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In our recent publication in Gut,1 we showed that preoperative gut microbiota was causally linked to the development of anastomotic leak (AL) after colorectal cancer (CRC) surgery. AL results from impaired healing of the colonic wound and leads to the leakage of intestinal content into the abdomen. Using faecal microbiota transplantation (FMT) in mice with faecal samples from 18 patients with CRC, we established that preanastomosis expression of mucosal proinflammatory cytokines, namely macrophage inflammatory protein-1 alpha (MIP-1α), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein 2 (MIP-2) and interleukin-17A/F (IL-17A/F), was increased in patients who later developed AL. Most importantly, these higher basal cytokine levels were driven by gut microbiota, as FMT from these patients led to higher cytokine levels in mice.
To corroborate these findings, we now expanded the analysis to our cohort of 77 patients with CRC who underwent a bowel resection with anastomosis (table 1): 13 were diagnosed with poor anastomotic healing and AL after surgery or at follow-up, while 64 did not. Colonic mucosal biopsies were collected during surgery from all patients and the levels of nine cytokines were measured (online supplemental material), confirming higher levels of MIP-1α, MIP-2, MCP-1 and IL-17A/F in patients who later developed AL (figure 1A). This larger cohort also revealed that the basal levels of IL-1β and tumour necrosis factor alpha, which we have previously shown to be increased after surgery in patients with AL,1 …
Footnotes
Contributors Conceptualisation: RH, CR and MMS. Methodology: RH, GF, MO, AAA, AC, HVR, TC, NT, ST, FD, RL, HS, FS, RW, RR, ED, CR and MMS. Visualisation and original draft: RH, MMS. Supervision: CR and MMS. Review and editing: RH, GF, MO, AAA, AC, HVR, TC, NT, ST, FD, RL, HS, FS, RW, RR, ED, CR and MMS. Guarantor and overall supervision: MMS.
Funding Canadian Institutes of Health Research grant FRN-159775 and PJT-175181 (MMS). New Frontiers in Research Fund – Exploration grant NFRFE-2020-00991 (MMS, CR). Canadian Society of Colon and Rectal Surgeons operating grant 2019 (CR, RH). Fonds de recherche du Québec – Santé (FRQ-S) and Ministère de la Santé et des Services sociaux Resident Physician Health Research Career Training Program (RH). Canadian Institutes of Health Research Graduate Scholarships program (RH). Institut du Cancer de Montréal (Canderel scholarship) (MO, TC).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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