Anastomotic Leakage after Colorectal Surgery is Associated with a Specific Tissue-Microbiome Signature

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Abstract Background Anastomotic leakage (AL) occurs in 5-15% of colorectal resections. In addition to well-known risk factors, recent evidence suggests that the gut microbiota might critically affect anastomotic healing. However, studies in humans are limited. Aims To explore differences in pre-operative microbiome of patients with or without AL and identify anastomosis-protective or damaging bacterial species. Methods Clinical records of patients undergoing left colon or rectal resection with anastomosis at our department between 2013 and 2021 were screened. AL cases were matched equally to controls by propensity score, based on common AL risk factors. The microbiome was analyzed by amplification and sequencing of the V4 region of the 16S gene of DNA extracted from formalin-fixed paraffin-embedded mucosa taken at the proximal and distal margin of the resected specimen, mixed in equal amounts. Differential abundance of identified operational taxonomic units (OTUs) in AL-cases and controls was tested by using the R-package DESeq2. Results Among 588 patients screened, 41 cases and 42 matched controls were eligible for microbiome analysis. Patient characteristics were similar except for a higher percentage of rectal resections in the AL group. Out of 5406 OTUs identified, 197 OTUs were differentially abundant between the two groups (adjusted-p value <0.05). Of those, 175 OTUs were more prevalent in the AL-group, in particular Fusobacterium periodonticum (32% vs. 5% of patients) and bacteria from the Hyphomicrobium genera (39-44% vs. 12-21%); 22 were more prevalent in the control group, in particular Akkermansia muciniphila (26 vs. 17%) and Eubacterium sireum (19 vs. 5% of patients). Conclusion Our analysis unravels AL-associated microbiome-signatures and identifies bacterial species highly prevalent in particular in patients with AL. These findings could be used for future research to develop targeted antibiotic therapy that helps prevent AL.

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