Characterization of the Small Bowel Microbiome Reveals Different Profiles in Human Subjects who are Overweight or have Obesity.

Abstract

OBJECTIVES Gut microbiome changes are linked to obesity, but findings are based on stool data. Here, we analyzed the duodenal microbiome and serum biomarkers in subjects with normal weight, overweight, and obesity. METHODS Duodenal aspirates and serum samples were obtained from subjects undergoing standard-of-care esophagogastroduodenoscopy without colon preparation. Aspirate DNAs were analyzed by 16S rRNA and shotgun sequencing. Predicted microbial metabolic functions and serum levels of metabolic and inflammatory biomarkers were also assessed. RESULTS Subjects with normal weight (N=105), overweight (N=67) and obesity (N=42) were identified. Overweight-specific duodenal microbial features include lower relative abundance (RA) of Bifidobacterium species and Escherichia coli strain K-12, and higher Lactobacillus intestinalis, L. johnsoni, and Prevotella loeschii RA. Obesity-specific features include higher Lactobacillus gasseri RA and lower L. reuteri (subspecies rodentium), Alloprevotella rava and Leptotrichia spp RA. Escalation features (progressive changes from normal weight through obesity) include decreasing Bacteroides pyogenes, Staphylococcus hominis, and unknown Faecalibacterium species RA, increasing RA of unknown Lactobacillus and Mycobacterium species, and decreasing microbial potential for biogenic amines metabolism. De-escalation features (direction of change altered in normal-to-overweight and overweight-to-obesity) include Lactobacillus acidophilus, L. hominis, L. iners, and Bifidobacterium dentium. An unknown Lactobacillus species is associated with Type IIa dyslipidemia and overweight, whereas Alloprevotella rava is associated with Type IIb and IV dyslipidemias. CONCLUSIONS Direct analysis of the duodenal microbiome has identified key genera associated with overweight and obesity, including some previously identified in stool, e.g. Bifidobacterium and Lactobacillus. Specific species and strains exhibit differing associations with overweight and obesity, including escalation and de-escalation features that may represent targets for future study and therapeutics.