Nod2 is essential for temporal development of intestinal microbial communities

Rehman, Ateequr; Sina, Christian; Gavrilova, Olga; Häsler, Robert; Ott, Stephan; Baines, John F.; Schreiber, Stefan; Rosenstiel, Philip

doi:10.1136/gut.2010.216259

Cited by 281 publications

(239 citation statements)

References 62 publications

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“…Variable regions V1 and V2 of the 16S rRNA gene and 16S cDNA were amplified and sequenced with 454 pyrosequencing as previously described. 47 Data processing Data were preprocessed using MOTHUR version 1.26.0 as previously reported. 48,49 …”

Section: Methodsmentioning

confidence: 99%

Dynamic changes of the luminal and mucosa-associated gut microbiota during and after antibiotic therapy with paromomycin

Heinsen

Knecht

Neulinger³

et al. 2015

Gut Microbes

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(2015) Dynamic changes of the luminal and mucosa-associated gut microbiota during and after antibiotic therapy with paromomycin, Gut Microbes, 6:4, 243-254, DOI: 10.1080/19490976.2015 To link to this article: https://doi.org/10. 1080/19490976.2015 Keywords: 16S rRNA gene, antibiotics, lumen, microbiota, mucosaGut microbiota play a key role in the host's health system. Broad antibiotic therapy is known to disrupt the microbial balance affecting pathogenic as well as host-associated microbes. The aim of the present study was to investigate the influence of antibiotic paromomycin on the luminal and mucosa-associated microbiota at the DNA (abundance) and RNA (potential activity) level as well as to identify possible differences. The influence of antibiotic treatment on intestinal microbiota was investigated in 5 healthy individuals (age range: 20-22 years). All participants received the antibiotic paromomycin for 3 d. Fecal samples as well as sigmoidal biopsies were collected before and immediately after cessation of antibiotic treatment as well as after a recovery phase of 42 d. Compartment-and treatment statusspecific indicator operational taxonomic units (OTUs) as well as abundance-and activity-specific patterns were identified by 16S rRNA and 16S rRNA gene amplicon libraries and high-throughput pyrosequencing. Microbial composition of lumen and mucosa were significantly different at the DNA compared to the RNA level. Antibiotic treatment resulted in changes of the microbiota, affecting the luminal and mucosal bacteria in a similar way. Several OTUs were identified as compartment-and/or treatment status-specific. Abundance and activity patterns of some indicator OTUs differed considerably. The study shows fundamental changes in composition of gut microbiota under antibiotic therapy at both the potential activity and the abundance level at different treatment status. It may help to understand the complex processes of gut microbiota changes involved in resilience mechanisms and on development of antibiotic-associated clinical diseases.

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Section: Methodsmentioning

confidence: 99%

Dynamic changes of the luminal and mucosa-associated gut microbiota during and after antibiotic therapy with paromomycin

Heinsen

Knecht

Neulinger³

et al. 2015

Gut Microbes

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show abstract

“…19,20 In brief, extraction was performed with the Fast DNA spin kit after homogenisation of tissue samples in 200 ll tissue lysis buffer (200 mM HEPES, pH 7.5, 1 M KCl, 100 mM MgCl 2 , 1 mM EDTA, 0.2% NaN 3 ). Twentyfive ll of proteinase K was added before incubating at 55 C for 2 h (PeqLab, Erlangen, Germany) and mechanical force was applied to maximize bacterial cell wall lysis.…”

Section: Taqman Low-density Arraysmentioning

confidence: 99%

Characteristic changes in microbial community composition and expression of innate immune genes in acute appendicitis

et al. 2013

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Appendicitis represents a common and severe gastrointestinal illness in younger individuals worldwide. The disease is characterized by an excessive inflammatory response and it is believed that bacterial overgrowth due to blockage of the appendix lumen might be involved. Despite the high incidence, only limited data on the pathophysiological changes exist; in particular, the innate immune responses involved are largely unknown. Real-time PCR analysis of tissue samples from inflamed and normal appendices demonstrated differentially regulated expression patterns of epithelial-derived antimicrobial peptides (AMP). The a-defensins human neutrophil peptides 1-3, HD5 and HD6, as well as the two b-defensins, human b-defensins (hBD)-2 and hBD-3, were up-regulated, whereas hBD-1 was down-regulated in acute appendicitis. Expression of upstream regulators of AMP expression, NOD-2 and TLRs 1, 2, 4, 5, 7, 8 and 10 was significantly increased as detected by real-time PCR. Finally, we confirmed the involvement of the pro-inflammatory cytokines IL-1b and IL-8, and detected characteristic changes in microbial community composition in appendicitis tissue specimens by 16S rDNA based detection techniques. In this study, we demonstrate a differential regulation of the innate immune system along with an altered bacterial diversity in acute appendicitis.

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“…Nod/Ripk2 activation has also been linked to the induction of autophagy (15,16), and Nod1 signaling is required for the formation of isolated lymphoid follicles in the small intestine (17). Mice with genetic disruption of the Nod/Ripk2 signaling pathway have a dysbiotic intestinal flora resulting in altered susceptibility to intestinal inflammation (17)(18)(19). Whether ILCs can sense bacteria directly through the Nod/Ripk2 pathway has not been studied.…”

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confidence: 99%

Nod/Ripk2 signaling in dendritic cells activates IL-17A–secreting innate lymphoid cells and drives colitis inT-bet^−/−.Rag2^−/−(TRUC) mice

Ermann

Staton

Glickman

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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T-bet −/− .Rag2 −/− (TRUC) mice spontaneously develop microbiotadriven, TNF-mediated large bowel inflammation that resembles human ulcerative colitis. We show here that IL-23 and IL-1-dependent secretion of IL-17A by innate lymphoid cells (ILCs; defined as CD45 + lin − Thy1 hi NKp46 − ) is a second critical pathway in this model. Using an in vitro coculture system of bone marrow-derived dendritic cells (DCs) and freshly isolated FACS-purified ILCs, we demonstrate that IL-23 and IL-1 secreted by DCs in response to microbial stimulation work together to induce IL-17A production by ILCs. TNF is not required for IL-17A secretion by ILCs in vitro but synergizes with IL-17A to induce the expression of neutrophilattracting chemokines. Upstream, activation of the IL-23/IL-17A axis is regulated by nucleotide-binding oligomerization domain containing (Nod)/receptor-interacting serine-threonine kinase 2 (Ripk2) signals in DCs. Genetic ablation of the Nod/Ripk2 signaling pathway protects TRUC mice from developing colitis without affecting the colitogenicity of the intestinal microbiota. Our data provide insight into the complex network of interactions between IL-17A-secreting ILCs and other components of the innate immune system in the development of colitis.

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Nod2 is essential for temporal development of intestinal microbial communities

Abstract: Our results point to an essential role of Nod2 for the temporal development and composition of the host microbiota, both in mice and in humans, which may contribute to the complex role of NOD2 for the aetiopathogenesis of Crohn's disease.

Cited by 281 publications

References 62 publications

Dynamic changes of the luminal and mucosa-associated gut microbiota during and after antibiotic therapy with paromomycin

Dynamic changes of the luminal and mucosa-associated gut microbiota during and after antibiotic therapy with paromomycin

Characteristic changes in microbial community composition and expression of innate immune genes in acute appendicitis

Nod/Ripk2 signaling in dendritic cells activates IL-17A–secreting innate lymphoid cells and drives colitis inT-bet^−/−.Rag2^−/−(TRUC) mice

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Nod2 is essential for temporal development of intestinal microbial communities

Abstract: Our results point to an essential role of Nod2 for the temporal development and composition of the host microbiota, both in mice and in humans, which may contribute to the complex role of NOD2 for the aetiopathogenesis of Crohn's disease.

Cited by 281 publications

References 62 publications

Dynamic changes of the luminal and mucosa-associated gut microbiota during and after antibiotic therapy with paromomycin

Dynamic changes of the luminal and mucosa-associated gut microbiota during and after antibiotic therapy with paromomycin

Characteristic changes in microbial community composition and expression of innate immune genes in acute appendicitis

Nod/Ripk2 signaling in dendritic cells activates IL-17A–secreting innate lymphoid cells and drives colitis inT-bet−/−.Rag2−/−(TRUC) mice

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Nod/Ripk2 signaling in dendritic cells activates IL-17A–secreting innate lymphoid cells and drives colitis inT-bet^−/−.Rag2^−/−(TRUC) mice