In situ gut microbiota editing: enhancing therapeutic efficacy for bacterial colitis by compatible oral hydrogel microspheres with phages.
| Title: | In situ gut microbiota editing: enhancing therapeutic efficacy for bacterial colitis by compatible oral hydrogel microspheres with phages. |
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| Authors: | Yang Y; National Key Laboratory of Agricultural Microbiology, Key Laboratory of Environment Correlative Dietology, College of Food Science and Technology, Huazhong Agricultural University, Wuhan, China.; Hubei Hongshan Laboratory, College of Biomedicine and Health, Huazhong Agricultural University, Wuhan, China.; Li R; National Key Laboratory of Agricultural Microbiology, Key Laboratory of Environment Correlative Dietology, College of Food Science and Technology, Huazhong Agricultural University, Wuhan, China.; Hubei Hongshan Laboratory, College of Biomedicine and Health, Huazhong Agricultural University, Wuhan, China.; College of Life Science and Technology, Huazhong Agricultural University, Wuhan, China.; Zhong Q; National Key Laboratory of Agricultural Microbiology, Key Laboratory of Environment Correlative Dietology, College of Food Science and Technology, Huazhong Agricultural University, Wuhan, China.; Hubei Hongshan Laboratory, College of Biomedicine and Health, Huazhong Agricultural University, Wuhan, China.; Guo Y; National Key Laboratory of Agricultural Microbiology, Key Laboratory of Environment Correlative Dietology, College of Food Science and Technology, Huazhong Agricultural University, Wuhan, China.; Hubei Hongshan Laboratory, College of Biomedicine and Health, Huazhong Agricultural University, Wuhan, China.; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.; Wu R; National Key Laboratory of Agricultural Microbiology, Key Laboratory of Environment Correlative Dietology, College of Food Science and Technology, Huazhong Agricultural University, Wuhan, China.; Chen H; National Key Laboratory of Agricultural Microbiology, Key Laboratory of Environment Correlative Dietology, College of Food Science and Technology, Huazhong Agricultural University, Wuhan, China.; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.; Zhou R; National Key Laboratory of Agricultural Microbiology, Key Laboratory of Environment Correlative Dietology, College of Food Science and Technology, Huazhong Agricultural University, Wuhan, China.; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.; Ye R; National Key Laboratory of Agricultural Microbiology, Key Laboratory of Environment Correlative Dietology, College of Food Science and Technology, Huazhong Agricultural University, Wuhan, China.; Hubei Hongshan Laboratory, College of Biomedicine and Health, Huazhong Agricultural University, Wuhan, China.; College of Chemistry, Huazhong Agricultural University, Wuhan, China.; Dąbrowska K; Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Faculty of Medicine, Wrocław University of Science and Technology, Wrocław, Poland.; Prajsnar TK; Department of Evolutionary Immunology, Jagiellonian University, Kraków, Poland.; Stafford GP; School of Clinical Dentistry, The University of Sheffield, Sheffield, United Kingdom.; Zou G; College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, China. zougeng19900918@126.com.; Zhou Y; National Key Laboratory of Agricultural Microbiology, Key Laboratory of Environment Correlative Dietology, College of Food Science and Technology, Huazhong Agricultural University, Wuhan, China. zhouyang@mail.hzau.edu.cn.; College of Fisheries, Huazhong Agricultural University, Wuhan, China. zhouyang@mail.hzau.edu.cn.; Li J; National Key Laboratory of Agricultural Microbiology, Key Laboratory of Environment Correlative Dietology, College of Food Science and Technology, Huazhong Agricultural University, Wuhan, China. lijinquan2007@gmail.com.; Hubei Hongshan Laboratory, College of Biomedicine and Health, Huazhong Agricultural University, Wuhan, China. lijinquan2007@gmail.com.; Hubei Jiangxia Laboratory, Wuhan, China. lijinquan2007@gmail.com.; Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, NY, USA. lijinquan2007@gmail.com.; Zhanjiang Key Laboratory of Metabolic Disease Research, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, China. lijinquan2007@gmail.com.; Song Z; National Key Laboratory of Agricultural Microbiology, Key Laboratory of Environment Correlative Dietology, College of Food Science and Technology, Huazhong Agricultural University, Wuhan, China. songzhiyong@mail.hzau.edu.cn.; Hubei Hongshan Laboratory, College of Biomedicine and Health, Huazhong Agricultural University, Wuhan, China. songzhiyong@mail.hzau.edu.cn.; College of Chemistry, Huazhong Agricultural University, Wuhan, China. songzhiyong@mail.hzau.edu.cn. |
| Source: | Nature communications [Nat Commun] 2025 Nov 06; Vol. 16 (1), pp. 9785. Date of Electronic Publication: 2025 Nov 06. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [London] : Nature Pub. Group |
| MeSH Terms: | Colitis*/microbiology ; Colitis*/therapy ; Gastrointestinal Microbiome*/drug effects ; Bacteriophages*/physiology ; Hydrogels*/chemistry ; Phage Therapy*/methods ; Microspheres*; Salmonella typhimurium/virology ; Dysbiosis/microbiology ; Dysbiosis/therapy ; Alginates/chemistry ; Anti-Bacterial Agents/pharmacology ; Salmonella Infections/therapy ; Salmonella Infections/microbiology ; Colon/microbiology ; Polymethacrylic Acids/chemistry ; Animals ; Mice ; Administration, Oral ; Disease Models, Animal ; Mice, Inbred C57BL ; Female |
| Abstract: | Gut microbiota editing represents a promising therapeutic strategy for dysbiosis-associated diseases. Bacteriophages (phages), with their host specificity, enable precise microbial manipulation but face challenges such as environmental vulnerability and low bioavailability, which limit their in vivo efficacy. Here, we develop double-responsive hydrogel microspheres (HMs) via electrohydrodynamic spraying to enhance oral phage delivery. Composed of sodium alginate, hyaluronic acid, and Eudragit S100, these HMs achieve 90% encapsulation efficiency for a Salmonella-targeting phage cocktail. Such formulation significantly protects phages from gastric conditions, prolongs their intestinal retention, and enables responsive payload release in the colon. In a murine model of Salmonella Typhimurium (STm)-induced colitis, HMs-encapsulated phages (HMs-Phages) reduce intestinal STm burden by nearly 2000-fold and lower levels of proinflammatory cytokines (TNF-α, IL-6, IL-1β) to 60% of those in infected group. Notably, HMs-Phages achieve potent antibacterial efficacy comparable to ciprofloxacin while selectively targeting STm. This targeted strategy circumvents antibiotics-associated microbiota dysbiosis and diarrhea, thereby effectively restoring gut homeostasis and improving host physical health. By integrating targeted pathogen eradication with microbiota conservation, this work provides a precise toolkit for gut microbiota editing and phage therapy, offering substantial advantages over antibiotics for managing dysbiosis-related diseases.; (© 2025. The Author(s).) |
| Competing Interests: | Competing interests: A patent application related to the phage-encapsulating hydrogel microsphere platform described in this work has been filed with the China National Intellectual Property Administration by Huazhong Agricultural University, with Y.Y., R.W., R.Y., G.Z., Y.Z., J.L., and Z.S. as inventors (application number CN202410757523.4). The remaining authors declare no competing interests. |
| References: | Adv Sci (Weinh). 2024 Aug;11(32):e2404049. (PMID: 38899839); Nat Med. 2022 Apr;28(4):690-703. (PMID: 35440726); Sci Bull (Beijing). 2024 Sep 15;69(17):2683-2687. (PMID: 38643060); Nat Rev Immunol. 2020 Jul;20(7):411-426. (PMID: 32005980); Artif Cells Nanomed Biotechnol. 2017 Mar;45(2):357-363. (PMID: 27018340); Gastroenterology. 2018 Mar;154(4):1037-1046.e2. (PMID: 29174952); Nat Commun. 2019 Dec 19;10(1):5783. (PMID: 31857577); J Control Release. 2021 Jan 10;329:1172-1197. (PMID: 33127450); Nat Methods. 2012 Mar 04;9(4):357-9. (PMID: 22388286); ACS Nano. 2023 Aug 8;17(15):14718-14730. (PMID: 37490035); J Control Release. 2023 Jan;353:634-649. (PMID: 36464065); Cell. 2023 Jan 5;186(1):17-31. (PMID: 36608652); Carbohydr Polym. 2022 Sep 1;291:119359. (PMID: 35698318); Genome Biol. 2019 Nov 28;20(1):257. (PMID: 31779668); Sci Adv. 2022 Jul 15;8(28):eabq2005. (PMID: 35857522); Nat Rev Endocrinol. 2020 Dec;16(12):731-739. (PMID: 33106657); Adv Colloid Interface Sci. 2017 Nov;249:100-133. (PMID: 28688779); Gut Microbes. 2022 Jan-Dec;14(1):2100197. (PMID: 35854629); Macromol Biosci. 2022 Jul;22(7):e2100493. (PMID: 35182103); Food Res Int. 2021 Sep;147:110492. (PMID: 34399488); Expert Rev Anti Infect Ther. 2019 Aug;17(8):583-606. (PMID: 31322022); Gut. 2019 Jun;68(6):1014-1023. (PMID: 30045880); Microorganisms. 2020 Feb 13;8(2):. (PMID: 32069865); Nat Rev Microbiol. 2023 Dec;21(12):772-788. (PMID: 37491458); Nat Commun. 2020 Oct 6;11(1):5030. (PMID: 33024097); Lancet Microbe. 2024 May;5(5):e489-e499. (PMID: 38452780); Science. 2012 Jun 8;336(6086):1255-62. (PMID: 22674335); Microbiome. 2022 Feb 9;10(1):29. (PMID: 35139923); Microorganisms. 2020 Jul 21;8(7):. (PMID: 32708328); Bioinformatics. 2018 Sep 1;34(17):i884-i890. (PMID: 30423086); Adv Sci (Weinh). 2022 May;9(14):e2105955. (PMID: 35285170); Cell Host Microbe. 2020 Sep 9;28(3):390-401.e5. (PMID: 32615090); Nat Rev Gastroenterol Hepatol. 2022 Feb;19(2):135-144. (PMID: 34782783); Nat Commun. 2024 Jun 4;15(1):4764. (PMID: 38834561); PeerJ Comput Sci. 2017;3:. (PMID: 40271438); Nat Rev Microbiol. 2022 Jan;20(1):49-62. (PMID: 34373631); Adv Drug Deliv Rev. 2019 Jun;146:209-239. (PMID: 30605737); FEMS Microbiol Rev. 2020 Nov 24;44(6):684-700. (PMID: 32472938); Nat Rev Gastroenterol Hepatol. 2019 Apr;16(4):235-246. (PMID: 30643227); FEMS Microbiol Rev. 2020 Jul 1;44(4):507-521. (PMID: 32495834); Nat Microbiol. 2022 Aug;7(8):1301-1311. (PMID: 35918425); Vet Microbiol. 2009 Apr 14;136(1-2):135-41. (PMID: 19058927); Nat Rev Gastroenterol Hepatol. 2017 Oct;14(10):573-584. (PMID: 28743984); Viruses. 2019 Sep 10;11(9):. (PMID: 31510005); Front Microbiol. 2022 Aug 04;13:906103. (PMID: 35992667); Food Res Int. 2023 Mar;165:112454. (PMID: 36869473); FEMS Microbiol Rev. 2022 Jan 18;46(1):. (PMID: 34289033); Crit Rev Microbiol. 2020 Feb;46(1):78-99. (PMID: 32091280) |
| Grant Information: | 22577034 National Natural Science Foundation of China (National Science Foundation of China); 32402264 National Natural Science Foundation of China (National Science Foundation of China); 32322082 National Natural Science Foundation of China (National Science Foundation of China) |
| Substance Nomenclature: | 0 (Hydrogels); 0 (Alginates); 0 (Anti-Bacterial Agents); 25086-15-1 (methylmethacrylate-methacrylic acid copolymer); 0 (Polymethacrylic Acids) |
| Entry Date(s): | Date Created: 20251106 Date Completed: 20251106 Latest Revision: 20260118 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC12808749 |
| DOI: | 10.1038/s41467-025-65498-1 |
| PMID: | 41198711 |
| Database: | MEDLINE |
Journal Article