Effects of Gluten on Gut Microbiota in Patients with Gastrointestinal Disorders, Migraine, and Dermatitis.

As gluten may trigger gastrointestinal disorders (GIDs), its presence or absence in the diet can change the diversity and proportion of gut microbiota. The effects of gluten after six weeks of a double-blind, placebo-controlled intervention with a gluten-free diet (GFD) were studied in participants with GIDs suffering from migraines and atopic dermatitis (n = 46). Clinical biomarkers, digestive symptoms, stool, the Migraine Disability Assessment questionnaire, and zonulin levels were analyzed. Next-generation sequencing was used to amplify the 16S rRNA gene of bacteria and the internal transcribed spacer (ITS) regions of fungi. The GFD increased Chao1 fungal diversity after the intervention, while the fungal composition showed no changes. Bacterial diversity and composition remained stable, but a positive association between bacterial and fungal Chao1 diversity and a negative association between Dothideomycetes and Akkermansia were observed. GIDs decreased in both groups and migraines improved in the placebo group. Our findings may aid the development of GID treatment strategies.

Exogenous Supplementation with DAO Enzyme in Women with Fibromyalgia: A Double-Blind Placebo-Controlled Clinical Trial.

Fibromyalgia (FM) is characterized by chronic musculoskeletal pain, muscle tension, joint mobility loss, and several psychological symptoms severely affecting patient well-being. Histamine is naturally degraded in the small intestine by diamine oxidase (DAO). Hereditary or acquired DAO deficiency causes extracellular histamine accumulation, leading to symptoms similar to those of individuals diagnosed with FM. Thus, this study aimed to assess the efficacy of adding DAO supplementation for 8 weeks to their standard therapy. We randomly assigned 100 women with FM (age: 33-61 years) to the supplementation and control groups. The Fibromyalgia Impact Questionnaire (FIQ), the Pain Catastrophizing Scale (PCS), and intensity scales were applied for a series of clinical symptoms together with the Bristol scale to assess the added value of DAO supplementation. Patients in both groups were receiving complete pharmacological support but some differences in the number of subjects receiving analgesics, antidepressants, and anxiolytics was noted. Patients in both study groups experienced favorable changes during the evaluation period as indicated by their final FIQ and PCS scores, particularly in the DAO group in the latter questionnaire. Qualitatively, the patients assigned to the DAO treatment group had lower scores for fatigue, anxiety, depression, burning and for rumination, magnification, and helplessness.

Effect of MetioNac® in patients with metabolic syndrome who are at risk of metabolic dysfunction associated fatty liver disease: a randomized controlled trial.

Introduction: Introduction: metabolic syndrome comprises a combination of diabetes, high blood pressure, and obesity, and metabolic associated fatty liver disease (MAFLD) is associated with it. Objective: to evaluate the effect of supplementation with S-adenosyl-L-methionine + N-acetylcysteine + thioctic acid + vitamin B6 (MetioNac®) for 3 months on lipidic and biochemical parameters in subjects with metabolic syndrome and at risk of MAFLD. The reduction in body weight and the oxidative stress markers malondialdehyde (MDA) and superoxide dismutase (SOD) were also evaluated. Methods: patients with metabolic syndrome, at risk of MAFLD (FIB-4 < 1.30), and with an indication for weight reduction were recruited (n = 15). Control group followed a semipersonalized Mediterranean diet (MD) for weight reduction, according to the recommendations of the Spanish Society for the Study of Obesity (SEEDO). Experimental group, in addition to the MD, took three capsules of MetioNac® supplement per day. Results: compared with the control group, subjects taking MetioNac® showed significant (p < 0.05) reductions in the levels of TG and VLDL-c, as well as in total cholesterol, LDL-c, and glucose levels. They also showed increased levels of HDL-c. Levels of AST and ALT decreased after the intervention with MetioNac®, but this decrease did not reach statistical significance. Weight loss was observed in both groups. Conclusion: supplementation with MetioNac® may be protective against hyperlipidemia, insulin resistance, and overweight among metabolic syndrome patients. Further studies on this issue are needed in a larger population.

Introducción: Introducción: el síndrome metabólico se define como una combinación de diabetes, hipertensión arterial y obesidad, que se asocia con la enfermedad del hígado graso asociada a disfunción metabólica. Objetivo: evaluar el efecto de la suplementación con S-adenosil-L-metionina + N-acetilcisteína + ácido tióctico + vitamina B6 (MetioNac®) durante 3 meses sobre parámetros lipídicos y bioquímicos en sujetos con síndrome metabólico y en riesgo de enfermedad del hígado graso asociada a disfunción metabólica. También se evaluaron la reducción del peso corporal y los marcadores de estrés oxidativo malondialdehído (MDA) y superóxido dismutasa (SOD). Métodos: se reclutaron pacientes con síndrome metabólico, riesgo de enfermedad del hígado graso asociada a disfunción metabólica (FIB-4 < 1,30) y con indicación de reducción de peso (n = 15). El grupo control siguió una dieta mediterránea (DM) semipersonalizada para la reducción de peso, de acuerdo con las recomendaciones de la Sociedad Española para el Estudio de la Obesidad (SEEDO). El grupo intervención, además de la DM, tomó tres cápsulas diarias de MetioNac®. Resultados: en comparación con el grupo de control, los sujetos que tomaron MetioNac® mostraron reducciones significativas (p < 0.05) en los niveles de TG y VLDL-c, así como en los niveles de colesterol total, LDL-c y glucosa. También mostraron niveles elevados de HDL-c. Los niveles de AST y ALT disminuyeron después de la intervención con MetioNac®, pero esta disminución no fue estadísticamente significativa. También se observó una pérdida de peso en ambos grupos. Conclusión: la suplementación con MetioNac® puede proteger contra la hiperlipidemia, la insulinorresistencia y el sobrepeso en pacientes con síndrome metabólico. Sin embargo, es necesario realizar más estudios y seleccionar un mayor número de participantes.

Cumulative effect of AOC1 gene variants on symptoms and pathological conditions in adult women with fibromyalgia: a pilot study.

Introduction: The amine oxidase copper-containing 1 (AOC1) gene encodes for the diamine oxidase (DAO) enzyme. DAO is an enzyme that catabolizes some molecules, including histamine, and is the degradative enzyme in the polyamine catabolic pathway that is active in intestinal mucosal cells. Variants of AOC1 are associated with reduced DAO activity, resulting in accumulation of high levels of histamine and causing a wide range of neurological, gastrointestinal, and epidermal disorders, which are present in people with fibromyalgia. This study aimed to evaluate the impact of four AOC1 gene variants, namely, rs10156191, rs1049742, rs1049793, and rs2052129, on fibromyalgia symptoms measured by the Fibromyalgia Impact Questionnaire (FIQ), such as sleep disorders, atopic dermatitis, migraine, gastrointestinal (GI) disorders, allergies, and intolerances, in adult women with fibromyalgia. Methods: The sample consisted of 100 unrelated women with fibromyalgia between 33 and 60 years of age (48.48 years ±7.35), whose were diagnosed by a rheumatologist based on symptoms such as pain, stiffness, and fatigue. Single-nucleotide polymorphisms (SNPs) of AOC1 were identified using oral mucosa samples collected following a standard hygiene protocol. DNA was extracted, and gene variants of interest were analyzed using multiplex single-nucleotide primer extension (SNPE). Clinical data were collected using the FIQ and a series of variables that quantified the intensity and frequency of the symptoms. Results: The minor allele frequencies of rs10156191, rs1049742, rs1049793, and rs2052129 were 31.5, 10, 32.5, and 27%, respectively. Each variant was found to be in Hardy-Weinberg equilibrium, but partial linkage disequilibrium between AOC1 SNPs is suspected. The results show that fibromyalgia symptoms measured using the FIQ tend to increase with the number of risk alleles and that the intensity of dry skin and low stool consistency may be associated with an increase in the number of these alleles. Conclusion: This study constitutes the first step in investigating associations between fibromyalgia symptoms and candidate variants of the AOC1 gene in DAO enzyme activity. Identification of reduced DAO activity may improve the quality of life and treatment of symptoms in fibromyalgia patients.

Prevalence of Genetic Diamine Oxidase (DAO) Deficiency in Female Patients with Fibromyalgia in Spain.

Diamine oxidase (DAO) is an enzyme that metabolizes intestinal histamine. Single nucleotide polymorphisms (SNPs) of the Amine Oxidase Copper Containing 1 (AOC1) gene can lead to low enzymatic activity or functionality in histamine metabolism. This study aimed to determine the prevalence of DAO deficiency for four variants of the AOC1 gene, p.Thr16Met (rs10156191), p.Ser332Phe (rs1049742), p.His664Asp (rs1049793), and c.691G > T (rs2052129), in 98 Spanish women with fibromyalgia between the ages of 33 and 60 years, and compare the distribution of allelic and genotypic frequencies with those of European population samples in Hardy-Weinberg equilibrium extracted from the Allele Frequency Aggregator (ALFA) database. The patients' DNA was extracted, and analyzed using SNPE Multiplex (Single Nucleotide Primer Extension). The prevalence of genetic DAO deficiency was 74.5% based on the four variants of the AOC1 gene. SNP deficits were found at frequencies of 53.1% for p.Thr16Met, 49% for c.691G > T, 48% for p.His664Asp, and 19.4% for p.Ser332Phe. The allele and genotypic frequencies of the women with fibromyalgia did not differ from the European population. Variants of the AOC1 gene that are associated with genetic DAO deficiency could serve as a disruptive biomarker in patients with fibromyalgia. This study was registered in ClinicalTrials.gov Identifier: NCT05389761.