Maternal nutritional status, C1 metabolism and offspring DNA methylation: a review of current evidence in human subjects.

: Evidence is growing for the long-term effects of environmental factors during early-life on later disease susceptibility. It is believed that epigenetic mechanisms (changes in gene function not mediated by DNA sequence alteration), particularly DNA methylation, play a role in these processes. This paper reviews the current state of knowledge of the involvement of C1 metabolism and methyl donors and cofactors in maternal diet-induced DNA methylation changes in utero as an epigenetic mechanism. Methyl groups for DNA methylation are mostly derived from the diet and supplied through C1 metabolism by way of choline, betaine, methionine or folate, with involvement of riboflavin and vitamins B6 and B12 as cofactors. Mouse models have shown that epigenetic features, for example DNA methylation, can be altered by periconceptional nutritional interventions such as folate supplementation, thereby changing offspring phenotype. Evidence of early nutrient-induced epigenetic change in human subjects is scant, but it is known that during pregnancy C1 metabolism has to cope with high fetal demands for folate and choline needed for neural tube closure and normal development. Retrospective studies investigating the effect of famine or season during pregnancy indicate that variation in early environmental exposure in utero leads to differences in DNA methylation of offspring. This may affect gene expression in the offspring. Further research is needed to examine the real impact of maternal nutrient availability on DNA methylation in the developing fetus

Developmental epigenetics in humans: Can maternal nutritional status mediate DNA methylation in their offspring?

Animal studies show that periconceptional maternal supplementation with nutrients involved in the provision of methyl-groups can alter DNA methylation patterns in the offspring. This thesis examines possible associations between maternal nutrition and offspring DNA methylation patterns in humans in the context of seasonal influences. Two complementary studies were conducted in rural Gambia. The ‘indicator’ group enrolled 30 non-pregnant women and followed them monthly for one year, to measure dietary intakes and blood biomarker levels of choline, betaine, folate, methionine and vitamins B2, B6 and B12, as well as plasma homocysteine, S-adenosyl-methionine (SAM), S-adenosyl-homocysteine (SAH), cysteine and dimethylglycine (DMG). The ‘main’ group enrolled 136 mother-infant pairs, with infants conceived at the peak of the rainy (July to September) or dry (February to April) season. The same panel of blood biomarkers were measured on maternal samples collected early in pregnancy. In the infants, DNA methylation at seven metastable epialleles (MEs) was assessed. Significant seasonal variation was observed within the indicator group for dietary intakes of choline, betaine, folate and B2 and all metabolic biomarkers. A possible change in dependence between the betaine and folate pathways between seasons was identified. Within the main group, a seasonal variation was observed in both maternal biomarker levels and infant DNA methylation. The rainy season was associated with a higher maternal SAM:SAH ratio, higher concentrations of most methyl-donors (folate, betaine and methionine) and cofactors (B2 and B6) and higher infant DNA methylation. DNA methylation at the MEs studied was associated with B2, cysteine and the SAM:SAH and DMG:betaine ratios, but not with the other biomarkers. These data suggest that Gambian seasonality influences maternal methyl-group supply, which may be linked to DNA methylation patterns in offspring. Future work is required to confirm this observation, and understand precise mechanisms, so optimal nutrition at critical phases can be determined

Maternal nutrition at conception modulates DNA methylation of human metastable epialleles.

In experimental animals, maternal diet during the periconceptional period influences the establishment of DNA methylation at metastable epialleles in the offspring, with permanent phenotypic consequences. Pronounced naturally occurring seasonal differences in the diet of rural Gambian women allowed us to test this in humans. We show that significant seasonal variations in methyl-donor nutrient intake of mothers around the time of conception influence 13 relevant plasma biomarkers. The level of several of these maternal biomarkers predicts increased/decreased methylation at metastable epialleles in DNA extracted from lymphocytes and hair follicles in infants postnatally. Our results demonstrate that maternal nutritional status during early pregnancy causes persistent and systemic epigenetic changes at human metastable epialleles

Transformation of animal agriculture should be evidence-driven and respectful of livestock’s benefits and contextual aspects

Response to a Letter to the Edito

Rates of depressive and anxiety symptoms in the perinatal period during the COVID-19 pandemic: Comparisons between countries and with pre-pandemic data

Background: The COVID-19 pandemic was a significant threat to perinatal mental health. This study examined differences in clinically significant depression, anxiety, and co-morbid symptoms among pregnant and postpartum women across several countries and compared prevalence of perinatal depression and anxiety before and during the pandemic in each participating country. Methods: Participants were 3326 pregnant and 3939 postpartum women (up to six months postpartum) living in Brazil, Chile, Cyprus, Greece, Israel, Portugal, Spain, Turkey, and the United Kingdom. An online survey was completed between June 7th and October 31st 2020, and included the Edinburgh Postnatal Depression Scale (EPDS) and the Generalized Anxiety Disorder Screener (GAD-7). The pre-pandemic studies were identified through literature review. Results: Prevalence of clinically significant depression (EPDS≥13), anxiety (GAD-7 ≥ 10), and co-morbid (EPDS≥13 and GAD-7 ≥ 10) symptoms was 26.7 %, 20 % and 15.2 %, in pregnant women, and 32.7 %, 26.6 % and 20.3 %, in postpartum women, respectively. Significant between-country differences were found in all mental health indicators in both perinatal periods. Higher levels of symptoms were observed during (versus before) the pandemic, especially among postpartum women. Limitations: Participants were mostly highly educated and cohabiting with a partner. The online nature of the survey may have limited the participation of women from vulnerable socio-economically backgrounds. Conclusions: Our findings expand previous literature on the negative impact of the COVID-19 pandemic on perinatal mental health, by highlighting that this may be influenced by country of residence. Mental health care policies and interventions should consider the unique needs of perinatal women in different parts of the world. © 2022Funding text 1: Sara Cruz acknowledges the Centro de Investigação em Psicologia para o Desenvolvimento (CIPD) [The Psychology for Positive Development Research Center] ( UID/PSI/04375 ), Lusíada University North, Porto, supported by national funds through the Portuguese Foundation for Science and Technology , I.P., and the Portuguese Ministry of Science, Technology and Higher Education ( UID/PSI/04375/2019 ).; Funding text 2: This paper is part of the COST Action Riseup-PPD CA18138 and was supported by COST under COST Action Riseup-PPD CA18138 . ; Funding text 3: Vera Mateus received financial support from CAPES /PrInt grant no. 88887.583508/2020-00 . ; Funding text 4: Raquel Costa was supported by the FSE and FCT under the Post-Doctoral Grant SFRH/BPD/117597/2016 [RC]. EPIUnit, ITR, and HEI-lab are supported by national funds through the Portuguese Foundation for Science and Technology , I.P., under the projects UIDB/04750/2020 , LA/P/0064/2020 , and UIDB/05380/2020 , respectively. ; Funding text 5: This publication is based upon work from COST Action 18138 - Research Innovation and Sustainable Pan-European Network in Peripartum Depression Disorder (Riseup-PPD), supported by COST (European Cooperation in Science and Technology). www.cost.eu . ; Funding text 6: Ana Osório received financial support from CAPES PROEX grant no. 0426/2021 , process no. 23038.006837/2021-73, CAPES /PrInt grant no. 88887.310343/2018-00 and MackPesquisa Fund . ; Funding text 7: Rena Bina received financial support from the Bar-Ilan Dangoor Centre for Personalized Medicine , grant no. REFU/DANGO/100. ; Funding text 8: This publication is based upon work from COST Action 18138 - Research Innovation and Sustainable Pan-European Network in Peripartum Depression Disorder (Riseup-PPD), supported by COST (European Cooperation in Science and Technology). www.cost.eu.Vera Mateus received financial support from CAPES/PrInt grant no. 88887.583508/2020-00.Ana Osório received financial support from CAPES PROEX grant no. 0426/2021, process no. 23038.006837/2021-73, CAPES/PrInt grant no. 88887.310343/2018-00 and MackPesquisa Fund.Rena Bina received financial support from the Bar-Ilan Dangoor Centre for Personalized Medicine, grant no. REFU/DANGO/100.Raquel Costa was supported by the FSE and FCT under the Post-Doctoral Grant SFRH/BPD/117597/2016 [RC]. EPIUnit, ITR, and HEI-lab are supported by national funds through the Portuguese Foundation for Science and Technology, I.P., under the projects UIDB/04750/2020, LA/P/0064/2020, and UIDB/05380/2020, respectively.This paper is part of the COST Action Riseup-PPD CA18138 and was supported by COST under COST Action Riseup-PPD CA18138. The authors would like to thank all women who participated in the survey. Sara Cruz acknowledges the Centro de Investigação em Psicologia para o Desenvolvimento (CIPD) [The Psychology for Positive Development Research Center] (UID/PSI/04375), Lusíada University North, Porto, supported by national funds through the Portuguese Foundation for Science and Technology, I.P. and the Portuguese Ministry of Science, Technology and Higher Education (UID/PSI/04375/2019)

Evidence for negative selection of gene variants that increase dependence on dietary choline in a Gambian cohort

Choline is an essential nutrient, and the amount needed in the diet is modulated by several factors. Given geographical differences in dietary choline intake and disparate frequencies of single-nucleotide polymorphisms (SNPs) in choline metabolism genes between ethnic groups, we tested the hypothesis that 3 SNPs that increase dependence on dietary choline would be under negative selection pressure in settings where choline intake is low: choline dehydrogenase (CHDH) rs12676, methylenetetrahydrofolate reductase 1 (MTHFD1) rs2236225, and phosphatidylethanolamine-N-methyltransferase (PEMT) rs12325817. Evidence of negative selection was assessed in 2 populations: one in The Gambia, West Africa, where there is historic evidence of a choline-poor diet, and the other in the United States, with a comparatively choline-rich diet. We used 2 independent methods, and confirmation of our hypothesis was sought via a comparison with SNP data from the Maasai, an East African population with a genetic background similar to that of Gambians but with a traditional diet that is higher in choline. Our results show that frequencies of SNPs known to increase dependence on dietary choline are significantly reduced in the low-choline setting of The Gambia. Our findings suggest that adequate intake levels of choline may have to be reevaluated in different ethnic groups and highlight a possible approach for identifying novel functional SNPs under the influence of dietary selective pressure

Roads to interdisciplinarity - working at the nexus among food systems, nutrition and health: 1st annual Agriculture, Nutrition and Health (ANH) Academy Week, Addis Ababa (Ethiopia), 20-24 June 2016

The development agenda over the next 15 years will be framed by the Sustainable Development Goals (SDGs), of which more than half relate either directly or indirectly to the agricultural sector, highlighting its importance in economic growth and development of low- and middle-income countries (LMICs) (FAO 2015). It is therefore imperative that agricultural systems are better understood, so that they may be strengthened and optimised to deliver outcomes in line with the SDGs. The interface between agriculture, nutrition and health is particularly multifaceted and complex, and the development of successful strategies will require an integrated and multi-sectoral approach (Dorward and Dangour 2012; Jones and Ejeta 2016). ‘Agri-health’ is an evolving paradigm seeking to unify research approaches and methodologies between agriculture and health. Research within the field encapsulates a broad range of disciplines, locations and actors, and aligns these into a common research agenda. In doing so, agri-health aims to transcend barriers imposed by the longstanding institutional and disciplinary silos. Much progress has been made in recent years in this regard (Harris et al. 2013; Kanter et al. 2014; Picchioni et al. 2015). However, more coordinated efforts are required to generate consensus and target strategic priorities amongst the many existing information gaps (Webb and Kennedy 2014). Understanding the linkages between complex issues such as globalisation, climate change, food systems, and evolving burdens of malnutrition is central to agri-health research. The Leverhulme Centre for Integrative Research on Agriculture and Health (LCIRAH) was created in 2010 with a key focus on agri-health interdisciplinary research. LCIRAH includes experts from across the member colleges of the University of London: the London School of Hygiene and Tropical Medicine (LSHTM), the School of Oriental and African Studies (SOAS), and the Royal Veterinary College (RVC). The Agriculture, Nutrition and Health Academy (ANH Academy), was established in 2015 as a platform to facilitate learning, knowledge sharing, capacity building and collaborative partnerships among the growing global community of researchers, practitioners and policy makers working within agri-health. It was developed with support from the Innovative Metrics and Methods for Agriculture and Nutrition Actions (IMMANA) research programme,Footnote1 led by LCIRAH and Tufts University, in partnership with the CGIAR Programme on Agriculture for Nutrition and Health (A4NH). Within this scope, the ANH Academy hosts an annual ANH Academy Week, building on the legacy of five agri-health research conferences organised by LCIRAH; as well as events and activities coordinated under the CGIAR A4NH. The inaugural ANH Academy Week took place in Addis Ababa, Ethiopia, in June 2016 and included two days of interactive ‘learning labs’ (training sessions on skills and methods across a broad range of disciplines in agri-health), followed by a three-day research conference. The conference included a mix of abstract-driven sessions, round table discussions, and keynote speeches from across the spectrum of agriculture, nutrition and health disciplines, and a wide range of countries. Hawkes et al. (2012) developed a conceptual framework (Fig. 2, hereafter referred to as the Framework), outlining the key pathways through which agriculture may affect nutritional status in Low and Middle Income Countries (LMICs), as well as broader drivers of these pathways. Drawing on this Framework, this paper aims to provide an analytical synthesis of the ANH Academy week by mapping the research and debates presented during the conference