Isolation of flagellated bacteria implicated in Crohnʼs disease

Duck, L. Wayne; Walter, Mark R.; Novák, Jaromír; Kelly, Denise; Tomasi, M.; Cong, Yingzi; Elson, Charles O.

doi:10.1002/ibd.20237

Cited by 110 publications

(113 citation statements)

References 41 publications

(55 reference statements)

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“…Because DSS treatment changes the characteristics of the inner and outer mucosal barriers, facilitating bacterial penetration by reduced thickness and permeability (42), it is possible that this group may also display increased invasiveness in undisturbed mucosa lacking protective ABO antigens. Furthermore, flagellins of this bacterial group serve as elicitors of inflammation in CD (57). Another noteworthy observation is an OTU belonging to Prevotella that is associated with sese controls.…”

Section: Discussionmentioning

confidence: 98%

Colonic mucosa-associated microbiota is influenced by an interaction of Crohn disease and FUT2 ( Secretor ) genotype

Rausch

Rehman

Künzel

et al. 2011

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

319

277

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The FUT2 (Secretor) gene is responsible for the presence of ABO histo-blood group antigens on the gastrointestinal mucosa and in bodily secretions. Individuals lacking a functional copy of FUT2 are known as “nonsecretors” and display an array of differences in susceptibility to infection and disease, including Crohn disease. To determine whether variation in resident microbial communities with respect to FUT2 genotype is a potential factor contributing to susceptibility, we performed 454-based community profiling of the intestinal microbiota in a panel of healthy subjects and Crohn disease patients and determined their genotype for the primary nonsecretor allele in Caucasian populations, W143X (G428A). Consistent with previous studies, we observe significant deviations in the microbial communities of individuals with Crohn disease. Furthermore, the FUT2 genotype explains substantial differences in community composition, diversity, and structure, and we identified several bacterial species displaying disease-by-genotype associations. These findings indicate that alterations in resident microbial communities may in part explain the variety of host susceptibilities surrounding nonsecretor status and that FUT2 is an important genetic factor influencing host–microbial diversity

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Section: Discussionmentioning

confidence: 98%

Colonic mucosa-associated microbiota is influenced by an interaction of Crohn disease and FUT2 ( Secretor ) genotype

Rausch

Rehman

Künzel

et al. 2011

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

319

277

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“…Flagellins bind to and activate the membrane bound toll-like receptor 5 and the cytosolic receptor IPAF, thus triggering a transcriptional cascade (Hayashi et al, 2001). Lachnospiraceae flagellins have been identified as dominant antigens in Crohn's disease (Duck et al, 2007) and in spontaneous colitis in IL-10 À / À mice, during which there is a loss of a flagellated Lachnospiraceae with high similarity (99%) to Lachnospiraceae bacterium A4 (DQ789118) (Ye et al, 2008). Although Lachnospiraceae phylotype OTU_11021, which in our study was an abundant colonizer of the healthy mouse gut but absent in DSS-treated mice, is only moderately related to Lachnospiraceae bacterium A4 (94% 16S rRNA sequence similarity), it is tempting to speculate that OTU_11021 cells are also flagellated.…”

Section: Discussionmentioning

confidence: 99%

Phylotype-level 16S rRNA analysis reveals new bacterial indicators of health state in acute murine colitis

et al. 2012

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Human inflammatory bowel disease and experimental colitis models in mice are associated with shifts in intestinal microbiota composition, but it is unclear at what taxonomic/phylogenetic level such microbiota dynamics can be indicative for health or disease. Here, we report that dextran sodium sulfate (DSS)-induced colitis is accompanied by major shifts in the composition and function of the intestinal microbiota of STAT1 À / À and wild-type mice, as determined by 454 pyrosequencing of bacterial 16S rRNA (gene) amplicons, metatranscriptomics and quantitative fluorescence in situ hybridization of selected phylotypes. The bacterial families Ruminococcaceae, Bacteroidaceae, Enterobacteriaceae, Deferribacteraceae and Verrucomicrobiaceae increased in relative abundance in DSS-treated mice. Comparative 16S rRNA sequence analysis at maximum possible phylogenetic resolution identified several indicator phylotypes for DSS treatment, including the putative mucin degraders Akkermansia and Mucispirillum. The analysis additionally revealed strongly contrasting abundance changes among phylotypes of the same family, particularly within the Lachnospiraceae. These extensive phylotype-level dynamics were hidden when reads were grouped at higher taxonomic levels. Metatranscriptomic analysis provided insights into functional shifts in the murine intestinal microbiota, with increased transcription of genes associated with regulation and cell signaling, carbohydrate metabolism and respiration and decreased transcription of flagellin genes during inflammation. These findings (i) establish the first in-depth inventory of the mouse gut microbiota and its metatranscriptome in the DSS colitis model, (ii) reveal that family-level microbial community analyses are insufficient to reveal important colitisassociated microbiota shifts and (iii) support a scenario of shifting intra-family structure and function in the phylotype-rich and phylogenetically diverse Lachnospiraceae in DSS-treated mice.

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“…The R. torques 91% phylotype was associated with IBSD and IBSM and the R. torques 93% phylotype was more abundant in IBSM than in healthy controls. The target sequences of R. torques 91%, 93% and 94% are affiliated with Lachnospiraceae as is the 16S rRNA sequence of the strain A4 (DQ789118) [57] carrying the IBS associated flagellin Fla2 [14] . As a further support to our previous results [11] , a significantly lower abundance of the C. aerofacienslike phylotype was associated with the IBSC and IBSD symptom subtypes at two of the timepoints analysed.…”

Section: Discussionmentioning

confidence: 99%

Diarrhoea-predominant irritable bowel syndromedistinguishable by 16S rRNA gene phylotype quantifcation

Lyra¹,

Rinttilä²,

Nikkilä³

et al. 2009

WJG

144

131

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AIM:To study whether selected bacterial 16S ribosomal RNA (rRNA) gene phylotypes are capable of distinguishing irritable bowel syndrome (IBS). METHODS:The faecal microbiota of twenty volunteers with IBS, subdivided into eight diarrhoea-predominant (IBS-D), eight constipation-predominant (IBS-C) and four mixed symptom-subtype (IBS-M) IBS patients, and fifteen control subjects, were analysed at three timepoints with a set of fourteen quantitative real-time polymerase chain reaction assays. All assays targeted 16S rRNA gene phylotypes putatively associated with IBS, based on 16S rRNA gene library sequence analysis.The target phylotypes were affiliated with Actinobacteria , Bacteroidetes and Firmicutes . Eight of the target phylotypes had less than 95% similarity to cultured bacterial species according to their 16S rRNA gene sequence. The data analyses were made with repeatedmeasures ANCOVA-type modelling of the data and principle component analysis (PCA) with linear mixed-effects models applied to the principal component scores. RESULTS:Bacterial phylotypes Clostridium cocleatum 88%, Clostridium thermosuccinogenes 85%, Coprobacillus catenaformis 91%, Ruminococcus bromii -like, Ruminococcus torques 91%, and R. torques 93% were detected from all samples analysed. A multivariate analysis of the relative quantities of all 14 bacterial 16S rRNA gene phylotypes suggested that the intestinal microbiota of the IBS-D patients differed from other sample groups. The PCA on the first principal component (PC1), explaining 30.36% of the observed variation in the IBS-D patient group, was significantly altered from all other sample groups (IBS-D vs control, P = 0.01; IBS-D vs IBS-M, P = 0.00; IBS-D vs IBS-C, P = 0.05). Significant differences were also observed in the levels of distinct phylotypes using relative values in proportion to the total amount of bacteria. A phylotype with 85% similarity to C. thermosuccinogenes was quantified in significantly different quantities among the IBS-D and control subjects (-4.08 ± 0.90 vs -3.33 ± 1.16, P = 0.04) and IBS-D and IBS-M subjects (-4.08 ± 0.90 vs -3.08 ± 1.38, P = 0.05). Furthermore, a phylotype with 94% similarity to R. torques was more prevalent in IBS-D patients' intestinal microbiota than in that of control subjects (-2.43 ± 1.49 vs -4.02 ± 1.63, P = 0.01). A phylotype with 93% similarity to R. torques was associated with control samples when compared with IBS-M (-2.41 ± 0.53 vs -2.92 ± 0.56, P = 0.00). Additionally, a R. bromii -like phylotype was associated with IBS-C patients in comparison to control subjects (-1.61 ± 1.83 vs -3.69 ± 2.42, P = 0.01). All of the above mentioned phylotype specific alterations were independent of the effect of time. CONCLUSION: Significant phylotype level alterations

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Isolation of flagellated bacteria implicated in Crohnʼs disease

Abstract: The conserved immune response in both mouse and human to these previously unknown flagellins of the microbiota indicate that they play an important role in host-microbe interactions in the intestine.

Cited by 110 publications

References 41 publications

Colonic mucosa-associated microbiota is influenced by an interaction of Crohn disease and FUT2 ( Secretor ) genotype

Colonic mucosa-associated microbiota is influenced by an interaction of Crohn disease and FUT2 ( Secretor ) genotype

Phylotype-level 16S rRNA analysis reveals new bacterial indicators of health state in acute murine colitis

Diarrhoea-predominant irritable bowel syndromedistinguishable by 16S rRNA gene phylotype quantifcation

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