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Carvalho LM, Carvalho BG, Souza LL, da Mota JC, Ribeiro AA, Nicoletti CF. Obesity as an aggravating factor of systemic lupus erythematosus disease: What we already know and what we must explore. A rapid scoping review. Nutrition 2024; 128:112559. [PMID: 39244807 DOI: 10.1016/j.nut.2024.112559] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Revised: 08/06/2024] [Accepted: 08/08/2024] [Indexed: 09/10/2024]
Abstract
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect various organs and systems. Symptoms of SLE can vary widely from person to person and over time, including fatigue, joint pain, skin rashes, fever, and inflammation of multiple organs. The association between SLE and excess body weight has been the subject of study, with evidence suggesting that overweight and obesity can worsen the disease´s clinical presentation. Obesity is linked to a state of low-grade chronic inflammation, which can exacerbate the inflammation present in SLE. Additionally, obesity may negatively impact treatment response, disease progression, and patient prognosis. Patients with SLE and obesity may face additional challenges in managing the disease, such as increased symptom severity, higher risk of cardiovascular and renal complications, and a reduced response to conventional treatments. Obesity can also influence the quality of life of patients with SLE, making a holistic approach that considers the individual's nutritional status essential. Therefore, understanding the relationship between obesity and SLE is crucial for optimizing treatment, improving clinical outcomes, and enhancing patients' quality of life. Further research is needed to elucidate the underlying pathophysiological mechanisms, develop more precise and personalized management strategies, and identify biomarkers that can predict disease prognosis and treatment response.
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Affiliation(s)
- Lucas M Carvalho
- Applied Physiology and Nutrition Research Group - School of Physical Education and Sport and Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil; Center of Lifestyle Medicine, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Beatriz G Carvalho
- Applied Physiology and Nutrition Research Group - School of Physical Education and Sport and Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil; Center of Lifestyle Medicine, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Leticia L Souza
- Applied Physiology and Nutrition Research Group - School of Physical Education and Sport and Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil; Center of Lifestyle Medicine, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Jhulia Cnl da Mota
- Applied Physiology and Nutrition Research Group - School of Physical Education and Sport and Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil; Center of Lifestyle Medicine, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Amanda A Ribeiro
- Applied Physiology and Nutrition Research Group - School of Physical Education and Sport and Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil; Center of Lifestyle Medicine, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Carolina F Nicoletti
- Applied Physiology and Nutrition Research Group - School of Physical Education and Sport and Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil; Center of Lifestyle Medicine, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil; Rheumatology Division, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, Brazil.
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Touma Z, Kayaniyil S, Parackal A, Bonilla D, Su J, Johnston A, Gahn J, Hille ED, Ohsfeldt R, Chandran S. Modelling long-term outcomes for patients with systemic lupus erythematosus. Semin Arthritis Rheum 2024; 68:152507. [PMID: 39029291 DOI: 10.1016/j.semarthrit.2024.152507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Revised: 05/13/2024] [Accepted: 07/01/2024] [Indexed: 07/21/2024]
Abstract
BACKGROUND New treatments for systemic lupus erythematosus (SLE) aim to improve tolerability and disease activity control over standard of care (SoC) treatment. SoC typically includes daily glucocorticoid (GC) which carries a risk of organ damage over time. This study sought to develop natural history models to identify predictors of long-term outcomes with current SoC SLE treatment. METHODS Generalized linear and parametric accelerated failure time survival models (GLM) and parametric accelerated failure time (AFT) survival models were designed to identify predictors of disease activity, flare rate, GC use, organ damage, and mortality beyond the first year of treatment in patients with SLE. Models were run using a longitudinal retrospective analysis of prospectively collected Toronto Lupus Cohort (TLC) study data, collected between 1997 and 2020. Covariates of clinical and statistical significance were selected by bivariate- then multi-variate regression to find the model of best fit. FINDINGS Of the 1255 subjects included, 89 % were female 89 % and 65 % Caucasian. Mean follow-up was 10·5 years. At first visit, 51 % of patients had moderate-to-severe disease activity (SLEDAI-2 K score ≥ 6). Mean organ damage scores gradually increased over the years following diagnosis. Median survival of the cohort was ∼35 years from study entry. In the GLM models, SLEDAI-2 K yearly average, and average GC dose were key for predicting change in SLEDAI-2 K, GC use/ dose, and flare (any/rate). Together, adjusted mean SLEDAI-2 K and GC dose were shown to be predictors of mortality and damage in at least 9 of 12 organ systems considered. INTERPRETATION These comprehensive, longitudinal, predictive models show that disease activity and GC use are significant predictors of organ damage and mortality in a patient population with predominantly moderate to severe SLE. This deepens understanding of SLE natural history and underscores the need for new treatment approaches that reduce disease activity and GC use with an aim to improve long-term SLE outcomes. FUNDING This study was funded by AstraZeneca.
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Affiliation(s)
- Z Touma
- Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University of Toronto Lupus Clinic, Toronto, Canada.
| | - S Kayaniyil
- Biopharmaceuticals, AstraZeneca, Mississauga, Canada
| | - A Parackal
- Biopharmaceuticals, AstraZeneca, Mississauga, Canada
| | - D Bonilla
- Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University of Toronto Lupus Clinic, Toronto, Canada
| | - J Su
- Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University of Toronto Lupus Clinic, Toronto, Canada
| | - A Johnston
- Medical Decision Modeling Inc., Indianapolis, IN, USA
| | - J Gahn
- Medical Decision Modeling Inc., Indianapolis, IN, USA
| | - E D Hille
- Medical Decision Modeling Inc., Indianapolis, IN, USA
| | - R Ohsfeldt
- Medical Decision Modeling Inc., Indianapolis, IN, USA; Department of Health Policy and Management, Texas A&M School of Public Health, College Station, Texas, USA
| | - S Chandran
- Biopharmaceuticals, AstraZeneca, Mississauga, Canada
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Zhao M, Wen X, Liu R, Xu K. Microbial dysbiosis in systemic lupus erythematosus: a scientometric study. Front Microbiol 2024; 15:1319654. [PMID: 38863759 PMCID: PMC11166128 DOI: 10.3389/fmicb.2024.1319654] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Accepted: 05/01/2024] [Indexed: 06/13/2024] Open
Abstract
Introduction Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Mounting evidence suggests microbiota dysbiosis augment autoimmune response. This study aims to provide a systematic overview of this research field in SLE through a bibliometric analysis. Methods We conducted a comprehensive search and retrieval of literature related to microbial researches in SLE from the Web of Science Core Collection (WOSCC) database. The retrieved articles were subjected to bibliometric analysis using VOSviewer and Bibliometricx to explore annual publication output, collaborative patterns, research hotspots, current research status, and emerging trends. Results In this study, we conducted a comprehensive analysis of 218 research articles and 118 review articles. The quantity of publications rises annually, notably surging in 2015 and 2018. The United States and China emerged as the leading contributors in microbial research of SLE. Mashhad University of Medical Sciences had the highest publication outputs among the institutions. Frontiers in Immunology published the most papers. Luo XM and Margolles A were the most prolific and highly cited contributors among individual authors. Microbial research in SLE primarily focused on changes in microbial composition, particularly gut microbiota, as well as the mechanisms and practical applications in SLE. Recent trends emphasize "metabolites," "metabolomics," "fatty acids," "T cells," "lactobacillus," and "dietary supplementation," indicating a growing emphasis on microbial metabolism and interventions in SLE. Conclusion This study provides a thorough analysis of the research landscape concerning microbiota in SLE. The microbial research in SLE mainly focused on three aspects: microbial dysbiosis, mechanism studies and translational studies (microbiota-based therapeutics). It identifies current research trends and focal points, offering valuable guidance for scholars in the field.
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Affiliation(s)
- Miaomiao Zhao
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China
| | - Xiaoting Wen
- Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China
| | - Ruiling Liu
- Department of Microbiology and Immunology, Basic Medical College, Shanxi Medical University, Jinzhong, China
| | - Ke Xu
- Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China
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Kalayci FNC, Ozen S. Possible Role of Dysbiosis of the Gut Microbiome in SLE. Curr Rheumatol Rep 2023; 25:247-258. [PMID: 37737528 DOI: 10.1007/s11926-023-01115-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/01/2023] [Indexed: 09/23/2023]
Abstract
PURPOSE OF REVIEW The resident gut microbiota serves as a double-edged sword that aids the host in multiple ways to preserve a healthy equilibrium and serve as early companions and boosters for the gradual evolution of our immune defensive layers; nevertheless, the perturbation of the symbiotic resident intestinal communities has a profound impact on autoimmunity induction, particularly in systemic lupus erythematosus (SLE). Herein, we seek to critically evaluate the microbiome research in SLE with a focus on intestinal dysbiosis. RECENT FINDINGS SLE is a complex and heterogeneous disorder with self-attack due to loss of tolerance, and there is aberrant excessive immune system activation. There is mounting evidence suggesting that intestinal flora disturbances may accelerate the formation and progression of SLE, presumably through a variety of mechanisms, including intestinal barrier dysfunction and leaky gut, molecular mimicry, bystander activation, epitope spreading, gender bias, and biofilms. Gut microbiome plays a critical role in SLE pathogenesis, and additional studies are warranted to properly define the impact of gut microbiome in SLE, which can eventually lead to new and potentially safer management approaches for this debilitating disease.
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Affiliation(s)
| | - Seza Ozen
- Department of Paediatric Rheumatology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
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Chen C, Wang Z, Ding Y, Qin Y. Tumor microenvironment-mediated immune evasion in hepatocellular carcinoma. Front Immunol 2023; 14:1133308. [PMID: 36845131 PMCID: PMC9950271 DOI: 10.3389/fimmu.2023.1133308] [Citation(s) in RCA: 97] [Impact Index Per Article: 48.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Accepted: 02/02/2023] [Indexed: 02/12/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is the third leading cause of tumor-related mortality worldwide. In recent years, the emergency of immune checkpoint inhibitor (ICI) has revolutionized the management of HCC. Especially, the combination of atezolizumab (anti-PD1) and bevacizumab (anti-VEGF) has been approved by the FDA as the first-line treatment for advanced HCC. Despite great breakthrough in systemic therapy, HCC continues to portend a poor prognosis owing to drug resistance and frequent recurrence. The tumor microenvironment (TME) of HCC is a complex and structured mixture characterized by abnormal angiogenesis, chronic inflammation, and dysregulated extracellular matrix (ECM) remodeling, collectively contributing to the immunosuppressive milieu that in turn prompts HCC proliferation, invasion, and metastasis. The tumor microenvironment coexists and interacts with various immune cells to maintain the development of HCC. It is widely accepted that a dysfunctional tumor-immune ecosystem can lead to the failure of immune surveillance. The immunosuppressive TME is an external cause for immune evasion in HCC consisting of 1) immunosuppressive cells; 2) co-inhibitory signals; 3) soluble cytokines and signaling cascades; 4) metabolically hostile tumor microenvironment; 5) the gut microbiota that affects the immune microenvironment. Importantly, the effectiveness of immunotherapy largely depends on the tumor immune microenvironment (TIME). Also, the gut microbiota and metabolism profoundly affect the immune microenvironment. Understanding how TME affects HCC development and progression will contribute to better preventing HCC-specific immune evasion and overcoming resistance to already developed therapies. In this review, we mainly introduce immune evasion of HCC underlying the role of immune microenvironment, describe the dynamic interaction of immune microenvironment with dysfunctional metabolism and the gut microbiome, and propose therapeutic strategies to manipulate the TME in favor of more effective immunotherapy.
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Affiliation(s)
| | | | | | - Yanru Qin
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Widhani A, Djauzi S, Suyatna FD, Dewi BE. Changes in Gut Microbiota and Systemic Inflammation after Synbiotic Supplementation in Patients with Systemic Lupus Erythematosus: A Randomized, Double-Blind, Placebo-Controlled Trial. Cells 2022; 11:3419. [PMID: 36359816 PMCID: PMC9658918 DOI: 10.3390/cells11213419] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Revised: 10/22/2022] [Accepted: 10/23/2022] [Indexed: 08/04/2023] Open
Abstract
Gut dysbiosis has a role in the pathogenesis of lupus. Synbiotic supplementation may restore the balance of gut microbiota. This study investigated whether synbiotics could improve gut microbiota and systemic inflammation in lupus patients. This randomized, double-blind, placebo-controlled trial was conducted in adult systemic lupus erythematosus (SLE) patients. Subjects were randomized to receive either synbiotics or a placebo. Fecal microbiota, hs-CRP, IL-6, and IL-17 were measured at baseline and after 60 days. Patients who fulfilled the inclusion criteria were randomized into synbiotic (n = 23) and placebo groups (n = 23). In the synbiotic group, hs-CRP was not significantly increased (1.8 [0.9; 4.85] vs. 2.1 [0.9; 4.25] mg/L; pre vs. post; p = 0.23), whereas in the placebo group hs-CRP was increased significantly (1.75 [0.4; 4.45] vs. 3.75 [0.58; 7.05] mg/L; pre vs. post; p = 0.005). In the synbiotic group, IL-6 decreased significantly (8.76 [6.62; 11.39] vs. 6.59 [4.96; 8.01]; pre vs. post; p = 0.02), while there was no significant change in IL-17 level. In the placebo group, there was no significant change in IL-6 and IL-17. Synbiotic supplementation increased the Firmicutes:Bacteroidetes ratio (0.05 ± 0.60 vs. -0.08 ± 0.63, synbiotic vs. placebo p = 0.48) and butyrate metabolism (p = 0.037) and decreased amino sugar and nucleotide sugar metabolism (p = 0.040). There was improvement in the SLE disease activity index 2K (SLEDAI-2K) score in the synbiotic group (14 [9; 16] vs. 8 [2; 12]; pre vs. post; p < 0.001), while no change in the placebo group (9 [8; 18.25] vs. 9 [5.5; 15]; pre vs. post; p = 0.31). Synbiotic supplementation could reduce systemic inflammation and SLE disease activity and alter the composition and functions of gut microbiota.
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Affiliation(s)
- Alvina Widhani
- Allergy and Clinical Immunology Division, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia
- Dr. Cipto Mangunkusumo Hospital, Jakarta 10430, Indonesia
- Doctoral Program in Biomedical Science, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia
| | - Samsuridjal Djauzi
- Allergy and Clinical Immunology Division, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia
- Dr. Cipto Mangunkusumo Hospital, Jakarta 10430, Indonesia
| | | | - Beti Ernawati Dewi
- Department of Microbiology, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia
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Zhan Y, Liu Q, Zhang B, Huang X, Lu Q. Recent advances in systemic lupus erythematosus and microbiota: from bench to bedside. Front Med 2022; 16:686-700. [DOI: 10.1007/s11684-022-0957-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Accepted: 08/18/2022] [Indexed: 11/19/2022]
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Zhang H, Lang X, Li X, Chen G, Wang C. Effect of Zanthoxylum bungeanum essential oil on rumen enzyme activity, microbiome, and metabolites in lambs. PLoS One 2022; 17:e0272310. [PMID: 35930558 PMCID: PMC9355197 DOI: 10.1371/journal.pone.0272310] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Accepted: 07/15/2022] [Indexed: 11/26/2022] Open
Abstract
Antibiotics were once used in animal production to improve productivity and resistance to pathogenic microbiota. However, due to its negative effects, the search for a new class of substances that can replace its efficacy has become one of the urgent problems to be solved. Plant essential oils (EOs) as a natural feed additive can maintain microbiota homeostasis and improve animal performance. However, its specific mechanism of action needs to be further investigated. Therefore, we added different doses of essential oil of Zanthoxylum bungeanum (EOZB) to the diets of Small Tail Han Sheep hybrid male lambs (STH lambs) to evaluate the effect of EOZB on rumen enzyme activity, rumen microbiology, and its metabolites in STH lambs. Twenty STH lambs were randomly divided into four groups (n = 5/group) and provided with the same diet. The dietary treatments were as follows: basal diet (BD) group; BD+EOZB 5 ml/kg group; BD+EOZB 10 ml/kg group; BD+EOZB 15 ml/kg group. We found that EOZB 10 ml/kg helped to increase rumen pectinase (P<0.05) and lipase (P<0.05) activities. Microbial 16S rRNA gene analysis showed that EOZB significantly altered the abundance of rumen microbiota (P<0.05). LC/GC-MS metabolomic analysis showed that the addition of EOZB produced a total of 1073 differential metabolites, with 58 differential metabolites remaining after raising the screening criteria. These differential metabolites were mainly enriched in glycerophospholipid metabolism, choline metabolism in cancer, retrograde endocannabinoid signaling, benzoxazinoid biosynthesis, and protein digestion and absorption. Correlation analysis showed that some rumen microbiota were significantly correlated with differential metabolite and enzyme activities.
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Affiliation(s)
- Hailong Zhang
- College of Animal Science and Technology, Gansu Agriculture University, Lanzhou, China
- Key laboratory for Sheep, Goat and Cattle Germplasm and Straw Feed in Gansu Province, Lanzhou, China
| | - Xia Lang
- Key laboratory for Sheep, Goat and Cattle Germplasm and Straw Feed in Gansu Province, Lanzhou, China
- Institute of Animal Science and Grass Science and Green Agriculture, Gansu Academy of Agricultural Sciences, Lanzhou, China
| | - Xiao Li
- College of Animal Science and Technology, Gansu Agriculture University, Lanzhou, China
| | - Guoshun Chen
- College of Animal Science and Technology, Gansu Agriculture University, Lanzhou, China
- * E-mail: (GC); (CW)
| | - Cailian Wang
- Key laboratory for Sheep, Goat and Cattle Germplasm and Straw Feed in Gansu Province, Lanzhou, China
- Institute of Animal Science and Grass Science and Green Agriculture, Gansu Academy of Agricultural Sciences, Lanzhou, China
- * E-mail: (GC); (CW)
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Targeting the gut and tumor microbiota in cancer. Nat Med 2022; 28:690-703. [PMID: 35440726 DOI: 10.1038/s41591-022-01779-2] [Citation(s) in RCA: 272] [Impact Index Per Article: 90.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Accepted: 03/09/2022] [Indexed: 02/07/2023]
Abstract
Microorganisms within the gut and other niches may contribute to carcinogenesis, as well as shaping cancer immunosurveillance and response to immunotherapy. Our understanding of the complex relationship between different host-intrinsic microorganisms, as well as the multifaceted mechanisms by which they influence health and disease, has grown tremendously-hastening development of novel therapeutic strategies that target the microbiota to improve treatment outcomes in cancer. Accordingly, the evaluation of a patient's microbial composition and function and its subsequent targeted modulation represent key elements of future multidisciplinary and precision-medicine approaches. In this Review, we outline the current state of research toward harnessing the microbiome to better prevent and treat cancer.
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Xiang S, Qu Y, Qian S, Wang R, Wang Y, Jin Y, Li J, Ding X. Association between systemic lupus erythematosus and disruption of gut microbiota: a meta-analysis. Lupus Sci Med 2022; 9:e000599. [PMID: 35346981 PMCID: PMC8961174 DOI: 10.1136/lupus-2021-000599] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Accepted: 03/06/2022] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Recent studies reported that SLE is characterised by altered interactions between the microbiome and immune system. We performed a meta-analysis of publications on this topic. METHODS Case-control studies that compared patients with SLE and healthy controls (HCs) and determined the diversity of the gut microbiota and the abundance of different microbes were examined. Stata/MP V.16 was used for the meta-analysis. A Bonferroni correction for multiple tests was used to reduce the likelihood of false-positive results. RESULTS We included 11 case-control studies that examined 373 patients with SLE and 1288 HCs. These studies were performed in five countries and nine cities. Compared with HCs, patients with SLE had gut microbiota with lower Shannon-Wiener diversity index (weighted mean difference=-0.22, 95% CI -0.32 to -0.13, p<0.001) and lower Chao1 richness (standardised mean difference (SMD)=-0.62, 95% CI -1.04 to -0.21, p=0.003). Patients with SLE had lower abundance of Ruminococcaceae (SMD = -0.49, 95% CI -0.84 to -0.15,p=0.005), but greater abundance of Enterobacteriaceae (SMD=0.45, 95% CI 0.01 to 0.89, p=0.045) and Enterococcaceae (SMD=0.53, 95% CI 0.05 to 1.01, p=0.03). However, only the results for Ruminococcaceae passed the Bonferroni correction (p=0.0071). The two groups had no significant differences in Lachnospiraceae and Bacteroides (both p>0.05). Patients with SLE who used high doses of glucocorticoids had altered gut microbiota based on the Chao1 species diversity estimator, and hydroxychloroquine use appeared to reduce the abundance of Enterobacteriaceae. CONCLUSIONS Patients with SLE have imbalanced gut microbiota, with a decrease in beneficial bacteria and an increase in harmful bacteria. Drugs used to treat SLE may also alter the gut microbiota of these patients.
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Affiliation(s)
- Shate Xiang
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yiqian Qu
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Suhai Qian
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Rongyun Wang
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yao Wang
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yibo Jin
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Jie Li
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Xinghong Ding
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
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Ma J, Huang L, Hu D, Zeng S, Han Y, Shen H. The role of the tumor microbe microenvironment in the tumor immune microenvironment: bystander, activator, or inhibitor? J Exp Clin Cancer Res 2021; 40:327. [PMID: 34656142 PMCID: PMC8520212 DOI: 10.1186/s13046-021-02128-w] [Citation(s) in RCA: 75] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Accepted: 10/04/2021] [Indexed: 02/08/2023] Open
Abstract
The efficacy of cancer immunotherapy largely depends on the tumor microenvironment, especially the tumor immune microenvironment. Emerging studies have claimed that microbes reside within tumor cells and immune cells, suggesting that these microbes can impact the state of the tumor immune microenvironment. For the first time, this review delineates the landscape of intra-tumoral microbes and their products, herein defined as the tumor microbe microenvironment. The role of the tumor microbe microenvironment in the tumor immune microenvironment is multifaceted: either as an immune activator, inhibitor, or bystander. The underlying mechanisms include: (I) the presentation of microbial antigens by cancer cells and immune cells, (II) microbial antigens mimicry shared with tumor antigens, (III) microbe-induced immunogenic cell death, (IV) microbial adjuvanticity mediated by pattern recognition receptors, (V) microbe-derived metabolites, and (VI) microbial stimulation of inhibitory checkpoints. The review further suggests the use of potential modulation strategies of the tumor microbe microenvironment to enhance the efficacy and reduce the adverse effects of checkpoint inhibitors. Lastly, the review highlights some critical questions awaiting to be answered in this field and provides possible solutions. Overall, the tumor microbe microenvironment modulates the tumor immune microenvironment, making it a potential target for improving immunotherapy. It is a novel field facing major challenges and deserves further exploration.
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Affiliation(s)
- Jiayao Ma
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Lingjuan Huang
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Die Hu
- Xiangya Medical College, Central South University, Changsha, 410013, Hunan, China
| | - Shan Zeng
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
- Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P.R. China.
| | - Ying Han
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
- Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
| | - Hong Shen
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
- Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P.R. China.
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Correlation Analysis between Gut Microbiota and Metabolites in Children with Systemic Lupus Erythematosus. J Immunol Res 2021; 2021:5579608. [PMID: 34341764 PMCID: PMC8325587 DOI: 10.1155/2021/5579608] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Revised: 05/30/2021] [Accepted: 07/02/2021] [Indexed: 12/14/2022] Open
Abstract
Systemic lupus erythematosus (SLE) is an autoimmune-mediated diffuse connective tissue disease characterized by immune inflammation with an unclear aetiology and pathogenesis. This work profiled the intestinal flora and faecal metabolome of patients with SLE using 16S RNA sequencing and gas chromatography-mass spectrometry (GC-MS). We identified unchanged alpha diversity and partially altered beta diversity of the intestinal flora. Another important finding was the increase in Proteobacteria and Enterobacteriales and the decrease in Ruminococcaceae among SLE patients. For metabolites, amino acids and short-chain fatty acids were enriched when long-chain fatty acids were downregulated in SLE faecal samples. KEGG analysis showed the significance of the protein digestion and absorption pathway, and association analysis revealed the key role of 3-phenylpropanoic acid and Sphingomonas. Sphingomonas were reported to be less abundant in healthy periodontal sites of SLE patients than in those of HCs, indicating transmission of oral species to the gut. This study contributes to the understanding of the pathogenesis of SLE disease from the perspective of intestinal microorganisms, explains the pathogenesis of SLE, and serves as a basis for exploring potential treatments for the disease.
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Zubeldia-Varela E, Barber D, Barbas C, Perez-Gordo M, Rojo D. Sample pre-treatment procedures for the omics analysis of human gut microbiota: Turning points, tips and tricks for gene sequencing and metabolomics. J Pharm Biomed Anal 2020; 191:113592. [PMID: 32947167 DOI: 10.1016/j.jpba.2020.113592] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Revised: 07/29/2020] [Accepted: 08/23/2020] [Indexed: 02/06/2023]
Abstract
The connection between gut microbiota and human health is becoming increasingly relevant and the number of groups working in this field is constantly growing. In this context, from high-throughput gene sequencing to metabolomics analysis, the omics technologies have contributed enormously to unveil the secret crosstalk between us and our microbes. All the omics technologies produce a great amount of information, and processing this information is time-consuming and expensive. For this reason, a correct experimental design and a careful pre-analytical planning are crucial. To study the human gut microbiota, faeces are the sample of choice. Faecal material is complex, and procedures for collecting and preserving faeces are not well-established. Furthermore, increasing evidence suggests that multiple confounding factors, such as antibiotics consumption, mode of delivery, diet, aging and several diseases and disorders can alter the composition and functionality of the microbiota. This review is focused on the discussion of critical general issues during the pre-analytical planning, from patient handling to faeces sampling, including collection procedures, transport, storage conditions and possible pre-treatments, which are critical for a successful research in omics with a special attention to metabolomics and gene sequencing. We also point out that the adoption of standard operating procedures in the field is needed to guarantee accuracy and reproducibility of results.
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Affiliation(s)
- Elisa Zubeldia-Varela
- Centre for Metabolomics and Bioanalysis (CEMBIO), Department of Chemistry and Biochemistry, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28660 Boadilla del Monte, Madrid, Spain; Departamento de Ciencias Médicas Básicas, Facultad de Medicina, Universidad San Pablo-CEU, CEU Universities, ARADyAL, Urbanización Montepríncipe, 28660 Boadilla del Monte, Madrid, Spain
| | - Domingo Barber
- Institute of Applied and Molecular Medicine (IMMA), Facultad de Medicina, Universidad San Pablo-CEU, CEU Universities, ARADyAL, Urbanización Montepríncipe, 28660 Boadilla del Monte, Madrid, Spain
| | - Coral Barbas
- Centre for Metabolomics and Bioanalysis (CEMBIO), Department of Chemistry and Biochemistry, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28660 Boadilla del Monte, Madrid, Spain
| | - Marina Perez-Gordo
- Departamento de Ciencias Médicas Básicas, Facultad de Medicina, Universidad San Pablo-CEU, CEU Universities, ARADyAL, Urbanización Montepríncipe, 28660 Boadilla del Monte, Madrid, Spain; Institute of Applied and Molecular Medicine (IMMA), Facultad de Medicina, Universidad San Pablo-CEU, CEU Universities, ARADyAL, Urbanización Montepríncipe, 28660 Boadilla del Monte, Madrid, Spain
| | - David Rojo
- Centre for Metabolomics and Bioanalysis (CEMBIO), Department of Chemistry and Biochemistry, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28660 Boadilla del Monte, Madrid, Spain.
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14
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15
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Choi SC, Brown J, Gong M, Ge Y, Zadeh M, Li W, Croker BP, Michailidis G, Garrett TJ, Mohamadzadeh M, Morel L. Gut microbiota dysbiosis and altered tryptophan catabolism contribute to autoimmunity in lupus-susceptible mice. Sci Transl Med 2020; 12:eaax2220. [PMID: 32641487 PMCID: PMC7739186 DOI: 10.1126/scitranslmed.aax2220] [Citation(s) in RCA: 163] [Impact Index Per Article: 32.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Revised: 10/04/2019] [Accepted: 01/27/2020] [Indexed: 12/12/2022]
Abstract
The autoimmune disease systemic lupus erythematosus (SLE) is characterized by the production of pathogenic autoantibodies. It has been postulated that gut microbial dysbiosis may be one of the mechanisms involved in SLE pathogenesis. Here, we demonstrate that the dysbiotic gut microbiota of triple congenic (TC) lupus-prone mice (B6.Sle1.Sle2.Sle3) stimulated the production of autoantibodies and activated immune cells when transferred into germfree congenic C57BL/6 (B6) mice. Fecal transfer to B6 mice induced autoimmune phenotypes only when the TC donor mice exhibited autoimmunity. Autoimmune pathogenesis was mitigated by horizontal transfer of the gut microbiota between co-housed lupus-prone TC mice and control congenic B6 mice. Metabolomic screening identified an altered distribution of tryptophan metabolites in the feces of TC mice including an increase in kynurenine, which was alleviated after antibiotic treatment. Low dietary tryptophan prevented autoimmune pathology in TC mice, whereas high dietary tryptophan exacerbated disease. Reducing dietary tryptophan altered gut microbial taxa in both lupus-prone TC mice and control B6 mice. Consequently, fecal transfer from TC mice fed a high tryptophan diet, but not a low tryptophan diet, induced autoimmune phenotypes in germfree B6 mice. The interplay of gut microbial dysbiosis, tryptophan metabolism and host genetic susceptibility in lupus-prone mice suggest that aberrant tryptophan metabolism may contribute to autoimmune activation in this disease.
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Affiliation(s)
- Seung-Chul Choi
- Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA
| | - Josephine Brown
- Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA
| | - Minghao Gong
- Department of Infectious Diseases and Immunology, University of Florida, Gainesville, FL 32610, USA
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Florida, Gainesville, FL 32610, USA
| | - Yong Ge
- Department of Infectious Diseases and Immunology, University of Florida, Gainesville, FL 32610, USA
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Florida, Gainesville, FL 32610, USA
| | - Mojgan Zadeh
- Department of Infectious Diseases and Immunology, University of Florida, Gainesville, FL 32610, USA
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Florida, Gainesville, FL 32610, USA
| | - Wei Li
- Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA
| | - Byron P Croker
- Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA
| | - George Michailidis
- Department of Statistics and the Informatics Institute, University of Florida, Gainesville, FL 32610, USA
| | - Timothy J Garrett
- Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA
| | - Mansour Mohamadzadeh
- Department of Infectious Diseases and Immunology, University of Florida, Gainesville, FL 32610, USA.
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Florida, Gainesville, FL 32610, USA
| | - Laurence Morel
- Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA.
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Niccolai E, Boem F, Emmi G, Amedei A. The link "Cancer and autoimmune diseases" in the light of microbiota: Evidence of a potential culprit. Immunol Lett 2020; 222:12-28. [PMID: 32145242 DOI: 10.1016/j.imlet.2020.03.001] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Revised: 02/20/2020] [Accepted: 03/03/2020] [Indexed: 12/15/2022]
Abstract
Evidence establishes that chronic inflammation and autoimmunity are associated with cancer development and patients with a primary malignancy may develop autoimmune-like diseases. Despite immune dysregulation is a common feature of both cancer and autoimmune diseases, precise mechanisms underlying this susceptibility are not clarified and different hypotheses have been proposed, starting from genetic and environmental common features, to intrinsic properties of immune system. Moreover, as the development and use of immunomodulatory therapies for cancer and autoimmune diseases are increasing, the elucidation of this relationship must be investigated in order to offer the best and most secure therapeutic options. The microbiota could represent a potential link between autoimmune diseases and cancer. The immunomodulation role of microbiota is widely recognized and under eubiosis, it orchestrates both the innate and adaptive response of immunity, in order to discriminate and modulate the immune response itself in the most appropriate way. Therefore, a dysbiotic status can alter the immune tonus rendering the host prone to exogenous or endogenous infections, breaking the tolerance against self-components and activating the immune responses in an excessive (i.e. chronic inflammation) or deficient way, favoring the onset of neoplastic and autoimmune diseases.
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Affiliation(s)
- Elena Niccolai
- Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134, Florence, Italy
| | - Federico Boem
- Department of Oncology and Hemato-Oncology, University of Milan, Via Festa del Perdono 7, 20122, Milan, Italy; Department of Philosophy and Educational Sciences. University of Turin, Via Verdi 8, 10124, Turin, Italy
| | - Giacomo Emmi
- Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134, Florence, Italy; Neuromusculoskeletal Department (Interdisciplinary Internal Medicine), Azienda Ospedaliera Universitaria Careggi, Largo Brambilla 3, 50134, Florence, Italy
| | - Amedeo Amedei
- Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134, Florence, Italy; Neuromusculoskeletal Department (Interdisciplinary Internal Medicine), Azienda Ospedaliera Universitaria Careggi, Largo Brambilla 3, 50134, Florence, Italy.
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17
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Zhang X, Chen BD, Zhao LD, Li H. The Gut Microbiota: Emerging Evidence in Autoimmune Diseases. Trends Mol Med 2020; 26:862-873. [PMID: 32402849 DOI: 10.1016/j.molmed.2020.04.001] [Citation(s) in RCA: 139] [Impact Index Per Article: 27.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Revised: 03/26/2020] [Accepted: 04/03/2020] [Indexed: 12/16/2022]
Abstract
The pathogenesis of autoimmune diseases (AIDs) is not only attributed to genetic susceptibilities but also environmental factors, among which, disturbed gut microbiota has attracted increasing attention. Compositional and functional changes of gut microbiota have been reported in various AIDs, and increasing evidence suggests that disturbed gut microbiota contributes to their immunopathogenesis. The accepted mechanisms include abnormal microbial translocation, molecular mimicry, and dysregulation of both local and systemic immunity. Studies have also suggested microbiota-based classification models and therapeutic interventions for patients with AIDs. Further in-depth mechanistic studies on microbiota-autoimmunity interplay in AIDs are urgently needed and underway to explore novel and precise diagnostic biomarkers and develop disease and patient-tailored therapeutic strategies.
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Affiliation(s)
- Xuan Zhang
- Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College Hospital, The Ministry of Education Key Laboratory, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China, 100730; Clinical Immunology Centre, Medical Epigenetics Research Centre, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, 100730.
| | - Bei-di Chen
- Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College Hospital, The Ministry of Education Key Laboratory, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China, 100730; Clinical Immunology Centre, Medical Epigenetics Research Centre, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, 100730
| | - Li-Dan Zhao
- Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College Hospital, The Ministry of Education Key Laboratory, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China, 100730
| | - Hao Li
- Division of Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
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18
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Zhang CX, Wang HY, Yin L, Mao YY, Zhou W. Immunometabolism in the pathogenesis of systemic lupus erythematosus. J Transl Autoimmun 2020; 3:100046. [PMID: 32743527 PMCID: PMC7388408 DOI: 10.1016/j.jtauto.2020.100046] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Revised: 03/07/2020] [Accepted: 03/08/2020] [Indexed: 12/25/2022] Open
Abstract
Systemic lupus erythematosus (SLE) is a typical autoimmune disease characterized by chronic inflammation and pathogenic auto-antibodies. Apart from B cells, dysregulation of other immune cells also plays an essential role in the pathogenesis and development of the disease including CD4+T cells, dendritic cells, macrophages and neutrophils. Since metabolic programs control immune cell fate and function, they are critical checkpoints in an effective immune response and are involved in the etiology of autoimmune disease. In addition, mitochondria and oxidative stress are both involved in cellular metabolism and is also essential in immune response. In this review, apart from the disturbed immune system, we will discuss mitochondrial dysfunction, oxidative stress, abnormal metabolism (including glucose, lipid and amino acid metabolism) of immune cells as well as epigenetic control of metabolism reprogramming to elucidate the underlying pathogenic mechanisms of systemic lupus erythematosus.
Mitochondria plays a vital role in cellular metabolism and is involved in immune response. There are alterations in glucose, lipid and amino acid metabolism of various immune cells in SLE patients. Epigenetic status is influenced by the presence of metabolic intermediates and certain autoimmunity-related genes are hypomethylated in CD4+T cells, CD19+ B cells as well as CD14+ monocytes of SLE.
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Affiliation(s)
- Chen-Xing Zhang
- Department of Nephrology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, 200127, Shanghai, China
| | - Hui-Yu Wang
- Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149, Muenster, Germany
| | - Lei Yin
- Department of Nephrology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, 200127, Shanghai, China
| | - You-Ying Mao
- Department of Nephrology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, 200127, Shanghai, China
| | - Wei Zhou
- Department of Nephrology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, 200127, Shanghai, China
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19
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Mayneris-Perxachs J, Fernández-Real JM. Exploration of the microbiota and metabolites within body fluids could pinpoint novel disease mechanisms. FEBS J 2019; 287:856-865. [PMID: 31709683 DOI: 10.1111/febs.15130] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Revised: 09/24/2019] [Accepted: 11/08/2019] [Indexed: 12/25/2022]
Abstract
Thanks to the emergence and recent advances in high-throughput sequencing technologies, it is becoming more evident every day that changes in the microbiome composition are linked to a myriad of health conditions. Despite this, the mechanisms of host-microbiota signalling remain largely unknown. The microbiome has an extensive metabolic activity that leads to the generation of a large number of compounds that are likely to influence host health. Therefore, the microbiome-host cross-talk is in part mediated by microbial-derived metabolites. Unlike metagenomics, which only provides information about microbial genes and thus the microbiome functional potential, metabolic phenotyping is well suited to capture their actual metabolic activity. Here, we provide an overview of these approaches and propose an integration of metagenomics, as a microbiome compositional readout, with faecal and plasma/urine metabolomics, as a functional readout, to unravel novel mechanisms linking the microbiome to host health and disease.
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Affiliation(s)
- Jordi Mayneris-Perxachs
- Department of Endocrinology, Diabetes and Nutrition, Hospital of Girona 'Dr Josep Trueta', University of Girona, Girona Biomedical Research Institute (IdibGi), Spain.,CIBERobn Pathophysiology of Obesity and Nutrition, Instituto de Salud Carlos III, Madrid, Spain
| | - José-Manuel Fernández-Real
- Department of Endocrinology, Diabetes and Nutrition, Hospital of Girona 'Dr Josep Trueta', University of Girona, Girona Biomedical Research Institute (IdibGi), Spain.,CIBERobn Pathophysiology of Obesity and Nutrition, Instituto de Salud Carlos III, Madrid, Spain
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20
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González-Riano C, Dudzik D, Garcia A, Gil-de-la-Fuente A, Gradillas A, Godzien J, López-Gonzálvez Á, Rey-Stolle F, Rojo D, Ruperez FJ, Saiz J, Barbas C. Recent Developments along the Analytical Process for Metabolomics Workflows. Anal Chem 2019; 92:203-226. [PMID: 31625723 DOI: 10.1021/acs.analchem.9b04553] [Citation(s) in RCA: 67] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Carolina González-Riano
- Centre for Metabolomics and Bioanalysis (CEMBIO), Chemistry and Biochemistry Department, Pharmacy Faculty , Universidad San Pablo-CEU , Boadilla del Monte , 28668 Madrid , Spain
| | - Danuta Dudzik
- Centre for Metabolomics and Bioanalysis (CEMBIO), Chemistry and Biochemistry Department, Pharmacy Faculty , Universidad San Pablo-CEU , Boadilla del Monte , 28668 Madrid , Spain.,Department of Biopharmaceutics and Pharmacodynamics, Faculty of Pharmacy , Medical University of Gdańsk , 80-210 Gdańsk , Poland
| | - Antonia Garcia
- Centre for Metabolomics and Bioanalysis (CEMBIO), Chemistry and Biochemistry Department, Pharmacy Faculty , Universidad San Pablo-CEU , Boadilla del Monte , 28668 Madrid , Spain
| | - Alberto Gil-de-la-Fuente
- Department of Information Technology, Escuela Politécnica Superior , Universidad San Pablo-CEU , 28003 Madrid , Spain
| | - Ana Gradillas
- Centre for Metabolomics and Bioanalysis (CEMBIO), Chemistry and Biochemistry Department, Pharmacy Faculty , Universidad San Pablo-CEU , Boadilla del Monte , 28668 Madrid , Spain
| | - Joanna Godzien
- Centre for Metabolomics and Bioanalysis (CEMBIO), Chemistry and Biochemistry Department, Pharmacy Faculty , Universidad San Pablo-CEU , Boadilla del Monte , 28668 Madrid , Spain.,Clinical Research Centre , Medical University of Bialystok , 15-089 Bialystok , Poland
| | - Ángeles López-Gonzálvez
- Centre for Metabolomics and Bioanalysis (CEMBIO), Chemistry and Biochemistry Department, Pharmacy Faculty , Universidad San Pablo-CEU , Boadilla del Monte , 28668 Madrid , Spain
| | - Fernanda Rey-Stolle
- Centre for Metabolomics and Bioanalysis (CEMBIO), Chemistry and Biochemistry Department, Pharmacy Faculty , Universidad San Pablo-CEU , Boadilla del Monte , 28668 Madrid , Spain
| | - David Rojo
- Centre for Metabolomics and Bioanalysis (CEMBIO), Chemistry and Biochemistry Department, Pharmacy Faculty , Universidad San Pablo-CEU , Boadilla del Monte , 28668 Madrid , Spain
| | - Francisco J Ruperez
- Centre for Metabolomics and Bioanalysis (CEMBIO), Chemistry and Biochemistry Department, Pharmacy Faculty , Universidad San Pablo-CEU , Boadilla del Monte , 28668 Madrid , Spain
| | - Jorge Saiz
- Centre for Metabolomics and Bioanalysis (CEMBIO), Chemistry and Biochemistry Department, Pharmacy Faculty , Universidad San Pablo-CEU , Boadilla del Monte , 28668 Madrid , Spain
| | - Coral Barbas
- Centre for Metabolomics and Bioanalysis (CEMBIO), Chemistry and Biochemistry Department, Pharmacy Faculty , Universidad San Pablo-CEU , Boadilla del Monte , 28668 Madrid , Spain
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21
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Gene-diet interactions associated with complex trait variation in an advanced intercross outbred mouse line. Nat Commun 2019; 10:4097. [PMID: 31506438 PMCID: PMC6736984 DOI: 10.1038/s41467-019-11952-w] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Accepted: 08/13/2019] [Indexed: 12/12/2022] Open
Abstract
Phenotypic variation of quantitative traits is orchestrated by a complex interplay between the environment (e.g. diet) and genetics. However, the impact of gene-environment interactions on phenotypic traits mostly remains elusive. To address this, we feed 1154 mice of an autoimmunity-prone intercross line (AIL) three different diets. We find that diet substantially contributes to the variability of complex traits and unmasks additional genetic susceptibility quantitative trait loci (QTL). By performing whole-genome sequencing of the AIL founder strains, we resolve these QTLs to few or single candidate genes. To address whether diet can also modulate genetic predisposition towards a given trait, we set NZM2410/J mice on similar dietary regimens as AIL mice. Our data suggest that diet modifies genetic susceptibility to lupus and shifts intestinal bacterial and fungal community composition, which precedes clinical disease manifestation. Collectively, our study underlines the importance of including environmental factors in genetic association studies. Complex traits associate with genetic variation and environment and their interaction. Here, the authors study the influence of different diets on trait variability in 1154 outbred mice from an advanced intercross line and find gene-diet interactions associated with spontaneous autoimmunity development in these animals.
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22
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Maslowski KM. Metabolism at the centre of the host-microbe relationship. Clin Exp Immunol 2019; 197:193-204. [PMID: 31107965 PMCID: PMC6642865 DOI: 10.1111/cei.13329] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/16/2019] [Indexed: 12/13/2022] Open
Abstract
Maintaining homoeostatic host–microbe interactions is vital for host immune function. The gut microbiota shapes the host immune system and the immune system reciprocally shapes and modifies the gut microbiota. However, our understanding of how these microbes are tolerated and how individual, or communities of, gut microbes influence host function is limited. This review will focus on metabolites as key mediators of this complex host–microbe relationship. It will look at the central role of epithelial metabolism in shaping the gut microbiota, how microbial metabolites influence the epithelium and the mucosal and peripheral immune system, and how the immune system shapes microbial composition and metabolism. Finally, this review will look at how metabolites are involved in cross‐talk between different members of the microbiota and their role during infections.
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Affiliation(s)
- K M Maslowski
- Institute of Immunology and Immunotherapy and Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
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23
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Meng X, Zhou HY, Shen HH, Lufumpa E, Li XM, Guo B, Li BZ. Microbe-metabolite-host axis, two-way action in the pathogenesis and treatment of human autoimmunity. Autoimmun Rev 2019; 18:455-475. [PMID: 30844549 DOI: 10.1016/j.autrev.2019.03.006] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Accepted: 11/05/2018] [Indexed: 12/14/2022]
Abstract
The role of microorganism in human diseases cannot be ignored. These microorganisms have evolved together with humans and worked together with body's mechanism to maintain immune and metabolic function. Emerging evidence shows that gut microbe and their metabolites open up new doors for the study of human response mechanism. The complexity and interdependence of these microbe-metabolite-host interactions are rapidly being elucidated. There are various changes of microbial levels in models or in patients of various autoimmune diseases (AIDs). In addition, the relevant metabolites involved in mechanism mainly include short-chain fatty acids (SCFAs), bile acids (BAs), and polysaccharide A (PSA). Meanwhile, the interaction between microbes and host genes is also a factor that must be considered. It has been demonstrated that human microbes are involved in the development of a variety of AIDs, including organ-specific AIDs and systemic AIDs. At the same time, microbes or related products can be used to remodel body's response to alleviate or cure diseases. This review summarizes the latest research of microbes and their related metabolites in AIDs. More importantly, it highlights novel and potential therapeutics, including fecal microbial transplantation, probiotics, prebiotics, and synbiotics. Nonetheless, exact mechanisms still remain elusive, and future research will focus on finding a specific strain that can act as a biomarker of an autoimmune disease.
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Affiliation(s)
- Xiang Meng
- School of Stomatology, Anhui Medical University, Hefei, Anhui, China
| | - Hao-Yue Zhou
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China; Anhui Province Key Laboratory of Major Autoimmune Diseases, 81 Meishan Road, Hefei, Anhui, China
| | - Hui-Hui Shen
- Department of Clinical Medicine, The second School of Clinical Medicine, Anhui Medical University, Anhui, Hefei, China
| | - Eniya Lufumpa
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Xiao-Mei Li
- Department of Rheumatology & Immunology, Anhui Provincial Hospital, Anhui, Hefei, China
| | - Biao Guo
- The Second Affiliated Hospital of Anhui Medical University, Anhui, Hefei, China
| | - Bao-Zhu Li
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China; Anhui Province Key Laboratory of Major Autoimmune Diseases, 81 Meishan Road, Hefei, Anhui, China.
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24
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Kim S, Chun SH, Park HJ, Lee SI. Systemic Sclerosis and Microbiota: Overview of Current Research Trends and Future Perspective. JOURNAL OF RHEUMATIC DISEASES 2019. [DOI: 10.4078/jrd.2019.26.4.235] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Suhee Kim
- Department of Internal Medicine and Institute of Health Science, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Korea
| | - Sung Hak Chun
- Department of Internal Medicine and Institute of Health Science, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Korea
| | - Hee Jin Park
- Department of Internal Medicine and Institute of Health Science, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Korea
| | - Sang-Il Lee
- Department of Internal Medicine and Institute of Health Science, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Korea
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25
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Abstract
Disruption of the gut microbiota is thought to contribute to disease onset in individuals with a genetic predisposition to autoimmunity. In a recent issue of Science, Manfredo Vieira et al. (2018) identify translocation of the gut commensal Enterococcus gallinarum into the liver as a trigger for the autoimmune disease systemic lupus erythematous.
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Affiliation(s)
- Matteo M Guerrini
- Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences, RIKEN Yokohama Institute,1-7-22 Suehiro-cho Tsurumi-ku, Yokohama, 230-0045 Kanagawa, Japan
| | - Alexis Vogelzang
- Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences, RIKEN Yokohama Institute,1-7-22 Suehiro-cho Tsurumi-ku, Yokohama, 230-0045 Kanagawa, Japan
| | - Sidonia Fagarasan
- Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences, RIKEN Yokohama Institute,1-7-22 Suehiro-cho Tsurumi-ku, Yokohama, 230-0045 Kanagawa, Japan.
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Vogelzang A, Guerrini MM, Minato N, Fagarasan S. Microbiota - an amplifier of autoimmunity. Curr Opin Immunol 2018; 55:15-21. [PMID: 30248521 DOI: 10.1016/j.coi.2018.09.003] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Accepted: 09/07/2018] [Indexed: 02/08/2023]
Abstract
Many studies describe dysbiosis as a change in the microbiota that accompanies autoimmune illnesses, but little is known about whether these changes are a cause or consequence of an altered immune state. The immune system actively shapes the composition of the microbiota, with divergent outcomes in healthy or autoimmune-prone individuals. The gut microbiota in turn acts as an acquired endocrine organ, influencing the physiology of the host via release of nutrients and chemical messengers. Dysbiosis arising from abnormal immune function can initiate or amplify autoimmunity through multiple mechanisms. We examine how the bidirectional relationship between resident microbes and the immune system contributes to autoimmune diseases.
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Affiliation(s)
- Alexis Vogelzang
- Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences, RIKEN Yokohama Institute, Tsurumi Ward, Suehirocho, 1 Chome-7-22, Yokohama, Kanagawa Prefecture, 230-0045, Japan
| | - Matteo M Guerrini
- Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences, RIKEN Yokohama Institute, Tsurumi Ward, Suehirocho, 1 Chome-7-22, Yokohama, Kanagawa Prefecture, 230-0045, Japan
| | - Nagahiro Minato
- Medical Innovation Center, Kyoto University Graduate School of Medicine, Sakyo Ward, Yoshida-Konoe, Kyoto, Kyoto Prefecture, 606-8501, Japan
| | - Sidonia Fagarasan
- Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences, RIKEN Yokohama Institute, Tsurumi Ward, Suehirocho, 1 Chome-7-22, Yokohama, Kanagawa Prefecture, 230-0045, Japan.
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27
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Abstract
PURPOSE OF REVIEW Accumulating evidence suggests that gut microbiota affect the development and function of the immune system and may play a role in the pathogenesis of autoimmune diseases. The purpose of this review is to summarize recent studies reporting gastrointestinal microbiota aberrations associated with the systemic sclerosis disease state. RECENT FINDINGS The studies described herein have identified common changes in gut microbial composition. Specifically, patients with SSc have decreased abundance of beneficial commensal genera (e.g., Faecalibacterium, Clostridium, and Bacteroides) and increased abundance of pathobiont genera (e.g., Fusobacterium, Prevotella, Erwinia). In addition, some studies have linked specific genera with the severity of gastrointestinal symptoms in systemic sclerosis. More research is needed to further characterize the gastrointestinal microbiota in systemic sclerosis and understand how microbiota perturbations can affect inflammation, fibrosis, and clinical outcomes. Interventional studies aimed at addressing/correcting these perturbations, either through dietary modification, pro/pre-biotic supplementation, or fecal transplantation, may lead to improved outcomes for patients with systemic sclerosis.
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Affiliation(s)
- Chiara Bellocchi
- Scleroderma Unit, Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, University of Milan, Milan, Italy
| | - Elizabeth R Volkmann
- Division of Rheumatology, Department of Medicine, David Geffen School of Medicine, University of California, 1000 Veteran Avenue, Ste 32-59, Los Angeles, CA, 90095, USA.
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28
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Rizzetto L, Fava F, Tuohy KM, Selmi C. Connecting the immune system, systemic chronic inflammation and the gut microbiome: The role of sex. J Autoimmun 2018; 92:12-34. [PMID: 29861127 DOI: 10.1016/j.jaut.2018.05.008] [Citation(s) in RCA: 226] [Impact Index Per Article: 32.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Revised: 05/18/2018] [Accepted: 05/21/2018] [Indexed: 12/12/2022]
Abstract
Unresolved low grade systemic inflammation represents the underlying pathological mechanism driving immune and metabolic pathways involved in autoimmune diseases (AID). Mechanistic studies in animal models of AID and observational studies in patients have found alterations in gut microbiota communities and their metabolites, suggesting a microbial contribution to the onset or progression of AID. The gut microbiota and its metabolites have been shown to influence immune functions and immune homeostasis both within the gut and systematically. Microbial derived-short chain fatty acid (SCFA) and bio-transformed bile acid (BA) have been shown to influence the immune system acting as ligands specific cell signaling receptors like GPRCs, TGR5 and FXR, or via epigenetic processes. Similarly, intestinal permeability (leaky gut) and bacterial translocation are important contributors to chronic systemic inflammation and, without repair of the intestinal barrier, might represent a continuous inflammatory stimulus capable of triggering autoimmune processes. Recent studies indicate gender-specific differences in immunity, with the gut microbiota shaping and being concomitantly shaped by the hormonal milieu governing differences between the sexes. A bi-directional cross-talk between microbiota and the endocrine system is emerging with bacteria being able to produce hormones (e.g. serotonin, dopamine and somatostatine), respond to host hormones (e.g. estrogens) and regulate host hormones' homeostasis (e.g by inhibiting gene prolactin transcription or converting glucocorticoids to androgens). We review herein how gut microbiota and its metabolites regulate immune function, intestinal permeability and possibly AID pathological processes. Further, we describe the dysbiosis within the gut microbiota observed in different AID and speculate how restoring gut microbiota composition and its regulatory metabolites by dietary intervention including prebiotics and probiotics could help in preventing or ameliorating AID. Finally, we suggest that, given consistent observations of microbiota dysbiosis associated with AID and the ability of SCFA and BA to regulate intestinal permeability and inflammation, further mechanistic studies, examining how dietary microbiota modulation can protect against AID, hold considerable potential to tackle increased incidence of AID at the population level.
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Affiliation(s)
- Lisa Rizzetto
- Department of Food Quality and Nutrition, Research and Innovation Centre, Fondazione Edmund Mach, San Michele all'Adige, Trento, Italy.
| | - Francesca Fava
- Department of Food Quality and Nutrition, Research and Innovation Centre, Fondazione Edmund Mach, San Michele all'Adige, Trento, Italy
| | - Kieran M Tuohy
- Department of Food Quality and Nutrition, Research and Innovation Centre, Fondazione Edmund Mach, San Michele all'Adige, Trento, Italy
| | - Carlo Selmi
- Division of Rheumatology and Clinical Immunology, Humanitas Research Hospital, Rozzano, Italy; BIOMETRA Department, University of Milan, Italy
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29
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Abstract
An abundant and diverse set of commensal microbial communities covers the body's surfaces, collectively so-called microbiome. It has a functional impact on various immune processes and modulates many health-related processes, including autoimmunity. An active site of microorganism-host interplay is the intestinal mucosa. Growing evidence has helped us to learn how a specific microbiota composition and its functionality determine the intestinal barrier function and, furthermore, modulate pro-inflammatory and anti-inflammatory immune mechanisms in remote organs. In addition, the microbial composition of the skin is important for the functionality of the skin barrier and autoimmune skin diseases. Here, we review the importance of the microbiome for the local and systemic immune system and how a disturbed microbiome-host interaction can affect the development and progression of autoimmune diseases. Understanding these associations will help to unravel new diagnostic and therapeutic approaches for those diseases.
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30
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Abstract
The microbiota, which is comprised of the collective of all microbes inhabiting the gut and its effect on the human host in which it resides, has become a growing field of interest. Various parameters of health and disease have been found to be associated with the variation in the human gut microbiome. In recent years, many studies have demonstrated an important role of gut microbes in the development of various illnesses including autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis, and multiple sclerosis. Although the mechanism of the disease involves both genetic and environmental factors, lupus has been found to be affected by the composition of the microbes lining the intestines. Several recent studies have suggested that alterations of the gut microbial composition may be correlated with SLE disease manifestations, while the exact roles of either symbiotic or pathogenic microbes in this disease have yet to be explored. Elucidation of the roles of gut microbes in SLE will shed light on how this autoimmune disorder develops and provide opportunities for improved biomarkers of the disease and the potential to probe new therapies. This new knowledge, along with that enabling alteration in composition of the gut microbiome, via diet modification, antibiotic, and probiotics, may bring forward a new era in the future of lupus treatment.
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Affiliation(s)
- Nurit Katz-Agranov
- Department of Internal Medicine, The University of Texas Houston, Health Science Center, Houston, TX, USA
| | - Gisele Zandman-Goddard
- Department of Medicine C, Wolfson Medical Center, Holon, Israel. .,Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel.
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Abstract
PURPOSE OF REVIEW Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown cause. In recent years, with the emergence of microbiome research, changes in the gut microbiota composition have been correlated with a variety of autoimmune disorders, and several mechanisms linking these together have been suggested, including the hygiene theory, immune system activation and hormonal effects. It has therefore been suggested that gut microbiota may play a role in SLE. In this review, we summarize recent findings on the SLE-related microbiota compositions in both humans and rodents. Evidence linking microbiome with SLE opens a new avenue in researching the cause of SLE as well as improved future treatments. RECENT FINDINGS Although two studies found a lower Firmicutes/Bacteroidetes ratio in SLE patients vs. controls, there were inconsistencies regarding significant differences in the abundance of specific genera or species. Studies of mouse disease models have shown some correlations between microbial compositions and disease states, also indicating differences between males and females. SUMMARY Current data support an association between microbiota composition and SLE. Further research is needed to fully unravel this connection, potentially shedding light on mechanisms in SLE development and on the female bias of the disease, improving diagnosis and treatment.
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32
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Metagenomics Biomarkers Selected for Prediction of Three Different Diseases in Chinese Population. BIOMED RESEARCH INTERNATIONAL 2018; 2018:2936257. [PMID: 29568746 PMCID: PMC5820663 DOI: 10.1155/2018/2936257] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/17/2017] [Revised: 10/14/2017] [Accepted: 10/24/2017] [Indexed: 12/15/2022]
Abstract
The dysbiosis of human microbiome has been proven to be associated with the development of many human diseases. Metagenome sequencing emerges as a powerful tool to investigate the effects of microbiome on diseases. Identification of human gut microbiome markers associated with abnormal phenotypes may facilitate feature selection for multiclass classification. Compared with binary classifiers, multiclass classification models deploy more complex discriminative patterns. Here, we developed a pipeline to address the challenging characterization of multilabel samples. In this study, a total of 300 biomarkers were selected from the microbiome of 806 Chinese individuals (383 controls, 170 with type 2 diabetes, 130 with rheumatoid arthritis, and 123 with liver cirrhosis), and then logistic regression prediction algorithm was applied to those markers as the model intrinsic features. The estimated model produced an F1 score of 0.9142, which was better than other popular classification methods, and an average receiver operating characteristic (ROC) of 0.9475 showed a significant correlation between these selected biomarkers from microbiome and corresponding phenotypes. The results from this study indicate that machine learning is a vital tool in data mining from microbiome in order to identify disease-related biomarkers, which may contribute to the application of microbiome-based precision medicine in the future.
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Complementary Methodologies To Investigate Human Gut Microbiota in Host Health, Working towards Integrative Systems Biology. J Bacteriol 2018; 200:JB.00376-17. [PMID: 28874411 DOI: 10.1128/jb.00376-17] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
In 1680, Antonie van Leeuwenhoek noted compositional differences in his oral and fecal microbiota, pioneering the study of the diversity of the human microbiome. From Leeuwenhoek's time to successful modern attempts at changing the gut microbial landscape to cure disease, there has been an exponential increase in the recognition of our resident microbes as part of ourselves. Thus, the human host and microbiome have evolved in parallel to configure a balanced system in which microbes survive in homeostasis with our innate and acquired immune systems, unless disease occurs. A growing number of studies have demonstrated a correlation between the presence/absence of microbial taxa and some of their functional molecules (i.e., genes, proteins, and metabolites) with health and disease states. Nevertheless, misleading experimental design on human subjects and the cost and lack of standardized animal models pose challenges to answering the question of whether changes in microbiome composition are cause or consequence of a certain biological state. In this review, we evaluate the state of the art of methodologies that enable the study of the gut microbiome, encouraging a change in broadly used analytic strategies by choosing effector molecules (proteins and metabolites) in combination with coding nucleic acids. We further explore microbial and effector microbial product imbalances that relate to disease and health.
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34
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Perl A. Review: Metabolic Control of Immune System Activation in Rheumatic Diseases. Arthritis Rheumatol 2017; 69:2259-2270. [PMID: 28841779 PMCID: PMC5711528 DOI: 10.1002/art.40223] [Citation(s) in RCA: 84] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2017] [Accepted: 07/25/2017] [Indexed: 02/06/2023]
Abstract
Metabolic pathways mediate lineage specification within the immune system through the regulation of glucose utilization, a process that generates energy in the form of ATP and synthesis of amino acids, nucleotides, and lipids to enable cell growth, proliferation, and survival. CD4+ T cells, a proinflammatory cell subset, preferentially produce ATP through glycolysis, whereas cells with an antiinflammatory lineage, such as memory and regulatory T cells, favor mitochondrial ATP generation. In conditions of metabolic stress or a shortage of nutrients, cells rely on autophagy to secure amino acids and other substrates, while survival depends on the sparing of mitochondria and maintenance of a reducing environment. The pentose phosphate pathway acts as a key gatekeeper of inflammation by supplying ribose‐5‐phosphate for cell proliferation and NADPH for antioxidant defenses. Increased lysosomal catabolism, accumulation of branched amino acids, glutamine, kynurenine, and histidine, and depletion of glutathione and cysteine activate the mechanistic target of rapamycin (mTOR), an arbiter of lineage development within the innate and adaptive immune systems. Mapping the impact of susceptibility genes to metabolic pathways allows for better understanding and therapeutic targeting of disease‐specific expansion of proinflammatory cells. Therapeutic approaches aimed at glutathione depletion and mTOR pathway activation appear to be safe and effective for treating lupus, while an opposing intervention may be of benefit in rheumatoid arthritis. Environmental sources of origin for metabolites within immune cells may include microbiota and plants. Thus, a better understanding of the pathways of immunometabolism could provide new insights into the pathogenesis and treatment of the rheumatic diseases.
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Affiliation(s)
- Andras Perl
- State University of New York, Upstate Medical University, Syracuse
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35
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Chen B, Sun L, Zhang X. Integration of microbiome and epigenome to decipher the pathogenesis of autoimmune diseases. J Autoimmun 2017; 83:31-42. [DOI: 10.1016/j.jaut.2017.03.009] [Citation(s) in RCA: 92] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2017] [Accepted: 03/15/2017] [Indexed: 02/07/2023]
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36
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Ruiz A, Cerdó T, Jáuregui R, Pieper DH, Marcos A, Clemente A, García F, Margolles A, Ferrer M, Campoy C, Suárez A. One-year calorie restriction impacts gut microbial composition but not its metabolic performance in obese adolescents. Environ Microbiol 2017; 19:1536-1551. [PMID: 28251782 DOI: 10.1111/1462-2920.13713] [Citation(s) in RCA: 52] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2016] [Revised: 02/20/2017] [Accepted: 02/24/2017] [Indexed: 01/01/2023]
Abstract
Recent evidence has disclosed a connection between gut microbial glycosidase activity and adiposity in obese. Here, we measured microbial α-glucosidase and β-galactosidase activities and sorted fluorescently labeled β-galactosidase containing (βGAL) microorganisms in faecal samples of eight lean and thirteen obese adolescents that followed a controlled calorie restriction program during one year. β-galactosidase is a highly distributed functional trait, mainly expressed by members of Blautia, Bacteroides, Alcaligenes, Acinetobacter and Propionibacterium. Only long-term calorie restriction induced clear changes in the microbiota of obese adolescents. Long-term calorie restriction induced significant shifts in total and βGAL gut microbiota, reducing the Firmicutes:Bacteroidetes ratio and enhancing the growth of beneficial microorganisms such as Bacteroides, Roseburia, Faecalibacterium and Clostridium XIVa. Moreover, the structure and composition of βGAL community in obese after long-term calorie restriction was highly similar to that of lean adolescents. However, despite this high compositional similarity, microbial metabolic performance was different, split in two metabolic states at a body mass index value of 25. Our study shows that calorie restriction is a strong environmental force reshaping gut microbiota though its metabolic performance is linked to host's adiposity, suggesting that functional redundancy and metabolic plasticity are fundamental properties of gut microbial ecosystem.
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Affiliation(s)
- Alicia Ruiz
- Department of Biochemistry and Molecular Biology 2, Biomedical Research Centre, University of Granada, Spain
| | - Tomás Cerdó
- Departmet of Pediatrics, School of Medicine, University of Granada, Granada, Spain.,EURISTIKOS Excellence Centre for Paediatric Research, Biomedical Research Centre, University of Granada, Granada, Spain
| | - Ruy Jáuregui
- Tennent Drive, AgResearch Grasslands, Private Bag 11008, Palmerston North, New Zealand
| | - Dietmar H Pieper
- Helmholtz Centre for Infection Research, Microbial Interactions and Processes Research Group, Braunschweig, Germany
| | - Ascensión Marcos
- Department of Metabolism and Nutrition, Institute of Food Science, Technology and Nutrition (ICTAN), Madrid, Spain
| | - Alfonso Clemente
- Department of Physiology and Biochemistry of Animal Nutrition, Estación Experimental del Zaidín, Granada, Spain
| | - Federico García
- Department of Microbiology, Complejo Hospitalario Universitario de Granada, Instituto de Investigación Biosanitaria (IBS), Granada, Spain
| | - Abelardo Margolles
- IPLA-CSIC, Department of Microbiology and Biochemistry of Dairy Products, Dairy Research Institute, Villaviciosa, Spain
| | | | - Cristina Campoy
- Departmet of Pediatrics, School of Medicine, University of Granada, Granada, Spain.,EURISTIKOS Excellence Centre for Paediatric Research, Biomedical Research Centre, University of Granada, Granada, Spain
| | - Antonio Suárez
- Department of Biochemistry and Molecular Biology 2, Biomedical Research Centre, University of Granada, Spain
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37
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The Microbiome in Connective Tissue Diseases and Vasculitides: An Updated Narrative Review. J Immunol Res 2017; 2017:6836498. [PMID: 28835902 PMCID: PMC5556609 DOI: 10.1155/2017/6836498] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2017] [Revised: 07/04/2017] [Accepted: 07/12/2017] [Indexed: 02/07/2023] Open
Abstract
Objective To provide a narrative review of the most recent data concerning the involvement of the microbiome in the pathogenesis of connective tissue diseases (CTDs) and vasculitides. Methods The PubMed database was searched for articles using combinations of words or terms that included systemic lupus erythematosus, systemic sclerosis, autoimmune myositis, Sjögren's syndrome, undifferentiated and mixed CTD, vasculitis, microbiota, microbiome, and dysbiosis. Papers from the reference lists of the articles and book chapters were reviewed, and relevant publications were identified. Abstracts and articles written in languages other than English were excluded. Results We found some evidence that dysbiosis participates in the pathogenesis of systemic lupus erythematosus, systemic sclerosis, Sjögren's syndrome, and Behçet's disease, but there are still few data concerning the role of dysbiosis in other CTDs or vasculitides. Conclusions Numerous studies suggest that alterations in human microbiota may be involved in the pathogenesis of inflammatory arthritides as a result of the aberrant activation of the innate and adaptive immune responses. Only a few studies have explored the involvement of dysbiosis in other CTDs or vasculitides, and further research is needed.
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38
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Ferrer M, Raczkowska BA, Martínez-Martínez M, Barbas C, Rojo D. Phenotyping of gut microbiota: Focus on capillary electrophoresis. Electrophoresis 2017; 38:2275-2286. [DOI: 10.1002/elps.201700056] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2017] [Revised: 05/04/2017] [Accepted: 06/01/2017] [Indexed: 01/29/2023]
Affiliation(s)
- Manuel Ferrer
- Institute of Catalysis; Consejo Superior de Investigaciones Científicas (CSIC); Madrid Spain
| | - Beata Anna Raczkowska
- Department of Endocrinology; Diabetology and Internal Medicine, Medical University of Bialystok; Bialystok Poland
| | | | - Coral Barbas
- Centro de Metabolómica y Bioanálisis (CEMBIO); Facultad de Farmacia, Universidad CEU San Pablo, Campus Montepríncipe; Madrid Spain
| | - David Rojo
- Centro de Metabolómica y Bioanálisis (CEMBIO); Facultad de Farmacia, Universidad CEU San Pablo, Campus Montepríncipe; Madrid Spain
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39
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Rojo D, Méndez-García C, Raczkowska BA, Bargiela R, Moya A, Ferrer M, Barbas C. Exploring the human microbiome from multiple perspectives: factors altering its composition and function. FEMS Microbiol Rev 2017; 41:453-478. [PMID: 28333226 PMCID: PMC5812509 DOI: 10.1093/femsre/fuw046] [Citation(s) in RCA: 96] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2016] [Accepted: 12/15/2016] [Indexed: 02/07/2023] Open
Abstract
Our microbiota presents peculiarities and characteristics that may be altered by multiple factors. The degree and consequences of these alterations depend on the nature, strength and duration of the perturbations as well as the structure and stability of each microbiota. The aim of this review is to sketch a very broad picture of the factors commonly influencing different body sites, and which have been associated with alterations in the human microbiota in terms of composition and function. To do so, first, a graphical representation of bacterial, fungal and archaeal genera reveals possible associations among genera affected by different factors. Then, the revision of sequence-based predictions provides associations with functions that become part of the active metabolism. Finally, examination of microbial metabolite contents and fluxes reveals whether metabolic alterations are a reflection of the differences observed at the level of population structure, and in the last step, link microorganisms to functions under perturbations that differ in nature and aetiology. The utilisation of complementary technologies and methods, with a special focus on metabolomics research, is thoroughly discussed to obtain a global picture of microbiota composition and microbiome function and to convey the urgent need for the standardisation of protocols.
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Affiliation(s)
- David Rojo
- Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, Universidad CEU San Pablo, Campus Montepríncipe, 28668 Madrid, Spain
| | | | - Beata Anna Raczkowska
- Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, 15-276 Bialystok, Poland
| | - Rafael Bargiela
- Institute of Catalysis, Consejo Superior de Investigaciones Científicas (CSIC), 28049 Madrid, Spain
| | - Andrés Moya
- Foundation for the Promotion of Health and Biomedical Research in the Valencian Community Public Health (FISABIO), 46020 Valencia, Spain
- Network Research Center for Epidemiology and Public Health (CIBER-ESP), 28029 Madrid, Spain
- Instituto Cavanilles de Biodiversidad y Biología Evolutiva, Universidad de Valencia, Paterna, 46980 Valencia, Spain
| | - Manuel Ferrer
- Institute of Catalysis, Consejo Superior de Investigaciones Científicas (CSIC), 28049 Madrid, Spain
| | - Coral Barbas
- Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, Universidad CEU San Pablo, Campus Montepríncipe, 28668 Madrid, Spain
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40
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Lupfer CR, Rodriguez A, Kanneganti TD. Inflammasome activation by nucleic acids and nucleosomes in sterile inflammation… or is it sterile? FEBS J 2017; 284:2363-2374. [PMID: 28374568 DOI: 10.1111/febs.14076] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2016] [Accepted: 03/30/2017] [Indexed: 12/23/2022]
Abstract
Inflammasomes are multiprotein complexes that form in the cytoplasm in response to cellular damage and cytosolic pathogen-associated molecules during infection. These complexes play important roles in initiating innate and adaptive immune responses to infectious disease. In addition, inflammasomes are now recognized as important mediators of sterile inflammation in various autoimmune and autoinflammatory diseases. Interestingly, microbiota and infection play critical roles in the development of 'sterile inflammation'. Herein, we highlight recent advances in our understanding of the role for inflammasomes in nucleic acid-, nucleosome-, and histone-driven sterile inflammation and discuss knowledge gaps and areas of potential future research.
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41
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Slingerland AE, Schwabkey Z, Wiesnoski DH, Jenq RR. Clinical Evidence for the Microbiome in Inflammatory Diseases. Front Immunol 2017; 8:400. [PMID: 28446909 PMCID: PMC5388779 DOI: 10.3389/fimmu.2017.00400] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2016] [Accepted: 03/21/2017] [Indexed: 12/11/2022] Open
Abstract
Clinical evidence is accumulating for a role of the microbiome in contributing to or modulating severity of inflammatory diseases. These studies can be organized by various organ systems involved, as well as type of study approach utilized, whether investigators compared the microbiome of cases versus controls, followed patients longitudinally, or intervened with antibiotics, prebiotics, or bacterial introduction. In this review, we summarize the clinical evidence supporting the microbiome as an important mechanism in the onset and maintenance of inflammation.
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Affiliation(s)
- Ann E Slingerland
- Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Zaker Schwabkey
- Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Diana H Wiesnoski
- Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Robert R Jenq
- Department of Genomic Medicine, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.,Department of Stem Cell Transplantation Cellular Therapy, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA
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42
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Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease mediated by pathogenic autoantibodies directed against nucleoprotein complexes. Beyond the activation of autoreactive B cells, this process involves dysregulation in many other types of immune cells, including CD4+ T cells, dendritic cells, macrophages and neutrophils. Metabolic substrate utilization and integration of cues from energy sensors are critical checkpoints of effector functions in the immune system, with common as well as cell-specific programmes. Patients with SLE and lupus-prone mice present with activated metabolism of CD4+ T cells, and the use of metabolic inhibitors to normalize these features is associated with therapeutic effects. Far less is known about the metabolic requirements of B cells and myeloid cells in SLE. This article reviews current knowledge of the alterations in metabolism of immune cells in patients with SLE and mouse models of lupus in the context of what is known about the metabolic regulation of these cells during normal immune responses. How these alterations might contribute to lupus pathogenesis and how they can be targeted therapeutically are also discussed.
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Affiliation(s)
- Laurence Morel
- Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, Florida 32610, USA
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43
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Shao T, Shao L, Li H, Xie Z, He Z, Wen C. Combined Signature of the Fecal Microbiome and Metabolome in Patients with Gout. Front Microbiol 2017; 8:268. [PMID: 28270806 PMCID: PMC5318445 DOI: 10.3389/fmicb.2017.00268] [Citation(s) in RCA: 139] [Impact Index Per Article: 17.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2016] [Accepted: 02/07/2017] [Indexed: 12/27/2022] Open
Abstract
This study employed microbiome and metabolome analysis to explore the fecal signatures of gout patients. Fecal samples from 52 male individuals (26 healthy controls and 26 gout patients) were analyzed by 1H NMR spectroscopy and Illumina Miseq sequencing. The signatures of microbiome showed being up-regulation of opportunistic pathogens, such as Bacteroides, Porphyromonadaceae Rhodococcus, Erysipelatoclostridium and Anaerolineaceae. The signatures of metabolome were some altered metabolites which may involve uric acid excretion, purine metabolism, and inflammatory responses. Meanwhile, the correlation between discrepant metabolites and microbial taxa indicated that they could be the combined signatures of gout. This study suggests that the combined analysis of the fecal microbiome and metabolome may effectively characterize diseases.
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Affiliation(s)
- Tiejuan Shao
- College of Basic Medical Science, Zhejiang Chinese Medical University Hangzhou, China
| | - Li Shao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou, China
| | - Haichang Li
- College of Basic Medical Science, Zhejiang Chinese Medical University Hangzhou, China
| | - Zhijun Xie
- College of Basic Medical Science, Zhejiang Chinese Medical University Hangzhou, China
| | - Zhixing He
- College of Basic Medical Science, Zhejiang Chinese Medical University Hangzhou, China
| | - Chengping Wen
- College of Basic Medical Science, Zhejiang Chinese Medical University Hangzhou, China
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Capillary electrophoresis mass spectrometry as a tool for untargeted metabolomics. Bioanalysis 2017; 9:99-130. [PMID: 27921456 DOI: 10.4155/bio-2016-0216] [Citation(s) in RCA: 62] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Highly polar and ionic metabolites, such as sugars, most amino acids, organic acids or nucleotides are not retained by conventional reversed-phase LC columns and polar stationary phases and hydrophilic-interaction LC lacks of robustness, which is still limiting their applications for untargeted metabolomics where reproducibility is a must. Biological samples such as blood, urine or even tissues include many hydrophilic compounds secreted from cells, their analysis is essential for biomarker discovery, disease progression or treatment effects. This review focuses on CE coupled to MS as a mature technique for untargeted metabolomics including sample pretreatment, types of matrices, analytical methods, applications and data treatment strategies for polar compound analysis in biological matrices. The main applications and results of CE-MS in untargeted metabolomics are discussed and presented in a tabulated format.
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Metabolic Disturbances in Adult-Onset Still's Disease Evaluated Using Liquid Chromatography/Mass Spectrometry-Based Metabolomic Analysis. PLoS One 2016; 11:e0168147. [PMID: 28005947 PMCID: PMC5179000 DOI: 10.1371/journal.pone.0168147] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2016] [Accepted: 11/25/2016] [Indexed: 11/25/2022] Open
Abstract
Objective Liquid chromatography/mass spectrometry (LC/MS)-based comprehensive analysis of metabolic profiles with metabolomics approach has potential diagnostic and predictive implications. However, no metabolomics data have been reported in adult-onset Still’s disease (AOSD). This study investigated the metabolomic profiles in AOSD patients and examined their association with clinical characteristics and disease outcome. Methods Serum metabolite profiles were determined on 32 AOSD patients and 30 healthy controls (HC) using ultra-performance liquid chromatography (UPLC)/MS analysis, and the differentially expressed metabolites were quantified using multiple reactions monitoring (MRM)/MS analysis in 44 patients and 42 HC. Pure standards were utilized to confirm the presence of the differentially expressed metabolites. Results Eighteen differentially expressed metabolites were identified in AOSD patents using LC/MS-based analysis, of which 13 metabolites were validated by MRM/MS analysis. Among them, serum levels of lysoPC(18:2), urocanic acid and indole were significantly lower, and L-phenylalanine levels were significantly higher in AOSD patients compared with HC. Moreover, serum levels of lysoPC(18:2), PhePhe, uridine, taurine, L-threonine, and (R)-3-Hydroxy-hexadecanoic acid were significantly correlated with disease activity scores (all p<0.05) in AOSD patients. A different clustering of metabolites was associated with a different disease outcome, with significantly lower levels of isovalerylsarcosine observed in patients with chronic articular pattern (median, 77.0AU/ml) compared with monocyclic (341.5AU/ml, p<0.01) or polycyclic systemic pattern (168.0AU/ml, p<0.05). Conclusion Thirteen differentially expressed metabolites identified and validated in AOSD patients were shown to be involved in five metabolic pathways. Significant associations of metabolic profiles with disease activity and outcome of AOSD suggest their involvement in AOSD pathogenesis.
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The role of the gastrointestinal tract in the pathogenesis of rheumatic diseases. Best Pract Res Clin Rheumatol 2016; 30:889-900. [PMID: 27964794 DOI: 10.1016/j.berh.2016.10.003] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2016] [Revised: 10/10/2016] [Accepted: 10/12/2016] [Indexed: 12/12/2022]
Abstract
Dysregulation of the intestinal epithelial barrier in genetically susceptible individuals may lead to both intestinal and extraintestinal autoimmune disorders. There is emerging literature on the role of microbiota changes in the pathogenesis of systemic rheumatic diseases such as rheumatoid arthritis, spondyloarthropathies, and connective tissue diseases. Although the role of the gastrointestinal tract in the pathogenesis of spondyloartropathies is well defined and many studies underline the importance of gastrointestinal inflammation in modulating local and systemic inflammation, the data are inconclusive regarding the effect of dysbiosis on rheumatoid arthritis and connective tissue diseases. This review aims to summarize current data on the role of the gastrointestinal involvement and intestinal microbiota in the pathogenesis of systemic rheumatic disease.
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Abstract
Anticancer immune responses can be considered a desirable form of autoimmunity that may be profoundly shaped by the microbiome. Here, we discuss evidence for the microbiome's influence on anti-tumor immunosurveillance, including those that are indirect and can act at a distance, and we put forward hypotheses regarding mechanisms of how these effects are implemented. These may involve cross-reactivity between microbial and tumor antigens shaping T cell repertoires and/or microbial products stimulating pattern recognition receptors that influence the type and intensity of immune responses. Understanding how the microbiome impacts natural cancer immunosurveillance as well as treatment-induced immune responses will pave the way for more effective therapies and prophylactics.
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Müller-Ladner U. [The microbiome in rheumatic diseases : Driving force or confusing factor?]. Z Rheumatol 2016; 75:854-858. [PMID: 27531193 DOI: 10.1007/s00393-016-0175-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Affiliation(s)
- U Müller-Ladner
- Abt. Rheumatologie und Klinische Immunologie, Kerckhoff Klinik Bad Nauheim, Justus-Liebig Universität Gießen, Benekestr. 2-8, 61231, Bad Nauheim, Deutschland.
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Rosser EC, Mauri C. A clinical update on the significance of the gut microbiota in systemic autoimmunity. J Autoimmun 2016; 74:85-93. [PMID: 27481556 DOI: 10.1016/j.jaut.2016.06.009] [Citation(s) in RCA: 98] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2016] [Accepted: 06/21/2016] [Indexed: 02/06/2023]
Abstract
Systemic lupus erythematosus (SLE) is a complex autoimmune disease where a loss of tolerance to nuclear antigens leads to inflammation in multiple organ systems. The cause of SLE remains ill defined, although it is known that a complex interplay between genes and environment is necessary for disease development. In recent years, case studies have reported that the incidence of SLE in the USA, for example, has increased by approximately 3 fold. Although the reason for this is likely to be multifactorial, it has been hypothesized that the increasing incidence of autoimmune disease is due to considerable shifts in the bacterial communities resident the gut, collectively known as the gut microbiota, following a change in diet and the widespread introduction of antibiotics. Furthermore, a growing body of evidence suggests that the gut microbiota plays a role in the development of a range of autoimmune diseases including inflammatory bowel disease, multiple sclerosis, type one diabetes and rheumatoid arthritis. In this review, we summarize how advances in DNA-based sequencing technologies have been critical in providing baseline information concerning the gut microbiota in health and how variation amongst individuals in controlled by multiples factors including age, genetics, environment and the diet. We also discuss the importance of the gut microbiota in the development of a healthy immune system and how changes in particular bacterial phyla have been associated with immune abnormalities in animal models of autoimmune disease. Finally, in order to place the data in a clinical context, we highlight recent findings showing that abnormalities in the gut microbiota can be detected in patients with SLE, which provides the rationale for greater investigation into whether microbiota-targeted therapies could be used for the treatment/prevention of disease.
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Affiliation(s)
| | - Claudia Mauri
- Centre for Rheumatology Research, Division of Medicine, University College London, London, UK.
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Gut microbiota in autoimmunity: potential for clinical applications. Arch Pharm Res 2016; 39:1565-1576. [DOI: 10.1007/s12272-016-0796-7] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2016] [Accepted: 07/15/2016] [Indexed: 01/09/2023]
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