Datterino Trial: A Double Blind, Randomized, Controlled, Crossover, Clinical Trial on the Use of Hydroponic Cultivated Tomato Sauce in Systemic Nickel Allergy Syndrome.

A low-nickel (Ni) diet, a key treatment for Systemic Nickel Allergy Syndrome (SNAS), is difficult in the long term and strongly impacts quality of life (QoL). Hydroponic agriculture could be an alternative to allow the reintroduction of tomato, an essential food in the global diet. In a first interventional, randomized, double-blind, single-center crossover study, we compared the possible effects of eating tomato puree deriving from hydroponic agriculture versus tomato puree from conventional cultivation, collecting data on subjective control of SNAS symptoms, adherence to treatment, and impact on QoL. Thirty subjects were randomly assigned to one of the following treatment groups: (1) a 12-week low-Ni diet plus 100% Italian Datterino tomato puree deriving from hydroponic technology; (2) a 12-week low-Ni diet plus 100% Italian Datterino tomato puree deriving from conventional cultivation. Then, after a 2-week washout period on the low-Ni diet, each patient crossed over to the other treatment. Patients reported lower symptom scores after eating Datterino tomato puree deriving from hydroponic technology; specifically, bloating (p = 0.0111, p = 0.0060), flatulence (p = 0.0090), abdominal cramps (p = 0.0207), constipation (p = 0.0395), and diarrhea (p = 0.0105). Overall, the adherence rate was high for both treatment arms. At baseline, QoL was poor, but significant improvement was observed after two treatments. In our study, precision medicine and precision agriculture merge in a holistic approach to the challenges of food allergies.

Beneficial Effects of a Low-Nickel Diet on Relapsing IBS-Like and Extraintestinal Symptoms of Celiac Patients during a Proper Gluten-Free Diet: Nickel Allergic Contact Mucositis in Suspected Non-Responsive Celiac Disease.

BACKGROUND AND AIM: Nickel (Ni)-rich foods can induce allergic contact mucositis (ACM) with irritable bowel syndrome (IBS)-like symptoms in predisposed subjects. Ni ACM has a high prevalence (>30%) in the general population and can be diagnosed by a Ni oral mucosa patch test (omPT). Many celiac disease (CD) patients on a gluten-free diet (GFD) often show a recrudescence of gastrointestinal and extraintestinal symptoms, although serological and histological remission has been achieved. Since a GFD often results in higher loads of ingested alimentary Ni (e.g., corn), we hypothesized that it would lead to a consequent intestinal sensitization to Ni in predisposed subjects. We wanted to (1) study Ni ACM prevalence in still symptomatic CD patients on a GFD and (2) study the effects of a low-Ni diet (LNiD) on their recurrent symptoms. MATERIAL AND METHODS: We recruited 102 consecutive CD patients (74 female, 28 male; age range 18-65 years, mean age 42.3 ± 7.4) on a GFD since at least 12 months, in current serological and histological remission (Marsh-Oberhuber type 0-I) who complained of relapsing gastrointestinal and/or extraintestinal symptoms. INCLUSION CRITERIA: presence of at least three gastrointestinal symptoms with a score ≥5 on the modified Gastrointestinal Symptom Rating Scale (GSRS) questionnaire. EXCLUSION CRITERIA: IgE-mediated food allergy; history of past or current cancer; inflammatory bowel diseases; infectious diseases including Helicobacter pylori; lactose intolerance. All patients enrolled underwent Ni omPT and followed a LNiD for 3 months. A 24 symptoms questionnaire (GSRS modified according to the Salerno Experts' Criteria, with 15 gastrointestinal and 9 extraintestinal symptoms) was administered at T0 (free diet), T1 (GFD, CD remission), T2 (recurrence of symptoms despite GFD), and T3 (GFD + LNiD) for comparisons. Comparisons were performed using Wilcoxon signed-rank test. RESULTS: Twenty patients (all female, age range 23-65 years, mean age 39.1 ± 2.9) out of 102 (19.6%) were finally included. All 20 patients enrolled (100%) showed positive Ni omPT, confirming an Ni ACM diagnosis. A correct GFD (T0 vs. T1) induced the improvement of 19 out of the total 24 (79.2%) symptoms, and 14 out of 24 (58.3%) were statistically significant (p-value < 0.0083 according to Bonferroni correction). Prolonged GFD (T1 vs. T2) revealed the worsening of 20 out of the total 24 (83.3%) symptoms, and 10 out of 24 (41.7%) were statistically significant. LNiD (T2 vs. T3) determined an improvement of 20 out of the total 24 (83.4%) symptoms, and in 10 out of 24 (41.7%) symptoms the improvement was statistically significant. CONCLUSIONS: Our data suggest that the recrudescence of gastrointestinal and extraintestinal symptoms observed in CD subjects during GFD may be due to the increase in alimentary Ni intake, once gluten contamination and persisting villous atrophy are excluded. Ni overload can induce Ni ACM, which can be diagnosed by a specific Ni omPT. Improvement of symptoms occurs after a proper LNiD. These encouraging data should be confirmed with larger studies.

The Effects of Low-Nickel Diet Combined with Oral Administration of Selected Probiotics on Patients with Systemic Nickel Allergy Syndrome (SNAS) and Gut Dysbiosis.

BACKGROUND: Nickel (Ni) oral consumption may elicit systemic reactions in patients affected by systemic nickel allergy syndrome (SNAS), including gastrointestinal symptoms, which in turn are associated with gut dysbiosis. We evaluated the effects of a low-Ni diet alone or in combination with the oral consumption of appropriate probiotics on Ni-sensitivity and urinary dysbiosis markers in SNAS patients. METHODS: n = 51 patients with SNAS and concomitant intestinal dysbiosis were enrolled in the study. According to the urinary indican/skatole levels, quantified through a colorimetric and a high-performance liquid chromatographic method, respectively, patients were assigned to a dysbiosis type/grade and followed a low-Ni diet for three months. Along with the diet, 22 patients also consumed probiotics based on the dysbiosis type. In particular, a Lactobacilli- or Bifidobacteria-containing formulation was administered to patients with fermentative or putrefactive dysbiosis, respectively, while a broad-spectrum probiotic formulation containing both Lactobacilli and Bifidobacteria was administered to patients with mixed dysbiosis. After three months, patients were invited to repeat the Ni-stimulation and the dysbiosis tests. RESULTS: The fermentative dysbiosis group represented the largest group followed by the mixed dysbiosis group, while only two patients had putrefactive dysbiosis. Overall, at three months of treatment in general (diet alone with or without probiotics), the Ni-sensitivity and dysbiosis levels were strongly ameliorated. The association of a low-Ni diet with a specific probiotic oral supplementation was significantly more effective in decreasing dysbiosis levels or reaching eubiosis than with diet alone. CONCLUSION: Our results, while confirming the benefits of a low-Ni diet in SNAS patients, strongly support that appropriate adjuvant treatment with probiotics significantly helps to improve intestinal dysbiosis or restore a healthy microbiota.

Irritable Bowel Syndrome-Like Disorders in Endometriosis: Prevalence of Nickel Sensitivity and Effects of a Low-Nickel Diet. An Open-Label Pilot Study.

Alimentary nickel (Ni) may result in allergic contact mucositis (ACM), whose prevalence is >30% and may present with IBS-like and extra-intestinal symptoms. These symptoms are also frequent in endometriosis, and Ni allergic contact dermatitis has already been observed in endometriosis. Therefore, intestinal and extra-intestinal symptoms in endometriosis may depend on a Ni ACM, and a low-Ni diet could improve symptoms. We studied the prevalence of Ni ACM in endometriosis and focused on the effects of a low-Ni diet on gastrointestinal, extra-intestinal, and gynecological symptoms. We recruited 84 women with endometriosis, symptomatic for gastrointestinal disorders. Thirty-one out of 84 patients completed the study. They underwent Ni oral mucosa patch test (omPT), questionnaire for intestinal/extra-intestinal/gynecological symptoms, and a low-Ni diet. Clinical evaluation was performed at baseline (T0) and after three months (T1). Twenty-eight out 31 (90.3%) patients showed Ni omPT positive results, with Ni ACM diagnosis, whereas three out of 31 (9.7%) patients showed negative Ni omPT. After three months of low-Ni diet, all gastrointestinal, extra-intestinal and gynecological symptoms showed a statistically significant reduction. Ni ACM has a high prevalence in endometriosis and a low-Ni diet may be recommended in this condition to reduce gastrointestinal, extra-intestinal and gynecological symptoms.

Probiotic supplementation in systemic nickel allergy syndrome patients: study of its effects on lactic acid bacteria population and on clinical symptoms.

AIMS: The study aimed to evaluate the effects of probiotic Lactobacillus reuteri DSM 17938 strain supplementation in patients suffering from systemic nickel allergy syndrome, in terms of modulation of faecal LAB population linked to a reduction of GI and cutaneous symptoms and to an increase of patient's quality of life. METHODS AND RESULTS: A preliminary double-blind randomized placebo-controlled study was planned and a culture-independent method based on denaturing gradient gel electrophoresis (DGGE) analysis coupled to the 16S rRNA gene sequencing was applied to investigate on the dynamics of faecal LAB communities before and during a low-Ni diet, supplemented with the probiotic strain. Moreover, the severity and the frequency of GI and cutaneous reactions as well as patient's clinical condition perception (VAS scores) were estimated by statistical analysis. PCR-DGGE fingerprinting obtained using LAB-specific primers revealed significant shift in faecal community with an increase in biodiversity in patients supplemented with probiotic Lact. reuteri strain. In addition, GI reactions such as symptoms related to meals and type of stools significantly improved only in patients treated with Lact. reuteri, while severity and frequency of cutaneous symptoms (urticaria, itch and eczema) and recurrent abdominal pain (RAP) as well as VAS scores statistically decreased in both groups. CONCLUSIONS: Our preliminary findings suggest that probiotic Lact. reuteri could be a useful supplementation during a low-Ni diet of patients with SNAS, to increase LAB population diversity, which could contribute to restore the intestinal homoeostasis conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: To date, no information is available on probiotics application and on their effects, in terms of intestinal microbiota modulation, on patients suffering from SNAS. Therefore, the identification of dominant LAB community and the study of its shift during the probiotic supplementation could enhance the knowledge of the SNAS syndrome.