Abstract
<h3>Background</h3> Obesity is associated with altered gut microbiota. Archaeome is an important part in intestinal microbiota, however, the role of archaea in obesity remains unknown. We aimed to delineate the alterations of gut archaea in subjects with obesity and explore the effect of bariatric surgery-associated weight loss intervention in modulating the gut archaeal composition. <h3>Methods</h3> A total of 231 obese subjects and 184 lean controls with shotgun metagenomic sequencing available were retracted from three public cohorts. Of which, 23 obese subjects undergone bariatric surgery were followed up for 3 months. Alterations of gut archaeome, bacteriome and archaeal-bacterial correlations were assessed in obese and lean subjects. <h3>Results</h3> Fecal archaea microbiota of obese subjects showed a significantly lower Chao1 richness and Shannon diversity compared to lean controls (<i>p</i><0.05). Principal component analysis of archaeome revealed distinct clusters in obese subjects and lean controls (<i>p</i><0.05). Two archaeal orders including Methanosarcinales and Methanococcales were increased and three orders including Natrialbales, Methanocellales and Thermoproteales were decreased in obese subjects compared with lean controls. Top 20 differentially abundant archaeal genera discriminated obese subjects from lean controls with an area under the receiver operating characteristic curve (AUC) of 0.79 (95% CI 0.72-0.85) in the discovery cohort. It was further validated in two independent cohorts, with AUC of 0.83 (0.73-0.92) and 0.86 (0.77-0.94), respectively. Further prediction analysis by archaeal genera revealed a significantly lower probability of obesity in subjects after bariatric surgery than their baseline (<i>p</i><0.05). Moreover, the ecological analysis showed significantly lower trans-kingdom correlations between archaea and bacteria in obese subjects compared with lean controls, and these correlations were partly recovered in subjects receiving bariatric surgery. <h3>Conclusions</h3> This study demonstrated for the first time that obesity is characterized by gut archaeome dysbiosis across multiple cohorts with different demographic characteristics. Weight loss by bariatric surgery-induced a significant change of gut archaeome, suggesting that gut archaeome may play an important role in treating obesity. Studies are needed to explore the potential benefit of reshaping gut archaeome to improve weight loss intervention efficacy.
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