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From metagenomic data to personalized in silico microbiotas: predicting dietary supplements for Crohn's disease.

ABSTRACT: Crohn's disease (CD) is associated with an ecological imbalance of the intestinal microbiota, consisting of hundreds of species. The underlying complexity as well as individual differences between patients contributes to the difficulty to define a standardized treatment. Computational modeling can systematically investigate metabolic interactions between gut microbes to unravel mechanistic insights. In this study, we integrated metagenomic data of CD patients and healthy controls with genome-scale metabolic models into personalized in silico microbiotas. We predicted short chain fatty acid (SFCA) levels for patients and controls, which were overall congruent with experimental findings. As an emergent property, low concentrations of SCFA were predicted for CD patients and the SCFA signatures were unique to each patient. Consequently, we suggest personalized dietary treatments that could improve each patient's SCFA levels. The underlying modeling approach could aid clinical practice to find dietary treatment and guide recovery by rationally proposing food aliments.

SUBMITTER: Bauer E

PROVIDER: S-EPMC6068170 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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From metagenomic data to personalized in silico microbiotas: predicting dietary supplements for Crohn's disease.

Bauer Eugen E Thiele Ines I

NPJ systems biology and applications 20180801

Crohn's disease (CD) is associated with an ecological imbalance of the intestinal microbiota, consisting of hundreds of species. The underlying complexity as well as individual differences between patients contributes to the difficulty to define a standardized treatment. Computational modeling can systematically investigate metabolic interactions between gut microbes to unravel mechanistic insights. In this study, we integrated metagenomic data of CD patients and healthy controls with genome-sca ...[more]

PMID: 30083388

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Project description:Patients with Crohn's disease frequently develop oral health problems and show a higher prevalence of oral manifestations, such as dental caries and periodontitis, than healthy individuals do. In this study, a metagenomic analysis was carried out to characterize the salivary microbiota in patients with either periodontitis or Crohn's disease-associated periodontitis. Saliva samples were collected from six patients with both Crohn's disease and periodontitis (Cm group), six patients with periodontitis alone (Pm group), and six healthy individuals (Hm group). Genomic DNA was collected from these samples for high-throughput Illumina HiSeq metagenomic sequencing. The composition of the bacterial communities and their metabolic pathways and gene functions were characterized and compared among the three study groups. The salivary microbial communities were significantly different among the three groups, with Firmicutes, Actinobacteria, and Bacteroidetes showing the most significant differences. The Cm and Pm groups had higher abundances of Bacteroides fragilis, Prevotella baroniae, Prevotella enoeca, and Prevotella dentasini than the Hm group. The Cm and Pm groups also showed differences in their salivary microbial communities, in that the Cm group had relatively high abundances of Firmicutes and Proteobacteria, whereas the Pm group had relatively high abundances of Actinobacteria, Bacteroidetes, and Fusobacteria. In total, 34 Pm-associated (e.g., Fusobacteria and Corynebacterium matruchotii), 18 Cm-associated (e.g., Capnocytophaga and Streptococcus oralis), and 18 Hm-associated (e.g., Streptococcus and Bacillales) predominant microbial species were identified. Most genes were involved in carbohydrate and amino acid metabolism, with those of the Cm and Pm groups showing more similarity to one another but significant differences from those of the Hm group. Most of the antibiotic resistance genes were found in the Pm group. In conclusion, the salivary microbial community structure and abundance were distinct among patients with Crohn's disease-associated periodontitis, patients with periodontitis, and healthy individuals. Further studies are needed to evaluate the potential value of these microbiota and microbiome differences in the clinical diagnosis and treatment of oral diseases.

Project description:Surveys of mitochondrial disease physicians conducted through the Mitochondrial Medicine Society have shown that virtually all providers recommend a variety of dietary supplements as treatments to their patients in an effort to enhance energy production and reduce oxidative stress. In this survey, we asked patients and their parents about their experiences taking these dietary supplements for mitochondrial disease. The survey was disseminated through the North American Mitochondrial Disease Consortium (NAMDC) and the Rare Disease Clinical Research Network (RDCRN) registries and gathered 162 responses. The study ascertained each patient's mitochondrial disease diagnosis, dietary supplements used, adjunct therapy, and effects of the supplements on symptoms and health. Regardless of the specific underlying mitochondrial disease, the majority of the survey respondents stated they are or have been on dietary supplements. Most patients take more than four supplements primarily coenzyme Q10, l-carnitine, and riboflavin. The majority of patients taking supplements reported health benefits from the supplements. The onset of perceived benefits was between 2weeks to 3months of initiating intake. Supplements seem to be safe, with only 28% of patients experiencing mild side-effects and only 5.6% discontinuing their intake due to intolerance. Only 9% of patients had insurance coverage for their supplements and when paying out of pocket, 95% of them spend up to $500/month. Despite the use of concomitant therapies (prescribed medications, physical therapy, diet changes and other), 45.5% of patients think that dietary supplements are the only intervention improving their symptoms. Some limitations of this study include the retrospective collection of data probably associated with substantial recall bias, lack of longitudinal follow up to document pre- and post-supplement clinical status and second hand reports by parents for children which may reflect parents' subjective interpretation of symptoms severity and supplements effect rather than real patients' experience. More extensive prospective studies will help further elucidate this topic.

Project description:In the past, many studies suggested a crucial role for dysbiosis of the gut microbiota in the etiology of Crohn's disease (CD). However, despite being important players in host-bacteria interaction, the role of bacterial membrane vesicles (MV) has been largely overlooked in the pathogenesis of CD. In this study, we addressed the composition of the bacterial and MV composition in fecal samples of CD patients and compared this to the composition in healthy individuals. Fecal samples from six healthy subjects (HC) in addition to twelve CD patients (six active, six remission) were analyzed in this study. Fecal bacterial membrane vesicles (fMVs) were isolated by a combination of ultrafiltration and size exclusion chromatography. DNA was obtained from the fMV fraction, the pellet of dissolved feces as bacterial DNA (bDNA), or directly from feces as fecal DNA (fDNA). The fMVs were characterized by nanoparticle tracking analysis and cryo-electron microscopy. Amplicon sequencing of 16s rRNA V4 hypervariable gene regions was conducted to assess microbial composition of all fractions. Beta-diversity analysis showed that the microbial community structure of the fMVs was significantly different from the microbial profiles of the fDNA and bDNA. However, no differences were observed in microbial composition between fDNA and bDNA. The microbial richness of fMVs was significantly decreased in CD patients compared to HC, and even lower in active patients. Profiling of fDNA and bDNA demonstrated that Firmicutes was the most dominant phylum in these fractions, while in fMVs Bacteroidetes was dominant. In fMV, several families and genera belonging to Firmicutes and Proteobacteria were significantly altered in CD patients when compared to HC. The microbial alterations of MVs in CD patients particularly in Firmicutes and Proteobacteria suggest a possible role of MVs in host-microbe symbiosis and induction or progression of inflammation in CD pathogenesis. Yet, the exact role for these fMV in the pathogenesis of the disease needs to be elucidated in future studies.

Dataset Information

From metagenomic data to personalized in silico microbiotas: predicting dietary supplements for Crohn's disease.

Publications

From metagenomic data to personalized in silico microbiotas: predicting dietary supplements for Crohn's disease.

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