Deciphering the role of adipose tissue microbial DNA in obesity-related metabolic dysfunction
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ID: 318581
2026
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Abstract
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.
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| Authors | Shámila Ismael, Vaz Ca, Catarina Durão, Ana Tavares, Catarina Rodrigues, Maria João Almeida, Gilberto Maia Santos, Inês Castela, F P Cabral, F Toscano, Luís Galindo, S. Brandt, Diogo Pestana, João Ricardo Araújo, Marta P. Silvestre, Conceição Calhau, A Faria, Diana Teixeira, Cláudia Marques |
| Journal | the journal of clinical endocrinology & metabolism |
| Year | 2026 |
| DOI |
10.1210/clinem/dgag246
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| URL | |
| Keywords | Keywords not found |
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