ProblemThe nature of the peptides found increased in urine from autism needs verification of their structure, especially those that show opioid activity.MethodsThe peptides were separated on reverse phase C-18 HPLC in Trifluoroacetic acid–acetonitril gradients. Peaks eluting where synthetic opioids appear, and peaks that are common to most autistic children were analyzed by mass spectrometry and fragmentation pattern on a quadropole mass-spectrometer.ResultsWe could demonstrate exorphins in the urine from autistic children, and their length varied from one patient to the next.ConclusionExorphins are found in urine of autistic children and may account for their symptoms.

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Background Autoimmune phenotypes are prevalent in major psychiatric disorders. Disequilibria of cellular processes occurring in the gastrointestinal (GI) tract likely contribute to immune dysfunction in psychiatric disorders. As the venue of a complex community of resident microbes, the gut in a homeostatic state equates with a functional digestive system, cellular barrier stability and properly regulated recognition of self and non-self antigens. When gut processes become disrupted as a result of environmental or genetic factors, autoimmunity may ensue. Methods Here, we review the issues pertinent to autoimmunity and the microbiome in psychiatric disorders and show that many of the reported immune risk factors for the development of these brain disorders are in fact related and consistent with dysfunctions occurring in the gut. We review the few human microbiome studies that have been done in people with psychiatric disorders and supplement this information with mechanistic data gleaned from experimental rodent studies. Results These investigations demonstrate changes in behavior and brain biochemistry directly attributable to alterations in the gut microbiome. We present a model by which autoantigens are produced by extrinsically-derived food and microbial factors bound to intrinsic components of the gut including receptors present in the enteric nervous system. Conclusion This new focus on examining activities outside of the CNS for relevance to the etiology and pathophysiology of psychiatric disorders may require new modalities or a re-evaluation of pharmaceutical targets found in peripheral systems.

BackgroundSerum IgG and IgA food antibodies have been used for dietary advice to subjects with gastrointestinal symptoms and perceived food intolerance, but the role of these antibodies in mediating intolerance is controversial. The present study investigated associations between perceived gastrointestinal intolerance to milk-or wheat and the corresponding s-IgG and s-IgA food antibodies in subjects with morbid obesity.MethodsSubjects with morbid obesity (BMI ≥ 40 kg/m2 or ≥35 kg/m2 with obesity-related complications) were included. Irritable Bowel Syndrome (IBS) was diagnosed based on the Rome III criteria. Severity of specific gastrointestinal symptoms were measured with the Gastrointestinal Symptom Rating Scale (GSRS)-IBS. S-IgG against cow’s milk, cheese, wheat and gluten, and s-IgA against casein and gliadin were measured.ResultsNinety-seven subjects (80 females) with mean age 45 (SD 8.4) years were included, 70 had gastrointestinal complaints, 25 had IBS, and 22 and 20 reported milk- and wheat- intolerance respectively. There were no significant differences in serum concentrations or proportions of subjects above defined cut-off values for the antibodies between subjects with and without gastrointestinal complaints. In the group with gastrointestinal complaints, no significant differences were found between subjects with and without perceived food intolerance. Except for a significant correlation between IgG against cheese and GSRS-diarrhea (Rho: -0.25, P = 0.04), no significant correlations were found between the antibodies and type or degree of gastrointestinal symptoms, including IBS.ConclusionsThe study showed no associations between perceived milk or wheat intolerance and the corresponding s-IgG and s-IgA food antibodies in subjects with morbid obesity.

Problem: Some researchers have not found the opioids in urine of autistic children. We have therefore looked at this problem again. Method: Mass spectrometry and fragmentation mass spectrometry (MS/MS) have been carried out on peaks from the HPLC that show co-chromatography with synthetic standards and peaks that are shared by different autistic children. Results: In quickly frozen urine we find the presence of exorphins, and can also demonstrate a rather fast break down at room temperature of these peptides in urine. Conclusion: Exorphins are present in urine in autistic children, but must be protected against break down and aggregation by fast freezing or acetic acid and adjusting declustering potential and collision potential during mass-spectroscopy. Specific antibody increases and the effect of removing precursor proteins from the diet reinforce this view.

Irritable bowel syndrome (IBS) is a chronic disease with recurrent abdominal pain, disturbed bowel emptying, and changes in stool consistency. We compared the effectiveness of three different dietary treatment plans (G1-FM-low FODMAP diet, G2-IP IgG based elimination-rotation-diet, and as control group, the G3-K control diet recommended by an attending gastroenterologist) in treating patients diagnosed with mixed irritable bowel syndrome. A total of seventy-three female patients diagnosed with a mixed form of irritable bowel syndrome (IBS-M) were enrolled in the study. The diet of each patient in Group 1 (G1-FM) and 2 (G2-IP) was determined individually during a meeting with a dietitian. Patients from Group 3 (G3-K) received nutrition advice from a gastroenterologist. Significant differences in the reduction of IBS symptoms were found between the groups. IBS symptoms as well as comorbid symptoms significantly improved or disappeared completely in the G2-IP group (idiopathic abdominal pain, p < 0.001; abdominal pain after a meal, p < 0.001; abdominal pain during defecation, p = 0.008), while in the G1-FM group, some of the IBS symptoms significantly improved (mucus in stool, p = 0.031; bloating, p < 0.001). In group G3-K no significant improvement was seen. Based on the results of this open-label study, it was concluded that various dietary interventions in the treatment of IBS-M patients do not uniformly affect the course and outcomes of disease management. Rotation diets based on IgG show significantly better results compared to other diets.

Background Irritable bowel syndrome (IBS) is a chronic disease with recurrent abdominal pain, disturbed bowel emptying and change in stool consistency. We compared the effectiveness of dietary treatment of three different diet plans (G1-FM-low FODMAP diet, G2-IP IgG based elimination-rotation-diet, and as control group, G3-K control diet recommended by an attending gastroenterologist) in treating patients diagnosed with mixed irritable bowel syndrome. Methods 73 female patients diagnosed with mixed form of irritable bowel syndrome (IBS-M) were enrolled in the study. The diet of each patient in group 1 (G1-FM) and 2 (G2-IP) was determined individually during a meeting with dietitian. Patients from group 3 (G3-K) received nutrition advice from a gastroenterologist. Results Significant differences in reduction of IBS symptoms were found between the groups. IBS symptoms as well as comorbid symptoms significantly improved or disappeared completely in the G2-IP group, while in the G1-FM group, some of the IBS symptoms significantly improved. In group G3-K no significant improvement was seen.Conclusion Based on the results of this open study it was found that the different dietary intervention in the treatment of patients with IBS-M was unlikely effective. The G2-IP IgG based elimination-rotation-diet demonstrating a significant overall superior result compared to the others. Trial registration The clinical trial was retrospective registered at ClinicalTrials.gov, March 12, 2020, ClinicalTrials.gov ID: NCT04307368.

Hyperpeptiduria and opioid excess have been reported in schizophrenia. According to Prof. Dr. L. Lindström, Sweden opioids may explain the pathophysiology of this syndrome. Therefore it is critical to elucidate the presence and nature of opioids in schizophrenia and diagnostic sub groups. First morning urine from untreated schizoaffective patients (ICD-10: F 25.1) was separated on HPLC and peaks that elute where different opioid standards appear, freeze dried, re-dissolved in methanol/water (50/50) and 10 mM formic acid. Mass spectrometry and MS/MS or fragmentation mass spectrometry was performed. We found fragmentation pattern of beta-casomorphin 1 -3 and 1 -4 (bovine) identical to synthetic standards from Bachem. The aggregation tendency of peptides was much in evidence. The reported exorphins were found in the urine from 8 of 12 untreated schizoaffective patients.