Gut microbiota influence anastomotic healing in colorectal cancer surgery through modulation of mucosal proinflammatory cytokines

Autor: 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
Rok vydání: 2022
Předmět:
Zdroj: Gut. 72:1143-1154
ISSN: 1468-3288
0017-5749
Popis: ObjectiveColorectal 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.DesignThe 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 bothin vitroandin vivo.ResultsMice 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 ofAlistipes onderdonkiiandParabacteroides goldsteinii. Oral supplementation withA. onderdonkiiresulted in a higher rate of leaks in mice, while gavage withP. goldsteiniiimproved 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.ConclusionGut 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.
Databáze: OpenAIRE
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