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      Alterations of gut bacteria Akkermansia muciniphila and Faecalibacterium prausnitzii in late post-transplant period after liver transplantation Translated title: Alteraciones de las bacterias intestinales Akkermansia muciniphila y Faecalibacterium prausnitzii en el postrasplante tardío tras trasplante hepático

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          Abstract

          Abstract Introduction: Recent studies have shown that the intestinal microbiota can modulate certain systemic metabolic and immune responses, including liver graft function and the development of complications in patients after liver transplantation (LT). Akkermansia muciniphila (AKM) and Faecalibacterium prausnitzii (FAEP) are two of the most abundant gut commensal bacteria, with mucosa-protective and anti-inflammatory effects that are important for maintaining normal intestinal homeostasis and gut barrier function. Our objective was to quantify levels of Akkermansia muciniphila and Faecalibacterium prausnitzii in immunosuppressed patients with LT. Materials and methods: Fecal samples from 23 liver transplant patients (15 adults and 8 children) and 9 non-LT controls were examined. Bacterial DNA was isolated from the samples using the stool DNA isolation kit and the obtained DNA was analyzed with commercially available qPCR kit for AKM and FAEP. Results: We found a statistically significant decrease in the amount of AKM and FAEP compared to the control group. The median values were: for AKM 8.75 for patients and 10.25 for the control group (p = 0.030), and for FAEP 9.72 and 10.47, p = 0.003, respectively. In children after LT, this difference was also statistically significant: AKM (p = 0.051) and FAEP (p = 0.014). In contrast no statistically significant differences were found between adult patients and controls, AKM (p = 0.283) and FAEP (p = 0.056), although the amount of both bacteria showed tendency for reduction. Conclusions: In this pilot study, we found a reduction in the total amount of the two studied bacteria in transplanted patients compared to the control healthy group.

          Translated abstract

          Resumen Introducción: Estudios recientes han demostrado que la microbiota intestinal puede modular determinadas respuestas metabólicas e inmunitarias sistémicas, entre ellas la función del injerto hepático y el desarrollo de complicaciones en pacientes tras un trasplante hepático (TH). Akkermansia muciniphila (AKM) y Faecalibacterium prausnitzii (FAEP) son dos de las bacterias comensales intestinales más abundantes, con efectos protectores de la mucosa y antiinflamatorios que son importantes para mantener la homeostasis intestinal normal y la función de barrera intestinal. Nuestro objetivo fue cuantificar los niveles de Akkermansia muciniphila y Faecalibacterium prausnitzii en pacientes inmunodeprimidos con TH. Materiales y métodos: Se examinaron muestras fecales de 23 pacientes trasplantados de hígado (15 adultos y 8 niños) y 9 controles sin TH. El ADN bacteriano se aisló de las muestras utilizando el kit de aislamiento de ADN de heces y el ADN obtenido se analizó con el kit qPCR disponible comercialmente para AKM y FAEP. Resultados: Encontramos una disminución estadísticamente significativa en la cantidad de AKM y FAEP en comparación con el grupo control. Los valores medianos fueron: para AKM 8,75 para los pacientes y 10,25 para el grupo control (p = 0,030), y para FAEP 9,72 y 10,47, p = 0,003, respectivamente. En niños tras TH, esta diferencia también fue estadísticamente significativa: AKM (p = 0,051) y FAEP (p = 0,014). Por el contrario, no se encontraron diferencias estadísticamente significativas entre pacientes adultos y controles, AKM (p = 0,283) y FAEP (p = 0,056), aunque la cantidad de ambas bacterias mostró tendencia a la reducción. Conclusiones: En este estudio piloto, encontramos una reducción en la cantidad total de las dos bacterias estudiadas en pacientes trasplantados en comparación con el grupo control sano.

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          Most cited references23

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          Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells.

          Gut commensal microbes shape the mucosal immune system by regulating the differentiation and expansion of several types of T cell. Clostridia, a dominant class of commensal microbe, can induce colonic regulatory T (Treg) cells, which have a central role in the suppression of inflammatory and allergic responses. However, the molecular mechanisms by which commensal microbes induce colonic Treg cells have been unclear. Here we show that a large bowel microbial fermentation product, butyrate, induces the differentiation of colonic Treg cells in mice. A comparative NMR-based metabolome analysis suggests that the luminal concentrations of short-chain fatty acids positively correlates with the number of Treg cells in the colon. Among short-chain fatty acids, butyrate induced the differentiation of Treg cells in vitro and in vivo, and ameliorated the development of colitis induced by adoptive transfer of CD4(+) CD45RB(hi) T cells in Rag1(-/-) mice. Treatment of naive T cells under the Treg-cell-polarizing conditions with butyrate enhanced histone H3 acetylation in the promoter and conserved non-coding sequence regions of the Foxp3 locus, suggesting a possible mechanism for how microbial-derived butyrate regulates the differentiation of Treg cells. Our findings provide new insight into the mechanisms by which host-microbe interactions establish immunological homeostasis in the gut.
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            Diversity, stability and resilience of the human gut microbiota.

            Trillions of microbes inhabit the human intestine, forming a complex ecological community that influences normal physiology and susceptibility to disease through its collective metabolic activities and host interactions. Understanding the factors that underlie changes in the composition and function of the gut microbiota will aid in the design of therapies that target it. This goal is formidable. The gut microbiota is immensely diverse, varies between individuals and can fluctuate over time - especially during disease and early development. Viewing the microbiota from an ecological perspective could provide insight into how to promote health by targeting this microbial community in clinical treatments.
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              The gut–liver axis and the intersection with the microbiome

              In the past decade, an exciting realization has been that diverse liver diseases, ranging from non-alcoholic steatohepatitis, alcoholic steatohepatitis, and cirrhosis, to hepatocellular carcinoma, are not unrelated but fall along a spectrum. Recent work on the biology of the gut-liver communication axis has assisted in understanding the basic biology of both alcoholic and nonalcoholic fatty liver disease. Of immense importance is the massive advancement in understanding of the role of the microbiome, driven by high-throughput DNA sequencing and improved computational techniques that allow the complexity of the microbiome to be interrogated, together with improved experimental designs. Here, we review the gut-liver communications of these various forms of liver disease, explore the molecular, genetic and microbiome relationships, discuss prospects for exploiting the microbiome to determine the stage of liver disease, and to predict the effects of pharmaceutical, dietary, and other interventions at a population and individual level. We conclude that although much remains to be done in understanding the relationship between the microbiome and liver disease, rapid progress towards clinical applications is being made, especially in study designs that complement human intervention studies with mechanistic work in mice that have been humanized in multiple respects, including the genetic, immunological and microbiome characteristics of individual patients. These “avatar mice” may be especially useful for guiding new microbiome-based or microbiome-informed therapies.
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                Author and article information

                Journal
                ijm
                Iberoamerican Journal of Medicine
                Iberoam J Med
                Hospital San Pedro (Logroño, La Rioja, Spain )
                2695-5075
                2695-5075
                2022
                : 4
                : 1
                : 45-51
                Affiliations
                [7] Sofia orgnameUniversity Hospital “Lozenets”, Clinic of Pediatrics orgdiv1Sofia University “St. Kliment Ohridski”, Faculty of Medicine Bulgaria
                [1] Sofia orgnameUniversity Hospital “Lozenets” orgdiv1Laboratory of Clinical Immunology Bulgaria
                [13] Sofia orgnameSofia University “St. Kliment Ohridski” orgdiv1Faculty of Medicine orgdiv2Department of Clinical Immunology Bulgaria
                [6] Sofia orgnameUniversity Hospital “Lozenets”, Clinic of Gastroenterology orgdiv1Sofia University “St. Kliment Ohridski”, Faculty of Medicine Bulgaria
                [5] Sofia orgnameSofia University “St. Kliment Ohridski” orgdiv1Faculty of Medicine orgdiv2Department of Clinical Immunology Bulgaria
                [4] Sofia orgnameUniversity Hospital “Lozenets” orgdiv1Laboratory of Clinical Immunology Bulgaria
                [9] Sofia orgnameUniversity Hospital “Lozenets” orgdiv1Laboratory of Clinical Immunology Bulgaria
                [3] Sofia orgnameUniversity Hospital “Lozenets”, Laboratory of Medical Genetics orgdiv1Sofia University “St. Kliment Ohridski”, Faculty of Medicine Bulgaria
                [2] Sofia orgnameUniversity Hospital “Lozenets”, Clinic of Gastroenterology orgdiv1Sofia University “St. Kliment Ohridski”, Faculty of Medicine Bulgaria
                [10] Sofia orgnameSofia University “St. Kliment Ohridski” orgdiv1Faculty of Medicine orgdiv2Department of Clinical Immunology Bulgaria
                [8] Sofia orgnameUniversity Hospital “Lozenets”, Laboratory of Medical Genetics orgdiv1Sofia University “St. Kliment Ohridski”, Faculty of Medicine Bulgaria
                [11] Sofia orgnameUniversity Hospital “Lozenets” orgdiv1Laboratory of Clinical Immunology Bulgaria
                Article
                S2695-50752022000100008 S2695-5075(22)00400100008
                10.53986/ibjm.2022.0010
                43b7f9cb-2010-47d5-a8e6-31acfd6c3312

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 17 January 2022
                : 18 November 2021
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 23, Pages: 7
                Product

                SciELO Spain

                Categories
                Original Article

                Akkermansia muciniphila,Faecalibacterium prausnitzii,Gut microbiota,Liver transplantation,Immunosuppression,Microbiota intestinal,Trasplante de hígado,Inmunosupresión

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