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Maternal stress signature and infant neurodevelopment: determining the beneficial effects of human milk oligosaccharides - an in vitro study
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Date
2024
Authors
Egan, Aisling
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Journal ISSN
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Publisher
University College Cork
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Abstract
Human Milk Oligosaccharides (HMOs), the third most abundant solid component of breast milk, are becoming increasingly popular as their role in human health is further understood. In breastfed infants, HMOs play roles in many essential functions, including shaping the gut microbiota, inhibiting pathogen adherence to prevent infection, development of the infant immune response, anti-inflammatory properties, gastrointestinal barrier function and brain development. Recent studies have found that not only are HMOs present in breast milk, but they can also be found in maternal blood during pregnancy, foetal cord blood and amniotic fluid, indicating that HMOs may play a role before birth. Their role during pregnancy has yet to be fully understood, but potential functions include foetal neurodevelopment and the development and support of the placental barrier function as they have already been shown to impact infant brain health and gastrointestinal barrier function post-birth. Environmental insults, such as stress, negatively impact both foetal neurodevelopment and placental development and function. Specifically, stress has been linked to an altered maternal gut barrier, an increase in inflammatory factors in maternal blood and a shift in tryptophan metabolism from the serotonin pathway towards the kynurenine pathway which impacts key metabolites associated with neurodevelopment. All of these changes can have negative effects on placental and foetal brain development in utero.
In this study, we used in vitro models to assess the potential for HMOs to support foetal brain health and placental function in the presence of stressors. Using SH-SY5Y cells, the role of the HMOs 2′-Fucosyllactose (2’-FL) and 3’-Sialyllactose (3’-SL) on neuronal development in the presence of different stressors was studied. We treated SH-SY5Y cells with 100ng/ml tumour necrosis factor-alpha (TNF-) to create a stressed SH-SY5Y cell model. 3 days of TNF- treatment induced a decrease in neurite length in SH-SY5Y cells while simultaneous treatment with 0.1-1.0mg/ml 2’-FL and 3’-SL prevented the decrease in neurite length. Treatment with 0.1-1.0mg/ml lactose, the backbone structure of HMOs, did not prevent the TNF- induced decrease in neurite length, indicating that the protective effects observed in the presence of HMOs were specific to the HMO treatment. We also exposed the SH-SY5Y cells to maternal serum collected during pregnancy, categorised as having either a low or high biological stress phenotype, and found that biologically high-stress serum reduced neurite length of SH-SY5Y cells but when simultaneously treated with 0.1 mg/ml 2’-FL, the effect was no longer seen. Treatment with serum from the low biologically stressed mother had no significant impact on neurite length when compared to the control group.
To investigate the effect of HMO treatment on placental barrier function in the presence of stress, we created an in vitro placental barrier using transwell inserts and BeWo cells. BeWo cells, a choriocarcinoma cell line replicating trophoblasts, were chosen as an in vitro placental barrier model as they are capable of replicating two important functions of the placenta - trophoblast fusion and transplacental transport. Using transwells to help create a barrier, BeWo cells were seeded on the apical side of the transwell and cultivated for 5 days before treatment with 100ng/ml TNF- or maternal serum and 0.1mg/ml 2’-FL or 3’-SL. Barrier integrity was measured using trans-epithelial electrical resistance (TEER) measurements. TNF- had no impact on TEER values, while 3’-SL appeared to increase barrier integrity in the TNF- treated barrier. Both high and low biologically stressed maternal serum treatment caused an increase in TEER values which 2’-FL treatment prevented in the case of treatment with high biologically stressed maternal serum. However, while this model shows promise, further optimisation is required to test our hypothesis accurately.
Taken together, the evidence from the literature and the data we generated highlights the potential for further investigations into the development of a safe and effective HMO-enriched supplement that can be consumed by mothers during pregnancy and after pregnancy to support both placental and foetal development, as well as recovery after childbirth by reducing inflammation, improving gut health and stabilising mood. The inclusion of HMOs in nutritional supplements represents a promising step forward in maternal and infant care. By addressing key challenges such as stress and inflammation, these exciting products offer a science-backed approach to improving health outcomes for both mother and baby.
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Keywords
Maternal stress , Neurodevelopment , Human milk oligosaccharide
Citation
Egan, A. M. 2024. Maternal stress signature and infant neurodevelopment: determining the beneficial effects of human milk oligosaccharides - an in vitro study. MRes Thesis, University College Cork.