Levothyroxine dose requirements, oral bioavailability and gut microbiome enterotype dynamics during the early post-bariatric period: a single-centre, prospective, cohort study

Bariatric surgery induces profound metabolic changes; however, its impact on levothyroxine (LT4) requirements, hormone pharmacokinetics, and gut microbiome composition remains incompletely understood. The current study is aimed to evaluate longitudinal changes in metabolic parameters, LT4 dose requirements, free thyroxin (FT4) absorption (AUC₀–₆h), and gut microbiome features following Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). In this prospective cohort study, 79 patients with hypothyroidism undergoing bariatric surgery (RYGB n = 40; SG n = 39) were followed at baseline, 3 month, and 6 months postoperatively. Metabolic parameters, thyroid function, LT4 dose, FT4 AUC₀–₆h, and gut microbiome diversity were assessed using linear mixed-effects models. Both groups showed significant metabolic improvement at 6 months, including reductions in body mass index (RYGB: 44.5 → 32.1 kg/m²; SG: 42.9 → 33.0 kg/m², p < 0.001) and fasting blood sugar (RYGB: 114.8 → 92.4 mg/dL; SG: 109.9 → 96.1 mg/dL, p < 0.001). LT4 requirements increased significantly, particularly in RYGB (137.5 → 158.2 µg/day; p = 0.018) and SG (133.3 → 144.8 µg/day; p = 0.067), with a stronger effect in weight-adjusted dose (both p < 0.05). FT4 AUC₀–₆h increased significantly after surgery (RYGB: +330 ± 210, p = 0.003; SG: +185 ± 190, p = 0.041), indicating altered LT4 pharmacokinetics. Gut microbiome analysis revealed increased Shannon diversity (RYGB p-trend = 0.048) and significant enrichment of Akkermansia muciniphila (1.20% → 2.40%, p < 0.001), particularly in RYGB. After false discovery rate (FDR) adjustment, the major longitudinal changes remained significant, particularly for metabolic parameters, LT4 dose (µg/kg/day), and Akkermansia muciniphila in the RYGB group. Patient-level analyses showed a modest positive association between changes in A. muciniphila abundance and FT4 AUC₀–₆h after multivariable adjustment, whereas other microbiome–LT4 associations were not significant. Bariatric surgery was associated with substantial metabolic improvement, increased LT4 requirements, increased systemic FT4 exposure, and changes in gut microbiome composition. The observed microbiome–LT4 association was modest and should be considered exploratory and hypothesis-generating rather than causal. These findings highlight the need for individualized thyroid function monitoring and LT4 dose adjustment during the postoperative period. Not applicable.