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The prevailing theory of autoimmune disease, that the body creates autoantibodies that attack “self,” was developed during
an era when culture-based methods vastly underestimated the number of microbes capable of persisting in and on Homo sapiens. Thanks to the advent of culture-independent tools, the human body is now known to harbor billions of m...
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Context 1
... team found that the expression of 12 nuclear receptors was downregulated in the longer- lasting, younger lymphoblastoid cells. Among them was the VDR and the Estrogen Receptor Beta (ERB), both downregulated by a factor of about 15 times (Figure 2). EBV is found in many common chronic disease states. ...
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Background: Vitamin D receptor (VDR) is a key nuclear receptor that is associated with the risk and progression of breast cancer (BC). Objectives: The present study investigated the Fok1, Bsm1, Taq1 and Cdx2 polymorphisms in the VDR gene and susceptibility to BC in a sample of Southeastern Iranian population. Methods: This case-control study was co...
Background: Vitamin D receptor (VDR) is a key nuclear receptor that is associated with the risk and progression of breast cancer
(BC).
Objectives: The present study investigated the Fok1, Bsm1, Taq1 and Cdx2 polymorphisms in the VDR gene and susceptibility to BC in
a sample of Southeastern Iranian population.
Methods: This case-control study was co...
Following the first isolation of nuclear receptor (NR) genes, genetic disorders caused by NR gene mutations were initially discovered by a candidate gene approach based on their known roles in endocrine pathways and physiologic processes. Subsequently, the identification of disorders has been informed by phenotypes associated with gene disruption i...
RESUMEN La vitamina D tiene un rol importante en la homeostasis del calcio/fosfato, respuesta inmune, proliferación y diferenciación celular, procesos cognitivos. Sin embargo, su aporte deficiente o adecuado puede llevar al desarrollo de patologías o no. El receptor de vitamina D (VDR), perteneciente a la familia de receptores nucleares, desencaden...
Background: Vitamin D receptor (VDR) is a key nuclear receptor that is associated with the risk and progression of breast cancer (BC). Objectives: The present study investigated the Fok1, Bsm1, Taq1 and Cdx2 polymorphisms in the VDR gene and susceptibility to BC in a sample of Southeastern Iranian population. Methods: This case-control study was co...
Citations
... Despite being the subject of numerous studies over the last 100 years and implicated in various diseases, L-forms continue to be largely misunderstood by the medical research community. According to Marshall Pathogenesis, L-forms are part of the metagenomic microbiota responsible for chronic diseases (Proal et al., 2011). Their tops and sides are irregular. ...
Microbiology is the branch of science that investigates microscopic organisms known as microorganisms and their isolation by various methods Microorganisms can have single or multicellular eukaryotic cell structure as well as prokaryotic unicellular structure. When prokaryotic cells are examined, they are cells that do not have organelles surrounded by membranes and whose genetic material is dispersed in the cytoplasm. Until 30-35 years ago, Archaea, which were included in a different class, were defined as having a prokaryotic cell structure and considered bacteria. It has been observed that some archaea can cause diseases in humans, animals, and many plant species. It is possible to come across many areas in nature. Microbiology is also divided into different branches within itself. Virology, mycology, bacteriology, and parasitology are examined from four primary areas. This study provides basic information for understanding the diversity and characteristics of microorganisms and bacteria. In this way, it is tried to recognize the interest of humanity in the world of microorganisms and to explain basic information in this way. Currently, when scientists classify species based on microorganisms and consider that only about 5% of the microorganisms existing in the world have been identified, it will be easily understood how important a field of study microbiology is.
... В условиях глобализации, миграции и урбанизации населения происходит изменение рациона питания без должной адаптации микробиома кишечника. Кишечная микрофлора попала в список возможных факторов риска возникновения ряда заболеваний, ученые и врачи отмечают при наличии того или иного заболевания в первую очередь проблемы с пищеварением [11,12,13,14]. Разнообразие кишечной микробиоты программирует как здоровое функционирование органов и систем организма, так и риски соматических заболеваний. ...
... Early childhood infections may predispose to dysbiosis at a later date (157). For example, measles depletes host B and T lymphocytes for up to 2-3 years after initial infection. ...
The illness ME/CFS has been repeatedly tied to infectious agents such as Epstein Barr Virus. Expanding research on the human microbiome now allows ME/CFS-associated pathogens to be studied as interacting members of human microbiome communities. Humans harbor these vast ecosystems of bacteria, viruses and fungi in nearly all tissue and blood. Most well-studied inflammatory conditions are tied to dysbiosis or imbalance of the human microbiome. While gut microbiome dysbiosis has been identified in ME/CFS, microbes and viruses outside the gut can also contribute to the illness. Pathobionts, and their associated proteins/metabolites, often control human metabolism and gene expression in a manner that pushes the body toward a state of illness. Intracellular pathogens, including many associated with ME/CFS, drive microbiome dysbiosis by directly interfering with human transcription, translation, and DNA repair processes. Molecular mimicry between host and pathogen proteins/metabolites further complicates this interference. Other human pathogens disable mitochondria or dysregulate host nervous system signaling. Antibodies and/or clonal T cells identified in patients with ME/CFS are likely activated in response to these persistent microbiome pathogens. Different human pathogens have evolved similar survival mechanisms to disable the host immune response and host metabolic pathways. The metabolic dysfunction driven by these organisms can result in similar clusters of inflammatory symptoms. ME/CFS may be driven by this pathogen-induced dysfunction, with the nature of dysbiosis and symptom presentation varying based on a patient's unique infectious and environmental history. Under such conditions, patients would benefit from treatments that support the human immune system in an effort to reverse the infectious disease process.
... Several studies have demonstrated that HDP expression regulation by VDR is not evolutionarily conserved, because it is restricted to humans and nonhuman primates and CAMP genes are not responsive to VDR in other animals, such as mice [28,36,38,39]. Thus, there is a difference between the immune responses of mice and humans [51]. Given that VDR and its calcitriol linker have a key role in the human immune response, current knowledge of the mechanisms involved in the HDP expression, especially those associated with nuclear receptors, and probably other aspects of innate immunity, is limited because mice are currently the most-studied animal model of the immune response [51]. ...
... Thus, there is a difference between the immune responses of mice and humans [51]. Given that VDR and its calcitriol linker have a key role in the human immune response, current knowledge of the mechanisms involved in the HDP expression, especially those associated with nuclear receptors, and probably other aspects of innate immunity, is limited because mice are currently the most-studied animal model of the immune response [51]. ...
Since the early 19th century, it has been known that host-defense peptides (HDPs) have a crucial role in innate host defense. Subsequent work has demonstrated their role in adaptive immunity as well as their involvement in different inflammatory diseases, autoimmune diseases, and cancer. In addition to these multiple functional activities, several studies have shown that HDP accumulation might be correlated with various human diseases and, therefore, could be used as a biomarker of such diseases. Thus, research has aimed to validate the clinical use of HDPs for diagnosis, prognosis, and further treatment. In this review, we outline the most recent findings related to the use of HDPs as biomarkers, their clinical and epidemiological value, and the techniques used to determine the levels of HDPs.
... If VDR-deac is present, it is increasingly likely that the body will not attack its own tissues in autoimmune diseases; rather, antibodies are produced that are directed against certain parts of the metagenome communities of microbes. 31 Intracellular microbes living in nuclear cells can interfere with DNA transcription and repair mechanisms, allowing them to trigger many of the dysfunctions associated with autoimmune diseases. Microbe immunosuppression succeeds as a result of VDR suppression. ...
Background
Recent research on vitamin D indicates that our current understanding of the factors leading to chronic inflammation should be revised. One of the key mechanisms by which microbial immunosuppression occurs is the suppression of one of the most common endogenous cell nucleus receptors: the vitamin D receptor (VDR). Autoimmune diseases may be correlated with VDR deactivation (VDR-deac) which occurs when the receptor is no longer able to transcribe antimicrobial agents. Excess 1,25-dihydroxyvitamin D (1,25D) is not converted to 25-hydroxyvitamin D (25D); thus, high 1,25D levels may be accompanied by low 25D values.
Patients and methods
Since 1,25D promotes osteoclast activity and may thereby cause osteoporosis, fatty-degenerative osteolysis of the jaw (FDOJ), as described by our team, may also be associated with VDR-deac. In 43 patients, vitamin D conversion, immune system function and the quality of bone resorption and formation in the jawbone were related factors that may enhance chronic inflammatory processes. Here, we examine the relationship between immunology and bone metabolism among 43 FDOJ patients and those with immune system diseases (ISDs).
Results
We provide a link between FDOJ, RANTES/CCL5 overexpression and VDR-deac.
Conclusion
The clinical data demonstrate the interaction between VDR-deac and proinflammatory RANTES/CCL5 overexpression in FDOJ patients.
... The emergence of new technologies, such as next-generation sequencing, as well as parallel optimization of bioinformatics software bring about opportunities in the field of infectious disease diagnostics. The rapidly growing field of metagenomics already provided new insights into the gut microflora (Human Microbiome Project, 2012;Karlsson et al., 2013;Sun and Relman, 2013) and has deepened our understanding of the importance and links of intestinal micro-organisms (De Filippo et al., 2010;Proal et al., 2011;Scher et al., 2013) with various health conditions. Metagenomics is a combination of research methodologies aimed at characterizing complex microbial communities without isolating or culturing organisms (Handelsman, 2004). ...
... In this field, much confusion has arisen historically because of a failure to recognize that most microbes reproduce by binary fission and that this reproduction must be a minimal property or hallmark of a microbial cell that possesses 'life' or is 'alive' (Proal, Albert and Marshall 2011). Thus, as with Schrödinger's cat (e.g. ...
Blood in healthy organisms is seen as a 'sterile' environment: it lacks proliferating microbes. Dormant or not-immediately-culturable forms are not absent, however, as intracellular dormancy is well established. We highlight here that a great many pathogens can survive in blood and inside erythrocytes. 'Non-culturability', reflected by discrepancies between plate counts and total counts, is commonplace in environmental microbiology. It is overcome by improved culturing methods, and we asked how common this would be in blood. A number of recent, sequence-based and ultramicroscopic studies have uncovered an authentic blood microbiome in a number of non-communicable diseases. The chief origin of these microbes is the gut microbiome (especially when it shifts composition to a pathogenic state, known as 'dysbiosis'). Another source is microbes translocated from the oral cavity. 'Dysbiosis' is also used to describe translocation of cells into blood or other tissues. To avoid ambiguity, we here use the term 'atopobiosis' for microbes that appear in places other than their normal location. Atopobiosis may contribute to the dynamics of a variety of inflammatory diseases. Overall, it seems that many more chronic, non-communicable, inflammatory diseases may have a microbial component than are presently considered, and may be treatable using bactericidal antibiotics or vaccines.
© FEMS 2015.
... Ikeda et al 55 identified with MRI and histology that in edentulous patients the IAN (higher signal intensity than the surrounding connective tissue) inside the mandibular canal is composed of 3 branches: a) retromolar branch, which is separated from the main stem of the IAN at the level of the mandibular foramen and travels at company with IAN for a 2-5 mm course; it continuous and turns up right at a level just behind the wisdom tooth; b) the second (molar) branch, which was responsible for innervation of posterior teeth and starts from the IAN at the retromolar region, follows a parallel course with the ridge and inferiorly to the teeth and when variations of the mandibular canal, i.e. bifid mandibular canal, retromolar mandibular canal and accessory mental canal [42][43][44][45][46][47][48][49]51,52,55,[67][68][69][70][71] . ...
... In a recent paper of the Journal of Indian Society of Periodontology (2012), it is stated that the oral cavity can act as a source of pathogenic microorganisms that can act in distant body parts, especially in immunocompromised hosts 42 . From 1920 until today, research has been driven to pleomorhpic bacteria (especially L forms and Mycoplasma) where there is strong evidence for their etiological role in cryptic etiology diseases and especially autoimmune diseases 43,44 . ...
... Christen et al. [130] explored this hypothesis, ''In theory, a structural similarity or identity between the host and an invading pathogen might cause the immune system of the host to react not only to the pathogen but also to self-components.'' Infections can act as environmental triggers inducing or promoting autoimmune disease in genetically predisposed individuals [131]; researchers have shown how antinuclear antibodies (ANA) are created in response to infectious agents [132,133]. ...
Introduction:
Inflammation is believed to be a contributing factor to many chronic diseases. The influence of vitamin D deficiency on inflammation is being explored but studies have not demonstrated a causative effect.
Methods:
Low serum 25(OH)D is also found in healthy persons exposed to adequate sunlight. Despite increased vitamin D supplementation inflammatory diseases are increasing. The current method of determining vitamin D status may be at fault. The level of 25(OH)D does not always reflect the level of 1,25(OH)2D. Assessment of both metabolites often reveals elevated 1,25(OH)2D, indicating abnormal vitamin D endocrine function.
Findings:
This article reviews vitamin D's influence on the immune system, examines the myths regarding vitamin D photosynthesis, discusses ways to accurately assess vitamin D status, describes the risks of supplementation, explains the effect of persistent infection on vitamin D metabolism and presents a novel immunotherapy which provides evidence of an infection connection to inflammation.
Conclusion:
Some authorities now believe that low 25(OH)D is a consequence of chronic inflammation rather than the cause. Research points to a bacterial etiology pathogenesis for an inflammatory disease process which results in high 1,25(OH)2D and low 25(OH)D. Immunotherapy, directed at eradicating persistent intracellular pathogens, corrects dysregulated vitamin D metabolism and resolves inflammatory symptoms.
... We have previously described how pathogens may interact in order to drive the dysregulation of metabolic function associated with autoimmune disease [46]. We believe that these same mechanisms drive the pathogenesis of CFS/ME. ...
... Furthermore, the ability of gut microbiota to communicate with the brain and thus modulate behavior is emerging as a provocative concept in health and disease [74]. It follows that successive infection may also contribute to many of the physical and neurological ''comorbidities'' associated with CFS/ME and that these seemingly disparate conditions may best be studied in concert [46]. ...
Chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) has long been associated with the presence of infectious agents, but no single pathogen has been reliably identified in all patients with the disease. Recent studies using metagenomic techniques have demonstrated the presence of thousands of microbes in the human body that were previously undetected and unknown to science. More importantly, such species interact together by sharing genes and genetic function within communities. It follows that searching for a singular pathogen may greatly underestimate the microbial complexity potentially driving a complex disease like CFS/ME. Intracellular microbes alter the expression of human genes in order to facilitate their survival. We have put forth a model describing how multiple species-bacterial, viral, and fungal-can cumulatively dysregulate expression by the VDR nuclear receptor in order to survive and thus drive a disease process. Based on this model, we have developed an immunostimulatory therapy that is showing promise inducing both subjective and objective improvement in patients suffering from CFS/ME.
