Table 2.

Factors affecting the gut microbiome, microbial mechanisms for anastomotic leak and measures to modify these

Factors affecting •Age, sex •Personal habits: nutrition, exercise, smoking, alcohol intake •Environment (e.g. home microbiome), geographical location •Coexisting diseases: obesity, diabetes, cancer, IBD •Adjuvant therapeutic measures: chemotherapy, radiotherapy, antibiotics, mechanical bowel preparation •Surgery: surgical trauma, resection of bowel and creation of anastomosis •Medications: opioids, NSAIDs, steroids, vasopressors, proton pump inhibitors •Tissue oxygenation: hypoxia (causes less aerobes, more anaerobes), hyperoxia (more aerobes, less anaerobes) •? Inhalation anaesthetic agents

Microbial mechanisms for AL: •Altered microbial–microbial and microbial–host interactions •Change in microbial genotype and phenotype leads to increased number and virulence of pathogenic bacteria •Harmful microbial metabolic products (e.g. Enterococcus faecalis, Staphylococcus, Pseudomonas aeruginosa, Serratia marcescens): collagenases, activation of host metalloproteinases in anastomotic tissues •Impairment of healing: inhibition of vascular remodelling (e.g. Bifidobacterium genus), inhibition of epithelial growth, tissue hypoxia •Effects on gastrointestinal secretions and pH

Measures to modify microbiome: •Preoperative microbial analysis (e.g. targeted bowel preparation, oral antibiotics) •Probiotics (the beneficial microbes themselves) •Prebiotics (compounds that act as a substrate on which beneficial microbes can grow) •Postoperative microbial analysis, e.g. faecal microbidata transplantation (microbe-rich faeces from healthy donors)