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      The central and biodynamic role of gut microbiota in critically ill patients

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          Abstract

          Gut microbiota plays an essential role in health and disease. It is constantly evolving and in permanent communication with its host. The gut microbiota is increasingly seen as an organ, and its failure, reflected by dysbiosis, is seen as an organ failure associated with poor outcomes. Critically ill patients may have an altered gut microbiota, namely dysbiosis, with a severe reduction in “health-promoting” commensal intestinal bacteria (such as Firmicutes or Bacteroidetes) and an increase in potentially pathogenic bacteria (e.g. Proteobacteria). Many factors that occur in critically ill patients favour dysbiosis, such as medications or changes in nutrition patterns. Dysbiosis leads to several important effects, including changes in gut integrity and in the production of metabolites such as short-chain fatty acids and trimethylamine N-oxide. There is increasing evidence that gut microbiota and its alteration interact with other organs, highlighting the concept of the gut–organ axis. Thus, dysbiosis will affect other organs and could have an impact on the progression of critical diseases. Current knowledge is only a small part of what remains to be discovered. The precise role and contribution of the gut microbiota and its interactions with various organs is an intense and challenging research area that offers exciting opportunities for disease prevention, management and therapy, particularly in critical care where multi-organ failure is often the focus. This narrative review provides an overview of the normal composition of the gut microbiota, its functions, the mechanisms leading to dysbiosis, its consequences in an intensive care setting, and highlights the concept of the gut–organ axis.

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          The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis.

          Regulatory T cells (Tregs) that express the transcription factor Foxp3 are critical for regulating intestinal inflammation. Candidate microbe approaches have identified bacterial species and strain-specific molecules that can affect intestinal immune responses, including species that modulate Treg responses. Because neither all humans nor mice harbor the same bacterial strains, we posited that more prevalent factors exist that regulate the number and function of colonic Tregs. We determined that short-chain fatty acids, gut microbiota-derived bacterial fermentation products, regulate the size and function of the colonic Treg pool and protect against colitis in a Ffar2-dependent manner in mice. Our study reveals that a class of abundant microbial metabolites underlies adaptive immune microbiota coadaptation and promotes colonic homeostasis and health.
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            Role of the microbiota in immunity and inflammation.

            The microbiota plays a fundamental role on the induction, training, and function of the host immune system. In return, the immune system has largely evolved as a means to maintain the symbiotic relationship of the host with these highly diverse and evolving microbes. When operating optimally, this immune system-microbiota alliance allows the induction of protective responses to pathogens and the maintenance of regulatory pathways involved in the maintenance of tolerance to innocuous antigens. However, in high-income countries, overuse of antibiotics, changes in diet, and elimination of constitutive partners, such as nematodes, may have selected for a microbiota that lack the resilience and diversity required to establish balanced immune responses. This phenomenon is proposed to account for some of the dramatic rise in autoimmune and inflammatory disorders in parts of the world where our symbiotic relationship with the microbiota has been the most affected. Copyright © 2014 Elsevier Inc. All rights reserved.
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              Enterotypes of the human gut microbiome.

              Our knowledge of species and functional composition of the human gut microbiome is rapidly increasing, but it is still based on very few cohorts and little is known about variation across the world. By combining 22 newly sequenced faecal metagenomes of individuals from four countries with previously published data sets, here we identify three robust clusters (referred to as enterotypes hereafter) that are not nation or continent specific. We also confirmed the enterotypes in two published, larger cohorts, indicating that intestinal microbiota variation is generally stratified, not continuous. This indicates further the existence of a limited number of well-balanced host-microbial symbiotic states that might respond differently to diet and drug intake. The enterotypes are mostly driven by species composition, but abundant molecular functions are not necessarily provided by abundant species, highlighting the importance of a functional analysis to understand microbial communities. Although individual host properties such as body mass index, age, or gender cannot explain the observed enterotypes, data-driven marker genes or functional modules can be identified for each of these host properties. For example, twelve genes significantly correlate with age and three functional modules with the body mass index, hinting at a diagnostic potential of microbial markers.
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                Author and article information

                Contributors
                Hannah.Wozniak@hcuge.ch
                Journal
                Crit Care
                Critical Care
                BioMed Central (London )
                1364-8535
                1466-609X
                18 August 2022
                18 August 2022
                2022
                : 26
                : 250
                Affiliations
                [1 ]GRID grid.150338.c, ISNI 0000 0001 0721 9812, Division of Intensive Care, Department of Acute Medicine, , Geneva University Hospitals and University of Geneva, ; Geneva, Switzerland
                [2 ]GRID grid.150338.c, ISNI 0000 0001 0721 9812, Division of Anesthesiology, Department of Acute Medicine, , Geneva University Hospitals and University of Geneva, ; Geneva, Switzerland
                [3 ]GRID grid.8534.a, ISNI 0000 0004 0478 1713, Emerging Antibiotic Resistance Unit, Medical and Molecular Microbiology, Department of Medicine, , University of Fribourg, ; Fribourg, Switzerland
                [4 ]GRID grid.150338.c, ISNI 0000 0001 0721 9812, Genomic Research Laboratory, Service of Infectious Diseases, , Geneva University Hospitals and University of Geneva, ; Geneva, Switzerland
                Article
                4127
                10.1186/s13054-022-04127-5
                9386657
                35982499
                3c4b041b-6e70-4358-a721-f770b719c8c7
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 19 June 2022
                : 13 August 2022
                Categories
                Review
                Custom metadata
                © The Author(s) 2022

                Emergency medicine & Trauma
                gut microbiota,dysbiosis,gut–organ axis,critical care
                Emergency medicine & Trauma
                gut microbiota, dysbiosis, gut–organ axis, critical care

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