Gut microbiota influence anastomotic healing in colorectal cancer surgery through modulation of mucosal proinflammatory cytokines
Abstract & Authors:展开
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.
Manuela M Santos
Roy Hajjar,Emmanuel Gonzalez,Gabriela Fragoso,Manon Oliero,Ahmed Amine Alaoui,Annie Calvé,Hervé Vennin Rendos,Souad Djediai,Thibault Cuisiniere,Patrick Laplante,Claire Gerkins,Ayodeji Samuel Ajayi,Khoudia Diop,Nassima Taleb,Sophie Thérien,Frédéricke Schampaert,Hefzi Alratrout,François Dagbert,Rasmy Loungnarath,Herawaty Sebajang,Frank Schwenter,Ramses Wassef,Richard Ratelle,Eric Debroux,Jean-François Cailhier,Bertrand Routy,Borhane Annabi,Nicholas J B Brereton,Carole Richard,Manuela M Santos
Colorectal cancer surgery: Modifying gut microbiota could reduce postoperative complications