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Probiotic-based biohybrid with gastrointestinal stress resistance and ROS-scavenging capacity to treat inflammatory bowel disease

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  • Corresponding author: wanhao424@ncu.edu.cn
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    1. Lp@AU@GN was bio-orthogonally fabricated.

      β-glucan (GN) shielded Lp from digestive insults and was metabolized into short-chain fatty acids (SCFAs).

      Au24Cu1/Au24Cd1 mixture (AU) scavenged reactive oxygen species (ROS) to enhance Lp viability.

      Oral administration of Lp@AU@GN effectively alleviated inflammatory bowel disease (IBD).

  • Oral probiotic-based therapy has emerged as a promising solution with multifaceted benefits for inflammatory bowel disease (IBD) treatment. However, their widespread and clinical utility is severely limited by the poor viability of probiotics under harsh gastrointestinal conditions and elevated oxidative stress in the inflamed intestine. To address these challenges, a probiotic-based biohybrid (Lp@AU@GN) was bio-orthogonally fabricated by covalently anchoring the gold nanocluster-based artificial enzyme (AU) to the probiotic Lactobacillus plantarum (Lp), a strain screened out with the IBD-alleviating potential, followed by covalent encapsulation with the prebiotic β-glucan (GN). Upon oral administration to mice with ulcerative colitis, GN performed as a shield to physically protect Lp from gastrointestinal stress insults. After reaching the intestine, GN was metabolized by the gut microbiota, facilitating the exposure of Lp@AU and the concurrent production of short-chain fatty acids (SCFAs). The incorporated AU with superoxide dismutase- and catalase-like activities efficiently scavenged excessive reactive oxygen species in situ, neutralizing oxidative stress and simultaneously enhancing Lp survival to synergize with SCFAs to advance the therapeutic process. Consequently, therapeutic benefits of reduced inflammation, restored intestinal barrier, and rebalanced gut microbiota were achieved. Furthermore, the therapeutic utility was extended to Crohn's disease, establishing the broad-spectrum effectiveness of Lp@AU@GN for addressing both major forms of IBD. Beyond IBD, our developed modular engineering strategy holds the great potential to be adapted to fabricate diverse biohybrids for other gastrointestinal or metabolic disorders’ treatments by tuning the probiotic strain, antioxidant moiety, or prebiotic polymer.
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  • [1] Wang W., Wu L., Wu X., et al. (2021). Combined analysis of serum SAP and PRSS2 for the differential diagnosis of CD and UC. Clin. Chim. Acta 514:8−14. DOI:10.1016/j.cca.2020.12.014

    View in Article CrossRef Google Scholar

    [2] Kaplan G. G. and Ng S. C. (2017). Understanding and preventing the global increase of inflammatory bowel disease. Gastroenterology 152:313−321.e31. DOI:10.1053/j.gastro.2016.10.020

    View in Article CrossRef Google Scholar

    [3] Loftus E. V. Jr. (2004). Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences. Gastroenterology 126:1504−1517. DOI:10.1053/j.gastro.2004.01.063

    View in Article CrossRef Google Scholar

    [4] Sienkiewicz M., Szymańska P. and Fichna J. (2021). Supplementation of bovine colostrum in inflammatory bowel disease: Benefits and contraindications. Adv. Nutr. 12:533−545. DOI:10.1093/advances/nmaa120

    View in Article CrossRef Google Scholar

    [5] Li F., Zhao, R., Ding W., et al. (2025). Chemical exchange saturation transfer MRI-trackable peptide hydrogel for drug release monitoring and targeted therapy in inflammatory bowel disease. Cell Biomaterials 1:100098. DOI:10.1016/j.celbio.2025.100098

    View in Article Google Scholar

    [6] Kappelman M. D., Rifas-Shiman, S. L., Porter C. Q., et al. (2008). Direct health care costs of Crohn's disease and ulcerative colitis in US children and adults. Gastroenterology 135:1907−1913. DOI:10.1053/j.gastro.2008.09.012

    View in Article CrossRef Google Scholar

    [7] Cai Z., Wang S. and Li J. (2021). Treatment of Inflammatory Bowel Disease: A Comprehensive Review. Front. Med. (Lausanne) 8:765474. DOI:10.3389/fmed.2021.765474

    View in Article CrossRef Google Scholar

    [8] D'Amico F., Peyrin-Biroulet L. and Danese S. (2022). Ustekinumab in Crohn's disease: New data for positioning in treatment algorithm. J. Crohns Colitis 16:ii30−ii41. DOI:10.1093/ecco-jcc/jjac011

    View in Article CrossRef Google Scholar

    [9] Wehkamp J., Götz M. and Herrlinger K. (2016). Inflammatory bowel disease: Crohn’s disease and ulcerative colitis. Dtsch. Arztebl. Int. 113:72. DOI:10.3238/arztebl.2016.0072

    View in Article CrossRef Google Scholar

    [10] Bourgonje A.R., Feelisch M. and Faber K.N. (2020). Oxidative stress and redox-modulating therapeutics in inflammatory bowel disease. Trends Mol. Med. 26:1034−1046. DOI:10.1016/j.molmed.2020.06.006

    View in Article CrossRef Google Scholar

    [11] Ramos G.P. and Papadakis K.A. (2019). Mechanisms of disease: Inflammatory bowel diseases, Mayo Clin. Proc. pp:155-165. DOI:10.1016/j.mayocp.2018.09.013

    View in Article Google Scholar

    [12] Glassner K.L., Abraham B.P. and Quigley E.M. (2020). The microbiome and inflammatory bowel disease. J. Allergy. Clin. Immun. 145:16−27. DOI:10.1016/j.jaci.2019.11.003

    View in Article CrossRef Google Scholar

    [13] Vemuri R., Gundamaraju R. and Eri R. (2017). Role of lactic acid probiotic bacteria in IBD. Curr. Pharm. Des. 23:2352−2355. DOI:10.2174/1381612823666170207100025

    View in Article CrossRef Google Scholar

    [14] Shen F., Wang Q., Ullah S., et al. (2024). Ligilactobacillus acidipiscis YJ5 modulates the gut microbiota and produces beneficial metabolites to relieve constipation by enhancing the mucosal barrier. Food Funct. 15:310−325. DOI:10.1039/d3fo03259k

    View in Article CrossRef Google Scholar

    [15] Rawal S. and Ali S. A. (2023). Probiotics and postbiotics play a role in maintaining dermal health. Food Funct. 14:3966−3981. DOI:10.1039/d3fo00152k

    View in Article CrossRef Google Scholar

    [16] La Fata G., Weber P. and Mohajeri M. H. (2018). Probiotics and the Gut Immune System: Indirect regulation. Probiotics Antimicrob. 10:11−21. DOI:10.1007/s12602-017-9322-6

    View in Article CrossRef Google Scholar

    [17] Hill C., Guarner F., Reid G., et al. (2014). Expert consensus document. The international scientific association for probiotics and prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat. Rev. Gastroenterol. Hepatol. 11:506−514. DOI:10.1038/nrgastro.2014.66

    View in Article CrossRef Google Scholar

    [18] Moon J. E., Heo W., Lee S. H., et al. (2020). Trehalose protects the probiotic yeast saccharomyces boulardii against oxidative stress-induced cell death. J. Microbiol. Biotechnol. 30:54−61. DOI:10.4014/jmb.1906.06041

    View in Article CrossRef Google Scholar

    [19] Liu J., Wang Y., Heelan W. J. et al. (2022). Mucoadhesive probiotic backpacks with ROS nanoscavengers enhance the bacteriotherapy for inflammatory bowel diseases. Sci. Adv. 8:eabp8798. DOI:10.1126/sciadv.abp8798

    View in Article CrossRef Google Scholar

    [20] Zhu Y., Ma R., Thakur K., et al. (2025). Layer-by-layer nanoencapsulation strategies for enhanced oral delivery and function of Lactobacillus plantarum B2. Food Hydrocolloids 160:110865. DOI:10.1016/j.foodhyd.2024.110865

    View in Article CrossRef Google Scholar

    [21] Circu M. L. and Aw T. Y. (2010). Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic. Biol. Med. 48:749−762. DOI:10.1016/j.freeradbiomed.2009.12.022

    View in Article CrossRef Google Scholar

    [22] Centurion F., Basit A. W., Liu J., et al. (2021). Nanoencapsulation for probiotic delivery. ACS Nano 15:18653−18660. DOI:10.1021/acsnano.1c09951

    View in Article CrossRef Google Scholar

    [23] Gani A., Shah A. and Ahmad M. (2018). β-d-glucan as an enteric delivery vehicle for probiotics. Int. J. Biol. Macromol. 106:864−869. DOI:10.1016/j.ijbiomac.2017.08.093

    View in Article CrossRef Google Scholar

    [24] Feng P., Cao Z. and Wang X. (2020). On-demand bacterial reactivation by restraining within a triggerable nanocoating. Adv. Mater. 32:e2002406. DOI:10.1002/adma.202002406

    View in Article CrossRef Google Scholar

    [25] Singh R.P. and Bhardwaj A. (2023). β-glucans: A potential source for maintaining gut microbiota and the immune system. Front. Nutr. 10:1143682. DOI:10.3389/fnut.2023.1143682

    View in Article CrossRef Google Scholar

    [26] Xie A., Ji H., Liu Z., et al. (2023). Modified prebiotic-based "shield" armed probiotics with enhanced resistance of gastrointestinal stresses and prolonged intestinal retention for synergistic alleviation of colitis. ACS Nano 17:14775−14791. DOI:10.1021/acsnano.3c02914

    View in Article CrossRef Google Scholar

    [27] Ji H., Wan Y., Li S., et al. (2025). Remolding probiotics for effective treatment of type 2 diabetes via oral administration. Biomaterials 315:122970. DOI:10.1016/j.biomaterials.2024.122970

    View in Article CrossRef Google Scholar

    [28] Ji H., Yan X., Zhang L., et al. (2025). Prebiotics empower probiotics with gastrointestinal stress resistance for colon-targeted release to synergistically alleviate colitis. J. Control. Release 380:297−316. DOI:10.1016/j.jconrel.2025.01.059

    View in Article CrossRef Google Scholar

    [29] Chen X., Zhang Y., Chen T., et al. (2025). Implement enhanced artificial “enteroendocrine L cells” via oral administration for effective treatment of type 2 diabetes. Cell Biomaterials 1:100024. DOI:10.1016/j.celbio.2025.100024

    View in Article CrossRef Google Scholar

    [30] Xie A., Gao M. and Du H. (2024). Next-generation probiotics delivery: Innovations and applications of single-cell encapsulation. Curr. Opin. Food Sci. 61:101234. DOI:10.1016/j.cofs.2024.101234

    View in Article CrossRef Google Scholar

    [31] Li C., Wang Z., Xiao H., et al. (2024). Intestinal delivery of probiotics: Mterials, strategies, and applications. Adv. Mater. 36:2310174. DOI:10.1002/adma.202310174

    View in Article CrossRef Google Scholar

    [32] Gong N., Han X., Xue L., et al (2023). In situ PEGylation of CAR T cells alleviates cytokine release syndrome and neurotoxicity. Nat. Mater. 22:1571-1580. DOI:10.1038/s41563-023-01646-6.

    View in Article Google Scholar

    [33] Yi W., Xiao, P., Liu X., et al. (2022). Recent advances in developing active targeting and multi-functional drug delivery systems via bioorthogonal chemistry. Signal Transduct. Target. Ther. 7:386. DOI:10.1038/s41392-022-01250-1

    View in Article CrossRef Google Scholar

    [34] Jin Z., Zhang Y., Hu H., et al. (2025). Closed-loop theranostic microgels for immune microenvironment modulation and microbiota remodeling in ulcerative colitis. Biomaterials 314:122834. DOI:10.1016/j.biomaterials.2024.122834

    View in Article CrossRef Google Scholar

    [35] Estelrich J. and Busquets M. A. (2021). Prussian blue: Ananozyme with versatile catalytic properties. Int. J. Mol. Sci. 22:5993. DOI:10.3390/ijms22115993

    View in Article CrossRef Google Scholar

    [36] Zhou C., Zhang L., Xu Z., et al. (2023). Self‐propelled ultrasmall AuNPs‐tannic acid hybrid nanozyme with ROS‐scavenging and anti‐inflammatory activity for drug‐iduced liver injury alleviation. Small 19:2206408. DOI:10.1002/smll.202206408

    View in Article CrossRef Google Scholar

    [37] Wang X., Jiao M., Tian F., et al. (2023). A biomimetic nanoplatform with improved inflammatory targeting behavior for ROS scavenging‐based treatment of ulcerative colitis. Adv. Healthc. Mater. 12:2301450. DOI:10.1002/adhm.202301450

    View in Article CrossRef Google Scholar

    [38] Ji H., Hu J., Zuo S., et al. (2022). In vitro gastrointestinal digestion and fermentation models and their applications in food carbohydrates. Crit. Rev. Food Sci. Nutr. 62:5349−5371. DOI:10.1080/10408398.2021.1884841

    View in Article CrossRef Google Scholar

    [39] Zhang B., Liu M. and Liu G. (2021). Oral absorption mechanism of the polysaccharides from Gastrodia elata Blume base on fluorescence labeling. Food Res. Int. 144:110342. DOI:10.1016/j.foodres.2021.110342

    View in Article CrossRef Google Scholar

    [40] Zhang D., Zhou X., Liu L. et al. (2021). Glucomannan from aloe vera gel promotes intestinal stem cell-mediated epithelial regeneration via the wnt/β-catenin pathway. J. Agric. Food Chem. 69:10581−10591. DOI:10.1021/acs.jafc.1c03814

    View in Article CrossRef Google Scholar

    [41] Zhang L., Miao C., Wang Z., et al. (2024). Preparation and characterisation of baicalin magnesium and its protective effect in ulcerative colitis via gut microbiota-bile acid axis modulation. Phytomedicine 126:155416. DOI:10.1016/j.phymed.2024.155416

    View in Article CrossRef Google Scholar

    [42] Clemens D. L., Duryee M. J., Hall J. H., et al. (2020). Relevance of the antioxidant properties of methotrexate and doxycycline to their treatment of cardiovascular disease. Pharmacol. Ther. 205:107413. DOI:10.1016/j.pharmthera.2019.107413

    View in Article CrossRef Google Scholar

    [43] Qi X., Li Y., Xiang Y. et al. (2025). Hyperthermia-enhanced immunoregulation hydrogel for oxygenation and ROS neutralization in diabetic foot ulcers. Cell Biomaterials 1:100020. DOI:10.1016/j.celbio.2025.100020

    View in Article CrossRef Google Scholar

    [44] Min D. K., Kim Y. E., Kim M. K., et al. (2023). Orally administrated inflamed colon-targeted nanotherapeutics for inflammatory bowel disease treatment by oxidative stress level modulation in colitis. ACS Nano 17:24404−24416. DOI:10.1021/acsnano.3c11089

    View in Article CrossRef Google Scholar

    [45] Porter N. T., Luis A. S. and Martens E. C. (2018). Bacteroides thetaiotaomicron. Trends Microbiol. 26:966−967. DOI:10.1016/j.tim.2018.08.005

    View in Article CrossRef Google Scholar

    [46] Huang B. D., Groseclose T. M. and Wilson C. J. (2022). Transcriptional programming in a Bacteroides consortium. Nat. Commun. 13:3901. DOI:10.1038/s41467-022-31614-8

    View in Article CrossRef Google Scholar

    [47] Hodgkinson K., El Abbar F., Dobranowski P., et al. (2023). Butyrate’s role in human health and the current progress towards its clinical application to treat gastrointestinal disease. Clin. Nutr. 42:61−75. DOI:10.1016/j.clnu.2022.10.024

    View in Article CrossRef Google Scholar

    [48] Wang X., Cai Z., Wang Q., et al. (2024). Bacteroides methylmalonyl-CoA mutase produces propionate that promotes intestinal goblet cell differentiation and homeostasis. Cell Host Microbe 32:63-78. e67. DOI:10.1016/j.chom.2023.11.005.

    View in Article Google Scholar

    [49] Zhang Y., Guo C., Li Y., et al. (2022). Alginate Oligosaccharides Ameliorate DSS-Induced Colitis through Modulation of AMPK/NF-κB Pathway and Intestinal Microbiota. Nutrients 14:14142864. DOI:10.3390/nu14142864

    View in Article CrossRef Google Scholar

    [50] Zhang X., Zhang F., Li Y. et al. (2024). Blockade of PI3K/AKT signaling pathway by Astragaloside IV attenuates ulcerative colitis via improving the intestinal epithelial barrier. J. Transl. Med. 22:406. DOI:10.1186/s12967-024-05168-w

    View in Article CrossRef Google Scholar

    [51] Li T., Li Y., Chen J., et al. (2024). Hyperibone J exerts antidepressant effects by targeting ADK to inhibit microglial P2X7R/TLR4-mediated neuroinflammation. J. Adv. Res. 72:571−589. DOI:10.1016/j.jare.2024.07.015

    View in Article CrossRef Google Scholar

    [52] Xu J., Liu M. and Yu P. (2019). Effect of recombinant Trichinella spiralis cysteine proteinase inhibitor on TNBS-induced experimental inflammatory bowel disease in mice. Int. Immunopharmacol. 66:28−40. DOI:10.1016/j.intimp.2018.10.043

    View in Article CrossRef Google Scholar

    [53] Sui Y., Jiang R., Niimi M., et al. (2024). Gut bacteria exacerbates TNBS-induced colitis and kidney injury through oxidative stress. Redox Biol. 72:103140. DOI:10.1016/j.redox.2024.103140

    View in Article CrossRef Google Scholar

    [54] Cecco De., Franceschelli S., Panella V., et al. (2024). Biological response of treatment with Saffron Petal extract on cytokine-induced oxidative stress and inflammation in the Caco-2/Human leukemia monocytic co-culture model. Antioxidants (Basel) 13:13101257. DOI:10.3390/antiox13101257

    View in Article CrossRef Google Scholar

    [55] García Mansilla M.J., Rodríguez Sojo M. J., Lista A. R. et al. (2025). Microbial-derived antioxidants in intestinal inflammation: A systematic review of their therapeutic potential. Antioxidants (Basel) 14:14030321. DOI:10.3390/antiox14030321

    View in Article CrossRef Google Scholar

    [56] Zeng Z., Huang Z., Yue W., et al. (2023). Lactobacillus plantarum modulate gut microbiota and intestinal immunity in cyclophosphamide-treated mice model. Biomed. Pharmacother. 169:115812. DOI:10.1016/j.biopha.2023.115812

    View in Article CrossRef Google Scholar

    [57] Yu P., Ke C. and Guo J. (2020). Lactobacillus plantarum L15 alleviates colitis by inhibiting LPS-mediated NF-κB activation and ameliorates DSS-induced gut microbiota dysbiosis. Front. Immunol. 11:575173. DOI:10.3389/fimmu.2020.575173

    View in Article CrossRef Google Scholar

    [58] Le B. and Yang S.H. (2018). Efficacy of Lactobacillus plantarum in prevention of inflammatory bowel disease. Toxicol. Rep. 5:314−317. DOI:10.1016/j.toxrep.2018.02.007

    View in Article CrossRef Google Scholar

  • Cite this article:

    Chen X., Ji H., Zhao D., et al. (2026). Probiotic-based biohybrid with gastrointestinal stress resistance and ROS-scavenging capacity to treat inflammatory bowel disease. The Innovation Materials 4:100203. https://doi.org/10.59717/j.xinn-mater.2026.100203
    Chen X., Ji H., Zhao D., et al. (2026). Probiotic-based biohybrid with gastrointestinal stress resistance and ROS-scavenging capacity to treat inflammatory bowel disease. The Innovation Materials 4:100203. https://doi.org/10.59717/j.xinn-mater.2026.100203

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