본문 바로가기
KERD
논문KCI 등재

Stable colonization of Akkermansia muciniphila educates host intestinal microecology and immunity to battle against inflammatory intestinal diseases

1

조회

0

다운로드

0

인용

0

참고문헌

주제분류생화학

초록

Gut microbial preparations are widely used in treating intestinal diseases but show mixed success. In this study, we found that the therapeutic efficacy of A. muciniphila for dextran sodium sulfate (DSS)-induced colitis as well as intestinal radiation toxicity was ~50%, and mice experiencing a positive prognosis harbored a high frequency of A. muciniphila in the gastrointestinal (GI) tract. Stable GI colonization of A. muciniphila elicited more profound shifts in the gut microbial community structure of hosts. Coexisting with A. muciniphila facilitated proliferation and reprogrammed the gene expression profile of Lactobacillus murinus, a classic probiotic that overtly responded to A. muciniphila addition in a time-dependent manner. Then, a magnetic-drove, mannose-loaded nanophase material was designed and linked to the surface of A. muciniphila. The modified A. muciniphila exhibited enhancements in inflammation targeting and intestinal colonization under an external magnetic field, elevating the positive-response rate and therapeutic efficacy against intestinal diseases. However, the unlinked cocktail containing A. muciniphila and the delivery system only induced negligible improvement of therapeutic efficacy. Importantly, heat-inactivated A. muciniphila lost therapeutic effects on DSS-induced colitis and was even retained in the GI tract for a long time. Further investigations revealed that the modified A. muciniphila was able to drive M2 macrophage polarization by upregulating the protein level of IL-4 at inflammatory loci. Together, our findings demonstrate that stable colonization of live A. muciniphila at lesion sites is essential for its anti-inflammatory function.

Abstract

Gut microbial preparations are widely used in treating intestinal diseases but show mixed success. In this study, we found that the therapeutic efficacy of A. muciniphila for dextran sodium sulfate (DSS)-induced colitis as well as intestinal radiation toxicity was ~50%, and mice experiencing a positive prognosis harbored a high frequency of A. muciniphila in the gastrointestinal (GI) tract. Stable GI colonization of A. muciniphila elicited more profound shifts in the gut microbial community structure of hosts. Coexisting with A. muciniphila facilitated proliferation and reprogrammed the gene expression profile of Lactobacillus murinus, a classic probiotic that overtly responded to A. muciniphila addition in a time-dependent manner. Then, a magnetic-drove, mannose-loaded nanophase material was designed and linked to the surface of A. muciniphila. The modified A. muciniphila exhibited enhancements in inflammation targeting and intestinal colonization under an external magnetic field, elevating the positive-response rate and therapeutic efficacy against intestinal diseases. However, the unlinked cocktail containing A. muciniphila and the delivery system only induced negligible improvement of therapeutic efficacy. Importantly, heat-inactivated A. muciniphila lost therapeutic effects on DSS-induced colitis and was even retained in the GI tract for a long time. Further investigations revealed that the modified A. muciniphila was able to drive M2 macrophage polarization by upregulating the protein level of IL-4 at inflammatory loci. Together, our findings demonstrate that stable colonization of live A. muciniphila at lesion sites is essential for its anti-inflammatory function.

참고문헌 (58)

  1. Ananthakrishnan, A. N., "Epidemiology and risk factors for IBD", Nat. Rev. Gastroenterol. Hepatol, 4, pp.205~217 (2015)
  2. Kudelka, M. R., "Intestinal epithelial glycosylation in homeostasis and gut microbiota interactions in IBD", Nat. Rev. Gastroenterol. Hepatol, 10, pp.597~617 (2020)
  3. Takemura, N., "Eosinophil depletion suppresses radiation-induced small intestinal fibrosis", Sci. Transl. Med, 10, pp.eaan0333~ (2018)
  4. Wastyk, H. C., "Gut-microbiota-targeted diets modulate human immune status", Cell, 16, pp.4137~4153 (2021)
  5. Cani, P. D., "Endocannabinoids-at the crossroads between the gut microbiota and host metabolism", Nat. Rev. Endocrinol, 3, pp.133~143 (2016)
  6. Yang, J., "High-Fat Diet Promotes Colorectal Tumorigenesis Through Modulating Gut Microbiota and Metabolites", Gastroenterology, 1, pp.135~149 (2022)
  7. Schirmer, M., "Microbial genes and pathways in inflammatory bowel disease", Nat. Rev. Microbiol, 8, pp.497~511 (2019)
  8. Ooijevaar, R. E., "Clinical Application and Potential of Fecal Microbiota Transplantation", Annu. Rev. Med, 70, pp.335~351 (2019)
  9. Ganji-Arjenaki, M., "Probiotics are a good choice in remission of inflammatory bowel diseases : A meta analysis and systematic review", J. Cell. Physiol, 3, pp.2091~2103 (2018)
  10. Hedin, C., "Evidence for the use of probiotics and prebiotics in inflammatory bowel disease : a review of clinical trials", Proc. Nutr. Soc, 3, pp.307~315 (2007)
  11. Suez, J., "The pros, cons, and many unknowns of probiotics", Nat. Med, 5, pp.716~729 (2019)
  12. Paramsothy, S., "600 Multi Donor Intense Faecal Microbiota Transplantation is an Effective Treatment for Resistant Ulcerative Colitis : A Randomised Placebo-Controlled Trial", Gastroenterology, 4, pp.S122~S123 (2016)
  13. Maldonado-Gómez, M. X., "Stable Engraftment of Bifidobacterium longum AH1206 in the Human Gut Depends on Individualized Features of the Resident Microbiome", Cell Host Microbe, 4, pp.515~526 (2016)
  14. Ianiro, G., "Antibiotics as deep modulators of gut microbiota : between good and evil", Gut, 11, pp.1906~1915 (2016)
  15. Zocco, M. A., "Efficacy of Lactobacillus GG in maintaining remission of ulcerative colitis", Aliment. Pharmacol. Ther, 11, pp.1567~1574 (2006)
  16. Damman, C., "Su1403 Single Colonoscopically Administered Fecal Microbiota Transplant for Ulcerative Colitis-A Pilot Study to Determine Therapeutic Benefit and Graft Stability", Gastroenterology, 5, pp.460~ (2014)
  17. Rossen, N. G., "Findings From a Randomized Controlled Trial of Fecal Transplantation for Patients With Ulcerative Colitis", Gastroenterology, 1, pp.110~118 (2015)
  18. Marcella, C., "Systematic review : the global incidence of faecal microbiota transplantation-related adverse events from 2000 to 2020", Aliment. Pharmacol. Ther, 1, pp.33~42 (2021)
  19. Zhang, Y., "Gut microbiome-related effects of berberine and probiotics on type 2 diabetes(the PREMOTE study)", Nat. Commun, 1, pp.5015~ (2020)
  20. Suez, J., "Post-Antibiotic Gut Mucosal Microbiome Reconstitution Is Impaired by Probiotics and Improved by Autologous FMT", Cell, 6, pp.1406~1423 (2018)
  21. Zmora, N., "Personalized Gut Mucosal Colonization Resistance to Empiric Probiotics Is Associated with Unique Host and Microbiome Features", Cell, 6, pp.1388~1405 (2018)
  22. Lee, S. H., "Bifidobacterium bifidum strains synergize with immune checkpoint inhibitors to reduce tumour burden in mice", Nat. Microbiol, 3, pp.277~288 (2021)
  23. Alam, A., "The microenvironment of injured murine gut elicits a local prorestitutive microbiota", Nat. Microbiol, 1, pp.15021~ (2016)
  24. Yoon, H. S., "Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice", Nat. Microbiol, 5, pp.563~573 (2021)
  25. Wang, L., "A purified membrane protein from Akkermansia muciniphila or the pasteurised bacterium blunts colitis associated tumourigenesis by modulation of CD8(+)T cells in mice", Gut, 11, pp.1988~1997 (2020)
  26. Wang, B., "Low-Intensity Exercise Modulates Gut Microbiota to Fight Against Radiation-Induced Gut Toxicity in Mouse Models", Front. Cell Dev. Bio, 9, pp.706755~ (2021)
  27. Wirtz, S., "Chemically induced mouse models of acute and chronic intestinal inflammation", Nat. Protoc, 7, pp.1295~1309 (2017)
  28. Liu, J., "Highly water-dispersible biocompatible magnetite particles with low cytotoxicity stabilized by citrate groups", Angew. Chem. Int. Ed. Engl, 32, pp.5875~5879 (2009)
  29. Kim, T. H., "Mix to validate : a facile, reversible PEGylation for fast screening of potential therapeutic proteins in vivo", Angew. Chem. Int. Ed. Engl, 27, pp.6880~6884 (2013)
  30. Darwish, S., "Synthesis and antiproliferative activities of doxorubicin thiol conjugates and doxorubicin-SS-cyclic peptide", Eur. J. Med. Chem, 161, pp.594~606 (2019)
  31. Jue, R., "Addition of sulfhydryl groups to Escherichia coli ribosomes by protein modification with 2-iminothiolane (methyl 4-mercaptobutyrimidate)", Biochemistry, 25, pp.5399~5406 (1978)
  32. Plovier, H., "A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice", Nat. Med, 1, pp.107~113 (2017)
  33. Zheng, D. W., "Prebiotics-Encapsulated Probiotic Spores Regulate Gut Microbiota and Suppress Colon Cancer", Adv. Mater, 45, pp.e2004529~ (2020)
  34. He, H., "Leutusome : A Biomimetic Nanoplatform Integrating Plasma Membrane Components of Leukocytes and Tumor Cells for Remarkably Enhanced Solid Tumor Homing", Nano Lett, 10, pp.6164~6174 (2018)
  35. Johansson, M. E., "Preservation of mucus in histological sections, immunostaining of mucins in fixed tissue, and localization of bacteria with FISH", Methods Mol. Biol, 842, pp.229~235 (2012)
  36. Wei, Z., "Boosting anti-PD-1 therapy with metformin-loaded macrophagederived microparticles", Nat. Commun, 1, pp.440~ (2021)
  37. Na, Y. R., "Macrophages in intestinal inflammation and resolution : a potential therapeutic target in IBD", Nat. Rev. Gastroenterol. Hepatol, 9, pp.531~543 (2019)
  38. Jayme, T. S., "Human interleukin-4-treated regulatory macrophages promote epithelial wound healing and reduce colitis in a mouse model", Sci. Adv, 23, pp.eaba4376~ (2020)
  39. Jackson, M. A., "Gut microbiota associations with common diseases and prescription medications in a population-based cohort", Nat. Commun, 1, pp.2655~ (2018)
  40. Tremaroli, V., "Functional interactions between the gut microbiota and host metabolism", Nature, 7415, pp.242~249 (2012)
  41. Groen, A. K., "An evaluation of the therapeutic potential of fecal microbiota transplantation to treat infectious and metabolic diseases", EMBO Mol. Med, 1, pp.1~3 (2017)
  42. Cui, M., "Faecal microbiota transplantation protects against radiation-induced toxicity", EMBO Mol. Med, 4, pp.448~461 (2017)
  43. Ljungquist, O., "Probiotics for intestinal decolonization of ESBL-producing Enterobacteriaceae : a randomized, placebo-controlled clinical trial", Clin. Microbiol. Infect, 4, pp.456~462 (2020)
  44. Roach, T. N. F., "A multiomic analysis of in situ coral-turf algal interactions", Proc. Natl Acad. Sci. USA, 24, pp.13588~13595 (2020)
  45. Han, H., "From gut microbiota to host appetite : gut microbiota-derived metabolites as key regulators", Microbiome, 1, pp.162~ (2021)
  46. Chen, L., "Ifnar gene variants influence gut microbial production of palmitoleic acid and host immune responses to tuberculosis", Nat. Metab, 3, pp.359~373 (2022)
  47. Hänninen, A., "Akkermansia muciniphila induces gut microbiota remodelling and controls islet autoimmunity in NOD mice", Gut, 8, pp.1445~1453 (2018)
  48. Hu, J., "Lactobacillus murinus alleviate intestinal ischemia", reperfusion injury through promoting the release of interleukin-10 from M2 macrophages via Tolllike receptor 2 signaling, 2022, pp.1, 38~
  49. Beaumont, M., "Amino acids in intestinal physiology and health", Adv. Exp. Med. Biol, 1265, pp.1~20 (2020)
  50. Li, Y., "Gut commensal derived-valeric acid protects against radiation injuries", Gut Microbes, 4, pp.789~806 (2020)
  51. Wang, X., "Bioinspired oral delivery of gut microbiota by self-coating with biofilms", Sci. Adv, 26, pp.eabb1952~ (2020)
  52. Xiao, Y., "Encapsulation of Lactobacillus rhamnosus in Hyaluronic Acid-Based Hydrogel for Pathogen-Targeted Delivery to Ameliorate Enteritis", ACS Appl. Mater. Interfac, 33, pp.36967~36977 (2020)
  53. Buss, M. T., "Spatial Control of Probiotic Bacteria in the Gastrointestinal Tract Assisted by Magnetic Particles", Adv. Mater, 17, pp.e2007473~ (2021)
  54. Kilinc, D., "Bio-Nano-Magnetic Materials for Localized Mechanochemical Stimulation of Cell Growth and Death", Adv. Mater, 27, pp.5672~5680 (2016)
  55. Shander, A., "Iron overload and toxicity : the hidden risk of multiple blood transfusions", Vox. Sang, 3, pp.185~197 (2009)
  56. Sayadi, M. H., "Exposure effects of iron oxide nanoparticles and iron salts in blackfish(Capoeta fusca) : Acute toxicity, bioaccumulation, depuration, and tissue histopathology", Chemosphere, 247, pp.125900~ (2020)
  57. Qu, S., "Akkermansia muciniphila Alleviates Dextran Sulfate Sodium(DSS)-Induced Acute Colitis by NLRP3 Activation", Microbiol. Spectr, 2, pp.e0073021~ (2021)
  58. Liu, Y., "NLRP3 regulates macrophage M2 polarization through up-regulation of IL-4 in asthma", Biochem. J, 12, pp.1995~2008 (2018)

관련 논문AI추천

Bifidobacterium infantis Induces Protective Colonic PD-L1 and Foxp3 Regulatory T Cells in an Acute Murine Experimental Model of Inflammatory Bowel DiseaseDongyan Liu, Linyan Zhou, Xinjie Yao, Yan Li, Ying Xie거트앤리버 소화기연관학회협의회 · Gut and Liver2019 · 제13권 제4호Synbiotic of Pediococcus acidilactici and Inulin Ameliorates Dextran Sulfate Sodium-Induced Acute Ulcerative Colitis in MiceCui Chengdu, Cui Lianhua, Jin Xin, Jin Yuanming, Piao Huiyan, Wang Mingzhu, Yan Chunri, Zhang Longzhou한국미생물·생명공학회 · Journal of Microbiology and Biotechnology2024 · 제34권 제3호Multiomics Integration Reveals Microbial Gene Interactions Shaping Host Responses in a DSS-Induced Colitis Mouse ModelHong Hyun-Hee, Jang Da Hae, Ju Si-Eun, Kang Hyung-Sik, Kim Su-Man, Kim Tae-Hwan, Lee Seo-Yeong, Shim Ji Eun한국미생물·생명공학회 · Journal of Microbiology and Biotechnology2025 · 제35권 Protective Potential of Limosilactobacillus fermentum Strains and Their Mixture on Inflammatory Bowel Disease via Regulating Gut Microbiota in MiceChoi Kayoung, Joung Jae Yeon, Lee Ju-Hoon, Oh Nam Su한국미생물·생명공학회 · Journal of Microbiology and Biotechnology2025 · 제35권 Microbial Modulation in Inflammatory Bowel DiseasesCheon Jae Hee, Yu Jongwook대한면역학회 · Immune Network2022 · 제22권 제6호Deinococcus radiodurans R1 Lysate Induces Tolerogenic Maturation in Lipopolysaccharide-Stimulated Dendritic Cells and Protects Dextran Sulfate Sodium-Induced Colitis in MiceByun Eui-Baek, Byun Eui-Hong, Han Jeong Moo, Kim Woo Sik, Lee Ji Hee, Park Woo Yong, Song Ha-Yeon한국미생물·생명공학회 · Journal of Microbiology and Biotechnology2022 · 제32권 제7호

이 간행물의 다른 논문 (225건)