Characterization of fecal microbial communities in patients with liver cirrhosis
TL;DR: Fecal microbial communities are distinct in patients with cirrhosis compared with healthy individuals, and the prevalence of potentially pathogenic bacteria, such as Enterobacteriaceae and Streptococcaceae, with the reduction of beneficial populations such as Lachnospiraceae in Patients with Cirrhosis may affect prognosis.
About: This article is published in Hepatology.The article was published on 2011-08-01 and is currently open access. It has received 773 citations till now. The article focuses on the topics: Chronic liver disease & Lachnospiraceae.
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TL;DR: The large-scale dynamics of the microbiome can be described by many of the tools and observations used in the study of population ecology, andiphering the metagenome and its aggregate genetic information can also be used to understand the functional properties of the microbial community.
Abstract: Interest in the role of the microbiome in human health has burgeoned over the past decade with the advent of new technologies for interrogating complex microbial communities. The large-scale dynamics of the microbiome can be described by many of the tools and observations used in the study of population ecology. Deciphering the metagenome and its aggregate genetic information can also be used to understand the functional properties of the microbial community. Both the microbiome and metagenome probably have important functions in health and disease; their exploration is a frontier in human genetics.
2,650 citations
TL;DR: The gut microbiome in liver cirrhosis is characterized by comparing 98 patients and 83 healthy control individuals and on the basis of only 15 biomarkers, a highly accurate patient discrimination index is created and validated on an independent cohort, suggesting microbiota-targeted biomarkers may be a powerful tool for diagnosis of different diseases.
Abstract: Liver cirrhosis occurs as a consequence of many chronic liver diseases that are prevalent worldwide. Here we characterize the gut microbiome in liver cirrhosis by comparing 98 patients and 83 healthy control individuals. We build a reference gene set for the cohort containing 2.69 million genes, 36.1% of which are novel. Quantitative metagenomics reveals 75,245 genes that differ in abundance between the patients and healthy individuals (false discovery rate < 0.0001) and can be grouped into 66 clusters representing cognate bacterial species; 28 are enriched in patients and 38 in control individuals. Most (54%) of the patient-enriched, taxonomically assigned species are of buccal origin, suggesting an invasion of the gut from the mouth in liver cirrhosis. Biomarkers specific to liver cirrhosis at gene and function levels are revealed by a comparison with those for type 2 diabetes and inflammatory bowel disease. On the basis of only 15 biomarkers, a highly accurate patient discrimination index is created and validated on an independent cohort. Thus microbiota-targeted biomarkers may be a powerful tool for diagnosis of different diseases. Invasion of the gut by oral bacteria in liver cirrhosis. Previous work has revealed an association between liver complications such as cirrhosis and the gut microbiome. Lanjuan Li and colleagues undertook a microbiome-wide association study of stool samples from 98 liver cirrhosis patients and 83 healthy controls. Quantitative metagenomics analysis revealed 75,245 genes that were significantly different in abundance between the two groups, many of which could be grouped into 66 clusters that represent cognate bacterial species. Of these, 28 species were enriched in liver cirrhosis patients and most were of buccal origin (mostly Veillonella and streptococci). The identified markers were unique liver cirrhosis-specific genes and the authors identify a set of just 15 of these genes that could form the basis of a highly accurate discrimination index that could be used as a diagnostic tool.
1,542 citations
08 Mar 2016
TL;DR: This review summarizes major achievements regarding intestinal dysfunction in cirrhosis for future gastroenterology research and suggests that delayed small bowel transit in liver Cirrhosis may lead to SIBO, which could contribute to the symptoms of abdominal pain and diarrhea.
Abstract: Background: Understanding of the gut-liver axis is important for the up-to-date management of liver cirrhosis, and changes of intestinal functions form the core o
1,311 citations
TL;DR: The results suggest that the intestinal microbiota is associated with CRC risk and that intestinal lumen microflora potentially influence CRC risk via cometabolism or metabolic exchange with the host.
Abstract: Recent reports have suggested the involvement of gut microbiota in the progression of colorectal cancer (CRC). We utilized pyrosequencing based analysis of 16S rRNA genes to determine the overall structure of microbiota in patients with colorectal cancer and healthy controls; we investigated microbiota of the intestinal lumen, the cancerous tissue and matched noncancerous normal tissue. Moreover, we investigated the mucosa-adherent microbial composition using rectal swab samples because the structure of the tissue-adherent bacterial community is potentially altered following bowel cleansing. Our findings indicated that the microbial structure of the intestinal lumen and cancerous tissue differed significantly. Phylotypes that enhance energy harvest from diets or perform metabolic exchange with the host were more abundant in the lumen. There were more abundant Firmicutes and less abundant Bacteroidetes and Proteobacteria in lumen. The overall microbial structures of cancerous tissue and noncancerous tissue were similar; howerer the tumor microbiota exhibited lower diversity. The structures of the intestinal lumen microbiota and mucosa-adherent microbiota were different in CRC patients compared to matched microbiota in healthy individuals. Lactobacillales was enriched in cancerous tissue, whereas Faecalibacterium was reduced. In the mucosa-adherent microbiota, Bifidobacterium, Faecalibacterium, and Blautia were reduced in CRC patients, whereas Fusobacterium, Porphyromonas, Peptostreptococcus, and Mogibacterium were enriched. In the lumen, predominant phylotypes related to metabolic disorders or metabolic exchange with the host, Erysipelotrichaceae, Prevotellaceae, and Coriobacteriaceae were increased in cancer patients. Coupled with previous reports, these results suggest that the intestinal microbiota is associated with CRC risk and that intestinal lumen microflora potentially influence CRC risk via cometabolism or metabolic exchange with the host. However, mucosa-associated microbiota potentially affects CRC risk primarily through direct interaction with the host.
821 citations
Cites background from "Characterization of fecal microbial..."
...1 were considered to be important contributors to the model [5,23,24,25]....
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TL;DR: In the longitudinal matched-cohort, microbiota were significantly different between infected/uninfected cirrhotics at baseline and a low CDR was associated with death and organ failures within 30days, indicating progressive changes in the gut microbiome accompany cirrhosis and become more severe in the setting of decompensation.
769 citations
Cites background from "Characterization of fecal microbial..."
...Enterobacteriaceae found in most cirrhotic patients [8,9,31]....
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...In a large, well-characterized population spanning the spectrum from healthy controls to terminal decompensation, we have demonstrated changes in the stool microbial composition characterized by the relative decrease of potentially beneficial autochthonous taxa, particularly Lachnospiraceae, Ruminococcaceae and Clostridiales XIV, with relative overgrowth of potentially pathogenic taxa; Staphylococcaeae, Enterobacteriaceae, and Enterococcaceae, are associated with disease progression and endotoxemia [7,8,11,18]....
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References
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TL;DR: Analysis of the genomic DNA from a bacterial biofilm grown under aerobic conditions suggests that sulfate-reducing bacteria, despite their anaerobicity, were present in this environment.
Abstract: We describe a new molecular approach to analyzing the genetic diversity of complex microbial populations. This technique is based on the separation of polymerase chain reaction-amplified fragments of genes coding for 16S rRNA, all the same length, by denaturing gradient gel electrophoresis (DGGE). DGGE analysis of different microbial communities demonstrated the presence of up to 10 distinguishable bands in the separation pattern, which were most likely derived from as many different species constituting these populations, and thereby generated a DGGE profile of the populations. We showed that it is possible to identify constituents which represent only 1% of the total population. With an oligonucleotide probe specific for the V3 region of 16S rRNA of sulfate-reducing bacteria, particular DNA fragments from some of the microbial populations could be identified by hybridization analysis. Analysis of the genomic DNA from a bacterial biofilm grown under aerobic conditions suggests that sulfate-reducing bacteria, despite their anaerobicity, were present in this environment. The results we obtained demonstrate that this technique will contribute to our understanding of the genetic diversity of uncharacterized microbial populations.
11,380 citations
"Characterization of fecal microbial..." refers methods in this paper
...Isolated fecal DNA was used as a template for the amplification of the 16S rRNA V3 region using the universal primer 341F (50-NNNNNN NNCCTACGGGAGGCAGCAG-30) and 534R (5 0NNNNNNNNATTACCGCGGCTGCTGG-30) and the hot-start touchdown protocol described by Muyzer et al.(24) The NNNNNNNN designated the unique eight-base barcode used to tag each PCR product....
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...Isolated fecal DNA was used as a template for the amplification of the 16S rRNA V3 region using the universal primer 341F (50-NNNNNN NNCCTACGGGAGGCAGCAG-30) and 534R (5 0- NNNNNNNNATTACCGCGGCTGCTGG-30) and the hot-start touchdown protocol described by Muyzer et al.24 The NNNNNNNN designated the unique eight-base barcode used to tag each PCR product....
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TL;DR: A scalable, highly parallel sequencing system with raw throughput significantly greater than that of state-of-the-art capillary electrophoresis instruments with 96% coverage at 99.96% accuracy in one run of the machine is described.
Abstract: The proliferation of large-scale DNA-sequencing projects in recent years has driven a search for alternative methods to reduce time and cost. Here we describe a scalable, highly parallel sequencing system with raw throughput significantly greater than that of state-of-the-art capillary electrophoresis instruments. The apparatus uses a novel fibre-optic slide of individual wells and is able to sequence 25 million bases, at 99% or better accuracy, in one four-hour run. To achieve an approximately 100-fold increase in throughput over current Sanger sequencing technology, we have developed an emulsion method for DNA amplification and an instrument for sequencing by synthesis using a pyrosequencing protocol optimized for solid support and picolitre-scale volumes. Here we show the utility, throughput, accuracy and robustness of this system by shotgun sequencing and de novo assembly of the Mycoplasma genitalium genome with 96% coverage at 99.96% accuracy in one run of the machine.
8,434 citations
"Characterization of fecal microbial..." refers background in this paper
...Pyrosequencing technology is a cost-effective means of comprehensive analysis of the intestinal microbial community that produce a large number of sequence reads at one time while reducing the cost of data acquisition, which greatly facilitates intestinal microbiota researches.(21) Short reads of 16S ribosomal RNA (16S rRNA), such as those produced by pyrosequencing, can yield the same clustering effect as full-length 16S rRNA sequences if the correct regions are chosen....
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TL;DR: Emergency ligation of bleeding oesophageal varices using the Milnes Walker technique was performed in 38 patients, and in patients with good preoperative liver function this rose to 71% and the simple scoring system for grading the severity of disturbance of liver function was found to be of value in predicting the outcome of surgery.
Abstract: Emergency ligation of bleeding oesophageal varices using the Milnes Walker technique was performed in 38 patients. Haemorrhage continued or recurred in hospital in 11 patients, all of whom subsequently died. A further 10 patients died in hospital following operation from hepatic failure and a variety of other causes. Five patients were finally considered suitable for elective shunt surgery, but of 12 patients who were discharged without a further operation, only 2 have re-bled. Although the overall 6-month survival was 32 per cent, in patients with good preoperative liver function this rose to 71 per cent, and the simple scoring system for grading the severity of disturbance of liver function was found to be of value in predicting the outcome of surgery.
Since the results of emergency ligation of bleeding oesophageal varices in our hands have been so disappointing we are currently using it less and are trying the mesenteric caval jump graft as an emergency operation for the control of bleeding varices.
7,262 citations
"Characterization of fecal microbial..." refers methods in this paper
...The Child-Turcotte-Pugh (CTP) scoring system was used to assess the prognosis of cirrhosis.(23) The control group consisted of 24 healthy individuals who visited the First Affiliated Hospital of Zhejiang University for routine health examinations....
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TL;DR: A majority of the bacterial sequences corresponded to uncultivated species and novel microorganisms, and significant intersubject variability and differences between stool and mucosa community composition were discovered.
Abstract: The human endogenous intestinal microflora is an essential “organ” in providing nourishment, regulating epithelial development, and instructing innate immunity; yet, surprisingly, basic features remain poorly described. We examined 13,355 prokaryotic ribosomal RNA gene sequences from multiple colonic mucosal sites and feces of healthy subjects to improve our understanding of gut microbial diversity. A majority of the bacterial sequences corresponded to uncultivated species and novel microorganisms. We discovered significant intersubject variability and differences between stool and mucosa community composition. Characterization of this immensely diverse ecosystem is the first step in elucidating its role in health and disease.
7,049 citations
"Characterization of fecal microbial..." refers background in this paper
...The human intestine harbors up to 10(14) microorganisms, approximately 80% of which are uncultivated and novel species.(16) The intestinal microbiome encodes 100-fold more unique genes than our own genome....
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TL;DR: The faecal microbial communities of adult female monozygotic and dizygotic twin pairs concordant for leanness or obesity, and their mothers are characterized to address how host genotype, environmental exposure and host adiposity influence the gut microbiome.
Abstract: The human distal gut harbours a vast ensemble of microbes (the microbiota) that provide important metabolic capabilities, including the ability to extract energy from otherwise indigestible dietary polysaccharides. Studies of a few unrelated, healthy adults have revealed substantial diversity in their gut communities, as measured by sequencing 16S rRNA genes, yet how this diversity relates to function and to the rest of the genes in the collective genomes of the microbiota (the gut microbiome) remains obscure. Studies of lean and obese mice suggest that the gut microbiota affects energy balance by influencing the efficiency of calorie harvest from the diet, and how this harvested energy is used and stored. Here we characterize the faecal microbial communities of adult female monozygotic and dizygotic twin pairs concordant for leanness or obesity, and their mothers, to address how host genotype, environmental exposure and host adiposity influence the gut microbiome. Analysis of 154 individuals yielded 9,920 near full-length and 1,937,461 partial bacterial 16S rRNA sequences, plus 2.14 gigabases from their microbiomes. The results reveal that the human gut microbiome is shared among family members, but that each person's gut microbial community varies in the specific bacterial lineages present, with a comparable degree of co-variation between adult monozygotic and dizygotic twin pairs. However, there was a wide array of shared microbial genes among sampled individuals, comprising an extensive, identifiable 'core microbiome' at the gene, rather than at the organismal lineage, level. Obesity is associated with phylum-level changes in the microbiota, reduced bacterial diversity and altered representation of bacterial genes and metabolic pathways. These results demonstrate that a diversity of organismal assemblages can nonetheless yield a core microbiome at a functional level, and that deviations from this core are associated with different physiological states (obese compared with lean).
6,970 citations
"Characterization of fecal microbial..." refers background in this paper
...It is hypothesized that in these patients, microbial communities are not constructed as diversely and evenly as a ‘‘rainforest’’ in healthy individuals, but is high in some particular members in favor of this specific condition.(30) Detailed compositional changes in the intestinal microbiota of patients with cirrhosis were investigated at different bacterial taxonomic levels....
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