FRI076 Colchicine Treatment Effects On The Gut Microbiome In Adults With Metabolic Syndrome, Insulin Resistance, And High C-reactive Protein (CRP): A Secondary Analysis Of A Randomized, Placebo-controlled Clinical Trial

Abstract

Abstract Disclosure: C.M. Kisimba: None. J.L. Donahue: None. K.K. Chivukula: None. P. Subramanian: None. S.D. Mistry: None. A. Wolska: None. A.T. Remaley: None. J.A. Yanovski: None. A.P. Demidowich: None. Background: Obesity-induced inflammation plays a substantial role in the development of insulin resistance and type 2 diabetes. The altered gut flora in obesity can also contribute to metabolic dysregulation and systemic inflammation. However, it remains unclear how dysregulation of systemic inflammation in obesity affects the gut microbiome. We hypothesized that colchicine’s systemic anti-inflammatory effects in obesity would be associated with improvements in gut microbial diversity. Methods: This study was a secondary analysis of a double-blind randomized placebo-controlled trial, in which 40 adults with obesity, high CRP (≥ 2.0 mg/L), insulin resistance (HOMA-IR ≥ 2.6 mg/L), and metabolic syndrome (MetS) were randomized to three months of colchicine 0.6mg or placebo tablets twice daily. Serum and stool samples were collected at baseline and final visit. Gut microbiota composition was characterized from stool DNA by dual-index amplification and sequencing of 16S ribosomal RNA. Results: Pre- and post-intervention stool samples were available for 15 colchicine- and 12 placebo-treated subjects. Circulating hsCRP, interleukin-6, resistin, white blood count, and neutrophils were significantly decreased in the colchicine arm as compared to placebo. However, changes in stool microbiome alpha diversity, as assessed by the Chao1, Shannon, and Pielou indices, were not significant between groups. Sequence variant counts were unchanged among all examined phyla or families. Oscillibacter was the only genus to demonstrate even a nominally significant change. Conclusion: Among adults with obesity and MetS, colchicine significantly improved systemic inflammation. However, this anti-inflammatory effect was not associated with significant changes in the gut microbiome. Further studies are warranted to investigate this relationship. Presentation: Friday, June 16, 2023