The double-edged sword of metabolic and bariatric surgery: extending the biliary limb can trigger bacterial translocation, sepsis, and liver inflammation - an experimental study.

BACKGROUND

Metabolic and bariatric surgery (MBS) procedures with extended biliary limb length are gaining popularity to expedite weight loss but can induce liver failure. We aimed to investigate the underlying pathophysiology for this potentially fatal complication.

MATERIALS AND

METHODS

We compared mouse models of vertical sleeve plication, sleeve gastrectomy, Roux-en-Y gastric bypass (RYGB), and one-anastomosis gastric bypass with three biliary limb lengths (25% = Ω 1 , 50% = Ω 2 , 75% = Ω 3 ) by analyzing mortality, weight loss, metabolic and liver health, bacterial translocation, inflammation, and biliary and fecal microbiome. Gut decontamination with oral antibiotics (amoxicillin, vancomycin, neomycin, and metronidazole) was performed in a subset of Ω 3 mice. Liver histology from mice with different biliary limb lengths was compared to samples from human patients who developed liver failure following biliopancreatic diversion or RYGB.

RESULTS

RYGB and Ω 1&2 significantly improved glucose intolerance and liver steatosis compared to sham surgery. However, extending the biliary limb (Ω 3 ) resulted in 100% mortality. The Ω 3 procedure induced bacterial translocation of Enterococcus genus to the spleen and biliary fluid, consistent with increased serum lipopolysaccharide levels and terminal ileum, biliary limb, and hepatic inflammation. Liver histology in Ω 3 mice was characterized by mediovesicular steatosis, closely resembling the histological picture observed in patients with liver failure after MBS. Oral gut decontamination significantly improved Ω 3 1-week-survival from 31.3% to 80.0%, prevented bacterial overgrowth in biliary fluid and spleen, and decreased liver damage.

CONCLUSION

Mortality in longer biliary limb MBS surgery is caused by bacterial overgrowth, translocation, and gut-liver axis inflammation, which were reversed by oral gut decontamination with antibiotics.