AccScience Publishing / ARNM / Online First / DOI: 10.36922/ARNM025230026
Submit to ARNM
Cite this article
2
Download
111
Views
Journal Browser
Volume | Year
Issue
Search
Forthcoming Issue
Current Issue
View All
News and Announcements
View All
ORIGINAL RESEARCH ARTICLE

CS@LGG as a therapeutic biomaterial for acute radiation-induced bowel injury alleviation

Xinyi Gu1 ,  Lu Yu1 ,  Xusheng Wang1 ,  Shengqi Yin1 ,  Yilin Zheng1 ,  Zhihao Zheng1 ,  Yaowei Zhang1 ,  Keli Chen2 ,  Yuqing Zhang1 ,  Yi Ding1*
Show Less
1 Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
2 Huiqiao Medical Care, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
ARNM, 025230026 https://doi.org/10.36922/ARNM025230026
Received: 3 June 2025 | Revised: 12 August 2025 | Accepted: 21 August 2025 | Published online: 10 September 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Download PDF
XML
Cite
Abstract

Acute radiation-induced bowel injury is a serious and inevitable adverse effect of pelvic radiotherapy, with few standardized therapies available in clinical practice. Interestingly, fecal microbiota transplantation (FMT) has been shown to be an effective therapeutic method. Among the probiotics, Lactobacillus rhamnosus GG (LGG) has the most prominent effect. However, due to its poor tolerance and viability in vitro and its potential to cause bacteremia in vivo, this study chose a natural and biosafe polymer called chitosan (CS) to act as a carrier, avoiding the aforementioned limitations of FMT. In this study, we successfully synthesized a curative probiotic biomaterial, named CS@LGG, to protect the intestinal epithelium from radiation-induced damage. It repaired the intestinal barrier with increased expression of occludin, claudin-3, and Ki-67, while decreasing γH2A.X. In addition, it enabled clearance of local and systemic pro-inflammatory factors, such as interleukin (IL)-6, IL1-β, and tumor necrosis factor alpha. Surprisingly, this biomaterial demonstrated good biosafety in vitro and in vivo, with a certain extent of tumor suppression. Furthermore, this study shed light on the possible mechanism underlying its therapeutic effect. RNA sequencing analysis indicated that overproduction of immunoglobulin A on local mucosa might be the core factor of damaged intestinal microenvironment leading to acute radiation-induced bowel injury. In conclusion, CS@LGG created in this work is a biosafe and effective new probiotic biomaterial that holds promise in the treatment and relief of acute radiation-induced bowel injury.

Keywords
Biomaterial
Probiotics
Acute radiation-induced bowel injury
Fecal microbiota transplantation
Radiation damage protection
Funding
This work was supported by the National Natural Science Foundation of China (grant numbers: 82473567, 82273564, and 81903125); the Key Science & Technology Brainstorm Project of Guangzhou (grant number: 202206010045); the Guangdong Basic and Applied Basic Research Foundation (grant numbers: 2023A1515030044, 2023A1515010502, and 2024A1515013292); and the Science and Technology Plan Project of Jiangxi Provincial Administration of Traditional Chinese Medicine (grant number: 2023A0060).
Conflict of interest
The authors declare that they have no competing interests.
References

 

  1. Radiation bowel disease. Lancet. 1984;324:963-964. doi: 10.1016/s0140-6736(84)91173-5

 

  1. Leighton C, Fisher B, Perera F. Acute radiation proctitis. Lancet. 2001;357(9252):306. doi: 10.1016/s0140-6736(05)71745-1

 

  1. Bujko K. Neoadjuvant chemoradiation for fixed cT3 or cT4 rectal cancer: Results of a Polish II multicentre phase III study. J Clin Oncol. 2016;34:489. doi: 10.1200/jco.2016.34.4_suppl.489

 

  1. Bahadoer RR, Dijkstra EA, van Etten B, et al. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): A randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22:29-42. doi: 10.1016/s1470-2045(20)30555-6

 

  1. Jin J, Tang Y, Hu C, et al. Multicenter, randomized, phase III trial of short-term radiotherapy plus chemotherapy versus long-term chemoradiotherapy in locally advanced rectal cancer (STELLAR). J Clin Oncol. 2022;40:1681-1692. doi: 10.1200/jco.21.01667

 

  1. Li P, Wuthrick E, Rappaport JA, et al. GUCY2C signaling opposes the acute radiation-induced GI syndrome. Cancer Res. 2017;77(18):5095-5106. doi: 10.1158/0008-5472.can-17-0859

 

  1. Lu L, Li W, Chen L, et al. Radiation-induced intestinal damage: Latest molecular and clinical developments. Future Oncol. 2019;15(35):4105-4118. doi: 10.2217/fon-2019-0416

 

  1. Bhanja P, Norris A, Gupta-Saraf P, Hoover A, Saha S. BCN057 induces intestinal stem cell repair and mitigates radiation-induced intestinal injury. Stem Cell Res Ther. 2018;9(1):26. doi: 10.1186/s13287-017-0763-3

 

  1. Rieder F, Brenmoehl J, Leeb S, Schölmerich J, Rogler G. Wound healing and fibrosis in intestinal disease. Gut. 2007;56:130-139. doi: 10.1136/gut.2006.090456

 

  1. Suman S, Kallakury BVS, Fornace AJ Jr., Datta K. Fractionated and acute proton radiation show differential intestinal tumorigenesis and DNA damage and repair pathway response in Apc(Min/+) mice. Int J Radiat Oncol Biol Phys. 2019;105(3):525-536. doi: 10.1016/j.ijrobp.2019.06.2532

 

  1. Husebye E, Skar V, Høverstad T, Iversen T, Melby K. Abnormal intestinal motor patterns explain enteric colonization with gram-negative bacilli in late radiation enteropathy. Gastroenterology. 1995;109:1078-1089. doi: 10.1016/0016-5085(95)90565-0

 

  1. Hauer-Jensen M, Denham JW, Andreyev HJN. Radiation enteropathy-pathogenesis, treatment and prevention. Nat Rev Gastroenterol Hepatol. 2014;11:470-479. doi: 10.1038/nrgastro.2014.46

 

  1. Thomas H. FMT for drug-induced colitis. Nat Rev Gastroenterol Hepatol. 2018;16:4. doi: 10.1038/s41575-018-0092-8

 

  1. Lavelle A, Sokol H. Understanding and predicting the efficacy of FMT. Nat Med. 2022;28:1759-1760. doi: 10.1038/s41591-022-01991-0

 

  1. Aumpan N, Chonprasertsuk S, Pornthisarn B, et al. Tu1644 long-term efficacy and safety of encapsulated fecal microbiota transplantation (FMT) and FMT via rectal enema for irritable bowel syndrome (IBS): A prospective cohort study. Gastroenterology. 2024;166:S1361-S1362. doi: 10.1016/s0016-5085(24)03581-9

 

  1. Cammarota G, Ianiro G. FMT for ulcerative colitis: Closer to the turning point. Nat Rev Gastroenterol Hepatol. 2019;16:266-268. doi: 10.1038/s41575-019-0131-0

 

  1. Schnadower D, Tarr PI, Casper TC, et al. Lactobacillus rhamnosus GG versus placebo for acute gastroenteritis in children. N Engl J Med. 2018;379:2002-2014. doi: 10.1056/nejmoa1802598

 

  1. Sánchez B. Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis: A role for bifidobacteria and lactobacilli? Nat Rev Gastroenterol Hepatol. 2018;15:205. doi: 10.1038/nrgastro.2018.23

 

  1. Isolauri E, Majamaa H, Arvola T, Rantala I, Virtanen E, Arvilommi H. Lactobacillus casei strain GG reverses increased intestinal permeability induced by cow milk in suckling rats. Gastroenterology. 1993;105:1643-1650. doi: 10.1016/0016-5085(93)91059-q

 

  1. Qing Z, Yijun C, Pingdong W, Yi Z, Chaoji C, Jie C. Extremely strong and tough chitosan films mediated by unique hydrated chitosan crystal structures. Mater Today. 2021;51:27-38. doi: 10.1016/j.mattod.2021.10.030

 

  1. Kesharwani P, Halwai K, Jha SK, et al. Folate-engineered chitosan nanoparticles: Next-generation anticancer nanocarriers. Mol Cancer. 2024;23:244. doi: 10.1186/s12943-024-02163-z

 

  1. Sashiwa H, Aiba SI. Chemically modified chitin and chitosan as biomaterials. Prog Polym Sci. 2004;29:887-908. doi: 10.1016/j.progpolymsci.2004.04.001

 

  1. Fernandez JG, Ingber DE. Chitosan‐fibroin laminates: Unexpected strength and toughness in chitosan‐fibroin laminates inspired by insect cuticle. Adv Mater. 2012;24:480-484. doi: 10.1002/adma.201290016

 

  1. Townsend S, Santos C, Baker S. Su1194 Novel therapeutic for the repair of gastrointestinal radiation injury. Gastroenterology. 2016;150:S492. doi: 10.1016/s0016-5085(16)31693-6

 

  1. Li H, Zhao S, Jiang M, et al. Biomodified extracellular vesicles remodel the intestinal microenvironment to overcome radiation enteritis. ACS Nano. 2023;17:14079-14098. doi: 10.1021/acsnano.3c04578

 

  1. Zhang D, Zhong D, Ouyang J, et al. Microalgae-based oral microcarriers for gut microbiota homeostasis and intestinal protection in cancer radiotherapy. Nat Commun. 2022;13:1413. doi: 10.1038/s41467-022-28744-4

 

  1. Feng Y, Luo X, Li Z, et al. A ferroptosis-targeting ceria anchored halloysite as orally drug delivery system for radiation colitis therapy. Nat Commun. 2023;14:5083. doi: 10.1038/s41467-023-40794-w

 

  1. Han K, Xie F, Animasahun O, et al. Inulin-gel-based oral immunotherapy remodels the small intestinal microbiome and suppresses food allergy. Nat Mater. 2024;23:1444-1455. doi: 10.1038/s41563-024-01909-w

 

  1. Liu Y, Tan Y, Cheng G, et al. Customized intranasal hydrogel delivering methylene blue ameliorates cognitive dysfunction against Alzheimer’s disease. Adv Mater. 2024;36:e2307081. doi: 10.1002/adma.202307081

 

  1. Pagels RF, Prud’homme RK. Polymeric nanoparticles and microparticles for the delivery of peptides, biologics, and soluble therapeutics. J Control Release. 2015;219:519-535. doi: 10.1016/j.jconrel.2015.09.001

 

  1. Zhang J, Ou A, Tang X, et al. “Two-birds-one-stone” colon-targeted nanomedicine treats ulcerative colitis via remodeling immune microenvironment and anti-fibrosis. J Nanobiotechnol. 2022;20:389. doi: 10.1186/s12951-022-01598-0

 

  1. Cook MT, Smith SL, Khutoryanskiy VV. Novel glycopolymer hydrogels as mucosa-mimetic materials to reduce animal testing. Chem Commun. 2015;51:14447-14450. doi: 10.1039/c5cc02428e

 

  1. Zhong Y, Seidi F, Wang Y, Zheng L, Jin Y, Xiao H. Injectable chitosan hydrogels tailored with antibacterial and antioxidant dual functions for regenerative wound healing. Carbohydr Polym. 2022;298:120103. doi: 10.1016/j.carbpol.2022.120103

 

  1. Garbacz K. Anticancer activity of lactic acid bacteria. Semin Cancer Biol. 2022;86:356-366. doi: 10.1016/j.semcancer.2021.12.013

 

  1. Bender MJ, McPherson AC, Phelps CM, et al. Dietary tryptophan metabolite released by intratumoral Lactobacillus reuteri facilitates immune checkpoint inhibitor treatment. Cell. 2023;186:1846-1862.e26. doi: 10.1016/j.cell.2023.03.011

 

  1. Zhang S, Han Y, Schofield W, et al. Select symbionts drive high IgA levels in the mouse intestine. Cell Host Microbe. 2023;31:1620-1638.e7. doi: 10.1016/j.chom.2023.09.001

 

  1. Doron I, Mesko M, Li XV, et al. Mycobiota-induced IgA antibodies regulate fungal commensalism in the gut and are dysregulated in Crohn’s disease. Nat Microbiol. 2021;6:1493-1504. doi: 10.1038/s41564-021-00983-z

 

  1. Kim CH. Complex regulatory effects of gut microbial short-chain fatty acids on immune tolerance and autoimmunity. Cell Mol Immunol. 2023;20:341-350. doi: 10.1038/s41423-023-00987-1

 

  1. Mann ER, Lam YK, Uhlig HH. Short-chain fatty acids: Linking diet, the microbiome and immunity. Nat Rev Immunol. 2024;24:577-595. doi: 10.1038/s41577-024-01014-8
Next article in this issue
Share
Back to top
Advances in Radiotherapy & Nuclear Medicine, Electronic ISSN: 2972-4392 Print ISSN: 3060-8554, Published by AccScience Publishing
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here
Accept