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      The Microbiome and Preterm Birth: A Change in Paradigm with Profound Implications for Pathophysiologic Concepts and Novel Therapeutic Strategies

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          Abstract

          Preterm birth poses a global challenge with a continuously increasing disease burden during the last decades. Advances in understanding the etiopathogenesis did not lead to a reduction of prematurely born infants so far. A balanced development of the host microbiome in early life is key for the maturation of the immune system and many other physiological functions. With the tremendous progress in new diagnostic possibilities, the contribution of microbiota changes to preterm birth and the acute and long-term sequelae of prematurity have come into the research focus. This review summarizes the latest advances in the understanding of microbiomes in the amniotic cavity and the female lower genital tract and how changes in microbiota structures contribute to preterm delivery. The exhibition of these highly vulnerable infants to the hostile environment in the neonatal intensive care unit necessarily entails the rapid colonization with a nonbalanced microbiome in a situation where the organism is still very prone and at an early stage of development. The global research efforts to decipher pathologic changes will pave the way to new pre- and postnatal therapeutic concepts.

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          Most cited references85

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          The maternal microbiota drives early postnatal innate immune development.

          Postnatal colonization of the body with microbes is assumed to be the main stimulus to postnatal immune development. By transiently colonizing pregnant female mice, we show that the maternal microbiota shapes the immune system of the offspring. Gestational colonization increases intestinal group 3 innate lymphoid cells and F4/80(+)CD11c(+) mononuclear cells in the pups. Maternal colonization reprograms intestinal transcriptional profiles of the offspring, including increased expression of genes encoding epithelial antibacterial peptides and metabolism of microbial molecules. Some of these effects are dependent on maternal antibodies that potentially retain microbial molecules and transmit them to the offspring during pregnancy and in milk. Pups born to mothers transiently colonized in pregnancy are better able to avoid inflammatory responses to microbial molecules and penetration of intestinal microbes.
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            Gastrointestinal flora and gastrointestinal status in children with autism -- comparisons to typical children and correlation with autism severity

            Background Children with autism have often been reported to have gastrointestinal problems that are more frequent and more severe than in children from the general population. Methods Gastrointestinal flora and gastrointestinal status were assessed from stool samples of 58 children with Autism Spectrum Disorders (ASD) and 39 healthy typical children of similar ages. Stool testing included bacterial and yeast culture tests, lysozyme, lactoferrin, secretory IgA, elastase, digestion markers, short chain fatty acids (SCFA's), pH, and blood presence. Gastrointestinal symptoms were assessed with a modified six-item GI Severity Index (6-GSI) questionnaire, and autistic symptoms were assessed with the Autism Treatment Evaluation Checklist (ATEC). Results Gastrointestinal symptoms (assessed by the 6-GSI) were strongly correlated with the severity of autism (assessed by the ATEC), (r = 0.59, p < 0.001). Children with 6-GSI scores above 3 had much higher ATEC Total scores than those with 6-GSI-scores of 3 or lower (81.5 +/- 28 vs. 49.0 +/- 21, p = 0.00002). Children with autism had much lower levels of total short chain fatty acids (-27%, p = 0.00002), including lower levels of acetate, proprionate, and valerate; this difference was greater in the children with autism taking probiotics, but also significant in those not taking probiotics. Children with autism had lower levels of species of Bifidobacter (-43%, p = 0.002) and higher levels of species of Lactobacillus (+100%, p = 0.00002), but similar levels of other bacteria and yeast using standard culture growth-based techniques. Lysozyme was somewhat lower in children with autism (-27%, p = 0.04), possibly associated with probiotic usage. Other markers of digestive function were similar in both groups. Conclusions The strong correlation of gastrointestinal symptoms with autism severity indicates that children with more severe autism are likely to have more severe gastrointestinal symptoms and vice versa. It is possible that autism symptoms are exacerbated or even partially due to the underlying gastrointestinal problems. The low level of SCFA's was partly associated with increased probiotic use, and probably partly due to either lower production (less sacchrolytic fermentation by beneficial bacteria and/or lower intake of soluble fiber) and/or greater absorption into the body (due to longer transit time and/or increased gut permeability).
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              The composition and stability of the vaginal microbiota of normal pregnant women is different from that of non-pregnant women

              Background This study was undertaken to characterize the vaginal microbiota throughout normal human pregnancy using sequence-based techniques. We compared the vaginal microbial composition of non-pregnant patients with a group of pregnant women who delivered at term. Results A retrospective case–control longitudinal study was designed and included non-pregnant women (n = 32) and pregnant women who delivered at term (38 to 42 weeks) without complications (n = 22). Serial samples of vaginal fluid were collected from both non-pregnant and pregnant patients. A 16S rRNA gene sequence-based survey was conducted using pyrosequencing to characterize the structure and stability of the vaginal microbiota. Linear mixed effects models and generalized estimating equations were used to identify the phylotypes whose relative abundance was different between the two study groups. The vaginal microbiota of normal pregnant women was different from that of non-pregnant women (higher abundance of Lactobacillus vaginalis, L. crispatus, L. gasseri and L. jensenii and lower abundance of 22 other phylotypes in pregnant women). Bacterial community state type (CST) IV-B or CST IV-A characterized by high relative abundance of species of genus Atopobium as well as the presence of Prevotella, Sneathia, Gardnerella, Ruminococcaceae, Parvimonas, Mobiluncus and other taxa previously shown to be associated with bacterial vaginosis were less frequent in normal pregnancy. The stability of the vaginal microbiota of pregnant women was higher than that of non-pregnant women; however, during normal pregnancy, bacterial communities shift almost exclusively from one CST dominated by Lactobacillus spp. to another CST dominated by Lactobacillus spp. Conclusion We report the first longitudinal study of the vaginal microbiota in normal pregnancy. Differences in the composition and stability of the microbial community between pregnant and non-pregnant women were observed. Lactobacillus spp. were the predominant members of the microbial community in normal pregnancy. These results can serve as the basis to study the relationship between the vaginal microbiome and adverse pregnancy outcomes.
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                Author and article information

                Contributors
                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi
                2314-6133
                2314-6141
                2018
                2 October 2018
                : 2018
                : 7218187
                Affiliations
                1Department of General Pediatrics and Neonatology, Justus-Liebig-University and Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Lung Research Center (DZL), Feulgenstrasse 12, D-35392 Gießen, Germany
                2Department of Gynecology and Obstetrics, Justus-Liebig-University, Feulgenstrasse 12, D-35392 Gießen, Germany
                3Department of General Pediatrics, University Clinic of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
                4Research Unit for Comparative Microbiome Analysis, Helmholtz Zentrum München GmbH, Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany
                5Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany
                6Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Max-Lebsche-Platz 31, D-81377 Munich, Germany
                7Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Borstel, Germany, Member of the German Center for Lung Research (DZL), Germany
                8Institute of Experimental Medicine, Christian-Albrechts-University of Kiel, Kiel, Germany
                Author notes

                Guest Editor: Aris Antsaklis

                Author information
                http://orcid.org/0000-0003-4307-8759
                http://orcid.org/0000-0003-4587-1734
                Article
                10.1155/2018/7218187
                6189679
                30370305
                edf9dc7f-a822-4eb8-85aa-f9de15ebaa11
                Copyright © 2018 Birte Staude et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 4 May 2018
                : 13 September 2018
                Funding
                Funded by: Deutsche Forschungsgemeinschaft
                Award ID: KFO 309
                Funded by: von Behring Röntgen Stiftung
                Award ID: 63-0009
                Award ID: 65-0019
                Funded by: Leibniz Competition 2016
                Categories
                Review Article

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