Association of gut microbial communities with plasma lipopolysaccharide-binding protein (LBP) in premenopausal women.

ABSTRACT

The mechanisms by which obesity increases cancer risk are unclear, but some lines of evidence suggest that gut microbial communities (GMC) may contribute to chronic inflammation in obese individuals through raised systemic levels of lipopolysaccharides (LPS). We evaluated associations of the GMC in stool with plasma LPS-binding protein (LBP, a measure of LPS) and C-reactive protein (CRP) concentrations in 110 premenopausal women in the United States. Diet was assessed using 3-day food records and GMCs were evaluated using pyrosequencing of the 16S rRNA gene. OTUs were identified at 97% sequence similarity. Taxonomic classification and functional genes were imputed from 16S rRNA genes, and alpha and beta diversity were assessed using the Shannon index and MRPP, respectively. Multivariable linear regression analysis was used to assess the relation between LBP, specific bacterial genera identified with indicator species analysis, and CRP. Dietary fat intake, particularly saturated fat, and CRP were positively associated with increased LBP. GMC beta diversity, but not alpha diversity, was statistically significantly different between groups using unweighted Unifrac. Several taxa, particularly those in the Clostridia class, were more prevalent in women with low LBP, while Bacteroides were more prevalent in those with high LBP. Genes associated with gram-negative cell wall material synthesis were also associated with LBP and CRP. In contrast, Phascolarctobacterium was associated with lower concentrations of LBP and CRP. We found distinct differences between tertiles of LBP regarding the diversity and composition of the microbiome, as well as differences in functional genes that potentially activate LBP.