Intestinal iron bio-accessibility changes by Lignin and the subsequent impact on cell metabolism and intestinal microbiome communities

Abstract

The detrimental effects of high concentrations of colonic iron have been linked to intestinal inflammation and microbial dysbiosis. Exploiting chelation against this luminal pool of iron may restore intestinal health and have beneficial impacts on microbial communities. This study aimed to explore whether lignin, a heterogenous polyphenolic dietary component, has iron-binding affinity and can sequester iron within the intestine and thus, potentially modulate the microbiome. Within in vitro cell-culture models, the treatment of RKO and Caco-2 cells with lignin almost abolished intracellular iron import (96% and 99% reduction of iron acquisition respectively) with corresponding changes in iron metabolism proteins (ferritin and transferrin receptor-1) and reductions in the labile-iron pool. In a Fe-59 supplemented murine model, intestinal iron absorption was significantly inhibited by 30% when lignin was co-administered compared to the control group with the residual iron lost in the faeces. The supplementation of lignin into a microbial bioreactor colonic model increased the solubilisation and bio-accessibility of iron present by 4.5-fold despite lignin-iron chelation previously restricting intracellular iron absorption in vitro and in vivo. The supplementation of lignin in the model increased the relative abundance of Bacteroides whilst levels of Proteobacteria decreased which could be attributed to the changes in iron bio-accessibility due to iron chelation. In summary, we demonstrate that lignin is an effective luminal iron chelator. Iron chelation leads to the limitation of intracellular iron import whilst, despite increasing iron solubility, favouring the growth of beneficial bacteria.