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1.
Curr Opin Infect Dis ; 35(3): 215-222, 2022 06 01.
Article in English | MEDLINE | ID: covidwho-1878849

ABSTRACT

PURPOSE OF REVIEW: The respiratory microbiota has a role in respiratory tract infection (RTI) pathogenesis. On the mucosa, the respiratory microbiota interacts with potential pathogenic viruses, bacteria and the host immune system, including secretory IgA (sIgA). This review discusses the role of the respiratory microbiota and its interaction with the (mucosal) immune system in RTI susceptibility, as well as the potential to exploit the microbiota to promote health and prevent RTIs. RECENT FINDINGS: Recent studies confirm that specific microbiota profiles are associated with RTI susceptibility and during susceptibility and found accompanying RTIs, although clear associations have not yet been found for SARS-CoV-2 infection. sIgA plays a central role in RTI pathogenesis: it stands under control of the local microbiota, while at the same time influencing bacterial gene expression, metabolism and defense mechanisms. Respiratory microbiota interventions are still newly emerging but promising candidates for probiotics to prevent RTIs, such as Corynebacterium and Dolosigranulum species, have been identified. SUMMARY: Improved understanding of the respiratory microbiota in RTIs and its interplay with the immune system is of importance for early identification and follow-up of individuals at risk of infection. It also opens doors for future microbiota interventions by altering the microbiota towards a healthier state to prevent and/or adjunctively treat RTIs.


Subject(s)
COVID-19 , Microbiota , Respiratory Tract Infections , Bacteria/genetics , Health Promotion , Humans , Immunoglobulin A, Secretory , Respiratory Tract Infections/prevention & control , SARS-CoV-2
2.
Signal Transduct Target Ther ; 7(1): 143, 2022 04 29.
Article in English | MEDLINE | ID: covidwho-1873480

ABSTRACT

The global coronavirus disease 2019 (COVID-19) pandemic is currently ongoing. It is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A high proportion of COVID-19 patients exhibit gastrointestinal manifestations such as diarrhea, nausea, or vomiting. Moreover, the respiratory and gastrointestinal tracts are the primary habitats of human microbiota and targets for SARS-CoV-2 infection as they express angiotensin-converting enzyme-2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) at high levels. There is accumulating evidence that the microbiota are significantly altered in patients with COVID-19 and post-acute COVID-19 syndrome (PACS). Microbiota are powerful immunomodulatory factors in various human diseases, such as diabetes, obesity, cancers, ulcerative colitis, Crohn's disease, and certain viral infections. In the present review, we explore the associations between host microbiota and COVID-19 in terms of their clinical relevance. Microbiota-derived metabolites or components are the main mediators of microbiota-host interactions that influence host immunity. Hence, we discuss the potential mechanisms by which microbiota-derived metabolites or components modulate the host immune responses to SARS-CoV-2 infection. Finally, we review and discuss a variety of possible microbiota-based prophylaxes and therapies for COVID-19 and PACS, including fecal microbiota transplantation (FMT), probiotics, prebiotics, microbiota-derived metabolites, and engineered symbiotic bacteria. This treatment strategy could modulate host microbiota and mitigate virus-induced inflammation.


Subject(s)
COVID-19 , Microbiota , COVID-19/complications , COVID-19/therapy , Cell Line , Humans , Peptidyl-Dipeptidase A/metabolism , SARS-CoV-2
3.
Environ Microbiol Rep ; 14(3): 325-329, 2022 06.
Article in English | MEDLINE | ID: covidwho-1865073

Subject(s)
Microbiota , Ecology
4.
Viruses ; 14(5)2022 05 01.
Article in English | MEDLINE | ID: covidwho-1862910

ABSTRACT

Viral infections are influenced by various microorganisms in the environment surrounding the target tissue, and the correlation between the type and balance of commensal microbiota is the key to establishment of the infection and pathogenicity. Some commensal microorganisms are known to resist or promote viral infection, while others are involved in pathogenicity. It is also becoming evident that the profile of the commensal microbiota under normal conditions influences the progression of viral diseases. Thus, to understand the pathogenesis underlying viral infections, it is important to elucidate the interactions among viruses, target tissues, and the surrounding environment, including the commensal microbiota, which should have different relationships with each virus. In this review, we outline the role of microorganisms in viral infections. Particularly, we focus on gaining an in-depth understanding of the correlations among viral infections, target tissues, and the surrounding environment, including the commensal microbiota and the gut virome, and discussing the impact of changes in the microbiota (dysbiosis) on the pathological progression of viral infections.


Subject(s)
Gastrointestinal Microbiome , Microbiota , Virus Diseases , Viruses , Dysbiosis , Humans
5.
Front Immunol ; 13: 889945, 2022.
Article in English | MEDLINE | ID: covidwho-1862612

ABSTRACT

This mini review describes the role of gut and lung microbiota during respiratory viral infection and discusses the implication of the microbiota composition on the immune responses generated by the vaccines designed to protect against these pathogens. This is a growing field and recent evidence supports that the composition and function of the microbiota can modulate the immune response of vaccination against respiratory viruses such as influenza and SARS-CoV-2. Recent studies have highlighted that molecules derived from the microbiome can have systemic effects, acting in distant organs. These molecules are recognized by the immune cells from the host and can trigger or modulate different responses, interfering with vaccination protection. Modulating the microbiota composition has been suggested as an approach to achieving more efficient protective immune responses. Studies in humans have reported associations between a better vaccine response and specific bacterial taxa. These associations vary among different vaccine strategies and are likely to be context-dependent. The use of prebiotics and probiotics in conjunction with vaccination demonstrated that bacterial components could act as adjuvants. Future microbiota-based interventions may potentially improve and optimize the responses of respiratory virus vaccines.


Subject(s)
COVID-19 , Gastrointestinal Microbiome , Influenza Vaccines , Microbiota , Bacteria , COVID-19/prevention & control , Humans , SARS-CoV-2
6.
Toxins (Basel) ; 14(5)2022 05 16.
Article in English | MEDLINE | ID: covidwho-1855791

ABSTRACT

Cemeteries are potential environmental reservoirs of pathogenic microorganisms from organic matter decomposition. This study aimed to characterize the microbial contamination in three cemeteries, and more specifically in grave diggers' facilities. One active sampling method (impingement method) and several passive sampling methods (swabs, settled dust, settled dust filters and electrostatic dust cloths-EDC) were employed. The molecular detection of Aspergillus sections and SARS-CoV-2, as well as mycotoxin analysis, screening of azole resistance, and cytotoxicity measurement were also conducted. Total bacteria contamination was 80 CFU·m-2 in settled dust samples, reached 849 CFU·m-2 in EDC and 20,000 CFU·m-2 in swabs, and ranged from 5000 to 10,000 CFU·m-2 in filters. Gram-negative bacteria (VRBA) were only observed in in settled dust samples (2.00 × 105 CFU·m-2). Regarding Aspergillus sp., the highest counts were obtained in DG18 (18.38%) and it was not observed in azole-supplemented SDA media. SARS-CoV-2 and the targeted Aspergillus sections were not detected. Mycophenolic acid was detected in one settled dust sample. Cytotoxic effects were observed for 94.4% filters and 5.6% EDC in A549 lung epithelial cells, and for 50.0% filters and 5.6% EDC in HepG2 cells. Future studies are needed in this occupational setting to implement more focused risk management measures.


Subject(s)
COVID-19 , Microbiota , Aspergillus , Azoles , Cemeteries , Dust/analysis , Portugal , SARS-CoV-2
7.
BMJ Open Gastroenterol ; 9(1)2022 Apr.
Article in English | MEDLINE | ID: covidwho-1816751

ABSTRACT

OBJECTIVE: The study objective was to compare gut microbiome diversity and composition in SARS-CoV-2 PCR-positive patients whose symptoms ranged from asymptomatic to severe versus PCR-negative exposed controls. DESIGN: Using a cross-sectional design, we performed shotgun next-generation sequencing on stool samples to evaluate gut microbiome composition and diversity in both patients with SARS-CoV-2 PCR-confirmed infections, which had presented to Ventura Clinical Trials for care from March 2020 through October 2021 and SARS-CoV-2 PCR-negative exposed controls. Patients were classified as being asymptomatic or having mild, moderate or severe symptoms based on National Institute of Health criteria. Exposed controls were individuals with prolonged or repeated close contact with patients with SARS-CoV-2 infection or their samples, for example, household members of patients or frontline healthcare workers. Microbiome diversity and composition were compared between patients and exposed controls at all taxonomic levels. RESULTS: Compared with controls (n=20), severely symptomatic SARS-CoV-2-infected patients (n=28) had significantly less bacterial diversity (Shannon Index, p=0.0499; Simpson Index, p=0.0581), and positive patients overall had lower relative abundances of Bifidobacterium (p<0.0001), Faecalibacterium (p=0.0077) and Roseburium (p=0.0327), while having increased Bacteroides (p=0.0075). Interestingly, there was an inverse association between disease severity and abundance of the same bacteria. CONCLUSION: We hypothesise that low bacterial diversity and depletion of Bifidobacterium genera either before or after infection led to reduced proimmune function, thereby allowing SARS-CoV-2 infection to become symptomatic. This particular dysbiosis pattern may be a susceptibility marker for symptomatic severity from SARS-CoV-2 infection and may be amenable to preinfection, intrainfection or postinfection intervention. TRIAL REGISTRATION NUMBER: NCT04031469 (PCR-) and 04359836 (PCR+).


Subject(s)
COVID-19 , Microbiota , Bifidobacterium/genetics , Cross-Sectional Studies , Faecalibacterium , Humans , SARS-CoV-2
8.
J Infect ; 84(3): 329-336, 2022 03.
Article in English | MEDLINE | ID: covidwho-1814745

ABSTRACT

This study aimed to analyse the diversity and taxonomic composition of the nasopharyngeal microbiota, to determine its association with COVID-19 clinical outcome. To study the microbiota, we utilized 16S rRNA sequencing of 177 samples that came from a retrospective cohort of COVID-19 hospitalized patients. Raw sequences were processed by QIIME2. The associations between microbiota, invasive mechanical ventilation (IMV), and all-cause mortality were analysed by multiple logistic regression, adjusted for age, gender, and comorbidity. The microbiota α diversity indexes were lower in patients with a fatal outcome, whereas the ß diversity analysis showed a significant clustering in these patients. After multivariate adjustment, the presence of Selenomonas spp., Filifactor spp., Actinobacillus spp., or Chroococcidiopsis spp., was associated with a reduction of more than 90% of IMV. Higher diversity and the presence of certain genera in the nasopharyngeal microbiota seem to be early biomarkers of a favourable clinical evolution in hospitalized COVID-19 patients.


Subject(s)
COVID-19 , Microbiota , Biomarkers , Humans , RNA, Ribosomal, 16S/genetics , Retrospective Studies , SARS-CoV-2
9.
Front Cell Infect Microbiol ; 12: 736397, 2022.
Article in English | MEDLINE | ID: covidwho-1793039

ABSTRACT

The ongoing pandemic coronavirus disease COVID-19 is caused by the highly contagious single-stranded RNA virus, SARS-coronavirus 2 (SARS-CoV-2), which has a high rate of evolution like other RNA viruses. The first genome sequences of SARS-CoV-2 were available in early 2020. Subsequent whole-genome sequencing revealed that the virus had accumulated several mutations in genes associated with viral replication and pathogenesis. These variants showed enhanced transmissibility and infectivity. Soon after the first outbreak due to the wild-type strain in December 2019, a genetic variant D614G emerged in late January to early February 2020 and became the dominant genotype worldwide. Thereafter, several variants emerged, which were found to harbor mutations in essential viral genes encoding proteins that could act as drug and vaccine targets. Numerous vaccines have been successfully developed to assuage the burden of COVID-19. These have different rates of efficacy, including, although rarely, a number of vaccinated individuals exhibiting side effects like thrombosis. However, the recent emergence of the Britain strain with 70% more transmissibility and South African variants with higher resistance to vaccines at a time when several countries have approved these for mass immunization has raised tremendous concern regarding the long-lasting impact of currently available prophylaxis. Apart from studies addressing the pathophysiology, pathogenesis, and therapeutic targets of SARS-CoV-2, analysis of the gut, oral, nasopharyngeal, and lung microbiome dysbiosis has also been undertaken to find a link between the microbiome and the pathogenesis of COVID-19. Therefore, in the current scenario of skepticism regarding vaccine efficacy and challenges over the direct effects of currently available drugs looming large, investigation of alternative therapeutic avenues based on the microbiome can be a rewarding finding. This review presents the currently available understanding of microbiome dysbiosis and its association with cause and consequence of COVID-19. Taking cues from other inflammatory diseases, we propose a hypothesis of how the microbiome may be influencing homeostasis, pro-inflammatory condition, and the onset of inflammation. This accentuates the importance of a healthy microbiome as a protective element to prevent the onset of COVID-19. Finally, the review attempts to identify areas where the application of microbiome research can help in reducing the burden of the disease.


Subject(s)
COVID-19 , Microbiota , Dysbiosis , Humans , SARS-CoV-2/genetics
10.
Front Public Health ; 10: 818777, 2022.
Article in English | MEDLINE | ID: covidwho-1792880

ABSTRACT

Introduction: The Survey of the Health of Wisconsin (SHOW) was established in 2008 by the University of Wisconsin (UW) School of Medicine and Public Health (SMPH) with the goals of (1) providing a timely and accurate picture of the health of the state residents; and (2) serving as an agile resource infrastructure for ancillary studies. Today, the SHOW program continues to serve as a unique and vital population health research infrastructure for advancing public health. Methods: SHOW currently includes 5,846 adult and 980 minor participants recruited between 2008 and 2019 in four primary waves. WAVE I (2008-2013) includes annual statewide representative samples of 3,380 adults ages 21 to 74 years. WAVE II (2014-2016) is a triannual statewide sample of 1,957 adults (age ≥18 years) and 645 children (age 0-17). WAVE III (2017) consists of follow-up of 725 adults from the WAVE I and baseline surveys of 222 children in selected households. WAVEs II and III include stool samples collected as part of an ancillary study in a subset of 784 individuals. WAVE IV consists of 517 adults and 113 children recruited from traditionally under-represented populations in biomedical research including African Americans and Hispanics in Milwaukee, Wisconsin. Findings to Date: The SHOW resource provides unique spatially granular and timely data to examine the intersectionality of multiple social determinants and population health. SHOW includes a large biorepository and extensive health data collected in a geographically diverse urban and rural population. Over 60 studies have been published covering a broad range of topics including, urban and rural disparities in cardio-metabolic disease and cancer, objective physical activity, sleep, green-space and mental health, transcriptomics, the gut microbiome, antibiotic resistance, air pollution, concentrated animal feeding operations and heavy metal exposures. Discussion: The SHOW cohort and resource is available for continued follow-up and ancillary studies including longitudinal public health monitoring, translational biomedical research, environmental health, aging, microbiome and COVID-19 research.


Subject(s)
COVID-19 , Gastrointestinal Microbiome , Microbiota , Population Health , Humans , Wisconsin
11.
Nutrients ; 14(9)2022 Apr 20.
Article in English | MEDLINE | ID: covidwho-1792584

ABSTRACT

The process of intrauterine programming is related to the quality of the microbiome formed in the fetus and the newborn. The implementation of probiotics, prebiotics, and psychobiotics shows immunomodulatory potential towards the organism, especially the microbiome of the pregnant woman and her child. Nutrigenomics, based on the observation of pregnant women and the developing fetus, makes it possible to estimate the biological effects of active dietary components on gene expression or silencing. Nutritional intervention for pregnant women should consider the nutritional status of the patient, biological markers, and the potential impact of dietary intervention on fetal physiology. The use of a holistic model of nutrition allows for appropriately targeted and effective dietary prophylaxis that can impact the physical and mental health of both the mother and the newborn. This model targets the regulation of the immune response of the pregnant woman and the newborn, considering the clinical state of the microbiota and the pathomechanism of the nervous system. Current scientific reports indicate the protective properties of immunobiotics (probiotics) about the reduction of the frequency of infections and the severity of the course of COVID-19 disease. The aim of this study was to test the hypothesis that intrauterine programming influences the development of the microbiome for the prevention of SARS-CoV-2 infection based on a review of research studies.


Subject(s)
COVID-19 , Microbiota , Pregnancy Complications, Infectious , COVID-19/prevention & control , Female , Humans , Infant, Newborn , Prebiotics , Pregnancy , SARS-CoV-2
12.
Front Cell Infect Microbiol ; 12: 824578, 2022.
Article in English | MEDLINE | ID: covidwho-1775646

ABSTRACT

Coronavirus disease 2019 (COVID-19) remains a serious emerging global health problem, and little is known about the role of oropharynx commensal microbes in infection susceptibility and severity. Here, we present the oropharyngeal microbiota characteristics identified by full-length 16S rRNA gene sequencing through the NANOPORE platform of oropharynx swab specimens from 10 mild COVID-19 patients and 10 healthy controls. Our results revealed a distinct oropharyngeal microbiota composition in mild COVID-19 patients, characterized by enrichment of opportunistic pathogens such as Peptostreptococcus anaerobius and Pseudomonas stutzeri and depletion of Sphingomonas yabuuchiae, Agrobacterium sullae, and Pseudomonas veronii. Based on the relative abundance of the oropharyngeal microbiota at the species level, we built a microbial classifier to distinguish COVID-19 patients from healthy controls, in which P. veronii, Pseudomonas fragi, and S. yabuuchiae were identified as the most prominent signatures for their depletion in the COVID-19 group. Several members of the genus Campylobacter, especially Campylobacter fetus and Campylobacter rectus, which were highly enriched in COVID-19 patients with higher severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and showed a significant correlation with disease status and several routine clinical blood indicators, indicate that several bacteria may transform into opportunistic pathogen in COVID-19 patients when facing the challenges of viral infection. We also found the diver taxa Streptococcus anginosus and Streptococcus alactolyticus in the network of disease patients, suggesting that these oropharynx microbiota alterations may impact COVID-19 severity by influencing the microbial association patterns. In conclusion, the low sample size of SARS-CoV-2 infection patients (n = 10) here makes these results tentative; however, we have provided the overall characterization that oropharyngeal microbiota alterations and microbial correlation patterns were associated with COVID-19 severity in Anhui Province.


Subject(s)
COVID-19 , Microbiota , Humans , Oropharynx/microbiology , RNA, Ribosomal, 16S/genetics , SARS-CoV-2
13.
J Dent Res ; 101(7): 785-792, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1775101

ABSTRACT

Many dental procedures are considered aerosol-generating procedures that may put the dental operator and patients at risk for cross-infection due to contamination from nasal secretions and saliva. This aerosol, depending on the size of the particles, may stay suspended in the air for hours. The primary objective of the study was to characterize the size and concentrations of particles emitted from 7 different dental procedures, as well as estimate the contribution of the nasal and salivary fluids of the patient to the microbiota in the emitted bioaerosol. This cross-sectional study was conducted in an open-concept dental clinic with multiple operators at the same time. Particle size characterization and mass and particle concentrations were done by using 2 direct reading instruments: Dust-Trak DRX (Model 8534) and optical particle sizer (Model 3330). Active bioaerosol sampling was done before and during procedures. Bayesian modeling (SourceTracker2) of long-reads of the 16S ribosomal DNA was used to estimate the contribution of the patients' nasal and salivary fluids to the bioaerosol. Aerosols in most dental procedures were sub-PM1 dominant. Orthodontic debonding and denture adjustment consistently demonstrated more particles in the PM1, PM2.5, PM4, and PM10 ranges. The microbiota in bioaerosol samples were significantly different from saliva and nasal samples in both membership and abundance (P < 0.05) but not different from preoperative ambient air samples. A median of 80.15% of operator exposure was attributable to sources other than the patients' salivary or nasal fluids. Median operator's exposure from patients' fluids ranged from 1.45% to 2.75%. Corridor microbiota showed more patients' nasal bioaerosols than oral bioaerosols. High-volume saliva ejector and saliva ejector were effective in reducing bioaerosol escape. Patient nasal and salivary fluids are minor contributors to the operator's bioaerosol exposure, which has important implications for COVID-19. Control of bioaerosolization of nasal fluids warrants further investigation.


Subject(s)
COVID-19 , Microbiota , Aerosols , Bayes Theorem , Cross-Sectional Studies , Humans , Particle Size
14.
Microb Pathog ; 165: 105506, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1763898

ABSTRACT

Since its first appearance, the SARS-CoV-2 has spread rapidly in the human population, reaching the pandemic scale with >280 million confirmed infections and more than 5 million deaths to date (https://covid19.who.int/). These data justify the urgent need to enhance our understanding of SARS-CoV-2 effects in the respiratory system, including those linked to co-infections. The principal aim of our study is to investigate existing correlations in the nasopharynx between the bacterial community, potential pathogens, and SARS-CoV-2 infection. The main aim of this study was to provide evidence pointing to possible relationships between components of the bacterial community and SARS-CoV-2 in the nasopharynx. Meta-transcriptomic profiling of the nasopharyngeal microbial community was carried out in 89 SARS-Cov-2 positive subjects from the Campania Region in Italy. To this end, RNA extracted from nasopharyngeal swabs collected at different times during the initial phases of the pandemic was analyzed by Next-Generation Sequencing (NGS). Results show a consistently high presence of members of the Proteobacteria (41.85%), Firmicutes (28.54%), and Actinobacteria (16.10%) phyla, and an inverted correlation between the host microbiome, co-infectious bacteria, and super-potential pathogens such as Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Neisseria gonorrhoeae. In depth characterization of microbiota composition in the nasopharynx can provide clues to understand its potential contribution to the clinical phenotype of Covid-19, clarifying the interaction between SARS-Cov-2 and the bacterial flora of the host, and highlighting its dysbiosis and the presence of pathogens that could affect the patient's disease progression and outcome.


Subject(s)
COVID-19 , Coinfection , Microbiota , Bacteria/genetics , Coinfection/epidemiology , High-Throughput Nucleotide Sequencing , Humans , Italy/epidemiology , Microbiota/genetics , Nasopharynx/microbiology , Pandemics , SARS-CoV-2/genetics
15.
Cells ; 11(5)2022 03 07.
Article in English | MEDLINE | ID: covidwho-1742341

ABSTRACT

The mucosal immune system of the respiratory tract possesses an effective "defense barrier" against the invading pathogenic microorganisms; therefore, the lungs of healthy organisms are considered to be sterile for a long time according to the strong pathogens-eliminating ability. The emergence of next-generation sequencing technology has accelerated the studies about the microbial communities and immune regulating functions of lung microbiota during the past two decades. The acquisition and maturation of respiratory microbiota during childhood are mainly determined by the birth mode, diet structure, environmental exposure and antibiotic usage. However, the formation and development of lung microbiota in early life might affect the occurrence of respiratory diseases throughout the whole life cycle. The interplay and crosstalk between the gut and lung can be realized by the direct exchange of microbial species through the lymph circulation, moreover, the bioactive metabolites produced by the gut microbiota and lung microbiota can be changed via blood circulation. Complicated interactions among the lung microbiota, the respiratory viruses, and the host immune system can regulate the immune homeostasis and affect the inflammatory response in the lung. Probiotics, prebiotics, functional foods and fecal microbiota transplantation can all be used to maintain the microbial homeostasis of intestinal microbiota and lung microbiota. Therefore, various kinds of interventions on manipulating the symbiotic microbiota might be explored as novel effective strategies to prevent and control respiratory diseases.


Subject(s)
Gastrointestinal Microbiome , Microbiota , Probiotics , Fecal Microbiota Transplantation , Gastrointestinal Microbiome/physiology , Lung , Microbiota/physiology , Probiotics/therapeutic use
16.
Am J Physiol Gastrointest Liver Physiol ; 322(6): G535-G552, 2022 06 01.
Article in English | MEDLINE | ID: covidwho-1736154

ABSTRACT

Systems biology studies have established that changes in gastrointestinal microbiome composition and function can adversely impact host physiology. Notable diseases synonymously associated with dysbiosis include inflammatory bowel diseases, cancer, metabolic disorders, and opportunistic and recurrent pathogen infections. However, there is a scarcity of mechanistic data that advances our understanding of taxonomic correlations with pathophysiological host-microbiome interactions. Generally, to survive a hostile gut environment, microbes are highly metabolically active and produce trans-kingdom signaling molecules to interact with competing microorganisms and the host. These specialized metabolites likely play important homeostatic roles, and identifying disease-specific taxa and their effector pathways can provide better strategies for diagnosis, treatment, and prevention, as well as the discovery of innovative therapeutics. The signaling role of microbial biotransformation products such as bile acids, short-chain fatty acids, polysaccharides, and dietary tryptophan is increasingly recognized, but little is known about the identity and function of metabolites that are synthesized by microbial biosynthetic gene clusters, including ribosomally synthesized and posttranslationally modified peptides (RiPPs), nonribosomal peptides (NRPs), polyketides (PKs), PK-NRP hybrids, and terpenes. Here we consider how bioactive natural products directly encoded by the human microbiome can contribute to the pathophysiology of gastrointestinal disease, cancer, autoimmune, antimicrobial-resistant bacterial and viral infections (including COVID-19). We also present strategies used to discover these compounds and the biological activities they exhibit, with consideration of therapeutic interventions that could emerge from understanding molecular causation in gut microbiome research.


Subject(s)
COVID-19 , Gastrointestinal Diseases , Gastrointestinal Microbiome , Microbiota , Dysbiosis/microbiology , Humans
17.
Periodontol 2000 ; 89(1): 9-18, 2022 06.
Article in English | MEDLINE | ID: covidwho-1735976

ABSTRACT

Periodontitis, a microbiome-driven inflammatory disease of the tooth-attachment apparatus, is epidemiologically linked with other disorders, including cardio-metabolic, cognitive neurodegenerative and autoimmune diseases, respiratory infections, and certain cancers. These associations may, in part, be causal, as suggested by interventional studies showing that local treatment of periodontitis reduces systemic inflammation and surrogate markers of comorbid diseases. The potential cause-and-effect connection between periodontitis and comorbidities is corroborated by studies in preclinical models of disease, which additionally provided mechanistic insights into these associations. This overview discusses recent advances in our understanding of the periodontitis-systemic disease connection, which may potentially lead to innovative therapeutic options to reduce the risk of periodontitis-linked comorbidities.


Subject(s)
Microbiota , Periodontal Diseases , Periodontitis , Humans , Inflammation , Periodontal Diseases/complications , Periodontal Diseases/epidemiology , Periodontal Diseases/therapy , Periodontitis/complications , Periodontitis/epidemiology , Periodontitis/therapy
18.
OMICS ; 26(4): 204-217, 2022 04.
Article in English | MEDLINE | ID: covidwho-1730629

ABSTRACT

The advances made by microbiome research call for new vocabulary and expansion of our thinking in microbiology. For example, the life-forms presenting in both unicellular and multicellular formats invite us to rethink microbial existence, organization, growth, pathogenicity, and therapeutics in the 21st century. A view of such populations as parts of single organisms with a loose, distributed multicellular organization, introduced here as a germ-ganism, rather than communities, might open up interesting prospects for diagnostics and therapeutics innovation. This study tested and further contextualized the concept of germ-ganism using solid cultures of bacteria and fungi. Based on our findings and the literature reviewed herein, we propose that germ-ganism has synergy with a systems medicine approach by broadening host-environment interactions from cells and microorganisms to a scale of biological ecosystems. Germ-ganism also brings about the possibility of studying the multilevel impacts of novel therapeutic agents within and across networks of microbial ecosystems. The germ-ganism would lend itself, in the long term, to a veritable biocybernetics system, while in the mid-term, we anticipate it will contribute to new diagnostics and therapeutics. Biosecurity applications would be immensely affected by germ-ganism. Industrial applications of germ-ganism are of interest as a more sustainable alternative to costly solutions such as tampered strains/microorganisms. In conclusion, germ-ganism is informed by lessons from microbiome research and invites rethinking microbial existence, organization, and growth as an organism. Germ-ganism has vast ramifications for understanding pathogenicity, and clinical, biosecurity, and biotechnology applications in the current historical moment of the COVID-19 pandemic and beyond.


Subject(s)
COVID-19 , Microbiota , Bacteria , Humans , Pandemics , Virulence
19.
BMC Oral Health ; 22(1): 50, 2022 03 03.
Article in English | MEDLINE | ID: covidwho-1724469

ABSTRACT

BACKGROUND: Several reports suggest that the microbiome of the digestive system affects vaccine efficacy and that the severity of coronavirus disease (COVID-19) is associated with decreased diversity of the oral and/or intestinal microbiome. The present study examined the effects of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine on the oral microbiome. METHODS: Forty healthy Japanese oral healthcare personnel were recruited, and unstimulated saliva was collected before vaccination, after the 1st vaccination, and after the 2nd vaccination. Genomic DNA was extracted from saliva samples, and PCR amplicons of the 16S rRNA gene were analyzed using next-generation sequencing. Microbial diversity and composition were analyzed using Quantitative Insights into Microbial Ecology 2. In addition, alterations in microbial function were assessed using PICRUSt2. RESULTS: SARS-CoV-2 mRNA vaccination significantly increased oral bacterial diversity and significantly decreased the proportion of the genus Bacteroides. CONCLUSIONS: The SARS-CoV-2 mRNA vaccine alters the oral microbiome; accordingly, vaccination might have beneficial effects on oral health.


Subject(s)
COVID-19 , Microbiota , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Microbiota/genetics , RNA, Ribosomal, 16S/genetics , SARS-CoV-2 , Vaccination , Vaccines, Synthetic
20.
Int Urogynecol J ; 33(5): 1157-1164, 2022 May.
Article in English | MEDLINE | ID: covidwho-1718659

ABSTRACT

INTRODUCTION AND HYPOTHESIS: The objective was to systemically review the current literature on the association of gut, vaginal, and urinary dysbiosis in female patients with overactive bladder (OAB). METHODS: We performed a comprehensive literature search following the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) protocols for systematic reviews. In the EMBASE, CINAHL, and Medline databases, a search was conducted using key words such as "microbiome," "microbiota," "microflora," "overactive bladder," "urge," "gut," "vaginal." Articles were screened using the online tool www.covidence.org . Two independent reviewers screened studies at each stage and resolved conflicts together. We excluded papers that discussed pediatric patients and animal studies. In total, 13 articles met this criterion, which included 6 abstracts. RESULTS: After identifying 817 unique references, 13 articles met the criteria for data extraction. Articles were published from 2017 to 2021. No study reported the same microbiota abundance, even in healthy individuals. Overall, there was a loss of bacterial diversity in OAB patients compared with controls. Additionally, the bacterial composition of the controls and OAB patients was not significantly different, especially if the urine was collected midstream. Overall, the composition of the microbiome is dependent on the specimen collection methodology, and the metagenomic sequencing technique utilized. OAB urine microbiome is more predisposed to alteration from the gut or vaginal influences than in controls. CONCLUSIONS: Current evidence suggested a potential relationship among gut, vaginal, and urinary microbiome in OAB patients, but there are very limited studies.


Subject(s)
Microbiota , Urinary Bladder, Overactive , Urinary Tract , Bacteria , Child , Female , Humans , Urinary Bladder, Overactive/microbiology , Urinary Tract/microbiology , Vagina
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