Fecal Microbiota Transplantation (FMT) has shown to possess impressive potential benefit for a wide range of clinical indications. Due to its inherent safety issues and efficacy constraints, the use of personalized FMT analogs could be a promising avenue. The development of such analogs will require a detailed understanding of their functionality, encompassing not only microbe-host interactions of the microbial taxa that are involved, but also of the ecological dimensions of the analogs and an overview of the gastrointestinal sites where these relevant microbial interactions take place. Moreover, characterization of taxa that have been lost due to diminished exposure to beneficial microbes, as a consequence of Western lifestyle, may lead to creation of future FMT analogs with the capacity to restore functionalities that we have lost.
Abstract ID 127906Poster Board 336Neuropsychiatric disorders present significant challenges due to their complex etiology, involving inflammatory responses, neurotransmitter dysregulation, and altered gut-brain interactions. Recent interdisciplinary research uncovers the gut-brain axis (GBA), connecting the central and enteric nervous systems through various pathways. The intestinal microbiota, crucial to the GBA, impacts brain function via bacterial metabolic products like butyrate. This study addresses these complexities by examining the role of butyrate in modulating the influence of proinflammatory responses and oxidative stress on the transport of neurotransmitter precursor amino acids tyrosine and tryptophan and gene expression of these transporters.Fibroblasts derived from human skin obtained from a healthy control were used as model cells for the blood-brain barrier in this research project. Fibroblasts were treated with proinflammatory cytokines (IL-1β, IL-6, IFN-γ, and TNF- α) and oxidative stress (hydrogen peroxide) to assess the uptake of 14C tyrosine. Additionally, fibroblasts were treated with oxidative stress and different concentrations of butyrate to measure the transport of 3H tryptophan across the cell membranes. Furthermore, gene expression profiles in response to oxidative stress and butyrate treatment of tyrosine and tryptophan amino acid transporters were analyzed.Proinflammatory cytokines and oxidative stress were found to significantly decrease tyrosine transport. Oxidative stress significantly decreased tryptophan uptake, while butyrate counteracted this effect. However, treatment of oxidative stressed and control cells with different concentrations of butyrate differentially regulated the gene expression of large amino acid transporters 1 and 2, which are the major transporters of tyrosine and tryptophan.In conclusion, this research project elucidated the pathophysiological mechanisms of proinflammatory responses in neuropsychiatric disorders. Moreover, it highlights the therapeutic potential of butyrate and emphasizes the significance of gut-brain interactions in these conditions. By shedding light on these aspects, this research contributes to the development of innovative and personalized treatment strategies for enhanced management of neuropsychiatric disorders.
Background: Faecal microbiota transplantation (FMT) is an emerging treatment modality, but its current clinical use and organisation are unknown. We aimed to describe the clinical use, conduct, and potential for FMT in Europe. Methods: We invited all hospital-based FMT centres within the European Council member states to answer a web-based questionnaire covering their clinical activities, organisation, and regulation of FMT in 2019. Responders were identified from trials registered at clinicaltrials.gov and from the United European Gastroenterology (UEG) working group for stool banking and FMT. Findings: In 2019, 31 FMT centres from 17 countries reported a total of 1,874 (median 25, quartile 10.64) FMT procedures; 1,077 (57%) with Clostridioides difficile infection (CDI) as indication, 791 (42%) with experimental indications, and 6 (0.3%) unaccounted for. Adjusted to population size, 0.257 per 100,000 population received FMT for CDI and 0-189 per 100,000 population for experimental indications. With estimated 12,400 (6,100-8,500) annual cases of multiple, recurrent CDI and indication for FMT in Europe, the current European FMT activity covers approximately 10% of the patients with indication. The participating centres demonstrated high safety standards and adherence to international consensus guidelines. Formal or informal regulation from health authorities was present at 21 (68%) centres. Interpretation: FMT is a widespread routine treatment for multiple, recurrent CDI and an experimental treatment. Embedded within hospital settings, FMT centres operate with high standards across Europe to provide safe FMT. A significant gap in FMT coverage suggests the need to raise clinical awareness and increase the FMT activity in Europe by at least 10-fold to meet the true, indicated need. (C) 2021 The Authors. Published by Elsevier Ltd.
The 2017 annual symposium organized by the University Medical Center Groningen in The Netherlands focused on the role of the gut microbiome in human health and disease. Experts from academia and industry examined interactions of prebiotics, probiotics, or vitamins with the gut microbiome in health and disease, the development of the microbiome in early-life and the role of the microbiome on the gut-brain axis. The gut microbiota changes dramatically during pregnancy and intrinsic factors (such as stress), in addition to extrinsic factors (such as diet, and drugs) influence the composition and activity of the gut microbiome throughout life. Microbial metabolites, e.g. short-chain fatty acids affect gut-brain signaling and the immune response. The gut microbiota has a regulatory role on anxiety, mood, cognition and pain which is exerted via the gut-brain axis. Ingestion of prebiotics or probiotics has been used to treat a range of conditions including constipation, allergic reactions and infections in infancy, and IBS. Fecal microbiota transplantation (FMT) highly effective for treating recurrent Clostridium difficile infections. The gut microbiome affects virtually all aspects of human health, but the degree of scientific evidence, the models and technologies and the understanding of mechanisms of action vary considerably from one benefit area to the other. For a clinical practice to be broadly accepted, the mode of action, the therapeutic window, and potential side effects need to thoroughly be investigated. This calls for further coordinated state-of-the art research to better understand and document the human gut microbiome's effects on human health.
The microbiome-gut-brain axis paradigm explains that alterations in the central nervous system and behavior may be secondary to functional changes in the gut in general and more specifically the enteric nervous system. An unfavorable development of the intestinal microbial ecosystem, leading to e.g. a diminished microbial diversity, may play a central role. This paper outlines, and describes the theoretical basis of, a novel integrative model explaining the etiology and pathogenesis of ADHD in a microbiota-gut-brain context, taking into account the complexity of the bi-directional signaling between the gut and the brain.