Markers of environmental enteric dysfunction are associated with poor growth and iron status in rural Ugandan infants

https://pubmed.ncbi.nlm.nih.gov/32455424/Published versio

Biomarkers of maternal environmental enteric dysfunction are associated with shorter gestation and reduced length in newborn infants in Uganda

https://pubmed.ncbi.nlm.nih.gov/30247538/Published versio

Maternal aflatoxin exposure during pregnancy and adverse birth outcomes in Uganda

Aflatoxins are toxic metabolites of Aspergillus moulds and are widespread in the food supply, particularly in low- and middle-income countries. Both in utero and infant exposure to aflatoxin B1 (AFB1 ) have been linked to poor child growth and development. The objective of this prospective cohort study was to investigate the association between maternal aflatoxin exposure during pregnancy and adverse birth outcomes, primarily lower birth weight, in a sample of 220 mother-infant pairs in Mukono district, Uganda. Maternal aflatoxin exposure was assessed by measuring the serum concentration of AFB1 -lysine (AFB-Lys) adduct at 17.8 ± 3.5 (mean ± SD)-week gestation using high-performance liquid chromatography. Anthropometry and birth outcome characteristics were obtained within 48 hr of delivery. Associations between maternal aflatoxin exposure and birth outcomes were assessed using multivariable linear regression models adjusted for confounding factors. Median maternal AFB-Lys level was 5.83 pg/mg albumin (range: 0.71-95.60 pg/mg albumin, interquartile range: 3.53-9.62 pg/mg albumin). In adjusted linear regression models, elevations in maternal AFB-Lys levels were significantly associated with lower weight (adj-β: 0.07; 95% CI: -0.13, -0.003; p = 0.040), lower weight-for-age z-score (adj-β: -0.16; 95% CI: -0.30, -0.01; p = 0.037), smaller head circumference (adj-β: -0.26; 95% CI: -0.49, -0.02; p = 0.035), and lower head circumference-for-age z-score (adj-β: -0.23; 95% CI: -0.43, -0.03; p = 0.023) in infants at birth. Overall, our data suggest an association between maternal aflatoxin exposure during pregnancy and adverse birth outcomes, particularly lower birth weight and smaller head circumference, but further research is warranted.K24 DK104676 - NIDDK NIH HHS; P30 DK040561 - NIDDK NIH HHS; AID-OAA-L-10-00006 - U.S. Agency for International Development; K24DK104676 and 2P30 DK040561 - National Institutes of Health (NIH)https://pubmed.ncbi.nlm.nih.gov/30242967/Published versio

Determinants of stunting and severe stunting among under-fives : evidence from the 2011 Nepal Demographic and Health Survey

Background: Stunting remains a major public health concern in Nepal as it increases the risk of illness, irreversible body damage and mortality in children. Public health planners can reshape and redesign new interventions to reduce stunting and severe stunting among children aged less than 5 years in this country by examining their determinants. Hence, this study identifies factors associated with stunting and severe stunting among children aged less than five years in Nepal. Methods: The sample is made up of 2380 children aged 0 to 59 months with complete anthropometric measurements from the 2011 Nepal Demographic and Health Survey (NDHS). Simple and multiple logistic regression analyses were used to examine stunting and severe stunting against a set of variables. Results: The prevalences of stunting and severe stunting were 26.3% [95% confidence Interval (CI): 22.8, 30.1] and 10.2% (95%CI: 7.9, 13.1) for children aged 0–23 months, respectively, and 40.6 (95%CI: 37.3, 43.2) and 15.9% (95%CI: 13.9, 18.3) for those aged 0–59 months, respectively. After adjusting for potential confounding factors, multivariable analyses showed that the most consistent significant risk factors for stunted and severely stunted children aged 0–23 and 0–59 months were household wealth index (poorest household), perceived size of baby (small babies) and breastfeeding for more than 12 months (adjusted odds ratio (AOR) for stunted children aged 0–23 months = 2.60 [95% CI: (1.87, 4.02)]; AOR for severely stunted children aged 0–23 months = 2.87 [95% CI: (1.54, 5.34)]; AOR for stunted children aged 0–59 months = 3.54 [95% CI: (2.41, 5.19)] and AOR for severely stunted children aged 0–59 months = 4.15 [95% CI: (2.45, 6.93)]. Conclusions: This study suggests that poorest households and prolonged breastfeeding (more than 12 months) led to increased risk of stunting and severe stunting among Nepalese children. However, community-based education intervention are needed to reduce preventable deaths triggered by malnutrition in Nepal and should target children born to mothers of low socioeconomic status

Hepatic DNA hydroxymethylation is site-specifically altered by chronic alcohol consumption and aging

Global DNA hydroxymethylation is markedly decreased in human cancers, including hepatocellular carcinoma, which is associated with chronic alcohol consumption and aging. Because gene-specific changes in hydroxymethylcytosine may affect gene transcription, giving rise to a carcinogenic environment, we determined genome-wide site-specific changes in hepatic hydroxymethylcytosine that are associated with chronic alcohol consumption and aging.Young (4 months) and old (18 months) male C57Bl/6 mice were fed either an ethanol-containing Lieber\u2013DeCarli liquid diet or an isocaloric control diet for 5 weeks. Genomic and gene-specific hydroxymethylcytosine patterns were determined through hydroxymethyl DNA immunoprecipitation array in hepatic DNA.Hydroxymethylcytosine patterns were more perturbed by alcohol consumption in young mice than in old mice (431 differentially hydroxymethylated regions, DhMRs, in young vs 189 DhMRs in old). A CpG island ~2.5 kb upstream of the glucocorticoid receptor gene, Nr3c1, had increased hydroxymethylation as well as increased mRNA expression (p = 0.015) in young mice fed alcohol relative to the control group. Aging alone also altered hydroxymethylcytosine patterns, with 331 DhMRs, but alcohol attenuated this effect. Aging was associated with a decrease in hydroxymethylcytosine ~1 kb upstream of the leptin receptor gene, Lepr, and decreased transcription of this gene (p = 0.029). Nr3c1 and Lepr are both involved in hepatic lipid homeostasis and hepatosteatosis, which may create a carcinogenic environment. These results suggest that the location of hydroxymethylcytosine in the genome is site specific and not random, and that changes in hydroxymethylation may play a role in the liver\u2019s response to aging and alcohol

Aging and alcohol interact to alter hepatic DNA hydroxymethylation

BACKGROUND:Aging and chronic alcohol consumption are both modifiers of DNA methylation, but it is not yet known whether chronic alcohol consumption also alters DNA hydroxymethylation, a newly discovered epigenetic mark produced by oxidation of methylcytosine. Furthermore, it has not been tested whether aging and alcohol interact to modify this epigenetic phenomenon, thereby having an independent effect on gene expression.METHODS:Old (18 months) and young (4 months) male C57BL/6 mice were pair-fed either a Lieber-DeCarli liquid diet with alcohol (18% of energy) or an isocaloric Lieber-DeCarli control diet for 5 weeks. Global DNA hydroxymethylation and DNA methylation were analyzed from hepatic DNA using a new liquid chromatography-tandem mass spectrometry method. Hepatic mRNA expression of the Tet enzymes were measured via quantitative real-time polymerase chain reaction.RESULTS:In young mice, mild chronic alcohol exposure significantly reduced global DNA hydroxymethylation compared with control mice (0.22 \ub1 0.01 vs. 0.29 \ub1 0.06%, p = 0.004). Alcohol did not significantly alter hydroxymethylcytosine levels in old mice. Old mice fed the control diet showed decreased global DNA hydroxymethylation compared with young mice fed the control diet (0.24 \ub1 0.02 vs. 0.29 \ub1 0.06%, p = 0.04). This model suggests an interaction between aging and alcohol in determining DNA hydroxymethylation (pinteraction = 0.009). Expression of Tet2 and Tet3 was decreased in the old mice relative to the young (p < 0.005).CONCLUSIONS:The observation that alcohol alters DNA hydroxymethylation indicates a new epigenetic effect of alcohol. This is the first study demonstrating the interactive effects of chronic alcohol consumption and aging on DNA hydroxymethylation

Aging alters hepatic DNA hydroxymethylation, as measured by liquid chromatography/mass spectrometry

BACKGROUND: Aging is one of the most important risk factors for cancer. It appears that aberrant epigenetic changes might be a common driver of aging and cancer. Among them are changes in DNA methylation and DNA hydroxymethylation. The 5' carbon of cytosines in CpG dinucleotides of DNA can be either methylated or hydroxymethylated. Like 5'-methylcytosine, changes in 5'-hydroxymethylcytosine may occur due to aging, potentially leading to downstream changes in transcription and cancer development. METHODS: We set up a method to measure 5'-methyl-2'-deoxycytidine and 5'-hydroxymethyl-2'-deoxycytidine in DNA using liquid chromatography/mass spectrometry (LC/MS-MS) and used this method to measure the percentage of total cytosine that was either methylated or hydroxymethylated in the liver tissues of young and old C57Bl/6 male mice. The DNA was enzymatically hydrolyzed by sequential digestion with nuclease P1, phosphodiesterase I and alkaline phosphatase. The isotopomers [(15)N3]-2'-deoxycytidine and (methyl-d 3, ring-6-d 1)-5-methyl-2'-deoxycytidine were added to the DNA hydrolysates as internal standards. DNA methylation and hydroxymethylation were calculated as a percentage of total deoxycytidine in genomic DNA. RESULTS: Within day variations for DNA methylation and hydroxymethylation were 3.45% and 8.40%, while day to day variations were 6.14% and 17.68%, respectively. Using this method it was determined that hepatic DNA of old mice had increased levels of hydroxymethylation relative to young (0.32 \ub1 0.02% vs. 0.24 \ub1 0.01%, P = 0.02), with no significant changes in 5'-methylcytosine. CONCLUSIONS: DNA hydroxymethylation measured by LC/MS-MS method can be a novel biomarker of aging. It will be useful to investigate the potential role of DNA hydroxymethylation in the development and prevention of age-associated cancer

Estimated number of cardiometabolic deaths attributable to suboptimal dietary intake in Kuwait in 2009.

Bars represent the estimated number of cardiometabolic deaths attributable to intake of individual dietary factors compared to the optimal intake (numbers in parentheses).</p