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result(s) for
"Bertrand Lauth"
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Evaluating Prophylactic Effect of Bovine Colostrum on Intestinal Barrier Function in Zonulin Transgenic Mice: A Transcriptomic Study
2023
The intestinal barrier comprises a single layer of epithelial cells tightly joined to form a physical barrier. Disruption or compromise of the intestinal barrier can lead to the inadvertent activation of immune cells, potentially causing an increased risk of chronic inflammation in various tissues. Recent research has suggested that specific dietary components may influence the function of the intestinal barrier, potentially offering a means to prevent or mitigate inflammatory disorders. However, the precise mechanism underlying these effects remains unclear. Bovine colostrum (BC), the first milk from cows after calving, is a natural source of nutrients with immunomodulatory, anti-inflammatory, and gut-barrier fortifying properties. This novel study sought to investigate the transcriptome in BC-treated Zonulin transgenic mice (Ztm), characterized by dysbiotic microbiota, intestinal hyperpermeability, and mild hyperactivity, applying RNA sequencing. Seventy-five tissue samples from the duodenum, colon, and brain of Ztm and wild-type (WT) mice were dissected, processed, and RNA sequenced. The expression profiles were analyzed and integrated to identify differentially expressed genes (DEGs) and differentially expressed transcripts (DETs). These were then further examined using bioinformatics tools. RNA-seq analysis identified 1298 DEGs and 20,952 DETs in the paired (Ztm treatment vs. Ztm control) and reference (WT controls) groups. Of these, 733 DEGs and 10,476 DETs were upregulated, while 565 DEGs and 6097 DETs were downregulated. BC-treated Ztm female mice showed significant upregulation of cingulin (Cgn) and claudin 12 (Cldn12) duodenum and protein interactions, as well as molecular pathways and interactions pertaining to tight junctions, while BC-treated Ztm males displayed an upregulation of transcripts like occludin (Ocln) and Rho/Rac guanine nucleotide exchange factor 2 (Arhgf2) and cellular structures and interfaces, protein–protein interactions, and organization and response mechanisms. This comprehensive analysis reveals the influence of BC treatment on tight junctions (TJs) and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling pathway gene expressions. The present study is the first to analyze intestinal and brain samples from BC-treated Ztm mice applying high-throughput RNA sequencing. This study revealed molecular interaction in intestinal barrier function and identified hub genes and their functional pathways and biological processes in response to BC treatment in Ztm mice. Further research is needed to validate these findings and explore their implications for dietary interventions aimed at improving intestinal barrier integrity and function. The MGH Institutional Animal Care and Use Committee authorized the animal study (2013N000013).
Journal Article
Prophylactic Effect of Bovine Colostrum on Intestinal Microbiota and Behavior in Wild-Type and Zonulin Transgenic Mice
2022
The microbiota–gut–brain axis (MGBA) involves bidirectional communication between intestinal microbiota and the gastrointestinal (GI) tract, central nervous system (CNS), neuroendocrine/neuroimmune systems, hypothalamic–pituitary–adrenal (HPA) axis, and enteric nervous system (ENS). The intestinal microbiota can influence host physiology and pathology. Dysbiosis involves the loss of beneficial microbial input or signal, diversity, and expansion of pathobionts, which can lead to loss of barrier function and increased intestinal permeability (IP). Colostrum, the first milk from mammals after birth, is a natural source of nutrients and is rich in oligosaccharides, immunoglobulins, growth factors, and anti-microbial components. The aim of this study was to investigate if bovine colostrum (BC) administration might modulate intestinal microbiota and, in turn, behavior in two mouse models, wild-type (WT) and Zonulin transgenic (Ztm)—the latter of which is characterized by dysbiotic microbiota, increased intestinal permeability, and mild hyperactivity—and to compare with control mice. Bioinformatics analysis of the microbiome showed that consumption of BC was associated with increased taxonomy abundance (p = 0.001) and diversity (p = 0.004) of potentially beneficial species in WT mice and shifted dysbiotic microbial community towards eubiosis in Ztm mice (p = 0.001). BC induced an anxiolytic effect in WT female mice compared with WT female control mice (p = 0.0003), and it reduced anxiogenic behavior in Ztm female mice compared with WT female control mice (p = 0.001), as well as in Ztm male mice compared with WT BC male mice (p = 0.03). As evidenced in MGBA interactions, BC supplementation may well be applied for prophylactic approaches in the future. Further research is needed to explore human interdependencies between intestinal microbiota, including eubiosis and pathobionts, and neuroinflammation, and the potential value of BC for human use. The MGH Institutional Animal Care and Use Committee authorized the animal study (2013N000013).
Journal Article
Zonulin-Dependent Intestinal Permeability in Children Diagnosed with Mental Disorders: A Systematic Review and Meta-Analysis
by
Asbjornsdottir, Birna
,
Halldorsson, Thorhallur Ingi
,
Lauth, Bertrand
in
Adolescent
,
Anxiety disorders
,
Ataxia
2020
Worldwide, up to 20% of children and adolescents experience mental disorders, which are the leading cause of disability in young people. Research shows that serum zonulin levels are associated with increased intestinal permeability (IP), affecting neural, hormonal, and immunological pathways. This systematic review and meta-analysis aimed to summarize evidence from observational studies on IP in children diagnosed with mental disorders. The review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search of the Cochrane Library, PsycINFO, PubMed, and the Web of Science identified 833 records. Only non-intervention (i.e., observational) studies in children (<18 years) diagnosed with mental disorders, including a relevant marker of intestinal permeability, were included. Five studies were selected, with the risk of bias assessed according to the Newcastle–Ottawa scale (NOS). Four articles were identified as strong and one as moderate, representing altogether 402 participants providing evidence on IP in children diagnosed with attention deficit and hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive–compulsive disorder (OCD). In ADHD, elevated serum zonulin levels were associated with impaired social functioning compared to controls. Children with ASD may be predisposed to impair intestinal barrier function, which may contribute to their symptoms and clinical outcome compared to controls. Children with ASD, who experience gastro-intestinal (GI) symptoms, seem to have an imbalance in their immune response. However, in children with OCD, serum zonulin levels were not significantly different compared to controls, but serum claudin-5, a transmembrane tight-junction protein, was significantly higher. A meta-analysis of mean zonulin plasma levels of patients and control groups revealed a significant difference between groups (p = 0.001), including the four studies evaluating the full spectrum of the zonulin peptide family. Therefore, further studies are required to better understand the complex role of barrier function, i.e., intestinal and blood–brain barrier, and of inflammation, to the pathophysiology in mental and neurodevelopmental disorders. This review was PROSPERO preregistered, (162208).
Journal Article
Meals, Microbiota and Mental Health in Children and Adolescents
by
Gudmundsdottir, Valborg
,
Birgisdottir, Bryndis Eva
,
Gudmundsson, Larus S
in
Care and treatment
,
Children
,
Demographic aspects
2022
Recent studies indicate that the interplay between diet, intestinal microbiota composition, and intestinal permeability can impact mental health. More than 10% of children and adolescents in Iceland suffer from mental disorders, and rates of psychotropics use are very high. The aim of this novel observational longitudinal case-control study, \"Meals, Microbiota and Mental Health in Children and Adolescents (MMM-Study)\" is to contribute to the promotion of treatment options for children and adolescents diagnosed with mental disorders through identification of patterns that may affect the symptoms. All children and adolescents, 5-15 years referred to the outpatient clinic of the Child and Adolescent Psychiatry Department at The National University Hospital in Reykjavik, Iceland, for one year (n[almost equal to]150) will be invited to participate. There are two control groups, i.e., sex-matched children from the same postal area (n[almost equal to]150) and same parent siblings (full siblings) in the same household close in age +/- 3 years (n<150). A three-day food diary, rating scales for mental health, and multiple questionnaires will be completed. Biosamples (fecal-, urine-, saliva-, blood samples, and buccal swab) will be collected and used for 16S rRNA gene amplicon sequencing of the oral and gut microbiome, measurements of serum factors, quantification of urine metabolites and host genotype, respectively. For longitudinal follow-up, data collection will be repeated after three years in the same groups. Integrative analysis of diet, gut microbiota, intestinal permeability, serum metabolites, and mental health will be conducted applying bioinformatics and systems biology approaches. Extensive population-based data of this quality has not been collected before, with collection repeated in three years' time, contributing to the high scientific value. The MMM-study follows the \"Strengthening the Reporting of Observational Studies in Epidemiology\" (STROBE) guidelines. Approval has been obtained from the Icelandic National Bioethics Committee, and the study is registered with Clinicaltrials.gov. The study will contribute to an improved understanding of the links between diet, gut microbiota and mental health in children through good quality study design by collecting information on multiple components, and a longitudinal approach. Furthermore, the study creates knowledge on possibilities for targeted and more personalized dietary and lifestyle interventions in subgroups.
Journal Article
Meals, Microbiota and Mental Health in Children and Adolescents (MMM-Study): A protocol for an observational longitudinal case-control study
by
Gudmundsdottir, Valborg
,
Halldorsson, Thorhallur I.
,
Birgisdottir, Bryndis Eva
in
Adolescent
,
Adolescents
,
Antigens
2022
Recent studies indicate that the interplay between diet, intestinal microbiota composition, and intestinal permeability can impact mental health. More than 10% of children and adolescents in Iceland suffer from mental disorders, and rates of psychotropics use are very high. The aim of this novel observational longitudinal case-control study, “Meals, Microbiota and Mental Health in Children and Adolescents (MMM-Study)” is to contribute to the promotion of treatment options for children and adolescents diagnosed with mental disorders through identification of patterns that may affect the symptoms. All children and adolescents, 5–15 years referred to the outpatient clinic of the Child and Adolescent Psychiatry Department at The National University Hospital in Reykjavik, Iceland, for one year ( n≈1 50) will be invited to participate. There are two control groups, i.e., sex-matched children from the same postal area ( n≈1 50) and same parent siblings (full siblings) in the same household close in age +/- 3 years ( n <150). A three-day food diary, rating scales for mental health, and multiple questionnaires will be completed. Biosamples (fecal-, urine-, saliva-, blood samples, and buccal swab) will be collected and used for 16S rRNA gene amplicon sequencing of the oral and gut microbiome, measurements of serum factors, quantification of urine metabolites and host genotype, respectively. For longitudinal follow-up, data collection will be repeated after three years in the same groups. Integrative analysis of diet, gut microbiota, intestinal permeability, serum metabolites, and mental health will be conducted applying bioinformatics and systems biology approaches. Extensive population-based data of this quality has not been collected before, with collection repeated in three years’ time, contributing to the high scientific value. The MMM-study follows the “Strengthening the Reporting of Observational Studies in Epidemiology” (STROBE) guidelines. Approval has been obtained from the Icelandic National Bioethics Committee, and the study is registered with Clinicaltrials.gov. The study will contribute to an improved understanding of the links between diet, gut microbiota and mental health in children through good quality study design by collecting information on multiple components, and a longitudinal approach. Furthermore, the study creates knowledge on possibilities for targeted and more personalized dietary and lifestyle interventions in subgroups. Trial registration numbers : VSN-19-225 & NCT04330703 .
Journal Article
DIET AND CHILDREN WITH ATTENTION DEFICIT HYPERACTIVITY DISORDER (ADHD) - A PILOT INTERVENTION STUDY FOCUSING ON COMPLIANCE AND SYMPTOMS
by
Halldorsson, Thorhallur
,
Lauth, Bertrand
,
Thorsdottir, Inga
in
Allergens
,
Attention deficit hyperactivity disorder
,
Check lists
2017
Background and objectives: The potential effect of food on Attention deficit hyperactivity disorder (ADHD) symptoms has long been debated. The aim of this pilot study was primarily to investigate compliance to two diets of interest, the healthy diet and the temporary few foods diet (few allergens) and secondary evaluate their effects on ADHD symptoms. Methods: Participants were children who had been diagnosed with ADHD at the two main psychiatric centers for children in Reykjavik, with 29 children randomized into three groups: healthy diet (n=10), few foods diet (n=10) and a control group (n=9). A three-day food diary and questionnaires for both parents and teachers gave background information and symptoms. The same questionnaires were answered five weeks later as well as questions regarding the participation. A blinded physician interviewed the children and parents before and after the intervention. Compliance checklists were designed for the intervention period. Full participation rate was 68%. Results: Baseline diet was not in line with dietary recommendations. Compliance to the diets was generally good (70-80%), although most children found it hard to follow the few foods diet and four dropped out. Using ADHD rating scale (ARS) the parents' total score decreased similarly on both diets (median from 35 to 27) or by 25% (p<0.05). Teachers found no change on ARS nor on Achenbach's Teacher Rating Form after the healthy diet, but significant improvement of symptoms were observed after the few foods diet (p=.027). No change was seen in the control group. The psychiatrist also found differences between groups (p<0.05). Conclusions: With good support, compliance was generally good. Parents reported a decrease in symptoms on both diets, while teachers only reported improvements for children on the few foods diet. Diet of children with ADHD can be substantially improved and nutritional status and food sensitivity should be examined at diagnosis. However, further studies are needed.
Journal Article