The microbiota shifts the iron sensing of intestinal cells

Abstract

The amount of iron in the diet directly influences the composition of the microbiota. Inversely, the effects of the microbiota on iron homeostasis have been little studied. So, we investigate whether the microbiota itself may alter host iron sensing. Duodenal cytochrome b and divalent metal transporter 1, involved in apical iron uptake, are 8- and 10-fold, respectively, more abundant in the duodenum of germ-free (GF) mice than in mice colonized with a microbiota. In contrast, the luminal exporter ferroportin is 2-fold less abundant in GF. The overall signature of microbiota on iron-related proteins is similar in the colon. The colonization does not modify systemic parameters as plasma transferrin saturation (20%), plasma ferritin (150 ng/L), and liver (85 µg/g) iron load. Commensal organisms (Bacteroides thetaiotaomicron VPI-5482 and Faecalibacterium prausnitzii A2-165) and a probiotic strain (Streptococcus thermophilus LMD-9) led to up to 12-fold induction of ferritin in colon. Our data suggest that the intestinal cells of GF mice are depleted of iron and that following colonization, the epithelial cells favor iron storage. This study is the first to demonstrate that gut microbes induce a specific iron-related protein signature, highlighting new aspects of the crosstalk between the microbiota and the intestinal epithelium.

Siderophore-mediated iron acquisition and modulation of host-bacterial interactions

“…About 5–15% of non-heme iron is absorbed in the duodenum [56], leaving the remaining unabsorbed iron to pass through the intestines. Supporting the role of diet as a modulator of colonic iron concentrations, consumption of an iron-fortified diet or oral iron supplements increases total non-heme iron concentrations in fecal contents (Table 2) [57] [58] [59] [52] [14] [60] [61]. However, measurements of total iron concentrations may not accurately reflect actual bioavailability of iron for resident bacteria, as this measurement includes bacterial intracellular iron stores and chemically inaccessible forms of iron.…”

“…Interestingly, in comparison to conventionalized mice (i.e. former germ free animals that have been colonized, such as via fecal transplantation), total cecal iron concentrations are 10-fold higher in germ free mice, while systemic parameters of host iron status remain unchanged [60]. Liver transcript levels of the hormone hepcidin, which limits duodenal iron absorption when increased, were also unaltered.…”

“…Liver transcript levels of the hormone hepcidin, which limits duodenal iron absorption when increased, were also unaltered. Colonization of germ free mice with representatives of two major phyla of the microbiota, the resident Bacteroidetes bacteria Bacteroides thetaiotamicron and Firmicutes bacteria Faecalibacterium prausnitzii , did not decrease cecal iron levels [60], suggesting that other specific resident bacteria modulate total iron concentrations through some undefined mechanism.…”

Microbiota Is Involved in Post-resection Adaptation in Humans with Short Bowel Syndrome

“…The intestinal microbiota plays a key role in energy salvage and digestive functions (Cherbuy et al, 2010; Tomas et al, 2015; Verbeke et al, 2015; Deschemin et al, 2016); but the SBS-microbiota is especially efficient in energy recovery as it provides more energy (up to 1000 Kcal) than the microbiota of healthy humans (up to 200 Kcal; McNeil, 1984; Nordgaard et al, 1994, 1996; Briet et al, 1995). The SBS-microbiota, since rich in Lactobacillus, leads to the accumulation of fecal lactate in some patients.…”

Modulation of urinary siderophores by the diet, gut microbiota and inflammation in mice

“…However, the level of urinary siderophores was comparable between conventional and autoclaved diet-fed mice (Fig 5C), thus reaffirming the involvement of microbiota in mediating generation of urinary siderophores. We also suspect that gut microbiota may alter iron status, since recent study has demonstrated that iron absorption could be altered by gut microbiota [32]. Yet, we did not observe significant difference for serum iron levels (data not shown).…”