Article Text
Abstract
Objective Colorectal cancer (CRC) is the third most diagnosed cancer, and requires surgical resection and reconnection, or anastomosis, of the remaining bowel to re-establish intestinal continuity. Anastomotic leak (AL) is a major complication that increases mortality and cancer recurrence. Our objective is to assess the causal role of gut microbiota in anastomotic healing.
Design The causal role of gut microbiota was assessed in a murine AL model receiving faecal microbiota transplantation (FMT) from patients with CRC collected before surgery and who later developed or not, AL. Anastomotic healing and gut barrier integrity were assessed after surgery. Bacterial candidates implicated in anastomotic healing were identified using 16S rRNA gene sequencing and were isolated from faecal samples to be tested both in vitro and in vivo.
Results Mice receiving FMT from patients that developed AL displayed poor anastomotic healing. Profiling of gut microbiota of patients and mice after FMT revealed correlations between healing parameters and the relative abundance of Alistipes onderdonkii and Parabacteroides goldsteinii. Oral supplementation with A. onderdonkii resulted in a higher rate of leaks in mice, while gavage with P. goldsteinii improved healing by exerting an anti-inflammatory effect. Patients with AL and mice receiving FMT from AL patients presented upregulation of mucosal MIP-1α, MIP-2, MCP-1 and IL-17A/F before surgery. Retrospective analysis revealed that patients with AL present higher circulating neutrophil and monocyte counts before surgery.
Conclusion Gut microbiota plays an important role in surgical colonic healing in patients with CRC. The impact of these findings may extend to a vast array of invasive gastrointestinal procedures.
- COLORECTAL SURGERY
- COLORECTAL CANCER
- COLONIC MICROFLORA
- INTESTINAL MICROBIOLOGY
- INFLAMMATORY MEDIATORS
Data availability statement
All data relevant to the study are included in the article or uploaded as online supplemental information.
Statistics from Altmetric.com
Data availability statement
All data relevant to the study are included in the article or uploaded as online supplemental information.
Footnotes
Twitter @Roy__Hajjar, @GonzalezEmBio, @NJBBrereton, @Nut_Microb_Lab
Contributors Conceptualisation: RH, CR, MMS. Methodology: RH, EG, MO, AAA, GF, AC, HVR, SD, TC, PL, CG, ASA, KD, NT, ST, FS, HA, FD, RL, HS, FS, RW, RR, ED, BR, J-FC, BA, NJBB, CR, MMS. Visualisation: RH, EG, TC, MMS. Supervision: CR, MMS. Original draft: RH, MMS. Review and editing: RH, EG, MO, AAA, GF, AC, HVR, SD, TC, PL, CG, ASA, KD, NT, ST, FS, HA, FD, RL, HS, FS, RW, RR, ED, BR, J-FC, BA, NJBB, CR, MMS. Overall supervisor and guarantor: MMS.
Funding Canadian Institutes of Health Research grants FRN-159775 and PJT-175181 (MMS). Natural Sciences and Engineering Research Council of Canada grants RGPIN-2018-06442 (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, CG, ASA). Fonds de recherche du Québec – Santé (FRQ-S) (Postdoctoral Fellowship) (KD). BA holds a Chair in Cancer Prevention and Treatment at UQAM
Competing interests None declared.
Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.
Provenance and peer review Not commissioned; externally peer reviewed.
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