Intestinal Barrier Impairment Induced by Gut Microbiome and Its Metabolites in School-Age Children with Zinc Deficiency.

Zinc deficiency affects the physical and intellectual development of school-age children, while studies on the effects on intestinal microbes and metabolites in school-age children have not been reported. School-age children were enrolled to conduct anthropometric measurements and serum zinc and serum inflammatory factors detection, and children were divided into a zinc deficiency group (ZD) and control group (CK) based on the results of serum zinc. Stool samples were collected to conduct metagenome, metabolome, and diversity analysis, and species composition analysis, functional annotation, and correlation analysis were conducted to further explore the function and composition of the gut flora and metabolites of children with zinc deficiency. Beta-diversity analysis revealed a significantly different gut microbial community composition between ZD and CK groups. For instance, the relative abundances of Phocaeicola vulgatus, Alistipes putredinis, Bacteroides uniformis, Phocaeicola sp000434735, and Coprococcus eutactus were more enriched in the ZD group, while probiotic bacteria Bifidobacterium kashiwanohense showed the reverse trend. The functional profile of intestinal flora was also under the influence of zinc deficiency, as reflected by higher levels of various glycoside hydrolases in the ZD group. In addition, saccharin, the pro-inflammatory metabolites, and taurocholic acid, the potential factor inducing intestinal leakage, were higher in the ZD group. In conclusion, zinc deficiency may disturb the gut microbiome community and metabolic function profile of school-age children, potentially affecting human health.

Analysis of similarities and differences between transient symptomatic zinc deficiency and acrodermatitis enteropathica in children: a case report of a Chinese Yi-ethnic infant.

BACKGROUND: Transient symptomatic zinc deficiency (TSZD), an acquired type of zinc deficiency, is a rare, but probably underrecognized disease, extremely in breastfed premature with low birthweight infants. Its clinical manefestations are similar to Acrodermatitis enteropathica (AE), which is a genetic zinc absorption disorder caused by SLC39A4 gene mutations. This gene encodes a member of the zinc/iron-regulated transporter-like protein (ZIP) family. The encoded protein localizes to cell membranes and is required for zinc uptake in the intestine. TSZD is often misdiagnosed as AE because of their extremely similar manefestations, characterized by a typical rash. Therefore, the differention between them is still a clinical challenging. CASE PRESENTATION: Here, we present a case of TSZD in a 4 month and 23 days female Chinese Yi-ethnic premature with AE-like skin lesions, mainly presenting periorificial, perianal and perineal crusted, eroded, erythemato-squamous eruption. Laboratory examination showed the patient's blood zinc level was significantly decreased. Further sequencing of the SLC39A4 gene showed no mutation in the infant and her parents. Skin lesions significantly improved after 6 days of initial zinc supplementation (3 mg/kg/d), and maintenance treatment with 1 mg/kg/day of zinc was discontinued after 8 months without recurrence. CONCLUSIONS: The clinical manifestations of TSZD and AE are extremely similar, leading to a high rate of clinical misdiagnosis. While genetic analysis of the SLC39A4 gene is a reliable method for differentiating TSZD from AE. It is recommended that SLC39A4 gene test should be performed as far as possible in children with AE-like rash.

Are the elements zinc, copper, magnesium, and rubidium related to nutrition and iodine deficiency in pregnant Bulgarian women from iodine deficient region?

OBJECTIVE: Trace elements are essential for the biochemistry of the cell. Their reference values have been found to differ considerably in pregnant women stratified by age, place of residence, anthropometric status, and length of pregnancy. In optimal amounts, these elements reduce the risk of pregnancy complications. Subclinical hypothyroidism in pregnancy is associated with adverse maternal and neonatal outcomes. The aim of the study was to determine the effects of zinc (Zn), copper (Cu), magnesium (Mg), and rubidium (Rb) on pregnant women in an iodine deficiency region and find the relationship with the thyroid status and nutrition. METHODS: We evaluated the iodine status of 61 healthy pregnant women from an iodine deficient region in Bulgaria. Thyroid stimulating hormone (TSH) and thyroxin free (FT4) levels were measured using ELISA. RESULTS: We found elevated levels of copper that differed the most between the first and second trimesters; Cu and TSH were found to be positively correlated (р < 0.05). Lower Cu levels were found in pregnant women consuming pulses more than 2-3 times a week (р = 0.033). The women consuming fish more than 2-3 times a week had higher levels of Rb. We found a pronounced iodine deficiency in more than half of the examined women in the first to third trimesters, without any effect of pregnancy on the ioduria (р=0.834). All second and third trimester cases were associated with severe ioduria (< 150 µg/L). CONCLUSION: The high Cu levels were associated with subclinical hypothyroidism (SCH) and less pulse consumption during pregnancy in an iodine deficiency endemic area. SCH was found in 24% of the pregnant women in such an area while in 13% of them SCH had progressed to overt hypothyroidism.

Enhancing Nutritional Status and Addressing Micronutrient Deficiencies: Evaluating the Impact of Workplace Nutrition Program on Female Workers in Vietnam.

This randomized controlled clinical study aimed to assess the effectiveness of a nutrition intervention program for non-pregnant female workers in Vietnam. A total of 500 female workers were randomly assigned to the intervention and control groups. Participants in the intervention group were provided nutrition education, personalized specific dietary, and received oral nutrition supplements (ONS)-which contained multi-minerals and vitamins according to recommendations for adults for a duration of 12 wk, while participants in the control group received only nutrition education. The result shows the percentage of malnutrition by BMI in the control group rose from 15.6% to 21.3% after 12 wk; the figure for counterpart experienced a remain unchanged (p<0.05). Additionally, the mean of serum zinc in the intervention group significantly increased from 49.0±21.2 µg/dL to 53.6±19.5 µg/dL after 12 wk. Moreover, the intervention group demonstrated significant increases in serum iron and total serum calcium levels (p<0.05), with from 13.9±5.6 µmol/L to 15.3±5.8 µmol/L, and from 2.36±0.15 mmol/L to 2.4±0.09 mmol/L, respectively. The participants of the intervention group were more likely to have higher total serum calcium (Coef=0.04, p<0.05), serum iron (Coef=1.99, p<0.05), and serum zinc (Coef=18.9, p<0.05), which presents a reduce micronutrient deficiency. In conclusion, workplace nutrition interventions effectively mitigate micronutrient deficiencies and improve the nutritional status of female workers.

Zinc and Chronic Kidney Disease: A Review.

Chronic kidney disease (CKD) poses a major global public health challenge. The World Health Organization's data shows that CKD affects about 10% of the world's population, particularly in low- and middle-income countries. Due to limited access to diagnosis and treatment, CKD has become the 12th leading cause of death worldwide. The advanced stage of CKD can lead to kidney failure, which is clinically referred to as end-stage renal disease (ESRD). In such cases, patients can only sustain life through dialysis or kidney transplantation. However, the long-term affordability of these treatments remains low. Moreover, the effectiveness of kidney transplantation is modest, posing a significant treatment barrier in resource-limited settings, and significantly impacting patient survival. To address this issue, we suggest using dietary supplementation of the trace element zinc to impede CKD development and prolong patient survival.

Transient Zn2+ deficiency induces replication stress and compromises daughter cell proliferation.

Cells must replicate their genome quickly and accurately, and they require metabolites and cofactors to do so. Ionic zinc (Zn2+) is an essential micronutrient that is required for hundreds of cellular processes, including DNA synthesis and adequate proliferation. Deficiency in this micronutrient impairs DNA synthesis and inhibits proliferation, but the mechanism is unknown. Using fluorescent reporters to track single cells via long-term live-cell imaging, we find that Zn2+ is required at the G1/S transition and during S phase for timely completion of S phase. A short pulse of Zn2+ deficiency impairs DNA synthesis and increases markers of replication stress. These markers of replication stress are reversed upon resupply of Zn2+. Finally, we find that if Zn2+ is chelated during the mother cell's S phase, daughter cells enter a transient quiescent state, maintained by sustained expression of p21, which disappears upon reentry into the cell cycle. In summary, short pulses of mild Zn2+ deficiency in S phase specifically induce replication stress, which causes downstream proliferation impairments in daughter cells.

Nutrition: Micronutrients.

Micronutrients are nutrients the body needs in small quantities, such as vitamins and minerals. Micronutrient deficiencies can occur when an individual is restricting calorie intake for weight loss or management, not consuming an adequate amount of food to meet energy requirements due to poor appetite or illness, eliminating one or more food groups from the diet on a regular basis, or consuming a diet low in micronutrient-rich foods despite adequate or excessive energy intake. Patient groups at risk include older adults, pregnant patients, patients with alcohol use disorder, patients with vegetarian or vegan diets, and patients with increased requirements secondary to medical conditions or long-term drug use that alters nutrient absorption, metabolism, or excretion. The micronutrients that most commonly require supplementation are vitamin D, iron, vitamin A, zinc, folate, and iodine. Results of large-scale randomized trials have shown no overall benefit of multivitamins for the majority of patients. However, a daily multivitamin may be beneficial, particularly for patients who do not consistently consume a well-balanced diet. Although dietary supplements can be helpful in correcting deficiencies, higher than recommended doses can cause adverse effects. Patients should be advised to take recommended dosages of supplements and consult their physician if they notice any adverse effects. Physicians should advise patients to consult drug labels and/or pharmacists about potential supplement interactions with drugs or other supplements.

Strategies for inducing and validating zinc deficiency and zinc repletion.

Given the growing interest in the role of zinc in the onset and progression of diseases, there is a crucial demand for reliable methods to modulate zinc homeostasis. Using a dietary approach, we provide validated strategies to alter whole-body zinc in mice, applicable across species. For confirmation of zinc status, animal growth rates as well as plasma and urine zinc levels were evaluated. The accessible and cost-effective methodology outlined will increase scientific rigor, ensuring reproducibility in studies exploring the impact of zinc deficiency and repletion on the onset and progression of diseases.NEW & NOTEWORTHY This methods paper details dietary approaches to alter zinc homeostasis in rodents and qualitative and quantitative methods to ensure the zinc status of experimental animals. The outlined accessible and cost-effective protocol will elevate scientific rigor, ensuring reproducibility in studies exploring the impact of zinc deficiency and repletion on the onset and progression of a multitude of health conditions and diseases.

Role of zinc in health and disease.

This review provides a concise overview of the cellular and clinical aspects of the role of zinc, an essential micronutrient, in human physiology and discusses zinc-related pathological states. Zinc cannot be stored in significant amounts, so regular dietary intake is essential. ZIP4 and/or ZnT5B transport dietary zinc ions from the duodenum into the enterocyte, ZnT1 transports zinc ions from the enterocyte into the circulation, and ZnT5B (bidirectional zinc transporter) facilitates endogenous zinc secretion into the intestinal lumen. Putative promoters of zinc absorption that increase its bioavailability include amino acids released from protein digestion and citrate, whereas dietary phytates, casein and calcium can reduce zinc bioavailability. In circulation, 70% of zinc is bound to albumin, and the majority in the body is found in skeletal muscle and bone. Zinc excretion is via faeces (predominantly), urine, sweat, menstrual flow and semen. Excessive zinc intake can inhibit the absorption of copper and iron, leading to copper deficiency and anaemia, respectively. Zinc toxicity can adversely affect the lipid profile and immune system, and its treatment depends on the mode of zinc acquisition. Acquired zinc deficiency usually presents later in life alongside risk factors like malabsorption syndromes, but medications like diuretics and angiotensin-receptor blockers can also cause zinc deficiency. Inherited zinc deficiency condition acrodermatitis enteropathica, which occurs due to mutation in the SLC39A4 gene (encoding ZIP4), presents from birth. Treatment involves zinc supplementation via zinc gluconate, zinc sulphate or zinc chloride. Notably, oral zinc supplementation may decrease the absorption of drugs like ciprofloxacin, doxycycline and risedronate.

Demographic and clinical characteristics of patients with zinc deficiency: analysis of a nationwide Japanese medical claims database.

Zinc deficiency, affecting more than 2 billion people globally, poses a significant public health burden due to its numerous unfavorable effects, such as impaired immune function, taste and smell disorders, pneumonia, growth retardation, visual impairment, and skin disorders. Despite its critical role, extensive large-scale studies investigating the correlation between patient characteristics and zinc deficiency still need to be completed. We conducted a retrospective, cross-sectional observational study using a nationwide Japanese claims database from January 2019 to December 2021. The study population included 13,100 patients with available serum zinc concentration data, excluding individuals under 20 and those assessed for zinc concentrations after being prescribed zinc-containing medication. Significant associations with zinc deficiency were noted among older adults, males, and inpatients. Multivariate analysis, adjusting for age and sex, indicated significant associations with comorbidities, including pneumonitis due to solids and liquids with an adjusted Odds Ratio (aOR) of 2.959; decubitus ulcer and pressure area (aOR 2.403), sarcopenia (aOR 2.217), COVID-19 (aOR 1.889), and chronic kidney disease (aOR 1.835). Significant association with medications, including spironolactone (aOR 2.523), systemic antibacterials (aOR 2.419), furosemide (aOR 2.138), antianemic preparations (aOR 2.027), and thyroid hormones (aOR 1.864) were also found. These results may aid clinicians in identifying patients at risk of zinc deficiency, potentially improving care outcomes.

Zinc deficiency or genetic mutations?-A case report of hair heterochromia in the context of MC1R genetic mutations.

Hair heterochromia may be caused by different mechanisms. At clinical work, we found a Chinese boy whose hair colour gradually turned to red. We record the diagnosis and treatment process and follow-up situation, finally find that altered hair colour phenotype is due to MC1R genetic mutations, rather than zinc deficiency. This rarely red hair colour phenotype improve our understanding of hair heterochromia caused by genetic mutations.

Dietary zinc inadequacy affects neurotrophic factors and proteostasis in the rat brain.

Zinc (Zn) deficiency has many adverse effects, including growth retardation, loss of appetite, vascular diseases, cognitive and memory impairment, and neurodegenerative diseases. In the current study, we investigated the hypothesis that dietary Zn inadequacy affects neurotrophic factors and proteostasis in the brain. Three-week-old Wistar/Kyoto male rats were fed either a Zn-deficient diet (D; < 1 mg Zn/kg diet; n = 18) or pair-fed with the control diet (C; 48 mg Zn/kg diet; n = 9) for 4 weeks. Subsequently, the rats in the D group were subdivided into two groups (n = 9), in which one group continued to receive a Zn-deficient diet, whereas the other received a Zn-supplemented diet (R; 48 mg Zn/kg diet) for 3 more weeks, after which the rats were sacrificed to collect their brain tissue. Markers of endoplasmic reticulum stress, ubiquitin-proteasome system, autophagy, and apoptosis, along with neurotrophic factors, were investigated by immunoblotting. Proteasomal activity was analyzed by the spectrofluorometric method. The results showed an altered ubiquitin-proteasome system and autophagy components and increased gliosis, endoplasmic reticulum stress, and apoptosis markers in Zn-deficient rats compared with the control group. Zinc repletion for 3 weeks could partially restore these alterations, indicating a necessity for an extended duration of Zn supplementation. In conclusion, a decline in Zn concentrations below a critical threshold may trigger multiple pathways, leading to brain-cell apoptosis.

Study on the Zinc Nutritional Status and Risk Factors of Chinese 6-18-Year-Old Children.

Zinc is an essential micronutrient that is involved in several metabolic processes, especially children's growth and development. Although many previous studies have evaluated the zinc nutritional status of children, there are very few reports on children aged 6-18 years old. Furthermore, there are few reports on children's zinc nutrition status based on the Chinese population. According to WHO data, the prevalence of zinc deficiency in Asian countries is rather high and has resulted in high child mortality. In this study, we aimed to comprehensively assess zinc nutritional status and the prevalence of zinc deficiency among children aged 6-18 years in China based on nationally representative cross-sectional data. Subgroup comparisons were made under possible influencing factors. The potential risk factors of zinc deficiency were also discussed. A total of 64,850 children, equally male and female, were recruited from 150 monitoring sites in 31 provinces through stratified random sampling from China National Nutrition and Health Survey of Children and Lactating Mothers (CNNHS 2016-2017). Median and interquartile intervals were used to represent the overall zinc concentration levels and different subgroups. A Chi-square test was used to compare serum zinc levels and the prevalence of zinc deficiency in children under different group variables. In order to study the influencing factors of zinc deficiency, multiple logistic regression was utilized. It was found that the median concentration of serum Zn was 88.39 µg/dL and the prevalence of Zn deficiency was 9.62%. The possible influence factors for Zn deficiency were sex, anemia, nutritional status, city type and income. By conducting a subgroup analysis of the factors, it was found that males; those with anemia, stunting and low income; and children living in rural areas have a higher risk of Zn deficiency. This study offers a comprehensive analysis of Zn nutritional status among Chinese children, which provides reliable data for policy formulation to improve the zinc nutrition status of children.

A Potential Association of Zinc Deficiency and Tyrosine Kinase Inhibitor-Induced Hand-Foot Skin Reaction.

Hand-foot skin reaction (HFSR) is a common skin-related adverse event induced by multikinase inhibitors targeting both platelet-derived growth factor receptor and vascular endothelial growth factor receptor, possibly due to inadequate repair following frictional trauma. Zinc is a trace element and essential nutrient in humans that plays critical roles in the development and differentiation of skin cells. Zinc transporters (Zrt- and Irt-like proteins and Zn transporters) and metallothioneins are involved in zinc efflux, uptake, and homeostasis and have been reported to be involved in skin differentiation. The underlying mechanism of HFSR remains unclear, and the association between HFSR and zinc has not been previously studied. However, some case reports and case series provide potential evidence to suggest that zinc deficiency may be involved in HFSR development and zinc supplementation may relieve HFSR symptoms. However, no large-scale clinical studies have been conducted to examine this role. Therefore, this review summarizes the evidence supporting a possible link between HFSR development and zinc and proposes potential mechanisms underlying this association based on current evidence.

Dietary zinc deficient condition increases the Bisphenol A toxicity in diabetic rat testes.

Bisphenol A (BPA) is a widely used endocrine disrupter that causes male reproductive dysfunction in humans and rodents. Diabetes-induced hyperglycemia alters spermatogenesis and antioxidant status, which negatively impacts male fertility in adults. Zinc (Zn) deficiency is a global health concern maintaining the testicular structure and functions in developing gonads. The present experiment was designed to investigate the role of Zn deficiency on BPA-induced germ cell and male gonadal toxicity in diabetic conditions. Rats were randomly divided into eight different groups - control (normal feed and water), BPA (10 mg/kg/day), ZDD (fed with a Zn-deficient diet), DIA (diabetic), BPA+ZDD, BPA+DIA, ZDD+DIA and BPA+ZDD+DIA for four weeks. Animals' body and organ weight, sperm count, motility and sperm morphology were examined; testes and epididymis histopathology were investigated. Testicular DNA damage and sperm apoptosis were evaluated by halo and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays respectively. Testicular catalase and octamer-binding transcription factor 4 (OCT4) expressions were evaluated by western blot analysis. The present results demonstrated that dietary Zn-deficient condition significantly increased the BPA-induced testicular, epididymal and sperm toxicity in diabetic rats due to hypogonadism, increased sperm abnormalities, epididymis, testicular structure and DNA damages, sperm apoptosis as well as decreased testicular catalase and OCT4 expressions. The present results revealed that dietary Zn-deficient condition exacerbated the BPA-induced testicular and epididymal toxicity as well as perturbed the general male reproductive health in diabetic rats.

Zinc deficiency and associated factors among pregnant women's attending antenatal clinics in public health facilities of Konso Zone, Southern Ethiopia.

BACKGROUND: Zinc is an essential mineral known to be important for the normal physiological functions of the immune system. It is one of the basic nutrients required during pregnancy for the normal development and growth of the fetus. However, Zinc deficiency during pregnancy causes irreversible effects on the newborn such as growth impairment, spontaneous abortion, congenital malformations and poor birth outcomes. Even though, the effect of Zinc deficiency is devastating during pregnancy, there is scarcity of evidence on Zinc deficiency and related factors among pregnant women in the current study area. OBJECTIVE: To assess Zinc deficiency and associated factors among pregnant women attending antenatal clinics in public health facilities of Konso Zone, Southern Ethiopia. METHODS: Institution based cross-sectional study was conducted among randomly selected 424 pregnant mothers. Data were collected using pre tested questionnaire (for interview part), and 5 blood sample was drawn for serum zinc level determination. Data were entered to Epi-Data version 3.1 software and exported to SPSS version 25 for analysis. Binary logistic regression analysis was computed and independent variables with a p-value ≤ 0.25 were included in multivariable analysis. Serum zinc level was determined using atomic absorption spectroscopy by applying clean and standard procedures in the laboratory. Finally adjusted odds ratio with 95% confidence level, P-value < 0.05 was used to identify significant factors for Zinc deficiency. RESULT: The prevalence of Zinc deficiency was found to be 128 (30.26%) with the mean serum zinc level of 0.56±0.12 g/dl. Age, 25-34 years [AOR 2.14 (1.19,3.82)], and 35-49 years [AOR 2.59 (1.15, 5.85)], type of occupation, farming [AOR 6.17 (1.36, 28.06)], lack of antenatal follow up during pregnancy [AOR 3.57 (1.05,12.14)], lack of freedom to purchase food items from market [AOR 3.61 (1.27, 10.27)], and inadequate knowledge on nutrition [AOR 3.10(1.58, 6.08)] were factors associated with Zinc deficiency. CONCLUSION: Zinc deficiency is a public health problem among pregnant mothers in the current study area. Improving maternal nutritional knowledge, motivating to have frequent antenatal follow up, and empowering to have financial freedom to purchase food items from market were the modifiable factors to reduce Zinc deficiency. Nutritional intervention that focused on improving nutritional knowledge and insuring access to Zinc sources food items should be delivered for pregnant mothers.

Impact of Zinc Transport Mechanisms on Embryonic and Brain Development.

The trace element zinc (Zn) binds to over ten percent of proteins in eukaryotic cells. Zn flexible chemistry allows it to regulate the activity of hundreds of enzymes and influence scores of metabolic processes in cells throughout the body. Deficiency of Zn in humans has a profound effect on development and in adults later in life, particularly in the brain, where Zn deficiency is linked to several neurological disorders. In this review, we will summarize the importance of Zn during development through a description of the outcomes of both genetic and early dietary Zn deficiency, focusing on the pathological consequences on the whole body and brain. The epidemiology and the symptomology of Zn deficiency in humans will be described, including the most studied inherited Zn deficiency disease, Acrodermatitis enteropathica. In addition, we will give an overview of the different forms and animal models of Zn deficiency, as well as the 24 Zn transporters, distributed into two families: the ZIPs and the ZnTs, which control the balance of Zn throughout the body. Lastly, we will describe the TRPM7 ion channel, which was recently shown to contribute to intestinal Zn absorption and has its own significant impact on early embryonic development.