|dc.description.abstract||Background: It has been shown that poor nutrition during early development has a causal relationship with adverse pregnancy outcomes, morbidity, mortality and the increased risk of short- and long-term adverse health outcomes for the child and future generations. Furthermore, a mother’s nutritional status has an impact on the unborn baby, possibly through epigenetic mechanisms.
In developing countries, women are reliant on poor-quality diets. In these circumstances, nutrient deficiencies do not occur in isolation, and it is likely that in pregnant women, iron deficiency (ID) and inadequate omega-3 polyunsaturated fatty acid (n-3 PUFA) status coexist. Both deficiencies play a role in the development of colon inflammation. Inflammation in the gut and colon can lead to dysbiosis of the microbiota, compromised tight junctions, increased gut permeability, and pathogens to enter the bloodstream. The result is low-grade systemic inflammation contributing to the development of gastrointestinal diseases such as irritable bowel syndrome and also to the development of adult diseases such as diabetes, obesity, cancer, and neuro-pathologies. Therefore, optimum nutrition before and during pregnancy is crucial for the gut development and future health of the offspring. Apart from being reliant on nutrients from the mother’s diet during gestation, offspring in the human situation will most likely also continue consuming a similar diet to that of their mother. Data on the combined ID and n-3 PUFA deficiency ((n-3)FAD), specifically in relation to gut inflammation, is scarce. Aim: Therefore, in this study, the pre-and postnatal effects of ID and (n-3)FAD, alone and in combination, on colon lining lipid mediator concentrations, which indicates colon inflammation, will be investigated in rats. Methods: Fifty-six female Wistar rats were allocated to one of four diets: 1) Control, 2) ID, 3) (n- 3)FAD, or 4) ID + (n-3)FAD and were maintained on the respective diets throughout pregnancy and lactation. Offspring (n=96) continued on the respective diets after weaning until postnatal day 42-45. Concentrations of lipid mediators were analysed in homogenized colon lining tissue from the offspring, with liquid chromatography-tandem mass spectrometry (LCMSMS). Pro-inflammatory lipid mediators, 5-, 8-, 11-, 12- and 15-hydroxyeicosatetraenoic acid (HETE), and pro-resolving lipid mediators, 17-hydroxydocosahexaenoic acid (HDHA); and 11-, 12-, 15- and 18 hydroxyeicosapentaenoic acid (HEPE) were measured. Results: ID resulted in higher colonic pro-inflammatory lipid mediator concentrations in offspring derived from arachidonic acid (ARA), including 5-, 12-, 15- and 8-HETE (all p<0.005). Omega-3 PUFA deficiency resulted in higher 12-HETE (p=0.010). ID resulted in higher pro-resolving lipid
mediators derived from docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), including 17-HDHA, 12- and 15-HEPE (all p<0.001), whereas (n-3)FAD, resulted in lower pro- resolving lipid mediators (17-HDHA, 12-, 15-, 18- and 11-HEPE, all p<0.005). Furthermore, a significant ID x (n-3)FAD interaction synergistically resulted in higher pro-inflammatory lipid mediators (12- and 15-HETE, both p<0.050). For 12-HEPE, however, the effect of ID for higher 12-HEPE was attenuated by (n-3)FAD (p=0.049). Conclusion: This study found that pre- and postnatal combined deficiency of iron and n-3 PUFA in rats increased inflammation in the colon of offspring in early adolescence more than the single deficiencies alone. Omega-3 FAD furthermore attenuated the resolving of inflammation which is still possible with ID alone, resulting in a pro-inflammatory profile that could not be resolved in double-deficient rats.||en_US