Oral microbiomes: more and more importance in oral cavity and whole body

Microbes appear in every corner of human life, and microbes affect every aspect of human life. The human oral cavity contains a number of different habitats. Synergy and interaction of variable oral microorganisms help human body against invasion of undesirable stimulation outside. However, imbalance of microbial flora contributes to oral diseases and systemic diseases. Oral microbiomes play an important role in the human microbial community and human health. The use of recently developed molecular methods has greatly expanded our knowledge of the composition and function of the oral microbiome in health and disease. Studies in oral microbiomes and their interactions with microbiomes in variable body sites and variable health condition are critical in our cognition of our body and how to make effect on human health improvement.     

Rapidly expanding knowledge on the role of the gut microbiome in health and disease

The human gut is colonized by a wide diversity of micro-organisms, which are now known to play a key role in the human host by regulating metabolic functions and immune homeostasis. Many studies have indicated that the genomes of our gut microbiota, known as the gut microbiome or our “other genome” could play an important role in immune-related, complex diseases, and growing evidence supports a causal role for gut microbiota in regulating predisposition to diseases. A comprehensive analysis of the human gut microbiome is thus important to unravel the exact mechanisms by which the gut microbiota are involved in health and disease. Recent advances in next-generation sequencing technology, along with the development of metagenomics and bioinformatics tools, have provided opportunities to characterize the microbial communities. Furthermore, studies using germ-free animals have shed light on how the gut microbiota are involved in autoimmunity. In this review we describe the different approaches used to characterize the human microbiome, review current knowledge about the gut microbiome, and discuss the role of gut microbiota in immune homeostasis and autoimmunity. Finally, we indicate how this knowledge could be used to improve human health by manipulating the gut microbiota. This article is part of a Special Issue entitled: From Genome to Function.     

The Effect of Fixed Orthodontic Appliances and Fluoride Mouthwash on the Oral Microbiome of Adolescents – A Randomized Controlled Clinical Trial

While the aesthetic effect of orthodontic treatment is clear, the knowledge on how it influences the oral microbiota and the consequential effects on oral health are limited. In this randomized controlled clinical trial we investigated the changes introduced in the oral ecosystem, during and after orthodontic treatment with fixed appliances in combination with or without a fluoride mouthwash, of 10–16.8 year old individuals (N = 91). We followed several clinical parameters in time, in combination with microbiome changes using next-generation sequencing of the bacterial 16S rRNA gene. During the course of our study, the oral microbial community displayed remarkable resilience towards the disturbances it was presented with. The effects of the fluoride mouthwash on the microbial composition were trivial. More pronounced microbial changes were related to gingival health status, orthodontic treatment and time. Periodontal pathogens (e.g. Selenomonas and Porphyromonas) were highest in abundance during the orthodontic treatment, while the health associated Streptococcus, Rothia and Haemophilus gained abundance towards the end and after the orthodontic treatment. Only minor compositional changes remained in the oral microbiome after the end of treatment. We conclude that, provided proper oral hygiene is maintained, changes in the oral microbiome composition resulting from orthodontic treatment are minimal and do not negatively affect oral health.     

Metaproteomic and Metabolomic Approaches for Characterizing the Gut Microbiome

The gut microbiome has been shown to play a significant role in human healthy and diseased states. The dynamic signaling that occurs between the host and microbiome is critical for the maintenance of host homeostasis. Analyzing the human microbiome with metaproteomics, metabolomics, and integrative multi‐omics analyses can provide significant information on markers for healthy and diseased states, allowing for the eventual creation of microbiome‐targeted treatments for diseases associated with dysbiosis. Metaproteomics enables functional activity information to be gained from the microbiome samples, while metabolomics provides insight into the overall metabolic states affecting/representing the host–microbiome interactions. Combining these functional ‐omic platforms together with microbiome composition profiling allows for a holistic overview on the functional and metabolic state of the microbiome and its influence on human health. Here the benefits of metaproteomics, metabolomics, and the integrative multi‐omic approaches to investigating the gut microbiome in the context of human health and diseases are reviewed.     

Fish Gut Microbiome: Current Approaches and Future Perspectives

In recent years, investigations of microbial flora associated with fish gut have deepened our knowledge of the complex interactions occurring between microbes and host fish. The gut microbiome not only reinforces the digestive and immune systems in fish but is itself shaped by several host-associated factors. Unfortunately, in the past, majority of studies have focused upon the structure of fish gut microbiome providing little knowledge of effects of these factors distinctively and the immense functional potential of the gut microbiome. In this review, we have highlighted the recently gained insights into the diversity and functions of the fish gut microbiome. We have also delved on the current approaches that are being employed to study the fish gut microbiome with an aim to collate all the knowledge gained and make accurate conclusions for their application based perspectives. The literature reviewed indicated that the future research should shift towards functional microbiomics to improve the maximum sustainable yield in aquaculture.     

Progress of analytical tools and techniques for human gut microbiome research

Massive DNA sequencing studies have expanded our insights and understanding of the ecological and functional characteristics of the gut microbiome. Advanced sequencing technologies allow us to understand the close association of the gut microbiome with human health and critical illnesses. In the future, analyses of the gut microbiome will provide key information associating with human individual health, which will help provide personalized health care for diseases. Numerous molecular biological analysis tools have been rapidly developed and employed for the gut microbiome researches; however, methodological differences among researchers lead to inconsistent data, limiting extensive share of data. It is therefore very essential to standardize the current methodologies and establish appropriate pipelines for human gut microbiome research. Herein, we review the methods and procedures currently available for studying the human gut microbiome, including fecal sample collection, metagenomic DNA extraction, massive DNA sequencing, and data analyses with bioinformatics. We believe that this review will contribute to the progress of gut microbiome research in the clinical and practical aspects of human health.     

Clinicians’ views and expectations of human microbiome science on asthma and its translations

Human microbiome science examines the microbiota that live in and on the human body and their role in human health. This paper examines clinicians’ views and expectations of microbiome science in asthma care. Drawing on qualitative interviews with 10 clinicians in Canada, we explore their perspectives for insights into translation of human microbiome science. The emphasis on novelty in much microbiome scholarship, we suggest, does not account fully for the ways in which microbiome science translations may be taken up in multiple ways that are both disruptive to and continuous with contemporary biomedicine. We suggest that clinicians drew on scientific discourses of “evidence” and “facts” as a form of boundary work to re-establish a separation between western biomedicine and alternative health practitioners, and clinical expertise and lay knowledge. We conclude with a discussion of human microbiome science and the emergence of post-Pasteurian modes of health in western biomedicine.     

Urban habitat restoration provides a human health benefit through microbiome rewilding: the Microbiome Rewilding Hypothesis

Restoration aims to return ecosystem services, including the human health benefits of exposure to green space. The loss of such exposure with urbanization and industrialization has arguably contributed to an increase in human immune dysregulation. The Biodiversity and Old Friends hypotheses have described the possible mechanisms of this relationship, and suggest that reduced exposure to diverse, beneficial microorganisms can result in negative health consequences. However, it is unclear whether restoration of biodiverse habitat can reverse this effect, and what role the environmental microbiome might have in such recovery. Here, we propose the Microbiome Rewilding Hypothesis, which specifically outlines that restoring biodiverse habitats in urban green spaces can rewild the environmental microbiome to a state that enhances primary prevention of human disease. We support our hypothesis with examples from allied fields, including a case study of active restoration that reversed the degradation of the soil bacterial microbiome of a former pasture. This case study used high‐throughput amplicon sequencing of environmental DNA to assess the quality of a restoration intervention in restoring the soil bacterial microbiome. The method is rapid, scalable, and standardizable, and has great potential as a monitoring tool to assess functional outcomes of green‐space restoration. Evidence for the Microbiome Rewilding Hypothesis will help motivate health professionals, urban planners, and restoration practitioners to collaborate and achieve co‐benefits. Co‐benefits include improved human health outcomes and investment opportunities for biodiversity conservation and restoration.     

The human microbiome: at the interface of health and disease

Interest in the role of the microbiome in human health has burgeoned over the past decade with the advent of new technologies for interrogating complex microbial communities. The large-scale dynamics of the microbiome can be described by many of the tools and observations used in the study of population ecology. Deciphering the metagenome and its aggregate genetic information can also be used to understand the functional properties of the microbial community. Both the microbiome and metagenome probably have important functions in health and disease; their exploration is a frontier in human genetics.     

Do Maternal Microbes Shape Newborn Oral Microbes?

Strong evidence suggests that the early composition of the oral microbiota of neonates plays an important role for the postnatal development of the oral health or immune system. However, the relationship between the maternal microbiome and the initial neonatal microbiome remains unclear. In this study, 25 pregnant women and their neonates were recruited, and the samples were collected from the maternal oral cavity, amniotic fluid, placenta and neonatal oral cavity. High-throughput sequencing of 16S rRNA was performed using the Illumina MiSeq platform to analyze the correlation with microbial community structure between the maternal and the neonatal oral cavity. The results indicated that the number of shared OTUs was up to 635 in four groups. The PCoA showed that there were certain similarities in the microbial community structure of the four groups. The dominant bacterial genera of the shared OTUs were consistent with human oral microbes, including Streptococcus, Fusobacterium and Prevotella. The results showed that there might be a correlation between the maternal and neonatal oral microbiome, through the amniotic fluid and placenta.Electronic supplementary materialThe online version of this article (10.1007/s12088-020-00901-7) contains supplementary material, which is available to authorized users.     

A new era in palaeomicrobiology: prospects for ancient dental calculus as a long-term record of the human oral microbiome

The field of palaeomicrobiology is dramatically expanding thanks to recent advances in high-throughput biomolecular sequencing, which allows unprecedented access to the evolutionary history and ecology of human-associated and environmental microbes. Recently, human dental calculus has been shown to be an abundant, nearly ubiquitous, and long-term reservoir of the ancient oral microbiome, preserving not only microbial and host biomolecules but also dietary and environmental debris. Modern investigations of native human microbiota have demonstrated that the human microbiome plays a central role in health and chronic disease, raising questions about changes in microbial ecology, diversity and function through time. This paper explores the current state of ancient oral microbiome research and discusses successful applications, methodological challenges and future possibilities in elucidating the intimate evolutionary relationship between humans and their microbes.     

Microbes,the gut and ankylosing spondylitis

It is increasingly clear that the interaction between host and microbiome profoundly affects health. There are 10 times more bacteria in and on our bodies than the total of our own cells, and the human intestine contains approximately 100 trillion bacteria. Interrogation of microbial communities by using classic microbiology techniques offers a very restricted view of these communities, allowing us to see only what we can grow in isolation. However, recent advances in sequencing technologies have greatly facilitated systematic and comprehensive studies of the role of the microbiome in human health and disease. Comprehensive understanding of our microbiome will enhance understanding of disease pathogenesis, which in turn may lead to rationally targeted therapy for a number of conditions, including autoimmunity.     

Gut microbiomes of free‐ranging and captive Namibian cheetahs: Diversity,putative functions and occurrence of potential pathogens

Although the significance of the gut microbiome for host health is well acknowledged, the impact of host traits and environmental factors on the interindividual variation of gut microbiomes of wildlife species is not well understood. Such information is essential; however, as changes in the composition of these microbial communities beyond the natural range might cause dysbiosis leading to increased susceptibility to infections. We examined the potential influence of sex, age, genetic relatedness, spatial tactics and the environment on the natural range of the gut microbiome diversity in free‐ranging Namibian cheetahs (Acinonyx jubatus). We further explored the impact of an altered diet and frequent contact with roaming dogs and cats on the occurrence of potential bacterial pathogens by comparing free‐ranging and captive individuals living under the same climatic conditions. Abundance patterns of particular bacterial genera differed between the sexes, and bacterial diversity and richness were higher in older (>3.5 years) than in younger individuals. In contrast, male spatial tactics, which probably influence host exposure to environmental bacteria, had no discernible effect on the gut microbiome. The profound resemblance of the gut microbiome of kin in contrast to nonkin suggests a predominant role of genetics in shaping bacterial community characteristics and functional similarities. We also detected various Operational Taxonomic Units (OTUs) assigned to potential pathogenic bacteria known to cause diseases in humans and wildlife species, such as Helicobacter spp., and Clostridium perfringens. Captive individuals did not differ in their microbial alpha diversity but exhibited higher abundances of OTUs related to potential pathogenic bacteria and shifts in disease‐associated functional pathways. Our study emphasizes the need to integrate ecological, genetic and pathogenic aspects to improve our comprehension of the main drivers of natural variation and shifts in gut microbial communities possibly affecting host health. This knowledge is essential for in situ and ex situ conservation management.     

The amphibian microbiome: natural range of variation,pathogenic dysbiosis,and role in conservation

Recent research in humans, livestock, and wildlife using high-throughput next-generation sequencing (NGS) has identified that resident microbiota play an essential role in disease resistance, host health, and adaptation to biotic and abiotic stressors. Since amphibians are currently facing population declines and extinctions attributable to anthropogenic pressures and emerging diseases, an understanding of the effects of microbiome dysbiosis and mitigation is a prerequisite for amphibian conservation and disease management. Interest is now growing with regard to understanding the influence of unfavorable environmental conditions on the amphibian microbiome and the effects of dysbiosis on the susceptibility to pathogenic infections. Here, we summarize information on the amphibian microbiome, specifically concerning intrinsic and extrinsic factors that shape the skin and gut microbiome. We explore diverse types of unfavorable environmental perturbations and the ways in which they can impact the microbiota of an individual so that we can better comprehend the consequences of stressors and dysbiosis on pathogen emergence and health. We discuss the role of the microbiome in amphibian conservation and identify gaps of knowledge that need to be filled if we are to achieve a meta-organism conservation approach. NGS studies should be complemented with other high-throughput “-omic” approaches to target microbiome functionality. Understanding the microbiome might be the missing piece in the overall strategy that will help maintain the health of amphibians in a world with highly affected environments and that will prevent/mitigate emerging infectious diseases.     

Gut microbiome and cancer immunotherapy

Gut microbiome has received significant attention for its influences on a variety of host functions, especially immune modulation. With the next-generation sequencing methodologies, more knowledge is gathered about gut microbiome and its irreplaceable role in keeping the balance between human health and diseases is figured out. Immune checkpoint inhibitors (ICIs) are one of the most innovational cancer immunotherapies across cancer types and significantly expand the therapeutic options of cancer patients. However, a proportion of patients show no effective responses or develop immune-related adverse events when responses do occur. More important, it is demonstrated that the therapeutic response or treatment-limiting toxicity of cancer immunotherapy can be ameliorated or diminished by gut microbiome modulation. In this review, we first introduce the relationship between gut microbiome and cancer immunotherapy. And then, we expound the impact of gut microbiome on efficacy and toxicity of cancer immunotherapy. Further, we review approaches to manipulating gut microbiome to regulate response to ICIs. Finally, we discuss the current challenges and propose future directions to improve cancer immunotherapy via gut microbiome manipulation.     

Deep sequencing of the oral microbiome reveals signatures of periodontal disease

The oral microbiome, the complex ecosystem of microbes inhabiting the human mouth, harbors several thousands of bacterial types. The proliferation of pathogenic bacteria within the mouth gives rise to periodontitis, an inflammatory disease known to also constitute a risk factor for cardiovascular disease. While much is known about individual species associated with pathogenesis, the system-level mechanisms underlying the transition from health to disease are still poorly understood. Through the sequencing of the 16S rRNA gene and of whole community DNA we provide a glimpse at the global genetic, metabolic, and ecological changes associated with periodontitis in 15 subgingival plaque samples, four from each of two periodontitis patients, and the remaining samples from three healthy individuals. We also demonstrate the power of whole-metagenome sequencing approaches in characterizing the genomes of key players in the oral microbiome, including an unculturable TM7 organism. We reveal the disease microbiome to be enriched in virulence factors, and adapted to a parasitic lifestyle that takes advantage of the disrupted host homeostasis. Furthermore, diseased samples share a common structure that was not found in completely healthy samples, suggesting that the disease state may occupy a narrow region within the space of possible configurations of the oral microbiome. Our pilot study demonstrates the power of high-throughput sequencing as a tool for understanding the role of the oral microbiome in periodontal disease. Despite a modest level of sequencing (~2 lanes Illumina 76 bp PE) and high human DNA contamination (up to ~90%) we were able to partially reconstruct several oral microbes and to preliminarily characterize some systems-level differences between the healthy and diseased oral microbiomes.     

The oral biome in the aetiology and management of dental disease: Current concepts and ethical considerations

Our understanding of the complexity of the oral biome and of the role of the various constituent bacteria in the aetiology of dental disease is growing. Probiotics and their relationship with prebiotics, as well as other microbiome‐based interventions, could be useful in preventing and treating dental disease and in promoting oral health. However, given the promise and early stage of this treatment approach, there are also a number of ethical, social and regulatory issues associated with innovative probiotic therapy. In this article, a brief update is given on contemporary theories of the aetiology and management of the two commonest dental diseases, and on the roles of pre‐ and probiotics and oral biome transplant in the management of these diseases. The focus is primarily on four core issues: informed consent, risk–benefit assessment, how to determine suitable healthy donors, and commercialization and regulation. We discuss the safety and benefits of oral probiotics, not only concerning the products and quality control during their manufacture, but also regarding the depth of public knowledge about this topic. We point out that the requirement of listing ingredients honestly might be insufficient, and that the prevalent rhetoric of ‘natural’ and ‘organic’ as well as some health claims in the translational, innovative probiotic industry and markets are themselves misleading and should be carefully scrutinized. Finally, we suggest an ethical imperative to find a balance between scientific research and industry, and public health in the regulation of probiotics.     

Metagenomics: the role of the microbiome in cardiovascular diseases

PURPOSE OF REVIEW: The human oral and intestinal microbiota interact with the host through poorly understood metabolic pathways. Investigation of such complex ecosystems and interactions has been difficult. In this paper, we assess the current evidence supporting the role of the microbiota as a significant determinant of cardiovascular disease risk. RECENT FINDINGS: The link between oral disease and cardiovascular disease was established about 15 years ago. The accumulated evidence supports, but does not prove a causal association between periodontal infection and cardiovascular disease and suggests some physiologically obvious connections between these pathologies, namely, inflammatory and immune responses, and hemostasis. Moreover, some studies have observed higher concentrations of total and LDL-cholesterol and triglycerides and lower concentrations of HDL-cholesterol in individuals with periodontitis before periodontal treatment. Likewise, recent reports suggest the influence of the gut microbiome in the risk of common age-related diseases such as cancer and potentially cardiovascular disease through modification of classical risk factors such as obesity, insulin resistance and plasma lipids. SUMMARY: The recognition that microorganisms may play an even more important role in maintaining human health than in generating diseases places metagenomics as one of the most relevant areas of future research. The knowledge of the hundreds of genomes that we host and their interaction with our own genome shall provide a much more complete understanding of the individual nutritional needs and may be an obligated part of future personalized healthcare approaches.