Commensal and Probiotic Bacteria Influence Intestinal Barrier Function and Susceptibility to Colitis in Nod1−/−;Nod2−/− Mice

Natividad, Jane M.; Petit, Valérie; Huang, Xianxi; Palma, Giada De; Jury, Jennifer; Sanz, Yolanda; Philpott, Dana J.; Rodenas, Clara L. Garcia; McCoy, Kathy D.; Verdú, Elena F.

doi:10.1002/ibd.22848

Cited by 113 publications

(91 citation statements)

References 58 publications

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“…For Nod2-deficient mice, we compared relative structure was also reported from DGGE fingerprinting of colon samples from Nod1Nod2 DKO and Het-Het littermates despite decreased expression of antimicrobial RegIII-γ and E-cadherin and increased paracellular permeability, other markers of a weakened epithelial barrier. 26 Our results are also in line with a recent report that found no differences in bacterial community structure between MyD88-, TLR2-, TLR4-, TLR5-and TLR9-deficient and their WT littermates using high-throughput sequencing. 21 These findings emphasize the need for robust experimental design for evaluating intestinal bacterial communities.…”

Section: Resultssupporting

confidence: 93%

Nod1 and Nod2 signaling does not alter the composition of intestinal bacterial communities at homeostasis

et al. 2013

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Section: Resultssupporting

confidence: 93%

Nod1 and Nod2 signaling does not alter the composition of intestinal bacterial communities at homeostasis

et al. 2013

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“…Epithelial regeneration is a crucial step in mucosal healing and this mechanism requires the coordinated activity of IEC, Paneth cells, and goblet cells to restore intestinal barrier function (32)(33)(34). Mice carrying both Nod1 and Nod2 deletion have decreased paracellular permeability and a higher susceptibility to dextran sulfate sodium-induced colitis, highlighting a potential role of Nod receptors in the maintenance of intestinal barrier function (35). Moreover, another study reported a new function for Nod2 in affording ISC survival and epithelial regeneration (8).…”

Section: Discussionmentioning

confidence: 99%

The Cytosolic Microbial Receptor Nod2 Regulates Small Intestinal Crypt Damage and Epithelial Regeneration following T Cell–Induced Enteropathy

Zanello

Goethel

Rouquier

et al. 2016

The Journal of Immunology

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Loss of function in the NOD2 gene is associated with a higher risk of developing Crohn’s disease (CD). CD is characterized by activation of T cells and activated T cells are involved in mucosal inflammation and mucosal damage. We found that acute T cell activation with anti-CD3 mAb induced stronger small intestinal mucosal damage in NOD2−/− mice compared with wild-type mice. This enhanced mucosal damage was characterized by loss of crypt architecture, increased epithelial cell apoptosis, delayed epithelial regeneration and an accumulation of inflammatory cytokines and Th17 cells in the small intestine. Partial microbiota depletion with antibiotics did not decrease mucosal damage 1 d after anti-CD3 mAb injection, but it significantly reduced crypt damage and inflammatory cytokine secretion in NOD2−/− mice 3 d after anti-CD3 mAb injection, indicating that microbial sensing by Nod2 was important to control mucosal damage and epithelial regeneration after anti-CD3 mAb injection. To determine which cells play a key role in microbial sensing and regulation of mucosal damage, we engineered mice carrying a cell-specific deletion of Nod2 in villin and Lyz2-expressing cells. T cell activation did not worsen crypt damage in mice carrying either cell-specific deletion of Nod2 compared with wild-type mice. However, increased numbers of apoptotic epithelial cells and higher expression of TNF-α and IL-22 were observed in mice carrying a deletion of Nod2 in Lyz2-expressing cells. Taken together, our results demonstrate that microbial sensing by Nod2 is an important mechanism to regulate small intestinal mucosal damage following acute T cell activation.

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“…Nod2 expression in the intestine is dependent on the presence of a gut microbiota, and Nod2 knockout mice are more susceptible to colonization by intestinal mouse pathogens (Petnicki-Ocwieja et al 2009). Mice deficient in Nod1 and Nod2 have altered gut microbiota composition as compared with their heterozygous littermates (Natividad et al 2012). NLRP6 is a NLR family member that functions in inflammasome, type 1 interferon, and NF-kB signaling.…”

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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Commensal and Probiotic Bacteria Influence Intestinal Barrier Function and Susceptibility to Colitis in Nod1−/−;Nod2−/− Mice

Abstract: The intestinal microbiota influences colitis severity in Nod1(-/-); Nod2(-/-) mice. The results suggest that colonization strategies with defined commensals or exogenous specific probiotic therapy may prevent intestinal inflammation in a genetically predisposed host.

Cited by 113 publications

References 58 publications

Nod1 and Nod2 signaling does not alter the composition of intestinal bacterial communities at homeostasis

Nod1 and Nod2 signaling does not alter the composition of intestinal bacterial communities at homeostasis

The Cytosolic Microbial Receptor Nod2 Regulates Small Intestinal Crypt Damage and Epithelial Regeneration following T Cell–Induced Enteropathy

Exploring host–microbiota interactions in animal models and humans

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