Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Sep;37(9):1756-1767.
doi: 10.1111/jgh.15946. Epub 2022 Jul 26.

Gut microbiota from nCAL patients promotes colon anastomotic healing by inducing collagen synthesis in epithelial cells

Xiangren Jin  1   2 , Yang Liu  1   3   4 , Wei Yan  1 , Shang Shi  1 , Lujia Liu  1 , Baiqiang Lin  1 , Xiao Guo  1 , Ting Cai  5   6   7 , Yunwei Wei  5   6   7
Affiliations

Gut microbiota from nCAL patients promotes colon anastomotic healing by inducing collagen synthesis in epithelial cells

Xiangren Jin et al. J Gastroenterol Hepatol. 2022 Sep.

Abstract

Background and aims: Colon anastomotic leak (CAL) is considered one of the most feared and serious postoperative complications in colorectal cancer (CRC) patients, with no effective prevention strategies to date. Based on previous studies, gut microbiota is associated with anastomotic healing, but its ability to effectively promote anastomotic healing remains largely unknown.

Methods: We performed a clinical study to analyze the gut microbiota profiling in CRC patients who developed CAL and those who did not (nCAL) using 16S-rRNA-based next-generation sequencing (NGS). To investigate these changes in an in vivo model, we performed fecal microbiota transplantation in a colon anastomosis rat experimental model to elucidate the causal effect between gut microbiota and anastomotic healing. Notably, RNA-seq in the anastomotic tissue of the latter experimental model was utilized to discover the potential molecular mechanism.

Results: Our analysis implicated that gut microbiota profiling was profoundly different between CAL and nCAL patients. Strikingly, the rat experimental model transplanted with fecal microbiota derived from nCAL patients demonstrated enhanced anastomotic healing properties. Moreover, collagen synthesis, EMT, and TGF-β/Smad signaling pathways were upregulated in the same rats. Concordantly, we discovered that the better anastomotic healing profiling displayed in gut microbiota derived from nCAL patients is dependent on the TGF-β/Smad-induced EMT in vitro and in vivo.

Conclusions: Collectively, our clinical study identified the postoperative gut microbiota profile is associated with CAL in CRC patients. On the contrary, fecal microbiota from nCAL patients promotes anastomotic healing via TGF-β/Smad-induced EMT, with subsequent collagen synthesis and enhanced anastomosis healing.

Keywords: Anastomotic leak; Epithelial-mesenchymal transformation; Fecal microbiota transplantation; Gut microbiota.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Shogan BD, An GC, Schardey HM et al. Proceedings of the first international summit on intestinal anastomotic leak, Chicago, Illinois, October 4-5, 2012. Surg. Infect. (Larchmt.) 2014; 15: 479-489.
    1. Frasson M, Flor-Lorente B, Rodriguez JL et al. Risk factors for anastomotic leak after colon resection for cancer: Multivariate analysis and nomogram from a multicentric, prospective, national study with 3193 patients. Ann. Surg. 2015; 262: 321-330.
    1. Penna M, Hompes R, Arnold S et al. Incidence and risk factors for anastomotic failure in 1594 patients treated by transanal total mesorectal excision: Results from the International TaTME registry. Ann. Surg. 2019; 269: 700-711.
    1. Shogan BD, Belogortseva N, Luong PM et al. Collagen degradation and MMP9 activation by Enterococcus faecalis contribute to intestinal anastomotic leak. Sci. Transl. Med. 2015; 7: 286ra268.
    1. Hyoju SK, Klabbers RE, Aaron M et al. Oral polyphosphate suppresses bacterial collagenase production and prevents anastomotic leak due to Serratia marcescens and Pseudomonas aeruginosa. Ann. Surg. 2018; 267: 1112-1118.

LinkOut - more resources