Microbiologists utilize ribosomal RNA genes as molecular markers of taxonomy in surveys of microbial communities. rRNA genes are often co-located as part of an rrn operon, and multiple copies of this operon are present in genomes across the microbial tree of life. rrn copy number variability provides valuable insight into microbial life history, but introduces systematic bias when measuring community composition in molecular surveys. Here we present an update to the ribosomal RNA operon copy number database (rrnDB), a publicly available, curated resource for copy number information for bacteria and archaea. The redesigned rrnDB (http://rrndb.umms.med.umich.edu/) brings a substantial increase in the number of genomes described, improved curation, mapping of genomes to both NCBI and RDP taxonomies, and refined tools for querying and analyzing these data. With these changes, the rrnDB is better positioned to remain a comprehensive resource under the torrent of microbial genome sequencing. The enhanced rrnDB will contribute to the analysis of molecular surveys and to research linking genomic characteristics to life history.
The gut microbiome is emerging as an important factor in regulating mental health yet it remains unclear what the target should be for psychiatric treatment. We aimed to elucidate the complement of the gut-microbiome community for individuals with bipolar disorder relative to controls; and test for relationships with burden of disease measures. We compared the stool microbiome from individuals with bipolar disorder (n=115) and control subjects (n=64) using 16S ribosomal RNA (rRNA) gene sequence analysis. Analysis of molecular variance (AMOVA) revealed global community case-control differences (AMOVA p=0.047). Operational Taxonomical Unit (OTU) level analysis revealed significantly decreased fractional representation (p<0.001) of Faecalibacterium after adjustment for age, sex, BMI and false discovery rate (FDR) correction at the p<0.05 level. Within individuals with bipolar disorder, the fractional representation of Faecalibacterium associated with better self-reported health outcomes based on the Short Form Health Survey (SF12); the Patient Health Questionnaire (PHQ9); the Pittsburg Sleep Quality Index (PSQI); the Generalized Anxiety Disorder scale (GAD7); and the Altman Mania Rating Scale (ASRM), independent of covariates. This study provides the first detailed analysis of the gut microbiome relationships with multiple psychiatric domains from a bipolar population. The data support the hypothesis that targeting the microbiome may be an effective treatment paradigm for bipolar disorder.
More than 100 trillion symbiotic microorganisms constitutively colonize throughout the human body, including the oral cavity, the skin, and the gastrointestinal tract. The oral cavity harbors one of the most diverse and abundant microbial communities within the human body, second to the community that resides in the gastrointestinal tract, and is composed of >770 bacterial species. Advances in sequencing technologies help define the precise microbial landscape in our bodies. Environmental and functional differences render the composition of resident microbiota largely distinct between the mouth and the gut and lead to the development of unique microbial ecosystems in the 2 mucosal sites. However, it is apparent that there may be a microbial connection between these 2 mucosal sites in the context of disease pathogenesis. Accumulating evidence indicates that resident oral bacteria can translocate to the gastrointestinal tract through hematogenous and enteral routes. The dissemination of oral microbes to the gut may exacerbate various gastrointestinal diseases, including irritable bowel syndrome, inflammatory bowel disease, and colorectal cancer. However, the precise role that oral microbes play in the extraoral organs, including the gut, remains elusive. Here, we review the recent findings on the dissemination of oral bacteria to the gastrointestinal tract and their possible contribution to the pathogenesis of gastrointestinal diseases. Although little is known about the mechanisms of ectopic colonization of the gut by oral bacteria, we also discuss the potential factors that allow the oral bacteria to colonize the gut.
Klebsiella pneumoniae (Kp) is an important cause of healthcare-associated infections, which increases patient morbidity, mortality, and hospitalization costs. Gut colonization by Kp is consistently associated with subsequent Kp disease, and patients are predominantly infected with their colonizing strain. Our previous comparative genomics study, between disease-causing and asymptomatically colonizing Kp isolates, identified a plasmid-encoded tellurite (TeO3-2)-resistance (ter) operon as strongly associated with infection. However, TeO3-2 is extremely rare and toxic to humans. Thus, we used a multidisciplinary approach to determine the biological link between ter and Kp infection. First, we used a genomic and bioinformatic approach to extensively characterize Kp plasmids encoding the ter locus. These plasmids displayed substantial variation in plasmid incompatibility type and gene content. Moreover, the ter operon was genetically independent of other plasmid-encoded virulence and antibiotic resistance loci, both in our original patient cohort and in a large set (n = 88) of publicly available ter operon-encoding Kp plasmids, indicating that the ter operon is likely playing a direct, but yet undescribed role in Kp disease. Next, we employed multiple mouse models of infection and colonization to show that 1) the ter operon is dispensable during bacteremia, 2) the ter operon enhances fitness in the gut, 3) this phenotype is dependent on the colony of origin of mice, and 4) antibiotic disruption of the gut microbiota eliminates the requirement for ter. Furthermore, using 16S rRNA gene sequencing, we show that the ter operon enhances Kp fitness in the gut in the presence of specific indigenous microbiota, including those predicted to produce short chain fatty acids. Finally, administration of exogenous short-chain fatty acids in our mouse model of colonization was sufficient to reduce fitness of a ter mutant. These findings indicate that the ter operon, strongly associated with human infection, encodes factors that resist stress induced by the indigenous gut microbiota during colonization. This work represents a substantial advancement in our molecular understanding of Kp pathogenesis and gut colonization, directly relevant to Kp disease in healthcare settings.
Introductory paragraphGut colonization by the pathogen Klebsiella pneumoniae (Kp) is consistently associated with subsequent Kp disease 1-5 , and patients are predominantly infected with their colonizing strain 1,2 . However, colonizing strains likely vary in their potential to cause infection. We previously identified the plasmid-encoded tellurium resistance (ter) operon as highly associated with infection when compared to asymptomatic colonization in hospitalized patients 1 . The ter operon bestows resistance to the toxic compound tellurite oxide (TeO3 -2 ), but this is unlikely to be its physiological function, as tellurium and TeO3 -2 are exceedingly rare. Here we show that terC is necessary and terZABCDEF is sufficient for phenotypic TeO3 -2 resistance. Next, we demonstrate that ter is encoded on a diverse group of plasmids without known plasmid-encoded virulence genes, suggesting an independent role in infection. Finally, our studies indicate that ter is a gut fitness factor, and its fitness advantage is conferred only when specific gut microbiota constituents are present. Collectively, these data reveal the Kp ter operon that is highly associated with human infection likely acts early in pathogenesis as a horizontally-transferrable fitness factor promoting robust gut colonization in the presence of the indigenous microbiota.3
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