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Background:Recent studies have revealed that metabolically healthy obese (MHO) population have different clinical profiles and prognosis than metabolically unhealthy obese patients.’ This study aims to investigate the characteristics of gut microbiome in the MHO patients, and how they correlate with metabolic and inflammatory profiles. Results: A total of 120 obese people without metabolic comorbidities were recruited, and their clinical phenotypes, metabolic and inflammatory parameters were analyzed. The fecal microbial markers originating from bacterial cell and extracellular vesicle (EV) were profiled using 16S rDNA sequencing. The total study population could be classified into two distinct enterotypes (group I: Prevotellaceae-predominant, group II: Akkermansia/Bacteroides abundant), based on their stool EV-derived microbiome profile. When comparing the metabolic and inflammatory profiles, enterotype I correlated with higher levels of body mass index, total body fat mass, serum IL-1β, serum resistin than enterotype II (all p < 0.05). The microbial diversity in enterotype I were lower than those in enterotype II (p < 0.001), and the microbial composition, analyzed by unweighted unifrac distance, revealed distinct distribution between the two enterotypes (PERMANOVA p = 0.001). Enterotype I had relatively higher abundance of Bacteroidetes, Prevotellaceae and Prevotella-derived EVs, and lower abundance of Actinobacteria, Firmicutes, Proteobacteria, Akkermansia and Bacteroides-derived EVs. Conclusion:HMO patients can be categorized into two distinct enterotypes by the faecal EV-derived microbiome profile. The enterotypes may be associated with different metabolic and inflammatory profiles. Further studies are warranted to elucidate the long-term prognostic impact of EV-derived microbiome in the obese population.

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