12-week preoperative probiotic supplementation versus placebo: effects on inflammation, endotoxemia, adipokines, and gastrointestinal peptides in patients six months after bariatric surgery - a double-blind, randomized, placebo-controlled clinical trial.

BACKGROUND: Disruption in gut microbiota has been identified as a contributor to obesity-related inflammation and metabolic disorders. This study investigates the effects of preoperative probiotic supplementation on inflammation, endotoxemia, adipokines, and gastrointestinal peptides after bariatric surgery.

METHODS: This randomized, double-blind, placebo-controlled clinical trial included patients undergoing laparoscopic sleeve gastrectomy (LSG) or one anastomosis gastric bypass (OAGB). Participants were randomized to receive a 12-week supplementation of either a probiotic mixture, Sanprobi Barrier, which contained nine strains of bacteria (Bifidobacterium bifidum W23, Bifidobacterium lactis W51 and W52, Lactobacillus acidophilus W37, Levilactobacillus brevis W63, Lacticaseibacillus casei W56, Ligilactobacillus salivarius W24, Lactococcus lactis W19, and Lactococcus lactis W58), or a placebo before surgery. The key outcomes measured at baseline and 6 months postoperatively included serum lipopolysaccharide (LPS), cytokines (interleukin-6 - IL-6, interleukin-2 receptor-IL-2R, and C-reactive-CRP protein), adipokines (leptin, adiponectin, resistin), and gastrointestinal peptides (glucagon-like peptide-1 - GLP-1, ghrelin, and trefoil factor 2). Relative mRNA expression of ghrelin and trefoil family factor 2 in gastric tissues was also analyzed at baseline and on the day of the surgery.

RESULTS: Out of the initial 110 participants, serum samples of 18 individuals in the probiotic group and 24 in the placebo group were analyzed. Both groups showed significant reductions in serum LPS levels six months after surgery; however, no significant differences were observed between the two groups. Adiponectin levels increased significantly in the placebo group (4.2 ± 2.3 vs. 2.2 ± 1.1 pg/mL; p < 0.001), while leptin levels decreased significantly in both groups without intergroup differences. IL-6 levels were significantly lower in the probiotic group compared to the placebo group at 6 months (2.2 ± 1.1 vs 4.2 ± 2.3 pg/mL; p = 0.004). No significant differences were observed in the remaining cytokine levels between the groups. Gastrointestinal peptides showed no significant differences between the groups, although GLP-1 levels improved within both groups. No changes were observed in ghrelin and trefoil factor 2 expression at the mRNA level.

CONCLUSIONS: Preoperative probiotic therapy was associated with significantly lower IL-6 levels compared to placebo six months after surgery, suggesting a potential anti-inflammatory effect. However, since the between-group difference in IL-6 changes from baseline was not statistically significant, the observed effect should be interpreted with caution. Other measured markers were not significantly affected, though low statistical power may have limited detection of subtle effects. These findings suggest that while probiotics may reduce certain inflammatory responses, their efficacy can be overshadowed by bariatric surgery impact. The further studies on this subject are warranted.

TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (NCT05407090).