Peanut supplementation affects compositions and functions of gut microbiome in Ugandan children.

Childhood malnutrition remains a serious global health concern, particularly in low-income nations like Uganda. This study investigated the impact of peanut supplementation on the compositions and functions of gut microbiome with nutritional improvement. School children aged 6-9 years from four rural communities were recruited, with half receiving roasted peanut snacks while the other half served as controls. Fecal samples were collected at the baseline (day 0), day 60, and day 90. Microbial DNA was extracted, and 16S rRNA sequencing was performed, followed by the measurement of SCFA concentration in fecal samples using UHPLC. Alpha and beta diversity analyses revealed significant differences between the control and supplemented groups after 90 days of supplementation. Leuconostoc lactis, Lactococcus lactis, Lactococcus garvieae, Eubacterium ventriosum, and Bacteroides thetaiotaomicron, associated with the production of beneficial metabolites, increased significantly in the supplemented group. Acetic acid concentration also increased significantly. Notably, pathogenic bacteria, including Clostridium perfringens and Leuconostoc mesenteroides, were decreased in the supplemented group. The study indicates the potential of peanut supplementation to modulate the gut metabolome, enrich beneficial bacteria, and inhibit pathogens, suggesting a novel approach to mitigating child malnutrition and improving health status.

The stage-specific toxicity of per- and polyfluoroalkyl substances (PFAS) in nematode Caenorhabditis elegans.

Per- and Polyfluoroalkyl Substances (PFAS) are a diverse class of industrial chemicals that have been used for decades in industrial and commercial applications. Due to their widespread usages, persistence in the environment, and bioaccumulation in animals and humans, great public health concerns have been raised on adverse health risks of PFAS. In this study, ten PFAS were selected according to their occurrence in different water bodies. The wild-type worms were exposed to individual PFAS at 0, 0.1, 1,10, 100, and 200 µM, and the toxic effects of PFAS on growth, development, fecundity, and behavior at different life stages were investigated using a high-throughput screening (HTS) platform. Our results showed that perfluorooctanesulfonic acid (PFOS), 1H,1H, 2H, 2H-perfluorooctanesulfonamidoacetic acid (NEtFOSAA), perfluorobutanesulfonic (PFBS), and perfluorohexanesulfonic acid (PFHxS) exhibited significant inhibitive effects on the growth in the L4 larva and later stages of worms with concentrations ranging from 0.1 to 200 µmol/L. PFOS and PFBS significantly decreased the brood size of worms across all tested concentrations (p < 0.05), and the most potent PFAS is PFOS with BMC of 0.02013 µM (BMCL, 1.6e-06 µM). During adulthood, all PFAS induced a significant reduction in motility (p < 0.01), while only PFOS can significantly induce behavior alteration at the early larvae stage. Furthermore, the adverse effects occurred in larval stages were found to be the most susceptible to the PFAS exposure. These findings provide valuable insights into the potential adverse effects associated with PFAS exposure and show the importance of considering developmental stages in toxicity assessments.

The occurrence and management of fumonisin contamination across the food production and supply chains.

BACKGROUND: Fumonisins (FUMs) are among the most common mycotoxins in plant-derived food products. FUMs contamination has considerably impacted human and animal health, while causing significant economic losses. Hence, management of FUMs contamination in food production and supply chains is needed. The toxicities of FUMs have been widely investigated. FUMs management has been reported and several available strategies have been developed successfully to mitigate FUMs contamination present in foods. However, currently available management of FUMs contamination from different phases of food chains and the mechanisms of some major strategies are not comprehensively summarized. AIM OF REVIEW: This review comprehensively characterize the occurrence, impacts, and management of FUMs contamination across food production and supply chains. Pre- and post-harvest strategies to prevent FUMs contamination also are reviewed, with an emphasis on the potential applications and the mechanisms of major mitigation strategies. The presence of modified FUMs products and their potential toxic effects are also considered. Importantly, the potential application of biotechnological approaches and emerging technologies are enunciated. KEY SCIENTIFIC CONCEPTS OF REVIEW: Currently available pre- and post-harvest management of FUMs contamination primarily involves prevention and decontamination. Prevention strategies are mainly based on limiting fungal growth and FUMs biosynthesis. Decontamination strategies are implemented through alkalization, hydrolysis, thermal or chemical transformation, and enzymatic or chemical degradation of FUMs. Concerns have been raised about toxicities of modified FUMs derivatives, which presents challenges for reducing FUMs contamination in foods with conventional methodologies. Integrated prevention and decontamination protocols are recommended to control FUMs contamination across entire value chains in developed countries. In developing countries, several other approaches, including cultivating, introducing Bt maize, simple sorting/cleaning, and dehulling, are suggested. Future studies should focus on biotechnological approaches, emerging technologies, and metagenomic/genomic identification of new degradation enzymes that could allow better opportunities to manage FUMs contamination in the entire food system.

Bacteria pyruvate metabolism modulates AFB1 toxicity in Caenorhabditis elegans.

Aflatoxin B1 (AFB1), the most potent mycotoxin and Group 1 human carcinogen, continues to pose a significant public health burden, particularly in developing countries. Increasing evidence has shown the gut microbiota as a key mediator of AFB1 toxicity through multiple interactive host-microbiota activities. In our previous study we observed that disturbances in bacterial pyruvate metabolism might have a significant impact on AFB1 in the host. To further investigate the impact of the pyruvate pathway on AFB1 toxicity in C. elegans, we engineered two bacterial strains (triple-overexpressed and triple-knockout strains with aceB, lpd, and pflB). Additionally, we employed two mutant worm strains (pyk-1 and pdha-1 mutants) known to affect pyruvate metabolism. Our results revealed that the co-metabolism of pyruvate by the host and bacterial strains synergistically influences AFB1 toxicity. Remarkable, we found that bacterial pyruvate metabolism, rather than that of the host, plays a pivotal role in modulating AFB1 toxicity in C. elegans. Our study sheds light on the role of gut microbiota involved in pyruvate metabolism in influencing AFB1 toxicity in C. elegans.

Host-microbiota affects the toxicity of Aflatoxin B1 in Caenorhabditis elegans.

Aflatoxins are a group of potent fungal metabolites produced by Aspergillus and commonly contaminate groundnuts and cereal grains. Aflatoxin B1 (AFB1), the most potent mycotoxin, has been classified as Group 1 human carcinogen because it can be metabolically activated by the cytochrome P450 (CYP450) in the liver to form AFB1-DNA adducts and induce gene mutations. Increasing evidence has shown the gut microbiota as a key mediator of AFB1 toxicity through multiple interactive host-microbiota activities. To identify specific bacterial activity that modulates AFB1 toxicity in Caenorhabditis (C.) elegans, we established a 3-way (microbe-worm-chemical) high-throughput screening system using C. elegans fed E. coli Keio collection on an integrated robotic platform, COPAS Biosort. We performed 2-step screenings using 3985 Keio mutants and identified 73 E. coli mutants that modulated C. elegans growth phenotype. Four genes (aceA, aceB, lpd, and pflB) involved in the pyruvate pathway were identified from the screening and confirmed to increase the sensitivity of all animals to AFB1. Taking together, our results indicated that disturbances in bacterial pyruvate metabolism might have a significant impact on AFB1 toxicity in the host.

Assessing an aflatoxin exposure biomarker: Exploring the interchangeability and correlation between venous and capillary blood samples.

Exposure to dietary aflatoxins has been recognized as a potential threat to child nutrition and growth, in addition to being a known carcinogen. The ability to accurately assess concentration of aflatoxin in the blood of at-risk individuals is therefore very important to inform public health policies and on-the-ground programs around the world. Venous blood is frequently used to quantify biomarkers of exposure such as AFB1-lysine adducts. However, venous blood collection methods are invasive, requiring highly trained staff, which makes this method challenging to implement, especially in resource-limited settings. In contrast, capillary blood collection by fingerprick is less invasive and has the potential for application in point-of-need monitoring. The aim of this exploratory study was to investigate the correlation and interchangeability of capillary and venous human blood samples in the quantification of AFB1-lysine adduct concentration. A total of 72 venous and capillary blood samples were collected from 36 women of reproductive age (16-49 years) in northern Uganda. All sample specimens were analyzed using high-performance liquid chromatography with fluorescence detection. Regression analysis and Bland-Altman analysis were performed to compare AFB1-lysine concentrations between venous and capillary sample pairs. Bland-Altman analysis of albumin-normalized AFB1-lysine data-bias was -0.023 pg/mg-albumin and the 95% limits of agreement were 0.51 to -0.56 pg/mg-albumin for log-transformed data. There was a positive correlation between albumin-normalized venous and capillary AFB1-lysine concentrations with r of 0.71 (p < .0001). A lack of any accepted clinical cutoff for aflatoxin exposure makes definition of an 'acceptable' limit for statistical analysis and comparison of methods challenging. Our data suggests a positive correlation between albumin-normalized AFB1-lysine concentrations in venous and capillary sample pairs, but relatively weak agreement and interchangeability based on Bland-Altman analysis.

Assessment of aflatoxin B1-lysine adduct in children and its effect on child growth in Lahore, Pakistan.

Aflatoxin B1 is an important toxic food contaminant and there is very little information available about its exposure and effects on the health of the Pakistani population. Therefore, children (n = 238) aged 1-11 years were recruited in this study to estimate the levels of aflatoxin B1-lysine adduct and to measure its adverse effects on growth. Blood samples were analyzed to detect AFB1-lysine adducts through high-performance liquid chromatography. Socio-demographic information and anthropometry measurements were also obtained. All participants had detectable levels of AFB1-lysine adduct with a median concentration of 10.66 pg/mg albumin (95% CI: 8.6-12.4). Differences in area of residence (p < 0.05) and the father's employment (p < 0.05) were significant predictors for aflatoxin concentration levels in ordinary least square and quantile regression models (residence in 75th quantile and father employment in 90th quantile). Children aged from 5 to 11 years in the 5th and 90th quantiles of the regression model had a significant association with aflatoxin levels. A very high (50.4%, 120/238) prevalence of growth impairment (stunting, wasting, and underweight) was also observed in this study. Although we couldn't establish the effect of aflatoxin on growth impairment, children with low serum albumin levels (OR = 0.18; 95% CI: 0.05-0.56; p = 0.004) were likely to be at risk of wasting. Also, low birth weight was strongly associated with wasting (OR = 3.11; 95% CI: 1.36-7.03; p = 0.006) and underweight (OR = 4.60; 95% CI: 2.21-10.05; p= <0.001), while the mother's school level education had a correlation with child stunting (OR = 1.84; 95% CI: 1.07-3.22; p = 0.029). The high prevalence of growth impairment and high concentration of serum AFB1-lysine adduct levels in study participants demand immediate efforts to mitigate the adverse health outcomes in children in Pakistan.

Dietary determinants of aflatoxin B1-lysine adduct among infants in Nepal.

BACKGROUND: Aflatoxins are mycotoxins produced by naturally occurring fungi on food, and aflatoxin B1 (AFB1) is carcinogenic, immunotoxic and hepatotoxic. This study assesses the relationship between AFB1 in Nepali infants at 12 months of age and their diet at 9 and 12 months of age. METHODS: The study used data collected from 1329 infants enrolled in the AflaCohort Study. Aflatoxin exposure was assessed at 12 months using serum AFB1-lysine pg/mg albumin biomarker measured using high performance liquid chromatography-fluorescent detection. Dietary data were collected using food frequency questionnaire. We conducted ordinary least squares and quantile regression analyses with backward elimination to assess lagged (9-month diet and 12-month AFB1) and contemporaneous (12-month diet and 12-month AFB1) associations. RESULTS: Eighty-one percent of children at 12 months had detectable levels of serum AFB1-lysine (geometric mean: 0.79 pg/mg albumin, 95% CI: 0.74-0.83). The levels ranged from 0.4 to 85 pg/mg albumin. Dietary diversity at 9 and 12 months were not associated with serum AFB1-lysine levels. Consumption of fish and groundnuts at both 9 and 12 months and infant formula and cauliflower at 9 months were associated with higher serum AFB1-lysine while consumption of bananas and mangoes at 12 months were negatively associated with serum AFB1-lysine (p < 0.05). CONCLUSIONS: High prevalence of detectable AFB1-lysine among infants, and possible links to their dietary patterns argues for more urgent research into which foods in children's diets are most contaminated, and into optimal entry points in the food chain that would allow for effective actions to minimize exposure.

Exposure to multiple mycotoxins, environmental enteric dysfunction and child growth: Results from the AflaCohort Study in Banke, Nepal.

Evidence of the impact of exposure to multiple mycotoxins and environment enteric dysfunction (EED) on child growth is limited. Using data from a birth cohort study, the objectives of this study were to (a) quantify exposure to multiple mycotoxins (serum aflatoxin [AFB1 ] and ochratoxin A [OTA], urinary fumonisin [UFB1 ] and deoxynivalenol [DON]), as well EED (lactulose:mannitol [L:M] ratio); (b) examine the potential combined effects of multiple mycotoxin exposure and EED on growth. Multivariate regressions were used to identify associations between growth measurements (length, weight, anthropometric z-scores, stunting and underweight) at 24-26 months of age and exposure to mycotoxins and EED at 18-22 months (n = 699). Prevalence of AFB1 , DON, OTA and UFB1 exposure ranged from 85% to 100%; average L:M ratio was 0.29 ± 0.53. In individual mycotoxin models, AFB1 exposure was negatively associated with weight, WAZ, increased odds of stunting (odds ratio [OR]: 1.28, 95% confidence interval [CI]: 1.08, 1.52; p = 0.004) and underweight (OR: 1.18, 95% CI: 1.00, 1.38; p = 0.046). Irrespective of other mycotoxin exposure and presence of EED, AFB1 was negatively associated with length, weight, head circumference, LAZ and WAZ, and with increased odds of stunting and underweight, UFB1 was associated with increased odds of underweight, and DON was negatively associated with head circumference. EED was associated with the impaired length and weight. These findings suggest that certain mycotoxins and EED may have independent impacts on different facets of growth and that aflatoxin dominates such impacts. Thus, programs reducing exposure to mycotoxin and EED through multi-sectoral nutrition-sensitive interventions have the potential to improve child growth.

High-Throughput Measurement for Toxic Effects of Metal Mixtures in Caenorhabditis elegans.

The contamination of heavy metals, a class of naturally occurring and persistent toxicants, has become a major public health concern due to increasing industrial and anthropogenic activities. The use of COPAS Biosort, a flow cytometer capable of measuring thousands of nematodes in minutes via high-throughput assays, has been widely applied in C. elegans studies for assessing toxicity of individual metals; however, such application yet to be seen for metals or other chemical mixtures. In the present protocol, we investigated toxic effects of individual metals, Cd, Pb, and Mn, as well as their binary and ternary mixtures, using nematode C. elegans. The toxic outcomes, including effects on growth, reproduction, and feeding behavior, were measured using high-throughput platform analysis (COAPS Biosort).

Aflatoxin exposure and child nutrition: measuring anthropometric and long-bone growth over time in Nepal.

BACKGROUND: Naturally occurring aflatoxins may contribute to poor growth and nutritional statuses in children. OBJECTIVES: We analyzed the relationship between contemporary and lagged aflatoxin exposure and 1) length-for-age z-score (LAZ); and 2) length, knee-heel length, stunting, weight-for-age z-score (WAZ), and weight-for-length z-score (WLZ). METHODS: We conducted a longitudinal birth cohort study involving 1675 mother-infant dyads in rural Nepal. Participants were repeatedly visited from pregnancy to 2 years of age (2015-2019). One blood sample was collected during pregnancy and 4 samples were collected from the children at 3, 6, 12, and 18-22 months of age to measure concentrations of aflatoxin B1 (AFB1)-lysine adduct. Multivariate linear fixed-effects and logistic models with generalized estimating equations were used to identify associations between child growth and aflatoxin exposure. RESULTS: AFB1-lysine adducts were detected in the majority of children (at 3 months, 80.5%; at 6 months, 75.3%; at 12 months, 81.1%; and at 18-22 months, 85.1%) and in 94.3% of pregnant women. Changes in contemporary ln child AFB1-lysine adduct concentrations were significantly associated with changes in LAZ (ß, -0.05; 95% CI, -0.09 to -0.02; P = 0.003), length (ß, -0.19; 95% CI, -0.29 to -0.10; P < 0.001), knee-heel length (ß, -0.09; 95% CI, -0.13 to -0.05; P < 0.001), and WAZ (ß, -0.04; 95% CI, -0.07 to -0.005; P = 0.022). Serum aflatoxin concentrations were associated with stunting (OR, 1.18; 95% CI, 1.05-1.32; P = 0.005). Similar results were found in the models using changes in contemporary ln AFB1 adjusted for changes in child weight, with significant associations with changes in WLZ (ß, -0.07; 95% CI, -0.10 to -0.03; P < 0.001). Changes in time-lagged ln AFB1 (unadjusted and adjusted for changes in child weight) were associated with changes in length and knee-heel length. CONCLUSIONS: Our results add to the growing body of evidence confirming chronic aflatoxin exposure and suggest that exposure is significantly correlated with various negative growth outcomes, which may vary by child weight status. This trial was registered at clinicaltrials.gov as NCT03312049.

Increase in aflatoxin exposure in two populations residing in East and West Texas, United States.

Although aflatoxin (AF) exposure has not been recognized as a major problem in the United States and other developed nations, recent global climate change may have a profound impact on distribution of toxigenic fungi growth and production of AFs in grain and groundnuts. Alterations in the contamination pattern can increase human dietary exposure, and further invoke public health concerns and associated disease risks. In this study, two populations from East and West Texas, known for their high risk of liver cancer, were examined for their AF exposure at three different time periods from 2004 to 2014. Serum samples (n = 1124) were collected from participants recruited for various studies from Bexar County and Lubbock County, TX, over the span of 2004 through 2014. The exposure biomarker, serum AFB1-lysine adduct, was analyzed by HPLC-FLD and confirmed by LC-MS. Both populations showed a significant increase in detection rate, as well as median levels of serum AFB1-lysine adduct over time, from 2.35 to 4.34 pg/mg albumin in East Texas (2007-2014), and 0.63-3.98 pg/mg albumin in West Texas (2004-2010). This observed shift in exposure likely represents a shift in the AF contamination pattern in the State of Texas, and may warrant further studies on risk assessment for the potential etiological effects of such increased exposures.

Nutrition and growth outcomes are affected by aflatoxin exposures in Kenyan children.

Aflatoxin exposure, malnutrition and growth impairment in children present significant public health problems in low- and middle-income countries. Recent epidemiology studies show that exposure to aflatoxins through dietary sources in early life contributes to growth retardation among children. However, the findings remain inconclusive due to limited comparative studies in high versus low aflatoxin exposure regions. This cross-sectional study presents aflatoxin exposure levels among children aged 6 to 12 years, and further evaluates the association between aflatoxin exposure levels, malnutrition and growth impairment in Kenya, East Africa. AFB1-lysine adducts are validated biomarkers of exposure and were quantified using HPLC with fluorescence detection. All children (n = 746) had detectable levels of AFB1-lysine adducts in serum, range 0.65-518.9 pg/mg albumin with a geometric mean (GM) of 10.5 (95%CI 9.4-11.7) pg/mg albumin. The Geometric Means (GM) of AFB1-lysine adducts were 14.0 (95%CI 12.5, 15.7) pg/mg albumin and 8.2 (95%CI 7.6, 8.8) pg/mg albumin (p-value < 0.001), among children recruited from Makueni and Siaya Counties, respectively. While the study confirms higher human exposure levels in Makueni county, it provides an initial data set for aflatoxin exposure levels among children recruited from Siaya County. In multivariate analysis, after adjusting for socio-economic indicators, farming practices, and household dietary patterns, increasing one unit of log AFB1-lysine was associated with decreasing Weight-for-age z-score (WAZ) by -0.13, p-value = 0.019 among all children aged 6-12 years. Among children 6 to 9 years, WAZ decreases by -0.11 (-0.54, -0.01), p-value = 0.049. Additional growth parameters Height-for-age z-score (HAZ) and Weight-for-height z-score (WHZ) do not reach statistical significance. HAZ decreases by -0.08, p-value = 0.337 and WHZ decreases by -0.17, p-value = 0.437 with every increase in log AFB1-lysine. These data suggest that efforts must be put in place to control for aflatoxin exposure in order to achieve better growth outcomes.

Detoxification mechanisms of nickel sulfate in nematode Caenorhabditis elegans.

Nickel is the most prevailing metal allergen with the highest sensitization rate among the "TOP 25" contact allergens and can affect about 15% of the human population. It is an essential trace metal in plants, animals, and humans. However, the environmental levels of nickel are considerably higher than what is needed for human life. Exposure to high levels of nickel can lead to skin allergies, lung fibrosis, and carcinogenesis. Few existing studies have closely examined the toxicity of nickel, let alone investigated the effective detoxification pathways. Here, we developed a high-throughput screening platform to comprehensively evaluate the nickel toxicity in wild-type C. elegans and explore the underlying detoxification mechanisms in transgenic nematodes. We demonstrated that nickel exerted multiple toxic effects on growth, brood size, feeding, and locomotion in C. elegans. Of which, brood size is the most sensitive endpoint. Nickel was found to first bind to phytochelatin (PC) after entering the worms' body and this PC-Ni complex was further transported by the ABC transporter, CeHMT-1, into the coelomocytes for further detoxification. Our study also demonstrated that the high-throughput screening platform is a promising system for evaluation and investigation of the ecological risks of heavy metals.

Dietary determinants of aflatoxin B1-lysine adduct in pregnant women consuming a rice-dominated diet in Nepal.

BACKGROUND: Aflatoxins are found in diverse foods widely consumed worldwide. This study investigated the association between aflatoxin exposure and (a) consumption of specific foods, (b) dietary diversity (DD), and (c) seasonality. METHODS: Women enrolled in the AflaCohort Study in Banke, Nepal (n = 1648) were asked how often they ate certain food items in the past 7 days and 24 h. Serum aflatoxin B1-lysine (AFB1-lys) adduct levels, measured during pregnancy, were determined using high-performance liquid chromatography. Multivariable ordinary least squares and quantile regression models were used to examine incremental increases in AFB1-lys adduct levels per frequency of food consumption and the relationship between DD, seasonality, and increases in AFB1-lys adduct. RESULTS: Roughly 94% of women were exposed to aflatoxin (geometric mean 1.37 pg/mg). Women in the 30th, 50th, and 70th quantiles of aflatoxin exposure who reported one more occasion of maize consumption in the past week showed increases in AFB1-lys adduct levels: 0.094, 0.112, and 0.109 pg/mg (p < 0.05, all). Women in the 30th, 50th, 70th, and 90th quantiles of exposure who reported one more occasion of groundnut consumption in the past week also showed increases in AFB1-lys adduct levels: 0.058 (p < 0.001), 0.085 (p < 0.01), 0.133 (p < 0.001), and 0.133 (p < 0.001) pg/mg. Winter month recruitment was positively associated with AFB1-lys adduct levels at all quantiles of aflatoxin exposure (range: 0.313-1.101 pg/mg, p < 0.001). DD was not predictive of aflatoxin exposure. CONCLUSIONS: Our findings justify integrated approaches to aflatoxin reduction, including regulatory, agricultural, and food safety interventions across the value chain and at the household level.

Aflatoxin in household maize for human consumption in Kenya, East Africa.

The objective of this study is to determine the occurrence and level of aflatoxins (AFs) contamination in freshly harvested maize for human consumption in rural Kenya. Maize kernels and freshly milled maize flour (n = 338) were collected from households in Siaya and Makueni counties. While both counties are representatives of different environmental and climate conditions, Makueni County is the area with reported outbreaks of aflatoxicosis. Samples were analysed for AFB1, AFB2, AFG1, and AFG2 using Ultra High-Pressure Liquid Chromatography with Fluorescence detection. AFs were detected in 100% of the samples with the range of 2.14-411 µg/kg. The geometric mean of total AFs in all samples from Makueni County is 62.5 µg/kg with 95% CI: 53.7, 71.4 while in Siaya County is 52.8 µg/kg with 95% CI: 44.0, 61.7. This study showed that AFs contamination is prevalent in maize-based foods in the region.

Mycotoxin exposure is associated with increased risk of esophageal squamous cell carcinoma in Huaian area, China.

BACKGROUND: Consumption of moldy food has previously been identified as a risk factor for esophageal squamous cell carcinoma (ESCC) in high-risk countries; however, what contributing roles these dietary carcinogenic mycotoxins play in the etiology of ESCC are largely unknown. METHODS: A mycotoxin biomarker-incorporated, population-based case-control study was performed in Huaian area, Jiangsu Province, one of the two high-risk areas in China. Exposure biomarkers of aflatoxins (AF) and fumonisins (FN) were quantitatively analyzed using HPLC-fluorescence techniques. RESULTS: Among the cases (n = 190), the median levels of AF biomarker, serum AFB1-lysine adduct, and FN biomarker, urinary FB1, were 1.77 pg/mg albumin and 176.13 pg/mg creatinine, respectively. Among the controls (n = 380), the median levels of AFB1-lysine adduct and urinary FB1 were 1.49 pg/mg albumin and 56.92 pg/mg creatinine, respectively. These mycotoxin exposure biomarker levels were significantly higher in cases as compared to controls (p <  0.05 and 0.01, respectively). An increased risk to ESCC was associated with exposure to both AFB1 and FB1 (p <  0.001 for both). CONCLUSIONS: Mycotoxin exposure, especially to AFB1 and FB1, was associated with the risk of ESCC, and a greater-than-additive interaction between co-exposures to these two mycotoxins may contribute to the increased risk of ESCC in Huaian area, China.

High-throughput assessment of toxic effects of metal mixtures of cadmium(Cd), lead(Pb), and manganese(Mn) in nematode Caenorhabditis elegans.

Heavy metals, a class of persistent environmental toxicants, are harmful to human health. Cd and Pb are two of the most common toxic heavy metals that have been linked with cancers and malfunction of the nervous system. Notably, contamination of Mn usually coexisted with Cd and Pb in environmental and occupational settings. Studies regularly examined the toxic effects on individual metals; however, potential health and toxic effects of mixtures containing two or more heavy metals are unknown. Here, we investigated toxic effects of Cd, Pb, Mn, and their binary and ternary mixtures in the nematode Caenorhabdities elegans. The toxic outcomes, including effects on growth, reproduction, and feeding, were measured via high-throughput platform analysis. The transgenic strain BY250 with GFP in dopaminergic neurons was used to explore the neurodegenerative effects induced by single metals or their mixtures. The combination index(CI) for mixtures effect was calculated using isobolograms methods. Following the exposure, we found significant toxic effects in C. elegans. For single metals, the toxicity order for growth, reproduction, and feeding were Pb > Cd > Mn. For mixtures, the mixture of Cd + Mn induced a less than addictive effect in C. elegans, whereas the mixtures of Cd + Pb, Pb + Mn, and Cd + Pb + Mn induced greater-than-additive effects. Both single metals and their mixtures induced abnormality in dopaminergic neurons. These results showed combinative toxic and neurodegenerative effects of heavy metal mixtures, and future studies will focus on characterization of concentration-response patterns and identification of potential molecular mechanisms in C. elegans model.

Validation of urinary sphingolipid metabolites as biomarker of effect for fumonisins exposure in Kenyan children.

Context: Fumonisins (FNs), a group of mycotoxins produced mainly by Fusarium species, are ubiquitous food contaminants, especially for maize. Fumonisin B1 (FB1) caused severe toxicities in farm animals, induced kidney and liver tumours in rodents and is associated with many human adverse health effects, including oesophageal cancer. International Agency for Research on Cancer (IARC) categorizes FB1 as a possible human carcinogen (Group 2B). Inhibition of ceramide synthesis and disruption of sphingolipids metabolism are well studied as the major mechanisms of FB1-induced toxicity. Increases in sphinganine (Sa) and decrease in sphingosine (So) levels and their ratio are validated biomarkers of FB1 effects. Methods: In this study, we measured urinary levels of Sa, So and Sa/So in 284 children aged 1-14 years who consume maize as a staple diet. Exfoliated cells from urine were processed and sphingolipids quantified by High Pressure Liquid Chromatography. Results and conclusions: Sa and So were detectable in 95.07% and 98.94% of samples, respectively. Creatinine adjusted mean levels and standard deviation of Sa, So and Sa/So ratio were 1.23 ± 2.18, 4.99 ± 8.3 and 0.296 ± 0.587 nM. These results further confirmed the findings in studies with human adults, i.e. urinary Sa, So levels and Sa/So ratio are good biomarkers to assess FNs exposure in children.

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-ß: 0.07; 95% CI: -0.13, -0.003; p = 0.040), lower weight-for-age z-score (adj-ß: -0.16; 95% CI: -0.30, -0.01; p = 0.037), smaller head circumference (adj-ß: -0.26; 95% CI: -0.49, -0.02; p = 0.035), and lower head circumference-for-age z-score (adj-ß: -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.