IBD patients harbor distinct microbial communities with functional capabilities different from those seen with healthy people. But is this cause or effect? Answering this question requires data on changes in gut microbial communities leading to disease onset. By performing weekly metagenomic sequencing and mixed-effects modeling on an established mouse model of IBD, we identified several functional pathways encoded by the gut microbiome that covary with host immune status. These pathways are novel early biomarkers that may either enable microbes to live inside an inflamed gut or contribute to immune activation in IBD mice. Future work will validate the potential roles of these microbial pathways in host-microbe interactions and human disease. This study was novel in its longitudinal design and focus on microbial pathways, which provided new mechanistic insights into the role of gut microbes in IBD development.

15The gut microbiome is linked to inflammatory bowel disease (IBD)

Iron is an essential element that is required for many cellular functions. Multiple symptoms of iron deficiency have been reported in humans, including anemia, hair loss, stunted growth, and reduced oxygen transport. Mammalian iron intake is mediated in two different ways, across the placenta during fetal growth, and through the intestine during postnatal growth and development. We previously identified hephaestin (Hp), a copper‐iron ferroxidase, which plays a key role in intestinal iron transport. Hephaestin oxidizes iron and works in conjunction with ferroportin to facilitate iron export from enterocytes and its efficient binding to plasma transferrin. Null mutations in the Hp gene cause an accumulation of intracellular iron, specifically in the intestine. During analysis of the Hp null mice, we discovered that neonates born to Hp knockout (Hp KO) dams developed truncal hair loss (the “mask” hair loss phenotype) that resolved after weaning. The same phenotype was also observed in pups born to mothers with intestine‐specific knockout of Hp (even WT (floxed) pups born to these mothers), suggesting that lack of maternal Hp in the intestine alone is responsible for the mask phenotype. In order to determine the stage (ante and/or post natal) at which lack of maternal Hp leads to pup hair loss, we performed cross‐fostering studies. Wild‐type pups fed by Hp KO dams presented with the “mask” phenotype, whereas, all pups fed by the WT dams had normal hair growth. Histology of the affected skin of pups fed by Hp KO dams showed disorientation and keratinization of the follicles, follicular infundibular plugging and some tortuosity to the hair canals. Our findings suggest the involvement of a “toxic milk” phenotype involving low iron levels in the milk causing this phenotype. Grant Funding Source: R01 GM083198‐01A1