ORIGINAL RESEARCH article
Front. Bioeng. Biotechnol.
Sec. Biomaterials
Enhancement of Gastrointestinal Anastomosis Healing via a Small Intestinal Submucosa Bio-Patch: Modulating IL-22 Secretion by Type 3 Innate Lymphoid Cells and Microbial Structures
Provisionally accepted
- 1Shenzhen Second People's Hospital, Shenzhen, China
- 2Hubei Cancer Hospital, Wuhan, China
- 3The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
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Purpose: Anastomotic leakage and impaired healing remain major complications in gastrointestinal (GI) surgery. Small intestinal submucosa (SIS), a biological scaffold, has shown regenerative potential but its mechanisms in GI anastomotic healing remain unclear. This study aimed to investigate the effects of an SIS bio-patch on intestinal anastomotic healing, focusing on immune modulation, microbiota reshaping, and metabolic changes. Methods: C57BL/6 mice underwent GI anastomosis with or without SIS bio-patch implantation. Five days post-operation, tissues were collected for histology, immunofluorescence, flow cytometry, 16S and ITS sequencing, and untargeted metabolomics. Immune cell composition, barrier protein expression, microbiota composition, and metabolic signatures were analyzed. Results: SIS bio-patch significantly reduced inflammation and enhanced mucosal barrier integrity, as evidenced by reduced TNF-α and IL-6 and increased ZO-1 and occludin expression. SIS increased IL-22⁺ILC3s (type 3 innate lymphoid cells) and decreased the Th17/Treg ratio without altering macrophage polarization. Microbiota analysis showed increased abundance of Bifidobacterium and Alloprevotella, correlating positively with IL-22⁺ILC3s. Fungal sequencing revealed higher Fungi gen. Incertae sedis levels, associated with beneficial immune profiles. Metabolomics showed elevated amino acids and biotin metabolism in SIS-treated tissues, which may support epithelial regeneration. Conclusion: SIS bio-patch promotes anastomotic healing by enhancing IL-22⁺ILC3-mediated repair, rebalancing adaptive immunity, reshaping microbial communities, and upregulating pro-regenerative metabolic pathways. These findings support the use of SIS as an immunomodulatory biomaterial for gastrointestinal repair.
Keywords: Fungi, Gastrointestinal anastomosis, Metabolites, microbiota, small intestinal submucosa bio-patch, Type 3 innate lymphoid cells
Received: 23 Nov 2025; Accepted: 30 Jan 2026.
Copyright: © 2026 Zhong, Zhou, Zhao, Chen, Zhan and Zhan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yong-Qiang Zhan
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