The effects of intestinal microbial community structure on disease manifestation in IL-10-/- mice infected with Helicobacter hepaticus

Nagalingam, Nabeetha A.; Robinson, Courtney J.; Bergin, Ingrid L.; Eaton, Kathryn A.; Huffnagle, Gary B.; Young, Vincent B.

doi:10.1186/2049-2618-1-15

Cited by 36 publications

(35 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Using T-RFLP and 16S rRNA sequencing, two previous studies showed that H. hepaticus becomes a dominant member of the microbiota and reduced microbial diversity within the mouse intestinal tract of WT and IL-10 KO mice [44], [45]. In this study, H. hepaticus infection did not significantly affect the alpha diversity in WT mice after 1 year of infection, and had a low relative abundance.…”

Section: Discussioncontrasting

confidence: 38%

Helicobacter hepaticus Infection Promotes Hepatitis and Preneoplastic Foci in Farnesoid X Receptor (FXR) Deficient Mice

et al. 2014

View full text Add to dashboard Cite

Farnesoid X receptor (FXR) is a nuclear receptor that regulates bile acid metabolism and transport. Mice lacking expression of FXR (FXR KO) have a high incidence of foci of cellular alterations (FCA) and liver tumors. Here, we report that Helicobacter hepaticus infection is necessary for the development of increased hepatitis scores and FCA in previously Helicobacter-free FXR KO mice. FXR KO and wild-type (WT) mice were sham-treated or orally inoculated with H. hepaticus. At 12 months post-infection, mice were euthanized and liver pathology, gene expression, and the cecal microbiome were analyzed. H. hepaticus induced significant increases hepatitis scores and FCA numbers in FXR KO mice (P<0.01 and P<0.05, respectively). H. hepaticus altered the beta diversity of cecal microbiome in both WT and FXR KO mice compared to uninfected mice (P<0.05). Significant upregulation of β-catenin, Rela, Slc10a1, Tlr2, Nos2, Vdr, and Cyp3a11 was observed in all FXR KO mice compared to controls (P<0.05). Importantly, H. hepaticus and FXR deficiency were necessary to significantly upregulate Cyp2b10 (P<0.01). FXR deficiency was also a potent modulator of the cecal microbiota, as observed by a strong decrease in alpha diversity. A significant decrease in Firmicutes, particularly members of the order Clostridiales, was observed in FXR KO mice (P<0.05 and FDR<5%, ANOVA). While FXR deficiency strongly affects expression of genes related to immunity and bile acid metabolism, as well as the composition of the microbiome; however, its deficiency was not able to produce significant histopathological changes in the absence of H. hepaticus infection.

show abstract

Section: Discussioncontrasting

confidence: 38%

Helicobacter hepaticus Infection Promotes Hepatitis and Preneoplastic Foci in Farnesoid X Receptor (FXR) Deficient Mice

et al. 2014

View full text Add to dashboard Cite

show abstract

“…To further delineate the role of NLRP6 in modulating intestinal inflammatory responses, we generated mice doubly deficient in NLRP6 and IL10. IL10 −/− B6 mice at our facility are resistant to the development of colitis (Nagalingam et al, 2013)(Figure S1A). However, by 8 weeks of age, IL10 −/− Nlrp6 −/− mice developed spontaneous colitis (Figure 1A).…”

Section: Resultsmentioning

confidence: 99%

NLRP6 Protects Il10 Mice from Colitis by Limiting Colonization of Akkermansia muciniphila

et al. 2017

View full text Add to dashboard Cite

Summary Dysfunction in host immune responses and pathologic alterations in the gut microbiota, referred to as dysbiosis, can both contribute to the development of inflammatory bowel disease (IBD). However, it remains unclear how specific changes in host immunity or the microbiota cause disease. We previously demonstrated that the loss of the innate immune receptor NLRP6 in mice resulted in impaired production of IL18 and increased susceptibility to epithelial-induced injury. Here, we show that NLRP6 is important for suppressing the development of spontaneous colitis in the IL10−/− mice model of IBD and that NLRP6-deficiency results in the enrichment of Akkermansia muciniphila. A. muciniphila was sufficient for promoting intestinal inflammation in both specific-pathogen free and germfree IL10−/− mice. Our results demonstrate that A. muciniphila can act as a pathobiont to promote colitis in a genetically-susceptible host and that NLRP6 is a key regulator of its abundance.

show abstract

“…The structure of the intestinal microbiota was shown to be essential for the development of typhlocolitis in H. hepaticus infected IL-10 deficient mice; in addition, where disease could be initiated, severity of histopathological lesions varied significantly in the presence of different microbial communities 32 . While H. hepaticus drives immune responses in this model, the specific structure of the microbiota was believed to modulate host gene expression pathways that lead to chronic intestinal inflammation.…”

Section: Discussionmentioning

confidence: 99%

Helicobacter bilis Infection Alters Mucosal Bacteria and Modulates Colitis Development in Defined Microbiota Mice

Atherly

Mosher

Wang

et al. 2016

Inflammatory Bowel Diseases

View full text Add to dashboard Cite

Background Helicobacter bilis infection of C3H/HeN mice harboring the altered Schaedler flora (ASF) triggers progressive immune responsiveness and the development of colitis. We sought to investigate temporal alterations in community structure of a defined (ASF-colonized) microbiota in normal and inflamed murine intestines, and to correlate microbiota changes to histopathologic lesions. Methods The colonic mucosal microbiota of healthy mice and ASF mice colonized with H. bilis for 3, 6, or 12 weeks was investigated by fluorescence in situ hybridization (FISH) targeting the 16S rRNA genes of total bacteria, group-specific organisms, and individual ASF bacterial species. Microbial profiling of ASF and H. bilis abundance was performed on cecal contents. Results H. bilis colonized mice developed colitis associated with temporal changes in composition and spatial distribution of the mucosal microbiota. The number of total bacteria, ASF519, and helicobacter-positive bacteria were increased (P<0.05) while ASF360/361-positive bacteria were decreased (P<0.05) versus controls. Adherent biofilms in colitic mice were most often (P<0.05) composed of total bacteria, ASF457, and H. bilis. Total numbers of ASF519 and H. bilis bacteria were positively correlated (P=0.03, r=0.39 and P<0.0001, r=0.73) and total numbers of ASF360/361 bacteria were negatively correlated (P=0.003, r=−0.53) to histopathologic score. Differences in cecal abundance of ASF members were not observed. Conclusions Altered community structure with murine colitis is characterized by distinct ASF bacteria that interact with the colonic mucosa, either by formation of an isolating interlaced layer, by attachment, or by invasion, and this interaction is differentially expressed over time.

show abstract

The effects of intestinal microbial community structure on disease manifestation in IL-10-/- mice infected with Helicobacter hepaticus

Cited by 36 publications

References 68 publications

Helicobacter hepaticus Infection Promotes Hepatitis and Preneoplastic Foci in Farnesoid X Receptor (FXR) Deficient Mice

Helicobacter hepaticus Infection Promotes Hepatitis and Preneoplastic Foci in Farnesoid X Receptor (FXR) Deficient Mice

NLRP6 Protects Il10 Mice from Colitis by Limiting Colonization of Akkermansia muciniphila

Helicobacter bilis Infection Alters Mucosal Bacteria and Modulates Colitis Development in Defined Microbiota Mice

Contact Info

Product

Resources

About