Dysbiotic Communities Research Articles

Thiamine Acquisition Strategies Impact Metabolism and Competition in the Gut Microbe Bacteroides thetaiotaomicron.

Thiamine (vitamin B1) is an essential cofactor for all organisms. Humans primarily acquire thiamine through their diet, and thiamine deficiencies have adverse neurological effects. However, the role gut microbes play in modulating thiamine availability is poorly understood, and little is known about how thiamine impacts the stability of microbial gut communities. To investigate thiamine's role in the gut, we utilized the model gut microbe Bacteroides thetaiotaomicron. Transcriptome sequencing (RNA-seq) revealed a global downregulation of thiamine and amino acid biosynthesis, glycolysis, and purine metabolism when thiamine was present. Using genetic mutants with thiamine biosynthesis and transport locus mutations, we determined both systems were critical for growth in thiamine-deficient medium. The defect in the double transport mutant suggests an uncharacterized feedback mechanism between thiamine transport and biosynthesis in B.thetaiotaomicron. Mutant phenotypes were recapitulated during pairwise competitions, reinforcing the importance of encoding versatile thiamine acquisition mechanisms when thiamine concentrations are variable. In addition, liquid chromatography-mass spectrometry (LC-MS) analyses corroborate that exogenous thiamine levels affect the internal thiamine pool of B.thetaiotaomicron. Furthermore, we computationally examined the ability of other gut microbes to acquire thiamine and identified lineage-specific differences in thiamine acquisition strategies. Among the Bacteroidetes, the capacities for both thiamine transport and biosynthesis are common. Together, these data show that thiamine acquisition mechanisms used by B.thetaiotaomicron not only are critical for its physiology and fitness but also provide the opportunity to model how other gut microbes may respond to the shifting availability of thiamine in the gut. IMPORTANCE Variation in the ability of gut microbes to transport, synthesize, and compete for vitamin B1 (thiamine) is expected to impact the structure and stability of the microbiota, and ultimately this variation may have both direct and indirect effects on human health. Our study identifies the diverse strategies employed by gut Bacteroidetes to acquire thiamine. We demonstrate how the presence or absence of thiamine biosynthesis or transport dramatically affects the abundance of B.thetaiotaomicron in a competitive environment. This study adds further evidence that altering the presence or concentrations of water-soluble vitamins such as thiamine may be an effective method for manipulating gut community composition. In turn, targeted thiamine delivery could be used therapeutically to alter dysbiotic communities linked to disease. Author Video: An author video summary of this article is available.

Metabolic crosstalk regulates Porphyromonas gingivalis colonization and virulence during oral polymicrobial infection.

Many human infections are polymicrobial in origin, and interactions among community inhabitants shape colonization patterns and pathogenic potential 1 . Periodontitis, which is the sixth most prevalent infectious disease worldwide 2 , ensues from the action of dysbiotic polymicrobial communities 3 . The keystone pathogen Porphyromonas gingivalis and the accessory pathogen Streptococcus gordonii interact to form communities in vitro and exhibit increased fitness in vivo 3,4 . The mechanistic basis of this polymicrobial synergy, however, has not been fully elucidated. Here we show that streptococcal 4-aminobenzoate/para-amino benzoic acid (pABA) is required for maximal accumulation of P. gingivalis in dual-species communities. Metabolomic and proteomic data showed that exogenous pABA is used for folate biosynthesis, and leads to decreased stress and elevated expression of fimbrial adhesins. Moreover, pABA increased the colonization and survival of P. gingivalis in a murine oral infection model. However, pABA also caused a reduction in virulence in vivo and suppressed extracellular polysaccharide production by P. gingivalis. Collectively, these data reveal a multidimensional aspect to P. gingivalis-S. gordonii interactions and establish pABA as a critical cue produced by a partner species that enhances the fitness of P. gingivalis while diminishing its virulence.

The bacteriome and mycobiome associated with oral squamous cell carcinoma: metagenomic analysis of samples from Yemeni and Sri Lankan cohorts

ABSTRACTThere is increasing interest in the possible role of the oral microbiome in oral squamous cell carcinoma (OSSC). However, studies on the possible association between the oral bacteriome and OSCC remain inconclusive, while the potential role of the “mycobiome” in oral carcinogenesis has never been explored. I hereby present results from our recent studies on the bacteriome and mycobiome associated with OSCC based on analysis of samples from Yemeni and Sri Lankan cohorts. Tissue biopsies were obtained from the cases while deep buccal swabs or fibro-epithelial polyps were collected from the controls. Sequencing of the bacterial V1-V3 region of the 16S rRNA gene and the fungal ITS2 region using Illumina’s 2x300 bp chemistry was employed to study the bacteriome and mycobiome, respectively. Merged reads were classified to species level using a BLASTN-algorithm. Downstream analyses were performed using QIIME, PICRUSt, and LEfSe. Fusobacterium nucleatum subsp. polymorphum, Pseudomonas aeruginosa, Prevotella and Campylobacter spp. were more abundant in OSCC samples while Streptococcus mitis and Rothia spp. were overrepresented in the controls. Functionally, inflammatory bacterial attributes including bacterial mobility, flagellar assembly, bacterial chemotaxis and LPS synthesis were enriched in the tumors. Mycobiome analysis revealed a dysbiotic fungal community dominated by C. albicans in association with OSCC.

Can Better Management of Periodontal Disease Delay the Onset and Progression of Alzheimer's Disease?

A risk factor relationship exists between periodontal disease and Alzheimer's disease (AD) via tooth loss, and improved memory following dental intervention. This links the microbial contribution from indigenous oral periodontal pathogens to the manifestation of chronic conditions, such as AD. Here, we use Porphyromonas gingivalis infection to illustrate its effect on mental health. P. gingivalis infection, in its primary sub-gingival niche, can cause polymicrobial synergy and dysbiosis. Dysbiosis describes the residency of select commensals from the oral cavity following co-aggregation around the dominant keystone pathogen, such as P. gingivalis, to gain greater virulence. The initial process involves P. gingivalis disturbing neutrophil mediated innate immune responses in the healthy gingivae and then downregulating adaptive immune cell differentiation and development to invade, and subsequently, establish new dysbiotic bacterial communities. Immune responses affect the host in general and functionally via dietary adjustments caused by tooth loss. Studies from animals orally infected with P. gingivalis confirm this bacterium can transmigrate to distant organ sites (the brain) and contribute toward peripheral and intracerebral inflammation, and compromise vascular and microvascular integrity. In another study, P. gingivalis infection caused sleep pattern disturbances by altering glial cell light/dark molecular clock activity, and this, in turn, can affect the clearance of danger associated molecular patterns, such as amyloid-β, via the glymphatic system. Since P. gingivalis can transmigrate to the brain and modulate organ-specific inflammatory innate and adaptive immune responses, this paper explores whether better management of indigenous periodontal bacteria could delay/prevent the onset and/or progression of dementia.

Giardia duodenalis induces pathogenic dysbiosis of human intestinal microbiota biofilms

Giardia duodenalis is a prevalent cause of acute diarrheal disease worldwide. However, recent outbreaks in Italy and Norway have revealed a link between giardiasis and the subsequent development of chronic post-infectious irritable bowel syndrome. While the mechanisms underlying the causation of post-infectious irritable bowel syndrome remain obscure, recent findings suggest that alterations in gut microbiota communities are linked to the pathophysiology of irritable bowel syndrome. In the present study, we use a laboratory biofilm system to culture and enrich mucosal microbiota from human intestinal biopsies. Subsequently, we show that co-culture with Giardia induces disturbances in biofilm species composition and biofilm structure resulting in microbiota communities that are intrinsically dysbiotic – even after the clearance of Giardia. These microbiota abnormalities were mediated in part by secretory-excretory Giardia cysteine proteases. Using in vitro cell culture and germ-free murine infection models, we show that Giardia-induced disruptions of microbiota promote bacterial invasion, resulting in epithelial apoptosis, tight junctional disruption, and bacterial translocation across an intestinal epithelial barrier. Additionally, these dysbiotic microbiota communities resulted in increased activation of the Toll-like receptor 4 signalling pathway, and overproduction of the pro-inflammatory cytokine IL-1beta in humanized germ-free mice. Previous studies that have sought explanations and risk factors for the development of post-infectious irritable bowel syndrome have focused on features of enteropathogens and attributes of the infected host. We propose that polymicrobial interactions involving Giardia and gut microbiota may cause persistent dysbiosis, offering a new interpretation of the reasons why those afflicted with giardiasis are predisposed to gastrointestinal disorders post-infection.

Distinct signatures of dental plaque metabolic byproducts dictated by periodontal inflammatory status

Onset of chronic periodontitis is associated with an aberrant polymicrobial community, termed dysbiosis. Findings regarding its etiology obtained using high-throughput sequencing technique suggested that dysbiosis holds a conserved metabolic signature as an emergent property. The purpose of this study was to identify robust biomarkers for periodontal inflammation severity. Furthermore, we investigated disease-associated metabolic signatures of periodontal microbiota using a salivary metabolomics approach. Whole saliva samples were obtained from adult subjects before and after removal of supragingival plaque (debridement). Periodontal inflamed surface area (PISA) was employed as an indicator of periodontal inflammatory status. Based on multivariate analyses using pre-debridement salivary metabolomics data, we found that metabolites associated with higher PISA included cadaverine and hydrocinnamate, while uric acid and ethanolamine were associated with lower PISA. Next, we focused on dental plaque metabolic byproducts by selecting salivary metabolites significantly decreased following debridement. Metabolite set enrichment analysis revealed that polyamine metabolism, arginine and proline metabolism, butyric acid metabolism, and lysine degradation were distinctive metabolic signatures of dental plaque in the high PISA group, which may be related to the metabolic signatures of disease-associated communities. Collectively, our findings identified potential biomarkers of periodontal inflammatory status and also provide insight into metabolic signatures of dysbiotic communities.

Dysbiosis in Crohn's disease - Joint action of stochastic injuries and focal inflammation in the gut

ABSTRACTGut homeostasis involves interrelated biological networks that include the immune system, specialized cells of the epithelium, such as Paneth and goblet cells, as well as triggers derived from the microbiota. Disruption of these homeostatic interactions may lead to the pathogenesis of inflammatory bowel diseases (IBD). To develop more targeted and individual treatments in Crohn's disease and ulcerative colitis, it becomes more and more important to link key mechanisms of the disease pathogenesis to distinct IBD subsets. For the first time, our laboratory demonstrated a causal role of the microbiota for the development of Crohn's disease (CD)-like ileitis, supporting the hypothesis that a non-infectious, dysbiotic microbial ecosystem harbors aggressive traits relevant for the induction of chronic inflammation in the disease-susceptible host (i.e. TNFΔARE mouse model). Despite a growing body of evidence claiming a primary role for Paneth cells in the pathogenesis of ileal CD, we showed in the TNFΔARE mouse model that Paneth cell failure or exhaustion is a secondary event to inflammation. Therefore, additional mechanisms may act synergistically to initialize the development of CD-like pathology. Hereby, we propose a novel hypothesis suggesting that individual development of dysbiotic communities is based on stochastic injury and focal inflammation of the epithelial lining that propagate radially, finally leading to an aggressive microbial milieu.

The gut microbiome and HIV-1 pathogenesis: a two-way street.

HIV-1 infection is associated with substantial damage to the gastrointestinal tract resulting in structural impairment of the epithelial barrier and a disruption of intestinal homeostasis. The accompanying translocation of microbial products and potentially microbes themselves from the lumen into systemic circulation has been linked to immune activation, inflammation, and HIV-1 disease progression. The importance of microbial translocation in the setting of HIV-1 infection has led to a recent focus on understanding how the communities of microbes that make up the intestinal microbiome are altered during HIV-1 infection and how they interact with mucosal immune cells to contribute to inflammation. This review details the dysbiotic intestinal communities associated with HIV-1 infection and their potential link to HIV-1 pathogenesis. We detail studies that begin to address the mechanisms driving microbiota-associated immune activation and inflammation and the various treatment strategies aimed at correcting dysbiosis and improving the overall health of HIV-1-infected individuals. Finally, we discuss how this relatively new field of research can advance to provide a more comprehensive understanding of the contribution of the gut microbiome to HIV-1 pathogenesis.

Evidence of microbiota dysbiosis in chronic rhinosinusitis.

Despite considerable research, the pathogenesis of chronic rhinosinusitis (CRS) remains poorly understood. Potential microbial roles in the etiology or progression of CRS have long been hypothesized, yet few specific associations have been identified. In this study we investigate associations between patterns in resident bacterial communities and clinical variants of CRS. Bacterial communities were assessed in 94 patients with extensive bilateral CRS undergoing endoscopic sinus surgery (ESS) and 29 controls undergoing ESS for indications other than CRS. Patients were grouped on the basis of phenotypic variants (with or without polyposis) and clinical parameters, including asthma and cystic fibrosis. Bacterial communities were characterized via 16S rRNA gene amplicon sequencing, and quantified by quantitative polymerase chain reaction. Controls and idiopathic CRS subjects tended to be dominated by members of the genera Corynebacterium and Staphylococcus, together with lower abundances of several other genera, including Streptococcus, Moraxella, and Haemophilus. Aberrant (dysbiotic) bacterial assemblages (with changes in community membership and structure, reduced diversity, and increased bacterial load) and increased inter- and intrasubject variability were more common in subjects with comorbidities such as asthma and cystic fibrosis. Dysbiotic communities were variably dominated by members of the genera Staphylococcus, Streptococcus, Haemophilus, Pseudomonas, Moraxella, or Fusobacterium. Bacterial community dysbiosis was more apparent than specific associations with examined phenotypes or endotypes, and may play a role in the pathogenesis or influence the severity of CRS. Reductions in several common core bacterial taxa, increased inter- and intrasubject variability, reduced bacterial diversity, and increased bacterial load characterized aberrant bacterial communities in CRS.

The road less traveled - defining molecular commensalism with Streptococcus sanguinis.

The commensal oral microbial flora has evolved with the human host to support colonization of the various intraoral sites without triggering a significant immune response. In exchange, the commensal microbes provide critical protection against invading pathogens. The intrinsic ability of the oral flora to create a symbiotic microbial community with the host can be disturbed, selecting for the overgrowth of a dysbiotic community that can result in dental diseases, such as caries and periodontitis. Although the mechanisms of molecular pathogenesis in oral diseases are well characterized, much less is known about the molecular mechanisms used by the commensal flora to maintain oral health. Here we focus on the commensal species Streptococcus sanguinis, which is found in abundance in the early oral biofilm and is strongly correlated with oral health. Streptococcus sanguinis exhibits a variety of features that make it ideally suited as a model organism to explore the molecular basis for commensalism. As such, this review will describe our current mechanistic understanding of S.sanguinis commensalism and speculate upon its molecular traits that may be exploitable to maintain or restore oral health under conditions that would otherwise lead to disease.

Skin microbiome before development of atopic dermatitis: Early colonization with commensal staphylococci at 2 months is associated with a lower risk of atopic dermatitis at 1 year

BackgroundDisease flares of established atopic dermatitis (AD) are generally associated with a low-diversity skin microbiota and Staphylococcus aureus dominance. The temporal transition of the skin microbiome between early infancy and the dysbiosis of established AD is unknown.MethodsWe randomly selected 50 children from the Cork Babies After SCOPE: Evaluating the Longitudinal Impact Using Neurological and Nutritional Endpoints (BASELINE) longitudinal birth cohort for microbiome sampling at 3 points in the first 6 months of life at 4 skin sites relevant to AD: the antecubital and popliteal fossae, nasal tip, and cheek. We identified 10 infants with AD and compared them with 10 randomly selected control infants with no AD. We performed bacterial 16S ribosomal RNA sequencing and analysis directly from clinical samples.ResultsBacterial community structures and diversity shifted over time, suggesting that age strongly affects the skin microbiome in infants. Unlike established AD, these patients with infantile AD did not have noticeably dysbiotic communities before or with disease and were not colonized by S aureus. In comparing patients and control subjects, infants who had affected skin at month 12 had statistically significant differences in bacterial communities on the antecubital fossa at month 2 compared with infants who were unaffected at month 12. In particular, commensal staphylococci were significantly less abundant in infants affected at month 12, suggesting that this genus might protect against the later development of AD.ConclusionsThis study suggests that 12-month-old infants with AD were not colonized with S aureus before having AD. Additional studies are needed to confirm whether colonization with commensal staphylococci modulates skin immunity and attenuates development of AD.

Human neutrophils and oral microbiota: a constant tug-of-war between a harmonious and a discordant coexistence.

Neutrophils are a major component of the innate host response, and the outcome of the interaction between the oral microbiota and neutrophils is a key determinant of oral health status. The composition of the oral microbiome is very complex and different in health and disease. Neutrophils are constantly recruited to the oral cavity, and their protective role is highlighted in cases where their number or functional responses are impeded, resulting in different forms of periodontal disease. Periodontitis, one of the more severe and irreversible forms of periodontal disease, is a microbial-induced chronic inflammatory disease that affects the gingival tissues supporting the tooth. This chronic inflammatory disease is the result of a shift of the oral bacterial symbiotic community to a dysbiotic more complex community. Chronic inflammatory infectious diseases such as periodontitis can occur because the pathogens are able to evade or disable the innate immune system. In this review, we discuss how human neutrophils interact with both the symbiotic and the dysbiotic oral community; an understanding of which is essential to increase our knowledge of the periodontal disease process.

Effects of Arabinoxylan and Resistant Starch on Intestinal Microbiota and Short-Chain Fatty Acids in Subjects with Metabolic Syndrome: A Randomised Crossover Study.

Recently, the intestinal microbiota has been emphasised as an important contributor to the development of metabolic syndrome. Dietary fibre may exert beneficial effects through modulation of the intestinal microbiota and metabolic end products. We investigated the effects of a diet enriched with two different dietary fibres, arabinoxylan and resistant starch type 2, on the gut microbiome and faecal short-chain fatty acids. Nineteen adults with metabolic syndrome completed this randomised crossover study with two 4-week interventions of a diet enriched with arabinoxylan and resistant starch and a low-fibre Western-style diet. Faecal samples were collected before and at the end of the interventions for fermentative end-product analysis and 16S ribosomal RNA bacterial gene amplification for identification of bacterial taxa. Faecal carbohydrate residues were used to verify compliance. The diet enriched with arabinoxylan and resistant starch resulted in significant reductions in the total species diversity of the faecal-associated intestinal microbiota but also increased the heterogeneity of bacterial communities both between and within subjects. The proportion of Bifidobacterium was increased by arabinoxylan and resistant starch consumption (P<0.001), whereas the proportions of certain bacterial genera associated with dysbiotic intestinal communities were reduced. Furthermore, the total short-chain fatty acids (P<0.01), acetate (P<0.01) and butyrate concentrations (P<0.01) were higher by the end of the diet enriched with arabinoxylan and resistant starch compared with those resulting from the Western-style diet. The concentrations of isobutyrate (P = 0.05) and isovalerate (P = 0.03) decreased in response to the arabinoxylan and resistant starch enriched diet, indicating reduced protein fermentation. In conclusion, arabinoxylan and resistant starch intake changes the microbiome and short-chain fatty acid compositions, with potential beneficial effects on colonic health and metabolic syndrome.Trial RegistrationClinicalTrials.gov NCT01618526

Gut barrier structure, mucosal immunity and intestinal microbiota in the pathogenesis and treatment of HIV infection.

Over the past 10 years, extensive work has been carried out in the field of microbial translocation in HIV infection, ranging from studies on its clinical significance to investigations on its pathogenic features. In the present work, we review the most recent findings on this phenomenon, focusing on the predictive role of microbial translocation in HIV-related morbidity and mortality, the mechanisms by which it arises and potential therapeutic approaches. From a clinical perspective, current work has shown that markers of microbial translocation may be useful in predicting clinical events in untreated HIV infection, while conflicting data exist on their role in cART-experienced subjects, possibly due to the inclusion of extremely varied patient populations in cohort studies. Results from studies addressing the pathogenesis of microbial translocation have improved our knowledge of the damage of the gastrointestinal epithelial barrier occurring in HIV infection. However, the extent to which mucosal impairment translates directly to increased gastrointestinal permeability remains an open issue. In this respect, novel work has established a role for IL-17 and IL-22-secreting T cell populations in limiting microbial translocation and systemic T-cell activation/inflammation, thus representing a possible target of immune-therapeutic interventions shown to be promising in the animal model. Further, recent reports have not only confirmed the presence of a dysbiotic intestinal community in the course of HIV infection but have also shown that it may be linked to mucosal damage, microbial translocation and peripheral immune activation. Importantly, technical advances have also shed light on the metabolic activity of gut microbes, highlighting the need for novel therapeutic approaches to correct the function, as well as the composition, of the gastrointestinal microbiota.

Dysbiosis in intestinal inflammation: Cause or consequence

The intestinal microbiota encompasses hundreds of bacterial species that constitute a relatively stable ecosystem. Alteration in the microbiota composition may arise from infections, immune defects, metabolic alterations, diet or antibiotic treatment. Dysbiosis is considered as an alteration in microbiota community structure and/or function, capable of causing/driving a detrimental distortion of microbe-host homeostasis. A variety of pathologies are associated with changes in the community structure and function of the gut microbiota, suggesting a link between dysbiosis and disease etiology. With an emphasis in this review on inflammatory bowel diseases (IBD), the non-trivial question is whether dysbiosis is the cause or consequence of inflammation. It is important to understand whether changes in microbial ecosystems are causally linked to the pathology and to what extend disease risk is predicable based on characteristic changes in community structure and/or function. Local changes in tissue integrity associated with focal areas of inflammation may result in the selection of a dysbiotic bacterial community associated with the propagation of a disease phenotype. This review outlines the role of dysbiosis in intestinal inflammation with particular focus on IBD-relevant gnotobiotic mouse models, the factors implicated in the development of dysbiosis and the means available to investigate dysbiosis in the context of human diseases.

Protein relative abundance patterns associated with sucrose-induced dysbiosis are conserved across taxonomically diverse oral microcosm biofilm models of dental caries.

BackgroundThe etiology of dental caries is multifactorial, but frequent consumption of free sugars, notably sucrose, appears to be a major factor driving the supragingival microbiota in the direction of dysbiosis. Recent 16S rRNA-based studies indicated that caries-associated communities were less diverse than healthy supragingival plaque but still displayed considerable taxonomic diversity between individuals. Metagenomic studies likewise have found that healthy oral sites from different people were broadly similar with respect to gene function, even though there was an extensive individual variation in their taxonomic profiles. That pattern may also extend to dysbiotic communities. In that case, shifts in community-wide protein relative abundance might provide better biomarkers of dysbiosis that can be achieved through taxonomy alone.ResultsIn this study, we used a paired oral microcosm biofilm model of dental caries to investigate differences in community composition and protein relative abundance in the presence and absence of sucrose. This approach provided large quantities of protein, which facilitated deep metaproteomic analysis. Community composition was evaluated using 16S rRNA sequencing and metaproteomic approaches. Although taxonomic diversity was reduced by sucrose pulsing, considerable inter-subject variation in community composition remained. By contrast, functional analysis using the SEED ontology found that sucrose induced changes in protein relative abundance patterns for pathways involving glycolysis, lactate production, aciduricity, and ammonia/glutamate metabolism that were conserved across taxonomically diverse dysbiotic oral microcosm biofilm communities.ConclusionsOur findings support the concept of using function-based changes in protein relative abundance as indicators of dysbiosis. Our microcosm model cannot replicate all aspects of the oral environment, but the deep level of metaproteomic analysis it allows makes it suitable for discovering which proteins are most consistently abundant during dysbiosis. It then may be possible to define biomarkers that could be used to detect at-risk tooth surfaces before the development of overt carious lesions.Electronic supplementary materialThe online version of this article (doi:10.1186/s40168-015-0136-z) contains supplementary material, which is available to authorized users.

Microbial protection and virulence in periodontal tissue as a function of polymicrobial communities: symbiosis and dysbiosis.

This review discusses polymicrobial interactions with the host in both health and disease. As our ability to identify specific bacterial clonal types, with respect to their abundance and location in the oral biofilm, improves, we will learn more concerning their contribution to both oral health and disease. Recent studies examining host- bacteria interactions have revealed that commensal bacteria not only protect the host simply by niche occupation, but that bacterial interactions with host tissue can promote the development of proper tissue structure and function. These data indicate that our host-associated polymicrobial communities, such as those found in the oral cavity, co-evolved with us and have become an integral part of who we are. Understanding the microbial community factors that underpin the associations with host tissue that contribute to periodontal health may also reveal how dysbiotic periodontopathic oral communities disrupt normal periodontal tissue functions in disease. A disruption of the oral microbial community creates dysbiosis, either by overgrowth of specific or nonspecific microorganisms or by changes in the local host response where the community can now support a disease state. Dysbiosis provides the link between systemic changes (e.g. diabetes) and exogenous risk factors (e.g. smoking), and the dysbiotic community, and can drive the destruction of periodontal tissue. Many other risk factors associated with periodontal disease, such as stress, aging and genetics, are also likely to affect the microbial community, and more research is needed, utilizing sophisticated bacterial taxonomic techniques, to elucidate these effects on the microbiome and to develop strategies to target the dysbiotic mechanisms and improve periodontal health.

Subgingival microbiome in patients with healthy and ailing dental implants.

Dental implants are commonly used to replace missing teeth. However, the dysbiotic polymicrobial communities of peri-implant sites are responsible for peri-implant diseases, such as peri-implant mucositis and peri-implantitis. In this study, we analyzed the microbial characteristics of oral plaque from peri-implant pockets or sulci of healthy implants (n = 10), peri-implant mucositis (n = 8) and peri-implantitis (n = 6) sites using pyrosequencing of the 16S rRNA gene. An increase in microbial diversity was observed in subgingival sites of ailing implants, compared with healthy implants. Microbial co-occurrence analysis revealed that periodontal pathogens, such as Porphyromonas gingivalis, Tannerella forsythia, and Prevotella intermedia, were clustered into modules in the peri-implant mucositis network. Putative pathogens associated with peri-implantitis were present at a moderate relative abundance in peri-implant mucositis, suggesting that peri-implant mucositis an important early transitional phase during the development of peri-implantitis. Furthermore, the relative abundance of Eubacterium was increased at peri-implantitis locations, and co-occurrence analysis revealed that Eubacterium minutum was correlated with Prevotella intermedia in peri-implantitis sites, which suggests the association of Eubacterium with peri-implantitis. This study indicates that periodontal pathogens may play important roles in the shifting of healthy implant status to peri-implant disease.

Viral Metagenomics Reveal Blooms of Anelloviruses in the Respiratory Tract of Lung Transplant Recipients

Few studies have examined the lung virome in health and disease. Outcomes of lung transplantation are known to be influenced by several recognized respiratory viruses, but global understanding of the virome of the transplanted lung is incomplete. To define the DNA virome within the respiratory tract following lung transplantation we carried out metagenomic analysis of allograft bronchoalveolar lavage (BAL), and compared with healthy and HIV+ subjects. Viral concentrates were purified from BAL and analyzed by shotgun DNA sequencing. All of the BAL samples contained reads mapping to anelloviruses, with high proportions in lung transplant samples. Anellovirus populations in transplant recipients were complex, with multiple concurrent variants. Quantitative polymerase chain reaction quantification revealed that anellovirus sequences were 56-fold more abundant in BAL from lung transplant recipients compared with healthy controls or HIV+ subjects (p < 0.0001). Anellovirus sequences were also more abundant in upper respiratory tract specimens from lung transplant recipients than controls (p = 0.006). Comparison to metagenomic data on bacterial populations showed that high anellovirus loads correlated with dysbiotic bacterial communities in allograft BAL (p = 0.008). Thus the respiratory tracts of lung transplant recipients contain high levels and complex populations of anelloviruses, warranting studies of anellovirus lung infection and transplant outcome.

Porphyromonas gingivalis neutrophil manipulation: risk factor for periodontitis?

Defining the contribution of individual members of dysbiotic host-associated bacterial communities has been difficult. The recent paper by Maekawa et al. in Cell Host & Microbe describes bacterial manipulation of neutrophil responses by Porphyromonas gingivalis as a mechanism that contributes to forming a dysbiotic community.