Increased Iron Availability Aggravates the Infection of Escherichia coli O157:H7 in Mice.

Iron plays an important role both in bacterial pathogenicity and in host defense mechanisms, which has frequently been underestimated. The primary purpose of this study was to investigate the influence of iron supplementation on the progression of bacterial infection. We used mice as an experimental model to supplement iron after Escherichia coli (E. coli) O157:H7 infection and found that iron supplementation exacerbated clinical symptoms of bacterial infection by increasing mortality and reducing body weight. Iron supplementation promoted the colonization of bacteria and enhanced inflammatory responses by increasing C-reaction protein level and the phagocytic capacity of PBMCs, as well as upregulating the expression of TNF-α and IL-1ß in E. coli O157:H7-challenged mice. In vitro cell experiment confirmed that an excess of iron would enhance the growth of E. coli O157:H7 and worsen the outcome of bacterial infection. Therefore, it is certainly plausible that iron supplementation in bacterial infection may worsen rather than improve host outcome.

Butyrate upregulates endogenous host defense peptides to enhance disease resistance in piglets via histone deacetylase inhibition.

Butyrate has been used to treat different inflammatory disease with positive outcomes, the mechanisms by which butyrate exerts its anti-inflammatory effects remain largely undefined. Here we proposed a new mechanism that butyrate manipulate endogenous host defense peptides (HDPs) which contributes to the elimination of Escherichia coli O157:H7, and thus affects the alleviation of inflammation. An experiment in piglets treated with butyrate (0.2% of diets) 2 days before E. coli O157:H7 challenge was designed to investigate porcine HDP expression, inflammation and E. coli O157:H7 load in feces. The mechanisms underlying butyrate-induced HDP gene expression and the antibacterial activity and bacterial clearance of macrophage 3D4/2 cells in vitro were examined. Butyrate treatment (i) alleviated the clinical symptoms of E. coli O157:H7-induced hemolytic uremic syndrome (HUS) and the severity of intestinal inflammation; (ii) reduced the E. coli O157:H7 load in feces; (iii) significantly upregulated multiple, but not all, HDPs in vitro and in vivo via histone deacetylase (HDAC) inhibition; and (iv) enhanced the antibacterial activity and bacterial clearance of 3D4/2 cells. Our findings indicate that butyrate enhances disease resistance, promotes the clearance of E. coli O157:H7, and alleviates the clinical symptoms of HUS and inflammation, partially, by affecting HDP expression via HDAC inhibition.

Iron Supplementation Attenuates the Inflammatory Status of Anemic Piglets by Regulating Hepcidin.

Iron deficiency is common throughout the world and has been linked to immunity impairments. Using piglets to model human infants, we assessed the impact of systemic iron homeostasis on proinflammatory status. Artificially reared piglets were parenterally supplied with iron dextran by intramuscular administration at the age of 3 days. Relative to no iron supplementation (control), iron dextran-treated (FeDex) piglets increased hematological parameters as well as iron levels in serum and tissues from days 21 to 49. High expression of hepcidin was observed in FeDex-treated piglets, which correlated with suppressed expression of ferroportin in duodenum. Lower levels of proinflammatory cytokine (IL-6, TNF-α, IFN-γ, and IL-1ß) transcripts were detected in ileum of FeDex-treated piglets, which indicated that iron supplementation could attenuate the increase of inflammatory cytokines caused by iron deficiency. Histopathological analysis of liver and duodenum proved the less inflammatory responses after iron supplementation. Hepcidin was highly stimulated by FeDex supplementation and attenuated the inflammation of anemia, which implied that hepcidin might had antiinflammatory function and is a candidate regulator of the cross-talk between iron regulation and inflammation.