Autism spectrum disorder (ASD) is a heterogeneous and complex group of life-long neurodevelopmental disorders. How this clinical condition impacts an individual’s intellectual, social and emotional capacities, contributing to alterations in the proprioceptive and sensory systems and increasing their selective attitude towards food, is well described in the literature. This complex condition or status exposes individuals with ASD to an increased risk of developing overweight, obesity and non-communicable diseases compared with the neurotypical population. Moreover, individuals with ASD are characterised by higher levels of inflammation, oxidative stress markers and intestinal dysbiosis. All these clinical features may also appear in zinc deficiency (ZD) condition. In fact, zinc is an essential micronutrient for human health, serving as a structural, catalytic and regulatory component in numerous physiological processes. The aim of this narrative review is to explore role of ZD in ASD. Factors affecting zinc absorption, excretion and dietary intake in this vulnerable population are taken into consideration. Starting from this manuscript, the authors encourage future research to investigate the role of ZD in ASD. The perspective is to potentially find another missing piece in the ‘ASD clinical puzzle picture’ to improve the health status of these individuals.

Zinc deficiency (ZD) during pregnancy has far-reaching consequences on the mother, fetus and subsequent child survival. Therefore, the present study aimed to assess the prevalence and associated factors of ZD among pregnant women around Lake Awasa, Hawassa City, Ethiopia. To this end, a facility-based cross-sectional study was conducted on 333 randomly sampled pregnant women from 08 April to 08 May 2021. The socio-economic, dietary intake, water, sanitation and hygiene, obstetric, and maternal health data were collected through face-to-face interviews. Moreover, on-spot blood and stool samples were taken. Descriptive statistics and binary and multivariable logistic regression analysis were conducted. The prevalence of ZD was 58⋅6 % (95 % CI 53⋅31, 63⋅89). The poorest (AOR = 3⋅28; 95 % CI 1⋅26, 8⋅50) and poor (AOR = 2⋅93; 95 % CI 1⋅14, 7⋅54) wealth quintiles, four of more family size (AOR = 1⋅84, 95 % CI 1⋅10, 3⋅35), poor dietary diversity (AOR = 4⋅11; 95 % CI 2⋅11, 7⋅62), not eating snacks (AOR = 3⋅40; 95 % CI 1⋅42, 8⋅15), not consuming fish (AOR = 3⋅53; 95 % CI 1⋅65, 7⋅56) and chicken (AOR = 2⋅53; 95 % CI 1⋅31, 4⋅88) at least once a month, and intestinal parasitic infection (AOR = 2⋅78; 95 % CI 1⋅52, 5⋅08) predicted zinc deficiency. In conclusion, ZD is a public health problem among pregnant women around Lake Awasa. The present study demonstrated that poor socio-economic status, large family size, poor nutritional practices and intestinal parasitic infection determine the zinc status in the present study area. The findings suggest the need for further analysis to deepen the understanding about ZD and consideration of livelihood in interventions to prevent and control ZD among pregnant women in Hawassa City, Ethiopia.

Zinc (Zn) is an essential mineral and its deficiency manifests in non-specific clinical signs that require long time to develop. The response of swine intestine to Zn restriction was evaluated to identify early changes that can be indicative of Zn deficiency. Twenty-seven pigs (body weight = 77⋅5 ± 2⋅5 kg) were assigned to one of three diets: diet without added Zn (Zn-restricted diet, ZnR), and ZnR-supplemented with either 50 (Zn50) or 100 mg of Zn/kg of diet (Zn100) of Zn supplied by ZnCl2. After 32 d consuming the diets, serum Zn concentration in ZnR pigs was below the range of 0⋅59–1⋅37 μg/ml considered sufficient, thereby confirming subclinical Zn deficiency. Pigs showed no obvious health or growth changes. RNA-seq analysis followed by qPCR showed decreased expression of metallothionein-1 (MT1) (P < 0⋅05) and increased expression of Zn transporter ZIP4 (P < 0⋅05) in jejunum and ileum of ZnR pigs compared with Zn-supplemented pigs. Ingenuity pathway analysis revealed that Zn50 and Zn100 induced changes in genes related to nucleotide excision repair and integrin signalling pathways. The top gene network in the ZnR group compared with Zn100 was related to lipid and drug metabolism; and compared with Zn50, was related to cellular proliferation, assembly and organisation. Dietary Zn concentrations resulted in differences in genes related to immune pathways. Our analysis showed that small intestine presents changes associated with Zn deficiency after 32 d of Zn restriction, suggesting that the intestine could be a sentinel organ for Zn deficiency.

The importance of Zn for human health becomes obvious during Zn deficiency. Even mild insufficiencies of Zn cause alterations in haematopoiesis and immune functions, resulting in a proinflammatory phenotype and a disturbed redox metabolism. Although immune system malfunction has the most obvious effect, the functions of several tissue cell types are disturbed if Zn supply is limiting. Adhesion molecules and tight junction proteins decrease, while cell death increases, generating barrier dysfunction and possibly organ failure. Taken together, Zn deficiency both weakens the resistance of the human body towards pathogens and at the same time increases the danger of an overactive immune response that may cause tissue damage. The case numbers of Corona Virus Disease 19 (COVID-19) are still increasing, which is causing enormous problems for health systems and economies. There is an urgent need to reduce both the number of severe cases and the resulting deaths. While therapeutic options are still under investigation, and first vaccines have been approved, cost-effective ways to reduce the likelihood of or even prevent infection, and the transition from mild symptoms to more serious detrimental disease, are highly desirable. Nutritional supplementation might be an effective option to achieve these aims. In this review, we discuss known Zn deficiency effects in the context of an infection with Severe Acute Respiratory Syndrome-Coronavirus-2 and its currently known pathogenic mechanisms and elaborate on how severe pre-existing Zn deficiency may pre-dispose patients to a severe progression of COVID-19. First published clinical data on the association of Zn homoeostasis with COVID-19 and registered studies in progress are listed.

Bangladesh is a country with a high burden of micronutrient malnutrition. Stunting affects 41 % of children aged under 5 years. Zn is one of the key micronutrients that is associated with stunting. The present study, as part of the national micronutrient survey 2011–2012, revealed for the first time the nationally representative prevalence of Zn deficiency and determined the associations of the condition. A cross-sectional ‘nationwide’ survey was conducted in pre-school-age children (6–59 months; PSAC) and non-pregnant non-lactating women (15–49 years; NPNLW). Multistage random sampling was done in 150 clusters; fifty in each of the rural, urban and slum strata. Data were analysed on 662 PSAC and 1073 NPNLW. Serum Zn was assayed by atomic absorption spectrophotometry. Zn deficiency was defined as serum Zn of <9·9 and <10·1 µmol/l in PSAC and NPNLW, respectively. The national prevalence of Zn deficiency was 44·6 and 57·3 % in PSAC and NPNLW, respectively. In PSAC, it was 29·5, 48·6 and 51·7 %, respectively, in urban, rural and slum strata. Household expenses (β = 0·13; P = 0·007), Hb (β = 0·10; P = 0·005), intake of animal-source Zn (β = 0·096; P = 0·02) and asset score (β = 0·11; P = 0·03) were positively associated with serum Zn in NPNLW. Residence in an urban area (β = 0·33; P = 0·03) and intake of plant-origin Zn (β = −0·13; P = 0·038) determined higher and lower status of Zn in PSAC, respectively. Zn deficiency was highly prevalent in Bangladesh, and it was principally related to inadequate quality of diet. To improve Zn nutrition, Bangladesh needs to strengthen research and programmes related to Zn biofortification, fortification and phytate-reducing technologies in the food system in the short and medium term. In addition, promotion of animal-source Zn for all is important in the long run.

This study investigated the effects of short-term subclinical Zn deficiency on exocrine pancreatic activity and changes in digestive capacity. A total of forty-eight weaned piglets were fed ad libitum a basal diet (maize and soyabean meal) with adequate Zn supply (88 mg Zn/kg diet) during a 2-week acclimatisation phase. Animals were then assigned to eight dietary treatment groups (n 6) according to a complete randomised block design considering litter, live weight and sex. All pigs were fed restrictively (450 g diet/d) the basal diet but with varying ZnSO4.7H2O additions, resulting in 28·1, 33·6, 38·8, 42·7, 47·5, 58·2, 67·8 and 88·0 mg Zn/kg diet for a total experimental period of 8 d. Pancreatic Zn concentrations and pancreatic activities of trypsin, chymotrypsin, carboxypeptidase A and B, elastase and α-amylase exhibited a broken-line response to stepwise reduction in dietary Zn by declining beneath thresholds of 39·0, 58·0, 58·0, 41·2, 47·5, 57·7 and 58·0 mg Zn/kg diet, respectively. Furthermore, carboxypeptidase B and α-amylase activities were significantly lower in samples with reduced pancreatic Zn contents. Coefficients of faecal digestibility of DM, crude protein, total lipids and crude ash responded similarly to pancreatic enzyme activities by declining below dietary thresholds of 54·7, 45·0, 46·9 and 58·2 mg Zn/kg diet, respectively. In conclusion, (1) subclinical Zn deficiency impaired pancreatic exocrine enzymes, (2) this response was connected to pancreatic Zn metabolism and (3) the decline in catalytic activity impaired faecal digestibility already after 1 week of insufficient alimentary Zn supply and very early before clinical deficiency symptoms arise.

Suboptimal intake of Zn is one of the most common nutritional problems worldwide. Previously, we have shown that Zn deficiency (ZD) produces oxidative and nitrosative stress in the lung of rats. We analyse the effect of moderate ZD on the expression of several intermediate filaments of the cytoskeleton, as well as the effect of restoring Zn during the refeeding period. Adult male rats were divided into three groups: Zn-adequate control (CO) group; ZD group; Zn-refeeding group. CerbB-2 and proliferating cell nuclear antigen (PCNA) expression was increased in the ZD group while the other parameters did not change. During the refeeding time, CerbB-2, cytokeratins, vimentin and PCNA immunostaining was higher than that in the CO group. The present findings indicate that the overexpression of some markers could lead to the fibrotic process in the lung. Perhaps ZD implications must be taken into account in health interventions because an inflammation environment is associated with ZD in the lung.

We examined the effect of dietary nicotinic acid (NA) variations before and after oxidative stress (OS) treatment on the antioxidant defence system, function and morphology of the liver along with Zn status in rats. OS was generated by three intraperitoneal injections of tert-butyl hydroperoxide in the first week for the pre-exposure group and in the third week for the post-exposure group, respectively. These groups were further divided into subgroups and fed on a diet with marginally deficient Zn (10 mg Zn/kg diet) and NA variations as NA deficient, normal and excess with 10, 30 and 1000 mg NA/kg diet, respectively. Aspartate aminotransferase and alanine aminotransferase levels were elevated in rats with OS coupled with the Zn- and NA-deficient diet, which decreased towards normal with excess dietary NA. Excess NA supplementation in the OS pre-exposure group resulted in nearly preserved hepatic architecture with normal hepatocytes, whereas maximum tissue destruction was evident in the post-exposure group with NA deficiency. Dose-dependent improvement in the antioxidant defence system, enhanced reduced glutathione levels, lowered lipid peroxidation and higher hepatic Zn levels were observed with NA supplementation. The effect was more prominent in the pre-exposure group. In conclusion, dietary NA supplementation improves hepatic Zn uptake and results in hepatoprotection against OS-induced damage in rats.

Patients with Fe-deficiency anaemia are often afflicted by hypotension. However, the mechanism of secondary hypotension in Fe-deficiency anaemia is unknown. To investigate the pathogenesis of secondary hypotension in Fe-deficiency anaemia, we examined the effects of Fe deprivation on plasma aldosterone concentration and blood pressure in rats. A total of forty 4-week-old male Sprague–Dawley rats were assigned into four treatment groups of ten each for the 4-week study: Fe-deficient group (FD), Zn-deficient group (ZD), Fe/Zn-deficient group (FZD) and control group (CON). At days 26 and 27, blood pressure was measured by the tail-cuff method. Plasma aldosterone concentration was determined by ELISA. The data were analysed by Tukey's multiple comparison test. Rats in the FZD had significantly lower mean blood pressure (P < 0·01) and diastolic blood pressures (P < 0·05) and plasma aldosterone concentration (P < 0·01) compared to the CON. These results suggest that blood pressure is decreased in Fe-deficiency anaemia combined with Zn deficiency partly due to decreased circulating aldosterone concentrations in addition to decreased haematocrit.

The present study investigated the effect of dietary Zn deficiency during sexual maturation on sperm integrity and testis phospholipid fatty acid composition. Male weanling Sprague–Dawley rats were randomised into four dietary groups for 3 weeks: Zn control (ZC; 30 mg Zn/kg); Zn marginally deficient (ZMD; 9 mg Zn/kg); Zn deficient (ZD; < 1 mg Zn/kg); pair fed (PF; 30 mg Zn/kg) to the ZD group. Morphology of cauda epididymal sperm and lipid profiles of testis phospholipids were analysed. The rats fed the ZD diet had a lower testis weight (P < 0·02). Seminal vesicles and prostate weight were also lower in the ZD and PF groups. Rats fed the ZD diet, but not the ZMD diet, had 34–35 % more abnormal spermatozoa and 24 % shorter sperm tail length than the ZC and PF rats (P < 0·001). Testis cholesterol concentration was higher in the ZD rats compared with the ZC and PF rats (P < 0·04). Testes were highly enriched with n-6 fatty acids by showing n-6 : n-3 fatty acid ratios of 27:1 in phosphatidylcholine (PC) and 23:1 in phosphatidylethanolamine (PE). The dominant fatty acid in testes was docosapentaenoic acid (22 : 5n-6), comprising 15 and 24 % of PC and PE, respectively. This fatty acid was significantly lower in the ZD rats, whereas 18 : 2n-6 was higher compared with the rats in the other diet groups. These results demonstrate that severe Zn deficiency adversely affects sperm integrity and modulates testis fatty acid composition by interrupting essential fatty acid metabolism. This suggests that Zn deficiency-associated abnormal testicular function is perhaps preceded by altered membrane fatty acid composition, especially of a major fatty acid, 22 : 5n-6.

Prebiotics may increase Zn absorption, a mineral known to play a central role in the immune system. Zn-deficient states are characterised by suppressed immune function, while prebiotics may improve both gut and cell-mediated immunity. Our objective was to determine if inulin alters the number and proportion of immune cells in the spleen, mesenteric lymph nodes (MLN) and Peyer's patches (PP), ex vivo cytokine secretion, intestinal permeability and Zn status in healthy as well as Zn-deficient rats. Weanling female rats were fed diets supplemented with 5 % cellulose (CEL) or 5 % inulin (PRE) for 4 weeks. The rats received the CEL or PRE diet ad libitum (ZN) or in restricted amounts (DR), or deficient in Zn (ZD) for another 4 weeks. The PRE-fed rats had a higher number and proportion of dendritic cells in PP, and greater ex vivo secretion of IL-2, IL-10 and interferon-γ from spleen and MLN cells compared with CEL-fed rats. PRE reduced the number and proportion of T cell receptor (TCR)-αβ+CD8+ cells in spleen and CD45RA+ cells in MLN compared with CEL. ZD rats had lower serum IgG2a and T cell numbers in MLN compared with ZN and DR rats. TCRγδ+ cell numbers in PP were higher in ZD-PRE rats compared with ZD-CEL rats. Femur Zn concentrations of DR-PRE rats were higher than those of DR-CEL rats. Intestinal permeability was unchanged. The higher proportion and number of dendritic cells in the PP of inulin-fed rats indicates a need for further research on how prebiotics and their metabolites affect immune function possibly through intestinal dendritic cells.

The objective of the present study was to examine the effects of dietary Zn deficiency on the ex vivo cytokine production (IL-2, interferon-γ (IFN-γ), IL-6 and IL-10) of isolated thymocytes and splenocytes after mitogenic stimulation with concavalin A and to explore the role of corticosterone in this regulation. Weanling rats were assigned to one of four dietary treatments for 3 weeks: Zn-deficient ( < 1 mg Zn/kg diet, ad libitum), pair-fed (30 mg Zn/kg diet, limited to amount of feed as consumed by the Zn-deficient group), marginally Zn-deficient (10 mg Zn/kg diet, ad libitum) and control (30 mg Zn/kg diet, ad libitum). Thymocytes and splenocytes were isolated for cytokine stimulation and determination of T-cell phenotypes. Serum corticosterone concentrations were determined by ELISA. The Zn-deficient and pair-fed groups had 14-fold higher serum corticosterone concentrations compared with the marginally Zn-deficient and control groups (P < 0·0001). The proportions of thymocyte subsets were not altered in the Zn-deficient, pair-fed or marginally Zn-deficient groups; however, thymocyte IL-2 and IL-6 production in these groups was 33–54 % lower compared with the control group (P < 0·05). The Zn-deficient group had an 18–28 % lower proportion of new T-cells (TCRαβ+CD90+), but no difference in the proportion of new T-cells that were cytotoxic or helper. The Zn-deficient group had a 49–62 % lower production of Th1 cytokines (IL-2), but no difference in the production of Th2 cytokines (IL-6, IL-10) by stimulated splenocytes compared with the pair-fed, marginally Zn-deficient and control groups (P < 0·01). These results indicate that Zn status is associated with altered cytokine production, while in vivo corticosterone concentrations are not associated with ex vivo cytokine production.

We previously reported that in rats, long-term Zn deficiency significantly reduced taste sensitivity and total carbonic anhydrase (CA) activity in the submandibular gland. We therefore investigated the effects of Zn deficiency on salivary secretion and the expressions of CA isozymes (II and VI) in the rat submandibular gland, since those isozymes are thought to be related to taste sensation and salivary secretion. Male Sprague–Dawley rats, age 4 weeks, were divided into three groups (Zn-def, low-Zn and pair-fed, that were fed a diet containing 2·2, 4·1 or 33·7 mg Zn/kg, respectively, for 42 d). Northern blot analysis indicated that Zn deficiency reduced CA II mRNA expression in the submandibular gland without reducing CA VI mRNA expression. In Western blot analysis, Zn deficiency significantly reduced CA II (erythrocyte CA) protein expression in the submandibular gland without reducing CA VI protein expression. Salivary secretion was lower in the Zn-def group than in the pair-fed group. These results suggest that decreased CA isozyme II expression underlies the decreased CA activity previously reported in the submandibular gland in Zn-def rats, and this may reduce regular salivary secretion.

Zn-deficient (ZD) rats have a lower proportion of splenic CD90+T-cells which could be due to fewer new T-cells exiting the thymus, defective post-thymic maturation or increased cell death. Post-thymic maturation of splenic lymphocytes and their viability were determined by flow cytometry in weanling rats assigned to ZD ( < 1 mg Zn/kg; ad libitum), diet-restricted (DR; 30 mg Zn/kg; limited to the amount of feed as consumed by ZD rats), marginally Zn-deficient (MZD; 10 mg Zn/kg; ad libitum) or control (30 mg Zn/kg; ad libitum) groups for 3 weeks. ZD rats had a 29 % lower percentage of splenic CD90+T-cells and both ZD and DR rats had a 30 % lower proportion of splenic CD90+B-cells compared with control rats. When the splenic CD90+T-cells were characterised further, there was no difference among the groups in the first two stages of post-thymic development; however, ZD, DR and MZD rats had a 42 % lower proportion of late thymic emigrants (TCRαβ+CD90+CD45RC+RT6.1+) compared with control rats. There was no difference among groups in the proportion of splenic CD90+T-cells in the non-viable region; however, ZD rats had a higher proportion of CD90+B-cells in the non-viable region compared with MZD and control animals, suggesting that this phenotype was more susceptible to cell death during deficiency. The lower proportion of splenic CD90+T-cells in ZD rats does not appear to be due to a defect in thymic production or increased cell death in the spleen. Future studies should determine if late thymic emigrants have homed to other peripheral organs.

Zn deficiency reduces food intake and growth rate in rodents. To determine the relationship between Zn deficiency and the regulation of food intake, we evaluated leptin gene expression in epididymal white adipose tissue (eWAT), and hypothalamic corticotropin-releasing hormone (hCRH) and hypothalamic neuropeptide Y (hNPY) of rats Zn-deficient only to show reduced food intake and growth rate but not food intake cycling. Growing male Sprague-Dawley rats (240 g) were randomly assigned to one of four dietary groups: Zn-adequate (ZA; 30 mg/kg diet), Zn-deficient (ZD; 3 mg/kg diet), pair-fed with ZD (PF; 30 mg/kg diet) and Zn-sufficient (ZS; 50 mg/kg diet) (n 8), and were fed for 3 weeks. Food intake and body weight were measured, as were blood mononuclear cells and pancreas Zn levels. eWAT leptin, hCRH and hNPY mRNA levels were determined. Food intake was decreased by about 10 % in ZD and PF rats compared to ZA and ZS rats. Growth and eWAT leptin mRNA levels were unaffected in PF rats but were significantly (P < 0·05) decreased in ZD rats. However, hNPY showed a tendency to increase, and hCRH significantly (P < 0·05) decreased, in both ZD and PF rats. These results suggest that while leptin gene expression may be directly affected by Zn, hNPY and hCRH are likely responding to reduced food intake caused by Zn deficiency.