Gut Microbiota in Lipodystrophies and Obesity: A Common Signature?

Lipodystrophies are rare syndromes characterized by partial or complete loss of subcutaneous adipose tissue leading to ectopic lipid deposition, insulin resistance, and the same metabolic derangements observed in obesity. Given the role of gut microbiota in metabolic disorders, we investigated whether its signature in obesity may be mirrored by that found in lipodystrophies, possibly contributing to their overlapping metabolic abnormalities. In this cross-sectional study, we included 8 individuals with lipodystrophy (LD), 16 individuals with obesity (Ob)-further categorized into 8 metabolically healthy (MHO) and 8 metabolically unhealthy (MUHO)-and 16 normal-weight controls (N). We assessed clinical and metabolic characteristics and performed 16S rRNA sequencing and bioinformatic analyses on fecal samples to characterize the gut microbiome. LD presented significantly lower body mass index (BMI) and waist circumference than Ob, but, from a metabolic perspective, LD showed similarity with MUHO and presented significantly lower levels of HDL-C and higher triglycerides compared to both N and MHO. Gut microbiota analysis revealed reduced α-diversity in LD, MHO and MUHO compared to N, whilst β-diversity and Firmicutes/Bacteroidetes ratio differences were not significant. At the phylum level, differential abundance analysis revealed that LD individuals exhibit similar microbial characteristics to MUHO and higher Verrucomicrobiota levels compared to MHO. The shared gut microbiota signature suggests another potential unexplored link between the pathogenesis of metabolic complications in lipodystrophies and obesity, providing novel insights into the complex interplay between dysbiosis and adiposopathy. Larger longitudinal studies are needed to explore the role of specific taxa and for a more precise characterization of different lipodystrophy subtypes.