The Toll‐like receptors TLR2 and TLR4 do not affect the intestinal microbiota composition in mice

Loh, Gunnar; Brodziak, Frances; Blaut, Michaël

doi:10.1111/j.1462-2920.2007.01493.x

Cited by 35 publications

(35 citation statements)

References 37 publications

(34 reference statements)

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“…A limited number of individuals of the same strain were cocaged to evaluate this effect on cecum bacterial communities. Similar to previous reports (Alexander et al, 2006;Loh et al, 2008;Terán-Ventura et al, 2010), some cagemates were more similar to one another than to isolated mice, but for many no difference was detected. This response varied by mouse and was not strong for most strains.…”

Section: Discussionsupporting

confidence: 80%

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Host genetic and environmental effects on mouse intestinal microbiota

et al. 2012

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The mammalian gut harbors complex and variable microbial communities, across both host phylogenetic space and conspecific individuals. A synergy of host genetic and environmental factors shape these communities and account for their variability, but their individual contributions and the selective pressures involved are still not well understood. We employed barcoded pyrosequencing of V1-2 and V4 regions of bacterial small subunit ribosomal RNA genes to characterize the effects of host genetics and environment on cecum assemblages in 10 genetically distinct, inbred mouse strains. Eight of these strains are the foundation of the Collaborative Cross (CC), a panel of mice derived from a genetically diverse set of inbred founder strains, designed specifically for complex trait analysis. Diversity of gut microbiota was characterized by complementing phylogenetic and distance-based, sequence-clustering approaches. Significant correlations were found between the mouse strains and their gut microbiota, reflected by distinct bacterial communities. Cohabitation and litter had a reduced, although detectable effect, and the microbiota response to these factors varied by strain. We identified bacterial phylotypes that appear to be discriminative and strainspecific to each mouse line used. Cohabitation of different strains of mice revealed an interaction of host genetic and environmental factors in shaping gut bacterial consortia, in which bacterial communities became more similar but retained strain specificity. This study provides a baseline analysis of intestinal bacterial communities in the eight CC progenitor strains and will be linked to integrated host genotype, phenotype and microbiota research on the resulting CC panel.

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Section: Discussionsupporting

confidence: 80%

“…Similar to Friswell et al (2010), we found C3HRI to have low intrastrain variation and BL6J mice to have high intrastrain variation. Gut communities in BL10J mice (Loh et al, 2008) have also been shown to vary among individuals.…”

Section: Discussionmentioning

confidence: 99%

Host genetic and environmental effects on mouse intestinal microbiota

et al. 2012

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“…Thus, it will be important in future studies to take into account the physiological amounts of bacterial components and the particular species of commensal bacteria when interpreting data involving exogenous administration of bacteria and/or bacterium-derived components. The role of host immune system such as IgA in the development of the microflora remains controversial (25,42,44). The microflora of NOD1-deficient mice was reported to contain higher numbers of Clostridiales in the ileal biofilm (5), and MyD88-deficient mice contained increased percentages of particular bacteria including Lactobacillaceae and Porphyromonadaceae species (51).…”

Section: Vol 78 2010mentioning

confidence: 99%

Transitions in Oral and Intestinal Microflora Composition and Innate Immune Receptor-Dependent Stimulation during Mouse Development

Hasegawa¹,

Osaka

Tawaratsumida³

et al. 2010

Infect Immun

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Commensal bacteria possess immunostimulatory activities that can modulate host responses to affect development and homeostasis in the intestine. However, how different populations of resident bacteria stimulate the immune system remains largely unknown. We characterized here the ability of intestinal and oral microflora to stimulate individual pattern recognition receptors (PRRs) in bone marrow-derived macrophages and mesothelial cells. The intestinal but not oral microflora elicited age-and cell type-specific immunostimulation. The immunostimulatory activity of the intestinal microflora varied among individual mice but was largely mediated via Toll-like receptor 4 (TLR4) during breast-feeding, whereas it became TLR4 independent after weaning. This transition was associated with a change from a microflora rich in TLR4-stimulatory proteobacteria to one dominated by Bacteroidales and/or Clostridiales that poorly stimulate TLR4. The major stimulatory activity of the intestinal microflora was still intact in NOD1-, NOD2-, TLR2-, TLR4-, TLR5-, TLR9-, TLR11-, ASC-, or RICK-deficient cells but still relied on the adaptor MyD88. These studies demonstrate a transition in the intestinal microflora accompanied by a dynamic change of its ability to stimulate different PRRs which control intestinal homeostasis.Accumulating evidence indicates that environmental bacteria can regulate the development and homeostasis of the host immune system, particularly within the gut, and affect susceptibility to a variety of diseases (3,5,6,9,10,40,44). Both humans and animals harbor a large number of nonpathogenic residential bacteria, especially in the intestine and oral cavity (41). Uncontrolled translocation of bacteria or bacterial components into systemic tissues of the host often results in bacteremia and sepsis (8), which causes significant mortality worldwide each year. On the other hand, intestinal bacteria contain immunostimulatory molecules that can regulate local immunity, epithelial development, immunotolerance, and susceptibility to inflammatory bowel disease (2, 41). The bacteriumderived molecules are recognized by innate immune receptors, including Toll-like receptors (TLRs) and Nod-like receptors (NLRs) (8,20). TLRs and NLRs, often referred as pattern recognition receptors (PRRs), are involved in the recognition of commensal and pathogenic bacteria, as well as in the clearance of pathogens through interaction with their cognate microbial molecules (8,20). Interactions between PRRs and commensal bacteria have been demonstrated to be important for gut homeostasis. MyD88, an essential adaptor for TLR signaling, has been shown to be important for epithelial homeostasis (40) and IgA secretion in the intestine (3, 44), and TLR9 has been shown to be important for the balance of regulatory T/Th17/Th1 cells (10). In addition, NOD1, an NLR family member, was shown to play a role in the development of intestinal lymphoid tissue via the recognition of commensal bacteria (5). Finally, genetic variation in NOD1 affects the susceptibilit...

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“…A denaturing gradient gel electrophoresis and fluorescence in situ hybridization (FISH)-based investigation (Loh et al 2008) and a more recent study using deep 16S rRNA gene surveys both call into question whether TLRs or MyD88 alter the gut microbiota in a genotypedependent fashion (Ubeda et al 2012). Ubeda et al (2012) generated MyD88-, TLR-2-, TLR-4-, TLR-6-, and TLR-9-deficient mouse lines from heterozygote 3 heterozygote breeding strategies.…”

Section: Micementioning

confidence: 99%

Exploring host–microbiota interactions in animal models and humans

2013

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The animal and bacterial kingdoms have coevolved and coadapted in response to environmental selective pressures over hundreds of millions of years. The meta'omics revolution in both sequencing and its analytic pipelines is fostering an explosion of interest in how the gut microbiome impacts physiology and propensity to disease. Gut microbiome studies are inherently interdisciplinary, drawing on approaches and technical skill sets from the biomedical sciences, ecology, and computational biology. Central to unraveling the complex biology of environment, genetics, and microbiome interaction in human health and disease is a deeper understanding of the symbiosis between animals and bacteria. Experimental model systems, including mice, fish, insects, and the Hawaiian bobtail squid, continue to provide critical insight into how host-microbiota homeostasis is constructed and maintained. Here we consider how model systems are influencing current understanding of host-microbiota interactions and explore recent human microbiome studies.The distinctive body plans of animals offer many niches for members of the archaeal and bacterial kingdoms. While the lumen of the human distal gut is one of the most densely populated ecosystems on our planet, humans and other animals harbor several microbiomes on and within their body surfaces such as the respiratory and urogenital tracts and the skin. As the gut has evolved from the relatively simple tube of the ancient cyclostomatida to the more highly compartmentalized gastrointestinal tracts of mammalian species, the diversity and complexity of the microbial inhabitants of those spaces has increased as well (Fig.

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The Toll‐like receptors TLR2 and TLR4 do not affect the intestinal microbiota composition in mice

Cited by 35 publications

References 37 publications

Host genetic and environmental effects on mouse intestinal microbiota

Host genetic and environmental effects on mouse intestinal microbiota

Transitions in Oral and Intestinal Microflora Composition and Innate Immune Receptor-Dependent Stimulation during Mouse Development

Exploring host–microbiota interactions in animal models and humans

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