Periodontitis and Alzheimer’s disease: oral systemic link still on the rise?

doi: 10.1111/j.1741‐2358.2012.00660.x Periodontitis and Alzheimer’s disease: Oral systemic link still on the rise? Over the past few years, there has been a rapid rise in the older segments of the world population, which has brought along with it a major health concern: dementia. Alzheimer’s disease, considered to be the most common cause of dementia, has become a prospect feared by the elderly. Inflammation of the brain is strongly implicated in Alzheimer’s disease which could be enhanced by systemic inflammation. Periodontitis being a chronic inflammatory condition, which can cause systemic inflammation, the question is whether chronic periodontitis can initiate or hasten the rate of progression of Alzheimer’s disease in susceptible individuals. In this article, the authors outline the proposed oral systemic link between periodontitis and Alzheimer’s disease.     

Antibacterials as anti-inflammatory agents: Dual action agents for oral health

Background Inflammatory processes with a range of specialized cells and biochemical mediators form a complex network of inter-related signal transducing pathways that relay information to preserve normal functions. Advances in molecular analyses of the information relay pathways for their constituents and principal ligands along with mechanisms utilized by the host for microbial recognition have stimulated interest in therapeutic agents with dual functionalities i.e. antibacterial and anti-inflammatory effects. Aim This review examines clinically tested agents for oral health applications with both antimicrobial and anti-inflammatory effects to include antibiotics, antimicrobials and phenolics. Results Bis-phenols such as triclosan, representing a unique dual functional therapeutic for routine oral hygiene, with its demonstrated clinical effects on inhibiting the dental plaque biofilm, reducing inflammation (gingivitis) and subsequent periodontitis is described. Cyclines, comprising another class of approved anti-inflammatory agents used at the patient level for oral health is discussed. Dual active agents in current clinical practice for systemic conditions are highlighted to summarize the clinical validity of dual function agents as an emerging therapeutic strategy. Conclusions Clinical studies demonstrate therapeutic benefits of agents with dual functionality with their effects on microorganisms and the concomitant host inflammatory response. Advances in microbial pathogenesis and resultant inflammation will facilitate progress in this emerging area poised to be a significant milestone for dental therapeutics     

Targeting Atp6v1c1 Prevents Inflammation and Bone Erosion Caused by Periodontitis and Reveals Its Critical Function in Osteoimmunology

Periodontal disease (Periodontitis) is a serious disease that affects a majority of adult Americans and is associated with other systemic diseases, including diabetes, rheumatoid arthritis, and other inflammatory diseases. While great efforts have been devoted toward understanding the pathogenesis of periodontitis, there remains a pressing need for developing potent therapeutic strategies for targeting this pervasive and destructive disease. In this study, we utilized novel adeno-associated virus (AAV)-mediated Atp6v1c1 knockdown gene therapy to treat bone erosion and inflammatory caused by periodontitis in mouse model. Atp6v1c1 is a subunit of the V-ATPase complex and regulator of the assembly of the V0 and V1 domains of the V-ATPase complex. We demonstrated previously that Atp6v1c1 has an essential function in osteoclast mediated bone resorption. We hypothesized that Atp6v1c1 may be an ideal target to prevent the bone erosion and inflammation caused by periodontitis. To test the hypothesis, we employed AAV RNAi knockdown of Atp6v1c1 gene expression to prevent bone erosion and gingival inflammation simultaneously. We found that lesion-specific injection of AAV-shRNA-Atp6v1c1 into the periodontal disease lesions protected against bone erosion (>85%) and gingival inflammation caused by P. gingivalis W50 infection. AAV-mediated Atp6v1c1 knockdown dramatically reduced osteoclast numbers and inhibited the infiltration of dendritic cells and macrophages in the bacteria-induced inflammatory lesions in periodontitis. Silencing of Atp6v1c1 expression also prevented the expressions of osteoclast-related genes and pro-inflammatory cytokine genes. Our data suggests that AAV-shRNA-Atp6v1c1 treatment can significantly attenuate the bone erosion and inflammation caused by periodontitis, indicating the dual function of AAV-shRNA-Atp6v1c1 as an inhibitor of bone erosion mediated by osteoclasts, and as an inhibitor of inflammation through down-regulation of pro-inflammatory cytokine expression. This study demonstrated that Atp6v1c1 RNAi knockdown gene therapy mediated by AAV-shRNA-Atp6v1c1 is a promising novel therapeutic approach for the treatment of bone erosion and inflammatory related diseases, such as periodontitis and rheumatoid arthritis.     

The Pros1/Tyro3 axis protects against periodontitis by modulating STAT/SOCS signalling

Periodontitis, an oral inflammatory disease caused by periodontal pathogen infection, is the most prevalent chronic inflammatory disease and a major burden on healthcare. The TAM receptor tyrosine kinases (Tyro3, Axl and Mertk) and their ligands (Gas6 and Pros1) play a pivotal role in the resolution of inflammation and have been associated with chronic inflammatory and autoimmune diseases. In this study, we evaluated the effects of exogenous Pros1 in in vitro and in vivo models of periodontitis. We detected higher Pros1 but lower Tyro3 levels in inflamed gingival specimens of periodontitis patients compared with healthy controls. Moreover, Pros1 was mostly localized in the gingival epithelium of all specimens. In cultured human gingival epithelial cells (hGECs), Porphyromonas gingivalis LPS (p.g‐LPS) stimulation down‐regulated Pros1 and Tyro3. Exogenous Pros1 inhibited p.g‐LPS–induced production of TNF‐α, IL‐6, IL‐1β, MMP9/2 and RANKL in a Tyro3‐dependent manner as revealed by PCR, Western blot analysis, ELISA and gelatin zymography. Pros1 also restored Tyro3 expression down‐regulated by p.g‐LPS in hGECs. In rats treated with ligature and p.g‐LPS, administration of Pros1 attenuated periodontitis‐associated gingival inflammation and alveolar bone loss. Our mechanistic studies implicated SOCS1/3 and STAT1/3 as mediators of the in vitro and in vivo anti‐inflammatory effects of Pros1. Collectively, the findings from this work supported Pros1 as a novel anti‐inflammatory therapy for periodontitis.     

Periodontal infections and atherosclerosis: mere associations?

PURPOSE OF REVIEW: Several lines of evidence from the last few decades suggest that periodontitis is an important risk factor for cardiovascular diseases. In this review we discuss the recent findings on the systemic effects of periodontitis, which may contribute to the pathogenesis of atherosclerosis, with a special emphasis on lipoproteins. RECENT FINDINGS: In addition to the epidemiological studies exploring the direct or indirect relationship between clinical periodontitis and cardiovascular diseases, studies utilizing serology, animal models, cell cultures, and biochemistry of lipoproteins have been published. Local infection in the periodontal pockets triggers a systemic inflammatory response releasing inflammatory mediators and awakens a strong immune response against periodontal pathogens. Elevated systemic antibody levels especially to Porphyromonas gingivalis are associated with an increased risk for atherosclerosis. Periodontitis is also accompanied by proatherogenic changes in both low and high density lipoproteins, which lead to enhanced cholesteryl ester uptake by and reduced cholesterol efflux from macrophages. Vesicles and lipopolysaccharide isolated from P. gingivalis activate macrophages to convert into foam cells. Moreover, animal studies have demonstrated that infection by P. gingivalis enhances progression of atherosclerosis. SUMMARY: Recent studies have clarified the mechanisms by which periodontitis may contribute to the development of atherosclerosis. Serological, animal, and cell culture studies provide evidence that infection by P. gingivalis may promote atherosclerosis. The influence of periodontitis on lipoprotein metabolism has emerged as a new, important factor. Recent studies provide experimental proof that periodontitis may predispose to atherosclerosis.     

Gene polymorphisms in pro-inflammatory cytokines are associated with systemic inflammation in patients with severe periodontal infections

The inflammatory response to chronic infections such as periodontitis may be central to the systemic implications of these diseases. This study examined the possible association between specific gene polymorphisms and the systemic inflammatory response in individuals suffering from severe generalized periodontitis. Ninety-four subjects with periodontitis were genotyped for polymorphisms in IL-1A (-889), IL-1B (-511, +3954), TNF-A (-308), IL-6 (-174) and TLR4 (-299, -399) genes. We found that the genotypes for IL-1A or IL-6 are associated with higher levels of serum IL-6 (P < 0.03) and serum CRP (P < 0.05), similarly the TNF-A genotype is associated with higher levels of serum IL-6 (P < 0.05) after correction for age, body mass index, gender, ethnicity and cigarette smoking. Systemic inflammatory responses are higher in severe periodontitis patients carrying rare alleles for functional inflammatory gene polymorphisms. These results suggest that cytokine genotypes are important determinants of the systemic inflammatory response in subjects with periodontitis. Genetic polymorphism therefore, may in part explain the reported association between periodontitis and systemic disease.     

Serum levels of oncostatin M (a gp 130 cytokine): an inflammatory biomarker in periodontal disease

Objective: Periodontitis is considered to be a risk factor for systemic diseases such as atherosclerosis, diabetes, etc., and cytokines play a key role. The present study was carried out to measure the level of serum oncostatin M (OSM) in patients with chronic periodontitis, and to evaluate the effect of non-surgical periodontal therapy on the serum OSM concentration.

Materials and methods: Sixty subjects were divided into three groups (each group n?=?20) based on the gingival index (GI), probing pocket depth (PPD) and clinical attachment level (CAL): group I healthy; group II gingivitis; and group III chronic periodontitis. Group III patients were followed for 8 weeks after non-surgical periodontal therapy as the after-treatment group (group IV). Estimation of serum OSM was done using an enzyme-linked immunosorbent assay.

Results: The mean OSM concentrations in serum were highest in the chronic periodontitis group (mean 68.05 pg ml^?1) and decreased following treatment (39.65 pg ml^?1) while OSM was undetectable in healthy subjects or in patients with gingivitis.

Conclusion: Increased serum OSM concentration in patients with chronic periodontitis and its positive correlation with PPD and CAL, suggest its role as an inflammatory biomarker in periodontal disease and it may exaggerate other systemic conditions such as atherosclerosis and rheumatoid arthritis.     

Periodontitis and Cognitive Decline in Alzheimer’s Disease

Periodontitis is common in the elderly and may become more common in Alzheimer’s disease because of a reduced ability to take care of oral hygiene as the disease progresses. Elevated antibodies to periodontal bacteria are associated with an increased systemic pro-inflammatory state. Elsewhere raised serum pro-inflammatory cytokines have been associated with an increased rate of cognitive decline in Alzheimer’s disease. We hypothesized that periodontitis would be associated with increased dementia severity and a more rapid cognitive decline in Alzheimer’s disease. We aimed to determine if periodontitis in Alzheimer’s disease is associated with both increased dementia severity and cognitive decline, and an increased systemic pro inflammatory state. In a six month observational cohort study 60 community dwelling participants with mild to moderate Alzheimer’s Disease were cognitively assessed and a blood sample taken for systemic inflammatory markers. Dental health was assessed by a dental hygienist, blind to cognitive outcomes. All assessments were repeated at six months. The presence of periodontitis at baseline was not related to baseline cognitive state but was associated with a six fold increase in the rate of cognitive decline as assessed by the ADAS-cog over a six month follow up period. Periodontitis at baseline was associated with a relative increase in the pro-inflammatory state over the six month follow up period. Our data showed that periodontitis is associated with an increase in cognitive decline in Alzheimer’s Disease, independent to baseline cognitive state, which may be mediated through effects on systemic inflammation.     

The association between rheumatoid arthritis and periodontal disease

Chronic, plaque-associated inflammation of the gingiva and the periodontium are among the most common oral diseases. Periodontitis (PD) is characterized by the inflammatory destruction of the periodontal attachment and alveolar bone, and its clinical appearance can be influenced by congenital as well as acquired factors. The existence of a rheumatic or other inflammatory systemic disease may promote PD in both its emergence and progress. However, there is evidence that PD maintains systemic diseases. Nevertheless, many mechanisms in the pathogenesis have not yet been examined sufficiently, so that a final explanatory model is still under discussion, and we hereby present arguments in favor of this. In this review, we also discuss in detail the fact that oral bacterial infections and inflammation seem to be linked directly to the etiopathogenesis of rheumatoid arthritis (RA). There are findings that support the hypothesis that oral infections play a role in RA pathogenesis. Of special importance are the impact of periodontal pathogens, such as Porphyromonas gingivalis on citrullination, and the association of PD in RA patients with seropositivity toward rheumatoid factor and the anti-cyclic citrullinated peptide antibody.     

Do oral bacteria alter the regenerative potential of stem cells? A?concise review

Mesenchymal stem cells (MSCs) are widely recognized as critical players in tissue regeneration. New insights into stem cell biology provide evidence that MSCs may also contribute to host defence and inflammation. In case of tissue injury or inflammatory diseases, e.g. periodontitis, stem cells are mobilized towards the site of damage, thus coming in close proximity to bacteria and bacterial components. Specifically, in the oral cavity, complex ecosystems of commensal bacteria live in a mutually beneficial state with the host. However, the formation of polymicrobial biofilm communities with pathogenic properties may trigger an inadequate host inflammatory‐immune response, leading to the disruption of tissue homoeostasis and development of disease. Because of their unique characteristics, MSCs are suggested as crucial regulators of tissue regeneration even under such harsh environmental conditions. The heterogeneous effects of bacteria on MSCs across studies imply the complexity underlying the interactions between stem cells and bacteria. Hence, a better understanding of stem cell behaviour at sites of inflammation appears to be a key strategy in developing new approaches for in situ tissue regeneration. Here, we review the literature on the effects of oral bacteria on cell proliferation, differentiation capacity and immunomodulation of dental‐derived MSCs.     

Oral health status and change in handgrip strength over a 5-year period in 80-year-old people

Objective: The number of remaining teeth may indicate the extent of life‐long exposure to inflammation, a known risk factor for muscle loss and consequent disability. The aim was to study dental health status as a risk factor for muscle strength loss in very old people. Design: Cross‐sectional and prospective cohort study over a 5‐year follow‐up. Setting: Research laboratory. Participants: One hundred and ninety‐three 80‐year‐old people participated in the baseline examinations. Five years later, 79 survivors were retested. Main outcome measures: Number of remaining teeth, presence of periodontitis and handgrip strength. Results: At baseline, grip strength of men correlated positively with number of teeth but not with the presence of periodontitis. In women, the cross‐sectional associations were not statistically significant. In the prospective analyses, the presence of periodontitis at baseline showed a clear association with a steeper decline in handgrip over the 5‐year follow‐up in both sexes. The values adjusted for gender, height, weight, number of chronic conditions and physical activity were ?28.3% (SE 5.7) among those with periodontitis vs. ?11.9% (SE 3.1, p = 0.015) among those with healthy gingiva. No association between the number of teeth at baseline and change in grip strength over 5 years was observed. Conclusions: The presence of oral inflammation may lead to loss in muscle strength increasing the risk of disability. Therefore, good dental care throughout the life span may decrease risk of disability in old age.     

Exosomal microRNA-155-5p from PDLSCs regulated Th17/Treg balance by targeting sirtuin-1 in chronic periodontitis

The mechanism of local inflammation and systemic injury in chronic periodontitis is complicated, in which and exosomes play an important role. In our study, we found that T helper cell 17 (Th17)/regulatory T cell (Treg) balance is destabilized in the peripheral blood of patients with periodontitis, with upregulated Th17 or downregulated Treg, respectively. Porphyromonas gingivalis lipopolysaccharide (LPS) was used to simulate the inflammatory microenvironment of chronic periodontitis. The exosomes were extracted from periodontal ligament stem cells (PDLSCs) in LPS-induced periodontitis environment, which inversely effected on CD4+ T cells under normal and inflammatory conditions. Furthermore, compared with exosomes from normal PDLSCs, lower expression of microRNA-155-5p (miR-155-5p) and higher expression of Sirtuin-1 (SIRT1) were observed in exosomes from LPS-stimulated PDLSCs. Exosomes from PDLSCs alleviated inflammatory microenvironment through Th17/Treg/miR-155-5p/SIRT1 regulatory network. This study aimed to find the “switching” factors that affected the further deterioration of periodontitis to maximally control the multiple downstream damage signal factors to further understand periodontitis and find new targets for its treatment.     

Association of ADHD and the Protogenin gene in the chromosome 15q21.3 reading disabilities linkage region

Twin studies indicate genetic overlap between symptoms of attention deficit hyperactivity disorder (ADHD) and reading disabilities (RD), and linkage studies identify several chromosomal regions possibly containing common susceptibility genes, including the 15q region. Based on a translocation finding and association to two specific alleles, the candidate gene, DYX1C1, has been proposed as the susceptibility gene for RD in 15q. Previously, we tested markers in DYX1C1 for association with ADHD. Although we identified association for haplotypes across the gene, we were unable to replicate the association to the specific alleles reported. Thus, the risk alleles for ADHD are yet to be identified. The susceptibility alleles may be in a remote regulatory element, or DYX1C1 may not be the risk gene. To continue study of 15q, we tested a coding region change in DYX1C1, followed by markers across the gene Protogenin (PRTG) in 253 ADHD nuclear families. PRTG was chosen based on its location and because it is closely related to DCC and Neogenin, two genes known to guide migratory cells and axons during development. The markers in DYX1C1 were not associated to ADHD when analyzed individually; however, six markers in PRTG showed significant association with ADHD as a categorical trait (P = 0.025–0.005). Haplotypes in both genes showed evidence for association. We identified association with ADHD symptoms measured as quantitative traits in PRTG, but no evidence for association with two key components of reading, word identification and decoding was observed. These findings, while preliminary, identify association of ADHD to a gene that potentially plays a role in cell migration and axon growth.     

Inflammation and free radicals in tumor development and progression

Abstract

Inflammation is thought to be one of the major contributors to carcinogenesis. Accumulated studies in this field revealed that free radicals produced by inflammatory cells not only cause direct damage to DNA but also exert indirect effects such as de-regulation of cell proliferation and apoptosis, stimulation of angiogenesis, and modification of gene/protein expressions and protein activities, all of which are a critical step toward carcinogenesis. Free radicals have also been reported to act as both initiator and promoter of carcinogenic process. Recent evidence shows that free radicals convert benign tumors to more malignant ones (i.e. tumor progression) leading to the final stage of carcinogenesis. This article reviews the current findings linking inflammation and cancer, and shed light on inflammatory cell-derived free radicals as major endogenous reactive substances for tumor development and progression.     

Orosomucoid,a New Biomarker in the Association between Obesity and Periodontitis

Epidemiological data indicate an association between periodontitis and obesity. The biological mechanisms of this relationship remain unclear. A cross-sectional study was conducted to evaluate the relationship between periodontitis and the common systemic inflammatory markers in 32 morbidly obese patients recruited in a Clinical Nutrition department. Periodontal condition was evaluated using pocket depth (PD) measurement, a classical clinical marker of ongoing periodontitis. Major periodontal risk factors were recorded (age, gender, diabetes and smoking status), as well as plasma levels of inflammatory markers (CRP, orosomucoid, IL-6) and adipokines (adiponectin, leptin). All patients included in the sample exhibited evidence of periodontitis, 16 of whom were diagnosed as having severe disease. Adjusted logistic regression analysis indicated that the severity of periodontitis was associated with the plasma level of orosomucoid (p<0.04) after adjustment for age, gender and smoking. Our study thus suggests that the severity of periodontitis, in morbidly obese patients, is associated with the increase of orosomucoid levels.     

Uric acid correlates to oxidation and inflammation in opposite directions in women

Abstract

Objective: To evaluate the association of uric acid (UA) levels with a panel of markers of oxidative stress and inflammation.

Methods: Plasma UA levels, along with a panel of oxidative stress and inflammatory markers, were measured in 755 Chinese women.

Results: Plasma UA levels were inversely associated with urinary levels of the oxidative stress marker F₂-isoprostanes and positively correlated to levels of inflammatory markers, such as C-reactive protein and some proinflammatory cytokines (tumor necrosis factor-α and interleukin-6) in blood as well as prostaglandin E₂ metabolites in urine.

Conclusions: Plasma UA levels correlate to oxidation and inflammation biomarkers in opposite directions in women.     

Possible relationship between periodontitis and dementia in a North Indian old age population: a pilot study

doi: 10.1111/j.1741‐2358.2010.00441.x Possible relationship between periodontitis and dementia in a North Indian old age population: a pilot study Background: Periodontitis and cognitive impairment or dementia is relatively common among older adults. Few cross‐sectional studies and some longitudinal studies have attempted to link oral health with dementia diagnosis or disease pathology but none has investigated the role of inflammation as a potential mediator. Objectives: This study was planned to establish a relation of inflammatory mediators between periodontitis and dementia. Materials and methods: Fifty‐five patients with severe periodontitis (range 60–69 years), 20 with dementia (10:10 M:F; range 59–69) and 32 healthy controls (range 58–69 years) were selected. The socio‐demographic characteristics, physical health, oral health, education status, and medical status were measured. Serum C‐reactive protein (CRP), matrix metalloproteinase (MMP)‐8, MMP‐9, total IGF‐I, free IGF‐I and TNF‐alpha and GCF MMP‐8 &MMP‐9 were calculated. Results: There was no significant difference between the three groups in the level of education, age, occupation, BMI, CAD, CHF and diabetes except dentate status. After adjusting for age, significant differences were found between patients and controls with respect to gingival inflammation, dental plaque, bleeding on probing and probing pocket depth. Total counts of WBCs, neutrophils, thrombocytic counts and serum CRP, MMP‐8, MMP‐9, TNF‐alpha levels were significantly higher in dementia and periodontitis patients in contrast to healthy controls, while, RBC counts, total IGF‐I and Hb levels were lowered in dementia and periodontitis patients in comparison to healthy controls, although higher in dementia as compared to periodontitis patients. Conclusions: This study data suggest a relationship of inflammatory mediators between periodontitis and dementia. Further exploration of this is warranted.     

Histochemistry of Tobacco Mesophyll Cell Walls Pretreated with Bacterial Protein-lipopolysaccharides

Prevention of hypersensitive confluent-necrosis in tobacco mesophyll, caused by Pseudomonas syringae pv. aptata, and tolerance towards the incompatible bacterium are induced 48 h after intercellular injection of protein-lipopolysaccharide complexes. Histochemical analysis and ultrastructural observations were carried out to determine whether there was an association between this tolerance state and cell wall alterations due to callose, lignin and/or suberin deposition either before or after challenge with the incompatible bacterium. No evidence was obtained for such wall alterations.     

Loss of Metabotropic Glutamate Receptor 5 Function on Peripheral Benzodiazepine Receptor in Mice Prenatally Exposed to LPS

Parental microglial induced neuroinflammation, triggered by bacterial- or viral infections, can induce neuropsychiatric disorders like schizophrenia and autism to offspring in animal models. Recent investigations suggest that microglia, the resident immune cells of the brain, provides a link between neurotransmission, immune cell activation, brain inflammation and neuronal dysfunction seen with the offspring. Relatively little is known about how reduction of brain inflammation and restoration of glial function are associated with diminution of brain degeneration and behavioral deficits in offspring. Increased mGluR5 expression and the long-lasting excitotoxic effects of the neurotoxin during brain development are associated with the glial dysfunctions. We investigated the relationship of mGluR5 and PBR and how they regulate glial function and inflammatory processes in mice prenatally exposed to LPS (120μg/kg, between gestational days 15 and 17), an inflammatory model of a psychiatric disorder. Using PET imaging, we showed that pharmacological activation of mGluR5 during 5 weeks reduced expression of classic inflammation marker PBR in many brain areas and that this molecular association was not present in LPS-exposed offspring. The post-mortem analysis revealed that the down regulation of PBR was mediated through activation of mGluR5 in astrocytes. In addition, we demonstrated that this interaction is defective in a mouse model of the psychiatric deficit offering a novel insight of mGluR5 involvement to brain related disorders and PBR related imaging studies. In conclusion, mGluR5 driven glutamatergic activity regulates astrocytic functions associated with PBR (cholesterol transport, neurosteroidogenesis, glial phenotype) during maturation and could be associated with neuropsychiatric disorders in offspring.     

Low-abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and complement

Porphyromonas gingivalis is a low-abundance oral anaerobic bacterium implicated in periodontitis, a polymicrobial inflammatory disease, and the associated systemic conditions. However, the mechanism by which P. gingivalis contributes to inflammation and disease has remained elusive. Here we show that P. gingivalis, at very low colonization levels, triggers changes to the amount and composition of the oral commensal microbiota leading to inflammatory periodontal bone loss. The commensal microbiota and complement were both required for P. gingivalis-induced bone loss, as germ-free mice or conventionally raised C3a and C5a receptor-deficient mice did not develop bone loss after inoculation with P. gingivalis. These findings demonstrate that a single, low-abundance species can disrupt host-microbial homeostasis to cause inflammatory disease. The identification and targeting of similar low-abundance pathogens with community-wide impact may be important for treating inflammatory diseases of polymicrobial etiology.