# 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

## TL;DR

A bio-patch made from small intestinal submucosa improves gut healing after surgery by boosting immune cells and reshaping gut microbes.

## Contribution

The study reveals that SIS bio-patch enhances healing via IL-22+ILC3s, microbiota shifts, and metabolic changes in GI anastomosis.

## Key findings

- SIS bio-patch reduced inflammation and improved mucosal barrier integrity in mice.
- The bio-patch increased IL-22+ILC3s and beneficial gut microbes like Bifidobacterium.
- Metabolomic changes in SIS-treated tissues suggest support for epithelial regeneration.

## Abstract

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.

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.

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.

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.