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Journal ArticleDOI

Meconium microbiota types dominated by lactic acid or enteric bacteria are differentially associated with maternal eczema and respiratory problems in infants.

TL;DR: Culture‐dependent methods have shown that meconium, the newborn's first intestinal discharge, is not sterile, but the diversity of bacteria present in this material needs to be further characterized by means of more sensitive molecular techniques.
Abstract: Background Culture-dependent methods have shown that meconium, the newborn's first intestinal discharge, is not sterile, but the diversity of bacteria present in this material needs to be further characterized by means of more sensitive molecular techniques. Objective Our aims were to characterize molecularly the meconium microbiota in term infants, to assess whether it contributes to the future microbiota of the infants' gastrointestinal tract, and to evaluate how it relates to lifestyle variables and atopy-related conditions. Methods We applied high-throughput pyrosequencing of the 16S rRNA gene to study the meconium microbiota in twenty term newborns from a Spanish birth cohort. For comparison, we characterized the microbiota in fecal samples from seven pregnant women days before delivery and in two series of infant samples spanning the first seven months of life. We also compared our data with vaginal and skin microbiota characterized in independent studies. Different types of meconium microbiota were defined based on taxonomic composition and abundance and their associations with different factors were statistically evaluated. Results The meconium microbiota differs from those in adult feces, vagina and skin, but resembles that of fecal samples from young infants. Meconium samples clustered into two types with different bacterial diversity, richness and composition. One of the types was less diverse, dominated by enteric bacteria and associated with a history of atopic eczema in the mother (P = 0.038), whereas the second type was dominated by lactic acid bacteria and associated with respiratory problems in the infant (P = 0.040). Conclusions & clinical relevance Our findings suggest that the meconium microbiota has an intrauterine origin and participates in gut colonization. Although based on a small population sample, our association analyses also suggest that the type of bacteria detected in meconium is influenced by maternal factors and may have consequences for childhood health.
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Journal Article
TL;DR: FastTree as mentioned in this paper uses sequence profiles of internal nodes in the tree to implement neighbor-joining and uses heuristics to quickly identify candidate joins, then uses nearest-neighbor interchanges to reduce the length of the tree.
Abstract: Gene families are growing rapidly, but standard methods for inferring phylogenies do not scale to alignments with over 10,000 sequences. We present FastTree, a method for constructing large phylogenies and for estimating their reliability. Instead of storing a distance matrix, FastTree stores sequence profiles of internal nodes in the tree. FastTree uses these profiles to implement neighbor-joining and uses heuristics to quickly identify candidate joins. FastTree then uses nearest-neighbor interchanges to reduce the length of the tree. For an alignment with N sequences, L sites, and a different characters, a distance matrix requires O(N^2) space and O(N^2 L) time, but FastTree requires just O( NLa + N sqrt(N) ) memory and O( N sqrt(N) log(N) L a ) time. To estimate the tree's reliability, FastTree uses local bootstrapping, which gives another 100-fold speedup over a distance matrix. For example, FastTree computed a tree and support values for 158,022 distinct 16S ribosomal RNAs in 17 hours and 2.4 gigabytes of memory. Just computing pairwise Jukes-Cantor distances and storing them, without inferring a tree or bootstrapping, would require 17 hours and 50 gigabytes of memory. In simulations, FastTree was slightly more accurate than neighbor joining, BIONJ, or FastME; on genuine alignments, FastTree's topologies had higher likelihoods. FastTree is available at http://microbesonline.org/fasttree.

2,436 citations

Journal ArticleDOI
TL;DR: The gut microbiota of infants delivered by C-section showed significantly less resemblance to their mothers and nutrition had a major impact on early microbiota composition and function, with cessation of breast-feeding, rather than introduction of solid food, being required for maturation into an adult-like microbiota.

2,227 citations


Cites background from "Meconium microbiota types dominated..."

  • ...…abundant genus were sampled earlier than those dominated by Bacteroides or Bifidobacterium (Figure S2D; on average 2.6, 3.6, and 5.4 days after birth, respectively), in agreement with high abundance of Escherichia DNA in the meconium and the placenta (Aagaard et al., 2014; Gosalbes et al., 2013)....

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Journal ArticleDOI
TL;DR: The large majority of studies on the role of the microbiome in the pathogenesis of disease are correlative and preclinical; several have influenced clinical practice.
Abstract: The large majority of studies on the role of the microbiome in the pathogenesis of disease are correlative and preclinical; several have influenced clinical practice.

2,083 citations

Journal ArticleDOI
TL;DR: A unique placental microbiome niche was characterized, composed of nonpathogenic commensal microbiota from the Firmicutes, Tenericute, Proteobacteria, Bacteroidetes, and Fusobacteria phyla, which was consistently different from those reported in other parts of the body, including the skin and urogenital tract.
Abstract: Humans and their microbiomes have coevolved as a physiologic community composed of distinct body site niches with metabolic and antigenic diversity. The placental microbiome has not been robustly interrogated, despite recent demonstrations of intracellular bacteria with diverse metabolic and immune regulatory functions. A population-based cohort of placental specimens collected under sterile conditions from 320 subjects with extensive clinical data was established for comparative 16S ribosomal DNA-based and whole-genome shotgun (WGS) metagenomic studies. Identified taxa and their gene carriage patterns were compared to other human body site niches, including the oral, skin, airway (nasal), vaginal, and gut microbiomes from nonpregnant controls. We characterized a unique placental microbiome niche, composed of nonpathogenic commensal microbiota from the Firmicutes, Tenericutes, Proteobacteria, Bacteroidetes, and Fusobacteria phyla. In aggregate, the placental microbiome profiles were most akin (Bray-Curtis dissimilarity <0.3) to the human oral microbiome. 16S-based operational taxonomic unit analyses revealed associations of the placental microbiome with a remote history of antenatal infection (permutational multivariate analysis of variance, P = 0.006), such as urinary tract infection in the first trimester, as well as with preterm birth <37 weeks (P = 0.001).

1,948 citations


Cites background or result from "Meconium microbiota types dominated..."

  • ...Consistent with these and other investigators’ observations, Escherichia has been shown in high abundance in meconium from one recent study of newborns (38), and is a strong contributor to...

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  • ...Although we did not characterize the infant microbiome in this study, Escherichia has been shown in high abundance in meconium from one recent study of neonates (38) and is a strong contributor to early-onset (within 48 hours of birth) sepsis among extremely low birth weight neonates (39)....

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Journal ArticleDOI
TL;DR: The normal gut microbiota imparts specific function in host nutrient metabolism, xenobiotic and drug metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens.
Abstract: Relation between the gut microbiota and human health is being increasingly recognised It is now well established that a healthy gut flora is largely responsible for overall health of the host The normal human gut microbiota comprises of two major phyla, namely Bacteroidetes and Firmicutes Though the gut microbiota in an infant appears haphazard, it starts resembling the adult flora by the age of 3 years Nevertheless, there exist temporal and spatial variations in the microbial distribution from esophagus to the rectum all along the individual's life span Developments in genome sequencing technologies and bioinformatics have now enabled scientists to study these microorganisms and their function and microbe-host interactions in an elaborate manner both in health and disease The normal gut microbiota imparts specific function in host nutrient metabolism, xenobiotic and drug metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens Several factors play a role in shaping the normal gut microbiota They include (1) the mode of delivery (vaginal or caesarean); (2) diet during infancy (breast milk or formula feeds) and adulthood (vegan based or meat based); and (3) use of antibiotics or antibiotic like molecules that are derived from the environment or the gut commensal community A major concern of antibiotic use is the long-term alteration of the normal healthy gut microbiota and horizontal transfer of resistance genes that could result in reservoir of organisms with a multidrug resistant gene pool

1,602 citations

References
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TL;DR: Copyright (©) 1999–2012 R Foundation for Statistical Computing; permission is granted to make and distribute verbatim copies of this manual provided the copyright notice and permission notice are preserved on all copies.
Abstract: Copyright (©) 1999–2012 R Foundation for Statistical Computing. Permission is granted to make and distribute verbatim copies of this manual provided the copyright notice and this permission notice are preserved on all copies. Permission is granted to copy and distribute modified versions of this manual under the conditions for verbatim copying, provided that the entire resulting derived work is distributed under the terms of a permission notice identical to this one. Permission is granted to copy and distribute translations of this manual into another language, under the above conditions for modified versions, except that this permission notice may be stated in a translation approved by the R Core Team.

272,030 citations

Journal ArticleDOI
TL;DR: This final installment of the paper considers the case where the signals or the messages or both are continuously variable, in contrast with the discrete nature assumed until now.
Abstract: In this final installment of the paper we consider the case where the signals or the messages or both are continuously variable, in contrast with the discrete nature assumed until now. To a considerable extent the continuous case can be obtained through a limiting process from the discrete case by dividing the continuum of messages and signals into a large but finite number of small regions and calculating the various parameters involved on a discrete basis. As the size of the regions is decreased these parameters in general approach as limits the proper values for the continuous case. There are, however, a few new effects that appear and also a general change of emphasis in the direction of specialization of the general results to particular cases.

65,425 citations

Journal ArticleDOI
TL;DR: M mothur is used as a case study to trim, screen, and align sequences; calculate distances; assign sequences to operational taxonomic units; and describe the α and β diversity of eight marine samples previously characterized by pyrosequencing of 16S rRNA gene fragments.
Abstract: mothur aims to be a comprehensive software package that allows users to use a single piece of software to analyze community sequence data. It builds upon previous tools to provide a flexible and powerful software package for analyzing sequencing data. As a case study, we used mothur to trim, screen, and align sequences; calculate distances; assign sequences to operational taxonomic units; and describe the alpha and beta diversity of eight marine samples previously characterized by pyrosequencing of 16S rRNA gene fragments. This analysis of more than 222,000 sequences was completed in less than 2 h with a laptop computer.

17,350 citations

Journal ArticleDOI
TL;DR: A 16S rRNA gene database (http://greengenes.lbl.gov) was used to provide chimera screening, standard alignment, and taxonomic classification using multiple published taxonomies as mentioned in this paper.
Abstract: A 16S rRNA gene database (http://greengenes.lbl.gov) addresses limitations of public repositories by providing chimera screening, standard alignment, and taxonomic classification using multiple published taxonomies. It was found that there is incongruent taxonomic nomenclature among curators even at the phylum level. Putative chimeras were identified in 3% of environmental sequences and in 0.2% of records derived from isolates. Environmental sequences were classified into 100 phylum-level lineages in the Archaea and Bacteria.

9,593 citations

Journal ArticleDOI
TL;DR: Cd-hit-2d compares two protein datasets and reports similar matches between them; cd- Hit-est clusters a DNA/RNA sequence database and cd- hit-est-2D compares two nucleotide datasets.
Abstract: Motivation: In 2001 and 2002, we published two papers (Bioinformatics, 17, 282--283, Bioinformatics, 18, 77--82) describing an ultrafast protein sequence clustering program called cd-hit. This program can efficiently cluster a huge protein database with millions of sequences. However, the applications of the underlying algorithm are not limited to only protein sequences clustering, here we present several new programs using the same algorithm including cd-hit-2d, cd-hit-est and cd-hit-est-2d. Cd-hit-2d compares two protein datasets and reports similar matches between them; cd-hit-est clusters a DNA/RNA sequence database and cd-hit-est-2d compares two nucleotide datasets. All these programs can handle huge datasets with millions of sequences and can be hundreds of times faster than methods based on the popular sequence comparison and database search tools, such as BLAST. Availability: http://cd-hit.org Contact: [email protected]

8,306 citations

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