Intestinal Dysbiosis and Depletion of Butyrogenic Bacteria in Clostridium difficile Infection and Nosocomial Diarrhea
01 Sep 2013-Journal of Clinical Microbiology (American Society for Microbiology)-Vol. 51, Iss: 9, pp 2884-2892
TL;DR: In this paper, the authors used high-density Roche 454 pyrosequencing to survey the distal gut microbiota for 39 individuals with CDI, 36 subjects with C. difficile-negative nosocomial diarrhea (CDN), and 40 healthy control subjects.
Abstract: Clostridium difficile infection (CDI) causes nearly half a million cases of diarrhea and colitis in the United States each year. Although the importance of the gut microbiota in C. difficile pathogenesis is well recognized, components of the human gut flora critical for colonization resistance are not known. Culture-independent high-density Roche 454 pyrosequencing was used to survey the distal gut microbiota for 39 individuals with CDI, 36 subjects with C. difficile-negative nosocomial diarrhea (CDN), and 40 healthy control subjects. A total of 526,071 partial 16S rRNA sequence reads of the V1 to V3 regions were aligned with 16S databases, identifying 3,531 bacterial phylotypes from 115 fecal samples. Genomic analysis revealed significant alterations of organism lineages in both the CDI and CDN groups, which were accompanied by marked decreases in microbial diversity and species richness driven primarily by a paucity of phylotypes within the Firmicutes phylum. Normally abundant gut commensal organisms, including the Ruminococcaceae and Lachnospiraceae families and butyrate-producing C2 to C4 anaerobic fermenters, were significantly depleted in the CDI and CDN groups. These data demonstrate associations between the depletion of Ruminococcaceae, Lachnospiraceae, and butyrogenic bacteria in the gut microbiota and nosocomial diarrhea, including C. difficile infection. Mechanistic studies focusing on the functional roles of these organisms in diarrheal diseases and resistance against C. difficile colonization are warranted.
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TL;DR: This article reviews the pathogenesis, epidemiology, diagnosis, and treatment of this nosocomial and potentially fatal infectious diarrhea, as well as the associated risk factors.
Abstract: This article reviews the pathogenesis, epidemiology, diagnosis, and treatment of this nosocomial and potentially fatal infectious diarrhea, as well as the associated risk factors New treatments include fecal microbiota transplantation for disease that is resistant to vancomycin
1,479 citations
TL;DR: It is demonstrated that high blood pressure is associated with gut microbiota dysbiosis, both in animal and human hypertension, and dietary intervention to correct gut microbiota could be an innovative nutritional therapeutic strategy for hypertension.
Abstract: Emerging evidence suggests that gut microbiota is critical in the maintenance of physiological homeostasis This study was designed to test the hypothesis that dysbiosis in gut microbiota is associated with hypertension because genetic, environmental, and dietary factors profoundly influence both gut microbiota and blood pressure Bacterial DNA from fecal samples of 2 rat models of hypertension and a small cohort of patients was used for bacterial genomic analysis We observed a significant decrease in microbial richness, diversity, and evenness in the spontaneously hypertensive rat, in addition to an increased Firmicutes/Bacteroidetes ratio These changes were accompanied by decreases in acetate- and butyrate-producing bacteria In addition, the microbiota of a small cohort of human hypertensive patients was found to follow a similar dysbiotic pattern, as it was less rich and diverse than that of control subjects Similar changes in gut microbiota were observed in the chronic angiotensin II infusion rat model, most notably decreased microbial richness and an increased Firmicutes/Bacteroidetes ratio In this model, we evaluated the efficacy of oral minocycline in restoring gut microbiota In addition to attenuating high blood pressure, minocycline was able to rebalance the dysbiotic hypertension gut microbiota by reducing the Firmicutes/Bacteroidetes ratio These observations demonstrate that high blood pressure is associated with gut microbiota dysbiosis, both in animal and human hypertension They suggest that dietary intervention to correct gut microbiota could be an innovative nutritional therapeutic strategy for hypertension
988 citations
TL;DR: The differences between PPI users and non-users observed in this study are consistently associated with changes towards a less healthy gut microbiome, in line with known changes that predispose to C. difficile infections.
Abstract: Background and aims Proton pump inhibitors (PPIs) are among the top 10 most widely used drugs in the world. PPI use has been associated with an increased risk of enteric infections, most notably Clostridium difficile. The gut microbiome plays an important role in enteric infections, by resisting or promoting colonisation by pathogens. In this study, we investigated the influence of PPI use on the gut microbiome. Methods The gut microbiome composition of 1815 individuals, spanning three cohorts, was assessed by tag sequencing of the 16S rRNA gene. The difference in microbiota composition in PPI users versus non-users was analysed separately in each cohort, followed by a meta-analysis. Results 211 of the participants were using PPIs at the moment of stool sampling. PPI use is associated with a significant decrease in Shannon9s diversity and with changes in 20% of the bacterial taxa (false discovery rate Rothia (p=9.8×10 −38 ). In PPI users we observed a significant increase in bacteria: genera Enterococcus , Streptococcus , Staphylococcus and the potentially pathogenic species Escherichia coli . Conclusions The differences between PPI users and non-users observed in this study are consistently associated with changes towards a less healthy gut microbiome. These differences are in line with known changes that predispose to C. difficile infections and can potentially explain the increased risk of enteric infections in PPI users. On a population level, the effects of PPI are more prominent than the effects of antibiotics or other commonly used drugs.
782 citations
TL;DR: The two main approaches for analyzing the microbiome, 16S ribosomal RNA gene amplicons and shotgun metagenomics, are illustrated with analyses of libraries designed to highlight their strengths and weaknesses and several methods for taxonomic classification of bacterial sequences are discussed.
Abstract: The advent of next generation sequencing (NGS) has enabled investigations of the gut microbiome with unprecedented resolution and throughput. This has stimulated the development of sophisticated bioinformatics tools to analyze the massive amounts of data generated. Researchers therefore need a clear understanding of the key concepts required for the design, execution and interpretation of NGS experiments on microbiomes. We conducted a literature review and used our own data to determine which approaches work best. The two main approaches for analyzing the microbiome, 16S ribosomal RNA (rRNA) gene amplicons and shotgun metagenomics, are illustrated with analyses of libraries designed to highlight their strengths and weaknesses. Several methods for taxonomic classification of bacterial sequences are discussed. We present simulations to assess the number of sequences that are required to perform reliable appraisals of bacterial community structure. To the extent that fluctuations in the diversity of gut bacterial populations correlate with health and disease, we emphasize various techniques for the analysis of bacterial communities within samples (α-diversity) and between samples (β-diversity). Finally, we demonstrate techniques to infer the metabolic capabilities of a bacteria community from these 16S and shotgun data.
647 citations
Cites background from "Intestinal Dysbiosis and Depletion ..."
...difficile infection have been reported associated with reduction of faecal bacterial diversity in the patients’ stools (Chang et al., 2008; Antharam et al., 2013; Vincent et al., 2013; Kostic et al., 2014; Norman et al., 2015)....
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...…of bacteria and yeast (Supplemental Figure 4), and both CD and C. difficile infection have been reported associated with reduction of faecal bacterial diversity in the patients’ stools (Chang et al., 2008; Antharam et al., 2013; Vincent et al., 2013; Kostic et al., 2014; Norman et al., 2015)....
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TL;DR: A diet high in fiber led to changes in the gut microbiota that played a protective role in the development of cardiovascular disease, and the favorable effects of fiber may be explained by the generation and distribution of one of the main metabolites of the Gut microbiota, the short-chain fatty acid acetate.
Abstract: Background:Dietary intake of fruit and vegetables is associated with lower incidence of hypertension, but the mechanisms involved have not been elucidated. Here, we evaluated the effect of a high-f...
611 citations
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TL;DR: A new method for metagenomic biomarker discovery is described and validates by way of class comparison, tests of biological consistency and effect size estimation to address the challenge of finding organisms, genes, or pathways that consistently explain the differences between two or more microbial communities.
Abstract: This study describes and validates a new method for metagenomic biomarker discovery by way of class comparison, tests of biological consistency and effect size estimation. This addresses the challenge of finding organisms, genes, or pathways that consistently explain the differences between two or more microbial communities, which is a central problem to the study of metagenomics. We extensively validate our method on several microbiomes and a convenient online interface for the method is provided at http://huttenhower.sph.harvard.edu/lefse/.
9,057 citations
"Intestinal Dysbiosis and Depletion ..." refers methods in this paper
...pled with effect size measurements (LEfSe) (28) was used to identify bac-...
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...Linear discriminant analysis coupled with effect size measurements (LEfSe) (28) was used to identify bacterial taxa that were differentially abundant or depleted between sample groups....
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...Next, we used LEfSe (28) to determine specific bacteria taxa that were differentially abundant....
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TL;DR: SILVA (from Latin silva, forest), was implemented to provide a central comprehensive web resource for up to date, quality controlled databases of aligned rRNA sequences from the Bacteria, Archaea and Eukarya domains.
Abstract: Sequencing ribosomal RNA (rRNA) genes is currently the method of choice for phylogenetic reconstruction, nucleic acid based detection and quantification of microbial diversity. The ARB software suite with its corresponding rRNA datasets has been accepted by researchers worldwide as a standard tool for large scale rRNA analysis. However, the rapid increase of publicly available rRNA sequence data has recently hampered the maintenance of comprehensive and curated rRNA knowledge databases. A new system, SILVA (from Latin silva, forest), was implemented to provide a central comprehensive web resource for up to date, quality controlled databases of aligned rRNA sequences from the Bacteria, Archaea and Eukarya domains. All sequences are checked for anomalies, carry a rich set of sequence associated contextual information, have multiple taxonomic classifications, and the latest validly described nomenclature. Furthermore, two precompiled sequence datasets compatible with ARB are offered for download on the SILVA website: (i) the reference (Ref) datasets, comprising only high quality, nearly full length sequences suitable for in-depth phylogenetic analysis and probe design and (ii) the comprehensive Parc datasets with all publicly available rRNA sequences longer than 300 nucleotides suitable for biodiversity analyses. The latest publicly available database release 91 (August 2007) hosts 547 521 sequences split into 461 823 small subunit and 85 689 large subunit rRNAs.
5,733 citations
TL;DR: A strategy to understand the microbial components of the human genetic and metabolic landscape and how they contribute to normal physiology and predisposition to disease.
Abstract: A strategy to understand the microbial components of the human genetic and metabolic landscape and how they contribute to normal physiology and predisposition to disease.
4,730 citations
TL;DR: The infusion of donor feces was significantly more effective for the treatment of recurrent C. difficile infection than the use of vancomycin and patients showed increased fecal bacterial diversity, similar to that in healthy donors, with an increase in Bacteroidetes species and clostridium clusters IV and XIVa and a decrease in Proteobacteria species.
Abstract: A b s t r ac t Results The study was stopped after an interim analysis. Of 16 patients in the infusion group, 13 (81%) had resolution of C. difficile-associated diarrhea after the first infu - sion. The 3 remaining patients received a second infusion with feces from a differ- ent donor, with resolution in 2 patients. Resolution of C. difficile infection occurred in 4 of 13 patients (31%) receiving vancomycin alone and in 3 of 13 patients (23%) receiving vancomycin with bowel lavage (P<0.001 for both comparisons with the infusion group). No significant differences in adverse events among the three study groups were observed except for mild diarrhea and abdominal cramping in the in- fusion group on the infusion day. After donor-feces infusion, patients showed in- creased fecal bacterial diversity, similar to that in healthy donors, with an increase in Bacteroidetes species and clostridium clusters IV and XIVa and a decrease in Proteobacteria species. Conclusions The infusion of donor feces was significantly more effective for the treatment of recurrent C. difficile infection than the use of vancomycin. (Funded by the Nether- lands Organization for Health Research and Development and the Netherlands Organization for Scientific Research; Netherlands Trial Register number, NTR1177.)
3,081 citations
TL;DR: This guideline updates recommendations regarding epidemiology, diagnosis, treatment, and infection control and environmental management of Clostridium difficile.
Abstract: Since publication of the Society for Healthcare Epidemiology of America position paper on Clostridium difficile infection in 1995, significant changes have occurred in the epidemiology and treatment of this infection. C. difficile remains the most important cause of healthcareassociated diarrhea and is increasingly important as a community pathogen. A more virulent strain of C. difficile has been identified and has been responsible for more-severe cases of disease worldwide. Data reporting the decreased effectiveness of metronidazole in the treatment of severe disease have been published. Despite the increasing quantity of data available, areas of controversy still exist. This guideline updates recommendations regarding epidemiology, diagnosis, treatment, and infection control and environmental management.
2,872 citations