosis: A Better Understanding of the Effects of Poor Diet and Nicotine on the Intestinal Microbiome. Front Endocrinol (Lausanne). 2021;12:667066. DOI: 10.3389/fendo.2021.667066 PMID: 34168615
9. Lloyd-Price J, Arze C, Ananthakrishnan AN, Schirmer M, Avila-Pacheco J, Poon TW, et al. Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases. Nature. 2019;569(7758):655-62. DOI: 10.1038/s41586-019-1237-9 PMID: 31142855
10. Portincasa P, Bonfrate L, Vacca M, De Angelis M, Farella I, Lanza E, et al. Gut Microbiota and Short Chain Fatty Acids: Implications in Glucose Homeostasis. Int J Mol Sci. 2022;23(3). DOI: 10.3390/ijms23031105 PMID: 35163038
11. Silva YP, Bernardi A, Frozza RL. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front Endocrinol (Lausanne). 2020;11:25. DOI: 10.3389/fendo.2020.00025 PMID: 32082260
12. Morais LH, Schreiber HLt, Mazmanian SK. The gut microbiota-brain axis in behaviour and brain disorders. Nat Rev Microbiol. 2021;19(4):241-55. DOI: 10.1038/s41579-020-00460-0 PMID: 33093662
13. Santana PT, Rosas SLB, Ribeiro BE, Marinho Y, de Souza HSP. Dysbiosis in Inflammatory Bowel Disease: Pathogenic Role and Potential Therapeutic Targets. Int J Mol Sci. 2022;23(7). DOI: 10.3390/ijms23073464 PMID: 35408838
14. Pisani A, Rausch P, Bang C, Ellul S, Tabone T, Marantidis Cordina C, et al. Dysbiosis in the Gut Microbiota in Patients with Inflammatory Bowel Disease during Remission. Microbiol Spectr. 2022;10(3):e0061622. DOI: 10.1128/spectrum.00616-22 PMID: 35532243
15. Lee SM, Kim N, Yoon H, Kim YS, Choi SI, Park JH, et al. Compositional and Functional Changes in the Gut Microbiota in Irritable Bowel Syndrome Patients. Gut Liver. 2021;15(2):253-61. DOI: 10.5009/gnl19379 PMID: 32457278
16. Mei L, Zhou J, Su Y, Mao K, Wu J, Zhu C, et al. Gut microbiota composition and functional prediction in diarrhea-predominant irritable bowel syndrome. BMC Gastroenterol. 2021;21(1):105. DOI: 10.1186/s12876-021-01693-w PMID: 33663411
17. Pittayanon R, Lau JT, Leontiadis GI, Tse F, Yuan Y, Surette M, et al. Differences in Gut Microbiota in Patients With vs Without Inflammatory Bowel Diseases: A Systematic Review. Gastroenterology. 2020;158(4):930-46 e1. DOI: 10.1053/j.gastro.2019.11.294 PMID: 31812509
18. Markelova M, Senina A, Khusnutdinova D, Siniagina M, Kupriyanova E, Shakirova G, et al. Association between Taxonomic Composition of Gut Microbiota and Host Single Nucleotide Polymorphisms in Crohn's Disease Patients from Russia. Int J Mol Sci. 2023;24(9). DOI: 10.3390/ijms24097998 PMID: 37175705
19. Imhann F, Vich Vila A, Bonder MJ, Fu J, Gevers D, Visschedijk MC, et al. Interplay of host genetics and gut microbiota underlying the onset and clinical presentation of inflammatory bowel disease. Gut. 2018;67(1):108-19. DOI: 10.1136/gutjnl-2016-312135 PMID: 27802154
20. Forbes JD, Chen CY, Knox NC, Marrie RA, El-Gabalawy H, de Kievit T, et al. A comparative study of the gut microbiota in immune-mediated inflammatory diseases-does a common dysbiosis exist? Microbiome. 2018;6(1):221. DOI: 10.1186/s40168-018-0603-4 PMID: 30545401
21. Tito RY, Chaffron S, Caenepeel C, Lima-Mendez G, Wang J, Vieira-Silva S, et al. Population-level analysis of Blastocystis subtype prevalence and variation in the human gut microbiota. Gut. 2019;68(7):1180-9. DOI: 10.1136/gutjnl-2018-316106 PMID: 30171064
22. Franzosa EA, Sirota-Madi A, Avila-Pacheco J, Fornelos N, Haiser HJ, Reinker S, et al. Gut microbiome structure and metabolic activity in inflammatory bowel disease. Nat Microbiol. 2019;4(2):293-305. DOI: 10.1038/s41564-018-0306-4 PMID: 30531976
23. Hang S, Paik D, Yao L, Kim E, Trinath J, Lu J, et al. Bile acid metabolites control T(H)17 and T(reg) cell differentiation. Nature. 2019;576(7785):143-8. DOI: 10.1038/s41586-019-1785-z PMID: 31776512
24. Chattopadhyay I, Dhar R, Pethusamy K, Seethy A, Srivastava T, Sah R, et al. Exploring the Role of Gut Microbiome in Colon Cancer. Appl Biochem Biotechnol. 2021;193(6):1780-99. DOI: 10.1007/s12010-021-03498-9 PMID: 33492552
25. Nikolaus S, Schulte B, Al-Massad N, Thieme F, Schulte DM, Bethge J, et al. Increased Tryptophan Metabolism Is Associated With Activity of Inflammatory Bowel Diseases. Gastroenterology. 2017;153(6):1504-16 e2. DOI: 10.1053/j.gastro.2017.08.028 PMID: 28827067
26. Fornelos N, Franzosa EA, Bishai J, Annand JW, Oka A, Lloyd-Price J, et al. Growth effects of N-acylethanolamines on gut bacteria reflect altered bacterial abundances in inflammatory bowel disease. Nat Microbiol. 2020;5(3):486-97. DOI: 10.1038/s41564-019-0655-7 PMID: 31959971
27. Schmitz JM, Tonkonogy SL, Dogan B, Leblond A, Whitehead KJ, Kim SC, et al. Murine Adherent and Invasive E. coli Induces Chronic Inflammation and Immune Responses in the Small and Large Intestines of Monoassociated IL-10-/- Mice Independent of Long Polar Fimbriae Adhesin A. Inflamm Bowel Dis. 2019;25(5):875-85. DOI: 10.1093/ibd/izy386 PMID: 30576451
28. Kamali Dolatabadi R, Feizi A, Halaji M, Fazeli H, Adibi P. The Prevalence of Adherent-Invasive Escherichia coli and Its Association With Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis. Front Med (Lausanne). 2021;8:730243. DOI: 10.3389/fmed.2021.730243 PMID: 34926490
29. Zhang Q, Su X, Zhang C, Chen W, Wang Y, Yang X, et al. Klebsiella pneumoniae Induces Inflammatory Bowel Disease Through Caspase-11-Mediated IL18 in the Gut Epithelial Cells. Cell Mol Gastroenterol Hepatol. 2023;15(3):613-32. DOI: 10.1016/j.jcmgh.2022.11.005 PMID: 36436756
30. Allen-Vercoe E. Fusobacterium varium in ulcerative colitis: is it population-based? Dig Dis Sci. 2015;60(1):7-8. DOI: 10.1007/s10620-014-3390-1 PMID: 25311584
31. Hayashi A, Nagao-Kitamoto H, Kitamoto S, Kim CH, Kamada N. The Butyrate-Producing Bacterium Clostridium butyricum Suppresses Clostridioides difficile Infection via Neutrophil- and Antimicrobial Cytokine-Dependent but GPR43/109a-Independent Mechanisms. J Immunol. 2021;206(7):1576-85. DOI: 10.4049/jimmunol.2000353 PMID: 33597149
32. Atarashi K, Tanoue T, Oshima K, Suda W, Nagano Y, Nishikawa H, et al. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature. 2013;500(7461):232-6. DOI: 10.1038/nature12331 PMID: 23842501
33. Oka A, Mishima Y, Bongers G, Liu B, Herzog J, Baltus A, et al. Tu1844 - IL-10-Independent Protective Activities of Human-Derived Clostridium Strains in Experimental Colitis. Gastroenterology. 2018;154(6):S-1036. DOI: 10.1016/s0016-5085(18)33470-x
34. Hu S, Vila AV, Gacesa R, Collij V, Stevens C, Fu JM, et al. Whole exome sequencing analyses reveal gene–microbiota interactions in the context of IBD. Gut. 2021;70(2):285-96.
35. Chelakkot C, Ghim J, Ryu SH. Mechanisms regulating intestinal barrier integrity and its pathological implications. Exp Mol Med. 2018;50(8):1-9. DOI: 10.1038/s12276-018-0126-x PMID: 30115904
36. Roy U, Galvez EJC, Iljazovic A, Lesker TR, Blazejewski AJ, Pils MC, et al. Distinct Microbial Communities Trigger Colitis Development upon Intestinal Barrier Damage via Innate or Adaptive Immune Cells. Cell Rep. 2017;21(4):994-1008. DOI: 10.1016/j.celrep.2017.09.097 PMID: 29069606
37. Kudelka MR, Stowell SR, Cummings RD, Neish AS. Intestinal epithelial glycosylation in homeostasis and gut microbiota interactions in IBD. Nat Rev Gastroenterol Hepatol. 2020;17(10):597-617. DOI: 10.1038/s41575-020-0331-7 PMID: 32710014
38. Zhou L, Zhang M, Wang Y, Dorfman RG, Liu H, Yu T, et al. Faecalibacterium prausnitzii Produces Butyrate to Maintain Th17/Treg Balance and to Ameliorate Colorectal Colitis by Inhibiting Histone Deacetylase 1. Inflamm Bowel Dis. 2018;24(9):1926-40. DOI: 10.1093/ibd/izy182 PMID: 29796620
39. Rolhion N, Chassaing B, Nahori MA, de Bodt J, Moura A, Lecuit M, et al. A Listeria monocytogenes Bacteriocin Can Target the Commensal Prevotella copri and Modulate Intestinal Infection. Cell Host Microbe. 2019;26(5):691-701 e5. DOI: 10.1016/j.chom.2019.10.016 PMID: 31726031
40. Cardoso MH, Meneguetti BT, Oliveira-Junior NG, Macedo MLR, Franco OL. Antimicrobial peptide production in response to gut microbiota imbalance. Peptides. 2022;157:170865. DOI: 10.1016/j.peptides.2022.170865 PMID: 36038014
41. Kayama H, Okumura R, Takeda K. Interaction Between the Microbiota, Epithelia, and Immune Cells in the Intestine. Annu Rev Immunol. 2020;38:23-48. DOI: 10.1146/annurev-immunol-070119-115104 PMID: 32340570
42. Gopalakrishna KP, Macadangdang BR, Rogers MB, Tometich JT, Firek BA, Baker R, et al. Maternal IgA protects against the development of necrotizing enterocolitis in preterm infants. Nat Med. 2019;25(7):1110-5. DOI: 10.1038/s41591-019-0480-9 PMID: 31209335
43. Palmela C, Chevarin C, Xu Z, Torres J, Sevrin G, Hirten R, et al. Adherent-invasive Escherichia coli in inflammatory bowel disease. Gut. 2018;67(3):574-87. DOI: 10.1136/gutjnl-2017-314903 PMID: 29141957
44. Read E, Curtis MA, Neves JF. The role of oral bacteria in inflammatory bowel disease. Nat Rev Gastroenterol Hepatol. 2021;18(10):731-42. DOI: 10.1038/s41575-021-00488-4 PMID: 34400822
45. Khaloian S, Rath E, Hammoudi N, Gleisinger E, Blutke A, Giesbertz P, et al. Mitochondrial impairment drives intestinal stem cell transition into dysfunctional Paneth cells predicting Crohn's disease recurrence. Gut. 2020;69(11):1939-51. DOI: 10.1136/gutjnl-2019-319514 PMID: 32111634
46. Allen-Vercoe E, Coburn B. A Microbiota-Derived Metabolite Augments Cancer Immunotherapy Responses in Mice. Cancer Cell. 2020;38(4):452-3. DOI: 10.1016/j.ccell.2020.09.005 PMID: 32976777
47. Subramenium GA, Sabui S, Marchant JS, Said HM, Subramanian VS. Enterotoxigenic Escherichia coli heat labile enterotoxin inhibits intestinal ascorbic acid uptake via a cAMP-dependent NF-kappaB-mediated pathway. Am J Physiol Gastrointest Liver Physiol. 2019;316(1):G55-G63. DOI: 10.1152/ajpgi.00259.2018 PMID: 30285481
48. Campbell C, McKenney PT, Konstantinovsky D, Isaeva OI, Schizas M, Verter J, et al. Bacterial metabolism of bile acids promotes generation of peripheral regulatory T cells. Nature. 2020;581(7809):475-9. DOI: 10.1038/s41586-020-2193-0 PMID: 32461639
49. Gadaleta RM, van Erpecum KJ, Oldenburg B, Willemsen EC, Renooij W, Murzilli S, et al. Farnesoid X receptor activation inhibits inflammation and preserves the intestinal barrier in inflammatory bowel disease. Gut. 2011;60(4):463-72. DOI: 10.1136/gut.2010.212159 PMID: 21242261
50. Alexeev EE, Lanis JM, Kao DJ, Campbell EL, Kelly CJ, Battista KD, et al. Microbiota-Derived Indole Metabolites Promote Human and Murine Intestinal Homeostasis through Regulation of Interleukin-10 Receptor. Am J Pathol. 2018;188(5):1183-94. DOI: 10.1016/j.ajpath.2018.01.011 PMID: 29454749
51. Langan D, Perkins DJ, Vogel SN, Moudgil KD. Microbiota-Derived Metabolites, Indole-3-aldehyde and Indole-3-acetic Acid, Differentially Modulate Innate Cytokines and Stromal Remodeling Processes Associated with Autoimmune Arthritis. Int J Mol Sci. 2021;22(4). DOI: 10.3390/ijms22042017 PMID: 33670600
52. Moayyedi P, Surette MG, Kim PT, Libertucci J, Wolfe M, Onischi C, et al. Fecal Microbiota Transplantation Induces Remission in Patients With Active Ulcerative Colitis in a Randomized Controlled Trial. Gastroenterology. 2015;149(1):102-9 e6. DOI: 10.1053/j.gastro.2015.04.001 PMID: 25857665
53. Castellanos JG, Woo V, Viladomiu M, Putzel G, Lima S, Diehl GE, et al. Microbiota-Induced TNF-like Ligand 1A Drives Group 3 Innate Lymphoid Cell-Mediated Barrier Protection and Intestinal T Cell Activation during Colitis. Immunity. 2018;49(6):1077-89 e5. DOI: 10.1016/j.immuni.2018.10.014 PMID: 30552020
54. Britton GJ, Contijoch EJ, Spindler MP, Aggarwala V, Dogan B, Bongers G, et al. Defined microbiota transplant restores Th17/RORgammat(+) regulatory T cell balance in mice colonized with inflammatory bowel disease microbiotas. Proc Natl Acad Sci U S A. 2020;117(35):21536-45. DOI: 10.1073/pnas.1922189117 PMID: 32817490
55. Inoue S, Nakase H, Chiba T. Etiopathogenesis and aggravating factors in ulcerative colitis. Nihon rinsho Japanese Journal of Clinical Medicine. 2005;63(5):757-62.
56. Ivanov, II, Tuganbaev T, Skelly AN, Honda K. T Cell Responses to the Microbiota. Annu Rev Immunol. 2022;40:559-87. DOI: 10.1146/annurev-immunol-101320-011829 PMID: 35113732
57. Powell N, Pantazi E, Pavlidis P, Tsakmaki A, Li K, Yang F, et al. Interleukin-22 orchestrates a pathological endoplasmic reticulum stress response transcriptional programme in colonic epithelial cells. Gut. 2020;69(3):578-90. DOI: 10.1136/gutjnl-2019-318483 PMID: 31792136
58. Zhao J, Lu Q, Liu Y, Shi Z, Hu L, Zeng Z, et al. Th17 Cells in Inflammatory Bowel Disease: Cytokines, Plasticity, and Therapies. J Immunol Res. 2021;2021:8816041. DOI: 10.1155/2021/8816041 PMID: 33553436
59. Chen L, Ruan G, Cheng Y, Yi A, Chen D, Wei Y. The role of Th17 cells in inflammatory bowel disease and the research progress. Front Immunol. 2022;13:1055914. DOI: 10.3389/fimmu.2022.1055914 PMID: 36700221
60. Ohnmacht C, Park JH, Cording S, Wing JB, Atarashi K, Obata Y, et al. MUCOSAL IMMUNOLOGY. The microbiota regulates type 2 immunity through RORgammat(+) T cells. Science. 2015;349(6251):989-93. DOI: 10.1126/science.aac4263 PMID: 26160380
61. Chu H, Khosravi A, Kusumawardhani IP, Kwon AH, Vasconcelos AC, Cunha LD, et al. Gene-microbiota interactions contribute to the pathogenesis of inflammatory bowel disease. Science. 2016;352(6289):1116-20. DOI: 10.1126/science.aad9948 PMID: 27230380
62. Sun X, He S, Lv C, Sun X, Wang J, Zheng W, et al. Analysis of murine and human Treg subsets in inflammatory bowel disease. Mol Med Rep. 2017;16(3):2893-8. DOI: 10.3892/mmr.2017.6912 PMID: 28677759
63. Qiu P, Ishimoto T, Fu L, Zhang J, Zhang Z, Liu Y. The Gut Microbiota in Inflammatory Bowel Disease. Front Cell Infect Microbiol. 2022;12:733992. DOI: 10.3389/fcimb.2022.733992 PMID: 35273921
64. Nishida A, Nishino K, Sakai K, Owaki Y, Noda Y, Imaeda H. Can control of gut microbiota be a future therapeutic option for inflammatory bowel disease? World J Gastroenterol. 2021;27(23):3317-26. DOI: 10.3748/wjg.v27.i23.3317 PMID: 34163114
65. Allegretti JR, Mullish BH, Kelly C, Fischer M. The evolution of the use of faecal microbiota transplantation and emerging therapeutic indications. Lancet. 2019;394(10196):420-31. DOI: 10.1016/S0140-6736(19)31266-8 PMID: 31379333
66. Levine A, Sigall Boneh R, Wine E. Evolving role of diet in the pathogenesis and treatment of inflammatory bowel diseases. Gut. 2018;67(9):1726-38. DOI: 10.1136/gutjnl-2017-315866 PMID: 29777041
67. Zhuang X, Tian Z, Feng R, Li M, Li T, Zhou G, et al. Fecal Microbiota Alterations Associated With Clinical and Endoscopic Response to Infliximab Therapy in Crohn's Disease. Inflamm Bowel Dis. 2020;26(11):1636-47. DOI: 10.1093/ibd/izaa253 PMID: 33026078
68. van der Lelie D, Oka A, Taghavi S, Umeno J, Fan TJ, Merrell KE, et al. Rationally designed bacterial consortia to treat chronic immune-mediated colitis and restore intestinal homeostasis. Nat Commun. 2021;12(1):3105. DOI: 10.1038/s41467-021-23460-x PMID: 34050144
69. Costea PI, Zeller G, Sunagawa S, Pelletier E, Alberti A, Levenez F, et al. Towards standards for human fecal sample processing in metagenomic studies. Nat Biotechnol. 2017;35(11):1069-76. DOI: 10.1038/nbt.3960 PMID: 28967887
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