Dysbiosis of Gut Archaea is Associated with Obesity and Could be Recovered after Bariatric Surgery.

Objective: Obesity is closely associated with an altered gut microbiota; however, the role of archaea in obesity remains unknown. We aimed to delineate the alterations in gut archaea in obese subjects and explore the changes in bariatric surgery-associated gut archaeal composition. Methods: Metagenomic sequencing data from 191 obese subjects and 184 lean controls were retrieved from three public cohorts. Of these, 23 obese patients who underwent bariatric surgery were followed up for 3 months. Results: The gut archaea of obese subjects showed significantly lower Shannon diversity index than those of lean controls. Principal component analysis of the gut archaea revealed distinct clusters in obese subjects and lean controls. A model using the 20 top archaeal genera discriminated obese from lean controls with an area under the receiver operating characteristic curve (AUC) of 0.79, 0.83, and 0.86 in three cohorts. Ecological analysis showed decreased trans-kingdom correlations between archaea and bacteria in obese subjects compared to those in lean controls, with partial restoration observed after bariatric surgery. Conclusion: This is the first study to demonstrate that obesity is characterized by gut archaeal dysbiosis across multiple cohorts. Bariatric surgery-induced weight loss is associated with significant changes in the gut archaea.