Deciphering the role of adipose tissue microbial DNA in obesity-related metabolic dysfunction.

CONTEXT: Obesity-related metabolic complications are especially driven by adipose tissue dysfunction. Gut dysbiosis and impaired intestinal barrier function facilitate microbial fragment translocation, potentially promoting metabolic impairment. However, presence and functional impact of microbial DNA in adipose tissue and contribution to metabolic dysfunction remain unclear.

OBJECTIVE

To investigate the role of gut microbiota, intestinal barrier function, and adipose tissue-associated microbial DNA in obesity-related metabolic dysfunction.

DESIGN

Exploratory cross-sectional study with complementary mechanistic in vitro experiments.

SETTING

Academic tertiary referral center in Lisbon, Portugal.

PARTICIPANTS

Fifty adults with severe obesity undergoing laparoscopic Roux-en-Y gastric bypass surgery were recruited and stratified according to metabolic phenotype into pre-clinical obesity and clinical obesity.

MAIN OUTCOME MEASURES: Gut microbiota composition, intestinal barrier markers, adipose tissue-associated microbial DNA profiles, and adipocyte functional responses to adipose tissue-derived microbial DNA.

RESULTS

Clinical obesity was associated with higher protein intake, impaired gut barrier function, and enrichment of hydrogen sulfide-producing genera (Bilophila, Desulfovibrio), whereas pre-clinical obesity showed higher Akkermansia and Bifidobacterium. Adipose tissue from clinical obesity contained more microbial DNA, with reduced diversity and partial overlap with gut profiles. Functionally, adipose-derived microbial DNA from clinical obesity induced increased oxidative stress, IL-1β and NFκB expression, and a lower adiponectin/leptin gene expression ratio in adipocytes compared with pre-clinical obesity DNA.

CONCLUSION

Clinical obesity is characterized by distinct gut microbiota signatures, impaired intestinal barrier function, and increased adipose-associated microbial DNA. Adipose tissue-derived DNA promoted adipocyte dysfunction in vitro, supporting a potential role for the gut-adipose tissue microbial axis in obesity-related metabolic complications.