Background and Aims: CD71 + erythroid cells are enriched during pregnancy with immuno suppressive properties. We investigated the frequency and functionality of CD71 + erythroid cells in peripheral blood, cord blood, and placenta of inflammatory bowel disease [IBD] patients versus healthy controls [HCs]. We aimed to determine their role in IBD pathogenesis during pregnancy. Methods: Peripheral blood was collected at preconception, the first, second and third trimesters, and postpartum. Cord blood and placental tissues were collected at the time of birth. Cells from different specimens were subjected to immunephenotyping and functional assays. CD71 + erythroid cells were purified for quantitative polymerase chain reaction [qPCR] analysis. Using an allogeneic mouse model of pregnancy, the effects of CD71 + erythroid cells depletion on intestinal homeostasis and dysbiosis was studied. Results: IBD patients had lower CD71 + erythroid cells during pregnancy compared with HCs. Placenta and cord blood CD71 + erythroid cells from IBD patients exhibited impaired functionality and expressed lower inhibitory molecules including VISTA, TGFβ, and reactive oxygen species [ROS]. Lower CD71 + erythroid cells were correlated with reduced regulatory T cells and increased immuneactivation in IBD patients. Depletion of CD71 + erythroid cells in an allogeneic pregnancy model resulted in upregulation of TLRs, IL6, and CXCL1, and enhanced production of TNFα, in intestinal tissues. In contrast, TGF β gene expression was reduced. Excessive inflammatory response in the gut [e.g. TNFα] affects intestinal integrity and CD71 + erythroid cells impact on the gut's bacterial composition. Conclusions: Reduced frequency and/or impaired functionality of CD71 + erythroid cells during pregnancy may predispose IBD patients to a more proinflammatory milieu in their gastrointestinal tract, characterised by lower Tregs, higher IL6, and TNFα, and dysbiosis.

Background and Aims: For women with inflammatory bowel disease [IBD], it is not very well known how IBD or IBD treatment affects their breast milk components. We aimed to investigate whether breast milk composition differs in healthy control [HC] versus IBD mothers in terms of antibodies, cytokines, and metabolite,s to identify potential impact of IBD breast milk on neonatal immune system. Methods: Breast milk specimens from HC [n = 17] and IBD [n = 31 for Crohn's disease [CD]; and n = 41 for ulcerative colitis [UC]; were collected at 3 and 6 months postpartum [PP3] and [PP6], respectively. Faecal samples were also collected. Cytokines and immunoglobulins [IgA/IgG/IgE] were analysed by multiplex Meso Scale Discovery [MSD] and commercial kits. Moreover, breast milk metabolites were analysed by 1 H nuclear magnetic resonance [NMR]. Results: We found that breast milk from IBD mothers showed significantly lower levels of IgA, sugar metabolite [lactose], and 2-aminobutyrate. In contrast, we observed that breast milk from mothers with IBD had increased levels of pro-inflammatory cytokines and higher energy metabolites [lactate and succinate] than milk from healthy mothers. In addition, we noticed that the type of treatment [5-aminosalicylic acid versus biologics] influenced the milk cytokines and metabolites profile. Conclusions: The reduction in immunoprotective components of IBD breast milk such as sIgA and lactose theoretically may modulate the potential protective effects of breastfeeding. On the other hand, presence of higher levels of pro-inflammatory cytokines, lactate, and succinate may predispose the offspring to an inflammatory condition or impact on the gut microbiome. Better understanding of the role of succinate in infants and its potential effects on microbiome or mucosal immunity merits further investigations.

No abstract