Microbiome: Deciphering the Last Organ of the Human Body

The human organism is a complex structure composed of cells belonging to all three domains of life on Earth, Eukarya, Bacteria and Archaea, as well as their viruses. Bacterial cells of more than a thousand taxonomic units are condensed in a particular functional collective domain, the intestinal microbiome. The microbiome constitutes the last human organ under active research microbiome is readily inherited. Like any other organ, the microbiome has physiology and pathology, and the individual health might be damaged when its collective population structure is altered. The diagnostic of microbiomic diseases involves metagenomic studies. The therapeutics of microbiome‐induced pathology include microbiota transplantation, a technique increasingly available microbiome can be regarded as a human organ from the physiological standpoint Perhaps we can envisage ‘microbiomology’ as a future specialty. Devoted to the study of the physiology, pathology, diagnostics, therapy and prevention of alterations of the community structure of the microbiome. The importance of the microbiome has been highlighted by the microbial ‘abnormalities’ found in pathological conditions such as inflammatory bowel diseases, obesity or malnutrition.Diagnosis of microbiome diseases is based at present on full metagenomic DNA sequencing and computational advances that can inform about and differentiate core microbiota and changing microbiota These ‘diagnostic’ techniques should also be able to evaluate the role of mobile genetic elements, which deeply influence the connectivity of the microbiome. The therapy of microbiome diseases will be part of future interventions based on eco‐evo drugs and strategies. Addressing microbiome restoration by transplantation is crucial to advance in the curing of microbiome diseases A more advanced field of research in the therapy of microbiome diseases will be the discovery of drugs acting on host–microbiome and intra‐microbiome signals and interactions.

Microbial colonization of mucosal tissues during infancy plays an instrumental role in the development and education of the host mammalian immune system. These early-life events can have long-standing consequences: facilitating tolerance to environmental exposures or contributing to the development of disease in later life, including inflammatory bowel disease, allergy, and asthma. Recent studies have begun to define a critical period during early development in which disruption of optimal host-commensal interactions can lead to persistent and in some cases irreversible defects in the development and training of specific immune subsets.

Large-scale alterations of the gut microbiota and its microbiome (gene content) are associated with Metabolic diseases, especially type 2 diabetes and obesity and are responsive to weight loss, are growing global health‐care concerns. Gut microbes can impact host metabolism via signaling pathways in the gut, with effects on inflammation, insulin resistance, and deposition of energy in fat stores. New therapeutic approaches are urgently needed to address the emerging epidemic of obesity and diabetes. Restoration of the gut microbiota to a healthy state may ameliorate the conditions associated with obesity and help maintain a healthy weight. The microbiome, the collective genomic and metabolic potential of the gut microbiota, may have a key role in many chronic diseases through its mitigation of immune‐inflammatory responses. 

Pharmacogenomics can play an important role in identifying responders and non-responders to medications, avoiding adverse events, and optimizing drug dose. Genetic polymorphisms in drug-metabolizing enzymes, transporters, receptors, and other drug targets have been linked to interindividual differences in the efficacy and toxicity of many medications. Pharmacogenomic studies are rapidly elucidating the inherited nature of these differences in drug disposition and effects, thereby enhancing drug discovery and providing a stronger scientific basis for optimizing drug therapy on the basis of each patient's genetic constitution.

The human body harbors enormous numbers of microbiota that influence cancer susceptibility, in part through their prodigious metabolic capacity and their profound influence on immune cell function. Even larger numbers of malignancies are associated with an altered composition of commensal microbiota (dysbiosis) based on microbiome studies using metagenomic sequencing. Microbiota can alter cancer susceptibility and progression by diverse mechanisms, such as modulating inflammation, inducing DNA damage, and producing metabolites involved in oncogenesis or tumor suppression. Microbiota can be manipulated for improving cancer treatment. By incorporating probiotics as adjuvants for checkpoint immunotherapy or by designing small molecules that target microbial enzymes, microbiota can be harnessed to improve cancer care. The efficacy of chemotherapy/immunotherapy likely depends on an individual's microbiota, maintenance of microbial diversity is critical for human health. Steps should be taken to prevent indiscriminate antibiotic usage. Furthermore, encouraging a diverse, plant‐based diet facilitates microbial diversity.

Diet and energy balance influence CRC by multiple mechanisms. They modulate the composition and function of gut microbiota, which have a prodigious metabolic capacity and can produce oncometabolites or tumor‐suppressive metabolites depending, in part, on which dietary factors and digestive components are present in the GI tract. Gut microbiota also have a profound effect on immune cells in the lamina propria, which influences inflammation and subsequently CRC. The nutrient availability, which is an outcome of diet and energy balance, determines the abundance of certain energy metabolites that are essential co‐factors for epigenetic enzymes and therefore impinges upon epigenetic regulation of gene expression. Aberrant epigenetic marks accumulate during CRC, and epimutations that are selected for drive tumorigenesis by causing transcriptome profiles to diverge from the cell of origin. In some instances, the above mechanisms are intertwined as exemplified by dietary fiber being metabolized by colonic bacteria into butyrate, which is both a short‐chain fatty acid (SCFA) and a histone deacetylase (HDAC) inhibitor that epigenetically upregulates tumor‐suppressor genes in CRC cells and anti‐inflammatory genes in immune cells.

There are two ways by which a baby can come into this world: vaginally or by Cesarean delivery.   The vast majority of our critical gut microbiome bacteria from our mothers during birth and breastfeeding. The method of delivery impacts the baby’s microbiome, with vaginal delivery (VD) having a strong, beneficial effect and cesarean delivery (CD) reducing the number and diversity of beneficial bacteria.  Cesarean delivery poses a health risk for newborns by way of changes in the gut microbiota there microbial species or genera that are uniformly present in all vaginally delivered infants and uniformly absent in all Cesarean‐born babies prolonged effects of birth mode on microbiota composition that co‐occurred with Cesarean delivery the mother’s collective microbiome is healthy and that baby receives as many essential bacteria as possible from her during birth and breastfeeding, as her microbiome forms the foundation for baby’s microbiome, which is essential for health, development, and metabolism from infancy through childhood. The infant’s gut microbiome is of critical importance since its bacteria build and strengthen baby’s immune system. the microbiomes of babies born via vaginal delivery (VD) and via cesarean delivery (CD) are different, due to the different microbiomes they are receiving from their mother and their physical environment, during a vaginal birth, the baby receives maternal vaginal, intestinal and fecal bacteria present in the birth canal; these bacteria are augmented with bacteria from mother’s skin, oral and breast milk microbiomes through holding, kissing and breastfeeding. A baby born by CD does not receive these initial bacteria, but rather the bacteria present in his mother’s skin and the hospital environment which contains harmful bacteria subsequently, CD babies have significantly lower bacterial amounts and diversity than vaginally born babies, which is less than ideal.  Since they were not seeded with the optimal array of bacteria at birth, their immune systems may fail to develop properly, leaving them more susceptible to pathogens. Scientists speculate this may account for the increased long-term risk and incidence of chronic, non-communicable diseases (including allergies, asthma, obesity and autoimmune diseases) among babies born via cesarean section. There are two ways by which a baby can come into this world: vaginally or by Cesarean delivery.   The vast majority of our critical gut microbiome bacteria from our mothers during birth and breastfeeding. The method of delivery impacts the baby’s microbiome, with vaginal delivery (VD) having a strong, beneficial effect and cesarean delivery (CD) reducing the number and diversity of beneficial bacteria.  Cesarean delivery poses a health risk for newborns by way of changes in the gut microbiota there microbial species or genera that are uniformly present in all vaginally delivered infants and uniformly absent in all Cesarean‐born babies prolonged effects of birth mode on microbiota composition that co‐occurred with Cesarean delivery the mother’s collective microbiome is healthy and that baby receives as many essential bacteria as possible from her during birth and breastfeeding, as her microbiome forms the foundation for baby’s microbiome, which is essential for health, development, and metabolism from infancy through childhood. The infant’s gut microbiome is of critical importance since its bacteria build and strengthen baby’s immune system. the microbiomes of babies born via vaginal delivery (VD) and via cesarean delivery (CD) are different, due to the different microbiomes they are receiving from their mother and their physical environment, during a vaginal birth, the baby receives maternal vaginal, intestinal and fecal bacteria present in the birth canal; these bacteria are augmented with bacteria from mother’s skin, oral and breast milk microbiomes through holding, kissing and breastfeeding. A baby born by CD does not receive these initial bacteria, but rather the bacteria present in his mother’s skin and the hospital environment which contains harmful bacteria subsequently, CD babies have significantly lower bacterial amounts and diversity than vaginally born babies, which is less than ideal.  Since they were not seeded with the optimal array of bacteria at birth, their immune systems may fail to develop properly, leaving them more susceptible to pathogens. Scientists speculate this may account for the increased long-term risk and incidence of chronic, non-communicable diseases (including allergies, asthma, obesity and autoimmune diseases) among babies born via cesarean section.

There is an increasing evidence to suggest that both caries and periodontal disease represent dysbiotic states of the oral microbiome, The human oral microbiome currently comprises 600–700 taxa, but estimates suggest that overall species numbers may turn out to be higher. . Within the oral cavity, groups of microbial species become arranged into surface‐localized communities that vary considerably in composition according to sites of establishment. Factors such as nutrient availability, pH, toxic metabolites, shear forces and host conditions contribute to modelling the structure and activities of these oral microbial communities. A repertoire of stable dysbiotic states may occur in both the caries and periodontitis involving different microbial community structures with potentially similar functional properties. The mode of acquisition of oral microbial communities may be less passive than previously recognized but once established remains relatively stable within an individual although there are very significant site variations, a number of issues pertinent to the community organization and functional activity of the bacterial populations resident on supra‐ and subgingival tooth surface and the influence of these populations on disease.

The Nobel laureate Joshua Lederberg suggested using the term ‘human microbiome’ to describe the collective genome of our indigenous microorganisms (microflora) colonizing the whole body. The skin is a complex barrier organ made of a symbiotic relationship between microbial communities and host tissue via complex signals provided by the innate and the adaptive immune systems.  It is constantly exposed to various endogenous and exogenous factors which impact this balanced system potentially leading to inflammatory skin conditions comprising infections, allergies or autoimmune diseases started using modern methods such as pyrosequencing assays of bacterial 16S rRNA genes to identify and characterize the different microorganisms present on the skin, to evaluate the bacterial diversity and their relative abundance and to understand how microbial diversity may contribute to skin health and dermatological conditions, Three main sampling methods are currently used to harvest the resident skin microbiota The skin barrier and the microbiota act like a shield that protects the body against external aggressions. There is a balanced interplay between the host and resident and/or transient bacterial populations. This balance is continuously affected by intrinsic (host) and extrinsic (environmental) factors that alter the composition of skin microorganism communities and the host skin barrier function. Altering this equilibrium is called dysbiosis. Underlying pathobiology or genetically determined variations in stratum corneum properties might result in a dysbiosis that changes the abundance and diversity of commensal species, which disturbs skin barrier function and aggravates chronic skin diseases such as atopic dermatitis and psoriasis dysbiosis does not only occur between bacteria, disequilibrium between bacteria and commensal fungi strains on the scalp has been observed in subjects prone to dandruff the impact of environmental factors such as climate, including temperature and UV exposure but also of lifestyle, including alcoholism or nutrition on microbial communities remains to be elucidated. Indeed, ultraviolet B and C light have been reported to be bactericidal, while excessive alcohol consumption has been shown to diminish host resistance and nutrient and vitamin deficiency has been shown to impact on the skin microbiota balance, resulting in infection and skin barrier disturbance, Cosmetics, hygiene products, makeup and moisturizers have also been implicated in modifying the skin microbiome, Radiotherapy and chemotherapy used to treat cancer may also impact the microbiota. Therefore, improving the knowledge about the skin microbiome may open new perspectives in the management of the healthy and diseased skin and of its microbiome.

Skin is subjected to harsh environmental conditions that favor the growth of primarily gram positive organisms, resident bacteria are capable of reproducing and are commensal with the host when skin is healthy. When skin is compromised, resident bacteria can become pathogens as is seen in acne and folliculitis. The skin microbiome is influenced by pH, sebum content, barrier function and hydration^, alterations in skin microflora play a significant role in conditions such as atopic dermatitis, psoriasis, acne and skin cancer.

Probiotics are live bacterial cultures that, when applied topically, influence the composition of skin microflora. Acidifying the skin discourages the growth of most pathogens favoring growth of resident flora. Probiotic strains produce potent antimicrobials such as bacteriocidins, organic acids and H²O² that prevent pathogen adhesion. Lactic acid acts as a natural moisturizing factor and antimicrobial, and acts on epidermal and dermal remodeling

Prebiotics are non-digestible plant-based carbohydrates that discourage the growth of pathogens while preserving beneficial bacteria. Prebiotics can be readily incorporated into skincare products and are an excellent alternative to live bacteria. Bacterial cell lysates are also used in cosmetic formulations.

The main therapeutic goal of modern cardiology is to develop novel approaches to minimize inflammation, myocardial necrosis/apoptosis, and enhance cardiac repair after MI. Though MI can be affected by genetic and environmental factors, the search for targeting lifestyle factors has been of greater interest. One such potential factor is the microbiota, the human intestinal microbial community. the disruption of intestinal flora structure provokes MI and poor prognosis. Since gut microbiota is readily modifiable through a variety of interventions, it can be targeted to modulate the host signaling pathways involved in inflammation and MI pathogenesis. Symbiosis bacteria can reduce ischemia/reperfusion injury and inflammation; moreover, they can regulate lipid metabolism, blood pressure, apoptosis, MI size, and overall cardiac survival. In this review, we provide an overview of the development of MI following the dysbiosis microbiota and give an update on a microbiota-based therapeutic strategy to delay or prevent MI.

Trillions of microbes inhabit the human intestine, forming a complex ecological community that influences normal physiology and susceptibility to disease through its collective metabolic activities and host interactions. Understanding the factors that underlie changes in the composition and function of the gut microbiota will aid in the design of therapies that target it. This goal is formidable. The gut microbiota is immensely diverse, varies between individuals and can fluctuate over time — especially during disease and early development. Viewing the microbiota from an ecological perspective could provide insight into how to promote health by targeting this microbial community in clinical treatments.The gut metagenome is the aggregate of all the genomes of gut microbiota. The gut microbiota plays a key role in digestion, metabolism and immune function, and has a widespread impact beyond the gastrointestinal tract. Changes in the biodiversity of the gut microbiota are associated with far-reaching consequences on host health and development. Diet, functional foods, and gut microbiota transplantation are areas that have yielded some therapeutic success in modulating the gut microbiota and warrant further investigation of their effects on various disease states.

The collection of microbes living in and on our body - have a significant impact on human health and well-being. They have been associated with numerous diseases, yet we have barely understood their role in the context of life-style and genetics. Various initiatives are underway around the world to survey the human microbiota at several body sites, characterise them, understand their interactions with the human hosts, elucidate their role in diseases, and design possible therapeutic or dietary interventions.

Prebiotics and probiotics may be useful in achieving positive effects which include the enhanced immune function, improved colonic integrity, decreased incidence and duration of intestinal infections, down-regulated allergic response, improved digestion and elimination. Probiotics and prebiotics share a unique role in human nutrition, largely centering on manipulation of populations or activities of the bacteria that colonize our bodies. There is a need to consolidate the basic and applied research on probiotics and prebiotics into useful tools for food and nutrition, for example LAB are gram-positive nonpathogenic bacteria that are widely distributed in the nature have long been used in food processing the LcS is widely used in the production of probiotic dairy products and is also used as a food ingredient. The probiotic bacteria have the potential to augment or modify the host immune function through the regulation of host immune cells.

Microbiota modulation appears as an interesting tool in the prevention and/or treatment of the dysbiosis associated with obesity and metabolic disorders. Colonization of mucosal surfaces is characterized by fluctuating changes in microbial diversity during the first few years of life, until reaching a point of equilibrium that remains relatively stable throughout adulthood in the absence of environmental insults, immune maturation is likely influenced directly and/or indirectly by the presence of commensal microbes the early-life ecological succession of mucosal colonization occurs concomitantly with the development, expansion, and education of the mucosal immune system.

Microbes inhabit virtually all sites of the human body, yet we know very little about the role they play in our health. In recent years, there has been increasing interest in studying human-associated microbial communities, particularly since microbial dysbioses have now been implicated in a number of human diseases. Recent advances in sequencing technologies have made it feasible to perform large-scale studies of microbial communities, providing the tools. Rapidly developing sequencing methods and analytical techniques,  the human microbiome on different spatial and temporal scales, including daily time series datasets spanning months. Furthermore, emerging concepts related to defining operational taxonomic units, diversity indices, core versus transient microbiomes, are enhancing our ability to understand the human microbiome.

16S ribosomal RNA (or 16S rRNA) is the component of the 30S small subunit of a prokaryotic ribosome that binds to the Shine-Dalgarno sequence.  16S rRNA sequencing has been used to characterize the complexity of microbial communities at each body sites, and to determine whether there is a core microbiome.The 16S rRNA sequence contains both highly conserved and variable regions. These variable regions, nine in number (V1 through V9), are routinely used to classify organisms according to phylogeny, making 16S rRNA sequencing particularly useful in metagenomics to help identify taxonomic groups present in a sample. 

In the last two decades, the widespread application of genetic and genomic approaches has revealed a bacterial world astonishing in its ubiquity and diversity. It examines how a growing knowledge of the vast range of animal–bacterial interactions, whether in shared ecosystems or intimate symbiosis, is fundamentally altering our understanding of animal biology. It highlights the recent technological and intellectual advances that have changed our thinking about five questions: how have bacteria facilitated the origin and evolution of animals; how do animals and bacteria affect each other’s genomes; how does normal animal development depend on bacterial partners; how is homeostasis maintained between animals and their symbionts; and how can ecological approaches deepen our understanding of the multiple levels of animal–bacterial interaction and to include investigations of the relationships between and among bacteria and their animal partners as we are going to seek a better understanding of the natural world.

Farmers have long tried to improve the chemical and physical condition of their soils, seeking to make more nutrients available to their plants, to retain more moisture in the soil, and to ease the growth of plant roots. But they have typically ignored the role of the teeming diversity of fungi and bacteria in the soil. Now, however, soil biologists are beginning to understand the significance of the interactions at work in the microbiome surrounding plants' root systems. Recent research has shown, for example, that major food crops can be made dramatically more stress tolerant by transplanting into them various microbiota, such as fungi or bacteria, that colonize other species.

Higher plants have evolved intimate, complex, subtle, and relatively constant relationships with a suite of microbes, the phytomicrobiome. This intercommunication dictates aspects of plant development, architecture, and productivity. Understanding this signaling via biochemical, genomics, proteomics, and metabolomic studies has added valuable knowledge regarding development of effective, low-cost, eco-friendly crop inputs that reduce fossil fuel intense inputs. This knowledge underpins phytomicrobiome engineering: manipulating the beneficial consortia that manufacture signals/products that improve the ability of the plant-phytomicrobiome community to deal with various soil and climatic conditions, leading to enhanced overall crop plant productivity. The goal of microbiome engineering is to manipulate the microbiome toward a certain type of community that will optimize plant functions of interest. For instance, in crop production the goal is to reduce disease susceptibility, increase nutrient availability increase abiotic stress tolerance and increase crop yields. 

Virtually every plant part is colonized by microorganisms, including bacteria, archaea, fungi, collectively designated as the plant–microbiome or phytomicrobiome.

Microorganisms are a key component of the plant, often inextricable from their host and the plant–microbiome is thought to function as a metaorganism or holobiont. Over the last few decades we have learned that plants and microbes can use molecular signals to communicate. This is well-established for the legume-rhizobia nitrogen-fixing symbiosis, and reasonably elucidated for mycorrhizal associations. Bacteria within the phytomircobiome communicate among themselves through quorum sensing and other mechanisms. Plants also detect materials produced by potential pathogens and activate pathogen-response systems. This intercommunication dictates aspects of plant development, architecture, and productivity.

Biostimulants may either directly interact with plant signaling cascades or act through stimulation of endophytic and non-endophytic bacteria, yeast, and fungi to produce molecules of benefit to the plant. These are the substances and materials with the exception of nutrients and pesticides, which, when applied to plant, seeds or growing substrates in specific formulations, have the capacity to modify the physiological processes of plants in a way that provides potential benefits to growth, development and/or stress response to enhance the nutrition efficiency and/or stress response

AMF support plant nutrition by absorbing and translocating mineral nutrients beyond the depletion zones of plant rhizosphere (biofertilisers) and induce changes in secondary metabolism leading to improved nutraceutical compounds. In addition, AMF interfere with the phytohormone balance of host plants, thereby influencing plant development (bioregulators) and inducing tolerance to soil and environmental stresses (bioprotector). Maximum benefits from AMF activity will be achieved by adopting beneficial farming practices (e.g. reduction of chemical fertilisers and biocides), by inoculating efficient AMF strains and also by the appropriate selection of plant host/fungus combinations.

Biostimulants can be used as a tool to complement the use of chemical inputs, by involving non-living-based products, or living-based products Elicitors and semiochemicals are considered to be the most promising tools for inducing plant resistance to various diseases and enhancing natural predation, respectively. These tools are still difficult to use because of their lack of reliability in the field and their uneasy integration in the cropping systems. Maintaining these performances is supported by research through the development of new tools to increase the tolerance of plants to biotic and abiotic stresses.

As agricultural production intensified over the past few decades, producers became more and more dependent on agrochemicals as a relatively reliable method of crop protection helping with economic stability of their operations. However, increasing use of chemical inputs causes several negative effects, i.e., development of pathogen resistance to the applied agents and their nontarget environmental impact. Furthermore, the growing cost of pesticides, particularly in less-affluent regions of the world, and consumer demand for pesticide-free food has led to a search for substitutes for these products. Biological control is thus being considered as an alternative or a supplemental way of reducing the use of chemicals in agriculture. There has been a large body of literature describing potential uses of plant associated bacteria as agents stimulating plant growth and managing soil and plant health, the most widely studied group of PGPB are PGPR colonizing the root surfaces and the closely adhering soil interface, the rhizosphere, some of these PGPR can also enter root interior and establish endophytic populations. Many of them are able to transcend the endodermis barrier, crossing from the root cortex to the vascular system, and subsequently thrive as endophytes in stem, leaves, tubers, and other organs, PGPB, PGPR have provided a greater understanding of the multiple facets of disease suppression by these biocontrol agents.

"Biostimulants," often used in plural form, is a broad term that literally means a group of ingredients that stimulate life. Stimulate plant responses and work In all weather conditions, Increase microbial root protection from soil pathogens, Increase natural plant toxins, repelling pests, Improve drought tolerance, Stimulate plants' immune system, Detoxify chemical residues and heavy metals, Enhances fertilization and reduces leaching, Produce deeper roots, Improve stress tolerance, Accelerate establishment, Increase soil nutrient reserve, Increase profits, cut operating costs, lead to 50% reduction in fertilizer.

In horticulture, hydroponics is a form of agriculture where plants are not grown in soil, but rather in trays or grow beds fed by a constant flow of nutrient solution. A hydroponic system refers to the tools and equipment that are packaged together in order to grow plants hydroponically. Hydroponics is one the fastest rising sectors in the horticultural industry. It is, however, a contested one.

Contemporary cannabis cultivation takes many different forms with variations in approach identifiable both within and between different countries, a simple typology of modern cannabis cultivation might therefore be “old” or “traditional” cultivation, cultivation in the developing world began to take on new dimensions, primarily for domestic consumption. With knowledge and technology (grow-lights, hydroponics, etc.) gradually becoming easily available, opportunities to cultivate cannabis grew. Global patterns of cannabis cultivation have followed a fascinating development, from highly concentrated production in certain developing countries to decentralized production in almost every country around the world. It is with the emergence of modern patterns of cannabis use in the developed world that we have seen major changes in patterns of cannabis production. As demand for cannabis increased globally, fuelled by the developments of the “counter-culture”. Cannabis cultivation may be too easily done, with demand for the product, alongside the knowledge and techniques needed for growing, too widespread to expect anything different.