Mucosal Healing Research Advances of Inflammatory Bowel Disease
DOI:
https://doi.org/10.53469/jcmp.2024.06(09).32Keywords:
Inflammatory bowel disease, Mucosal healing, Hydrogel, Organs, Probiotics and prebioticsAbstract
Inflammatory bowel disease (IBD) refers to a group of chronic intestinal diseases, including Crohn's disease (CD) and ulcerative colitis (UC). These diseases cause chronic inflammation of the intestinal mucosa and wall, leading to symptoms such as diarrhea, abdominal pain, constipation, fatigue, etc. Intestinal mucosal barrier can prevent microbial and other antigens enter the intestinal wall, maintain its healthy function. However, Immune system dysregulation, dysbiosis of the gut microbiome, and dysfunction of the intestinal epithelial barrier are key pathogenic mechanisms of IBD. The treatment of IBD remains an important medical challenge, the current treatment mainly by inhibiting immune activity, blocking certain inflammatory molecules. Although these methods can induce mucosal healing (MH), but infection and tumor adverse reactions associated with immunosuppression still need to solve. Therefore, researchers are exploring new treatments, to promote the healing of the intestinal mucosa and maintain intestinal health. This review summarizes the traditional treatment of IBD and the application of new technologies such as hydrogels, organoids, probiotics and prebiotics, which aim to safely and effectively promote mucosal barrier healing and restore intestinal function and balance.
References
ANANTHAKRISHNAN A N, BERNSTEIN C N, ILIOPOULOS D, et al. Environmental triggers in IBD: a review of progress and evidence [J]. Nat Rev Gastroenterol Hepatol, 2018, 15(1): 39-49.
FAKHOURY M, NEGRULJ R, MOORANIAN A, et al. Inflammatory bowel disease: clinical aspects and treatments [J]. J Inflamm Res, 2014, 7: 113-20.
PARIENTE B, HU S, BETTENWORTH D, et al. Treatments for Crohn's Disease-Associated Bowel Damage: A Systematic Review [J]. Clin Gastroenterol Hepatol, 2019, 17(5): 847-56.
KOSTIC A D, XAVIER R J, GEVERS D. The microbiome in inflammatory bowel disease: current status and the future ahead [J]. Gastroenterology, 2014, 146(6): 1489-99.
FILIDOU E, KOLIOS G. Probiotics in Intestinal Mucosal Healing: A New Therapy or an Old Friend? [J]. Pharmaceuticals (Basel), 2021, 14(11).
BROMKE M A, NEUBAUER K, KEMPIŃSKI R, et al. Faecal Calprotectin in Assessment of Mucosal Healing in Adults with Inflammatory Bowel Disease: A Meta-Analysis [J]. J Clin Med, 2021, 10(10).
FERNANDES S R, RODRIGUES R V, BERNARDO S, et al. Transmural Healing Is Associated with Improved Long-term Outcomes of Patients with Crohn's Disease [J]. Inflamm Bowel Dis, 2017, 23(8): 1403-9.
AN J, LIU Y, WANG Y, et al. The Role of Intestinal Mucosal Barrier in Autoimmune Disease: A Potential Target [J]. Front Immunol, 2022, 13: 871713.
SCHOULTZ I, KEITA Å V. The Intestinal Barrier and Current Techniques for the Assessment of Gut Permeability [J]. Cells, 2020, 9(8).
GROSCHWITZ K R, HOGAN S P. Intestinal barrier function: molecular regulation and disease pathogenesis [J]. J Allergy Clin Immunol, 2009, 124(1): 3-20; quiz 1-2.
DENG F, WU Z, ZOU F, et al. The Hippo-YAP/TAZ Signaling Pathway in Intestinal Self-Renewal and Regeneration After Injury [J]. Front Cell Dev Biol, 2022, 10: 894737.
DONALDSON G P, LEE S M, MAZMANIAN S K. Gut biogeography of the bacterial microbiota [J]. Nat Rev Microbiol, 2016, 14(1): 20-32.
HOU Q, HUANG J, AYANSOLA H, et al. Intestinal Stem Cells and Immune Cell Relationships: Potential Therapeutic Targets for Inflammatory Bowel Diseases [J]. Front Immunol, 2020, 11: 623691.
BITON M, HABER A L, ROGEL N, et al. T Helper Cell Cytokines Modulate Intestinal Stem Cell Renewal and Differentiation [J]. Cell, 2018, 175(5): 1307-20.e22.
HILL D A, ARTIS D. Intestinal bacteria and the regulation of immune cell homeostasis [J]. Annu Rev Immunol, 2010, 28: 623-67.
CUMMINGS J H, MACFARLANE G T. The control and consequences of bacterial fermentation in the human colon [J]. J Appl Bacteriol, 1991, 70(6): 443-59.
NASTASI C, CANDELA M, BONEFELD C M, et al. The effect of short-chain fatty acids on human monocyte-derived dendritic cells [J]. Sci Rep, 2015, 5: 16148.
BABBIN B A, SASAKI M, GERNER-SCHMIDT K W, et al. The bacterial virulence factor lymphostatin compromises intestinal epithelial barrier function by modulating rho GTPases [J]. Am J Pathol, 2009, 174(4): 1347-57.
WU S, RHEE K J, ZHANG M, et al. Bacteroides fragilis toxin stimulates intestinal epithelial cell shedding and gamma-secretase-dependent E-cadherin cleavage [J]. J Cell Sci, 2007, 120(Pt 11): 1944-52.
HYUN C K. Molecular and Pathophysiological Links between Metabolic Disorders and Inflammatory Bowel Diseases [J]. Int J Mol Sci, 2021, 22(17).
CAI J, SUN L, GONZALEZ F J. Gut microbiota-derived bile acids in intestinal immunity, inflammation, and tumorigenesis [J]. Cell Host Microbe, 2022, 30(3): 289-300.
HAN X, SONG H, WANG Y, et al. Sodium butyrate protects the intestinal barrier function in peritonitic mice [J]. Int J Clin Exp Med, 2015, 8(3): 4000-7.
WANG C C, WU H, LIN F H, et al. Sodium butyrate enhances intestinal integrity, inhibits mast cell activation, inflammatory mediator production and JNK signaling pathway in weaned pigs [J]. Innate Immun, 2018, 24(1): 40-6.
SCHIRMER M, GARNER A, VLAMAKIS H, et al. Microbial genes and pathways in inflammatory bowel disease [J]. Nat Rev Microbiol, 2019, 17(8): 497-511.
NA S Y, MOON W. Perspectives on Current and Novel Treatments for Inflammatory Bowel Disease [J]. Gut Liver, 2019, 13(6): 604-16.
MOWAT C, COLE A, WINDSOR A, et al. Guidelines for the management of inflammatory bowel disease in adults [J]. Gut, 2011, 60(5): 571-607.
SANDBORN W J, DANESE S, D'HAENS G, et al. Induction of clinical and colonoscopic remission of mild-to-moderate ulcerative colitis with budesonide MMX 9 mg: pooled analysis of two phase 3 studies [J]. Aliment Pharmacol Ther, 2015, 41(5): 409-18.
CAI Z, WANG S, LI J. Treatment of Inflammatory Bowel Disease: A Comprehensive Review [J]. Front Med (Lausanne), 2021, 8: 765474.
KHARE V, LYAKHOVICH A, DAMMANN K, et al. Mesalamine modulates intercellular adhesion through inhibition of p-21 activated kinase-1 [J]. Biochem Pharmacol, 2013, 85(2): 234-44.
KHARE V, KRNJIC A, FRICK A, et al. Mesalamine and azathioprine modulate junctional complexes and restore epithelial barrier function in intestinal inflammation [J]. Sci Rep, 2019, 9(1): 2842.
SHIN J Y, WEY M, UMUTESI H G, et al. Thiopurine Prodrugs Mediate Immunosuppressive Effects by Interfering with Rac1 Protein Function [J]. J Biol Chem, 2016, 291(26): 13699-714.
RöMKENS T E, KAMPSCHREUR M T, DRENTH J P, et al. High mucosal healing rates in 5-ASA-treated ulcerative colitis patients: results of a meta-analysis of clinical trials [J]. Inflamm Bowel Dis, 2012, 18(11): 2190-8.
RUTZ S, EIDENSCHENK C, OUYANG W. IL-22, not simply a Th17 cytokine [J]. Immunol Rev, 2013, 252(1): 116-32.
CONNELL W R, KAMM M A, RITCHIE J K, et al. Bone marrow toxicity caused by azathioprine in inflammatory bowel disease: 27 years of experience [J]. Gut, 1993, 34(8): 1081-5.
WALKER T R, LEICHTER A M. 6-Thioguanine can cause serious liver injury in inflammatory bowel disease patients [J]. J Pediatr Gastroenterol Nutr, 2004, 38(2): 232-3.
JHARAP B, SEINEN M L, DE BOER N K, et al. Thiopurine therapy in inflammatory bowel disease patients: analyses of two 8-year intercept cohorts [J]. Inflamm Bowel Dis, 2010, 16(9): 1541-9.
ZEISSIG S, BOJARSKI C, BUERGEL N, et al. Downregulation of epithelial apoptosis and barrier repair in active Crohn's disease by tumour necrosis factor alpha antibody treatment [J]. Gut, 2004, 53(9): 1295-302.
RYAN C, THRASH B, WARREN R B, et al. The use of ustekinumab in autoimmune disease [J]. Expert Opin Biol Ther, 2010, 10(4): 587-604.
LI K, MARANO C, ZHANG H, et al. Relationship Between Combined Histologic and Endoscopic Endpoints and Efficacy of Ustekinumab Treatment in Patients With Ulcerative Colitis [J]. Gastroenterology, 2020, 159(6): 2052-64.
FEAGAN B G, GREENBERG G R, WILD G, et al. Treatment of active Crohn's disease with MLN0002, a humanized antibody to the alpha4beta7 integrin [J]. Clin Gastroenterol Hepatol, 2008, 6(12): 1370-7.
FEAGAN B G, GREENBERG G R, WILD G, et al. Treatment of ulcerative colitis with a humanized antibody to the alpha4beta7 integrin [J]. N Engl J Med, 2005, 352(24): 2499-507.
DEBNATH P, RATHI P M. Vedolizumab in Inflammatory Bowel Disease: West versus East [J]. Inflamm Intest Dis, 2021, 6(1): 1-17.
PEYRIN-BIROULET L, ARKKILA P, ARMUZZI A, et al. Comparative efficacy and safety of infliximab and vedolizumab therapy in patients with inflammatory bowel disease: a systematic review and meta-analysis [J]. BMC Gastroenterol, 2022, 22(1): 291.
CHUDY-ONWUGAJE K O, CHRISTIAN K E, FARRAYE F A, et al. A State-of-the-Art Review of New and Emerging Therapies for the Treatment of IBD [J]. Inflamm Bowel Dis, 2019, 25(5): 820-30.
D'AMICO F, FIORINO G, FURFARO F, et al. Janus kinase inhibitors for the treatment of inflammatory bowel diseases: developments from phase I and phase II clinical trials [J]. Expert Opin Investig Drugs, 2018, 27(7): 595-9.
DUDEK P, FABISIAK A, ZATORSKI H, et al. Efficacy, Safety and Future Perspectives of JAK Inhibitors in the IBD Treatment [J]. J Clin Med, 2021, 10(23).
ANTONELLI E, VILLANACCI V, BASSOTTI G. Novel oral-targeted therapies for mucosal healing in ulcerative colitis [J]. World J Gastroenterol, 2018, 24(47): 5322-30.
PYNE N J, PYNE S. Sphingosine 1-Phosphate Receptor 1 Signaling in Mammalian Cells [J]. Molecules, 2017, 22(3).
ELHAG D A, KUMAR M, SAADAOUI M, et al. Inflammatory Bowel Disease Treatments and Predictive Biomarkers of Therapeutic Response [J]. Int J Mol Sci, 2022, 23(13).
WHITE J R, PHILLIPS F, MONAGHAN T, et al. Review article: novel oral-targeted therapies in inflammatory bowel disease [J]. Aliment Pharmacol Ther, 2018, 47(12): 1610-22.
PEYRIN-BIROULET L, FERRANTE M, MAGRO F, et al. Results from the 2nd Scientific Workshop of the ECCO. I: Impact of mucosal healing on the course of inflammatory bowel disease [J]. J Crohns Colitis, 2011, 5(5): 477-83.
WEHKAMP J, GöTZ M, HERRLINGER K, et al. Inflammatory Bowel Disease [J]. Dtsch Arztebl Int, 2016, 113(5): 72-82.
ARAKI T, MITSUYAMA K, YAMASAKI H, et al. Therapeutic Potential of a Self-Assembling Peptide Hydrogel to Treat Colonic Injuries Associated with Inflammatory Bowel Disease [J]. J Crohns Colitis, 2021, 15(9): 1517-27.
GE X, WEN H, FEI Y, et al. Structurally dynamic self-healable hydrogel cooperatively inhibits intestinal inflammation and promotes mucosal repair for enhanced ulcerative colitis treatment [J]. Biomaterials, 2023, 299: 122184.
OUYANG Y, ZHAO J, WANG S. Multifunctional hydrogels based on chitosan, hyaluronic acid and other biological macromolecules for the treatment of inflammatory bowel disease: A review [J]. Int J Biol Macromol, 2023, 227: 505-23.
ALVEN S, ADERIBIGBE B A. Chitosan and Cellulose-Based Hydrogels for Wound Management [J]. Int J Mol Sci, 2020, 21(24).
MARINHO A, NUNES C, REIS S. Hyaluronic Acid: A Key Ingredient in the Therapy of Inflammation [J]. Biomolecules, 2021, 11(10).
GRAçA M F P, MIGUEL S P, CABRAL C S D, et al. Hyaluronic acid-Based wound dressings: A review [J]. Carbohydr Polym, 2020, 241: 116364.
ABATANGELO G, VINDIGNI V, AVRUSCIO G, et al. Hyaluronic Acid: Redefining Its Role [J]. Cells, 2020, 9(7).
STERN R, ASARI A A, SUGAHARA K N. Hyaluronan fragments: an information-rich system [J]. Eur J Cell Biol, 2006, 85(8): 699-715.
DAY A J, DE LA MOTTE C A. Hyaluronan cross-linking: a protective mechanism in inflammation? [J]. Trends Immunol, 2005, 26(12): 637-43.
SAMMARCO G, SHALABY M, ELANGOVAN S, et al. Hyaluronan Accelerates Intestinal Mucosal Healing through Interaction with TSG-6 [J]. Cells, 2019, 8(9).
LEE Y, SUGIHARA K, GILLILLAND M G, 3RD, et al. Hyaluronic acid-bilirubin nanomedicine for targeted modulation of dysregulated intestinal barrier, microbiome and immune responses in colitis [J]. Nat Mater, 2020, 19(1): 118-26.
KOTLA N G, ISA I L M, RASALA S, et al. Modulation of Gut Barrier Functions in Ulcerative Colitis by Hyaluronic Acid System [J]. Adv Sci (Weinh), 2022, 9(4): e2103189.
KORNBLUTH A, SACHAR D B. Ulcerative colitis practice guidelines in adults: American College Of Gastroenterology, Practice Parameters Committee [J]. Am J Gastroenterol, 2010, 105(3): 501-23; quiz 24.
SEIBOLD F, FOURNIER N, BEGLINGER C, et al. Topical therapy is underused in patients with ulcerative colitis [J]. J Crohns Colitis, 2014, 8(1): 56-63.
PANDEY M, CHOUDHURY H, SK D O S S, et al. Budesonide-Loaded Pectin/Polyacrylamide Hydrogel for Sustained Delivery: Fabrication, Characterization and In Vitro Release Kinetics [J]. Molecules, 2021, 26(9).
APRODU A, MANTAJ J, RAIMI-ABRAHAM B, et al. Evaluation of a Methylcellulose and Hyaluronic Acid Hydrogel as a Vehicle for Rectal Delivery of Biologics [J]. Pharmaceutics, 2019, 11(3).
SOHAIL M, MUDASSIR, MINHAS M U, et al. Natural and synthetic polymer-based smart biomaterials for management of ulcerative colitis: a review of recent developments and future prospects [J]. Drug Deliv Transl Res, 2019, 9(2): 595-614.
TIROSH B, KHATIB N, BARENHOLZ Y, et al. Transferrin as a luminal target for negatively charged liposomes in the inflamed colonic mucosa [J]. Mol Pharm, 2009, 6(4): 1083-91.
SATO T, VRIES R G, SNIPPERT H J, et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche [J]. Nature, 2009, 459(7244): 262-5.
OKAMOTO R, WATANABE M. Cellular and molecular mechanisms of the epithelial repair in IBD [J]. Dig Dis Sci, 2005, 50 Suppl 1: S34-8.
OKAMOTO R, WATANABE M. Role of epithelial cells in the pathogenesis and treatment of inflammatory bowel disease [J]. J Gastroenterol, 2016, 51(1): 11-21.
LANCASTER M A, KNOBLICH J A. Organogenesis in a dish: modeling development and disease using organoid technologies [J]. Science, 2014, 345(6194): 1247125.
LUCAFò M, MUZZO A, MARCUZZI M, et al. Patient-derived organoids for therapy personalization in inflammatory bowel diseases [J]. World J Gastroenterol, 2022, 28(24): 2636-53.
WATANABE S, KOBAYASHI S, OGASAWARA N, et al. Transplantation of intestinal organoids into a mouse model of colitis [J]. Nat Protoc, 2022, 17(3): 649-71.
TAKAHASHI T. Organoids for Drug Discovery and Personalized Medicine [J]. Annu Rev Pharmacol Toxicol, 2019, 59: 447-62.
XU P, ELIZALDE M, MASCLEE A, et al. Corticosteroid enhances epithelial barrier function in intestinal organoids derived from patients with Crohn's disease [J]. J Mol Med (Berl), 2021, 99(6): 805-15.
BOZZETTI V, SENGER S. Organoid technologies for the study of intestinal microbiota-host interactions [J]. Trends Mol Med, 2022, 28(4): 290-303.
WU Q, LIU J, WANG X, et al. Organ-on-a-chip: recent breakthroughs and future prospects [J]. Biomed Eng Online, 2020, 19(1): 9.
SALMINEN S, COLLADO M C, ENDO A, et al. The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics [J]. Nat Rev Gastroenterol Hepatol, 2021, 18(9): 649-67.
LUKIC J, CHEN V, STRAHINIC I, et al. Probiotics or pro-healers: the role of beneficial bacteria in tissue repair [J]. Wound Repair Regen, 2017, 25(6): 912-22.
AL-SADI R, DHARMAPRAKASH V, NIGHOT P, et al. Bifidobacterium bifidum Enhances the Intestinal Epithelial Tight Junction Barrier and Protects against Intestinal Inflammation by Targeting the Toll-like Receptor-2 Pathway in an NF-κB-Independent Manner [J]. Int J Mol Sci, 2021, 22(15).
ARBOLEYA S, SALAZAR N, SOLíS G, et al. Assessment of intestinal microbiota modulation ability of Bifidobacterium strains in in vitro fecal batch cultures from preterm neonates [J]. Anaerobe, 2013, 19: 9-16.
CHICHLOWSKI M, DE LARTIGUE G, GERMAN J B, et al. Bifidobacteria isolated from infants and cultured on human milk oligosaccharides affect intestinal epithelial function [J]. J Pediatr Gastroenterol Nutr, 2012, 55(3): 321-7.
NIU M M, GUO H X, CAI J W, et al. Bifidobacterium breve Alleviates DSS-Induced Colitis in Mice by Maintaining the Mucosal and Epithelial Barriers and Modulating Gut Microbes [J]. Nutrients, 2022, 14(18).
WU Y, LI A, LIU H, et al. Lactobacillus plantarum HNU082 alleviates dextran sulfate sodium-induced ulcerative colitis in mice through regulating gut microbiome [J]. Food Funct, 2022, 13(19): 10171-85.
WU H, XIE S, MIAO J, et al. Lactobacillus reuteri maintains intestinal epithelial regeneration and repairs damaged intestinal mucosa [J]. Gut Microbes, 2020, 11(4): 997-1014.
SANDERS M E, MERENSTEIN D J, REID G, et al. Probiotics and prebiotics in intestinal health and disease: from biology to the clinic [J]. Nat Rev Gastroenterol Hepatol, 2019, 16(10): 605-16.
WILSON B, WHELAN K. Prebiotic inulin-type fructans and galacto-oligosaccharides: definition, specificity, function, and application in gastrointestinal disorders [J]. J Gastroenterol Hepatol, 2017, 32 Suppl 1: 64-8.
BEISNER J, FILIPE ROSA L, KADEN-VOLYNETS V, et al. Prebiotic Inulin and Sodium Butyrate Attenuate Obesity-Induced Intestinal Barrier Dysfunction by Induction of Antimicrobial Peptides [J]. Front Immunol, 2021, 12: 678360.
ROSE E C, ODLE J, BLIKSLAGER A T, et al. Probiotics, Prebiotics and Epithelial Tight Junctions: A Promising Approach to Modulate Intestinal Barrier Function [J]. Int J Mol Sci, 2021, 22(13).
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Changming Zhang, Dong Ming, Gang Ji
This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License.
