The Profile of Human Milk Metabolome, Cytokines, and Antibodies in Inflammatory Bowel Diseases Versus Healthy Mothers, and Potential Impact on the Newborn

Abstract

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.

Human Milk From Atopic Mothers Has Lower Levels of Short Chain Fatty Acids

“…Acetate, butyrate, and formate have been found in HM of women worldwide (20)(21)(22)(23)(24)(25)(26) (20)(21)(22). We also confirm the positive correlations of HM acetate with butyrate and formate reported by Prentice et al The failure by us and others to detect propionate in HM is curious.…”

“…Butyrate has also been documented in studies of HM fat or fatty acids ( 23 , 24 ). Meng et al reported the presence of acetate and butyrate in HM from women with and without irritable bowel disease, finding higher acetate levels in women treated with aminosalicylates ( 25 ). Finally, Gómez-Gallego et al performed NMR metabolic profiling of 79 HM samples from 4 international cohorts.…”

Intrauterine Exposure to Biologics in Inflammatory Autoimmune Diseases: A Systematic Review

“…In some of the included publications the type of biologic used was not specified for the outcomes. In general, these studies did not show any abnormal outcomes in children exposed to biologics during pregnancy/lactation [155][156][157][158][159][160][161][162][163][164][165][166][167].…”

Transfer of monoclonal antibodies into breastmilk in neurologic and non-neurologic diseases

“…Furthermore, these samples could also be used to determine whether the immune and metabolic profile of breastmilk differs in women with and without chronic conditions. 57 Once additional data are available for mAb transfer into breastmilk when used in neurologic disorders, this should be incorporated into treatment guidelines in neurology. While awaiting additional studies, data presented here may provide some reassurance for low mAb transfer to breastmilk, although study of breastmilk transfer of individual therapies and effects on children is needed.…”