Randomised trial of 1-kestose supplementation in metabolic dysfunction-associated steatotic liver disease

Gut microbiota dysbiosis is implicated in metabolic dysfunction-associated steatotic liver disease (MASLD), but the clinical utility of prebiotic modulation remains unclear. We conducted a randomised, double-blind, placebo-controlled pilot trial of oral 1-kestose in patients with MASLD and chronically elevated alanine aminotransferase (ALT) levels. Sixty participants were randomised to receive 1-kestose or placebo for 8 weeks and followed until week 16. The primary endpoint was the change in serum ALT from baseline to week 8, analysed as a continuous outcome. In baseline-adjusted ANCOVA, the between-group difference at week 8 was 3.4 U/L (95% CI, − 11.0 to 17.9; p = 0.636), indicating no significant treatment effect. In a supportive responder analysis, an ALT reduction of ≥ 20 U/L occurred in 20.7% of the 1-kestose group and 27.6% of the placebo group. In contrast, 1-kestose increased the relative abundance of Bifidobacterium at week 8; increased abundance was observed in 23/26 participants in the 1-kestose group and 10/26 in the placebo group. Faecal short-chain fatty acid concentrations did not differ between groups. 1-Kestose was well tolerated and modulated the gut microbiota during treatment but did not demonstrate short-term hepatic efficacy.