Characterization of Citrus Pectin Oligosaccharides and Their Microbial Metabolites as Modulators of Immunometabolism on Macrophages

We characterized the structure of prepared citrus pectin oligosaccharides (POS) and investigated the immunometabolism-modulating effects of POS and their microbial metabolites on human macrophages. Both POS and metabolites activated immune responses and exhibited anti-inflammatory properties in the presence of lipopolysaccharide (LPS) via regulating expressions of inflammatory cytokines and nuclear factor-kappa B. Cholesterol efflux was also facilitated via increased gene expressions of the liver X receptor-α-adenosine triphosphate-binding cassette transporter (ABC) A1/ABCG1 pathway and suppressed cholesterol synthesis via suppressing expressions of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Microbial degradation prevented POS from attenuating palmitoyl-3-cysteine-serine-lysine-4-induced inflammation and promoting M2 polarization, but it is capable of inhibiting cholesterol uptake-related genes CD36 and SR-A. These findings indicate that immunometabolism-modulating effects of POS are not solely microbiota-dependent effects. Both POS and their microbial metabolites are potential immunometabolism modulators via different mechanisms.