COVID-19 vaccine hesitancy: a survey in a population highly compliant to common vaccinations.

Vaccination is a key protective factor against COVID-19. Some vaccines have already received emergency authorization from Health Agencies, but growing skepticism and vaccine hesitancy will probably affect COVID-19 vaccination campaigns. In the attempt to shed light on this issue, we conducted an online survey in a population of parents referring to 4 pediatric practices in Naples, Italy in whom we evaluated potential vaccine acceptability in relation to socio-demographic characteristics, perception of personal health and of the impact of COVID-19, and attitudes toward general vaccination practices. Vaccination rates were analyzed also in the corresponding pediatric population.Almost 27% of participants declared they were in favor of vaccinations, and in fact real life vaccination rates in children exceeded the national mean. Only 26.5% of respondents declared they would receive COVID-19 vaccine. Vaccine refusal was attributed to safety concerns in 76% of parents. Specific vaccine attributes further reduced the acceptance rate. Female gender, younger age and lower education level were associated with non-adherence to vaccination. Among extrinsic factors of COVID-19 vaccination, only information from National Health Authorities was significantly associated to vaccine acceptance.The rate of potential COVID-19 vaccine acceptability was very poor in our population of parents. Vaccine hesitancy was mainly due to safety concerns. Demographic and educational factors were correlated to vaccine acceptability. Health education and communication strategies are needed to achieve large-scale vaccine acceptability and finally herd immunity.

Efficacy of ginger as antiemetic in children with acute gastroenteritis: a randomised controlled trial.

BACKGROUND: Ginger is a spice with a long history of use as a traditional remedy for nausea and vomiting. No data on the efficacy of ginger are presently available for children with vomiting associated with acute gastroenteritis (AGE). AIM: To test whether ginger can reduce vomiting in children with AGE. METHODS: Double-blind, randomised placebo-controlled trial in outpatients aged 1 to 10 years with AGE-associated vomiting randomised to ginger or placebo. The primary outcome was the occurrence of ≥1 episode of vomiting after the first dose of treatment. Severity of vomiting and safety were also assessed. RESULTS: Seventy-five children were randomised to the ginger arm and 75 to the placebo arm. Five children in the ginger arm and 4 in the placebo arm refused to participate in the study shortly after randomisation, leaving 70 children in the ginger arm and 71 in the placebo arm (N = 141). At intention-to-treat analysis (N = 150), assuming that all children lost to follow-up had reached the primary outcome, the incidence of the main outcome was 67% (95% CI 56 to 77) in the ginger group and 87% (95% CI 79 to 94) in the placebo group, corresponding to the absolute risk reduction for the ginger versus the placebo group of -20% (95% CI -33% to -7%, P = 0.003), with a number needed to treat of 5 (95% CI 3 to 15). CONCLUSION: Oral administration of ginger is effective and safe at improving vomiting in children with AGE. TRIAL REGISTRATION: The trial was registered on https://clinicaltrials.gov/ with the identifier NCT02701491.

Preventive Effect of Cow's Milk Fermented with Lactobacillus paracasei CBA L74 on Common Infectious Diseases in Children: A Multicenter Randomized Controlled Trial.

Background: Fermented foods have been proposed to prevent common infectious diseases (CIDs) in children attending day care or preschool. OBJECTIVES: To investigate the efficacy of dietary supplementation with cow's skim milk fermented with the probiotic Lactobacillus paracasei CBA L74 in reducing CIDs in children attending day care or preschool. Methods: Multicenter, randomized, double-blind, placebo-controlled trial on healthy children (aged 12-48 months) consuming daily 7 grams of cow's skim milk fermented with L. paracasei CBA L74 (group A), or placebo (maltodextrins group B) attending day care or preschool during the winter season. The main outcome was the proportion of children who experienced ≥1 episode of CID during a 3-month follow-up. Fecal biomarkers of innate (α- and ß-defensins, cathelicidin) and acquired immunity (secretory IgA) were also monitored. Results: A total of 126 children (71 males, 56%) with a mean (SD) age of 33 (9) months completed the study, 66 in group A and 60 in group B. At intention to treat analysis, the proportion of children presenting ≥1 CID was 60% in group A vs. 83% in group B, corresponding to an absolute risk difference (ARD) of -23% (95% CI: -37% to -9%, p < 0.01). At per-protocol-analysis (PPA), the proportion of children presenting ≥1 CID was 18% in group A vs. 40% in group B, corresponding to an absolute risk difference (ARD) of -22% (95% CI: -37% to -6%, p < 0.01). PPA showed that the proportion of children presenting ≥1 acute gastroenteritis (AGE) was significantly lower in group A (18% vs. 40%, p < 0.05). The ARD for the occurrence of ≥1 AGE was -22% (95% CI: -37% to -6%, p < 0.01) in group A. Similar findings were obtained at PPA regarding the proportion of children presenting ≥1 upper respiratory tract infection (URTI), which was significantly lower in group A (51% vs. 74%, p < 0.05), corresponding to an ARD of -23% (95% CI: -40% to -7%, p < 0.01). Significant changes in innate and acquired immunity biomarkers were observed only in subjects in group A. Conclusions: Dietary supplementation with cow's skim milk fermented with L. paracasei CBA L74 is an efficient strategy in preventing CIDs in children.

Cow's milk and rice fermented with Lactobacillus paracasei CBA L74 prevent infectious diseases in children: A randomized controlled trial.

BACKGROUND & AIM: Fermented foods have been proposed for the prevention of infectious diseases. We evaluated the efficacy of fermented foods in reducing common infectious diseases (CIDs) in children attending daycare. METHODS: Prospective randomized, double-blind, placebo-controlled trial (registered under Clinical Trials.gov identifier NCT01909128) on healthy children (aged 12-48 months) consuming daily cow's milk (group A) or rice (group B) fermented with Lactobacillus paracasei CBA L74, or placebo (group C) for three months during the winter season. The main study outcome was the proportion of children who experienced at least one CID. All CIDs were diagnosed by family pediatricians. Fecal concentrations of innate (α- and ß-defensins and cathelicidin LL-37) and acquired immunity biomarkers (secretory IgA) were also evaluated. RESULTS: 377 children (193 males, 51%) with a mean (SD) age of 32 (10) months completed the study: 137 in group A, 118 in group B and 122 in group C. Intention-to-treat analysis showed that the proportion of children who experienced at least one CID was lower in group A (51.8%) and B (65.9%) compared to group C (80.3%). Per-protocol analysis showed that the proportion of children presenting upper respiratory tract infections was lower in group A (48.2%) and group B (58.5%) compared with group C (70.5%). The proportion of children presenting acute gastroenteritis was also lower in group A (13.1%) and group B (19.5%) compared with group C (31.1%). A net increase of all fecal biomarkers of innate and acquired immunity was observed for groups A and B compared to group C. Moreover, there was a negative association between fecal biomarkers and the occurrence of CID. CONCLUSION: Dietary supplementation with cow's milk or rice fermented with L. paracasei CBA L74 prevents CIDs in children attending daycare possibly by means of a stimulation of innate and acquired immunity.

Acceptability and efficacy of a gel hypotonic oral rehydration solution in children with acute gastroenteritis.

OBJECTIVE: Oral rehydration solution remains the mainstay of acute gastroenteritis therapy. The aim of this study was to investigate the acceptability of a new zinc-containing hypotonic super-oral rehydration solution (ORS) in a gel formulation and its efficacy in reducing the duration and severity of diarrhea in children. METHODS: This was a randomized-controlled trial of children (5-36 months of age) observed for diarrhea lasting less than 24 h. Children were randomized to receive standard hypotonic ORS (group 1) or a gel hypotonic super-ORS containing zinc (group 2). The main study outcome was ORS intake in the first 24 h. ORS intake at 4 h, rate of diarrhea resolution at 72 h of treatment, total duration and severity of diarrhea, hospitalization, and adverse effects were also evaluated. RESULTS: Eighty-three children were enrolled (group 1: 40; group 2: 43). The amount of ORS consumed at 24 h was significantly higher in group 2 than in group 1. A similar result was observed at 4 h. The number of children who refused ORS (<10 ml/kg/day) was lower in group 2 versus group 1 (P=0.001). The number of children presenting diarrhea after 72 h of treatment was lower in group 2 versus group 1 (P=0.028). Also, the mean duration of diarrhea was shorter in group 2 than in group 1 (P=0.001). The hypotonic super-ORS containing zinc in a gel formulation had a positive effect on the severity of diarrhea. No patient required hospitalization. No adverse events were observed in either of the two study groups. CONCLUSION: The new zinc-containing hypotonic super-ORS in a gel formulation is effective in the management of childhood acute gastroenteritis.

Efficacy of a new hypotonic oral rehydration solution containing zinc and prebiotics in the treatment of childhood acute diarrhea: a randomized controlled trial.

OBJECTIVE: To evaluate the efficacy of a hypotonic oral rehydration solution (ORS) containing zinc and prebiotics for treatment of acute diarrhea in children. STUDY DESIGN: We conducted a single-blind, prospective, controlled trial including children (age range, 3-36 months) with acute diarrhea randomly assigned to standard hypotonic ORS (group 1) or to new hypotonic ORS containing zinc and prebiotics (group 2). The main outcome was the rate of resolution of diarrhea at 72 hours. RESULTS: A total of 60 children in group 1 (34 male; mean age, 18.58 months; 95% CI, 15.5-21.6) and 59 in group 2 (36 male; mean age, 19.26 months; 95% CI, 15.9-22.6) completed the study protocol. The rate of diarrhea resolution at 72 hours was higher in group 2 (50% versus 72.9%, P = .010). Total ORS intake in the first 24 hours was higher in group 2 (50 mL/kg; 95% CI, 41-59 versus 22 mL/kg; 95% CI, 17-29; P < .001). The mean number of missed working days by the parents of children in group 2 was lower (0.39; 95% CI, 0.08-0.70 versus 1.45; 95% CI 1.02-1.88; P < .001). Fewer patients in group 2 needed adjunctive drugs for the treatment of diarrhea 6/59 versus 19/60, P = .004. No adverse events were observed in either of the two groups. CONCLUSION: The addition of zinc and prebiotics to ORS limits diarrhea duration in children.

Rotavirus induces a biphasic enterotoxic and cytotoxic response in human-derived intestinal enterocytes, which is inhibited by human immunoglobulins.

The mechanisms of diarrhea due to rotavirus infection in humans are not fully understood; no specific therapy is available, but orally administered human serum immunoglobulins are effective in blocking stool output. We aimed to investigate the effect of rotavirus on ion transport and the role of NSP4 in human-derived enterocytes, and to test the efficacy of human serum immunoglobulin in a model of rotavirus infection. Soon after infection, rotavirus induces active chloride secretion in enterocytes. This effect is evident before viral replication leads to cell damage and correlates with NSP4 production. Inhibition of NSP4 prevents the early secretory phase but not cell damage. Incubation with human serum immunoglobulin blocks both ion secretion and cell damage. Rotavirus exerts an early NSP4-dependent ion secretion and subsequent tissue damage. The combined enterotoxic and cytotoxic effects may be responsible for the increased severity of diarrhea due to rotavirus infection, and both are counteracted by human serum immunoglobulin.

Probiotics for treatment of acute diarrhoea in children: randomised clinical trial of five different preparations.

OBJECTIVE: To compare the efficacy of five probiotic preparations recommended to parents in the treatment of acute diarrhoea in children. Design Randomised controlled clinical trial in collaboration with family paediatricians over 12 months. SETTING: Primary care. PARTICIPANTS: Children aged 3-36 months visiting a family paediatrician for acute diarrhoea. INTERVENTION: Children's parents were randomly assigned to receive written instructions to purchase a specific probiotic product: oral rehydration solution (control group); Lactobacillus rhamnosus strain GG; Saccharomyces boulardii; Bacillus clausii; mix of L delbrueckii var bulgaricus, Streptococcus thermophilus, L acidophilus, and Bifidobacterium bifidum; or Enterococcus faecium SF68. MAIN OUTCOME MEASURES: Primary outcomes were duration of diarrhoea and daily number and consistency of stools. Secondary outcomes were duration of vomiting and fever and rate of admission to hospital. Safety and tolerance were also recorded. RESULTS: 571 children were allocated to intervention. Median duration of diarrhoea was significantly shorter (P<0.001) in children who received L rhamnosus strain GG (78.5 hours) and the mix of four bacterial strains (70.0 hours) than in children who received oral rehydration solution alone (115.0 hours). One day after the first probiotic administration, the daily number of stools was significantly lower (P<0.001) in children who received L rhamnosus strain GG and in those who received the probiotic mix than in the other groups. The remaining preparations did not affect primary outcomes. Secondary outcomes were similar in all groups. CONCLUSIONS: Not all commercially available probiotic preparations are effective in children with acute diarrhoea. Paediatricians should choose bacterial preparations based on effectiveness data. TRIAL REGISTRATION NUMBER: Current Controlled Trials ISRCTN56067537 [controlled-trials.com].

Lactoferrin induces concentration-dependent functional modulation of intestinal proliferation and differentiation.

Human milk stimulates intestinal development through the effects of various moieties. Lactoferrin (LF) is a glycoprotein of human milk whose concentration is highest in colostrum decreasing in mature milk. LF promotes enterocyte growth in intestinal cell lines. We tested the hypothesis that LF induces a distinct effect on enterocyte proliferation and differentiation, depending on its concentration. We examined the dose-related effects by human-native LF (N-LF) in Caco-2 (human colon adenocarcinoma) cells. At high concentrations, N-LF stimulated cell proliferation in immature Caco-2 cells, as judged by 3H-thymidine incorporation. In contrast, sucrase and lactase activities were increased at low but not high LF concentrations and their mRNA were also increased, indicating a transcriptional effect. Because iron binds specific LF sites, we compared the potency of N-LF and iron-saturated LF (I-LF) and found the native form more potent. Finally, we tested the effects by bovine LF (bLF) in the same system and found the latter more potent than the human isoform in inducing cell growth and lactase expression. These results suggest that LF directly induces enterocyte growth and proliferation, depending on its concentration, thereby regulating the earlyx postnatal intestinal development. bLF could be added to infant formula as a growth factor in selected intestinal diseases.

Effect of Lactobacillus GG supplementation on pulmonary exacerbations in patients with cystic fibrosis: a pilot study.

BACKGROUND & AIMS: Probiotics reduce intestinal inflammation in children with cystic fibrosis (CF). We want to determine the effects of Lactobacillus GG (LGG) on pulmonary exacerbations in CF. METHODS: A prospective, randomized, placebo-controlled, cross-over study was performed. Nineteen children received LGG for 6 months and then shifted to oral rehydration solution (ORS) for 6 months. In parallel nineteen received ORS and then shifted to LGG. Main outcome parameters were: incidence of pulmonary exacerbations and of hospital admissions, forced expiratory volume (FEV1), and modifications of body weight. RESULTS: Patients treated with LGG showed a reduction of pulmonary exacerbations (Median 1 vs. 2 , range 4 vs. 4, median difference 1, CI 95% 0.5-1.5; p=0.0035) and of hospital admissions (Median 0 vs. 1, range 3 vs. 2, median difference 1, CI 95% 1.0-1.5; p=0.001) compared to patients treated with ORS. LGG resulted in a greater increase in FEV1 (3.6% +/- 5.2 vs. 0.9% +/- 5; p=0.02) and body weight (1.5 kg +/- 1.8 vs. 0.7 kg +/- 1.8; p=0.02). CONCLUSIONS: LGG reduces pulmonary exacerbations and hospital admissions in patients with CF. These suggest that probiotics may delay respiratory impairment and that a relationship exists between intestinal and pulmonary inflammation.

Cancer rates after year 2000 significantly decrease in children with perinatal HIV infection: a study by the Italian Register for HIV Infection in Children.

PURPOSE: To evaluate the impact of highly active antiretroviral therapy (HAART) on cancer incidence in HIV-infected children throughout a 20-year period. PATIENTS AND METHODS: An observational population study was conducted on 1,190 perinatally HIV-infected children enrolled onto the Italian Register for HIV Infection in Children from 1985 to 2004 and never lost to follow-up (total observation time, 10,037.66 years). Cancer rates were calculated in the pre-HAART (1985 to 1995), early HAART (1996 to 1999), and late HAART (2000 to 2004) periods and compared using Poisson regression adjusted for age. The proportion of HAART-treated children increased from 4.1% in 1996 to 60.4% in 1999 and to 81.5% in 2004. In the same time frame, the proportion of children receiving HAART for at least 2 years increased from 3.1% to 77.0%. RESULTS: Overall, 35 cancers occurred. Cancer rates were 4.49 (95% CI, 2.37 to 6.64), 4.09 (95% CI, 1.68 to 6.50), and 0.76 (95% CI, 0.00 to 1.80) per 1,000 children per year in 1985 to 1995, 1996 to 1999, and 2000 to 2004, respectively. Notably, there was no significant difference comparing the periods from 1985 to 1995 and 1996 to 1999 (P = .081). By contrast, cancer rates were significantly lower in the period from 2000 to 2004 than in 1996 to 1999 (P < .0001). Results were confirmed by separately analyzing data from children observed from birth (P = .418 for 1985 to 1995 v 1996 to 1999; P = .001 for 1996 to 1999 v 2000 to 2004). CONCLUSION: Dramatically reduced cancer rates were observed only in the late HAART period in parallel to the increasing proportion of children receiving HAART therapy.

Antiemetics for children with gastroenteritis: off-label but still on in clinical practice.

Antiemetics are not included for treatment of vomiting associated with acute gastroenteritis (AGE) in children by standard guidelines. We performed a survey to determine antiemetic prescribing rates by Italian pediatricians. A structured questionnaire was distributed at a pediatric national conference. The majority of responders reported prescribing antiemetics for pediatric gastroenteritis. Although there is insufficient evidence to justify their use, the use of antiemetics is widely present among pediatricians.

Growth hormone regulates intestinal ion transport through a modulation of the constitutive nitric oxide synthase-nitric oxide-cAMP pathway.

AIM: Growth hormone (GH) directly interacts with the enterocyte stimulating ion absorption and reducing ion secretion induced by agonists of cAMP. Since nitric oxide (NO) is involved in the regulation of transepithelial ion transport and acts as a second messenger for GH hemodynamic effects, we tested the hypothesis that NO may be involved in the resulting effects of GH on intestinal ion transport. METHODS: Electrical parameters reflecting trans-epithelial ion transport were measured in Caco-2 cell monolayers mounted in Ussing chambers and exposed to GH and cholera toxin (CT) alone or in combination, in the presence or absence of the NO synthase (NOS) inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME). Similar experiments were conducted to determine cAMP and nitrite/nitrate concentrations. NOS expression was assayed by Western blot analysis. RESULTS: L-NAME causes total abrogation of absorptive and anti-secretory effects by GH on intestinal ion transport. In addition, L-NAME was able to inhibit the GH-effects on intracellular cAMP concentration under basal conditions and in response to CT. GH induced a Ca(2+)-dependent increase of nitrites/nitrates production, indicating the involvement of the constitutive rather than the inducible NOS isoform, which was directly confirmed by Western blot analysis. CONCLUSION: These results suggest that the GH effects on intestinal ion transport, either under basal conditions or in the presence of cAMP-stimulated ion secretion, are mediated at an intracellular level by the activity of cNOS.

Network approach to the child with primary intestinal failure.

Intestinal failure (IF) is a rare condition resulting from short gut and other heterogeneous intestinal diseases. Major centers in Italy merged in a national network to build common diagnostic and management approaches and to investigate the natural history of IF. Gastroenterological reference centers with specific expertise in intestinal morphology, diagnosis of autoimmune conditions, intestinal microbiology and parenteral nutrition were identified to act as consultants to the network. These centers of expertise provided specific diagnostic approaches while ensuring high technical standards. The approach allowed each center to learn from a larger cohort of patient samples. A database was set up to investigate etiology, epidemiology and natural history of IF. A common diagnostic algorithm for intractable diarrhea was designed. This process was largely based on electronic communication among centers and specimen shipping. Etiologic diagnosis was obtained in almost all cases of IF secondary to severe protracted diarrhea. The study of the natural history of IF showed a close association between etiology of IF and its outcome. The natural history of IF also provided the starting point for specific therapeutic approaches to its complications such as parenteral nutrition-associated cholestasis and catheter-related sepsis. The network approach to IF provides an effective model to optimize resources and prospectively investigate the natural history of IF, essential steps to design interventions, including intestinal transplantation and improve the outcome of IF.

Inhibitory effect of HIV-1 Tat protein on the sodium-D-glucose symporter of human intestinal epithelial cells.

OBJECTIVE: The pathophysiology of HIV-1-related intestinal dysfunction is largely unknown. We previously found that the transactivator factor peptide (Tat) produced by HIV-1 induces ion secretion and inhibits cell proliferation in human enterocytes. Because sugar malabsorption is a frequent feature in AIDS patients, we evaluated whether Tat inhibits intestinal glucose absorption. DESIGN AND METHODS: We measured Na-D-glucose symporter (SGLT-1) activity and determined its phenotypic expression in Caco-2 cells, in the presence and absence of Tat, in uptake experiments using a non-metabolized radiolabelled glucose analogue, and by western blot analysis, respectively. alpha-Tubulin staining was used to study the effects exerted by Tat on cell structure. RESULTS: Tat dose dependently inhibited glucose uptake by human enterocytes. This effect was prevented by anti-Tat polyclonal antibodies and by L-type Ca channels agonist Bay K8644. Western blot analysis of cellular lysates and brush-border membrane preparations showed that Tat induced SGLT-1 missorting. Tat also caused a dramatic decrease in alpha-tubulin staining, which indicates dysruption of the cytoskeleton organization. CONCLUSIONS: Tat acutely impairs intestinal glucose absorption through SGLT-1 missorting. This result indicates that Tat is directly involved in AIDS-associated intestinal dysfunction.

Reduction of inappropriate hospital admissions of children with influenza-like illness through the implementation of specific guidelines: a case-controlled study.

BACKGROUND: In an attempt to reduce the burden of influenza-like illness (ILI) on health resources, the Italian Ministry of Health released clinical practice guidelines (CPGs) on ILI management that include specific indications for the admission of children to the hospital. The aim of this study was to evaluate whether application of these CPGs reduced the rate of inappropriate hospital admissions. METHODS: In the first phase, 2 independent observers recorded the number and clinical condition of children presenting with ILI to the emergency department (ED) of a large urban pediatric hospital and the main reasons for hospital admission. The latter were compared with the CPG indications for hospital admission to evaluate appropriateness. One year later (phase 2), we recorded the number of children with ILI admitted to the hospital by pediatricians trained in a 3-hour course on CPGs and by "untrained" control pediatricians. RESULTS: In phase 1 of the study, 854 children accessed the ED; 318 (37.2%) had ILI. Of the latter, 26.2% were admitted to the hospital, and 33.7% of admissions were inappropriate according to CPG criteria. In phase 2, 16% of the children with ILI were admitted by CPG-trained pediatricians and 25.8% by control pediatricians. The number of inappropriate hospital admissions was higher among control than among CPG-trained pediatricians. CONCLUSIONS: ILI in children is associated with a high rate of inappropriate hospital admissions. Training of ED pediatricians in the application of a specific CPG may result in a substantial decrease of the admission rate and of inappropriate admissions.

Guanylin and E. coli heat-stable enterotoxin induce chloride secretion through direct interaction with basolateral compartment of rat and human colonic cells.

We previously detected specific binding activity of Escherichia coli heat-stable enterotoxin (ST), the guanylin exogenous ligand, in rat colonic basolateral membranes. Because guanylin circulates in the bloodstream, we tested the hypothesis that it modulates intestinal ion transport by acting on the serosal side of intestinal cells. The effects of the mucosal and serosal addition of ST and guanylin on ion transport were investigated in the rat proximal colon and in Caco-2 cells in Ussing chambers, by monitoring short-circuit current (Isc). cGMP concentration was measured in Caco-2 cells by RIA. Mucosal ST addition induced an increase in Isc in rat proximal colon consistent with anion secretion. Serosal addition induced the same effects but to a lesser extent. The electrical effects observed in Caco-2 cells paralleled those observed in rat proximal colon. A pattern similar to the electrical response was observed with cGMP concentration. Guanylin addition to either side of Caco-2 cells induced the same effects as ST, although to a lesser extent. In all conditions, the electrical effect disappeared in the absence of chloride. ST directly interacts with basolateral receptors in the large intestine inducing chloride secretion through an increase of cGMP. However, the serosal effects are less pronounced compared with those observed with mucosal addition. Guanylin shows the same pattern, suggesting that it plays a role in the regulation of ion transport in the colon, but the relative importance of serosally mediated secretion remains to be determined.

Zinc inhibits cholera toxin-induced, but not Escherichia coli heat-stable enterotoxin-induced, ion secretion in human enterocytes.

BACKGROUND: Because zinc deficiency in malnourished children is associated with severe diarrhea, use of zinc supplementation has been proposed as an adjunct to oral rehydration. However, the effects of zinc on enterocyte ion transport are largely unknown. The objective of the present study was to investigate the effects of zinc on transepithelial ion transport under basal conditions and under conditions of enterotoxin-induced ion secretion. METHODS: Ion transport was investigated by monitoring electrical parameters in human intestinal Caco-2 cells that were mounted in Ussing chambers and exposed to increasing concentrations of zinc, both in the absence and presence of either cholera toxin (CT) or Escherichia coli heat-stable enterotoxin (ST). Intracellular cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) concentrations were also determined. RESULTS: The addition of zinc to the luminal or basolateral side of enterocytes induced a chloride-dependent, dose-related decrease in short-circuit current, indicating ion absorption. It also resulted in a substantial reduction in CT-induced ion secretion and in cAMP concentration. E. coli ST-induced ion secretion and cGMP concentration were not affected. Ion absorption peaked at 35 mu mol/L zinc, whereas excess zinc load induced active ion secretion. CONCLUSIONS: By causing a decrease in cAMP concentration, zinc directly promotes ion absorption and substantially reduces CT-induced, but not E. coli ST-induced, ion secretion.