Oral Microbiome Dysbiosis Is Associated With Symptoms Severity and Local Immune/Inflammatory Response in COVID-19 Patients: A Cross-Sectional Study

The human oral microbiome (HOM) is the second largest microbial community after the gut and can impact the onset and progression of several localized and systemic diseases, including those of viral origin, especially for viruses entering the body via the oropharynx. However, this important aspect has not been clarified for the new pandemic human coronavirus SARS-CoV-2, causing COVID-19 disease, despite it being one of the many respiratory viruses having the oropharynx as the primary site of replication. In particular, no data are available about the non-bacterial components of the HOM (fungi, viruses), which instead has been shown to be crucial for other diseases. Consistent with this, this study aimed to define the HOM in COVID-19 patients, to evidence any association between its profile and the clinical disease. Seventy-five oral rinse samples were analyzed by Whole Genome Sequencing (WGS) to simultaneously identify oral bacteria, fungi, and viruses. To correlate the HOM profile with local virus replication, the SARS-CoV-2 amount in the oral cavity was quantified by digital droplet PCR. Moreover, local inflammation and secretory immune response were also assessed, respectively by measuring the local release of pro-inflammatory cytokines (L-6, IL-17, TNFα, and GM-CSF) and the production of secretory immunoglobulins A (sIgA). The results showed the presence of oral dysbiosis in COVID-19 patients compared to matched controls, with significantly decreased alpha-diversity value and lower species richness in COVID-19 subjects. Notably, oral dysbiosis correlated with symptom severity (p = 0.006), and increased local inflammation (p < 0.01). In parallel, a decreased mucosal sIgA response was observed in more severely symptomatic patients (p = 0.02), suggesting that local immune response is important in the early control of virus infection and that its correct development is influenced by the HOM profile. In conclusion, the data presented here suggest that the HOM profile may be important in defining the individual susceptibility to SARS-CoV-2 infection, facilitating inflammation and virus replication, or rather, inducing a protective IgA response. Although it is not possible to determine whether the alteration in the microbial community is the cause or effect of the SARS-CoV-2 replication, these parameters may be considered as markers for personalized therapy and vaccine development.

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Single-Cell Genomics and the Oral Microbiome

Journal of Dental Research ◽

10.1177/0022034520907380 ◽

2020 ◽

Vol 99 (6) ◽

pp. 613-620 ◽

Cited By ~ 2

Author(s):

M. Balachandran ◽

K.L. Cross ◽

M. Podar

Keyword(s):

Microbial Community ◽

Single Cell ◽

Single Cells ◽

Oral Bacteria ◽

Oral Microbiome ◽

Oral Microbiota ◽

Oral Diseases ◽

Interspecies Interactions ◽

Single Cell Genomics

The human oral cavity is one of the first environments where microbes have been discovered and studied since the dawn of microbiology. Nevertheless, approximately 200 types of bacteria from the oral microbiota have remained uncultured in the laboratory. Some are associated with a healthy oral microbial community, while others are linked to oral diseases, from dental caries to gum disease. Single-cell genomics has enabled inferences on the physiology, virulence, and evolution of such uncultured microorganisms and has further enabled isolation and cultivation of several novel oral bacteria, including the discovery of novel interspecies interactions. This review summarizes some of the more recent advances in this field, which is rapidly moving toward physiologic characterization of single cells and ultimately cultivation of the yet uncultured. A combination of traditional microbiological approaches with genomic-based physiologic predictions and isolation strategies may lead to the oral microbiome being the first complex microbial community to have all its members cultivable in the laboratory. Studying the biology of the individual microbes when in association with other members of the community, in controlled laboratory conditions and in vivo, should lead to a better understanding of oral dysbiosis and its prevention and reversion.

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The association between body mass index and the oral Firmicutes and Bacteroidetes profiles of healthy individuals

Malaysian Family Physician ◽

10.51866/oa1129 ◽

2021 ◽

Vol 16 (3) ◽

pp. 36-43

Author(s):

Roshna Mohamed Qadir ◽

Mahde Saleh Assafi

Keyword(s):

Body Mass Index ◽

Body Mass ◽

Bacterial Species ◽

Oral Bacteria ◽

Normal Weight ◽

The Body ◽

Oral Microbiome ◽

Bacterial Phyla ◽

Obese Subjects ◽

Health Objective

Introduction: Microbiome status is considered an important factor that contributes to obesity. Investigations have shown that the oral microbiome comprises a vast array of bacterial species that can influence human health. Objective: To determine the association between the presence of the bacterial phyla Firmicutes and Bacteroidetes and the body mass index (BMI) status of normal, overweight and obese subjects in Duhok, Iraq. Additionally, to investigate the composition of oral Firmicutes and Bacteroidetes profiles for individuals with different BMI statuses. Methods: A total of 155 saliva samples were collected from participants in Duhok, Iraq. Bacterial genomic DNA was then extracted from the collected saliva. The presence of Firmicutes and Bacteroidetes phyla was detected via polymerase chain reaction. Results: Firmicutes and Bacteroidetes were detected in 63.2 and 37.4% of the population, respectively. Differences in the carriage rates of oral Firmicutes in overweight (78%) and obese individuals (83%) were statistically significant when compared to normal weight individuals (36%) (P<0.0001). The percentage rates of Bacteroidetes in obese individuals (26.4%) was statistically significant when compared to normal weight individuals (50.8%) (P=0.0078). The Firmicutes/Bacteroidetes ratios (obese=3.1, overweight=2.5 and normal weight=0.7) were higher with increasing BMI. Conclusion: This study provides evidence of the Firmicutes/Bacteroidetes ratio growing with increasing BMI. High rates of Firmicutes could serve a role in the development of obesity. Further studies are required to clarify the exact relationship between oral bacteria and obesity, which could lead to a promising therapeutic method for improving the physical health of humans.

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HIV-1 Accessory Proteins: Which one is Potentially Effective in Diagnosis and Vaccine Development?

Protein and Peptide Letters ◽

10.2174/0929866528999201231213610 ◽

2020 ◽

Vol 28 ◽

Author(s):

Alireza Milani ◽

Kazem Baesi ◽

Elnaz Agi ◽

Ghazal Marouf ◽

Maryam Ahmadi ◽

...

Keyword(s):

Immune Response ◽

Vaccine Development ◽

Treated Group ◽

Vaccine Antigen ◽

Accessory Proteins ◽

Serological Method ◽

Th2 Immune Response ◽

Untreated Individuals ◽

Immunogenic Properties ◽

Hiv 1

Background:: The combination antiretroviral therapy (cART) could increase the number of circulating naive CD4 T lymphocytes, but was not able to eradicate human immunodeficiency virus-1 (HIV-1) infection. Objective:: Thus, induction of strong immune responses is important for control of HIV-1 infection. Furthermore, a simple and perfect serological method is required to detect virus in untreated-, treated- and drug resistant- HIV-1 infected individuals. Methods:: This study was conducted to assess and compare immunogenic properties of Nef, Vif, Vpr and Vpu accessory proteins as an antigen candidate in mice and their diagnostic importance in human as a biomarker. Results:: Our data showed that in mice, all heterologous prime/ boost regimens were more potent than homologous prime/ boost regimens in eliciting Th1 response and Granzyme B secretion as CTL activity. Moreover, the Nef, Vpu and Vif proteins could significantly increase Th1 immune response. In contrast, the Vpr protein could considerably induce Th2 immune response. On the other hand, among four accessory proteins, HIV-1 Vpu could significantly detect treated group from untreated group as a possible biomarker in human. Conclusion:: Generally, among accessory proteins, Nef, Vpu and Vif antigens were potentially more suitable vaccine antigen candidates than Vpr antigen. Human antibodies against all these proteins were higher in HIV-1 different groups than healthy group. Among them, Vpu was known as a potent antigen in diagnosis of treated from untreated individuals. The potency of accessory proteins as an antigen candidate in an animal model and a human cohort study are underway.

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A multi-method and structure-based in silico vaccine designing against Helicobacter pylori employing immuno-informatics approach

Current Proteomics ◽

10.2174/1570164617999200414120231 ◽

2020 ◽

Vol 17 ◽

Author(s):

Anam Naz ◽

Tahreem Zaheer ◽

Hamza Arshad Dar ◽

Faryal Mehwish Awan ◽

Ayesha Obaid ◽

...

Keyword(s):

Helicobacter Pylori ◽

Vaccine Development ◽

Amino Acid Sequences ◽

The Body ◽

New Drugs ◽

Toll Like Receptor ◽

Peptide Vaccines ◽

Hla Alleles ◽

Vaccine Candidates ◽

H Pylori

Background: Helicobacter pylori infection and its treatment still remains a challenge to human health worldwide. A variety of antibiotics and combination therapies are currently used to treat H. pylori induced ulcers and carcinoma; however, no effective treatment is available to eliminate the pathogen from the body. Additionally, antibiotic resistance is also one of the main reasons for prolonged and persistent infection. Aim of the study: Until new drugs are available for this infection, vaccinology seems the only alternative opportunity to exploit against H. pylori induced diseases. Methods: Multiple epitopes prioritized in our previous study have been tested for their possible antigenic combinations, and results in 169-mer and 183-mer peptide vaccines containing the amino acid sequences of 3 and 4 epitopes respectively, along with adjuvant (Cholera Toxin Subunit B adjuvant at 5’ end) and linkers (GPGPG and EAAAK). Results: Poly-epitope proteins proposed as potential vaccine candidates against H. pylori include SabAHP0289-Omp16-VacA (SHOV), VacA-Omp16-HP0289-FecA (VOHF), VacA-Omp16-HP0289-SabA (VOHS), VacA-Omp16-HP0289-BabA (VOHB), VacA-Omp16-HP0289-SabA-FecA (VOHSF), VacAOmp16-HP0289-SabA-BabA (VOHSB) and VacA-Omp16-HP0289-BabA-SabA (VOHBS). Structures of these poly-epitope peptide vaccines have been modelled and checked for their affinity with HLA alleles and receptors. These proposed poly-epitope vaccine candidates bind efficiently with A2, A3, B7 and DR1 superfamilies of HLA alleles. They can also form stable and significant interactions with Toll-like receptor 2 and Toll-like receptor 4. Conclusion: Results suggest that these multi-epitopic vaccines can elicit a significant immune response against H. pylori and can be tested further for efficient vaccine development.

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Rebalance the oral microbiota as efficacy tool in endocrine, metabolic, and immune disorders

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320666200729142504 ◽

2020 ◽

Vol 20 ◽

Cited By ~ 5

Author(s):

Ciro Gargiulo Isacco ◽

Andrea Ballini ◽

Danila De Vito ◽

Kieu Cao Diem Nguyen ◽

Stefania Cantore ◽

...

Keyword(s):

Systemic Disease ◽

Current Treatment ◽

Oral Bacteria ◽

The Body ◽

Oral Microbiota ◽

Oral Diseases ◽

Philosophical Approach ◽

Treatment And Prevention ◽

Cardio Vascular Disease ◽

Cardio Vascular

: The current treatment and prevention of oral disorders follow a very sectoral control and procedures considering mouth and its structures as system completely independent from the rest of the body. The main therapeutic approach is carried out on just to keep the levels of oral bacteria and hygiene in an acceptable range compatible with one-way vision of oral-mouth health completely separated from a systemic microbial homeostasis (eubiosis vs dysbiosis). This can negatively impact on the diagnosis of more complex systemic disease and its progression. Dysbiosis is consequence of oral and gut microbiota unbalance with consequences, as reported in current literature, in cardio vascular disease, diabetes mellitus, rheumatoid arthritis, and Alzheimer’s disease. Likewise, there is the need to highlight and develop a novel philosophical approach in the treatments for oral diseases that will necessarily involve non-conventional approaches.

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Oral Microbiota Identifies Patients in Early Onset Rheumatoid Arthritis

Microorganisms ◽

10.3390/microorganisms9081657 ◽

2021 ◽

Vol 9 (8) ◽

pp. 1657

Author(s):

Anders Esberg ◽

Linda Johansson ◽

Ingegerd Johansson ◽

Solbritt Rantapää Dahlqvist

Keyword(s):

Rheumatoid Arthritis ◽

Early Onset ◽

Amplicon Sequencing ◽

Oral Bacteria ◽

Oral Microbiome ◽

Rrna Gene ◽

Oral Microbiota ◽

Disease Manifestation ◽

Periodontal Status ◽

Quality Register

Rheumatoid arthritis (RA) is the most common autoimmune inflammatory disease, and single periodontitis-associated bacteria have been suggested in disease manifestation. Here, the oral microbiota was characterized in relation to the early onset of RA (eRA) taking periodontal status into consideration. 16S rRNA gene amplicon sequencing of saliva bacterial DNA from 61 eRA patients without disease-modifying anti-rheumatic drugs and 59 matched controls was performed. Taxonomic classification at 98.5% was conducted against the Human Oral Microbiome Database, microbiota functions were predicted using PICRUSt, and periodontal status linked from the Swedish quality register for clinically assessed caries and periodontitis. The participants were classified into three distinct microbiota-based cluster groups with cluster allocation differences by eRA status. Independently of periodontal status, eRA patients had enriched levels of Prevotella pleuritidis, Treponema denticola, Porphyromonas endodontalis and Filifactor alocis species and in the Porphyromonas and Fusobacterium genera and functions linked to ornithine metabolism, glucosylceramidase, beta-lactamase resistance, biphenyl degradation, fatty acid metabolism and 17-beta-estradiol-17-dehydrogenase metabolism. The results support a deviating oral microbiota composition already in eRA patients compared with healthy controls and highlight a panel of oral bacteria that may be useful in eRA risk assessment in both periodontally healthy and diseased persons.

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Comparison of oral microbiome profiles in 18-month-old infants and their parents

Scientific Reports ◽

10.1038/s41598-020-78295-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ryutaro Jo ◽

Kazuma Yama ◽

Yuto Aita ◽

Kota Tsutsumi ◽

Chikako Ishihara ◽

...

Keyword(s):

Next Generation Sequencing ◽

Dental Caries ◽

Oral Bacteria ◽

Oral Microbiome ◽

Commensal Bacteria ◽

16S Rrna Genes ◽

Rrna Genes ◽

Deciduous Dentition ◽

The Difference ◽

Generation Sequencing

AbstractThe onset and progress of dental caries and periodontal disease is associated with the oral microbiome. Therefore, it is important to understand the factors that influence oral microbiome formation. One of the factors that influence oral microbiome formation is the transmission of oral bacteria from parents. However, it remains unclear when the transmission begins, and the difference in contributions of father and mother. Here, we focused on the oral microbiome of 18-month-old infants, at which age deciduous dentition is formed and the oral microbiome is likely to become stable, with that of their parents. We collected saliva from forty 18-month-old infants and their parents and compared the diversity and composition of the microbiome using next-generation sequencing of 16S rRNA genes. The results showed that microbial diversity in infants was significantly lower than that in parents and composition of microbiome were significantly different between infants and parents. Meanwhile, the microbiome of the infants was more similar to that of their mothers than unrelated adults. The bacteria highly shared between infants and parents included not only commensal bacteria but also disease related bacteria. These results suggested that the oral microbiome of the parents influences that of their children aged < 18 months.

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Host reproductive cycle influences the pouch microbiota of wild southern hairy-nosed wombats (Lasiorhinus latifrons)

Animal Microbiome ◽

10.1186/s42523-021-00074-8 ◽

2021 ◽

Vol 3 (1) ◽

Author(s):

Sesilje Weiss ◽

David Taggart ◽

Ian Smith ◽

Kristofer M. Helgen ◽

Raphael Eisenhofer

Keyword(s):

Microbial Community ◽

Reproductive Cycle ◽

Tammar Wallaby ◽

The Body ◽

Rrna Gene ◽

Microbial Composition ◽

Birth Canal ◽

Gram Positive Bacteria ◽

Rigorous Framework ◽

The 16S Rrna Gene

Abstract Background Marsupials are born much earlier than placental mammals, with most crawling from the birth canal to the protective marsupium (pouch) to further their development. However, little is known about the microbiology of the pouch and how it changes throughout a marsupial’s reproductive cycle. Here, using stringent controls, we characterized the microbial composition of multiple body sites from 26 wild Southern Hairy-nosed Wombats (SHNWs), including pouch samples from animals at different reproductive stages. Results Using qPCR of the 16S rRNA gene we detected a microbial community in the SHNW pouch. We observed significant differences in microbial composition and diversity between the body sites tested, as well as between pouch samples from different reproductive stages. The pouches of reproductively active females had drastically lower microbial diversity (mean ASV richness 19 ± 8) compared to reproductively inactive females (mean ASV richness 941 ± 393) and were dominated by gram positive bacteria from the Actinobacteriota phylum (81.7–90.6%), with the dominant families classified as Brevibacteriaceae, Corynebacteriaceae, Microbacteriaceae, and Dietziaceae. Three of the five most abundant sequences identified in reproductively active pouches had closest matches to microbes previously isolated from tammar wallaby pouches. Conclusions This study represents the first contamination-controlled investigation into the marsupial pouch microbiota, and sets a rigorous framework for future pouch microbiota studies. Our results indicate that SHNW pouches contain communities of microorganisms that are substantially altered by the host reproductive cycle. We recommend further investigation into the roles that pouch microorganisms may play in marsupial reproductive health and joey survival.

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The Koala Immune Response to Chlamydial Infection and Vaccine Development—Advancing Our Immunological Understanding

Animals ◽

10.3390/ani11020380 ◽

2021 ◽

Vol 11 (2) ◽

pp. 380

Author(s):

Bonnie L Quigley ◽

Peter Timms

Keyword(s):

Immune Response ◽

Chlamydial Infection ◽

Vaccine Development ◽

Interleukin 17 ◽

Phascolarctos Cinereus ◽

Post Vaccination ◽

Research Systems ◽

Cytokine Levels ◽

Nucleic Acid Assay ◽

Immunological Research

Chlamydia is a significant pathogen for many species, including the much-loved Australian marsupial, the koala (Phascolarctos cinereus). To combat this situation, focused research has gone into the development and refinement of a chlamydial vaccine for koalas. The foundation of this process has involved characterising the immune response of koalas to both natural chlamydial infection as well as vaccination. From parallels in human and mouse research, it is well-established that an effective anti-chlamydial response will involve a balance of cell-mediated Th1 responses involving interferon-gamma (IFN-γ), humoral Th2 responses involving systemic IgG and mucosal IgA, and inflammatory Th17 responses involving interleukin 17 (IL-17) and neutrophils. Characterisation of koalas with chlamydial disease has shown increased expression within all three of these major immunological pathways and monitoring of koalas’ post-vaccination has detected further enhancements to these key pathways. These findings offer optimism that a chlamydial vaccine for wider distribution to koalas is not far off. Recent advances in marsupial genetic knowledge and general nucleic acid assay technology have moved koala immunological research a step closer to other mammalian research systems. However, koala-specific reagents to directly assay cytokine levels and cell-surface markers are still needed to progress our understanding of koala immunology.

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The Role of Th17 Response in COVID-19

Cells ◽

10.3390/cells10061550 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1550

Author(s):

Diana Martonik ◽

Anna Parfieniuk-Kowerda ◽

Magdalena Rogalska ◽

Robert Flisiak

Keyword(s):

Immune Response ◽

Treg Cells ◽

The Body ◽

System Response ◽

Th17 Response ◽

Monocyte Chemoattractant Protein 1 ◽

Acute Infectious Disease ◽

Cytokine Cascade ◽

Necrosis Factor

COVID-19 is an acute infectious disease of the respiratory system caused by infection with the SARS-CoV-2 virus (Severe Acute Respiratory Syndrome Coronavirus 2). Transmission of SARS-CoV-2 infections occurs through droplets and contaminated objects. A rapid and well-coordinated immune system response is the first line of defense in a viral infection. However, a disturbed and over-activated immune response may be counterproductive, causing damage to the body. Severely ill patients hospitalised with COVID-19 exhibit increased levels of many cytokines, including Interleukin (IL)-1β, IL-2, IL-6, IL-7, IL-8, IL-10, IL-17, granulocyte colony stimulating factor (G-CSF), monocyte chemoattractant protein 1 (MCP-1) and tumor necrosis factor (TNF). Increasing evidence suggests that Th17 cells play an important role in the pathogenesis of COVID-19, not only by activating cytokine cascade but also by inducing Th2 responses, inhibiting Th1 differentiation and suppressing Treg cells. This review focuses on a Th17 pathway in the course of the immune response in COVID-19, and explores plausible targets for therapeutic intervention.

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