Small-Intestinal Motility Interrelates With Fecal Microbiota, Metabolites and Metabolic Tissue Gene Expression in Metabolic Dysfunction-Associated Steatotic Liver Disease

Background/Aims:Recent studies show that the gut microbiota may affect both small-intestinal motility and metabolic dysfunction-associated steatotic liver disease (MASLD).However, human studies of this triangle are lacking.Our aim was to leverage the unique potential of cine-MRI to quantify small-intestinal motility in patients with MASLD and investigate its association with gut microbiota, metabolic tissues and metabolites.Methods: Fifteen patients with histology proven MASLD participated in a 12-week exercise intervention.At baseline and endpoint, small-intestinal motility and liver status were assessed using MRI.Stool consistency and composition of fecal microbiome as well as mRNA expression of liver, skeletal muscle, and subcutaneous adipose tissue biopsies were studied.Non-targeted metabolomics was performed on stool, fasted plasma, and urine samples.Results: At baseline, small-intestinal motility did not correlate to liver histology scores or MRI-determined markers of liver fat, stiffness, or inflammation.However, small-intestinal motility did correlate with fecal microbiota, including Verrucomicrobia and Bacteroidetes phyla as well as 41 species such as Prevotella species incertae sedis (false discovery rate [FDR]-P < 0.2).Moreover, liver RNA sequencing revealed correlations of small-intestinal motility with liver mRNA expression of CBS (FDR-P < 0.001), linked to hydrogen sulfide production, and adipose tissue mRNA expression of SCARB1 and SCD1 (FDR-P < 0.05), involved in lipid metabolism.Several stool, plasma, and urine metabolites correlated with small-intestinal motility.Exercise had no effect.Conclusions: In MASLD patients, small-intestinal motility associates with gut microbiota, metabolites and mRNA expression in metabolic tissues.These findings warrant further investigation to determine causality and effect directionality.Additionally, this exploratory study demonstrates the potential of cine-MRI for fundamental small-intestinal motility research.