Key result
Oral gut decontamination with antibiotics significantly improved 1-week survival from 31.3% to 80.0% and decreased liver damage in mice undergoing metabolic surgery with an extended 75% biliary limb.
Why the study?
Metabolic and bariatric surgery with extended biliary limb length can expedite weight loss but induce liver failure, prompting investigation into the underlying pathophysiology.
Does extending the biliary limb in metabolic and bariatric surgery cause liver failure and mortality via bacterial translocation in a mouse model?
Does extending the biliary limb in metabolic and bariatric surgery cause liver failure and mortality via bacterial translocation in a mouse model?
Absolute Event Rate: 80% vs 31.3%
Extending the biliary limb in bariatric surgery can trigger fatal liver inflammation and sepsis via bacterial translocation, which can be mitigated by oral antibiotics.
Extended biliary limbs in OAGB may cause liver failure via bacterial translocation; leaves open whether gut decontamination prevents this clinically.
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.
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Onghena et al. (2025) studied Obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) (n=89). Oral gut decontamination (amoxicillin, vancomycin, neomycin, and metronidazole) vs. Vehicle (no antibiotics) was evaluated on 1-week survival in mice with 75% biliary limb length (Ω3). Oral gut decontamination with antibiotics significantly improved 1-week survival from 31.3% to 80.0% and decreased liver damage in mice undergoing metabolic surgery with an extended 75% biliary limb.
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