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COVID-19 infection alters kynurenine and fatty acid metabolism, correlating with IL-6 levels and renal status.
Thomas, T, Stefanoni, D, Reisz, JA, Nemkov, T, Bertolone, L, Francis, RO, Hudson, KE, Zimring, JC, Hansen, KC, Hod, EA, et al
JCI insight. 2020;5(14)
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There is increasing urgency for the development of Covid-19 therapies. Treatments preventing infection and decreasing the amount of virus in the body have largely been unsuccessful and so the focus has turned to host biological pathways, which may be altered by Covid-19 infection. This observational study of forty-nine Covid-19 positive and negative individuals aimed to determine alterations in the hosts metabolism. The results showed that Covid-19 infection was associated with disrupted host inflammatory and immune pathways. Markers for kidney dysfunction were also increased alongside raised blood sugar levels and fatty acids in the blood. It was concluded that inflammatory markers may be an indicator for disease severity and a target for Covid-19 therapy. Dietary therapy could be used to target blood fatty acid changes brought about by Covid-19 infection. This study could be used by healthcare professionals to understand that inflammation is increased in Covid-19 patients and in lieu of approved therapies, dietary intervention may be of benefit.
Abstract
BACKGROUNDReprogramming of host metabolism supports viral pathogenesis by fueling viral proliferation, by providing, for example, free amino acids and fatty acids as building blocks.METHODSTo investigate metabolic effects of SARS-CoV-2 infection, we evaluated serum metabolites of patients with COVID-19 (n = 33; diagnosed by nucleic acid testing), as compared with COVID-19-negative controls (n = 16).RESULTSTargeted and untargeted metabolomics analyses identified altered tryptophan metabolism into the kynurenine pathway, which regulates inflammation and immunity. Indeed, these changes in tryptophan metabolism correlated with interleukin-6 (IL-6) levels. Widespread dysregulation of nitrogen metabolism was also seen in infected patients, with altered levels of most amino acids, along with increased markers of oxidant stress (e.g., methionine sulfoxide, cystine), proteolysis, and renal dysfunction (e.g., creatine, creatinine, polyamines). Increased circulating levels of glucose and free fatty acids were also observed, consistent with altered carbon homeostasis. Interestingly, metabolite levels in these pathways correlated with clinical laboratory markers of inflammation (i.e., IL-6 and C-reactive protein) and renal function (i.e., blood urea nitrogen).CONCLUSIONIn conclusion, this initial observational study identified amino acid and fatty acid metabolism as correlates of COVID-19, providing mechanistic insights, potential markers of clinical severity, and potential therapeutic targets.FUNDINGBoettcher Foundation Webb-Waring Biomedical Research Award; National Institute of General and Medical Sciences, NIH; and National Heart, Lung, and Blood Institute, NIH.
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Brain-Behavior-Immune Interaction: Serum Cytokines and Growth Factors in Patients with Eating Disorders at Extremes of the Body Mass Index (BMI) Spectrum.
Caroleo, M, Carbone, EA, Greco, M, Corigliano, DM, Arcidiacono, B, Fazia, G, Rania, M, Aloi, M, Gallelli, L, Segura-Garcia, C, et al
Nutrients. 2019;11(9)
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Eating disorders such as anorexia, binge eating and night-time eating cause great fluctuations in body mass and have also been shown to alter the immune system, and more specifically markers of inflammation called cytokines. In this observational study of 90 patients with known eating disorders, the researchers tried to identify how much BMI, ‘underweightness’ and malnutrition influenced the body’s pro-inflammatory response and upset the normal immune response. They found that many inflammatory cytokines were elevated in the blood samples taken, a likely response to the conditions of stress in the body. These cytokines are known to interact with the nervous system and were also influenced by other common symptoms such as depression. They were able to group the differences in cytokines for anorexia nervosa, binge-eating disorder, post-dinner eating, night-eating, sweet-eating and fasting. These markers of dysfunctional eating behaviours may help form part of a therapeutic approach to treating eating disorders based on supporting the immune response and reducing inflammation to stabilise metabolic processes. Future studies in a larger population of patients is necessary to determine the relevance of these findings.
Abstract
Alterations of the immune system are known in eating disorders (EDs), however the importance of cytokine balance in this context has not been clarified. We compared cytokines and growth factors at opposite ends of BMI ranges, in 90 patients classified in relation to BMI, depressive and EDs comorbidities. Serum concentrations of interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF) were determined by a biochip analyzer (Randox Labs). Differences were calculated through ANOVA. Possible predictors of higher cytokine levels were evaluated through regression analysis. IL-1α, IL-10, EGF, and IFN-γ were altered individuals with anorexia nervosa (AN) and binge eating disorder (BED). Night-eating was associated with IL-8 and EGF levels, IL-10 concentrations with post-dinner eating and negatively with sweet-eating, long fasting with higher IFN-γ levels. IL-2 increase was not linked to EDs, but to the interaction of depression and BMI. Altogether, for the first time, IL-1α, IL-10, EGF, and IFN-γ were shown to differ between AN and HCs, and between AN and individuals with obesity with or without BED. Only IL-2 was influenced by depression. Dysfunctional eating behaviors predicted abnormal concentrations of IL-10, EGF, IL-8 and IFN-γ.
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Impact of red meat, processed meat and fibre intake on risk of late-onset chronic inflammatory diseases: prospective cohort study on lifestyle factors using the Danish 'Diet, Cancer and Health' cohort (PROCID-DCH): protocol.
Rasmussen, NF, Rubin, KH, Stougaard, M, Tjønneland, A, Stenager, E, Lund Hetland, M, Glintborg, B, Bygum, A, Andersen, V
BMJ open. 2019;9(3):e024555
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Chronic inflammatory diseases (CIDs) can be considered as systemic diseases which primarily affect one organ such as the intestine, skin, joints or the brain. The primary aim of this study was to investigate the impact of fibre, red meat and processed meat on disease risk outcomes of late-onset CID in the ‘Diet, Cancer and Health’ (DCH) cohort. The study is an observational prospective cohort study. The study will use data from 57,053 persons from the prospective Danish cohort study ‘Diet, Cancer and Health’ together with National Health Registry data. The study does not only target one CID but it looks at several CIDs. Furthermore, the linkage to Danish health registries will ensure almost complete follow-up of the study population since the Danish health registries are considered the internationally most comprehensive with high validity.
Abstract
INTRODUCTION Chronic inflammatory diseases (CIDs) (Crohn's disease, ulcerative colitis, psoriasis, psoriatic arthritis, rheumatoid arthritis and multiple sclerosis) are diseases of the immune system that have some shared genetic and environmental predisposing factors, but still few studies have investigated the effects of lifestyle on disease risk of several CIDs. The primary aim of this prospective cohort study is to investigate the impact of fibre, red meat and processed meat on risk of late-onset CID, with the perspective that results of this study can contribute in supporting future diet recommendations for effective personalised prevention. METHODS AND ANALYSIS The study will use data from 57 053 persons from the prospective Danish cohort study 'Diet, Cancer and Health' together with National Health Registry data. The follow-up period is from December 1993 to December 2018. Questionnaire data on diet and lifestyle were collected at entry to the Diet, Cancer and Health study. The outcome CID is defined as having a diagnosis of one of the CIDs registered in the National Patient Registry or, for multiple sclerosis, in the Danish Multiple Sclerosis Registry during follow-up and being treated with a drug used for the specific disease. The major outcome of the analyses will be to detect variability in risk of late onset of any CID and, if power allows, disease risk of late onset of each CID diagnosis between persons with different fibre and red meat, and processed meat intake. The outcome will be adjusted for age, sex, body mass index, physical activity, energy, alcohol, fermented dairy products, education, smoking status, hormone replacement therapy and comorbidity. ETHICS AND DISSEMINATION The study is approved by the Danish Data Protection Agency (2012-58-0018). The core study is an open register-based cohort study. The study does not need approval from the Ethics committee or Institutional Review Board by Danish law. Study findings will be disseminated through peer-reviewed journals, patient associations and presentations at international conferences. TRIAL REGISTRATION NUMBER NCT03456206; Post-results.
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Profiling of lung microbiota in the patients with obstructive sleep apnea.
Lu, D, Yao, X, Abulimiti, A, Cai, L, Zhou, L, Hong, J, Li, N
Medicine. 2018;97(26):e11175
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Obstructive sleep apnoea is a disease of lower airways of the lungs. Numerous studies have reported that various commensal bacteria such as Streptococcus, Veillonella, Prevotella, and Actinomyces are predominant in healthy human lungs. Therefore the current study was designed to analyse and assess the lower airway microbiota in patients with Obstructive sleep apnoea (OSA) and compared it to that of control group (who did not have OSA but had other lung disease). Sleep apnoea was examined with a sleep diagnostic device and data were analysed with Profusion PSG software. The study was conducted in China and total number of subjects who took part in the study was 19. On comparison between the two groups revealed that, Fusobacteria species of bacteria was higher in OSA patients whilst firmicutes species was significantly less. The result from the study indicated that lung microbiota in OSA patients were different from those of control group(non OSA )patients and maybe manipulation of the microbiota could be considered as an intervention to increase airway immunity and decrease susceptibility to airway infections. Though the authors concluded that more studies are needed before these findings and interventions can be confirmed.
Abstract
Lung microbiota may affect innate immunity and treatment consequence in the obstructive sleep apnea (OSA) patients. Bronchoalveolar lavage fluid (BALF) was obtained from 11 OSA patients and 8 patients with other lung diseases as control, and used for lung microbiota profiling by PCR amplification and sequencing of the microbial samples. It was demonstrated that phyla of Firmicutes, Fusobacteria, and Bacteriodetes were relatively abundant in the lung microbiota. Alpha-diversity comparison between OSA and control group revealed that Proteobacteria and Fusobacteria were significantly higher in OSA patients (0.3863 ± 0.0631 and 0.0682 ± 0.0159, respectively) than that in control group (0.119 ± 0.074 and 0.0006 ± 0.0187, respectively, P < .05 for both phyla). In contrast, Firmicutes was significantly less in OSA patients (0.1371 ± 0.0394) compared with that in the control group (0.384 ± 0.046, P < .05). Comparison within a group (ß-diversity) indicated that the top 5 phyla in the OSA lung were Proteobacteria, Bacteroidetes, Firmicutes, Fusobacteria, and Acidobacteria, while the top 5 phyla in the control group were Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, and Acidobacteria. These findings indicated that lung microbiota in OSA is distinct from that of non-OSA patients. Manipulation of the microbiota may be an alternative strategy to augment airway immunity and to reduce susceptibility to airway infection.
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Fecal Microbiome and Food Allergy in Pediatric Atopic Dermatitis: A Cross-Sectional Pilot Study.
Fieten, KB, Totté, JEE, Levin, E, Reyman, M, Meijer, Y, Knulst, A, Schuren, F, Pasmans, SGMA
International archives of allergy and immunology. 2018;175(1-2):77-84
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Atopic diseases, such as atopic dermatitis (AD), asthma and rhinitis, are on the increase worldwide. Exposure to microbes may be important in the development of an atopic disease. Specifically, reduced early-life exposure is thought to be a contributing factor because microbial colonisation of the intestines during infancy plays a crucial role in the maturation of the immune system. AD, also called eczema, is an inflammatory skin disease often seen in small children. Food allergies are common in children with AD, the most common allergens being eggs, cow’s milk, peanuts, soy and wheat. This cross-sectional observational pilot study with 82 young children with a diagnosis of AD set out to identify distinct microbial patterns in the children’s faecal microbiomes associated with a clinical diagnosis of food allergy. Stool and blood samples were collected for a microbiome analysis and IgE antibody measurement, respectively. 20 children had a confirmed food allergy (most commonly to cow’s milk and peanuts), while almost half of the children without a diagnosed food allergy were sensitised to common food allergens after a food challenge. The study identified a faecal microbial signature in children with AD that differentiates between the presence and absence of food allergy. Children with AD and food allergy had more Escherichia coli and Bifidobacterium pseudocatenulatum species and less Bifidobacterium breve, Faecalibacterium prausnitzii and Akkermansia muciniphila species than children without food allergy. The authors concluded that the study supports a hypothesis that the intestinal microbiome differs in children with AD, depending on whether they have a food allergy or not. They call for future studies to confirm these findings.
Abstract
BACKGROUND Exposure to microbes may be important in the development of atopic disease. Atopic diseases have been associated with specific characteristics of the intestinal microbiome. The link between intestinal microbiota and food allergy has rarely been studied, and the gold standard for diagnosing food allergy (double-blind placebo-controlled food challenge [DBPCFC]) has seldom been used. We aimed to distinguish fecal microbial signatures for food allergy in children with atopic dermatitis (AD). METHODS Pediatric patients with AD, with and without food allergy, were included in this cross-sectional observational pilot study. AD was diagnosed according to the UK Working Party criteria. Food allergy was defined as a positive DBPCFC or a convincing clinical history, in combination with sensitization to the relevant food allergen. Fecal samples were analyzed using 16S rRNA microbial analysis. Microbial signature species, discriminating between the presence and absence food allergy, were selected by elastic net regression. RESULTS Eighty-two children with AD (39 girls) with a median age of 2.5 years, and 20 of whom were diagnosed with food allergy, provided fecal samples. Food allergy to peanut and cow's milk was the most common. Six bacterial species from the fecal microbiome were identified, that, when combined, distinguished between children with and without food allergy: Bifidobacterium breve, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Escherichia coli, Faecalibacterium prausnitzii, and Akkermansia muciniphila (AUC 0.83, sensitivity 0.77, specificity 0.80). CONCLUSIONS In this pilot study, we identified a microbial signature in children with AD that discriminates between the absence and presence of food allergy. Future studies are needed to confirm our findings.