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The role of gut microbiome in inflammatory skin disorders: A systematic review.
Widhiati, S, Purnomosari, D, Wibawa, T, Soebono, H
Dermatology reports. 2022;14(1):9188
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Gut-skin axis refers to the complex cross-talk between gut bacteria and skin. Although the exact mechanism underlying chronic inflammatory skin conditions is unknown, imbalances in the composition of gut microbes are believed to play a role. Twenty-three studies were included in this systematic review to assess whether gut microbial imbalance may contribute to inflammatory skin conditions such as Psoriasis, Acne Vulgaris, Atopic Dermatitis, and Urticaria. According to this systematic review, immune stimulation, inflammation, and disruption of bacterial composition are common mechanisms in all these skin disorders. A western diet and environmental exposures are found to be contributing to the disruption of bacteria and the pathology of these skin disorders. It has been observed that friendly gut bacteria such as Bifidobacterium are reduced in people with inflammatory skin conditions, whereas elevated levels of pathogenic bacteria such as E. coli and Proteobacteria are present in the gut of patients with inflammatory skin conditions. The abundance of anti-inflammatory bacteria such as Akkermansia muciniphila, Faecalibacterium prausnitzii, Clostridium leptum, Lactobacillus, and Bifidobacterium may protect against inflammatory skin conditions. Further robust studies are required to evaluate the pathogenesis behind inflammatory skin conditions as well as the involvement of gut bacteria in the development and progression of the disease. Healthcare professionals can gain a deeper understanding of gut bacteria that contribute to the pathology of inflammatory diseases as well as how clinically using anti-inflammatory bacterial species may improve the condition of individuals suffering from inflammatory skin conditions.
Abstract
The close relationship between the intestine and the skin has been widely stated, seen from gastrointestinal (GI) disorders often accompanied by skin manifestations. Exactly how the gut microbiome is related to skin inflammation and influences the pathophysiology mechanism of skin disorders are still unclear. Many studies have shown a two-way relationship between gut and skin associated with GI health and skin homeostasis and allostasis. This systematic review aimed to explore the associations between the gut microbiome with inflammatory skin disorders, such as acne, psoriasis, atopic dermatitis, and urticaria, and to discover the advanced concept of this relationship. The literature search was limited to any articles published up to December 2020 using PubMed and EBSCOHost. The review followed the PRISMA guidelines for conducting a systematic review. Of the 319 articles screened based on title and abstract, 111 articles underwent full-text screening. Of these, 23 articles met our inclusion criteria, comprising 13 atopic dermatitis (AD), three psoriasis, four acne vulgaris, and four chronic urticaria articles. Acne vulgaris, atopic dermatitis, psoriasis, and chronic urticaria are inflammation skin disorders that were studied recently to ascertain the relationship of these disorders with dysbiosis of the GI microbiome. All acne vulgaris, psoriasis, and chronic urticaria studies stated the association of gut microbiome with skin manifestations. However, the results in atopic dermatitis are still conflicting. Most of the articles agree that Bifidobacterium plays an essential role as anti-inflammation bacteria, and Proteobacteria and Enterobacteria impact inflammation in inflammatory skin disorders.
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A Deep Look at the Vaginal Environment During Pregnancy and Puerperium.
Severgnini, M, Morselli, S, Camboni, T, Ceccarani, C, Laghi, L, Zagonari, S, Patuelli, G, Pedna, MF, Sambri, V, Foschi, C, et al
Frontiers in cellular and infection microbiology. 2022;12:838405
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In healthy reproductive-aged women, the vaginal microbiome is generally dominated by members of the Lactobacillus genus. Lactobacilli promote the maintenance of the vaginal health, preventing the colonization and growth of adverse microorganisms through various mechanisms. The composition of the vaginal bacterial communities and related metabolites play a crucial role in maternal-foetal health. The aim of this study was to deepen the characteristics of the vaginal environment in a cohort of Caucasian women with a normal pregnancy throughout their different gestational ages (i.e., first, second, third trimester) and puerperium. This study is a prospective study of sixty-three Caucasian pregnant women. Participants were enrolled and sampled during all gestational ages; for 30 of them, clinical and microbiological data were also available for the puerperium. Additionally, 9 women who had a spontaneous miscarriage at the first trimester of pregnancy (gestational age: 11-13 weeks) during the study were included. Results show that: - irrespective of the period and type of pregnancy, bacterial vaginosis cases were characterised by a dramatic reduction of Lactobacillus and an increase of anaerobic bacteria. - the vaginal microbiome becomes more stable throughout the entire pregnancy, being less diverse and mainly dominated by lactobacilli. - women receiving an intrapartum antibiotic prophylaxis for Group B Streptococcus were characterized by a vaginal abundance of Prevotella compared to untreated women. - at the puerperium, a significantly lower content of Lactobacillus and higher levels of Gardnerella, Prevotella, Atopobium, and Streptococcus were observed. Authors conclude that their findings may help implement ‘prognostic’ criteria (e.g., evaluation of the risk of spontaneous miscarriage based on the microbiome/metabolome profiles), as well as strategies for the prevention of early pregnancy loss, based on the ‘manipulation’ of the vaginal bacterial inhabitants.
Abstract
A deep comprehension of the vaginal ecosystem may hold promise for unraveling the pathophysiology of pregnancy and may provide novel biomarkers to identify subjects at risk of maternal-fetal complications. In this prospective study, we assessed the characteristics of the vaginal environment in a cohort of pregnant women throughout their different gestational ages and puerperium. Both the vaginal bacterial composition and the vaginal metabolic profiles were analyzed. A total of 63 Caucasian women with a successful pregnancy and 9 subjects who had a first trimester miscarriage were enrolled. For the study, obstetric examinations were scheduled along the three trimester phases (9-13, 20-24, 32-34 gestation weeks) and puerperium (40-55 days after delivery). Two vaginal swabs were collected at each time point, to assess the vaginal microbiome profiling (by Nugent score and 16S rRNA gene sequencing) and the vaginal metabolic composition (1H-NMR spectroscopy). During pregnancy, the vaginal microbiome underwent marked changes, with a significant decrease in overall diversity, and increased stability. Over time, we found a significant increase of Lactobacillus and a decrease of several genera related to bacterial vaginosis (BV), such as Prevotella, Atopobium and Sneathia. It is worth noting that the levels of Bifidobacterium spp. tended to decrease at the end of pregnancy. At the puerperium, a significantly lower content of Lactobacillus and higher levels of Gardnerella, Prevotella, Atopobium, and Streptococcus were observed. Women receiving an intrapartum antibiotic prophylaxis for Group B Streptococcus (GBS) were characterized by a vaginal abundance of Prevotella compared to untreated women. Analysis of bacterial relative abundances highlighted an increased abundance of Fusobacterium in women suffering a first trimester abortion, at all taxonomic levels. Lactobacillus abundance was strongly correlated with higher levels of lactate, sarcosine, and many amino acids (i.e., isoleucine, leucine, phenylalanine, valine, threonine, tryptophan). Conversely, BV-associated genera, such as Gardnerella, Atopobium, and Sneathia, were related to amines (e.g., putrescine, methylamine), formate, acetate, alcohols, and short-chain fatty-acids (i.e., butyrate, propionate).
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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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The Effect of Exogenous Sex Steroids on the Vaginal Microbiota: A Systematic Review.
Ratten, LK, Plummer, EL, Bradshaw, CS, Fairley, CK, Murray, GL, Garland, SM, Bateson, D, Tachedjian, G, Masson, L, Vodstrcil, LA
Frontiers in cellular and infection microbiology. 2021;11:732423
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A vaginal microbiota associated with optimal reproductive and sexual health outcomes is characterised by Lactobacillus spp., although microbiome composition varies across geographical locations and specific populations. The aim of this study was to summarise the effect of specific oestrogen-containing or progestin-only contraceptives as well as menopausal hormonal therapy (MHT) on the vaginal microbiota, and evaluate the strength of these findings. This study is a systematic review of twenty-nine studies out of which 25 studies reported on the effect of hormonal contraception among reproductive-aged women and four on the effect of MHT among post-menopausal women. This review shows that: - oestrogen-containing contraceptives, particularly the combined oestrogen and progestin-containing oral contraceptive pill, had a positive effect on the composition of the vaginal microbiota. - among post-menopausal women using MHT, exogenous oestrogen also appeared to positively influence the vaginal microbiota. - exogenous-oestrogen as an adjunctive therapy does not impact the composition of the vaginal microbiota in a detrimental way. - the impact of progestin-only hormonal contraceptives was less consistent as there was equal evidence that they have either a negative or neutral impact on the vaginal microbiota. Authors conclude that their findings confirm the potential benefits of exogenous oestrogen in conferring a vaginal microbiota associated with optimal health outcomes for women.
Abstract
BACKGROUND Exogenous sex steroids within hormonal contraception and menopausal hormone therapy (MHT) have been used for family planning and management of menopausal symptoms, without consideration of their effects on the vaginal microbiota. This is largely because their use predates our understanding of the importance of the vaginal microbiome on human health. We conducted a systematic review (PROSPERO CRD42018107730) to determine the influence of exogenous sex steroids, stratified by oestrogen-containing or progestin-only types of contraception, and MHT on the vaginal microbiome, as measured by molecular methods. METHODS Embase, PubMed and Medline were searched for relevant literature published through to December 1st 2020. Eligible studies reported on the effect of specific exogenous sex steroids on the vaginal microbiome using a molecular method. Data regarding the 'positive', 'negative' or 'neutral' effect of each type of contraceptive or MHT on the vaginal microbiome was extracted and summarised. A positive effect reflected sex steroid exposure that was associated with increased abundance of lactobacilli, a change to, or maintenance of, an optimal vaginal microbiota composition, or a decrease in bacterial diversity (specifically reflecting a low-diversity optimal microbiota state), relative to the control group. An exogenous sex steroid was designated as having a negative effect on the vaginal microbiome if it resulted in opposing effects (i.e. loss of lactobacilli, a non-optimal microbiota state). When no significant change was found, this was considered neutral/inconclusive. RESULTS We identified 29 manuscripts reporting on the effect of exogenous sex steroids on the vaginal microbiome; 25 investigating hormonal contraceptives, and 4 investigating MHT. Oestrogen-containing contraception, particularly reflecting the combined oestrogen and progestin-containing contraceptive pill, had a positive effect on the composition of the vaginal microbiota. Progestin-only contraception, particularly reflecting depo-medroxyprogesterone acetate, had mixed effects on the microbiota. Among post-menopausal women using MHT, exogenous oestrogen applied topically was associated with increased prevalence of lactobacilli. CONCLUSION Our findings suggest that oestrogen-containing compounds may promote an optimal vaginal microbiota, which could have clinical applications. The impact of progestin-only contraceptives on the vaginal microbiota is less clear; more data is needed to determine how progestin-only contraceptives contribute to adverse reproductive and sexual health outcomes.
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Improvement of Inflammation and Pain after Three Months' Exclusion Diet in Rheumatoid Arthritis Patients.
Guagnano, MT, D'Angelo, C, Caniglia, D, Di Giovanni, P, Celletti, E, Sabatini, E, Speranza, L, Bucci, M, Cipollone, F, Paganelli, R
Nutrients. 2021;13(10)
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Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease typically affecting the synovial joints, in which autoimmunity drives dysregulated proinflammatory cytokine secretion. A decrease in dietary fibres and an increase in fat and sugar intake, which is typical in Western diets, contributes to gut microbial dysbiosis, leading to immune dysfunction. In fact, the changes in the gastrointestinal microbiota are thought to influence the pathogenesis and progression of RA. The aim of this diet was to investigate the effect of a diet deprived of meat, gluten, and lactose (excluding all dairy products and foods containing them) in patients with long-standing, well-controlled RA, in comparison with a control balanced diet including those items, followed for three months. This study is a randomised controlled study. All participants (n=40) were females with ages ranging between 31 and 72 years. They were randomly assigned to one of the two experimental groups and asked to follow a diet excluding meat, gluten and lactose (group A) or a balanced diet (group B). Results show that: - exclusion of meat, gluten and lactose, all of which reported as suspected of worsening of symptoms in RA, with the inclusion of fish, may carry additional health benefits to overweight patients compared with those obtained by a standard weight-reduction program (group B). - both diets, despite not affecting the disease activity, tended to reduce the arthritic pain perception and to improve the quality of life of the patients. - metabolic and inflammatory parameters showed a trend to normalise. - the immunological correlates of RA were not sensitive to either diet. Authors conclude that prevention of complications of RA might be better achieved by the exclusion diet. Thus, a diet prescription should be included in therapeutic plans for RA.
Abstract
INTRODUCTION Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease affecting the synovial joints and causing severe disability. Environmental and lifestyle factors, including diet, have been proposed to play a role in the onset and severity of RA. Dietary manipulation may help to manage the symptoms of RA by lowering inflammation and potentially decreasing pain. METHODS In 40 patients with long-standing RA with stable symptoms and treated with conventional (c-) and biological (b-) disease modifying anti-rheumatic drugs (DMARDs), the effect of a 3-month diet avoiding meat, gluten, and lactose (and all dairy products; privative diet) was evaluated in comparison with a control balanced diet including those foods. Both diets were designed to reduce weight since all patients were overweight or obese. Patients were randomly assigned to one of the diets, and RA was clinically assessed at Time 0 (T0), through the Visual Analogue Scale (VAS), for pain, and the Disease Activity Score of 28 joints (DAS 28) for RA activity. Patients were also administered the Short Form Health survey (SF-36) and the Health Assessment Questionnaire (HAQ). At T0, a blood sample was collected for laboratory tests and adipokines measurements, and anthropometric measurements were compared. These evaluations were repeated at the end of the 3 months' dietary regimens. RESULTS A significant decrease in VAS and the improvement of the overall state of physical and mental health, assessed through SF-36, was observed in patients assigned to the privative diet. Both dietary regimens resulted in the improvement of quality of life compared to baseline values; however, the change was significant only for the privative diet. With either diet, patients showed significant decreases in body weight and body mass index, with a reduction in waist and hips circumference and lower basal glucose and circulating leptin levels. A privative diet was also able to significantly reduce systolic (p = 0.003) and diastolic (p = 0.025) arterial pressure. The number of circulating leukocytes and neutrophils, and the level of hs-C-Reactive Protein also decreased after 3 months of the meat-, lactose-, and gluten-free diet. CONCLUSIONS Our results suggest that a privative diet can result in a better control of inflammation in RA patients under stable optimized drug treatment.
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Small Intestinal Bacterial Overgrowth in Children: A State-Of-The-Art Review.
Avelar Rodriguez, D, Ryan, PM, Toro Monjaraz, EM, Ramirez Mayans, JA, Quigley, EM
Frontiers in pediatrics. 2019;7:363
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Small intestinal bacterial overgrowth (SIBO) occurs when microorganisms overpopulate the small intestine and is characterised by gastrointestinal symptoms such as abdominal pain, diarrhoea, and flatulence. This review focuses on paediatric SIBO, known to be increasing, with emphasis on the impact on gut microbiota. The gut microbiota is influenced by several factors including genetics, vaginal delivery, exercise and diet. SIBO in children has been studied in the context of stunting, irritable bowel syndrome (IBS), obesity, and related to use of proton pump inhibitors (PPIs). This review analysed 149 studies published since 2000 through till May 2019 with the aim of presenting the most up-to-date information. Risk factors included gastric acids and medications which suppress this activity, intestinal motility disturbances leading to bacterial overgrowth, anatomical anomalies where there is an absence of one or more intestinal valves, and poor socioeconomic status and diet. The review concluded that the recommended diagnosis is by methane and hydrogen breath testing and that Gold Standard treatment is antibiotic ‘rifaximin’ at 1,200 mg/d, reduced to 600 mg/d for 1 week in children. Alternative treatments discussed include FODMAP diets and probiotic protocols with best results coming from combining antibiotic and probiotic protocols. It concludes that SIBO in children is heterogenous and poorly understood and that a better diagnostic criteria is necessary in paediatrics.
Abstract
Small intestinal bacterial overgrowth (SIBO) is a heterogenous and poorly understood entity characterised by an excessive growth of select microorganisms within the small intestine. This excessive bacterial biomass, in turn, disrupts host physiology in a myriad of ways, leading to gastrointestinal and non-gastrointestinal symptoms and complications. SIBO is a common cause of non-specific gastrointestinal symptoms in children, such as chronic abdominal pain, abdominal distention, diarrhoea, and flatulence, amongst others. In addition, it has recently been implicated in the pathophysiology of stunting, a disease that affects millions of children worldwide. Risk factors such as acid-suppressive therapies, alterations in gastrointestinal motility and anatomy, as well as impoverished conditions, have been shown to predispose children to SIBO. SIBO can be diagnosed via culture-dependant or culture-independent approaches. SIBO's epidemiology is limited due to the lack of uniformity and consensus of its diagnostic criteria, as well as the paucity of literature available. Antibiotics remain the first-line treatment option for SIBO, although emerging modalities such as probiotics and diet manipulation could also have a role. Herein, we present a state-of-the-art-review which aims to comprehensively outline the most current information on SIBO in children, with particular emphasis on the gut microbiota.
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Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome?
Newberry, F, Hsieh, SY, Wileman, T, Carding, SR
Clinical science (London, England : 1979). 2018;132(5):523-542
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Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) (ME/CFS) is a disabling and debilitating disease. Several studies have shown alterations in the gut microbiome (dysbiosis) in patients with ME/CFS. However, in focusing on the bacterial components of the microbiome, the viral component of the microbiome (known as the virome) has been neglected. Viruses can change the microbiome which can influence the health. This area is therefore important for research into ME/CFS. This article provides a comprehensive review of the current evidence supporting microbiome alterations in ME/CFS patients. Additionally, the challenges associated with microbiome studies are discussed. A literature search was done and 11 papers were found that had examined the microbiome ME/CFS patients, dating from 1998 to 2017. It was not possible to compare the studies statistically but from looking at each one individually there is sufficient evidence to support the claim of an altered intestinal microbiome in ME/CFS patients. ME/CFS is multifactorial and potential dysbiosis should be considered to be only part of the picture. Future studies are needed to adopt standardized techniques and analyses. As research increases, it is becoming clear that the virome can directly and indirectly affect host health, and may play a role in the pathogenesis of ME/CFS.
Abstract
Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) (ME/CFS) is a disabling and debilitating disease of unknown aetiology. It is a heterogeneous disease characterized by various inflammatory, immune, viral, neurological and endocrine symptoms. Several microbiome studies have described alterations in the bacterial component of the microbiome (dysbiosis) consistent with a possible role in disease development. However, in focusing on the bacterial components of the microbiome, these studies have neglected the viral constituent known as the virome. Viruses, particularly those infecting bacteria (bacteriophages), have the potential to alter the function and structure of the microbiome via gene transfer and host lysis. Viral-induced microbiome changes can directly and indirectly influence host health and disease. The contribution of viruses towards disease pathogenesis is therefore an important area for research in ME/CFS. Recent advancements in sequencing technology and bioinformatics now allow more comprehensive and inclusive investigations of human microbiomes. However, as the number of microbiome studies increases, the need for greater consistency in study design and analysis also increases. Comparisons between different ME/CFS microbiome studies are difficult because of differences in patient selection and diagnosis criteria, sample processing, genome sequencing and downstream bioinformatics analysis. It is therefore important that microbiome studies adopt robust, reproducible and consistent study design to enable more reliable and valid comparisons and conclusions to be made between studies. This article provides a comprehensive review of the current evidence supporting microbiome alterations in ME/CFS patients. Additionally, the pitfalls and challenges associated with microbiome studies are discussed.
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The microbiome and autoimmunity: a paradigm from the gut-liver axis.
Li, B, Selmi, C, Tang, R, Gershwin, ME, Ma, X
Cellular & molecular immunology. 2018;15(6):595-609
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The incidence of autoimmune and inflammatory diseases has been increasing worldwide. Changes in environmental factors, such as modern lifestyle, diet, antibiotics and hygiene are thought to play a critical role in the development of various autoimmune diseases. It is the mucosal microbial flora that is shaped by our environment and communicates with the innate and adaptive immune systems, and when disrupted, can lead to the loss of immune tolerance and dysregulated immune cells. This review paper provides an overview of the interactions between the intestinal microbiome and the immune system. It explains how these interactions affect host autoimmunity locally and systemically and sheds light on the molecular mechanisms, utilised by microbes that may contribute to systemic autoimmunity in genetically susceptible individuals. The links between the gut microbiome and various autoimmune diseases, such as rheumatoid arthritis, type 1 diabetes and multiple sclerosis, as well as the gut-liver axis, involving intestinal microbiome and autoimmune liver diseases, are discussed in more detail.
Abstract
Microbial cells significantly outnumber human cells in the body, and the microbial flora at mucosal sites are shaped by environmental factors and, less intuitively, act on host immune responses, as demonstrated by experimental data in germ-free and gnotobiotic studies. Our understanding of this link stems from the established connection between infectious bacteria and immune tolerance breakdown, as observed in rheumatic fever triggered by Streptococci via molecular mimicry, epitope spread and bystander effects. The availability of high-throughput techniques has significantly advanced our capacity to sequence the microbiome and demonstrated variable degrees of dysbiosis in numerous autoimmune diseases, including rheumatoid arthritis, type 1 diabetes, multiple sclerosis and autoimmune liver disease. It remains unknown whether the observed differences are related to the disease pathogenesis or follow the therapeutic and inflammatory changes and are thus mere epiphenomena. In fact, there are only limited data on the molecular mechanisms linking the microbiota to autoimmunity, and microbial therapeutics is being investigated to prevent or halt autoimmune diseases. As a putative mechanism, it is of particular interest that the apoptosis of intestinal epithelial cells in response to microbial stimuli enables the presentation of self-antigens, giving rise to the differentiation of autoreactive Th17 cells and other T helper cells. This comprehensive review will illustrate the data demonstrating the crosstalk between intestinal microbiome and host innate and adaptive immunity, with an emphasis on how dysbiosis may influence systemic autoimmunity. In particular, a gut-liver axis involving the intestinal microbiome and hepatic autoimmunity is elucidated as a paradigm, considering its anatomic and physiological connections.
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Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome.
Nagy-Szakal, D, Williams, BL, Mishra, N, Che, X, Lee, B, Bateman, L, Klimas, NG, Komaroff, AL, Levine, S, Montoya, JG, et al
Microbiome. 2017;5(1):44
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Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained persistent fatigue, cognitive dysfunction, sleep disturbances, orthostatic intolerance, fever, swollen lymph glands and irritable bowel syndrome (IBS). It is associated with gut bacterial dysbiosis, systemic inflammation and both gastro intestinal (GI) and neurological disturbances. The extent to which the gastrointestinal microbiome and peripheral inflammation are associated with ME/CFS remains unclear. This experiment looked at fecal bacterial samples and metabolic pathway markers in 50 ME/CFS patients and 50 healthy controls. In ME/CFS subgroups, measures of symptom severity including pain, fatigue, and reduced motivation were correlated with the amounts and types of gut bacteria and certain metabolic pathways. Future prospective studies should consider more detailed exploration of IBS subtypes, associated GI symptoms, and their relationship to ME/CFS dysbiosis. This may enable more accurate diagnosis and the development of specific therapeutic strategies.
Abstract
BACKGROUND Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained persistent fatigue, commonly accompanied by cognitive dysfunction, sleeping disturbances, orthostatic intolerance, fever, lymphadenopathy, and irritable bowel syndrome (IBS). The extent to which the gastrointestinal microbiome and peripheral inflammation are associated with ME/CFS remains unclear. We pursued rigorous clinical characterization, fecal bacterial metagenomics, and plasma immune molecule analyses in 50 ME/CFS patients and 50 healthy controls frequency-matched for age, sex, race/ethnicity, geographic site, and season of sampling. RESULTS Topological analysis revealed associations between IBS co-morbidity, body mass index, fecal bacterial composition, and bacterial metabolic pathways but not plasma immune molecules. IBS co-morbidity was the strongest driving factor in the separation of topological networks based on bacterial profiles and metabolic pathways. Predictive selection models based on bacterial profiles supported findings from topological analyses indicating that ME/CFS subgroups, defined by IBS status, could be distinguished from control subjects with high predictive accuracy. Bacterial taxa predictive of ME/CFS patients with IBS were distinct from taxa associated with ME/CFS patients without IBS. Increased abundance of unclassified Alistipes and decreased Faecalibacterium emerged as the top biomarkers of ME/CFS with IBS; while increased unclassified Bacteroides abundance and decreased Bacteroides vulgatus were the top biomarkers of ME/CFS without IBS. Despite findings of differences in bacterial taxa and metabolic pathways defining ME/CFS subgroups, decreased metabolic pathways associated with unsaturated fatty acid biosynthesis and increased atrazine degradation pathways were independent of IBS co-morbidity. Increased vitamin B6 biosynthesis/salvage and pyrimidine ribonucleoside degradation were the top metabolic pathways in ME/CFS without IBS as well as in the total ME/CFS cohort. In ME/CFS subgroups, symptom severity measures including pain, fatigue, and reduced motivation were correlated with the abundance of distinct bacterial taxa and metabolic pathways. CONCLUSIONS Independent of IBS, ME/CFS is associated with dysbiosis and distinct bacterial metabolic disturbances that may influence disease severity. However, our findings indicate that dysbiotic features that are uniquely ME/CFS-associated may be masked by disturbances arising from the high prevalence of IBS co-morbidity in ME/CFS. These insights may enable more accurate diagnosis and lead to insights that inform the development of specific therapeutic strategies in ME/CFS subgroups.
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Ability of Lactobacillus kefiri LKF01 (DSM32079) to colonize the intestinal environment and modify the gut microbiota composition of healthy individuals.
Toscano, M, De Grandi, R, Miniello, VL, Mattina, R, Drago, L
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2017;49(3):261-267
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The importance of diversity in human gut microbiome to host health is well established. However there are fewer data on the ability of oral probiotics to change the composition of the intestinal bacterial environment. This small randomised study of 20 individuals, aimed to assess the ability of Lactobacillus kefiri to colonise the intestines of healthy individuals and change microbial diversity. Following a one month period of eating a Mediterranean style diet and avoiding fermented foods, probiotics and antibiotics, the study participants were randomised to receive a 1010 suspension of Lactobacillus kefiri either ½ hour before eating or ½ hour after eating. Fecal samples were collected at baseline, after one month of supplementation and one month after finishing the probiotic course. Lactobacillus kefiri was found in fecal samples of all subjects after one month of oral probiotic consumption and was still present in about a quarter of samples one month after finishing supplementation. Changes were observed in overall microbial diversity from baseline, with a reduction in some bacteria and pathogens associated with disease. In conclusion, Lactobacillus kefiri altered intestinal bacterial composition, leading a significant reduction in some bacteria associated with inflammation and intestinal disease. These effects were not affected with timing (i.e. before or after food) of taking the probiotic supplement.
Abstract
BACKGROUND Probiotics have been observed to positively influence the host's health, but to date few data about the ability of probiotics to modify the gut microbiota composition exist. AIMS To evaluate the ability of Lactobacillus kefiri LKF01 DSM32079 (LKEF) to colonize the intestinal environment of healthy subjects and modify the gut microbiota composition. METHODS Twenty Italian healthy volunteers were randomized in pre-prandial and post-prandial groups. Changes in the gut microbiota composition were detected by using a Next Generation Sequencing technology (Ion Torrent Personal Genome Machine). RESULTS L. kefiri was recovered in the feces of all volunteers after one month of probiotic administration, while it was detected only in three subjects belonging to the pre-prandial group and in two subjects belonging to the post-prandial group one month after the end of probiotic consumption. After one month of probiotic oral intake we observed a reduction of Bilophila, Butyricicomonas, Flavonifractor, Oscillibacter and Prevotella. Interestingly, after the end of probiotic administration Bacteroides, Barnesiella, Butyricicomonas, Clostridium, Haemophilus, Oscillibacter, Salmonella, Streptococcus, Subdoligranolum, and Veillonella were significantly reduced if compared to baseline samples. CONCLUSION L. kefiri LKF01 showed a strong ability to modulate the gut microbiota composition, leading to a significant reduction of several bacterial genera directly involved in the onset of pro-inflammatory response and gastrointestinal diseases.