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SARS-CoV-2 and immune-microbiome interactions: Lessons from respiratory viral infections.
Cyprian, F, Sohail, MU, Abdelhafez, I, Salman, S, Attique, Z, Kamareddine, L, Al-Asmakh, M
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases. 2021;105:540-550
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped RNA beta-coronavirus. This virus caused the coronavirus disease 2019 (COVID-19) pandemic. The aim of this review was to investigate the relationship between microbiota, immunity, and COVID-19, with particular focus on how microbiome-associated immune crosstalk can shape outcome of COVID-19. The study included 118 articles which investigated or reviewed COVID-19 or coronavirus and the microbiome of the gut or respiratory tract. Findings indicate that: - an over-activated immune system leads to massive pulmonary damage in COVID-19 patients. - the effect of aging and comorbidities, and the use of antibiotics have an effect on the diversity of the microbiota. - the milieu of gut flora can exert influence on pulmonary immune responses. - a unique cross-talk exists between the pulmonary and gut microbial compartments. Authors conclude by highlighting the need of further studies that delineate the role of the microbiota and their products in the immune dysregulation observed in SARS-CoV-2 infections.
Abstract
By the beginning of 2020, infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had rapidly evolved into an emergent worldwide pandemic, an outbreak whose unprecedented consequences highlighted many existing flaws within public healthcare systems across the world. While coronavirus disease 2019 (COVID-19) is bestowed with a broad spectrum of clinical manifestations, involving the vital organs, the respiratory system transpires as the main route of entry for SARS-CoV-2, with the lungs being its primary target. Of those infected, up to 20% require hospitalization on account of severity, while the majority of patients are either asymptomatic or exhibit mild symptoms. Exacerbation in the disease severity and complications of COVID-19 infection have been associated with multiple comorbidities, including hypertension, diabetes mellitus, cardiovascular disorders, cancer, and chronic lung disease. Interestingly, a recent body of evidence indicated the pulmonary and gut microbiomes as potential modulators for altering the course of COVID-19, potentially via the microbiome-immune system axis. While the relative concordance between microbes and immunity has yet to be fully elucidated with regards to COVID-19, we present an overview of our current understanding of COVID-19-microbiome-immune cross talk and discuss the potential contributions of microbiome-related immunity to SARS-CoV-2 pathogenesis and COVID-19 disease progression.
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Updated Review and Meta-Analysis of Probiotics for the Treatment of Clinical Depression: Adjunctive vs. Stand-Alone Treatment.
Nikolova, VL, Cleare, AJ, Young, AH, Stone, JM
Journal of clinical medicine. 2021;10(4)
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Major depressive disorder is a common, complex, and heterogeneous illness that is characterized by persistent low mood and anhedonia, and a combination of sleep disturbances, changes in appetite, feelings of worthlessness or guilt, poor concentration, and suicidal ideation. The aim of this study was to identify and evaluate all current evidence from randomised controlled trials on the efficacy of probiotics in reducing depressive symptoms among people with clinical depression. This study is a review and meta-analysis of randomised controlled trials which included seven studies for qualitative and quantitative analysis. Results demonstrate that probiotics significantly reduce depressive symptoms after eight weeks of use, but only when used in addition to an approved antidepressant. Authors conclude that their findings support the clinical use of probiotics in depressed populations and provides an insight into the mode of administration more likely to yield antidepressant effects.
Abstract
Recent years have seen a rapid increase in the use of gut microbiota-targeting interventions, such as probiotics, for the treatment of psychiatric disorders. The objective of this update review was to evaluate all randomised controlled clinical trial evidence on the efficacy of probiotics for clinical depression. Cochrane guidelines for updated reviews were followed. By searching PubMed and Web of Science databases, we identified 546 new records since our previous review. A total of seven studies met selection criteria, capturing 404 people with depression. A random effects meta-analysis using treatment type (stand-alone vs. adjunctive) as subgroup was performed. The results demonstrated that probiotics are effective in reducing depressive symptoms when administered in addition to antidepressants (SMD = 0.83, 95%CI 0.49-1.17), however, they do not seem to offer significant benefits when used as stand-alone treatment (SMD = -0.02, 95%CI -0.34-0.30). Potential mechanisms of action may be via increases in brain-derived neurotrophic factor (BDNF) and decreases in C-reactive protein (CRP), although limited evidence is available at present. This review offers stronger evidence to support the clinical use of probiotics in depressed populations and provides an insight into the mode of administration more likely to yield antidepressant effects.
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Gut and Reproductive Tract Microbiota Adaptation during Pregnancy: New Insights for Pregnancy-Related Complications and Therapy.
Siena, M, Laterza, L, Matteo, MV, Mignini, I, Schepis, T, Rizzatti, G, Ianiro, G, Rinninella, E, Cintoni, M, Gasbarrini, A
Microorganisms. 2021;9(3)
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During pregnancy, several adaptations occur in the female organism. In fact, from fertilization until delivery, the maternal body changes and activates a series of physiological transformations to welcome the new life. The microbiota as a component of human bodies is subject to these modifications. This study is a review that focused on gut and reproductive tract microbiota variations during physiologic pregnancy and in case of pregnancy complications, particularly gestational diabetes mellitus (GDM), pre-eclampsia (PE), and preterm birth (PTB). Results show that: - during pregnancy, major changes have been seen in mothers’ gut microbiota. Between the first and third trimester of pregnancy, to support the foetus growth, there is a shift towards communities of microbes implicated in energy production and storage. - in nonpregnant women, vaginal microbiota could be classified into five major types, representing the community state types. - meconium’s microbes seems to be dominated by the Enterobacteriaceae family, suggesting prenatally stepwise colonization. - gut microbiota may contribute to enhanced insulin resistance in early pregnancy (1st and 2nd trimester). - microbiota imbalances in PE women are related not only with blood pressure levels but also with markers of kidney dysfunction. Thus, it is of key importance to understand the role of microbiota and other factors involved in the etiopathogenesis of PE - dysbiosis is related to PTB (however, further studies are necessary to better understand the correlation between this pregnancy complication and the specific microbiota alteration). Authors conclude that microbiota modulation could be a novel strategy to reduce the morbidity and mortality related to pregnancy complications in the future.
Abstract
Pregnancy is characterized by maternal adaptations that are necessary to create a welcoming and hospitable environment for the fetus. Studies have highlighted how the microbiota modulates several networks in humans through complex molecular interactions and how dysbiosis (defined as quantitative and qualitative alterations of the microbiota communities) is related to human pathologies including gynecological diseases. This review analyzed how maternal uterine, vaginal, and gut microbiomes could impact on fetus health during the gestational period. We evaluated the role of a dysbiotic microbiota in preterm birth, chorioamnionitis, gestational diabetes mellitus and pre-eclampsia. For many years it has been hypothesized that newborns were sterile organisms but in the past few years this paradigm has been questioned through the demonstration of the presence of microbes in the placenta and meconium. In the future, we should go deeper into the concept of in utero colonization to better understand the role of microbiota through the phases of pregnancy. Numerous studies in the literature have already showed interesting results regarding the role of microbiota in pregnancy. This evidence gives us the hope that microbiota modulation could be a novel strategy to reduce the morbidity and mortality related to pregnancy complications in the future.
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Contribution of Lactobacillus iners to Vaginal Health and Diseases: A Systematic Review.
Zheng, N, Guo, R, Wang, J, Zhou, W, Ling, Z
Frontiers in cellular and infection microbiology. 2021;11:792787
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The vaginal microbiome is an important contributor to vaginal health. Here the dominance of Lactobacilli species, alongside their antimicrobial compounds play a critical role in contributing and protecting the vaginal milieu. Conversely the disruption or absence of Lactobacilli dominance is frequently associated with vaginal disease and infections. One of the Lactobacilli species prevalent in the vaginal microbiome is Lactobacillus iners. It was long overlooked in research due to it being so difficult to culture, and it was first identified in 1999 thanks to DNA sequencing. Researchers since discovered that the relationship between L. iners and vaginal health is far more complicated and ambiguous compared to the other Lactobacilli species. This systematic review explores the current knowledge of the characteristics of L. iners and its role in vaginal health and disease. The article discusses L. iners identification, genetic make up and differences to other Lactobacilli species and how they relate to vaginal health. The article also summarizes L. iners nutrient requirements and its role in diseases like dysbiosis, bacterial vaginosis, sexually transmitted infections and biofilm formation. Furthermore the authors look at the relation between L. iners and premature birthing, fertility and menstrual cycles. A final section in discusses the antimicrobial and immune sytem activating qualities of L. iners. In light of all these findings the authors describe L . iners as a very unique Lactobacilli due to its unusual characteristics. Whether L. iners is beneficial or pathogenic for the host remains controversial, as it can adapt to high and low pH environment and is seen in health and equally dysbiotic states of infection. Hence some describe it as a transitional species that colonizes the vagina after disturbances. It may be a risk factor for infections by contributing to the onset and maintenance of dysbiotic disturbances. Further studies are needed to clarify the role of L. iners and its role on vaginal health and whether it could serve as a biomarker for vaginal inflammation. This article is a useful summary about the characteristics and role of L. iners in vaginal health in disease.
Abstract
Lactobacillus iners, first described in 1999, is a prevalent bacterial species of the vaginal microbiome. As L. iners does not easily grow on de Man-Rogosa-Sharpe agar, but can grow anaerobically on blood agar, it has been initially overlooked by traditional culture methods. It was not until the wide application of molecular biology techniques that the function of L. iners in the vaginal microbiome was carefully explored. L. iners has the smallest genome among known Lactobacilli and it has many probiotic characteristics, but is partly different from other major vaginal Lactobacillus species, such as L. crispatus, in contributing to the maintenance of a healthy vaginal microbiome. It is not only commonly present in the healthy vagina but quite often recovered in high numbers in bacterial vaginosis (BV). Increasing evidence suggests that L. iners is a transitional species that colonizes after the vaginal environment is disturbed and offers overall less protection against vaginal dysbiosis and, subsequently, leads to BV, sexually transmitted infections, and adverse pregnancy outcomes. Accordingly, under certain conditions, L. iners is a genuine vaginal symbiont, but it also seems to be an opportunistic pathogen. Further studies are necessary to identify the exact role of this intriguing species in vaginal health and diseases.
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Current Perspectives on Gut Microbiome Dysbiosis and Depression.
Capuco, A, Urits, I, Hasoon, J, Chun, R, Gerald, B, Wang, JK, Kassem, H, Ngo, AL, Abd-Elsayed, A, Simopoulos, T, et al
Advances in therapy. 2020;37(4):1328-1346
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The gut microbiome has been implicated in several neurological disorders; however exact mechanisms are still not fully understood. This review of recent studies, aimed to investigate the relationship between an imbalanced gut microbiome and depression. The authors first looked at the epidemiology of disease, concluding that significant burden needs to be assessed through improved preventative measures. This will depend upon the correct identification of risk factors, and the study focused on the role of the gut microbiome in this through animal and human studies. Imbalances in inflammation through altered gut microbiota, depleted biodiversity and stress induced microbiome changes were all implicated in the development of depression. It was concluded that studies on the role of microbiota in depression remain promising but are small and follow many different methodologies. This study could be used by healthcare professionals to better understand the role of gut microbiota in the development of depression and that ensuring a healthy gut may improve symptoms.
Abstract
The human gut microbiome partakes in a bidirectional communication pathway with the central nervous system (CNS), named the microbiota-gut-brain axis. The microbiota-gut-brain axis is believed to modulate various central processes through the vagus nerve as well as production of microbial metabolites and immune mediators which trigger changes in neurotransmission, neuroinflammation, and behavior. Little is understood about the utilization of microbiome manipulation to treat disease. Though studies exploring the role of the microbiome in various disease processes have shown promise, mechanisms remain unclear and evidence-based treatments for most illnesses have not yet been developed. The animal studies reviewed here offer an excellent array of basic science research that continues to clarify mechanisms by which the microbiome may affect mental health. More evidence is needed, particularly as it relates to translating this work to human subjects. The studies presented in this paper largely demonstrate encouraging results in the treatment of depression. Limitations include small sample sizes and heterogeneous methodology. The exact mechanism by which the gut microbiota causes or alters neuropsychiatric disease states is not fully understood. In this review, we focus on recent studies investigating the relationship between gut microbiome dysbiosis and the pathogenesis of depression. This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors.
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Gut Microbiome and Depression: How Microbes Affect the Way We Think.
Limbana, T, Khan, F, Eskander, N
Cureus. 2020;12(8):e9966
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Recent findings have shown that a healthy gut microflora transmits signals to the brain through various pathways, namely the gut-brain axis. With the gut and brain working in a bidirectional relationship, emerging research suggests this could potentially impact stress, anxiety, depression and cognition. Therefore the aim of this review was to determine the role of the gut microbiome in mental health and depression. A total of 26 articles were reviewed and based on these articles, a strong link exists between the gut microbiome and its impact on mental health. Additionally, the literature supports the notion that the gut-brain axis serves as an essential pathway. Based on these findings, the authors agree there is a strong association between the gut microbiome and mental health, while also acknowledging the need to establish a causal link between these two entities. The authors conclude that the microbiome is a promising approach when considering the prevention, treatment and management of mental health diseases in the future.
Abstract
The gut microbiome serves an important role in the human body. Reportedly, one of the benefits of these microflora is on mental health. Once established, food and other dietary sources that enhance quality microbiome content in our gastrointestinal system will be a significant consideration in individuals' day to day lives. This literature review conducted a PubMed search for studies about the gut microbiome and its relation to depression. In using several Medical Subject Heading (MeSH) keywords, relevant literature was selected. A total of 26 articles were selected after applying the inclusion and exclusion criteria, and after checking the articles' accessibility. This literature would like to establish the role of the gut microbiome in depression. This study's findings showed that there is a strong association of microbiome function to mental well-being.
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Gut microbes in neurocognitive and mental health disorders.
Halverson, T, Alagiakrishnan, K
Annals of medicine. 2020;52(8):423-443
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Adequately and effectively treating and managing neurocognitive disorders remains a challenge. Increasing evidence suggests gut microbes may contribute to common mental health disorders through the microbiota-gut-brain axis, and better understanding this interaction could lead to improved clinical outcomes. The aim of this review is to discuss the impact of the gut microbiome on neurocognitive and mental health disorders and the mechanisms by which they act. This review reveals that the gut microbiome can influence brain and intestinal cells and that there is an association between gut dysbiosis with different mental health and neurocognitive disorders. Additionally, evidence shows the antimicrobial effect of current pharmaceutical treatments used in mental disorders may adversely affect the gut microbiome. Based on these findings, the authors conclude the gut microbiome is likely involved in the pathophysiology of neurocognitive and mental health conditions. Treatment strategies focusing on the gut microbiome may have a role in the treatment and management of mental health disorders, however further evidence is needed before applying these strategies in clinical practice.
Abstract
INTRODUCTION As individuals age, the prevalence of neurocognitive and mental health disorders increases. Current biomedical treatments do not completely address the management of these conditions. Despite new pharmacological therapy the challenges of managing these diseases remain.There is increasing evidence that the Gut Microbiome (GM) and microbial dysbiosis contribute to some of the more prevalent mental health and neurocognitive disorders, such as depression, anxiety, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), schizophrenia, bipolar disorder (BP), and dementia as well as the behavioural and psychological symptoms of dementia (BPSD) through the microbiota-gut-brain axis. Methodology: Scoping review about the effect of gut microbiota on neurocognitive and mental health disorders. RESULTS This scoping review found there is an evolving evidence of the involvement of the gut microbiota in the pathophysiology of neurocognitive and mental health disorders. This manuscript also discusses how the psychotropics used to treat these conditions may have an antimicrobial effect on GM, and the potential for new strategies of management with probiotics and faecal transplantation. CONCLUSIONS This understanding can open up the need for a gut related approach in these disorders as well as unlock the door for the role of gut related microbiota management. KEY MESSAGES Challenges of managing mental health conditions remain in spite of new pharmacological therapy. Gut dysbiosis is seen in various mental health conditions. Various psychotropic medications can have an influence on the gut microbiota by their antimicrobial effect.
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You Are What You Eat-The Relationship between Diet, Microbiota, and Metabolic Disorders-A Review.
Moszak, M, Szulińska, M, Bogdański, P
Nutrients. 2020;12(4)
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The gut microbiota (GM) is a collection of microorganisms living in the digestive tract of humans, which if unbalanced, may have a role in the development of certain disorders such as type 2 diabetes and obesity. A number of factors can imbalance the gut microbiota, one of the main being diet. This review paper of 190 papers aimed to summarise the relationship between GM, diet and modifiable diseases such as type 2 diabetes and obesity. Dietary components and the role of carbohydrates, protein and fats in shaping the GM were discussed. It was determined that carbohydrates have the greatest influence, with simple carbohydrates such as the sugars fructose and sucrose having a negative impact and the more complex forms being beneficial. Diet types were also reviewed. Vegetarian and vegan diets appear to increase the diversity of the GM, the Mediterranean diet changes the species balance, and the Western diet imbalances the GM causing diseases such as heart disease. Interestingly the literature points towards a negative impact of the gluten free diet. Diseases such as type 2 diabetes, obesity and increased fats in the blood all display an imbalanced GM causing increased energy harvest from food and disruption of various energy pathways in the body. It was concluded that a balanced diet rich in fruit, vegetables, fibre and healthy fats can promote GM diversity and activity. This study could be used by health care professionals to understand the importance of certain dietary components to promote GM diversity in order to reduce the risk of diseases such as obesity and type 2 diabetes.
Abstract
The gut microbiota (GM) is defined as the community of microorganisms (bacteria, archaea, fungi, viruses) colonizing the gastrointestinal tract. GM regulates various metabolic pathways in the host, including those involved in energy homeostasis, glucose and lipid metabolism, and bile acid metabolism. The relationship between alterations in intestinal microbiota and diseases associated with civilization is well documented. GM dysbiosis is involved in the pathogenesis of diverse diseases, such as metabolic syndrome, cardiovascular diseases, celiac disease, inflammatory bowel disease, and neurological disorders. Multiple factors modulate the composition of the microbiota and how it physically functions, but one of the major factors triggering GM establishment is diet. In this paper, we reviewed the current knowledge about the relationship between nutrition, gut microbiota, and host metabolic status. We described how macronutrients (proteins, carbohydrates, fat) and different dietary patterns (e.g., Western-style diet, vegetarian diet, Mediterranean diet) interact with the composition and activity of GM, and how gut bacterial dysbiosis has an influence on metabolic disorders, such as obesity, type 2 diabetes, and hyperlipidemia.
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Non-Systematic Review of Diet and Nutritional Risk Factors of Cardiovascular Disease in Obesity.
Rychter, AM, Ratajczak, AE, Zawada, A, Dobrowolska, A, Krela-Kaźmierczak, I
Nutrients. 2020;12(3)
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Nutrition is a major factor influencing obesity associated heart disease risk, however many people with this disease do not follow nutritional recommendations. This review of 155 studies aimed to summarise dietary aspects of heart disease prevention. The paper began by outlining the role of obesity through the development of other disorders that contribute to heart disease, such as type 2 diabetes, high blood pressure and blood sugar imbalance. The quantity and distribution of fat tissue also can contribute to heart disease risk, especially if it is located within the heart or around the major organs of the body. Dietary factors which can increase heart disease risk were described as an increased intake of processed foods, sugar, salt and certain fats and low intakes of fruit, vegetables, fibre, whole grains, beans and nuts. The Mediterranean diet, the dietary approaches to stop hypertension (DASH) diet, plant-based diets, the portfolio dietary pattern and low carbohydrate diets were all reviewed and although mixed results were stated for low carbohydrate diets, most of the diets reviewed reported improved heart disease outcomes. The role of intestinal microbiota in heart disease were also reviewed and the influence of a poor diet was implicated in imbalanced gut microbiota and the development of heart disease. It was concluded that an unhealthy diet can contribute to heart disease and that dietary patterns such as the Mediterranean diet and plant-based diets may be favourable for its management. This study could be used by healthcare professionals to individualise dietary recommendations for patients with heart disease or who are at risk of it.
Abstract
Although cardiovascular disease and its risk factors have been widely studied and new methods of diagnosis and treatment have been developed and implemented, the morbidity and mortality levels are still rising-cardiovascular disease is responsible for more than four million deaths each year in Europe alone. Even though nutrition is classified as one of the main and changeable risk factors, the quality of the diet in the majority of people does not follow the recommendations essential for prevention of obesity and cardiovascular disease. It demonstrates the need for better nutritional education in cardiovascular disease prevention and treatment, and the need to emphasize dietary components most relevant in cardiovascular disease. In our non-systematic review, we summarize the most recent knowledge about nutritional risk and prevention in cardiovascular disease and obesity.
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Recent Advances in Psoriasis Research; the Clue to Mysterious Relation to Gut Microbiome.
Komine, M
International journal of molecular sciences. 2020;21(7)
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Psoriasis is a chronic inflammatory disease where the skin forms bumpy red patches covered with white scales. There is no cure, but medications have focused on supressing the immune response. There is a link between the gut microbiome and psoriasis but it is poorly understood. This review includes the current understanding of how psoriasis develops and discusses the recent findings to support further research in this area. The composition of the gut microbiome affects inflammation in the whole body. This inflammation is associated with cardiovascular disease, diabetes mellitus and other inflammatory disorders. Recent studies have linked cardiovascular disease, insulin resistance, and metabolic syndrome to an imbalance in the gut microbiome. Psoriasis is often found alongside these conditions with similar abnormalities in gut bacteria. An imbalance in gut microbiome could cause certain people to develop psoriasis. The role of the gut microbiome needs to be further clarified but mounting evidence for this gut/skin link means that other therapeutic options may be available for treatment in the future.
Abstract
Psoriasis is a chronic inflammatory cutaneous disease, characterized by activated plasmacytoid dendritic cells, myeloid dendritic cells, Th17 cells, and hyperproliferating keratinocytes. Recent studies revealed skin-resident cells have pivotal roles in developing psoriatic skin lesions. The balance in effector T cells and regulatory T cells is disturbed, leading Foxp3-positive regulatory T cells to produce proinflammatory IL-17. Not only acquired but also innate immunity is important in psoriasis pathogenesis, especially in triggering the disease. Group 3 innate lymphoid cell are considered one of IL-17-producing cells in psoriasis. Short chain fatty acids produced by gut microbiota stabilize expression of Foxp3 in regulatory T cells, thereby stabilizing their function. The composition of gut microbiota influences the systemic inflammatory status, and associations been shown with diabetes mellitus, cardiovascular diseases, psychomotor diseases, and other systemic inflammatory disorders. Psoriasis has been shown to frequently comorbid with diabetes mellitus, cardiovascular diseases, psychomotor disease and obesity, and recent report suggested the similar abnormality in gut microbiota as the above comorbid diseases. However, the precise mechanism and relation between psoriasis pathogenesis and gut microbiota needs further investigation. This review introduces the recent advances in psoriasis research and tries to provide clues to solve the mysterious relation of psoriasis and gut microbiota.