ABSTRACT: Bacterial species cultivated from multiple sites across the human microbiota (oral, nasal, skin, gastrointestinal tract, reproductive tract).
Project description:Background Alterations of the gut microbiome have been linked to multiple chronic diseases. However, the drivers of such changes remain largely unknown. The oral cavity acts as a major route of exposure to exogenous factors including pathogens, and processes therein may affect the communities in the subsequent compartments of the gastrointestinal tract. Here, we perform strain-resolved, integrated multi-omic analyses of saliva and stool samples collected from eight families with multiple cases of type 1 diabetes mellitus (T1DM). Results We identified distinct oral microbiota mostly reflecting competition between streptococcal species. More specifically, we found a decreased abundance of the commensal Streptococcus salivarius in the oral cavity of T1DM individuals, which is linked to its apparent competition with the pathobiont Streptococcus mutans. The decrease in S. salivarius in the oral cavity was also associated with its decrease in the gut as well as higher abundances in facultative anaerobes including Enterobacteria. In addition, we found evidence of gut inflammation in T1DM as reflected in the expression profiles of the Enterobacteria as well as in the human gut proteome. Finally, we were able to follow transmitted strain-variants from the oral cavity to the gut at the metagenomic, metatranscriptomic and metaproteomic levels, highlighting not only the transfer, but also the activity of the transmitted taxa along the gastrointestinal tract. Conclusions Alterations of the oral microbiome in the context of T1DM impact the microbial communities in the lower gut, in particular through the reduction of “oral-to-gut” transfer of Streptococcus salivarius. Our results indicate that the observed oral-cavity-driven gut microbiome changes may contribute towards the inflammatory processes involved in T1DM. Through the integration of multi-omic analyses, we resolve strain-variant “mouth-to-gut” transfer in a disease context.
Project description:<p>This first clinical study of the Human Microbiome Project (HMP) addresses whether individuals share a core human microbiome. It involves broad determination of the microbiota found in five anatomical sites: the oral cavity, skin, nasal cavity, gastrointestinal tract and vagina. This study will enroll approximately 300 healthy male and female adults, 18-40 years old, from two geographic regions of the US: Houston, TX and St. Louis, MO. The participation of healthy individuals will create a baseline for discovery of the core microbiota typically found in various areas of the human body. The information from this initial study can then be used to help assess the changes in the complement of microbiota found on or within diseased individuals.</p>
Project description:Indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract (iNKLPD) is a newly recognized entity in the 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours: Lymphoid Neoplasms. Initially described as "NK-cell enteropathy" and "lymphomatoid gastropathy" over a decade ago, recent molecular and cytogenetic studies have confirmed its neoplastic nature. Although primarily affecting the gastrointestinal tract, iNKLPD has also been reported in rare extra-intestinal sites, including the gallbladder, lymph nodes, nasopharynx, and vagina. Case presentation We present a unique case involving the nasal cavity, which has not been previously reported as a site of involvement. A 67-year-old female patient presented with recurrent postnasal drip symptoms persisting for one year following an upper respiratory tract infection. Imaging studies revealed a nasal mass on head computed tomography (CT), prompting endoscopic resection. Intraoperatively, a mulberry-like neoplasm was identified in the left nasal septum. Histopathological examination using hematoxylin-eosin (HE) staining revealed diffuse infiltration by medium to large round cells. Immunohistochemical profiling demonstrated positive expression of CD56, CD3, BCL-2, TIA-1, and Granzyme B, with a Ki-67 proliferation index of 50%. CD5, CD20, CD21, CD23, CD10, BCL-6, CD30, PAX-5, and PD-1 were negative. Notably, in situ hybridization for Epstein-Barr virus (EBV)-encoded RNA was negative, and T-cell receptor (TCR) gene rearrangement was not detected by polymerase chain reaction (PCR) analysis, confirming the diagnosis of indolent NK-cell lymphoproliferative disorder (iNKLPD) of the gastrointestinal tract. After 11 months of follow-up, the patient showed no local recurrence or signs of lymph node enlargement in other anatomical regions. Furthermore, proteomics analysis of the case was conducted in conjunction with Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Conclusion Although iNKLPD is a rare tumor, cases involving the nasal cavity are exceptionally uncommon and have not been reported in the literature. This unique case represents the first documented instance of iNKLPD in the nasal cavity, contributing to the comprehensive understanding of its pathological diagnosis and clinical management. Proteomics analysis of the case has provided valuable insights into the molecular mechanisms underlying this rare disease.
Project description:Asymptomatic colonization of the upper respiratory tract is a common trait of the two exclusive human pathogens, Neisseria gonorrhoeae and Neisseria meningitidis. In vivo models of pathogenic neisserial infections are heterologous systems that permit short-term persistence but do not fully recapitulate infections in humans. Studying Neisseria musculi (Nmus), an oral commensal, in laboratory mice allows investigation of Neisseria-host interactions that avoids host restriction barriers. Nmus produces smooth and rough morphotypes on solid media. We compared the in vitro phenotypes, biofilm transcriptomes, and in vivo colonization patterns and burdens of the Nmus morphotypes. We observed that the two morphotypes differ in biofilm formation, aggregation, pilin production, and transformation frequency in vitro. These phenotypes strongly correlated with differential expression of a set of genes in the Nmus biofilms including those that encoded factors for bacterial attachment. In vivo, the smooth morphotype stably colonized the oral cavities of all inoculated A/J and C57BL/6J mice at higher burdens compared to the rough. Following nasal inoculations, we detected transient Nmus nasal colonization. The smooth morphotype was able to reach higher burdens more quickly in the nasal cavity and on oral swabs following dissemination to the oral cavity. Gut colonization burdens fluctuated over time. Interestingly, both morphotypes colonized the oral cavities of A/Js at higher magnitudes than in C57BL/6Js. Collectively, our results demonstrate that colonization by Nmus can be affected by various factors including Nmus morphotypes, inoculation routes, anatomical niches, and host backgrounds. The Nmus-mouse model can use variable morphotype-host combinations to study the dynamics of neisserial asymptomatic colonization and persistence in multiple extragenital niches.
Project description:Keratinocytes are the major constituent of epithelial cells at mucosal surfaces and skin, which cover organs, internal cavities and the body. Traditionally, keratinocytes have been considered as an inert component of the multilayered epithelium to protect the subepithelial compartments from the pathogenic microorganisms, toxic stimuli and physical trauma. However, accumulated researches of the airway, gastrointestinal tract and skin have demonstrated that keratinocytes function in the development of the immune system, promotion of pathologic inflammation and even impose diverse decisions on immune cells. We used microarrays to detail the global gene expression of oral keratinocyte during oral adaptive immune response. Oral keratinocyte were collected at three time points (control, 48h and 96h) in oral adaptive immune response for RNA extraction and hybridization on Affymetrix microarrays
Project description:<p>This first clinical study of the Human Microbiome Project (HMP) addresses whether individuals share a core human microbiome. It involves broad determination of the microbiota found in five anatomical sites: the oral cavity, skin, nasal cavity, gastrointestinal tract and vagina. This study will enroll approximately 300 healthy male and female adults, 18-40 years old, from two geographic regions of the US: Houston, TX and St. Louis, MO. The participation of healthy individuals will create a baseline for discovery of the core microbiota typically found in various areas of the human body. The information from this initial study can then be used to help assess the changes in the complement of microbiota found on or within diseased individuals.</p>