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      Intestinal permeability before and after albendazole treatment in low and high socioeconomic status schoolchildren in Makassar, Indonesia

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          Abstract

          Intestinal helminths are highly prevalent in low-SES children and could contribute to poor health outcomes either directly or via alteration of the gut microbiome and gut barrier function. We analysed parasitic infections and gut microbiota composition in 325 children attending high- and low-SES schools in Makassar, Indonesia before and after albendazole treatment. Lactulose/Mannitol Ratio (LMR, a marker of gut permeability); I-FABP (a surrogate marker of intestinal damage) as well as inflammatory markers (LBP) were measured. Helminth infections were highly prevalent (65.6%) in low-SES children. LMR and I-FABP levels were higher in low-SES children (geomean (95%CI): 4.03 (3.67–4.42) vs. 3.22 (2.91–3.57); p. adj < 0.001; and 1.57 (1.42–1.74) vs. 1.25 (1.13–1.38); p. adj = 0.02, respectively) while LBP levels were lower compared to the high-SES (19.39 (17.09–22.01) vs. 22.74 (20.07–26.12); p.adj = 0.01). Albendazole reduced helminth infections in low-SES and also decreased LMR with 11% reduction but only in helminth-uninfected children (estimated treatment effect: 0.89; p.adj = 0.01). Following treatment, I-FABP decreased in high- (0.91, p.adj < 0.001) but increased (1.12, p.adj = 0.004) in low-SES children. Albendazole did not alter the levels of LBP. Microbiota analysis showed no contribution from specific bacterial-taxa to the changes observed. Intestinal permeability and epithelial damage are higher while peripheral blood inflammatory marker is lower in children of low-SES in Indonesia. Furthermore, treatment decreased LMR in helminth-uninfected only.

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          Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2

          In comparative high-throughput sequencing assays, a fundamental task is the analysis of count data, such as read counts per gene in RNA-seq, for evidence of systematic changes across experimental conditions. Small replicate numbers, discreteness, large dynamic range and the presence of outliers require a suitable statistical approach. We present DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates. This enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression. The DESeq2 package is available at http://www.bioconductor.org/packages/release/bioc/html/DESeq2.html. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0550-8) contains supplementary material, which is available to authorized users.
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            phyloseq: An R Package for Reproducible Interactive Analysis and Graphics of Microbiome Census Data

            Background The analysis of microbial communities through DNA sequencing brings many challenges: the integration of different types of data with methods from ecology, genetics, phylogenetics, multivariate statistics, visualization and testing. With the increased breadth of experimental designs now being pursued, project-specific statistical analyses are often needed, and these analyses are often difficult (or impossible) for peer researchers to independently reproduce. The vast majority of the requisite tools for performing these analyses reproducibly are already implemented in R and its extensions (packages), but with limited support for high throughput microbiome census data. Results Here we describe a software project, phyloseq, dedicated to the object-oriented representation and analysis of microbiome census data in R. It supports importing data from a variety of common formats, as well as many analysis techniques. These include calibration, filtering, subsetting, agglomeration, multi-table comparisons, diversity analysis, parallelized Fast UniFrac, ordination methods, and production of publication-quality graphics; all in a manner that is easy to document, share, and modify. We show how to apply functions from other R packages to phyloseq-represented data, illustrating the availability of a large number of open source analysis techniques. We discuss the use of phyloseq with tools for reproducible research, a practice common in other fields but still rare in the analysis of highly parallel microbiome census data. We have made available all of the materials necessary to completely reproduce the analysis and figures included in this article, an example of best practices for reproducible research. Conclusions The phyloseq project for R is a new open-source software package, freely available on the web from both GitHub and Bioconductor.
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              Intestinal permeability – a new target for disease prevention and therapy

              Data are accumulating that emphasize the important role of the intestinal barrier and intestinal permeability for health and disease. However, these terms are poorly defined, their assessment is a matter of debate, and their clinical significance is not clearly established. In the present review, current knowledge on mucosal barrier and its role in disease prevention and therapy is summarized. First, the relevant terms ‘intestinal barrier’ and ‘intestinal permeability’ are defined. Secondly, the key element of the intestinal barrier affecting permeability are described. This barrier represents a huge mucosal surface, where billions of bacteria face the largest immune system of our body. On the one hand, an intact intestinal barrier protects the human organism against invasion of microorganisms and toxins, on the other hand, this barrier must be open to absorb essential fluids and nutrients. Such opposing goals are achieved by a complex anatomical and functional structure the intestinal barrier consists of, the functional status of which is described by ‘intestinal permeability’. Third, the regulation of intestinal permeability by diet and bacteria is depicted. In particular, potential barrier disruptors such as hypoperfusion of the gut, infections and toxins, but also selected over-dosed nutrients, drugs, and other lifestyle factors have to be considered. In the fourth part, the means to assess intestinal permeability are presented and critically discussed. The means vary enormously and probably assess different functional components of the barrier. The barrier assessments are further hindered by the natural variability of this functional entity depending on species and genes as well as on diet and other environmental factors. In the final part, we discuss selected diseases associated with increased intestinal permeability such as critically illness, inflammatory bowel diseases, celiac disease, food allergy, irritable bowel syndrome, and – more recently recognized – obesity and metabolic diseases. All these diseases are characterized by inflammation that might be triggered by the translocation of luminal components into the host. In summary, intestinal permeability, which is a feature of intestinal barrier function, is increasingly recognized as being of relevance for health and disease, and therefore, this topic warrants more attention.
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                Author and article information

                Contributors
                firdaus.hamid@gmail.com
                m.yazdanbakhsh@lumc.nl
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                1 March 2022
                1 March 2022
                2022
                : 12
                : 3394
                Affiliations
                [1 ]GRID grid.412001.6, ISNI 0000 0000 8544 230X, Department of Parasitology, Faculty of Medicine, , Hasanuddin University, ; Makassar, 90245 Indonesia
                [2 ]GRID grid.10419.3d, ISNI 0000000089452978, Department of Parasitology, , Leiden University Medical Center, ; PO Box 9600, 2300 RC Leiden, The Netherlands
                [3 ]GRID grid.412001.6, ISNI 0000 0000 8544 230X, Department of Pharmacology, Faculty of Medicine, , Hasanuddin University, ; Makassar, Indonesia
                [4 ]GRID grid.412966.e, ISNI 0000 0004 0480 1382, Department of Surgery, , NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, ; 6229 HX Maastricht, The Netherlands
                [5 ]GRID grid.10419.3d, ISNI 0000000089452978, Experimental Bacteriology, Department of Medical Microbiology, , Leiden University Medical Center, ; 2333 ZA Leiden, The Netherlands
                [6 ]GRID grid.10419.3d, ISNI 0000000089452978, Center for Microbiome Analyses and Therapeutics, Department of Medical Microbiology, , Leiden University Medical Center, ; 2333 ZA Leiden, The Netherlands
                [7 ]GRID grid.412001.6, ISNI 0000 0000 8544 230X, Department of Microbiology, Faculty of Medicine, , Hasanuddin University, ; Jalan Perintis Kemerdekaan Km. 10 Kampus Tamalanrea, Makassar, 90245 Indonesia
                Article
                7086
                10.1038/s41598-022-07086-7
                8888571
                35233023
                5ea4e68b-f4fc-4df5-adc7-644e634950da
                © The Author(s) 2022

                Open Access This 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/.

                History
                : 9 August 2021
                : 7 February 2022
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                © The Author(s) 2022

                Uncategorized
                microbiota,small intestine,epidemiology,parasitic infection
                Uncategorized
                microbiota, small intestine, epidemiology, parasitic infection

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