Assessment of Fecal Microbiota and Fecal Metabolome in Symptomatic Uncomplicated Diverticular Disease of the Colon

Tursi, Antonio; Mastromarino, Paola; Capobianco, Daniela; Elisei, Walter; Miccheli, Alfredo; Capuani, Giorgio; Tomassini, Alberta; Campagna, Giuseppe; Picchio, Marcello; Giorgetti, GianMarco; Fabiocchi, F.; Brandimarte, Giovanni

doi:10.1097/mcg.0000000000000626

Cited by 82 publications

(109 citation statements)

References 15 publications

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“…38 Existing metabolomics studies of humans with expansion of mucolytic organisms such as Akkermansia have not shown consistent metabolite signatures. 39,40 Although the Tsyn and Cosmc SNPs described here were not found to be associated with IBD in a large meta-analysis of Immunochip data, the SNP-associated changes in the colonic mucosal microbiome are reminiscent of changes seen in IBD patients. 41 In particular, Cosmc minor allele carriers had changes paralleling IBD including increased Enterobacteriaceae, Veillonella parvula, and H. parainfluenzae.…”

Section: Discussionmentioning

confidence: 98%

Microbial, metabolomic, and immunologic dynamics in a relapsing genetic mouse model of colitis induced by T-synthase deficiency

et al. 2016

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(2017) Microbial, metabolomic, and immunologic dynamics in a relapsing genetic mouse model of colitis induced by T-synthase deficiency, Gut Microbes, 8:1, 1-16, DOI: 10.1080/19490976.2016 To link to this article: https://doi.org/10. 1080/19490976.2016 ABSTRACTIntestinal dysbiosis is thought to confer susceptibility to inflammatory bowel disease (IBD), but it is unknown whether dynamic changes in the microbiome contribute to fluctuations in disease activity. We explored this question using mice with intestine-specific deletion of C1galt1 (also known as T-synthase) (Tsyn mice). These mice develop spontaneous microbiota-dependent colitis with a remitting/relapsing course due to loss of mucin core-1 derived O-glycans. 16S rRNA sequencing and untargeted metabolomics demonstrated age-specific perturbations in the intestinal microbiome and metabolome of Tsyn mice compare with littermate controls at weeks 3 (disease onset), 5 (during remission), and 9 (after relapse). Colitis remission corresponded to increased levels of FoxP3CRORgtCCD4C T cells in the colonic lamina propria that were positively correlated with operational taxonomic units (OTUs) in the S24-7 family and negatively correlated with OTUs in the Clostridiales order. Relapse was characterized by marked expansion of FoxP3-RORgtCCD4C T cells expressing IFNg and IL17A, which were associated with Clostridiales OTUs distinct from those negatively correlated with FoxP3CRORgtCCD4C T cells. Our findings suggest that colitis remission and relapse in the Tsyn model may reflect alterations in the microbiome due to reduced core-1 O-glycosylation that shift the balance of regulatory and pro-inflammatory T cell subsets. We investigated whether genetic variation in C1galt1 correlated with the microbiome in a cohort of 78 Crohn's disease patients and 101 healthy controls. Polymorphisms near C1galt1 (rs10486157) and its molecular chaperone, Cosmc (rs4825729), were associated with altered composition of the colonic mucosal microbiota, supporting the relevance of core-1 O-glycosylation to host regulation of the microbiome.

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Section: Discussionmentioning

confidence: 98%

Microbial, metabolomic, and immunologic dynamics in a relapsing genetic mouse model of colitis induced by T-synthase deficiency

et al. 2016

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“…Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) are widely implemented for the detection of metabolites in stool samples for disease research (15,16). Metabolome profiling is frequently conducted in conjunction with gut microbiome studies to study the microbiome's metabolic potential (17,18).…”

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confidence: 99%

Systematic Analysis of Impact of Sampling Regions and Storage Methods on Fecal Gut Microbiome and Metabolome Profiles

Liang

Dong

Chen

et al. 2020

mSphere

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The contribution of human gastrointestinal (GI) microbiota and metabolites to host health has recently become much clearer. However, many confounding factors can influence the accuracy of gut microbiome and metabolome studies, resulting in inconsistencies in published results. In this study, we systematically investigated the effects of fecal sampling regions and storage and retrieval conditions on gut microbiome and metabolite profiles from three healthy children. Our analysis indicated that compared to homogenized and snap-frozen samples (standard control [SC]), different sampling regions did not affect microbial community alpha diversity, while a total of 22 of 176 identified metabolites varied significantly across different sampling regions. In contrast, storage conditions significantly influenced the microbiome and metabolome. Short-term room temperature storage had a minimal effect on the microbiome and metabolome profiles. Sample storage in RNALater showed a significant level of variation in both microbiome and metabolome profiles, independent of the storage or retrieval conditions. The effect of RNALater on the metabolome was stronger than the effect on the microbiome, and individual variability between study participants outweighed the effect of RNALater on the microbiome. We conclude that homogenizing stool samples was critical for metabolomic analysis but not necessary for microbiome analysis. Short-term room temperature storage had a minimal effect on the microbiome and metabolome profiles and is recommended for short-term fecal sample storage. In addition, our study indicates that the use of RNALater as a storage medium of stool samples for microbial and metabolomic analyses is not recommended. IMPORTANCE The gastrointestinal microbiome and metabolome can provide a new angle to understand the development of health and disease. Stool samples are most frequently used for large-scale cohort studies. Standardized procedures for stool sample handling and storage can be a determining factor for performing microbiome or metabolome studies. In this study, we focused on the effects of stool sampling regions and stool sample storage conditions on variations in the gut microbiome composition and metabolome profile.

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“…(15)(16)(17)(18)(19)(20)(21) Global geographical differences in the intestinal microbial community also correspond to differences in the prevalence of diverticular disease. (21)(22)(23) Several studies have examined the intestinal microbial composition in patients with symptomatic asymptomatic diverticular disease (24)(25)(26) and in asymptomatic diverticulosis. (27,28) Only two small studies have explored the intestinal microbiota in patients with diverticulitis.…”

Section: Introductionmentioning

confidence: 99%

“…adjusted for multiple comparisons. Nonetheless, a supervised clustering approach was able to distinguish diverticulitis cases from diverticulosis controls 80% of the time based on the relative abundance of the 7 genera.A few studies have examined the intestinal microbiota in patients with symptomatic asymptomatic diverticular disease (SUDD) (24,26). SUDD is an incompletely understood condition generally defined as the presence of abdominal symptoms in patients with diverticulosis and gastrointestinal symptoms in the absence of evidence of diverticulitis.Barbara et al, compared the fecal and mucosal microbiota in 14 controls without diverticulosis, 16 patients with asymptomatic diverticulosis and 8 patients with SUDD.…”

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confidence: 99%

The fecal microbiome in diverticulitis and asymptomatic diverticulosis: A case-control study in the US

Hullar

Sandstrom

Stamatoyannopoulos

et al. 2019

Preprint

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Objective: The intestinal microbiota are hypothesized to play a role in the pathogenesis of diverticulitis. We compared fecal microbial communities in individuals with diverticulitis to those with uncomplicated diverticulosis. Methods: We used 16S ribosomal RNA gene sequencing to assess and compare the microbiota composition of fecal samples from 10 patients presenting with acute diverticulitis (cases) and 10 controls with asymptomatic diverticulosis matched on age and sex. Results: We found differences in the distribution of relative abundances of bacterial phyla and genera in diverticulitis cases versus diverticulosis controls. At the phyla level, Verrucomicrobia was more abundant on average in diverticulitis cases at the time of diagnosis than in diverticulosis controls (p=0.07). Univariate analysis identified a significant increase in the genera Coriobacteria (p=0.050), Anaerotruncus (0.046), Subdoliganulum (p=0.034), Marvinabryantia (p=0.006), and Akkermansia (p=0.04), and a decrease in Barnesiella (p=0.035) and Coprococcus (p=0.035) in diverticulitis cases at the time of diagnosis compared to diverticulosis controls. However, after correction for multiple comparisons, these differences were no longer significant. Partial least squares discriminant analysis on all microbial genera showed partial separation of diverticulitis cases at diagnosis and diverticulosis controls. The microbial alpha diversity was higher in diverticulitis cases at time of diagnosis vs controls but this was not significant (Shannon diversity index 7.4±0.6 vs 6.8±0.7, p=0.08). Conclusions: Individuals with diverticulitis differ

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Assessment of Fecal Microbiota and Fecal Metabolome in Symptomatic Uncomplicated Diverticular Disease of the Colon

Abstract: SUDD and AD do not show colonic bacterial overgrowth, but a significant difference in the levels of fecal A. muciniphila was observed. Moreover, increasing expression of some metabolites as expression of different AD and SUDD metabolic activity was found.

Cited by 82 publications

References 15 publications

Microbial, metabolomic, and immunologic dynamics in a relapsing genetic mouse model of colitis induced by T-synthase deficiency

Microbial, metabolomic, and immunologic dynamics in a relapsing genetic mouse model of colitis induced by T-synthase deficiency

Systematic Analysis of Impact of Sampling Regions and Storage Methods on Fecal Gut Microbiome and Metabolome Profiles

The fecal microbiome in diverticulitis and asymptomatic diverticulosis: A case-control study in the US

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