Sandra J. Holasek

Non-celiac gluten sensitivity: people without celiac disease avoiding gluten—is it due to histamine intolerance?

IntroductionFood intolerance/malabsorption is caused by food ingredients, carbohydrates (mainly lactose and fructose), proteins (gluten), and biogenic amines (histamine) which cause nonspecific gastrointestinal and extra-intestinal symptoms. Here we focus on possible etiologic factors of intolerance/malabsorption especially in people with non-celiac gluten sensitivity (NCGS) or the so-called people without celiac disease avoiding gluten (PWCDAG) and histamine intolerance.MethodsRecognizing the recently described symptoms of NCGS (PWCDAG) we review correlations and parallels to histamine intolerance (HIT).ResultsWe show that intestinal and extra-intestinal NCGS (PWCDAG) symptoms are very similar to those which can be found in histamine intolerance.ConclusionsAfter a detailed diagnostic workup for all possible etiologic factors in every patient, a targeted dietary intervention for single or possibly combined intolerance/malabsorption might be more effective than a short-term diet low in fermentable oligo-, di- and monosaccharides and polyols (FODMAP) or the untargeted uncritical use of gluten-free diets.

The Role of Nutrition and the Gut-Brain Axis in Psychiatry: A Review of the Literature

Introduction: Individuals suffering from psychiatric disorders experience high levels of illness burden and a significantly reduced quality of life. Despite targeted psychopharmacological strategies and complementary psychotherapeutic procedures only moderate effects are obtained, and the risk of relapse is high in many patients. Worldwide, psychiatric diseases such as depression are continuously increasing, challenging the personal life of the affected as well as their families, but also whole societies by increasing disability, early retirement and hospitalization. According to current scientific knowledge psychiatric disorders are caused by a multifactorial pathogenesis, including genetics, inflammation and neurotransmitter imbalance; furthermore, also lifestyle-associated factors gain rising importance. In line with this, there is growing evidence that the gut microbiota and nutrition have an impact on the onset and course of psychiatric disorders. Aim: This narrative review highlights the important role of nutrition in psychiatric care and underlines the significance of nutritional advice in the multifactorial, biopsychosocial treatment of patients. It focuses on current dietary interventions such as the Mediterranean diet, dietary supplements and modifications of the gut microbiota with pre-, pro- and postbiotics. Results: Recent studies support the connection between the quality of diet, gut microbiota and mental health through regulation of metabolic functions, anti-inflammatory and antiapoptotic properties and the support of neurogenesis. Dietary coaching to improve mental health seems to be an additional, cost-effective, practical, nonpharmacological intervention for individuals with psychiatric disorders. Conclusion: The use of nutritional interventions in psychiatry equips therapists with a promising tool for both the prevention and treatment of psychiatric disorders. Besides pharmacological therapy, psychotherapy and physical activity, nutritional interventions are an important pillar in the multifactorial, biopsychosocial treatment of psychiatric disease and could be used as a potential therapeutic target.

Pilotstudie: Mikrobiom und Darmbarriere bei Anorexia nervosa

INTRODUCTION Recent research has shown changes of the intestinal flora in anorexia nervosa (AN) patients. Alpha diversity (AD) represents the number of different bacterial species in the gut. Reduced AD and a leaky gut (zonulin) lead to inflammation and changes in nutrient absorption. METHODS AD was calculated from stool samples of 18 AN patients and 20 normal weight controls (NC) after 16S ribosomal RNA sequencing. Furthermore, Zonulin as an indicator of gut barrier function and inflammation parameters were investigated. RESULTS AN patients had significantly lower AD compared to NC (number of observed species p=0.042, Chao1 Diversity Index p=0.043). Zonulin was not significantly altered in AN patients compared to NC. There were no significant correlations of serum parameters and AD. DISCUSSION Regardless of gut permeability, AN patients showed significantly decreased AD compared to NC. Decreased AD can have an additional negative impact on calorie intake in AN. These results contribute to a better understanding of the illness and the development of new therapeutic options.

β-thalassemia minor, carbohydrate malabsorption and histamine intolerance

ABSTRACT Background: β-thalassemia minor is characterized by reduced β-haemoglobin chain synthesis and sometimes mild anaemia, although carriers of β-thalassemia minorare usually clinically asymptomatic.Nonspecific abdominal complaints may be caused by gastrointestinal carbohydrate malabsorption (lactose and fructose) and/or malabsorption of biogenic amines (histamine), or proteins (gluten). Objectives: We report on two patients with β-thalassemia minor suffering nonspecific abdominal symptoms due to a carbohydrate and histamine malabsorption. Design/methods: The diagnosis of β-thalassemia minorwas done with peripheral blood smear and cellulose acetate electrophoresis. Carbohydrate malabsorption was diagnosed with hydrogen breath tests and, histamine intolerance (HIT) with a serum diamine oxidase value <10 U/ml and more than two gastrointestinal symptoms described for HIT. Conclusion: The symptoms of gastrointestinal malabsorption in these two patients with β-thalassemia minor were treated successfully with an individually-tailored diet free of symptom causing carbohydrates and histamine.

Short-term Beneficial Effects of 12 Sessions of Neurofeedback on Avoidant Personality Accentuation in the Treatment of Alcohol Use Disorder

This study evaluated the effects of alpha/theta neurofeedback on Clinical Personality Accentuations in individuals with alcohol use disorder. Twenty-five males were investigated using a pre-test/post-test design with a waiting-list control group. Participants were randomly assigned either to an experimental group (n = 13) receiving 12 sessions of neurofeedback twice a week as a treatment adjunct over a period of 6 weeks, or to a control group (n = 12) receiving treatment as usual. The Inventory of Clinical Personality Accentuations and the NEO-Five-Factor Inventory were applied at pre- and post-test. The neurofeedback protocol focused on enhancement of the EEG alpha (8–12 Hz) and theta (4–7 Hz) and used a visual feedback paradigm. Analyses of covariance showed improvements in Avoidant Personality Accentuation within the experimental group. Our data suggest that 12 sessions of this neurofeedback intervention might be effective in reducing avoidant and stress-related personality traits in patients with alcohol use disorder.

Benign Pancreatic Hyperenzymemia (Gullo Syndrome), Histamine Intolerance, and Carbohydrate Malabsorption

Benign pancreatic hyperenzymemia (Gullo syndrome) is characterized by a more than threefold increase of the pancreatic enzymes lipase and amylase in the absence of a pancreatic disease over a period of more than 1 year, with elevations and significant undulations of pancreatic enzyme serum concentrations occurring on a day-to-day basis for 5 consecutive days. Nonspecific abdominal complaints may be caused by carbohydrate and/or protein malabsorption. We report a patient with benign pancreatic hyperenzymemia with lactose and histamine malabsorption; the symptoms of gastrointestinal malabsorption were treated successfully with an individually tailored lactose- and histamine-free diet.

Endoplasmic reticulum stress in bipolar disorder? – BiP and CHOP gene expression- and XBP1 splicing analysis in peripheral blood

BACKGROUND Endoplasmic Reticulum stress activates the Unfolded Protein Response, which is partially impaired in Bipolar Disorder (BD) according to previous in-vitro studies. Thus, BiP and CHOP gene expression and XBP1 splicing were analyzed in peripheral blood of study participants with BD and controls. METHODS RNA was isolated from fasting blood of study participants with BD (n = 81) and controls (n = 54) and reverse transcribed into cDNA. BiP and CHOP gene expression was analyzed with quantitative RT-PCR. Atypical splicing of XBP1 mRNA was measured by semi-quantitative RT-PCR, gel-electrophoresis and densitometry. ANCOVAs with the covariates age, BMI, sex, lithium and anticonvulsants intake were used with SPSS. Bonferroni correction was used to correct for multiple testing (adjusted p = 0.0083). RESULTS BiP gene expression was significantly higher in BD than in controls (F(1/128) = 10.076, p = 0.002, Partial η2 = 0.073). Total XBP1 (F(1/126) = 9.550, p = 0.002, Partial η2 = 0.070) and unspliced XBP1 (F(1/128)= 8.803, p= 0.004, Patial η2 = 0.065) were significantly decreased in BD. Spliced XBP1 (F(1/126) = 5.848, p = 0.017, Partial η2 = 0.044) and the ratio spliced XBP1/ unspliced XBP1 did not differ between BD and controls (F(1/126) = 0.599, p = 0.441, Partial η2 = 0.005). Gene expression did not differ between euthymia, depression and mania. DISCUSSION BiP gene expression was significantly higher in BD compared to controls. Total and unspliced XBP1 were significantly lower in BD than in the control group. Thus, both genes may be considered as putative trait markers. Nevertheless, XBP1 splicing itself did not differ between both groups.

Response to Letter to the Editor to Gut microbiota, dietary intakes and intestinal permeability reflected by serum zonulin in women

Dear Prof. Rowland, Thank you for giving us the opportunity to answer the letter to the editor by Lucas Scheffler et al. which raised some important and interesting points regarding the zonulin ELISA kit by Immundiagnostik AG which was used in our study “Gut microbiota, dietary intakes and intestinal permeability reflected by serum zonulin in women” [1]. In 2009, Tripathi and co-workers from Fasano’s group published findings pointing to zonulin’s identity with prehaptoglobin-2 [2]. 15% of the general population (with a HP1-1 genotype) do not express pre-HP2 (zonulin). Hence, zonulin should not be detected in this subpopulation [3]. Nevertheless, the ELISA kit used in our study seems to measure zonulin-like immunoreactivity also in serum samples of Hp1-1 individuals. Importantly, this ELISA kit— using antibodies raised against a zonulin sequence earlier published by Fasano’s group [4]—does not recognize preHP2 (zonulin) but rather some other members of the zonulin family (such as properdin) with similar effects on gut permeability. This was recently described in a publication by Scheffler et al. [5]. Properdin is a plasma glycoprotein which is released from neutrophils, T-cells and macrophages in response to microbial exposure (alternate complement pathway). It has been intensively investigated during the last decade and owns important functions in inflammation and adipose tissue [6]. Thus, it is involved in cardiovascular diseases, arthritis, asthma and kidney diseases [7]. Alterations of complement activity by properdin caused changes in the innate and adaptive immune responses including pro-inflammatory cytokine production, immune cell infiltration, antigen presenting cell maturation and tissue damage subsequently leading to increased endothelial permeability [7–9]. Interestingly, up to now, to our best knowledge, there is only one study investigating serum properdin in patients with anorexia nervosa. Anorexia nervosa patients were also included in our aforementioned study [1]. Wyatt et al. described significantly decreased serum levels of properdin in five anorexia nervosa patients which did not increase after nutritional treatment [10]. In our pilot study, we could not identify differences of serum zonulin family members in anorexia nervosa patients compared to normal weight controls [11]. Further, we detected also no differences between serum levels of zonulin family members when the participants were segregated according to BMI [12] [AN patients (n = 17), NW participants (n = 25), OW participants (n = 21), OB participants (n = 19) and normal weight athletes (n = 20)] [1]. Therefore, gut permeability should be measured by overall immunoreactivity, zonulin and other members of the zonulin family. Future studies should also identify whether this zonulin subfamilies have different functional properties in regard to inflammation and gut permeability. In this context, the results of the Immundiagnostik ELISA correlated with metabolic traits linked to increased gut permeability [5]. Hence, we totally agree with the letter This response letter to a letter to the editor refers to the original publication by Mörkl et al. “Gut microbiota, dietary intakes and intestinal permeability reflected by serum zonulin in women” available under https ://doi.org/10.1007/s0039 4-018-1784-0 and the letter to the editor available here: https ://doi.org/10.1007/s0039 4-018-1835-6.

Histamine-reduced diet and increase of serum diamine oxidase correlating to diet compliance in histamine intolerance

Diagnosis of histamine intolerance (HIT) has been based on low serum diamine oxidase (DAO) values, functional gastrointestinal disorders and improvement of symptoms with a histamine-reduced diet (HRD). In a retrospective analysis of outpatients’ charts we identified 101 patients with HIT. After a median of 13 months, a questionnaire was distributed to the patients so that they could be classified into four diet-compliance groups. Calculated with all 101 patients we found an increase of serum DAO values due to a HRD. In the 63 patients that completed the questionnaire, we found that 50 patients had improvement of symptoms or no continuing symptoms. A significant increase of serum DAO levels was found in the patients with strict and occasional diet compliance. Therefore, we demonstrate that a HRD is not only improving symptoms in HIT, but is causing an increase in serum DAO values that correlates with the degree of diet compliance.