Molecular analysis of the gut microbiota of identical twins with Crohn's disease

Department of Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
The ISME Journal (Impact Factor: 9.3). 08/2008; 2(7):716-27. DOI: 10.1038/ismej.2008.37
Source: PubMed


Increasing evidence suggests that a combination of host genetics and the composition of the gut microbiota are important for development of Crohn's disease (CD). Our aim was to study identical twins with CD to determine microbial factors independent of host genetics. Fecal samples were studied from 10 monozygotic twin pairs with CD (discordant n=6 and concordant n=4) and 8 healthy twin pairs. DNA was extracted, 16S rRNA genes were PCR amplified and T-RFLP fingerprints generated using general bacterial and Bacteroides group-specific primers. The microbial communities were also profiled based on their percentage G+C contents. Bacteroides 16S rRNA genes were cloned and sequenced from a subset of the samples. The bacterial diversity in each sample and similarity indices between samples were estimated based on the T-RFLP data using a combination of statistical approaches. Healthy individuals had a significantly higher bacterial diversity compared to individuals with CD. The fecal microbial communities were more similar between healthy twins than between twins with CD, especially when these were discordant for the disease. The microbial community profiles of individuals with ileal CD were significantly different from healthy individuals and those with colonic CD. Also, CD individuals had a lower relative abundance of B. uniformis and higher relative abundances of B. ovatus and B. vulgatus. Our results suggest that genetics and/or environmental exposure during childhood, in part, determine the gut microbial composition. However, CD is associated with dramatic changes in the gut microbiota and this was particularly evident for individuals with ileal CD.

Download full-text


Available from: Curt Tysk,
  • Source
    • "Bacteroidetes, Lachnospiraceae Decrease IBD, Crohn's disease Bacteroides ovatus, Bacteroides vulgatus Increase [49] "
    [Show abstract] [Hide abstract]
    ABSTRACT: The human gut commensal microbiota forms a complex population of microorganisms that survive by having maintaining a symbiotic relationship with the host. Amongst the metabolic benefits it brings, formation of adaptive immune system and maintenance of its homeostasis are functions that play as important role. This review discusses the integral elements of commensal microbiota that stimulate responses of different parts of the immune system and leads to health or disease. It aims to establish conditions and factors that contribute to gut commensal microbiota's transformation from symbiotic to antibiotic relationship with human. We suggest that a the host-microbiota relationship has been evolved to benefit both parties and any changes that may lead to disease, are not due to unfriendly properties of the gut microbiota but due to host genetics or environmental changes such as diet or infection.
    Medicina (Kaunas, Lithuania) 03/2015; 464(2). DOI:10.1016/j.medici.2015.03.001 · 0.49 Impact Factor
  • Source
    • "The human microbiome comprises trillions of bacteria, archaea, fungi, protozoa, and viruses. Disruptions in host-microbe balance are associated with a wide range of diseases, including obesity (Ley et al., 2006; Turnbaugh et al., 2006), malnutrition (Smith et al., 2013a), inflammatory bowel disease (IBD) (Dicksved et al., 2008; Morgan et al., 2012), liver disease (Wong et al., 2013; Zhu et al., 2013), and cancer (Castellarin et al., 2012; Iida et al., 2013; Kostic et al., 2012). The microbiota of healthy populations, which have been cataloged by efforts such as the Human Microbiome Project (HMP) (Human Microbiome Project Consortium, 2012b) and MetaHIT (Qin et al., 2010), encode at least 100-fold more genes than do their human hosts, and it is estimated that 10% of all circulating metabolites in the human body are microbially derived (Wikoff et al., 2009). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Human-associated microbes are the source of many bioactive microbial products (proteins and metabolites) that play key functions both in human host pathways and in microbe-microbe interactions. Culture-independent studies now provide an accelerated means of exploring novel bioactives in the human microbiome; however, intriguingly, a substantial fraction of the microbial metagenome cannot be mapped to annotated genes or isolate genomes and is thus of unknown function. Meta’omic approaches, including metagenomic sequencing, metatranscriptomics, metabolomics, and integration of multiple assay types, represent an opportunity to efficiently explore this large pool of potential therapeutics. In combination with appropriate follow-up validation, high-throughput culture-independent assays can be combined with computational approaches to identify and characterize novel and biologically interesting microbial products. Here we briefly review the state of microbial product identification and characterization and discuss possible next steps to catalog and leverage the large uncharted fraction of the microbial metagenome.
    Cell Metabolism 11/2014; 20(5):731-741. DOI:10.1016/j.cmet.2014.10.003 · 17.57 Impact Factor
  • Source
    • "Although an individual's genetic predisposition likely plays a role in this establishment (Zoetendal et al., 2001; Dicksved et al., 2008; Johansson et al., 2011), it is highly influenced by environmental (lifestyle) factors (Dominguez-Bello et al., 2011). The initial gut microbiota of infants delivered by caesarean section differs from that of vaginally delivered infants and resembles the skin microbiota rather than the mother's vaginal microbiota (Dominguez-Bello et al., 2010, 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: An anthroposophic lifestyle, which has been associated with reduced allergy risk in children, has several characteristics that could influence gut microbiota. This study aimed to investigate the impact of anthroposophic lifestyle as well as specific early life exposures, on the gut microbiota. In total, 665 stool samples from 128 mother-child pairs from the ALADDIN birth cohort study were included. Samples collected from infants at ages six days, three weeks, two months and six months and from their mothers before and after delivery, respectively, were analyzed using 454-pyrosequencing. Information regarding lifestyle exposures was collected prospectively through interviews and questionnaires. Six month-old infants in anthroposophic families had a significantly higher abundance of Bifidobacterium and lower abundances of Bacteroides and Veillonella. Caesarean section and breastfeeding had a significant impact on the microbiota whereby caesarean section was primarily associated with delayed colonization of Bifidobacterium and Bacteroides, whereas breastfed children had a higher relative abundance of Bifidobacterium and a lower abundance of Clostridiales. However, despite large differences in lifestyle exposures, we determined no significant differences in the gut microbiota between the anthroposophic and non-anthroposophic mothers or their infants’ before six months of age.This article is protected by copyright. All rights reserved.
    FEMS Microbiology Ecology 10/2014; 90(3). DOI:10.1111/1574-6941.12434 · 3.57 Impact Factor
Show more