Table 1 Preclinical and translational studies investigating the role of GM in determining AL

Cohn

(1955) [1]

14 cases

Dogs

1. 8 dogs -antibiotic at the site of anastomosis and orally (achromycin)

2. 6 dogs – no topical antibiotics

Bowel viability after

colic anastomoses with devascularization

1. 75% dogs had viable colon

2. 100% dogs in the control group died after ischemic perforation

Topic antibiotics help maintaining viability of the ischemic bowel and allow for regeneration

Abrams

(1963) [2]

44 cases

Mice

1. Germ-free mice (24 cases)

2. Conventional mice (20 cases)

Status of the ileal mucosa and lamina propria

1. Lamina propria poor of vessels, lymphocites and mononuclear cells; small Peyer’s patches with low mitotic activity; thin mucosal layer

2. Lamina propria rich of lymphocites, mononuclear and plasma cells; well-represented Peyer’s patches with high mitotic activity; well-represented mucosal layer

GM promotes the trophism of the ileal mucosa

Schardey

(1994) [3]

57 cases

Mice

1. Pseudomonas inoculation

2. Controls

3. Decontaminated

AL (esophagojejunal anastomosis)

AL rate:

1. 95%

2. 80%

3. 6%

Bacteria could play a major role in the pathogenesis of AL following gastrectomy

Okada

(1999) [4]

49 cases

Mice

1. Germ-free,

2. Conventional

3. monocontamina

ted with Lacto- bacillus acidophilus La5

4. Escherichia coli X7

5. ex-germ-free (repopulated)

Anastomotic healing

(ileum and colon)

2. and 5. had higher anastomotic bursting pressure both in the ileum and in the colon compared with the other groups

The establishment of a normal intestinal flora restores the healing capacity of the anastomosis

Jones

(2013) [5]

NA

Drosophila larvae, Mice

Germ-free drosophilia colonized with 6 different bacteria (3 g + and 3 g-);

Germ-free wild-type mice vs Nox-1 deficient mice feeded with L. rhamnosus and E. Coli

Response of gut epithelia to different bacteria

Drosophilia’s gut colonized by L. Plantarum shows increased niche cells proliferation.;

Germ-free WT mice feeded with L. Rhamnosus have an increased ROS production in the small intestine

Lactobacillus induces ROS production

Bacteria-induced ROS production promotes epithelial proliferation and intestinal barrier functions

Van Praagh

(2016) [6]

16 cases

Human tissue (donuts from colorectal surgery)

1. Patients who developed AL

2. Patients without AL

AL

Lachnospiraceae family in GM found on the doughnuts is significantly higher in the AL group

Correlation between Lachnospiraceae, BMI and anastomotic leak

Van Praagh

(2019) [7]

123 cases

Human tissue (donuts from colorectal surgery)

1. Patients who developed AL

2. Patients without AL

3. Patients treated with C-seal

4. Patients not treated with C-seal

AL

3. High AL rates. No association between AL and GM

4. AL linked with low microbial diversity, high level of Bacteroidaceae and Lachnospiraceae families

Low microbial diversity of GM is linked with AL in patients not treated with C-Seal