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Stable core virome despite variable microbiome after fecal transfer.

ABSTRACT: We recently described the 4.5-year time course of the enteric bacterial microbiota and virome of a patient cured from recurrent Clostridium difficile infection (rCDI) by fecal microbiota transplantation (FMT). Here, we extended the virome analyses and found the patient's phage population to exhibit highly donor-similar characteristics following FMT, which remained stable for the whole period tested (up to 7 months). Moreover, the detected viral populations of donor and patient exhibited comparable diversity and richness. These findings were unexpected since enteric viromes are normally highly variable, assumed to influence the bacterial host community and change with environmental conditions. In contrast to the virome, the bacterial microbiota varied indeed for more than 7 months with ongoing dysbiosis before it reached donor similarity. Our findings that are based on sequence information and protein domain analysis seem to suggest that stable phage properties correlate with successful FMT better than the changing bacterial communities. We speculate that we here preferentially detected a stable core virome, which dominated over a variable flexible virome that may have been too heterogeneous for experimental detection or was underrepresented in the databases. It will be interesting to analyze whether the enteric virome allows predictions for the clinical outcome of FMT for rCDI and other diseases such as inflammatory bowel disease or obesity.

SUBMITTER: Broecker F

PROVIDER: S-EPMC5479397 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Stable core virome despite variable microbiome after fecal transfer.

Broecker Felix F Russo Giancarlo G Klumpp Jochen J Moelling Karin K

Gut microbes 20161209 3

We recently described the 4.5-year time course of the enteric bacterial microbiota and virome of a patient cured from recurrent Clostridium difficile infection (rCDI) by fecal microbiota transplantation (FMT). Here, we extended the virome analyses and found the patient's phage population to exhibit highly donor-similar characteristics following FMT, which remained stable for the whole period tested (up to 7 months). Moreover, the detected viral populations of donor and patient exhibited comparab ...[more]

PMID: 27935413

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Project description:IntroductionPatients who suffer a traumatic brain injury (TBI) often experience chronic and sometimes debilitating sequelae. Recent reports have illustrated both acute and long-term dysbiosis of the gastrointestinal microbiome with significant alterations in composition and predicted functional consequences.MethodsWorking with participants from past research, metagenomic stability of the TBI- associated fecal microbiome (FMB) was evaluated by custom qPCR array comparing a fecal sample from 2015 to one collected in 2020. Metatranscriptomics identified differently expressed bacterial genes and biochemical pathways in the TBI FMB. Microbiota that contributed the largest RNA amounts identified a set of core bacteria most responsible for functional consequences of the TBI FMB.ResultsA remarkably stable FMB metagenome with significant similarity (two-tail Spearman nonparametric correlation p < 0.001) was observed between 2015 and 2020 fecal samples from subjects with TBI. Comparing the 2020 TBI FMB metagenome to FMBs from healthy controls confirmed and extended the dysbiotic genera and species. Abundance differences between average TBI and healthy FMBs revealed Bacteroides caccae, B. uniformis, Blautia spp., Collinsella spp., Dialister spp., and Ordoribacter spp. were significantly different. Functionally, the Parabacteroides genus contributed the highest percentage of RNA sequences in control FMBs followed by the Bacteroides genus as the second highest contributor. In the TBI FMB, the Corynebacterium genus contributed the most RNA followed by the Alistipes genus. Corynebacterium and Pseudomonas were distinct in the top 10 contributing genera in the TBI FMB while Parabacteroides and Ruminococcus were unique to the top 10 in controls. Comparing RNA profiles, TBI samples had ∼1.5 fold more expressed genes with almost 700 differently expressed genes (DEGs) mapped to over 100 bacterial species. Bioinformatic analysis associated DEGs with pathways led identifying 311 functions in the average TBI FMB profile and 264 in the controls. By average profile comparison, 30 pathways had significantly different abundance (p < 0.05, t-test) or were detected in >80% of the samples in only one of the cohorts (binary distinction).DiscussionFunctional differences between TBI and healthy control FMBs included amino acid metabolism, energy and carbon source usage, fatty acid metabolism, bacterial cell wall component production and nucleic acid synthesis and processing pathways. Together these data shed light on the functional consequences of the dysbiotic TBI FMB decades after injury.

Project description:Background:Metagenomic analysis of the gut microbiome and resistome is instrumental for understanding the dynamics of diarrheal pathogenesis and antimicrobial resistance transmission (AMR). Metagenomic sequencing of 20 diarrheal fecal samples from Kolkata was conducted to understand the core and variable gut microbiota. Five of these samples were used for resistome analysis. The pilot study was conducted to determine a microbiota signature and the source of antimicrobial resistance genes (ARGs) in the diarrheal gut. Results:16S rRNA amplicon sequencing was performed using Illumina MiSeq platform and analysed using the MGnify pipeline. The Genome Taxonomy Database (GTDB-Tk) was used for bacterial taxonomic identification. Diarrheal etiology was determined by culture method. Phylum Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria were consistently present in 20 samples. Firmicutes was the most abundant phylum in 11 samples. The Bacteroidetes/Firmicutes ratio was less than 1 in 18 samples. 584 genera were observed. 18 of these were present in all the 20 samples. Proteobacteria was the dominant phylum in 6 samples associated with Vibrio cholerae infection. Conservation of operational taxonomic units (OTUs) among all the samples indicated the existence of a core microbiome. Asymptomatic carriage of pathogens like Vibrio cholerae and Helicobacter pylori was found. Signature of Candidate phyla or "microbial dark matter" occurred. Significant correlation of relative abundance of bacterial families of commensals and pathogens were found. Whole-genome sequencing (WGS) on Illumina MiSeq system and assembly of raw reads using metaSPAdes v3.9.1 was performed to study the resistome of 5 samples. ABRicate was used to assign ARG function. 491 resistance determinants were identified. In 80% of the samples tetracycline resistance was the most abundant resistance determinant. High abundance of ARGs against ?-lactams, aminoglycosides, quinolones and macrolides was found. Eschericia sp. was the major contributor of ARGs. Conclusions:This is the first comparative study of the gut microbiome associated with different diarrheal pathogens. It presents the first catalogue of different bacterial taxa representing the core and variable microbiome in acute diarrheal patients. The study helped to define a trend in the gut microbiota signature associated with diarrhea and revealed which ARGs are abundantly present and the metagenome-assembled genomes (MAGs) contributing to AMR.

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Project description:The gut microbiome has an important role in health, and diet represents a key lever for shaping the gut microbiome across all stages of life. Maternal milk consumption in neonates leads to long-term health effects, indicating that pliability in the infant gut microbiome in response to diet can drive enduring change. The ability of diet to drive lasting changes in the adult gut microbiome is less understood. We studied the effect of an extreme dietary shift on the fecal microbiome of 46 Labrador retriever dogs (mean age, 4.6 years) over 11 months. Dogs were fed a nutritionally complete, commercially available complex diet (CD) for a minimum of 5 weeks, followed by highly purified diets (PDs) for 36 weeks, and the initial CD for at least a further 4 weeks. Fecal samples were collected at regular intervals for DNA extraction. By analyzing 16S rRNA genes and the metagenomes, we observed minor effects on microbial diversity but significant changes in bacterial taxa and genetic potential when a PD was fed. Specifically, metagenomics identified an enrichment of quinone- and GABA-related pathways on PD, providing insights into dietary effects on cross-feeding strategies impacting community structure. When dogs returned to the CD, no significant differences were found with the initial time point. These findings are consistent with the gut microbiome being rapidly adaptable but capable of being reconstituted when provided with similar diets. These data highlight that long-term changes in the adult dog gut microbiome may only be achieved through long-term maintenance on a specified diet, rather than through feeding a transitionary diet.IMPORTANCE Diet can influence the adult gut microbiome (the community of bacteria) and health outcomes, but the ability to make changes persisting beyond feeding of a particular diet is poorly understood. We investigated whether feeding highly purified diets to adult dogs for 36 weeks would alter bacterial populations sufficiently to result in a persistent change following the dogs' return to a commercial diet. As expected, the microbiome changed when the purified diet was fed, but the original microbiome was reconstituted within weeks of the dogs returning to the commercial diet. The significance of these findings is in identifying an intrinsic stability of the host microbiome in healthy dogs, suggesting that dietary changes to support adult dog health through modifying the gut microbiome may be achieved only through maintenance on a specified diet, rather than through feeding transitionary diets.

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Stable core virome despite variable microbiome after fecal transfer.

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Stable core virome despite variable microbiome after fecal transfer.

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