Project description:Persistent mucosal inflammation and microbial infection are characteristic of Chronic Rhinosinusitis (CRS). Though mucosal microbiota dysbiosis is a characteristic feature of other chronic inflammatory diseases, the relationship between sinus microbiota composition and CRS is unknown. Here we demonstrate, using comparative microbiome profiling of a cohort of CRS patients and healthy subjects, that the sinus microbiota of CRS patients exhibit significantly reduced bacterial diversity. Characteristic of this community collapse is the depletion of multiple, phylogenetically distinct, Lactic Acid Bacteria and the concomitant increase in relative abundance of a single species, Corynebacterium tuberculostearicum. Recapitulating the conditions observed in our human cohort in a murine model confirmed the pathogenic potential of C. tuberculostearicum and the critical necessity for a replete mucosal microbiota to protect against this species. Moreover, we provide evidence that Lactobacillus sakei, identified from our comparative microbiome analyses as a potentially protective species, affords defense against C. tuberculostearicum sinus infection, even in the context of a depleted sinus bacterial community. These studies demonstrate that sinus mucosal health is highly dependent on the composition of the resident microbiota, and identifies a new sino-pathogen and a strong bacterial candidate for therapeutic intervention. A total of 14 samples were profiled for microbiome composition: 7 from non-sinusitis patients, and 7 from patients with clinically diagnosed chronic sinusitis.
Project description:Persistent mucosal inflammation and microbial infection are characteristic of Chronic Rhinosinusitis (CRS). Though mucosal microbiota dysbiosis is a characteristic feature of other chronic inflammatory diseases, the relationship between sinus microbiota composition and CRS is unknown. Here we demonstrate, using comparative microbiome profiling of a cohort of CRS patients and healthy subjects, that the sinus microbiota of CRS patients exhibit significantly reduced bacterial diversity. Characteristic of this community collapse is the depletion of multiple, phylogenetically distinct, Lactic Acid Bacteria and the concomitant increase in relative abundance of a single species, Corynebacterium tuberculostearicum. Recapitulating the conditions observed in our human cohort in a murine model confirmed the pathogenic potential of C. tuberculostearicum and the critical necessity for a replete mucosal microbiota to protect against this species. Moreover, we provide evidence that Lactobacillus sakei, identified from our comparative microbiome analyses as a potentially protective species, affords defense against C. tuberculostearicum sinus infection, even in the context of a depleted sinus bacterial community. These studies demonstrate that sinus mucosal health is highly dependent on the composition of the resident microbiota, and identifies a new sino-pathogen and a strong bacterial candidate for therapeutic intervention.
Project description:Opioid analgesics are frequently prescribed in the United States and worldwide. However, serious side effects such as addiction, immunosuppression and gastrointestinal symptoms limit long term use. In the current study using a chronic morphine-murine model a longitudinal approach was undertaken to investigate the role of morphine modulation of gut microbiome as a mechanism contributing to the negative consequences associated with opioids use. The results revealed a significant shift in the gut microbiome and metabolome within 24 hours following morphine treatment when compared to placebo. Morphine induced gut microbial dysbiosis exhibited distinct characteristic signatures profiles including significant increase in communities associated with pathogenic function, decrease in communities associated with stress tolerance. Collectively, these results reveal opioids-induced distinct alteration of gut microbiome, may contribute to opioids-induced pathogenesis. Therapeutics directed at these targets may prolong the efficacy long term opioid use with fewer side effects.
Project description:Opportunistic oral infections are ultimately presented in a vast majority of HIV-infected patients, often causing debilitating lesions that also contribute to deterioration in nutritional health. Although appreciation for the role that the microbiota is likely to play in the initiation and/or enhancement of oral infections has grown considerably in recent years, little is known about the impact of HIV infection on host-microbe interactions within the oral cavity. In the current study, we characterize modulations in the bacterial composition of the lingual microbiome in patients with treated and untreated HIV infection. Bacterial species profiles were elucidated by microarray assay and compared between untreated HIV infected patients, HIV infected patients receiving antiretroviral therapy, and healthy HIV negative controls. The relationship between clinical parameters (viral burden and CD4+ T cell depletion) and the loss or gain of bacterial species was evaluated in each HIV patient group. Characterization of modulations in the dorsal tongue (lingual) microbiota that are associated with chronic HIV infection.
Project description:Background: While the luminal microbiome composition in the human cervicovaginal tract has been defined, the presence and impact of tissue-adherent ectocervical microbiota remain incompletely understood. Studies of luminal and tissue-associated bacteria in the gastrointestinal tract suggest that they may have distinct roles in health and disease. Here, we performed a multi-omics characterization of paired luminal and tissue samples collected from a clinically well-characterized cohort of Kenyan women. Results: We identified a tissue-adherent bacterial microbiome, with a higher alpha diversity than the luminal microbiome, in which dominant genera overall included Gardnerella and Lactobacillus, followed by Prevotella, Atopobium, and Sneathia. About half of the L. iners dominated luminal samples had a corresponding Gardnerella dominated tissue microbiome. Broadly, the tissue-adherent microbiome was associated with fewer differentially expressed host genes than the luminal microbiome. Gene set enrichment analysis revealed that L. crispatus-dominated tissue-adherent communities were associated with protein translation and antimicrobial activity, whereas a highly diverse microbiome was associated with epithelial remodeling and pro-inflammatory pathways. Communities dominated by L. iners and Gardnerella were associated with low host transcriptional activity. Tissue-adherent microbiomes dominated by Lactobacillus and Gardnerella correlated with host protein profiles associated with epithelial barrier stability, and with a more pro-inflammatory profile for the Gardnerella-dominated microbiome group. Tissue samples with a highly diverse composition had a protein profile representing cell proliferation and pro-inflammatory activity. Conclusion: We identified ectocervical tissue-adherent bacterial communities in all study participants. These communities were distinct from cervicovaginal luminal microbiota in a significant proportion of individuals. This difference could possibly explain that L. iners dominant luminal communities have a high probability of transitioning to high diverse bacterial communities including high abundance of Gardnerella. By performing integrative multi-omics analyses we further revealed that bacterial communities at both sites correlated with distinct host gene expression and protein levels. The tissue-adherent bacterial community is similar to vaginal biofilms that significantly impact women’s reproductive and sexual health.
Project description:Chronic rhinosinusitis (CRS) is a prevalent chronic rhinologic disease, characterized by persistent symptomatic inflammation of the nasal mucosa and paranasal sinuses. Sinonasal tissues were obtained during sinus surgeries performed at Northwestern University. For the microarray, NP tissues and uncinate tissues from normal healthy controls were divided into elderly (≥65 years old, each n=3-4), or non-elderly (18-49 years old, each n=3-4) according to age. This study protocol was approved by the independent ethics committees or institutional review boards (IRB) at Northwestern University. Total RNA was isolated from NP tissues and control uncinate tissues. RNA concentration was calculated, and the highest quality RNA used for microarray. The quality of total RNA was evaluated by Bioanalyzer (Agilent Technologies, Santa Clara, CA). The samples were at a concentration ≥125ng/μl and a A260/A280 ratio that was ≥1.80 and a RIN value that was ≥7.0 were considered acceptable. The highest quality RNA was used to generate labeled cRNA and hybridized to Affymetrix Human Gene 2.1ST array following the manufacturer’s protocol (Affymetrix Inc., Santa Clara, CA). Chip processing and image capturing were performed using Affymetrix AGCC software. We investigated age- and disease-related differential gene expression in chronic rhinosinusitis with nasal polyps.