1956-LB: Altered Gut Microbiota and Short-Chain Fatty Acids in Children with Diabetic Ketoacidosis at Onset of Type 1 Diabetes

Objective: Diabetic ketoacidosis (DKA) stands as the most common acute hyperglycaemic complication with relatively high mortality rate among children diagnosed with type 1 diabetes (T1D). Previous studies have shed light on gut dysbiosis in newly-onset T1D children, but research specifically targeting the gut microbiota and microbial metabolites in patients with DKA remains scarce.

Methods: Shotgun metagenomic analysis was conducted on fecal samples of 90 healthy children (HC) and 96 newly diagnosed T1D children, including 32 patients who presented with DKA upon admission. Additionally, short-chain fatty acids (SCFAs) were quantified using GC/MS.

Results: Gut microbiome indicated evident differences between T1D and healthy controls. At baseline, the phylum Bacteroidetes exhibited predominance in the DKA subgroup, while Firmicutes prevailed in the children without DKA. Compositional analysis unveiled increased levels of enteroviruses in the DKA group, encompassing Staphylococcus aureus and Streptococcus viridans, among others. Concurrently, various SCFA-producing microbiota (Anaerobutyricum, Dialister, Ruminococcus, Roseburia, Dorea, and Butyricicoccus) were significantly reduced in the DKA group. Correspondingly, targeted metabolomics analysis further corroborated significant reductions in the concentrations of SCFAs in children with DKA. Subsequent Spearman correlation analysis revealed the significant correlations between clinical parameters indicative of disease severity (bicarbonate, pH, urinary ketone, HbA1c), SCFAs, and SCFA-producing microbiota.

Conclusions: We reported a reduction of SCFAs and SCFA-producing bacteria in the fecal samples of T1D children experiencing DKA at onset. Our findings suggest a potential therapeutic avenue involving the modulation of gut microbiota and associated SCFA metabolism in the pathogenesis of T1D and onset DKA.