Comparative Metatranscriptomics of Periodontitis Supports a Common Polymicrobial Shift in Metabolic Function and Identifies Novel Putative Disease-Associated ncRNAs

Ram-Mohan, Nikhil; Meyer, Michelle M.

doi:10.3389/fmicb.2020.00482

Cited by 18 publications

(19 citation statements)

References 78 publications

(123 reference statements)

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“…However, three metatranscriptomic surveys into the metabolic activity of chronic periodontal disease progression provided further insight that the conservation of the community functionality rather than the specific microbial effecters of disease exists (Duran-Pinedo et al, 2014a , b ; Yost et al, 2015 ). A very recent work, examining the existing metatranscriptome datasets (Duran-Pinedo et al, 2014b ; Jorth et al, 2014 ; Yost et al, 2015 ) to identify the commonly differentially expressed transcripts from both chronic and aggressive periodontitis patients and potential underlying RNA regulatory mechanisms behind the metabolic shifts, has revealed that many ncRNAs (both known and putative) may facilitate the metabolic shifts associated with periodontitis (Ram-Mohan and Meyer, 2020 ). Some of the notable highlights of this new analysis are: (1) Only a fraction of the differentially expressed transcripts originate from red/orange complex; (2) The differentially expressed transcripts from these Red/Orange complexes show the greatest magnitude of change; (3) Enrichment of genes generally grouped into the biological process of localization could be important in the establishment of red complex pathogens in the periodontal pocket to drive pathogenesis; (4) Most metabolic pathways enriched in disease state have multiple contributing species fulfilling the metabolic niche; and (5) By applying de novo pipelines on the differentially expressed genes, the authors identified several putative sense and anti-sense regulators of bacterial ribosomal proteins that could be associated with periodontitis.…”

Section: Current and Future Methodologies For The Evaluation Of Healtmentioning

confidence: 99%

“…Some of the notable highlights of this new analysis are: (1) Only a fraction of the differentially expressed transcripts originate from red/orange complex; (2) The differentially expressed transcripts from these Red/Orange complexes show the greatest magnitude of change; (3) Enrichment of genes generally grouped into the biological process of localization could be important in the establishment of red complex pathogens in the periodontal pocket to drive pathogenesis; (4) Most metabolic pathways enriched in disease state have multiple contributing species fulfilling the metabolic niche; and (5) By applying de novo pipelines on the differentially expressed genes, the authors identified several putative sense and anti-sense regulators of bacterial ribosomal proteins that could be associated with periodontitis. Additionally, seven novel antisense ncRNAs targeting ribosomal proteins may be involved in maintaining ribosomal protein stoichiometry during the disease associated metabolic shift (Ram-Mohan and Meyer, 2020 ). In summary, metatranscriptomics analyses suggest a common shift in metabolic signatures in disease vs. healthy communities with up-regulated processes including pyruvate fermentation, histidine degradation, amino acid metabolism, and TonB-dependent receptors.…”

Section: Current and Future Methodologies For The Evaluation Of Healtmentioning

confidence: 99%

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Dysbiosis From a Microbial and Host Perspective Relative to Oral Health and Disease

et al. 2021

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The significance of microbiology and immunology with regard to caries and periodontal disease gained substantial clinical or research consideration in the mid 1960's. This enhanced emphasis related to several simple but elegant experiments illustrating the relevance of bacteria to oral infections. Since that point, the understanding of oral diseases has become increasingly sophisticated and many of the original hypotheses related to disease causality have either been abandoned or amplified. The COVID pandemic has reminded us of the importance of history relative to infectious diseases and in the words of Churchill “those who fail to learn from history are condemned to repeat it.” This review is designed to present an overview of broad general directions of research over the last 60 years in oral microbiology and immunology, reviewing significant contributions, indicating emerging foci of interest, and proposing future directions based on technical advances and new understandings. Our goal is to review this rich history (standard microbiology and immunology) and point to potential directions in the future (omics) that can lead to a better understanding of disease. Over the years, research scientists have moved from a position of downplaying the role of bacteria in oral disease to one implicating bacteria as true pathogens that cause disease. More recently it has been proposed that bacteria form the ecological first line of defense against “foreign” invaders and also serve to train the immune system as an acquired host defensive stimulus. While early immunological research was focused on immunological exposure as a modulator of disease, the “hygiene hypothesis,” and now the “old friends hypothesis” suggest that the immune response could be trained by bacteria for long-term health. Advanced “omics” technologies are currently being used to address changes that occur in the host and the microbiome in oral disease. The “omics” methodologies have shaped the detection of quantifiable biomarkers to define human physiology and pathologies. In summary, this review will emphasize the role that commensals and pathobionts play in their interaction with the immune status of the host, with a prediction that current “omic” technologies will allow researchers to better understand disease in the future.

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Section: Current and Future Methodologies For The Evaluation Of Healtmentioning

confidence: 99%

Section: Current and Future Methodologies For The Evaluation Of Healtmentioning

confidence: 99%

Dysbiosis From a Microbial and Host Perspective Relative to Oral Health and Disease

et al. 2021

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“…Exploring the response of microbiome may help to find the induction factor of AILDs. Metagenomics is limited to reveal the functional activities of microorganisms, while metatranscriptomics is applied to explore the rapid response and expressed biological signatures of microorganisms to the external stimuli (Franzosa et al, 2014;Ram-Mohan and Meyer, 2020). However, there is still no metatranscriptomics research in AILDs.…”

Section: Functional Analyses Of the Microbiome In Autoimmune Liver Diseasesmentioning

confidence: 99%

The Microbiome in Autoimmune Liver Diseases: Metagenomic and Metabolomic Changes

et al. 2021

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Recent studies have identified the critical role of microbiota in the pathophysiology of autoimmune liver diseases (AILDs), including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). Metagenomic studies reveal significant decrease of gut bacterial diversity in AILDs. Although profiles of metagenomic vary widely, Veillonella is commonly enriched in AIH, PBC, and PSC. Apart from gut microbiome, the oral and bile microbiome seem to be associated with these diseases as well. The functional analysis of metagenomics suggests that metabolic pathways changed in the gut microbiome of the patients. Microbial metabolites, including short-chain fatty acids (SCFAs) and microbial bile acid metabolites, have been shown to modulate innate immunity, adaptive immunity, and inflammation. Taken together, the evidence of host–microbiome interactions and in-depth mechanistic studies needs further accumulation, which will offer more possibilities to clarify the mechanisms of AILDs and provide potential molecular targets for the prevention and treatment in the future.

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“…The use of metatranscriptomics in natural polymicrobial infections is not as well reported. The first documented use was in relation to the onset of pediatric asthma ( 13 ) and oral disease ( 14 , 15 ). However, its application to bovine digital dermatitis (BDD) ( 16 ), which has a clinical presentation and bacteria similar to those associated with footrot ( 17 – 20 ), highlighted its suitability to further our understanding of the intercellular microbial populations associated with agricultural diseases.…”

Section: Introductionmentioning

confidence: 99%

A Trifecta of New Insights into Ovine Footrot for Infection Drivers, Immune Response, and Host-Pathogen Interactions

et al. 2021

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Footrot is a polymicrobial infectious disease in sheep causing severe lameness, leading to one of the industry’s biggest welfare problems. The complex aetiology of footrot makes in-situ or in-vitro investigations difficult. Computational methods offer a solution to understanding the bacteria involved, how they may interact with the host and ultimately providing a way to identify targets for future hypotheses driven investigative work. Here we present the first combined global analysis of the bacterial community transcripts together with the host immune response in healthy and diseased ovine feet during a natural polymicrobial infection state using metatranscriptomics. The intra tissue and surface bacterial populations and the most abundant bacterial transcriptome were analysed, demonstrating footrot affected skin has a reduced diversity and increased abundances of, not only the causative bacteria Dichelobacter nodosus , but other species such as Mycoplasma fermentans and Porphyromonas asaccharolytica . Host transcriptomics reveals a suppression of biological processes relating to skin barrier function, vascular functions, and immunosurveillance in unhealthy interdigital skin, supported by histological findings that type I collagen (associated with scar tissue formation) is significantly increased in footrot affected interdigital skin comparted to outwardly healthy skin. Finally, we provide some interesting indications of host and pathogen interactions associated with virulence genes and the host spliceosome which could lead to the identification of future therapeutic targets. Impact Statement Lameness in sheep is a global welfare and economic concern and footrot is the leading cause of lameness, affecting up to 70% of flocks in the U.K. Current methods for control of this disease are labour intensive and account for approximately 65% of antibiotic use in sheep farming, whilst preventative vaccines suffer from poor efficacy due to antigen competition. Our limited understanding of cofounders, such as strain variation and polymicrobial nature of infection mean new efficacious, affordable and scalable control measures are not receiving much attention. Here we examine the surface and intracellular bacterial populations and propose potential interactions with the host. Identification of these key bacterial species involved in the initiation and progression of disease and the host immune mechanisms could help form the basis of new therapies.

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Comparative Metatranscriptomics of Periodontitis Supports a Common Polymicrobial Shift in Metabolic Function and Identifies Novel Putative Disease-Associated ncRNAs

Cited by 18 publications

References 78 publications

Dysbiosis From a Microbial and Host Perspective Relative to Oral Health and Disease

Dysbiosis From a Microbial and Host Perspective Relative to Oral Health and Disease

The Microbiome in Autoimmune Liver Diseases: Metagenomic and Metabolomic Changes

A Trifecta of New Insights into Ovine Footrot for Infection Drivers, Immune Response, and Host-Pathogen Interactions

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