Development of the Human Gastrointestinal Microbiota and Insights From High-Throughput Sequencing

University of Colorado at Boulder, Boulder, Colorado, United States
Gastroenterology (Impact Factor: 16.72). 05/2011; 140(6):1713-9. DOI: 10.1053/j.gastro.2011.02.011
Source: PubMed


Little was known about the development of the gastrointestinal (GI) tract microbiota, until recently, because of difficulties in obtaining sufficient sequence information from enough people or time points. Now, with decreased costs of DNA sequencing and improved bioinformatic tools, we can compare GI tract bacterial communities among individuals, of all ages from infancy to adulthood. Some key recent findings are that the initial bacterial community, even in the GI tract, depends strongly on delivery mode; that the process of early development of the microbiota is highly unstable and idiosyncratic; that the microbiota differs considerably among children from different countries; and that older adults have substantially different GI tract communities than younger adults, indicating that the GI tract microbiota can change throughout life. We relate these observations to different models of evolution including the evolution of senescence and suggest that probiotics be selected based on patient age. Studies of the microbiota in older people might tell us which probiotics could increase longevity. Drug metabolism varies among individuals with different microbial communities, so age- and region-specific clinical trials are required to ensure safety and efficacy.

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Available from: Ruth Ley, Nov 08, 2014
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    • "Infants go from the womb to abruptly encountering the full microbial diversity of their new ex-utero environment. Early microbial colonization impacts the long-term adult microbial ecosystem (Biasucci et al., 2008), and is likely a critical ecological window that influences health trajectory throughout life (Blaser & Falkow, 2009;Dominguez-bello et al., 2011;Scholtens et al., 2012;Cho et al., 2012). Infant fecal samples are commonly studied to investigate the impacts of factors such as breastfeeding on the development of the gut microbiota and subsequent health effects. "
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    ABSTRACT: Infant fecal samples are commonly studied to investigate the impacts of breastfeeding on the development of the microbiota and subsequent health effects. Comparisons of infants living in different geographic regions and environmental contexts are needed to aid our understanding of evolutionarily-selected milk adaptations. However, the preservation of fecal samples from individuals in remote locales until they can be processed can be a challenge. Freeze-drying (lyophilization) offers a cost-effective way to preserve some biological samples for transport and analysis at a later date. Currently, it is unknown what, if any, biases are introduced into various analyses by the freeze-drying process. Here, we investigated how freeze-drying affected analysis of two relevant and intertwined aspects of infant fecal samples, marker gene amplicon sequencing of the bacterial community and the fecal oligosaccharide profile (undigested human milk oligosaccharides). No differences were discovered between the fecal oligosaccharide profiles of wet and freeze-dried samples. The marker gene sequencing data showed an increase in proportional representation of Bacteriodes and a decrease in detection of bifidobacteria and members of class Bacilli after freeze-drying. This sample treatment bias may possibly be related to the cell morphology of these different taxa (Gram status). However, these effects did not overwhelm the natural variation among individuals, as the community data still strongly grouped by subject and not by freeze-drying status. We also found that compensating for sample concentration during freeze-drying, while not necessary, was also not detrimental. Freeze-drying may therefore be an acceptable method of sample preservation and mass reduction for some studies of microbial ecology and milk glycan analysis.
    Full-text · Article · Jan 2016 · PeerJ
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    • "In the gastrointestinal tract, there are greater densities of bacterial species, which are also known as intestinal flora, and the common bacterial divisions are Firmicutes, Bacteroidetes, Actinobacteria , Proteobacteria, and Verrucomicrobia [23] [24]. To date, increasing data have reported massive diversity of bacterial species and Bacteroidetes and Firmicutes are referred to be the dominant bacterial groups in the gut [25]. Recently, evidence has demonstrated that gut microbiota are involved in the pathogenesis and etiology of IBD, reinforcing the view that interactions between intestinal microbes and the mucosal immune system promote the progression of IBD [26] [27]. "
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    ABSTRACT: Objectives: Interactions between the host and gut microbial community contribute to the pathogenesis of Crohn's disease (CD). In this study, we aimed to detect lipopolysaccharide (LPS) and 1,3-β-D-glucan (BG) in the sera of CD patients and clarify the potential role in the diagnosis and therapeutic approaches. Materials and methods: Serum samples were collected from 46 patients with active CD (A-CD), 22 CD patients at remission stage (R-CD), and 20 healthy controls, and the levels of LPS, BG, and TNF in sera were determined by ELISA. Moreover, sixteen patients with A-CD received anti-TNF monoclonal antibody therapy (infliximab, IFX) at a dose of 5 mg/kg body weight at weeks 0, 2, and 6, and the levels of LPS and BG were also tested at week 12 after the first intravenous infusion. Results: Serum levels of LPS and BG were found to be markedly increased in A-CD patients compared with R-CD patients and healthy controls (P < 0.05). They were also observed to be positively correlated with CDAI, ESR, and SES-CD, respectively (P < 0.05). Furthermore, the levels of TNF in sera had a significant correlation with LPS and BG, respectively. The concentrations of LPS and BG were demonstrated to be significantly downregulated in the sera of A-CD patients 12 weeks after IFX treatment (P < 0.05), suggesting that blockade of TNF could inhibit bacterial endotoxin absorption, partially through improving intestinal mucosal barrier. Conclusions: Serum levels of LPS and BG are significantly increased in A-CD patients and positively correlated with the severity of the disease. Blockade of intestinal mucosal inflammation with IFX could reduce the levels of LPS and BG in sera. Therefore, this study has shed some light on measurement of serum LPS and BG in the diagnosis and treatment of CD patients.
    Full-text · Article · Jun 2015 · Mediators of Inflammation
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    • "It is known that colonization initiates from maternally acquired bacteria during birth [6] and breastfeeding and continues throughout our life [7] [8] [9]. Over the lifetime of the individual, or at least until stabilization of colonizing microbiota in adulthood, there is a change in the profile of the predominant phyla in the gastrointestinal tract, migrating from a community dominated by Actinobacteria and Proteobacteria to one dominated by Firmicutes and Bacteroidetes [10]. The metagenome of an infant gut is characterized by an enrichment of genes required for the breakdown of simple sugars, such as lactose and galactose, while the weaned infant microbiota is enriched in genes for polysaccharide breakdown and vitamin production [11] [12]. "
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    ABSTRACT: The commensal microbiota is in constant interaction with the immune system, teaching immune cells to respond to antigens. Studies in mice have demonstrated that manipulation of the intestinal microbiota alters host immune cell homeostasis. Additionally, metagenomic-sequencing analysis has revealed alterations in intestinal microbiota in patients suffering from inflammatory bowel disease, asthma, and obesity. Perturbations in the microbiota composition result in a deficient immune response and impaired tolerance to commensal microorganisms. Due to altered microbiota composition which is associated to some inflammatory diseases, several strategies, such as the administration of probiotics, diet, and antibiotic usage, have been utilized to prevent or ameliorate chronic inflammatory diseases. The purpose of this review is to present and discuss recent evidence showing that the gut microbiota controls immune system function and onset, development, and resolution of some common inflammatory diseases.
    Full-text · Article · Sep 2014 · Research Journal of Immunology
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