THE ROLE OF INTESTINAL MICROBIOTE IN NEUROMUSCULAR DISEASES IN PARALIZED DOGS
GIURGIU GHEORGHE1, COJOCARU MANOLE2
1Deniplant-Aide Sante Medical Center, Biomedicine, Bucharest, 012371, Romania 2Titu Maiorescu University, Faculty of Medicine, Bucharest, 031593, Romania e-mail correspondence author: firstname.lastname@example.org
In order to be able to move, animals like man need the nervous and muscular system to function optimally. The brain, spine, nerves and muscles must work together. If there is a disturbance, the messages will not reach the destination and the animal will not be able to move. Depending on the location and extent of the neurological lesions, the dog may paralyze in whole or in part. Post-traumatic paralysis is a complex condition that requires proper treatment and thorough investigations to establish an accurate diagnosis. There are several conditions that can cause paralysis in the dog. The interaction between the health of the microbiome and that of the brain as well as the way it communicates immune and neuronal cells has been studied. Intestinal cells affect the cells of the central nervous system in the brain. The intestinal-brain axis may influence different neurological disorders and it is possible that dysbiosis in the intestinal tract may lead to disturbance of the transmission of nerve controls on the neuromuscular plate. By-products of microorganisms in the intestine, which appear as a result of tryptophan processing in the diet, can limit the level of inflammation in the brain by the influence they have on microglial cells. The current research focuses on the influence that the gut microbiota has on microglial cells and astrocytes that play an important role in the health of the central nervous system. To reach these observations, the authors examined how intestinal microbiota and diet influence amelioration of paralysis in dogs. In conclusion, the link between the health of the microbiome and the health of the brain, shows how the microorganisms in the intestine influence the evolution of paralysis. Keywords: microbiome, intestinal dysbiosis, neuroimmunomodulation, paralysis, dog The motivation of the communication was the study of the influence of the canine intestinal microbiota on the health and the appearance of the neurological diseases. The research focuses on maintaining the balance of the normal intestinal microbiota and its interaction with those of two types of cells that play an important role in the health of the central nervous system: microglial cells and astrocytes. In this presentation, we will discuss the biological interaction on the intestinal-brain axis and explore how this communication may be involved in neurological diseases. Moreover, we highlight new ideas in altering the composition of the gut microbiota, which may appear as a promising therapeutic approach to treat CNS disorders. Recent specialist studies draw attention to the relationships between canine microbiome health and brain health, how the gut microbiota influences the appearance and evolution of neurological disorders. There are important factors in this interaction regarding the health of the gut and brain microbiota, as well as the maintenance of immune and neuronal cell communication. The new findings help us to understand more clearly how to care for intestinal epithelial cells that affect nerve cells. The microglial cells are an integral part of the immune system and are responsible for normal functions in the body. On the other hand, microglia can secrete substances with the protective role of neurons. Figure 1 Current studies refer to the modulation of the microbiota that influences microglial cells to prevent inflammation. Research into efforts for effective therapies may also apply to neurological diseases. There are several causes that can cause paralysis in dogs. Any process that disrupts the communication of the intestinal-brain axis can lead to loss of coordination and movement, inability to move. As in the human intestinal axis the brain can cause neurological disorders and in dogs it is possible that the dysbiosis of the intestinal microbiota may lead to the dysfunction of the transmission of nervous controls at the level of the neuromuscular plate. Paralysis in dogs can occur when the ability of nerve coordination of body movements is diminished or completely lost. The human gut contains 1013-1014 microorganisms, far more than the body's cells and 100 times more genes than the human genome. The weight of the microbiota is about 1 kg per adult. The vast majority of bacteria reside in the colon. The last decade has made remarkable progress in understanding the significant role that intestinal microbial metabolites play in modulating host health. Moreover, to fully utilize the potential of the gut microbiota for disease prevention, it is necessary to understand how dietary components and host genetics affect the production of different microbial metabolites (1 Zhang). However, little is known about how the gut microbiome influences the host's locomotion or the molecular and cellular mechanisms involved (2. Schretter). The literature has shown that bidirectional signaling between the brain and the gut microbiome involves multiple neurocrine and endocrine signaling mechanisms (3. Mayer). Fig 1 (Mayer) A link between the gut microbiota and the brain has long been suggested, but in recent decades, studies have begun to report the causal effects of the gut microbiota on the brain and host behavior, and basic molecular mechanisms have begun to be elucidated (4 Yano). Some animal studies have provided evidence that stress can disrupt the gut microbiota composition and affect host behavior. Indeed, much research has focused on serotonin as a key substance in gut-brain microbiota interactions. The gut microbiome-brain signal was at the center of countless researches (5 Hasiao). Evidence from multiple sclerosis and stroke models has suggested that changes in the gut microbiota may indirectly influence the central nervous system through effects on immune homeostasis and immune responses (6 Sampson). In fact, subsequent research has begun to discover other means of intestinal-brain communication, in particular, products derived from microorganisms that can directly or indirectly signal the nervous system. The presence of the intestinal microbiota, of the short-chain fatty acids produced in the intestine causes neuro-inflammation, motor deficiencies and α-synuclein pathology. Metagenomic analyzes were performed which indicated that the potential of microorganisms to synthesize certain neuroactive metabolites may also be correlated with mental well-being (7 Valles). The intestinal-brain axis provides the biochemical signaling that occurs between the gastrointestinal tract (GI tract) and the central nervous system (CNS). The term "gut-brain axis" is sometimes used to refer to the role of the gut microbiota in interaction, while the term "gut-microbiome-brain" axis explicitly includes the role of the gut microbiota in biochemical signaling events that occur between the GI tract and SNC (8 De Vedder). Limited, the intestinal-brain axis includes the central nervous system, neuroendocrine and neuroimmune systems, the hypothalamus-pituitary-adrenal (HPA) axis, the sympathetic and parasympathetic branches of the autonomic nervous system, including the enteric nervous system. The intestinal microbiota is the complex community of microorganisms that live in the digestive tract of humans and animals. The gut is a niche in which the human microbiota exists. In humans, the gut microbiota has the highest number of bacteria and the highest number of species compared to other areas of the body. The composition of the human gut microbiota changes over time, when the diet changes and, with the change of the general state of health. The intestinal-brain axis, a two-way neurobehavioral communication system is important for maintaining homeostasis and is regulated through the central and enteric nervous system and on the nerve, endocrine, immune and metabolic pathways, in particular through the HPA axis. This term has been extended to include the role of the gut microbiota as part of the "gut microbiome-brain" axis (10 Wang). Figure 2 The intestinal microbiota produces a range of neuroactive molecules, such as acetylcholine, catecholamines, γ-aminobutyric acid, histamine, melatonin and serotonin, which are essential for the regulation of intestinal peristalsis. Changes in the composition of the intestinal microflora due to diet, drugs or diseases are correlated with changes in circulating cytokine levels, some of which may affect brain function. Research on the intestinal-brain axis has traditionally been focused on the psychological state that influences the function of the GI tract. These recent discoveries regarding the new role of the gut microbiota in the gut-brain axis imply that the gut microbiota may be associated with brain functions, as well as with neurological diseases through the gut-brain axis (11 Chen). The aim of the study was to systematically review the effects of probiotics on the function of the central nervous system in animals and humans, to summarize the effective interventions (probiotic species, dose, duration). As many of the baseline studies have shown some efficacy of probiotics on CNS function, this context may guide and promote further preclinical and clinical studies (10. Wang). Recent studies suggest that many of these metabolites that derive from microbial transformation of dietary components have significant effects on physiological processes, such as intestinal and immune homeostasis, energy metabolism, vascular function and neurological behavior. The impact of microbiota metabolites on health and disease is discussed in detail and current strategies for modulating the levels of these metabolites for promoting human health are analyzed (1 Zhang). This detailed understanding of diet-microbiota-host interactions suggests significant possibilities for creating new therapeutic approaches, including selectively modifying the microbial production of molecules to promote human health and prevent disease (12 Holmes). The microbiota, the intestine and the brain communicate through the microbiota-gut-brain axis in a bidirectional way that involves the autonomic nervous system (13 Bonaz). A huge amount of data has highlighted a potential role of microbial dysbiosis in various chronic conditions (14 Lynch and Pedersen). The microbiota, intestine and brain communicate through the microbiota-intestinal-brain axis and a disturbance of this axis is involved in the pathophysiology of neurodegenerative disorders (15 Quigley). The brain and intestine communicate bidirectionally (13 Bonaz). Most of these microorganisms, including bacteria, archaea, fungi and viruses are in the human gastrointestinal tract and are generically referred to as the gut microbiota (16 Qianquan). Evidence suggests that the microbiota is involved in the physiology and pathology of cellular organisms and therefore has implications for both health and disease (17 Maynard). It has been reported that microglia protect the brain against various pathological disorders, by implicating in the activation of the immune response, phagocytosis and cytokine production. In addition, microglia regulates synaptic transmission, synaptic disruption and neuronal circuit formation, which are involved in homeostasis. Recent studies have shown that the microbiome has an influence on the properties and function of microglia (18-20 Pekny). Research on the secondary mediators of the gut microbiota, which acts in the processes of transforming tryptophan assimilated by the body in the diet, may limit inflammation in the microglial cells. There is a need for consensus on how to examine the gut microbiota and diet that may influence the onset of multiple sclerosis. The study showed that compounds resulting from tryptophan breakdown can cross the blood-brain barrier by activating the anti-inflammatory pathway that limits neurodegeneration. It is very likely that the mechanisms will be valid in the event of manifestation of other neurological diseases besides multiple sclerosis. All cases of canine paralysis are motivated for care and visit to the veterinarian. Symptoms of canine paralysis may vary depending on the cause. The paralysis of the posterior train may have several causes and the complexity of care required, appropriate treatment and thorough investigations to establish an accurate diagnosis are possible. The possible cause that can be related to the paralysis of the posterior train is the degeneration of the spinal cord that exists especially in the older dogs. The diagnosis is made in a veterinary clinic. It is possible to check how well you can stay on your feet, the reflex analysis test and the sensitivity to touch. A hemogram, biochemical blood tests, a drug test if it can cause a bacterial or viral infection, or a toxin are required. An X-ray of the spine is often needed, which may reveal an infection, or malformation, in the vertebrae or a disc that presses the spinal cord. Most have interrupted nerve pathways. Treatment for paralyzing dogs depends on the causes of the condition. Depending on the cause of the paralysis, the treatment given during the recovery period may be shorter or longer. If the gut microbiota of the dog is not healthy, the dog cannot be healthy. Bacteria in the gut microbiota have key functions in the dog's body. For example, bacteria in the gut of the dog are responsible for the production of many vitamins that help absorb nutrients. Intestinal bacteria help the absorption of vitamins and other micronutrients that are essential to the health of the dog, regulate immunity. The microbiota is an important part of the immune system and can increase or decrease inflammation in the body. Bacteria in the gut microbiome can be beneficial. If the gut microbiota is balanced, everything will be fine for the dog, but it can be messy and then the dog's health will suffer. A delicate balance lies between the two types of beneficial and harmful bacteria. The microbiome is most commonly affected by antibiotics. The problem with antibiotics is possible because they are destroyed without being able to discriminate against bacteria. This can only disturb the balance, but it can destroy the entire microbial species, only germs remain resistant. Dysbiosis occurs, and the intestinal mucosa becomes inflamed, increasing the permeability of the intestinal epithelium as a consequence of the passage of bacterial neurotoxins called lipopolysaccharides. These are in circulation reaching the liver, kidneys, heart and other organs causing chronic inflammation. Dysbiosis of the microbiome can cause hypersensitivity reactions, neurological diseases. Prebiotics help intestinal bacteria produce fatty acids that protect cells in the intestinal epithelium. 40 years ago, being psoriasis patient, to cure myself, I discovered a combination of medicinal plants that proved to be the only way to act on the internal causes that trigger and maintain this disease. Some of the plants used grow them personally, others are of spontaneous flora. Watching how the bees visit the flowers of the plants, I thought to use in addition to honey and pollen, propolis and other bee-keeping products (cinnamon sticks, pods). With the pollen of these plants and other ingredients, we created the product Polenoplasmin, which acts as a modulator of the gut microbiome in animals. After I healed my own dog that was paralyzed with the hind legs, I watched over 50 cases of paralyzed dogs, and the healing rate was over 80%. Negative results were recorded in paralyzed dogs for a long time (4-6) months.
http://www.deniplant.ro/polenoplasmin_catel.htm An interesting case of a puppy from Cyprus, who was hit by a car was broken in his spine and was paralyzed with his back legs. http://www.deniplant.ro/catelusa.mp4 https://youtu.be/OcQ2NXgZnXs For 4 months he was given Polenoplasmin, in addition to the physical recovery treatments and the dog was able to walk again. This puppy lives and walks alone and today as can be seen in the following video: Movie https://youtu.be/lwzywDfKsnI
(1) Paralysis in dogs being not only an inflammatory condition but also one of the muscular and nervous system, which affects approximately .....% of the canine population, must be treated multidisciplinary and personalized, the microbiome of each dog being a unique entity that responds in particular for allopathic and natural treatment. (2) The realization of functional foods (nutraceuticals) with a dual role of nutrition and health, is a desire of both food producers and those who care for the health of animals, as they can naturally modulate the activity of the canine microbiome, restore eubiosis, the processes of nerve cell recovery and healing of paralysis. Although it is known how and where prebiotics and probiotics work, it is necessary to find ways to personalize them according to the medical condition we want to solve, and their recommendation is not generally indicated. (3) Since we have first observations that prove the relationship between the modulation of the intestinal microbiome and human diseases, future research will focus on modulating the human intestinal microbiome with the help of dietary restrictions.
1. Zhang LS, Davies SS. Microbial metabolism of dietary components to bioactive metabolites: opportunities for new therapeutic interventions. Genome Med. 2016; 8 (1): 46. 2. Schretter CE, et al. A gut microbial factor modulates locomotor behaviour in Drosophila. Nature. 2018; 563: 402-406. 3. Mayer EA, Knight R, Mazmanian, SK, et al. Gut microbes and the brain: paradigm shift in neuroscience. J Neurosci. 2014; 34(46): 15490-15496. 4. Yano J, et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. 2015; 161: 264-276. 5. Hsiao EY, et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders Cell. 2013; 155: 1451-1463. 6. Sampson TR, et al. Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson' s disease Cell. 2016; 167: 1469-1480. 7. Valles-Colomer M, et al. The neuroactive potential of the human gut microbiota in quality of life and depression. Nat Microbiol. 2019; 4: 623-632. 8. De Vedder F, et al. Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell. 2014; 156: 84-96. 9. Clarke G, et al. Gut microbiota: the neglected endocrine organ. Mol Endocrinol. 2014; 28(8): 1221-1238. 10. Wang H, Lee IS, Braun C, Enck P. Effect of probiotics on central nervous system functions in animals and humans - a systematic review. J. Neurogastroenterol Motil. 2016; 22 (4): 589-605. 11. Chen X, D'Souza R, Hong ST. The role of gut microbiota in the gut-brain axis: current challenges and perspectives. Protein Cell. 2013; 4(6): 403-414. 12. Holmes E, Kinross J, Gibson GR, Burcelin R, Jia W, Pettersson S, et al. Therapeutic modulation of microbiota-host metabolic interactions. Sci Transl Med. 2012; 4(137): 137. 13. Bonaz B, Bazin T, Pellissier S The Vagus Nerve at the Interface of the Microbiota-Gut-Brain Axis. Front Neurosci. 2018; 12: 49. 14. Lynch S. V., Pedersen O. (2016). The human intestinal microbiome in health and disease. N. Engl. J. Med. 2016; 375: 2369-2379. 15. Quigley E. M. M. (2017). Microbiota-brain-gut axis and neurodegenerative diseases. Curr. Neurol. Neurosci. Rep. 2017; 17: 94. 16. Qianquan Ma, Changsheng Xing, Wenyong Long, Helen Y. Wang, Qing Liu, Rong-Fu Wang. Impact of microbiota on central nervous system and neurological diseases: the gut-brain axis. Journal of Neuroinflammation. 2019; 16(1): 53. 17. Maynard CL, Elson CO, Hatton RD, Weaver CT. Reciprocal interactions of the intestinal microbiota and immune system. Nature. 2012; 489: 231-241. 18. Pekny M, et al. Astrocytes: a central element in neurological diseases. Acta Neuropathol. 2016; 131: 323-345. 19. Nayak D, Roth TL, McGavern DB. Microglia development and function. Annu Rev Immunol. 2014; 32: 367-402. 20. Sofroniew MV, Vinters HV. Astrocytes: biology and pathology. Acta Neuropathol. 2010; 119: 7-35.
Figure 1 The human microbiome plays an important role in control of vital homeostatic mechanisms in the body. These include enhanced metabolism, resistance to infection and inflammation, prevention against autoimmunity as well as an effect on the gut–brain axis. SCFA, short-chain fatty acid. (https://commons.wikimedia.org/wiki/File:Microbiota_roles.png) Figure 2 The gut-brain microbiome axis
NATURAL MODULATION OF INTESTINAL AND CUTANATE MICROBIOME IN PATIENTS WITH PSORIASIS
1. Major (r) Giurgiu Gheorghe Deniplant Aide-Sante Biomedicine Center, Bucharest 2. Conf. Univ. Dr. Cojocaru Manole Titu Maiorescu University, Faculty of Medicine, Bucharest
Summary: Through the modulatory effect on the body's immune system, the intestinal and cutaneous microbiome exert influences on the skin homeostasis. The microbiome exhibits beneficial actions in the body under conditions of eubiosis, however, when dysbiosis occurs, the microbiome can trigger various autoimmune, metabolic, neurological conditions (eg allergies, eczema, asthma, psoriasis, diabetes, central nervous disorders). This can happen when fragments of microbial DNA cross the intestinal barrier and reach the bloodstream and even into the nervous system. Although modern medicine is trying to modulate the microbiome, to use it for the treatment of certain conditions, this has not been achieved so far. By using antibiotics and other medicines, the microbiome can be severely affected by affecting the health of the body. In the last five years, discoveries in the field of genetics and immunology have allowed the initiation of new studies on the role of the intestinal and skin microbiome in patients with psoriasis. Using natural herbal remedies and fruit tree buds, we developed a natural modulator of the intestinal and cutaneous microbiome with which it was able to slow down and even stop the evolution of psoriasis, without ointments or other drugs and without food restrictions. Thus, the path has been opened to the realization of functional foods (nutraceuticals) with dual role: nutrition and health, which can naturally modulate the activity of the human microbiome, restore the eubiosis, the processes of cell restoration and healing of the organism.
Keywords: microbiome, psoriasis, autoimmune diseases, natural remedies, functional foods (nutraceuticals)
Introduction: (1) The paper presents new ways of preventing and treating psoriasis disease through the natural modulation of the intestinal and skin microbiome. (2) Although psoriasis is a disease that has been present for hundreds of years, dermatology treats it as a strict skin condition and for this reason the treatments are generally aimed at healing the surface skin. For this reason the cure of the disease is only partial, with multiple relapses and extensions. Although we are trying to find an effective treatment of internal causes, so far this has not been achieved and for this reason the psoriasis disease is classified as incurable. (3) With the help of phytotherapy and gemotherapy, respectively with medicinal plants and fruit buds, acting on the dysbiosis of the intestinal and skin microbiome, it can intervene on the immune system and the process of apoptosis of the epithelial cells and by triggering self-healing reactions in the body, psoriatic lesions disappear by themselves. (4) During the last five years the discoveries in the genetic and immunological field, have allowed the initiation of new studies regarding the role played by the skin and intestinal microbiome in the patients with psoriasis. Thus, Golden Staphylococcus or Pyogenes Streptococcus may induce maintenance or exacerbation of psoriasis lesions. An important role in the occurrence and maintenance of psoriasis lesions is also the microbial flora of the intestine, through the systemic effects exerted by it. Studies have shown increased bacterial diversity in patients with psoriasis compared to healthy subjects, with reduced Actinobacter colonization and predominant cutaneous Firmicutes, which may characterize a phenotype specific to chronic inflammation found in psoriasis. When dysbiosis of the gut microbiome occurs, microbes and metabolites in the gut induce regulatory T cell and lymphocyte reactions, which facilitate an anti-inflammatory response. Studies have also been performed on translocation of some fragments of transgenic DNA into blood samples in patients with psoriasis. This suggests that new outbreaks of psoriasis may be related to the presence of bacterial DNA circulating in the blood, originating from the intestinal lumen. Healthy intestinal bacterial composition may reduce intestinal permeability and the risk of bacterial DNA translocation.
Literature review on the topics covered In the history of mankind, often after a great discovery, it took many years for decision makers in that field to accept and promote the value of discovery. This is what happened with the discovery of the microbiome with which we are contemporaries. In 1958 the biologist Joshua Lederber defined the term "microbiome", for which, at the age of 33, he received the Nobel Prize. Why, for 50 years, the medical world has not given importance to this discovery, and it was not until 2008 that the European project entitled MetaHIT was launched, which led to the discovery that people also differ by the bacteria that live through them, not just by blood type elements. Dusko Ehrlich, (1) project coordinator at MetaHIT, explains why the microbiome will play an important role in personalized medicine: ''by analyzing the genes of the organisms that live in us, physicians can identify unique aspects of each patient, which will allow conception of personalized treatments''. Another microbiologist, Julian Davies, (2) from the University of British Columbia, states that: "the effort for a better understanding of the microbiome is the most important scientific project of all time". In 2018 researchers from three countries, Belgium, Holland and Malta wrote a well-documented psoriasis and microbiota: ''Psoriasis and Microbiota: A Systematic Review'' (3). The purpose of the paper was that, through a thorough review of the literature, to discuss the skin and intestinal microbiota and to redefine their role in the pathogenesis of psoriasis.
Theoretical foundation Recent studies (2015-2016) of Japanese specialists confirm the importance of the gut microbiome on antitumor immunotherapy and emphasize the importance of eubiosis (8.9). The skin microbiome influences the functions of T cells in the skin by producing IL-2 but also IL-17 (10) and modulates memory T cells (11). Dysbiosis of the skin microbiome can be caused by changes in the skin microbiome, alteration of the skin barrier and immune functions, but also dysbiosis of the intestinal mycobiome. Since 2010 researchers have been seeking to find oral prebiotics and probiotics with which to influence the axis of the intestine-nervous system-skin (12).
Content of the article As a result of my own experience, during which for 7 years I was ill with psoriasis, I learned how traumatic this disease can be and what psycho-emotional implications it can have. Although we did repeated treatments in the Central Military Hospital, at first all the lesions disappeared, but as the disease was chronic and the lesions were on larger areas on the body, even after long-term treatments, the injuries did not disappear completely. The fact that the doctors told me that this disease is incurable, made me look for solutions in herbal medicine and gemotherapy. After two and a half years of searching and testing on the body, the medicinal plants and buds of the fruit trees have proved to be the only effective remedy in my case against the internal causes that trigger and sustain this disease. After obtaining a patent for a process for obtaining a herbal extract for the treatment of psoriasis, we founded the Speranța Medical Foundation with the aim of supporting the activities of those who know the mysteries of nature in the field of medicine and their application for human benefit. Thus, with the help of scientifically used medicinal plants, the foundation has shown that certain so-called incurable diseases (for allopathic medicine) can be ameliorated or even cured. The cases of cases solved in Romania, and dozens of cases abroad, as well as obtaining the gold medal at the '97 technical news salon, have proved this. In 2005 the natural remedies discovered by me receive a name: Deniplant - Deniplant brand with the slogan "Health above all" is registered at OSIM-Romania. Four years later the Deniplant trademark becomes a Community trademark and the current EUIPO (Office of the European Union for Intellectual Property) is registered at OHIM. The use of the natural remedies Deniplant by the patients attending recovery sessions based on the treatment from Sovata, emphasized that by intervening on the skin with water and mud from Lake Ursu, the cure of the disease was much faster. Seeing these results, we began the study to find an explanation of the phenomena that occur within the body and which lead to the healing of these conditions. Following for one year the courses organized by Prof. Dr. Manole Cojocaru (13) in which the human microbiome was presented, I came to the conclusion that these natural remedies discovered by me act on the human microbiota that influence autoimmune, metabolic and neurological disorders. The use of water and sludge from Sovata, salt water from Călimănești-Căciulata or mud from Techirghiol, allowed the modulation of the skin microbiome to trigger the reactions needed to heal the skin. However, following the patients who used Deniplant tea in parallel with the aforementioned procedures, we concluded that only modulation of the skin microbiome cannot definitively solve the problem of psoriasis, if it does not intervene on the gut microbiome. The intestinal microbiome triggers the modulation of the skin microbiome and if it is influenced from the outside, the results can be amplified (14). This is also deduced from the fact that in psoriasis when intervening with ointments or other medicines for external use, the skin microbiome is affected, but in the long term the changes at that level can negatively affect the intestinal microbiome and hence those reactions of rebaund and generalization of the disease. That is why I think we are facing a new discovery, namely a natural modulator of the human microbiome. This year, in collaboration with the Aide-Sante Clinic, we set up a Biomedicine Center where we are trying to highlight with medical analysis and evidence this possibility of natural modulation of the human microbiome with the help of food.
Conclusions (1) Psoriasis being a common inflammatory skin condition, affecting about 3% of the world population, must be treated multidisciplinary and personalized, the microbiome of each patient being a unique entity that responds in particular to the allopathic and naturalistic treatment. (2) The realization of functional foods (nutraceuticals) with a dual role of nutrition and health, is a desire of both food producers and those who care about human health, because they can naturally modulate the activity of the human microbiome, restore eubiosis, the processes of cellular recovery and healing of the body. Although it is known how and where prebiotics and probiotics work, it is necessary to find ways to personalize them according to the medical condition we want to solve, not being recommended in general. (3) Future research will focus on the relationship between the human microbiome and cellular apoptosis in other diseases as well as the modulation of the intestinal microbiome with the help of dietary restrictions.
It is already known that the human microbiome influences the health of all people. Medications in some patients give results, in others not, because each of us has a different microbiome. Food plays an important role in modulating and influencing the microbiome. To measure the state of the microbiome we will create a device that will analyze the expired air. The EGO application has the role of monitoring the factors that influence the microbiome. Deniplant already creates natural modulators of the microbiome for autoimmune, metabolic and neurological disorders. Nutraceuticals will be the foods of the year 2050 that will have a dual role, nutrition and healing
NATURAL NEUROIMUNOMODULATION IN CORONAVIRUS INFECTION
GIURGIU GHEORGHE1, COJOCARU MANOLE2
1Deniplant-Aide Sante Medical Center, Biomedicine, Bucharest, 012371, Romania
2Titu Maiorescu University, Faculty of Medicine, Bucharest, 031593, Romania
email correspondence author: email@example.com
Current state of knowledge
During these months of 2020, all the attention of doctors and researchers is directed towards discovering the extremely efficient methods of treating Covid-19 infected patients. As soon as it appeared at the end of 2019, SARS-CoV-2, renamed Covid-19 a few weeks later by the Health Organization (WHO), looked like a flu, but the virus actually produced a much more complex disease. Covid-19 infection is a very complex respiratory, renal, neurological disease. Covid-19 infection causes symptoms such as dry cough, respiratory problems, fever, but there are lesser known symptoms that may indicate the presence of Covid-19 in some patients. Among these less well-known signs of illness are digestive problems, chills, confusion, headaches. About 8% of patients infected with Covid-19 have frequent headaches, according to a medical study published in the Lancet. Also, dizziness is quite common, if it is intense, it is most likely a patient with a more severe form of Covid-19 infection. Disease and confusion may be the only symptoms that prove Covid-19 presence in the body. A report from a health care center in Washington showed that of 35% of people who were Covid-19 positive, half had no symptoms. Lymph node follicles are the most important tissue reservoir for Covid-19. In asymptomatic patients, Covid-19 is present only in the lymph, where the contact with the immune system begins where the virus infects the follicular CD4+ T cells (Th cells) present there and the existing bacteria, and if the virus does not circulate further the disease does not appear. If the virus reaches the bloodstream (1-2% of cases), complications, inflammatory cytokine storm and hypercoagulability occur. Dysbiosis of the nasopharyngeal microbiome attracts dysbiosis of the intestinal microbiome and activation of the intestinal microbiome-brain axis. If you intervene quickly at the first sign of disease with the modulation of the activity of the microbiome, the implication of the immune system (neuroimmunomodulation) is suppressed the appearance of the disease. There is the microbiome: buccal, nasal, intestinal, cardiac, dermal, even the microbiome in the brain with which Covid-19 interacts. When the evolution is complicated, it is necessary to intervene with drug treatment to support the affected organs. Although there is renal impairment, coronaviruses and their traces were not found in the urine of patients. Knowing that the infection also causes digestive symptoms, coronaviruses have been shown in faeces. It is said that in 1-2% of cases Covid-19 reaches the bloodstream. Some patients have symptoms such as confusion, restlessness, anxiety, malaise. These manifestations raise questions about the impact of Covid-19 on the brain and nervous system. Neurological symptoms are manifested by loss of smell, taste, neurological pain, even thrombotic strokes. In patients with confusion or agitation, brain scans revealed inflammatory processes. Virulent and deadly, Covid-19 even spreads to the brain in some patients. The microbiome is essential for promoting immune function for disease prevention and control. Specifically, with regard to viral infections, there must be an adequate immune response to protect the body. The intestinal microbiota with low diversity will consequently lead to a deficient immune function. Eighty percent of immune cells reside in the gastrointestinal tract. Strokes and cases of encephalitis have been reported. To a lesser extent, the impairment of the olfactory nerve has been described, which causes difficulties in the perception of smell, taste. Any process that disrupts bowel-brain communication can lead to neurological complications. It seems that some of the patients have serious problems of mental disorder, confusion that even generates forgetting where they are. This state of disorder of spatio-temporal orientation due to lack of oxygen in the blood, many patients end up having the brain (with microthrombosis) more affected than the lungs. Dysbiosis of the intestinal microbiota may lead to impaired brain function. The microbiota, the intestine and the brain communicate through the microbiota-intestine-brain axis in a bidirectional way. With the help of natural remedies the brand Deniplant the authors have made several products for autoimmune, metabolic and neurological disorders that act as immunomodulators of the human microbiome. We assume that the Covid-19 virus creates a dysbiosis of the intestinal microbiome. Virologists have reported that Covid-19 can affect the brain and nervous system (this link has been seen with other viruses). Viruses can affect the brain in two main ways. The first pathway is triggered by an abnormal immune response, called a "cytokine storm", which causes inflammation of the brain: this process is called autoimmune encephalitis. The second pathway consists of a direct infection of the brain and is called viral encephalitis. The brain is protected by the blood-brain barrier to block invasive substances, but it can sometimes be crossed. Some researchers have hypothesized that the nose may be a pathway to the brain, as odor loss is a common symptom for many patients with Covid-19, but the theory is not verified and many patients who lose their odor have no neurological problems. serious. The intestinal microbiota may influence the permeability of the blood-brain barrier. Project motivation The reason why the discovery could be important is to continue learning how the gut microbiome can influence brain function and behavior, and the fact that it may have its own population of bacteria could be a real benchmark. A healthy gut microbiome is crucial in creating an adequate response to coronavirus. A diverse microbiome is a healthy microbiome, which contains many different species that each play a role in immunity and health. Specialists from all over the world are trying to unravel the mysteries around the coronavirus, trying to understand how it works in the body. These neurological manifestations are thought to raise questions about the impact of Covid-19 on the brain and nervous system. The motivation of the project is the study of the influence of the intestinal microbiota in terms of health and the appearance of symptoms in Covid-19 infection. In all the conditions that are determined by Covid-19 there is a close link between the microbiome and these conditions. The diversity of the microbiome decreases as we age, it could help to explain some of the symptoms related to age, changes in immune responses, so it is necessary to maintain a healthy microbiome throughout life. If the patient feels confused, if he has trouble thinking, there are reasons to analyze the bidirectional bowel-brain relationship. The main objective Increased immunity is the best barrier to viruses, including Covid-19. The most important barrier in its pathway is a competent immune system. A varied diet is essential for immunity. Natural therapies (neuroimmunomodulation) targeting the microbiome may play a role in the fight with Covid-19. The research focuses on the topic of maintaining the balance of the normal intestinal microbiota and its interaction with Covid-19. Specific objectives The diagnosis of Covid-19 infection is currently based on the detection of viral nucleic acid by real-time PCR in nasopharyngeal exudate, brohoalveolar lavage or tracheobronchial aspiration. In this project, we will discuss the biological interaction on the intestinal-brain microbiome axis and explore how this communication may be involved in neurological complications in Covid-19 infection. We aim to highlight new ideas in changing the composition of the intestinal microbiota, which may occur as a result of Covid-19 infection, and to try a promising therapeutic approach to treat CNS disorders by neuroimmunomodulation using natural remedies (bacteriophage Deniplant). Expected results Currently the treatment is symptomatic and supportive, there is no etiological treatment. The new findings will help us better understand how to care for the patient infected with Covid-19 and the nerve complications that occur. It was surprisingly concluded that probiotics could be useful in therapy against Covid-19. The composition of the human gut microbiota changes over time, when the diet changes and with the change of health. The authors are convinced that in the near future natural remedies that act as neuroimmunomodulators of the intestinal microbiome will be effective in the infection with Covid-19, thus achieving the desire to create those foods with a dual role of function, nutrition and health. Project evaluation The present studies refer to the immunomodulation of the intestinal microbiota that influences the immune system to prevent the storm of inflammatory cytokines in the brain. The brain and gastrointestinal tract are tightly connected to form a two-way neuro-neural communication system. The communication between the intestine and the brain is based on the intestine-brain axis, which is so well established that the functional state of the intestine is always linked to the functional state of the brain. These findings suggest the role of the intestinal microbiome in modulating Covid-19 infection. The results of the studies are promising, but so far there are no certainties. Too many people talk about Covid-19 without relying on scientific data and without proper knowledge.