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Liu H, Wang J, Zhao J, Gu S, Chen S, Jia W, Huang S, Wu J. Potentilla anserina L. polysaccharide ameliorates LPS-induced acute lung injury and relevant intestinal mucosal barrier impairment. Int J Biol Macromol 2025; 305:140667. [PMID: 39922353 DOI: 10.1016/j.ijbiomac.2025.140667] [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: 10/28/2024] [Revised: 01/26/2025] [Accepted: 02/02/2025] [Indexed: 02/10/2025]
Abstract
Acute lung injury (ALI) is a life-threatening condition that occurs in patients triggered with complex factors, contributing to multiple organ dysfunction and mortality. Therefore, it is crucial to seek novel targets for treating ALI. To investigate the effects of Potentilla anserina L. polysaccharide (PAP) on ALI and associated damage to the intestinal mucosal barrier induced by lipopolysaccharide (LPS), ALI mouse model was adopted. Mice were intraperitoneal injection of LPS, with or without PAP., then serum, lung, spleen, small intestine, and bronchoalveolar lavage fluid (BALF) samples of mice obtained were used to discuss the treatment of PAP on ALI and relevant organ damage. Meanwhile, the underlying signal pathway was searched from GeneCards and DisGeNET databases, and then verified it by western blot. These results indicated that PAP effectively reduced inflammatory levels in LPS-induced ALI and associated intestinal mucosal barrier impairment, as well as the M1 macrophage immune response by activating the Rap1 signal pathway. These results suggested that the medicinal herb PAP is a therapeutic potential anti-inflammatory agent for ALI and relevant organ dysfunction.
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Affiliation(s)
- Heng Liu
- Department of Otorhinolaryngology, Qilu Hospital of Shandong University, National Health Commission Key Laboratory of Otorhinolaryngology (Shandong University), NO. 107 of Wenhuaxi Road, LiXia District, Jinan, Shandong 250012, China
| | - Juan Wang
- Department of Otorhinolaryngology, Qilu Hospital of Shandong University, National Health Commission Key Laboratory of Otorhinolaryngology (Shandong University), NO. 107 of Wenhuaxi Road, LiXia District, Jinan, Shandong 250012, China
| | - Jiping Zhao
- Department of Pulmonary and Critical Care Medicine, Qilu Hospital, Shandong University, National Health Commission Key Laboratory of Otorhinolaryngology (Shandong University), No. 107 Wenhuaxi Road, LiXia District, Jinan, Shandong 250012, China
| | - Shaowei Gu
- Department of Otorhinolaryngology, Qilu Hospital of Shandong University, National Health Commission Key Laboratory of Otorhinolaryngology (Shandong University), NO. 107 of Wenhuaxi Road, LiXia District, Jinan, Shandong 250012, China
| | - Shuai Chen
- Department of Otorhinolaryngology, Qilu Hospital of Shandong University, National Health Commission Key Laboratory of Otorhinolaryngology (Shandong University), NO. 107 of Wenhuaxi Road, LiXia District, Jinan, Shandong 250012, China
| | - Wenming Jia
- Department of Otorhinolaryngology, Qilu Hospital of Shandong University, National Health Commission Key Laboratory of Otorhinolaryngology (Shandong University), NO. 107 of Wenhuaxi Road, LiXia District, Jinan, Shandong 250012, China
| | - Shanying Huang
- The National Key Laboratory for Innovation and Transformation of Luobing Theory, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Science, Department of Cardiology, Qilu Hospital of Shandong University, NO. 107 of Wenhuaxi Road, LiXia District, Jinan, Shandong 250012, China
| | - Jinxiang Wu
- Department of Pulmonary and Critical Care Medicine, Qilu Hospital, Shandong University, National Health Commission Key Laboratory of Otorhinolaryngology (Shandong University), No. 107 Wenhuaxi Road, LiXia District, Jinan, Shandong 250012, China.
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Henoun Loukili N, Perrin A, Gaillot O, Bruandet A, Boudis F, Sendid B, Nseir S, Zahar JR. Is intestinal colonization with multidrug-resistant Enterobacterales associated with higher rates of nosocomial Enterobacterales bloodstream infections? Int J Infect Dis 2025; 150:107274. [PMID: 39510310 DOI: 10.1016/j.ijid.2024.107274] [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: 07/24/2024] [Revised: 10/14/2024] [Accepted: 10/15/2024] [Indexed: 11/15/2024] Open
Abstract
OBJECTIVES Intestinal colonization with multidrug-resistant Enterobacterales (MDRE-IC) increases the risk of MDRE bloodstream infection (BSI). However, its impact on the overall risk of nosocomial Enterobacterales bloodstream infections (nE-BSIs) remains unclear. This study aimed to determine this risk and identify associated factors in hospitalized patients. DESIGN This retrospective cohort study at a 3200-bed tertiary institution including patients hospitalized in 2019 who underwent MDRE rectal swab (RS) screening. Inclusion criteria were age ≥18 years, first RS in 2019, follow-up ≥7 days, and Enterobacterales BSIs >48 hours after RS. The primary outcome was the first nE-BSI during the follow-up period, analyzed using a Cox model. RESULTS Among 7006 patients, 817 (11.9%) had MDRE-IC. Most were male and primarily hospitalized in acute wards. nE-BSIs occurred in 433 (6.1%) patients and were more frequent in patients with MDRE-IC than the non-colonized group (adjusted hazard ratio [aHR] = 1.78, 95% confidence interval [CI]: 1.40-2.26). Intestinal colonization with extended-spectrum β-lactamase-producing and carbapenemase-resistant Enterobacterales showed similar risks for Enterobacterales BSI onset: aHR = 1.73 (95% CI: 1.33-2.24) and aHR = 2.02 (95% CI: 1.27-3.22), respectively. CONCLUSIONS In hospitalized patients, MDRE-IC is associated with a higher rate of nE-BSI than those without MDRE-IC, underscoring the urgent need for improved infection prevention and control measures, as well as optimized antibiotic use to mitigate this risk.
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Affiliation(s)
- Noureddine Henoun Loukili
- INSERM, IAME UMR 1137, University of Paris, Paris, France; Glycobiology in Fungal Pathogenesis & Clinical Applications Inserm U1285 - CNRS UMR 8576, Lille University, France; Infection Prevention and control Unit, CHU Lille, Lille, France.
| | - Agnes Perrin
- Infection Prevention and control Unit, CHU Lille, Lille, France
| | | | | | - Fabio Boudis
- Medical Information Department, CHU Lille, Lille, France
| | - Boualem Sendid
- Glycobiology in Fungal Pathogenesis & Clinical Applications Inserm U1285 - CNRS UMR 8576, Lille University, France; Laboratory of Parasitology and Mycology, Institute of Microbiology, CHU Lille, Lille, France
| | - Saadalla Nseir
- Glycobiology in Fungal Pathogenesis & Clinical Applications Inserm U1285 - CNRS UMR 8576, Lille University, France; Laboratory of Parasitology and Mycology, Institute of Microbiology, CHU Lille, Lille, France
| | - Jean-Ralph Zahar
- INSERM, IAME UMR 1137, University of Paris, Paris, France; Microbiology, Infection Control Unit, GH Paris Seine Saint-Denis, APHP, Bobigny, France
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Borghi-Silva A, Camargo PF, Caruso FCR, da Luz Goulart C, Trimer R, Darlan Santos-Araújo A, Dourado IM, da Silva ALG. Current perspectives on the rehabilitation of COPD patients with comorbidities. Expert Rev Respir Med 2025; 19:11-28. [PMID: 39804026 DOI: 10.1080/17476348.2025.2452441] [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: 10/12/2024] [Accepted: 01/08/2025] [Indexed: 01/18/2025]
Abstract
INTRODUCTION Chronic obstructive pulmonary disease (COPD) is frequently accompanied by a variety of comorbidities, complicating management and rehabilitation efforts. Understanding this interplay is crucial for optimizing patient outcomes. AREAS COVERED This review, based on the MEDLINE, Embase and Cochrane Library databases, summarizes the main research on the rehabilitation of patients with COPD, with an emphasis on relevant comorbidities, such as cardiovascular diseases, pulmonary hypertension, lung cancer, metabolic, musculoskeletal, and gastrointestinal disorders. anxiety/depression and cognitive disorders. The study highlights the importance of pre-participation assessments, ongoing monitoring and personalized rehabilitation programs. A review includes a comprehensive literature search to assess the scientific evidence on these interventions and their impact. EXPERT OPINION The integration of cardiorespiratory rehabilitation program is essential for improving physical capacity and quality of life in COPD patients with comorbidities. While existing studies highlight positive outcomes, challenges such as interdisciplinary collaboration and access to rehabilitation services remain. Future strategies must prioritize personalized and integrated approaches programs combining pharmacological optimization and a close monitoring during cardiopulmonary rehabilitation to significantly reduce hospital readmissions and mortality, even in patients with complex multimorbidities. Continued research is necessary to refine rehabilitation protocols and better understand the complexities of managing COPD alongside cardiac conditions.
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Affiliation(s)
- Audrey Borghi-Silva
- Cardiopulmonary Physiotherapy Laboratory, Federal University of São Carlos, São Carlos, SP, Brazil
| | - Patrícia Faria Camargo
- Cardiopulmonary Physiotherapy Laboratory, Federal University of São Carlos, São Carlos, SP, Brazil
| | | | - Cássia da Luz Goulart
- Cardiopulmonary Physiotherapy Laboratory, Federal University of São Carlos, São Carlos, SP, Brazil
- Postgraduate Program of Health Sciences and Technologies, University of Brasilia (UnB),Brasilia, DF, Brazil
| | - Renata Trimer
- Cardiopulmonary Physiotherapy Laboratory, Federal University of São Carlos, São Carlos, SP, Brazil
| | | | - Izadora Moraes Dourado
- Cardiopulmonary Physiotherapy Laboratory, Federal University of São Carlos, São Carlos, SP, Brazil
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Tao L, Zhang Q, Liu L, Wang K, Wang J, Liu X, Zhao P, Li J. Inhibition of AhR disrupts intestinal epithelial barrier and induces intestinal injury by activating NF-κB in COPD. FASEB J 2024; 38:e70256. [PMID: 39679871 DOI: 10.1096/fj.202402320r] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2024] [Revised: 11/25/2024] [Accepted: 12/05/2024] [Indexed: 12/17/2024]
Abstract
Chronic obstructive pulmonary disease (COPD) is frequently associated with intestinal comorbidities. Damage to the intestinal barrier plays a crucial role in these disorders, leading to increased intestinal and systemic inflammation, and thereby promoting the progression of COPD. This study aims to investigate the mechanism of intestinal epithelial barrier damage, focusing on the roles of the Aryl hydrocarbon Receptor (AhR) and NF-κB in COPD-related intestinal damage. A COPD rat model was induced by cigarette smoke and bacterial infection, while Caco-2/HT29 intestinal epithelial cells were treated with TNF-α or IL-1β to assess intestinal disorder and the underlying mechanisms of barrier damage. COPD rats exhibited significant lung function decline, pathological damage, and inflammatory response in lung tissues. Additionally, significant intestinal injury was observed, accompanied by pronounced colonic pathological damage, an enhanced inflammatory response, and intestinal barrier disruption. This was evidenced by decreased expression of apical junction proteins and elevated serum diamine oxidase levels. Pro-inflammatory cytokines TNF-α or IL-1β significantly downregulated the expression of apical junction proteins in Caco-2/HT29 cells, reduced transepithelial electrical resistance of Caco-2 cells, and increased FD-4 permeability. Moreover, TNF-α or IL-1β induction activated NF-κB in Caco-2/HT29 cells, with a similar activation observed in the colonic tissues of COPD rats. The NF-κB inhibitor PDTC suppressed this activation and protected against intestinal epithelial barrier damage. Furthermore, AhR inhibition was observed both in vitro and in vivo. The AhR activator FICZ inhibited NF-κB activation and mitigated intestinal epithelial barrier damage, whereas the AhR inhibitor CH223191 inhibited AhR and exacerbated intestinal epithelial barrier damage by facilitating NF-κB activation. However, the NF-κB inhibitor PDTC did not significantly affect AhR. Additionally, TNF-α/IL-1β inhibited the binding of AhR and p-NF-κB. Consequently, AhR inhibition can downregulate the expression of apical junction proteins, probably through activation of NF-κB signaling leading to intestinal epithelial barrier damage. This study confirmed the presence of lesions in the lungs and intestines of COPD rats, as well as the associated damage to the intestinal epithelial barrier. The inhibition of AhR followed by the activation of NF-κB has been identified as a critical mechanism underlying the injury to the intestinal epithelial barrier.
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Affiliation(s)
- Liuying Tao
- Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, Henan, China
- Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-Constructed by Henan province & Education Ministry of P.R. China, Zhengzhou, Henan, China
- Department of Respiratory Diseases, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, China
| | - Qin Zhang
- Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, Henan, China
- Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-Constructed by Henan province & Education Ministry of P.R. China, Zhengzhou, Henan, China
- Department of Respiratory Diseases, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, China
- Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, Henan, China
| | - Lan Liu
- Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, Henan, China
- Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-Constructed by Henan province & Education Ministry of P.R. China, Zhengzhou, Henan, China
- Department of Respiratory Diseases, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, China
| | - Kun Wang
- Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, Henan, China
- Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-Constructed by Henan province & Education Ministry of P.R. China, Zhengzhou, Henan, China
- Department of Respiratory Diseases, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, China
| | - Juanhui Wang
- Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, Henan, China
- Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-Constructed by Henan province & Education Ministry of P.R. China, Zhengzhou, Henan, China
- Department of Respiratory Diseases, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, China
| | - Xuefang Liu
- Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, Henan, China
- Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-Constructed by Henan province & Education Ministry of P.R. China, Zhengzhou, Henan, China
- Department of Respiratory Diseases, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, China
| | - Peng Zhao
- Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, Henan, China
- Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-Constructed by Henan province & Education Ministry of P.R. China, Zhengzhou, Henan, China
- Department of Respiratory Diseases, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, China
- Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, Henan, China
| | - Jiansheng Li
- Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, Henan, China
- Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-Constructed by Henan province & Education Ministry of P.R. China, Zhengzhou, Henan, China
- Department of Respiratory Diseases, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, China
- Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, Henan, China
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Zhang J, Zheng X, Luo W, Sun B. Cross-domain microbiomes: the interaction of gut, lung and environmental microbiota in asthma pathogenesis. Front Nutr 2024; 11:1346923. [PMID: 38978703 PMCID: PMC11229079 DOI: 10.3389/fnut.2024.1346923] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Accepted: 06/03/2024] [Indexed: 07/10/2024] Open
Abstract
Recent experimental and epidemiological studies underscore the vital interaction between the intestinal microbiota and the lungs, an interplay known as the "gut-lung axis". The significance of this axis has been further illuminated following the identification of intestinal microbial metabolites, such as short-chain fatty acids (SCFA), as key mediators in setting the tone of the immune system. Through the gut-lung axis, the gut microbiota and its metabolites, or allergens, are directly or indirectly involved in the immunomodulation of pulmonary diseases, thereby increasing susceptibility to allergic airway diseases such as asthma. Asthma is a complex outcome of the interplay between environmental factors and genetic predispositions. The concept of the gut-lung axis may offer new targets for the prevention and treatment of asthma. This review outlines the relationships between asthma and the respiratory microbiome, gut microbiome, and environmental microbiome. It also discusses the current advancements and applications of microbiomics, offering novel perspectives and strategies for the clinical management of chronic respiratory diseases like asthma.
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Affiliation(s)
- Jiale Zhang
- Department of Clinical Laboratory, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
- Guangzhou Laboratory, Guangzhou, China
| | - Xianhui Zheng
- Department of Clinical Laboratory, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
- Guangzhou Laboratory, Guangzhou, China
| | - Wenting Luo
- Department of Clinical Laboratory, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
- Guangzhou Laboratory, Guangzhou, China
| | - Baoqing Sun
- Department of Clinical Laboratory, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
- Guangzhou Laboratory, Guangzhou, China
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Li Y, Chen J, Xing Y, Wang J, Liang Q, Zeng J, Wang S, Yang Q, Lu J, Hu J, Lu W. Bufei Huoxue capsule attenuates COPD-related inflammation and regulates intestinal microflora, metabolites. Front Pharmacol 2024; 15:1270661. [PMID: 38659586 PMCID: PMC11041376 DOI: 10.3389/fphar.2024.1270661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 03/14/2024] [Indexed: 04/26/2024] Open
Abstract
Background: Bufei Huoxue capsule (BFHX) is widely used for the clinical treatment of chronic obstructive pulmonary disease (COPD) in China. Objectives: The aim of this study is to explore the effects on COPD and the underlying mechanism of BFHX. The process and methods: In this study, we established a COPD mouse model through cigarette smoke (CS) exposure in combination with lipopolysaccharide (LPS) intratracheal instillation. Subsequently, BFHX was orally administrated to COPD mice, and their pulmonary function, lung pathology, and lung inflammation, including bronchoalveolar lavage fluid (BALF) cell count and classification and cytokines, were analyzed. In addition, the anti-oxidative stress ability of BFHX was detected by Western blotting, and the bacterial diversity, abundance, and fecal microbiome were examined using 16S rRNA sequencing technology. Outcome: BFHX was shown to improve pulmonary function, suppress lung inflammation, decrease emphysema, and increase anti-oxidative stress, whereas 16S rRNA sequencing indicated that BFHX can dynamically regulate the diversity, composition, and distribution of the intestinal flora microbiome and regulate the lysine degradation and phenylalanine metabolism of COPD mice. These results highlight another treatment option for COPD and provide insights into the mechanism of BFHX.
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Affiliation(s)
- Yuanyuan Li
- Guangzhou Medicine University,Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical, Guangzhou, China
| | - Jiali Chen
- Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yue Xing
- Guangzhou Medicine University,Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical, Guangzhou, China
| | - Jian Wang
- Guangzhou Medicine University,Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical, Guangzhou, China
| | - Qiuling Liang
- First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Jiamin Zeng
- Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Siyi Wang
- Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Qiong Yang
- Key Laboratory of National Health Commission for the Diagnosis and Treatment of COPD, Inner Mongolia People’s Hospital, Hohhot, China
| | - Jianing Lu
- Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jieying Hu
- Guangzhou Medicine University,Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical, Guangzhou, China
| | - Wenju Lu
- Guangzhou Medicine University,Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical, Guangzhou, China
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Ruiz-Margáin A, Macías-Rodríguez RU, Flores-García NC, Román Calleja BM, Fierro-Angulo OM, González-Regueiro JA. Assessing nutrition status, sarcopenia, and frailty in adult transplant recipients. Nutr Clin Pract 2024; 39:14-26. [PMID: 38097210 DOI: 10.1002/ncp.11107] [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: 09/01/2023] [Revised: 11/15/2023] [Accepted: 11/15/2023] [Indexed: 01/13/2024] Open
Abstract
The assessment of nutrition status, sarcopenia, and frailty holds significant relevance in the context of adult transplantation, as these factors are associated with an unfavorable prognosis; thus, transplant candidates must undergo a full nutrition assessment. Screening tools may be used to prioritize patients, this can be done using the Nutrition Risk Screening 2002 or Royal Free Hospital-Nutritional Prioritizing Tool. Subsequently, a thorough nutrition-focused physical examination should be conducted to evaluate clinical signs of nutrition deficiencies, fat and muscle loss, and fluid overload; dietary history and current intake must also be assessed. Apart from physical examination, specific testing for sarcopenia and frailty are recommended. For sarcopenia assessment, specifically for muscle quantification, the gold standard is the cross-sectional measurement of the muscle at L3 obtained from a computed tomography scan or magnetic resonance imaging; dual-energy x-ray absorptiometry is also a good tool especially when appendicular skeletal muscle index is calculated. Other more readily available options include phase angle from bioelectrical impedance or bioimpedance spectroscopy. In the sarcopenia assessment, muscle function evaluation is required, handgrip strength stands as the primary test for this purpose; this test is also part of the subjective global assessment and is included in some frailty scores. Finally, for frailty assessment, the Short Physical Performance Battery is useful for evaluating physical frailty, and for a multidimensional evaluation, the Fried frailty phenotype can be used. Specifically for liver transplant candidates, the use of Liver Frailty Index is recommended.
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Affiliation(s)
- Astrid Ruiz-Margáin
- Division of Hepatology, Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Ricardo U Macías-Rodríguez
- Division of Hepatology, Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Nayelli C Flores-García
- Division of Hepatology, Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Berenice M Román Calleja
- Division of Hepatology, Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Oscar M Fierro-Angulo
- Division of Hepatology, Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - José A González-Regueiro
- Division of Hepatology, Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
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Zhou Y, Lin Z, Xie S, Gao Y, Zhou H, Chen F, Fu Y, Yang C, Ke C. Interplay of chronic obstructive pulmonary disease and colorectal cancer development: unravelling the mediating role of fatty acids through a comprehensive multi-omics analysis. J Transl Med 2023; 21:587. [PMID: 37658368 PMCID: PMC10474711 DOI: 10.1186/s12967-023-04278-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Accepted: 06/14/2023] [Indexed: 09/03/2023] Open
Abstract
BACKGROUND Chronic obstructive pulmonary disease (COPD) patients often exhibit gastrointestinal symptoms, A potential association between COPD and Colorectal Cancer (CRC) has been indicated, warranting further examination. METHODS In this study, we collected COPD and CRC data from the National Health and Nutrition Examination Survey, genome-wide association studies, and RNA sequence for a comprehensive analysis. We used weighted logistic regression to explore the association between COPD and CRC incidence risk. Mendelian randomization analysis was performed to assess the causal relationship between COPD and CRC, and cross-phenotype meta-analysis was conducted to pinpoint crucial loci. Multivariable mendelian randomization was used to uncover mediating factors connecting the two diseases. Our results were validated using both NHANES and GEO databases. RESULTS In our analysis of the NHANES dataset, we identified COPD as a significant contributing factor to CRC development. MR analysis revealed that COPD increased the risk of CRC onset and progression (OR: 1.16, 95% CI 1.01-1.36). Cross-phenotype meta-analysis identified four critical genes associated with both CRC and COPD. Multivariable Mendelian randomization suggested body fat percentage, omega-3, omega-6, and the omega-3 to omega-6 ratio as potential mediating factors for both diseases, a finding consistent with the NHANES dataset. Further, the interrelation between fatty acid-related modules in COPD and CRC was demonstrated via weighted gene co-expression network analysis and Kyoto Encyclopedia of Genes and Genomes enrichment results using RNA expression data. CONCLUSIONS This study provides novel insights into the interplay between COPD and CRC, highlighting the potential impact of COPD on the development of CRC. The identification of shared genes and mediating factors related to fatty acid metabolism deepens our understanding of the underlying mechanisms connecting these two diseases.
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Affiliation(s)
- Youtao Zhou
- The First Clinical Medical School, Guangzhou Medical University, Guangzhou, China
| | - Zikai Lin
- Nanshan School, Guangzhou Medical University, Guangzhou, China
| | - Shuojia Xie
- Nanshan School, Guangzhou Medical University, Guangzhou, China
| | - Yuan Gao
- The First Clinical Medical School, Guangzhou Medical University, Guangzhou, China
| | - Haobin Zhou
- The First Clinical Medical School, Guangzhou Medical University, Guangzhou, China
| | - Fengzhen Chen
- The First Clinical Medical School, Guangzhou Medical University, Guangzhou, China
| | - Yuewu Fu
- Department of General Surgery, School of Medicine, The First Affiliated Hospital, Ji'nan University, Guangzhou, China
| | - Cuiyan Yang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
| | - Chuanfeng Ke
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
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Du B, Fu Y, Han Y, Sun Q, Xu J, Yang Y, Rong R. The lung-gut crosstalk in respiratory and inflammatory bowel disease. Front Cell Infect Microbiol 2023; 13:1218565. [PMID: 37680747 PMCID: PMC10482113 DOI: 10.3389/fcimb.2023.1218565] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2023] [Accepted: 07/28/2023] [Indexed: 09/09/2023] Open
Abstract
Both lung and gut belong to the common mucosal immune system (CMIS), with huge surface areas exposed to the external environment. They are the main defense organs against the invasion of pathogens and play a key role in innate and adaptive immunity. Recently, more and more evidence showed that stimulation of one organ can affect the other, as exemplified by intestinal complications during respiratory disease and vice versa, which is called lung-gut crosstalk. Intestinal microbiota plays an important role in respiratory and intestinal diseases. It is known that intestinal microbial imbalance is related to inflammatory bowel disease (IBD), this imbalance could impact the integrity of the intestinal epithelial barrier and leads to the persistence of inflammation, however, gut microbial disturbances have also been observed in respiratory diseases such as asthma, allergy, chronic obstructive pulmonary disease (COPD), and respiratory infection. It is not fully clarified how these disorders happened. In this review, we summarized the latest examples and possible mechanisms of lung-gut crosstalk in respiratory disease and IBD and discussed the strategy of shaping intestinal flora to treat respiratory diseases.
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Affiliation(s)
- Baoxiang Du
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Yan Fu
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Yuxiu Han
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Qihui Sun
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Jinke Xu
- Shandong Center for Disease Control and Prevention, Jinan, China
| | - Yong Yang
- Shandong Antiviral Engineering Research Center of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
- Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Rong Rong
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China
- Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan, China
- Shandong Provincial Key Laboratory of Traditional Chinese Medicine for Basic Research, Shandong University of Traditional Chinese Medicine, Jinan, China
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10
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Chinese patent medicines for childhood diseases of the respiratory and digestive systems: A scoping review protocol. Eur J Integr Med 2023. [DOI: 10.1016/j.eujim.2023.102244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/13/2023]
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11
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Dysbiosis and leaky gut in hyper-inflated COPD patients: Have smoking and exercise training any role? Respir Med Res 2023; 83:100995. [PMID: 36822132 DOI: 10.1016/j.resmer.2023.100995] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 12/16/2022] [Accepted: 01/05/2023] [Indexed: 01/11/2023]
Abstract
BACKGROUND To characterize the leaky gut syndrome in a cohort of COPD patients with lung hyperinflation according to their clinical history (i.e. hyperinflation severity, chronic respiratory failure [CRF] presence, GOLD stage, prescribed therapy, smoking history) and with or without recent exercise training activity. METHODS At the ambulatory visit, we evaluated selected COPD patients with lung hyperinflation [residual volume (RV)≥110% pred, TLC≤120% pred)] in clinical stability, identifying them as those who have attended a recent program of exercise training and those who were waiting for it. Clinical and respiratory characteristics (forced expiratory volume at the first second, forced vital capacity, and arterial blood gasses) were collected. Microbiota composition (CFU/ml), and intestinal permeability (i.e., Zonulin ng/ml) were measured in the stool and normalized to the normality cutoff value. RESULTS All patients [n = 32, median age: 67 years, median RV: 185.0% pred (IQR: 162.0-206.0) and TLC 125.0% pred (IQR: 113.0-138.0)] showed depletion of Lactobacilli, Bacteroides and a great increase in E. Coli, KES (2 and 6.4 times) and Saccharomyces concentrations (2.5 times) other than normality. All evaluations on gut microbiota composition in the whole population were independent of BMI, CRF, GOLD stage or hyperinflation severity, and inhaled steroid therapy. Smoking habits (smokers vs ex-smokers) influenced only Bacteroides species (p<0.05) and no systemic inflammation was present in these patients. On the contrary, Zonulin concentration, a marker of intestinal permeability, was significantly higher than normal (2.8 times) and was correlated with Saccharomyces (p = 0.013). Zonulin (p = 0.001) and Saccharomyces (p<0.0001) were also significantly different in patients undergoing exercise training with respect to those on the waiting list for training. These findings were not influenced by smoking habits. CONCLUSIONS A marked dysbiosis and leaky gut alteration characterize all COPD hyper-inflated patients, being worse in patients waiting for exercise training. A pre-to-post study is necessary to confirm these preliminary findings.
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12
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Gastrointestinal consequences of lipopolysaccharide-induced lung inflammation. Inflamm Res 2023; 72:57-74. [PMID: 36322182 PMCID: PMC9628607 DOI: 10.1007/s00011-022-01657-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Accepted: 09/15/2022] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND Respiratory inflammation is the body's response to lung infection, trauma or hypersensitivity and is often accompanied by comorbidities, including gastrointestinal (GI) symptoms. Why respiratory inflammation is accompanied by GI dysfunction remains unclear. Here, we investigate the effect of lipopolysaccharide (LPS)-induced lung inflammation on intestinal barrier integrity, tight-junctions, enteric neurons and inflammatory marker expression. METHODS Female C57bl/6 mice (6-8 weeks) were intratracheally administered LPS (5 µg) or sterile saline, and assessed after either 24 or 72 h. Total and differential cell counts in bronchoalveolar lavage fluid (BALF) were used to evaluate lung inflammation. Intestinal barrier integrity was assessed via cross sectional immunohistochemistry of tight junction markers claudin-1, claudin-4 and EpCAM. Changes in the enteric nervous system (ENS) and inflammation in the intestine were quantified immunohistochemically using neuronal markers Hu + and nNOS, glial markers GFAP and S100β and pan leukocyte marker CD45. RESULTS Intratracheal LPS significantly increased the number of neutrophils in BALF at 24 and 72 h. These changes were associated with an increase in CD45 + cells in the ileal mucosa at 24 and 72 h, increased goblet cell expression at 24 h, and increased expression of EpCAM at 72 h. LPS had no effect on the expression of GFAP, S100β, nor the number of Hu + neurons or proportion of nNOS neurons in the myenteric plexus. CONCLUSIONS Intratracheal LPS administration induces inflammation in the ileum that is associated with enhanced expression of EpCAM, decreased claudin-4 expression and increased goblet cell density, these changes may contribute to systemic inflammation that is known to accompany many inflammatory diseases of the lung.
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13
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Neag MA, Vulturar DM, Gherman D, Burlacu CC, Todea DA, Buzoianu AD. Gastrointestinal microbiota: A predictor of COVID-19 severity? World J Gastroenterol 2022; 28:6328-6344. [PMID: 36533107 PMCID: PMC9753053 DOI: 10.3748/wjg.v28.i45.6328] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 10/26/2022] [Accepted: 11/17/2022] [Indexed: 12/02/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19), caused by a severe acute respiratory syndrome coronavirus 2 infection, has raised serious concerns worldwide over the past 3 years. The severity and clinical course of COVID-19 depends on many factors (e.g., associated comorbidities, age, etc) and may have various clinical and imaging findings, which raises management concerns. Gut microbiota composition is known to influence respiratory disease, and respiratory viral infection can also influence gut microbiota. Gut and lung microbiota and their relationship (gut-lung axis) can act as modulators of inflammation. Modulating the intestinal microbiota, by improving its composition and diversity through nutraceutical agents, can have a positive impact in the prophylaxis/treatment of COVID-19.
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Affiliation(s)
- Maria Adriana Neag
- Department of Pharmacology, Toxicology and Clinical Pharmacology, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca 400337, Romania
| | - Damiana-Maria Vulturar
- Department of Pneumology, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca 400332, Romania
| | - Diana Gherman
- Department of Radiology, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca 400347, Romania
| | - Codrin-Constantin Burlacu
- Faculty of Medicine, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca 400347, Romania
| | - Doina Adina Todea
- Department of Pneumology, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca 400332, Romania
| | - Anca Dana Buzoianu
- Department of Pharmacology, Toxicology and Clinical Pharmacology, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca 400337, Romania
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14
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Ashique S, De Rubis G, Sirohi E, Mishra N, Rihan M, Garg A, Reyes RJ, Manandhar B, Bhatt S, Jha NK, Singh TG, Gupta G, Singh SK, Chellappan DK, Paudel KR, Hansbro PM, Oliver BG, Dua K. Short Chain Fatty Acids: Fundamental mediators of the gut-lung axis and their involvement in pulmonary diseases. Chem Biol Interact 2022; 368:110231. [DOI: 10.1016/j.cbi.2022.110231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 10/11/2022] [Accepted: 10/21/2022] [Indexed: 11/24/2022]
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15
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Freuer D, Linseisen J, Meisinger C. Asthma and the risk of gastrointestinal disorders: a Mendelian randomization study. BMC Med 2022; 20:82. [PMID: 35292014 PMCID: PMC8925069 DOI: 10.1186/s12916-022-02283-7] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Accepted: 02/03/2022] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND The question of whether asthma is causally related to gastrointestinal disorders remained unanswered so far. Thus, this study investigated whether there is such a relation and whether the time of onset of asthma plays a role in the occurrence of the following gastrointestinal disorders: peptic ulcer disease (PUD), gastroesophageal reflux disease (GORD), irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD) including the distinction between Crohn's disease (CD) and ulcerative colitis (UC). METHODS Using summary data of genome-wide association studies (GWASs), we ran Mendelian randomization analyses based on up to 456,327 European participants. Outlier assessment, a series of sensitivity analyses and validation of IBD results in a second GWAS were performed to confirm the results. RESULTS Presented ORs represent the average change in the outcome per 2.72-fold increase in the prevalence of the exposure. Genetically predicted childhood-onset asthma was positively associated with PUD, GORD, and IBS with similar odds ratios near 1.003 and adjusted P-values from 0.007 (GORD) to 0.047 (PUD). Furthermore, it was inversely related to IBD (OR = 0.992, 95% CI: 0.986, 0.998, adjusted P = 0.023) and suggestively associated with its UC subtype (OR = 0.990, 95% CI: 0.982, 0.998, adjusted P = 0.059). There were no associations between genetically predicted adult-onset asthma and the mentioned gastrointestinal disorders. CONCLUSIONS This study provides evidence that the presence of asthma onset in childhood increases the risk for GORD, PUD, and IBS but decreases the risk for IBD in adults. The lower risk for IBD may be attributed to a lower risk primarily for UC.
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Affiliation(s)
- Dennis Freuer
- University of Augsburg, University Hospital Augsburg, Stenglinstr. 2, 86156, Augsburg, Germany. .,Institute for Medical Information Processing, Biometry, and Epidemiology, Ludwig-Maximilians-Universität München, Munich, Germany.
| | - Jakob Linseisen
- University of Augsburg, University Hospital Augsburg, Stenglinstr. 2, 86156, Augsburg, Germany.,Institute for Medical Information Processing, Biometry, and Epidemiology, Ludwig-Maximilians-Universität München, Munich, Germany.,Independent Research Group Clinical Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany
| | - Christa Meisinger
- University of Augsburg, University Hospital Augsburg, Stenglinstr. 2, 86156, Augsburg, Germany
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16
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Cai Y, Chen L, Zhang S, Zeng L, Zeng G. The role of gut microbiota in infectious diseases. WIREs Mech Dis 2022; 14:e1551. [PMID: 34974642 DOI: 10.1002/wsbm.1551] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2021] [Revised: 12/07/2021] [Accepted: 12/10/2021] [Indexed: 12/14/2022]
Abstract
The intestine, the largest immune organ in the human body, harbors approximately 1013 microorganisms, including bacteria, fungi, viruses, and other unknown microbes. The intestine is a most important crosstalk anatomic structure between the first (the host) and second (the microorganisms) genomes. The imbalance of the intestinal microecology, especially dysbiosis of the composition, structure, and function of gut microbiota, is linked to human diseases. In this review, we investigated the roles and underlying mechanisms of gut microecology in the development, progression, and prognosis of infectious diseases. Furthermore, we discussed potential new strategies of prevention and treatment for infectious diseases based on manipulating the composition, structure, and function of intestinal microorganisms in the future. This article is categorized under: Infectious Diseases > Molecular and Cellular Physiology.
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Affiliation(s)
- Yongjie Cai
- Department of Microbiology, Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, Guangzhou, China
| | - Lingming Chen
- Department of Microbiology, Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, Guangzhou, China
| | - Sien Zhang
- Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory, Sun Yat-Sen University, Guangzhou, China
| | - Lingchan Zeng
- Clinical Research Center, Department of Medical Records Management, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Gucheng Zeng
- Department of Microbiology, Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, Guangzhou, China
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17
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Abstract
Coronavirus disease 2019 (COVID-19) is the leading pandemic facing the world in 2019/2020; it is caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which necessitates clear understanding of the infectious agent. The virus manifests aggressive behavior with severe clinical presentation and high mortality rate, especially among the elderly and patients living with chronic diseases. In the recent years, the role of gut microbiota, in health and disease, has been progressively studied and highlighted. It is through gut microbiota-organ bidirectional pathways, such as gut-brain axis, gut-liver axis, and gut-lung axis, that the role of gut microbiota in prompting lung disease, among other diseases, has been proposed and accepted. It is also known that respiratory viral infections, such as COVID-19, induce alterations in the gut microbiota, which can influence immunity. Based on the fact that gut microbiota diversity is decreased in old age and in patients with certain chronic diseases, which constitute two of the primary fatality groups in COVID-19 infections, it can be assumed that the gut microbiota may play a role in COVID-19 pathology and fatality rate. Improving gut microbiota diversity through personalized nutrition and supplementation with prebiotics/probiotics will mend the immunity of the body and hence could be one of the prophylactic strategies by which the impact of COVID-19 can be minimized in the elderly and immunocompromised patients. In this chapter, the role of dysbiosis in COVID-19 will be clarified and the possibility of using co-supplementation of personalized prebiotics/probiotics with current therapies will be discussed.
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18
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Gut-Lung Dysbiosis Accompanied by Diabetes Mellitus Leads to Pulmonary Fibrotic Change through the NF-κB Signaling Pathway. THE AMERICAN JOURNAL OF PATHOLOGY 2021; 191:838-856. [PMID: 33705752 DOI: 10.1016/j.ajpath.2021.02.019] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Revised: 01/25/2021] [Accepted: 02/10/2021] [Indexed: 02/07/2023]
Abstract
Growing evidence shows that the lungs are an unavoidable target organ of diabetic complications. However, the pathologic mechanisms of diabetic lung injury are still controversial. This study demonstrated the dysbiosis of the gut and lung microbiome, pulmonary alveolar wall thickening, and fibrotic change in streptozotocin-induced diabetic mice and antibiotic-induced gut dysbiosis mice compared with controls. In both animal models, the NF-κB signaling pathway was activated in the lungs. Enhanced pulmonary alveolar well thickening and fibrotic change appeared in the lungs of transgenic mice expressing a constitutively active NF-κB mutant compared with wild type. When lincomycin hydrochloride-induced gut dysbiosis was ameliorated by fecal microbiota transplant, enhanced inflammatory response in the intestine and pulmonary fibrotic change in the lungs were significantly decreased compared with lincomycin hydrochloride-treated mice. Furthermore, the application of fecal microbiota transplant and baicalin could also redress the microbial dysbiosis of the gut and lungs in streptozotocin-induced diabetic mice. Taken together, these data suggest that multiple as yet undefined factors related to microbial dysbiosis of gut and lungs cause pulmonary fibrogenesis associated with diabetes mellitus through an NF-κB signaling pathway.
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19
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Ma Y, Yang X, Chatterjee V, Wu MH, Yuan SY. The Gut-Lung Axis in Systemic Inflammation. Role of Mesenteric Lymph as a Conduit. Am J Respir Cell Mol Biol 2021; 64:19-28. [PMID: 32877613 DOI: 10.1165/rcmb.2020-0196tr] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Emerging evidence shows that after injury or infection, the mesenteric lymph acts as a conduit for gut-derived toxic factors to enter the blood circulation, causing systemic inflammation and acute lung injury. Neither the cellular and molecular identity of lymph factors nor their mechanisms of action have been well understood and thus have become a timely topic of investigation. This review will first provide a summary of background knowledge on gut barrier and mesenteric lymphatics, followed by a discussion focusing on the current understanding of potential injurious factors in the lymph and their mechanistic contributions to lung injury. We also examine lymph factors with antiinflammatory properties as well as the bidirectional nature of the gut-lung axis in inflammation.
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Affiliation(s)
- Yonggang Ma
- Department of Molecular Pharmacology and Physiology, and
| | - Xiaoyuan Yang
- Department of Molecular Pharmacology and Physiology, and
| | | | - Mack H Wu
- Department of Surgery, University of South Florida Morsani College of Medicine, Tampa, Florida
| | - Sarah Y Yuan
- Department of Molecular Pharmacology and Physiology, and.,Department of Surgery, University of South Florida Morsani College of Medicine, Tampa, Florida
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20
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Walrath T, Dyamenahalli KU, Hulsebus HJ, McCullough RL, Idrovo JP, Boe DM, McMahan RH, Kovacs EJ. Age-related changes in intestinal immunity and the microbiome. J Leukoc Biol 2020; 109:1045-1061. [PMID: 33020981 DOI: 10.1002/jlb.3ri0620-405rr] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2020] [Revised: 09/11/2020] [Accepted: 09/13/2020] [Indexed: 12/19/2022] Open
Abstract
The gastrointestinal (GI) tract is a vitally important site for the adsorption of nutrients as well as the education of immune cells. Homeostasis of the gut is maintained by the interplay of the intestinal epithelium, immune cells, luminal Ags, and the intestinal microbiota. The well-being of the gut is intrinsically linked to the overall health of the host, and perturbations to this homeostasis can have severe impacts on local and systemic health. One factor that causes disruptions in gut homeostasis is age, and recent research has elucidated how critical systems within the gut are altered during the aging process. Intestinal stem cell proliferation, epithelial barrier function, the gut microbiota, and the composition of innate and adaptive immune responses are all altered in advanced age. The aging population continues to expand worldwide, a phenomenon referred to as the "Silver Tsunami," and every effort must be made to understand how best to prevent and treat age-related maladies. Here, recent research about changes observed in the intestinal epithelium, the intestinal immune system, the microbiota, and how the aging gut interacts with and influences other organs such as the liver, lung, and brain are reviewed. Better understanding of these age-related changes and their impact on multi-organ interactions will aid the development of therapies to increase the quality of life for all aged individuals.
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Affiliation(s)
- Travis Walrath
- Department of Surgery, Division of GI, Trauma and Endocrine Surgery, and Burn Research Program, University of Colorado Denver, Aurora, Colorado, USA
| | - Kiran U Dyamenahalli
- Department of Surgery, Division of GI, Trauma and Endocrine Surgery, and Burn Research Program, University of Colorado Denver, Aurora, Colorado, USA
| | - Holly J Hulsebus
- Department of Surgery, Division of GI, Trauma and Endocrine Surgery, and Burn Research Program, University of Colorado Denver, Aurora, Colorado, USA.,Immunology Graduate Program, University of Colorado Denver, Aurora, Colorado, USA
| | - Rebecca L McCullough
- Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora, Colorado, USA.,GI and Liver Innate Immune Program, University of Colorado Denver, Aurora, Colorado, USA
| | - Juan-Pablo Idrovo
- Department of Surgery, Division of GI, Trauma and Endocrine Surgery, and Burn Research Program, University of Colorado Denver, Aurora, Colorado, USA
| | - Devin M Boe
- Department of Surgery, Division of GI, Trauma and Endocrine Surgery, and Burn Research Program, University of Colorado Denver, Aurora, Colorado, USA.,Immunology Graduate Program, University of Colorado Denver, Aurora, Colorado, USA.,Medical Scientist Training Program, University of Colorado Denver, Aurora, Colorado, USA
| | - Rachel H McMahan
- Department of Surgery, Division of GI, Trauma and Endocrine Surgery, and Burn Research Program, University of Colorado Denver, Aurora, Colorado, USA
| | - Elizabeth J Kovacs
- Department of Surgery, Division of GI, Trauma and Endocrine Surgery, and Burn Research Program, University of Colorado Denver, Aurora, Colorado, USA.,Immunology Graduate Program, University of Colorado Denver, Aurora, Colorado, USA.,Medical Scientist Training Program, University of Colorado Denver, Aurora, Colorado, USA.,GI and Liver Innate Immune Program, University of Colorado Denver, Aurora, Colorado, USA
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21
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Ren X, Gamallat Y, Liu D, Zhu Y, Meyiah A, Yan C, Shang D, Xin Y. The distribution characteristics of intestinal microbiota in children with community-acquired pneumonia under five Years of age. Microb Pathog 2020; 142:104062. [PMID: 32058024 DOI: 10.1016/j.micpath.2020.104062] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2018] [Revised: 08/29/2019] [Accepted: 02/10/2020] [Indexed: 02/08/2023]
Abstract
Pneumonia is the leading cause of morbidity and mortality in children under five years of age worldwide. Over the past decades, studies have shown that the upper respiratory pathogens are closely related to the occurrence of pneumonia. However, the co-occurrence of gut microbiome dysbiosis may have clinical manifestation in the prognosis of childhood pneumonia. The aim of the present study is to investigate the differences in gut microbial communities between children's diagnosed community-acquired pneumonia (CAP) under five compared to healthy controls in Inner Mongolia. Fecal samples were collected from children with CAP and healthy controls (<5 years old) and the genomic microbiome 16S rRNA was amplified using the hypervariable V4 region and subjected to MiSeq Illumina sequencing, and then analyzed for microbiota composition and phenotype. Finally functional profiling was performed by KEGG pathways analyses. Our results revealed a gut microbiota dysbiosis in children with CAP. Distinct gut microbiome composition and structure were associated with childhood CAP between two age categories compared to healthy controls. In addition, the phylogenic phenotype's prediction was found to be significantly different between the groups. The prominent genera in age group of 0-3 were Bifidobacterium and Enterococcus. On the contrary, Escherichia-Shigella, Prevotella, Faecalibacterium and Enterobacter were remarkably decreased in most of the fecal samples from CAP patients in age group of 0-3 compared to the control. At the genus level, the CAP children in the age group of 4-5 showed an increase in the abundance of Escherichia/Shigella, Bifidobacterium, Streptococcus and Psychrobacter and, a decrease in the abundance of Faecalibacterium, Bacteroides, Lachnospiraceae and Ruminococcus compared with the matched healthy controls. Moreover, CAP children in both age groups exhibited distinct profiles in the KEGG functional analysis. Our data revealed that the gut microbiota differ between CAP patients and health children and certain gut microbial species are associated with CAP. Further research to identify specific microbial species which may contribute to the development CAP are merited. In addition, rectification of microbiota dysbiosis may provide supplemental benefits for treatment of the childhood CAP.
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Affiliation(s)
- Xiaomeng Ren
- School of Food Science and Technology, National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian, 116034, China; Department of Biotechnology, College of Basic Medical Science, Dalian Medical University, Dalian, 116044, China.
| | - Yaser Gamallat
- Department of Biotechnology, College of Basic Medical Science, Dalian Medical University, Dalian, 116044, China.
| | - Dongjie Liu
- Department of Rehabilitation, Dalian Rehabilitation Recuperation Center of PLA Joint Logistics Support Force, No. 30, Binhaixi Road, Xigang District, Dalian, 116013, China.
| | - Yanyan Zhu
- Department of Biotechnology, College of Basic Medical Science, Dalian Medical University, Dalian, 116044, China.
| | - Abdo Meyiah
- Department of Biotechnology, College of Basic Medical Science, Dalian Medical University, Dalian, 116044, China.
| | - Chunhong Yan
- School of Food Science and Technology, National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian, 116034, China.
| | - Dong Shang
- Department of Acute Abdominal Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China.
| | - Yi Xin
- Department of Biotechnology, College of Basic Medical Science, Dalian Medical University, Dalian, 116044, China.
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22
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Nibbering B, Ubags NDJ. Microbial interactions in the atopic march. Clin Exp Immunol 2019; 199:12-23. [PMID: 31777060 DOI: 10.1111/cei.13398] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/29/2019] [Indexed: 12/13/2022] Open
Abstract
The human body is populated by a large number of microorganisms and exist in symbiosis with these immensely diverse communities, which are suggested to influence health and disease. The microbiota plays an essential role in the maturation and function of the immune system. The prevalence of atopic diseases has increased drastically over the past decades, and the co-occurrence of multiple allergic diseases and allergic sensitization starting in early life has gained a great deal of attention. Immune responses in different organs affected by allergic diseases (e.g. skin, intestine and lung) may be linked to microbial changes in peripheral tissues. In the current review, we provide an overview of the current understanding of microbial interactions in allergic diseases and their potential role in the atopic march.
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Affiliation(s)
- B Nibbering
- Faculty of Biology and Medicine, University of Lausanne, Service de Pneumologie, CHUV, Lausanne, Switzerland
| | - N D J Ubags
- Faculty of Biology and Medicine, University of Lausanne, Service de Pneumologie, CHUV, Lausanne, Switzerland
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23
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Vaughan A, Frazer ZA, Hansbro PM, Yang IA. COPD and the gut-lung axis: the therapeutic potential of fibre. J Thorac Dis 2019; 11:S2173-S2180. [PMID: 31737344 DOI: 10.21037/jtd.2019.10.40] [Citation(s) in RCA: 68] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Current management strategies for chronic obstructive pulmonary disease (COPD) incorporate a step-wise, multidisciplinary approach to effectively manage patient symptoms and prevent disease progression. However, there has been limited advancement in therapies to address the underlying cause of COPD pathogenesis. Recent research has established the link between the lungs and the gut-the gut-lung axis -and the gut microbiome is a major component. The gut microbiome is likely perturbed in COPD, contributing to chronic inflammation. Diet is a readily modifiable factor and the diet of COPD patients is often deficient in nutrients such as fibre. The metabolism of dietary fibre by gut microbiomes produces anti-inflammatory short chain fatty acid (SCFAs), which could protect against inflammation in the lungs. By addressing the 'fibre gap' in the diet of COPD patients, this targeted dietary intervention may reduce inflammation, both systemically and in the airways, and value-add to the paradigm shift in respiratory medicine, from reactive to personalised and participatory medicine.
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Affiliation(s)
- Annalicia Vaughan
- UQ Thoracic Research Centre, Faculty of Medicine, The University of Queensland, Chermside, Brisbane, Australia.,Department of Thoracic Medicine, The Prince Charles Hospital, Brisbane, Australia
| | - Zoe A Frazer
- UQ Thoracic Research Centre, Faculty of Medicine, The University of Queensland, Chermside, Brisbane, Australia.,Department of Thoracic Medicine, The Prince Charles Hospital, Brisbane, Australia
| | - Philip M Hansbro
- Centre for Inflammation, Centenary Institute, University of Technology Sydney, Faculty of Science, Camperdown, Australia.,Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, The University of Newcastle, Callaghan, Australia
| | - Ian A Yang
- UQ Thoracic Research Centre, Faculty of Medicine, The University of Queensland, Chermside, Brisbane, Australia.,Department of Thoracic Medicine, The Prince Charles Hospital, Brisbane, Australia
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Barcik W, Pugin B, Brescó MS, Westermann P, Rinaldi A, Groeger D, Van Elst D, Sokolowska M, Krawczyk K, Frei R, Ferstl R, Wawrzyniak M, Altunbulakli C, Akdis CA, O'Mahony L. Bacterial secretion of histamine within the gut influences immune responses within the lung. Allergy 2019; 74:899-909. [PMID: 30589936 DOI: 10.1111/all.13709] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2018] [Revised: 11/20/2018] [Accepted: 11/30/2018] [Indexed: 12/17/2022]
Abstract
BACKGROUND Histamine is an important immunomodulator influencing both the innate and adaptive immune system. Certain host cells express the histidine decarboxylase enzyme (HDC), which is responsible for catalysing the decarboxylation of histidine to histamine. We and others have shown that bacterial strains can also express HDC and secrete histamine; however, the influence of bacterial-derived histamine on the host immune responses distant to the gut is unclear. METHODS The Escherichia coli BL21 (E coli BL21) strain was genetically modified to express the Morganella morganii (M morganii)-derived HDC gene (E coli BL21_HTW). E coli BL21 and E coli BL21_HTW were gavaged to ovalbumin (OVA) sensitized and challenged mice to investigate the effect of bacterial-derived histamine on lung inflammatory responses. RESULTS Oral administration of E coli BL21_HTW, which is able to secrete histamine, to wild-type mice reduced lung eosinophilia and suppressed ex vivo OVA-stimulated cytokine secretion from lung cells in the OVA respiratory inflammation mouse model. In histamine receptor 2 (H2R)-deficient mice, administration of histamine-secreting bacteria also reduced inflammatory cell numbers in bronchoalveolar lavage (BAL). However, the suppressive effect of bacterial-derived histamine on BAL inflammation was lost in HDC-deficient mice. This loss of activity was associated with increased expression of histamine degrading enzymes and reduced histamine receptor expression. CONCLUSION Histamine secretion from bacteria within the gut can have immunological consequences at distant mucosal sites, such as within the lung. These effects are influenced by host histamine receptor expression and the expression of histamine degrading enzymes.
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Affiliation(s)
- Weronika Barcik
- Swiss Institute of Allergy and Asthma Research (SIAF) University of Zurich Davos Switzerland
| | - Benoit Pugin
- Swiss Institute of Allergy and Asthma Research (SIAF) University of Zurich Davos Switzerland
| | - Marina Sabaté Brescó
- Swiss Institute of Allergy and Asthma Research (SIAF) University of Zurich Davos Switzerland
| | - Patrick Westermann
- Swiss Institute of Allergy and Asthma Research (SIAF) University of Zurich Davos Switzerland
| | - Arturo Rinaldi
- Swiss Institute of Allergy and Asthma Research (SIAF) University of Zurich Davos Switzerland
- Christine Kühne‐Center for Allergy Research and Education Davos Switzerland
| | - David Groeger
- Alimentary Health Pharma Davos (AHPD) Davos Switzerland
| | - Dries Van Elst
- Swiss Institute of Allergy and Asthma Research (SIAF) University of Zurich Davos Switzerland
| | - Milena Sokolowska
- Swiss Institute of Allergy and Asthma Research (SIAF) University of Zurich Davos Switzerland
- Christine Kühne‐Center for Allergy Research and Education Davos Switzerland
| | - Krzysztof Krawczyk
- Swiss Institute of Allergy and Asthma Research (SIAF) University of Zurich Davos Switzerland
| | - Remo Frei
- Swiss Institute of Allergy and Asthma Research (SIAF) University of Zurich Davos Switzerland
- Christine Kühne‐Center for Allergy Research and Education Davos Switzerland
| | - Ruth Ferstl
- Swiss Institute of Allergy and Asthma Research (SIAF) University of Zurich Davos Switzerland
- Christine Kühne‐Center for Allergy Research and Education Davos Switzerland
| | - Marcin Wawrzyniak
- Swiss Institute of Allergy and Asthma Research (SIAF) University of Zurich Davos Switzerland
| | - Can Altunbulakli
- Swiss Institute of Allergy and Asthma Research (SIAF) University of Zurich Davos Switzerland
- Christine Kühne‐Center for Allergy Research and Education Davos Switzerland
| | - Cezmi A. Akdis
- Swiss Institute of Allergy and Asthma Research (SIAF) University of Zurich Davos Switzerland
- Christine Kühne‐Center for Allergy Research and Education Davos Switzerland
| | - Liam O'Mahony
- Swiss Institute of Allergy and Asthma Research (SIAF) University of Zurich Davos Switzerland
- Departments of Medicine and Microbiology APC Microbiome Ireland National University of Ireland Cork Ireland
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Ojha UC, Singh DP, Choudhari OK, Gothi D, Singh S. Correlation of Severity of Functional Gastrointestinal Disease Symptoms with that of Asthma and Chronic Obstructive Pulmonary Disease: A Multicenter Study. Int J Appl Basic Med Res 2018; 8:83-88. [PMID: 29744319 PMCID: PMC5932929 DOI: 10.4103/ijabmr.ijabmr_258_17] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Introduction There is a growing clinical awareness about the influence of gut-lung axis on lung injury and coexisting manifestations of disease processes in both the intestine and lungs. Patients of chronic lung diseases such as chronic obstructive pulmonary disease (COPD) and asthma very often present with coexistent gut symptoms. In the present study, we have tried to establish the correlation of severity of pulmonary pathology of COPD and asthma patients with functional gastrointestinal (GI) symptoms of the patients. Materials and Methods This is a prospective, questionnaire-based study comprising patients with asthma and COPD. After following strict inclusion and exclusion criteria, a total of 200 patients (100 patients of bronchial asthma and 100 patients of COPD) were included in the study. Functional GI symptom questionnaire [Annexure 1-Bowel Disease Questionnaire] is based on ROME III diagnostic criteria. On the basis of GOLD (Global Initiative for Obstructive Lung Disease) guidelines, COPD patients were divided into 4 categories (mild - GOLD 1, moderate - GOLD2, severe - GOLD3 and very severe - GOLD4). Asthma patients were divided into three categories (well controlled, partly controlled, uncontrolled) on the basis of GINA (Global Initiative for Asthma) guidelines. Results Highest percentage of patients with maximum GI symptoms was found in "GOLD-4" group among COPD patients and "uncontrolled" group among asthma patients. Highest percentage of patients with least GI symptoms was found in "GOLD-1" group among COPD patients and "well controlled" group among asthma patients. Conclusion We can conclude from our study that the phenomenon of gut-lung axis not only exists but also the severity of symptoms of one system (gut) carries a high degree of concordance with severity of other (lung).
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Affiliation(s)
- Umesh Chandra Ojha
- Department of Pulmonary Medicine, ESI Post Graduate Institute of Medical Sciences and Research, New Delhi, India
| | - Devesh Pratap Singh
- Department of TB and Respiratory Diseases, Hind Institute of Medical Sciences, Barabanki, Uttar Pradesh, India
| | - Omkar Kalidasrao Choudhari
- Department of Pulmonary Medicine, ESI Post Graduate Institute of Medical Sciences and Research, New Delhi, India
| | - Dipti Gothi
- Department of Pulmonary Medicine, ESI Post Graduate Institute of Medical Sciences and Research, New Delhi, India
| | - Shweta Singh
- Department of Obstetrics and Gynecology, Hind Institute of Medical Sciences, Barabanki, Uttar Pradesh, India
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Jonker R, Deutz NE, Erbland ML, Anderson PJ, Engelen MP. Effectiveness of essential amino acid supplementation in stimulating whole body net protein anabolism is comparable between COPD patients and healthy older adults. Metabolism 2017; 69:120-129. [PMID: 28285641 PMCID: PMC5351771 DOI: 10.1016/j.metabol.2016.12.010] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2016] [Revised: 11/22/2016] [Accepted: 12/14/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND The development of effective nutritional strategies in support of muscle growth for patients with chronic obstructive pulmonary disease (COPD) remains challenging. Dietary essential amino acids (EAAs) are the main driver of postprandial net protein anabolism. In agreement, EAA supplements in healthy older adults are more effective than supplements with the composition of complete proteins. In patients with COPD it is still unknown whether complete protein supplements can be substituted with only EAAs, and whether they are as effective as in healthy older adults. METHODS According to a double-blind randomized crossover design, we examined in 23 patients with moderate to very severe COPD (age: 65±2 years, FEV1: 40±2% of predicted) and 19 healthy age-matched subjects (age: 64±2 years), whether a free EAA mixture with a high proportion (40%) of leucine (EAA mixture) stimulated whole body net protein gain more than a similar mixture of balanced free EAAs and non-EAAs as present in whey protein (TAA mixture). Whole body net protein gain and splanchnic extraction of phenylalanine (PHE) were assessed by continuous IV infusion of L-[ring-2H5]-PHE and L-[ring-2H2]-tyrosine, and enteral intake of L-[15N]-PHE (added to the mixtures). RESULTS Besides an excellent positive linear relationship between PHE intake and net protein gain in both groups (r=0.84-0.91, P<0.001), net protein gain was 42% higher in healthy controls and 49% higher in COPD patients after intake of the EAA mixture compared to the TAA mixture (P<0.0001). These findings could not be attributed to the high LEU content, as in both groups net protein gain per gram EAA intake was lower for the EAA mixture (P<0.0001). Net protein gain was higher in COPD patients for both mixtures due to a 40% lower splanchnic extraction (P<0.0001), but was similarly related to dietary PHE (i.e. EAA) plasma appearance. CONCLUSIONS In COPD patients, similarly to healthy older adults, free EAA supplements stimulate whole body protein anabolism more than free amino acid supplements with the composition of complete proteins. Therefore, free EAA supplements may aid in the prevention and treatment of muscle wasting in this patient population.
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Affiliation(s)
- Renate Jonker
- Center for Translational Research in Aging & Longevity, Dept. of Health and Kinesiology, Texas A&M University, College Station, TX, U.S.A.; Dept. of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR, U.S.A..
| | - Nicolaas Ep Deutz
- Center for Translational Research in Aging & Longevity, Dept. of Health and Kinesiology, Texas A&M University, College Station, TX, U.S.A.; Dept. of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR, U.S.A
| | - Marcia L Erbland
- Dept. of Pulmonary and Critical Care Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, U.S.A
| | - Paula J Anderson
- Dept. of Pulmonary and Critical Care Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, U.S.A
| | - Mariëlle Pkj Engelen
- Center for Translational Research in Aging & Longevity, Dept. of Health and Kinesiology, Texas A&M University, College Station, TX, U.S.A.; Dept. of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR, U.S.A
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Barfod KK, Roggenbuck M, Al-Shuweli S, Fakih D, Sørensen SJ, Sørensen GL. Alterations of the murine gut microbiome in allergic airway disease are independent of surfactant protein D. Heliyon 2017; 3:e00262. [PMID: 28367508 PMCID: PMC5361934 DOI: 10.1016/j.heliyon.2017.e00262] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2016] [Revised: 02/09/2017] [Accepted: 03/08/2017] [Indexed: 02/07/2023] Open
Abstract
Background SP-D is an important host defense lectin in innate immunity and SP-D deficient mice show several abnormal immune effects and are susceptible to allergen-induced airway disease. At the same time, host microbiome interactions play an important role in the development of allergic airway disease, and alterations to gut microbiota have been linked to airway disease through the gut-lung axis. Currently, it is unknown if the genotype (Sftpd-/- or Sftpd+/+) of the standard SP-D mouse model can affect the host microbiota to such an degree that it would overcome the cohousing effect on microbiota and interfere with the interpretation of immunological data from the model. Generally, little is known about the effect of the SP-D protein in itself and in combination with airway disease on the microbiota. In this study, we tested the hypothesis that microbiome composition would change with the lack of SP-D protein and presence of allergic airway disease in the widely used SP-D-deficient mouse model. Results We describe here for the first time the lung and gut microbiota of the SP-D mouse model with OVA induced allergic airway disease. After the challenge animals were killed and fecal samples were taken from the caecum and lungs were subjected to bronchoalveolar lavage for comparison of gut and lung microbiota by Illumina 16S rRNA gene sequencing. A significant community shift was observed in gut microbiota after challenge with OVA. However, the microbial communities were not significantly different between SP-D deficient and wild type mice from the same cages in either naïve or OVA treated animals. Wild type animals did however show the largest variation between mice. Conclusions Our results show that the composition of the microbiota is not influenced by the SP-D deficient genotype under naïve or OVA induced airway disease. However, OVA sensitization and pulmonary challenge did alter the gut microbiota, supporting a bidirectional lung-gut crosstalk. Future mechanistic investigations of the influence of induced allergic airway disease on gut microbiota are warranted.
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Affiliation(s)
- Kenneth K Barfod
- National Research Centre for the Working Environment, Lersø Parkallé 105, 2100 Copenhagen O, Denmark
| | - Michael Roggenbuck
- University of Copenhagen, Department of Biology, Microbiology, Universitetsparken 15, 2100 Copenhagen O, Denmark
| | - Suzan Al-Shuweli
- National Research Centre for the Working Environment, Lersø Parkallé 105, 2100 Copenhagen O, Denmark
| | - Dalia Fakih
- Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark; Laboratory of Immunology, Faculty of public health, Lebanese University, Fanar, Lebanon
| | - Søren J Sørensen
- University of Copenhagen, Department of Biology, Microbiology, Universitetsparken 15, 2100 Copenhagen O, Denmark
| | - Grith L Sørensen
- Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark
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Tulic MK, Piche T, Verhasselt V. Lung-gut cross-talk: evidence, mechanisms and implications for the mucosal inflammatory diseases. Clin Exp Allergy 2016; 46:519-28. [PMID: 26892389 DOI: 10.1111/cea.12723] [Citation(s) in RCA: 94] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
The mucosal immune system (including airway, intestinal, oral and cervical epithelium) is an integrated network of tissues, cells and effector molecules that protect the host from environmental insults and infections at mucous membrane surfaces. Dysregulation of immunity at mucosal surfaces is thought to be responsible for the alarming global increase in mucosal inflammatory diseases such as those affecting the gastrointestinal (Crohn's disease, ulcerative colitis and irritable bowel syndrome) and respiratory (asthma, allergy and chronic obstructive pulmonary disorder) system. Although immune regulation has been well-studied in isolated mucosal sites, the extent of the immune interaction between anatomically distant mucosal sites has been mostly circumstantial and the focus of much debate. With novel technology and more precise tools to examine histological and functional changes in tissues, today there is increased appreciation of the 'common mucosal immunological system' originally proposed by Bienenstock nearly 40 years ago. Evidence is amounting which shows that stimulation of one mucosal compartment can directly and significantly impact distant mucosal site, however the mechanisms are unknown. Today, we are only beginning to understand the complexity of relationships and communications that exist between different mucosal compartments. A holistic approach to studying the mucosal immune system as an integrated global organ is imperative for future advances in understanding mucosal immunology and for future treatment of chronic diseases. In this review, we particularly focus on the latest evidence and the mechanisms operational in driving the lung-gut cross-talk.
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Affiliation(s)
- M K Tulic
- Université de Nice Sophia-Antipolis, EA 6302 Tolérance Immunitaire, Nice, France.,The International Inflammation 'in-FLAME' Network, Worldwide Universities Network, Perth, WA, Australia
| | - T Piche
- Université de Nice Sophia-Antipolis, EA 6302 Tolérance Immunitaire, Nice, France.,Department of Gastroenterology and Nutrition, Hôpital de l'Archet 2, CHU de Nice, Nice, France
| | - V Verhasselt
- Université de Nice Sophia-Antipolis, EA 6302 Tolérance Immunitaire, Nice, France.,The International Inflammation 'in-FLAME' Network, Worldwide Universities Network, Perth, WA, Australia
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Gomez-Cabrero D, Menche J, Vargas C, Cano I, Maier D, Barabási AL, Tegnér J, Roca J. From comorbidities of chronic obstructive pulmonary disease to identification of shared molecular mechanisms by data integration. BMC Bioinformatics 2016; 17:441. [PMID: 28185567 PMCID: PMC5133493 DOI: 10.1186/s12859-016-1291-3] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Background Deep mining of healthcare data has provided maps of comorbidity relationships between diseases. In parallel, integrative multi-omics investigations have generated high-resolution molecular maps of putative relevance for understanding disease initiation and progression. Yet, it is unclear how to advance an observation of comorbidity relations (one disease to others) to a molecular understanding of the driver processes and associated biomarkers. Results Since Chronic Obstructive Pulmonary disease (COPD) has emerged as a central hub in temporal comorbidity networks, we developed a systematic integrative data-driven framework to identify shared disease-associated genes and pathways, as a proxy for the underlying generative mechanisms inducing comorbidity. We integrated records from approximately 13 M patients from the Medicare database with disease-gene maps that we derived from several resources including a semantic-derived knowledge-base. Using rank-based statistics we not only recovered known comorbidities but also discovered a novel association between COPD and digestive diseases. Furthermore, our analysis provides the first set of COPD co-morbidity candidate biomarkers, including IL15, TNF and JUP, and characterizes their association to aging and life-style conditions, such as smoking and physical activity. Conclusions The developed framework provides novel insights in COPD and especially COPD co-morbidity associated mechanisms. The methodology could be used to discover and decipher the molecular underpinning of other comorbidity relationships and furthermore, allow the identification of candidate co-morbidity biomarkers. Electronic supplementary material The online version of this article (doi:10.1186/s12859-016-1291-3) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- David Gomez-Cabrero
- Department of Medicine, Karolinska Institutet, Unit of Computational Medicine, Stockholm, 171 77, Sweden. .,Karolinska Institutet, Center for Molecular Medicine, Stockholm, 171 77, Sweden. .,Department of Medicine, Unit of Clinical Epidemiology, Karolinska University Hospital, Solna, L8, 17176, Sweden. .,Science for Life Laboratory, Solna, 17121, Sweden. .,Mucosal and Salivary Biology Division, King's College London Dental Institute, London, UK.
| | - Jörg Menche
- Center for Complex Networks Research and Department of Physics, Northeastern University, Boston, MA, USA.,Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.,Center for Network Science, Central European University, Budapest, Hungary
| | - Claudia Vargas
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clinic de Barcelona, Universitat de Barcelona, Barcelona, Spain.,Center for Biomedical Network Research in Respiratory Diseases (CIBERES), Madrid, Spain
| | - Isaac Cano
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clinic de Barcelona, Universitat de Barcelona, Barcelona, Spain.,Center for Biomedical Network Research in Respiratory Diseases (CIBERES), Madrid, Spain
| | | | - Albert-László Barabási
- Center for Complex Networks Research and Department of Physics, Northeastern University, Boston, MA, USA.,Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.,Center for Network Science, Central European University, Budapest, Hungary.,Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Jesper Tegnér
- Department of Medicine, Karolinska Institutet, Unit of Computational Medicine, Stockholm, 171 77, Sweden.,Karolinska Institutet, Center for Molecular Medicine, Stockholm, 171 77, Sweden.,Department of Medicine, Unit of Clinical Epidemiology, Karolinska University Hospital, Solna, L8, 17176, Sweden.,Science for Life Laboratory, Solna, 17121, Sweden
| | - Josep Roca
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clinic de Barcelona, Universitat de Barcelona, Barcelona, Spain. .,Center for Biomedical Network Research in Respiratory Diseases (CIBERES), Madrid, Spain.
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He Y, Wen Q, Yao F, Xu D, Huang Y, Wang J. Gut-lung axis: The microbial contributions and clinical implications. Crit Rev Microbiol 2016; 43:81-95. [PMID: 27781554 DOI: 10.1080/1040841x.2016.1176988] [Citation(s) in RCA: 194] [Impact Index Per Article: 21.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Gut microbiota interacts with host immune system in ways that influence the development of disease. Advances in respiratory immune system also broaden our knowledge of the interaction between host and microbiome in the lung. Increasing evidence indicated the intimate relationship between the gastrointestinal tract and respiratory tract. Exacerbations of chronic gut and lung disease have been shown to share key conceptual features with the disorder and dysregulation of the microbial ecosystem. In this review, we discuss the impact of gut and lung microbiota on disease exacerbation and progression, and the recent understanding of the immunological link between the gut and the lung, the gut-lung axis.
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Affiliation(s)
- Yang He
- a Department of Cancer Center, Union Hospital , Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China
| | - Qu Wen
- a Department of Cancer Center, Union Hospital , Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China
| | - Fangfang Yao
- a Department of Cancer Center, Union Hospital , Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China
| | - Dong Xu
- b Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China
| | - Yuancheng Huang
- b Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China
| | - Junshuai Wang
- c Department of Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China
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Vutcovici M, Brassard P, Bitton A. Inflammatory bowel disease and airway diseases. World J Gastroenterol 2016; 22:7735-7741. [PMID: 27678355 PMCID: PMC5016372 DOI: 10.3748/wjg.v22.i34.7735] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2016] [Revised: 06/14/2016] [Accepted: 07/06/2016] [Indexed: 02/06/2023] Open
Abstract
Airway diseases are the most commonly described lung manifestations of inflammatory bowel disease (IBD). However, the similarities in disease pathogenesis and the sharing of important environmental risk factors and genetic susceptibility suggest that there is a complex interplay between IBD and airway diseases. Recent evidence of IBD occurrence among patients with airway diseases and the higher than estimated prevalence of subclinical airway injuries among IBD patients support the hypothesis of a two-way association. Future research efforts should be directed toward further exploration of this association, as airway diseases are highly prevalent conditions with a substantial public health impact.
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Abstract
Host-microorganism interactions shape local cell functionality, immune responses, and can influence disease development. Evidence indicates that the impact of host-microbe interactions reaches far beyond the local environment, thus influencing responses in peripheral tissues. There is a vital cross-talk between the mucosal tissues of our body, as exemplified by intestinal complications during respiratory disease and vice versa. Although, mechanistically, this phenomenon remains poorly defined, the existence of the gut-lung axis and its implications in both health and disease could be profoundly important for both disease etiology and treatment. In this review, we highlight how changes in the intestinal microenvironment, with a particular focus on the intestinal microbiota, impact upon respiratory disease.
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Tulic MK, Vivinus-Nébot M, Rekima A, Rabelo Medeiros S, Bonnart C, Shi H, Walker A, Dainese R, Boyer J, Vergnolle N, Piche T, Verhasselt V. Presence of commensal house dust mite allergen in human gastrointestinal tract: a potential contributor to intestinal barrier dysfunction. Gut 2016; 65:757-766. [PMID: 26646935 DOI: 10.1136/gutjnl-2015-310523] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2015] [Accepted: 11/05/2015] [Indexed: 12/15/2022]
Abstract
BACKGROUND Abnormal gut barrier function is the basis of gut inflammatory disease. It is known that house dust mite (HDM) aero-allergens induce inflammation in respiratory mucosa. We have recently reported allergen from Dermatophagoides pteronyssinus (Der p1) to be present in rodent gut. OBJECTIVE To examine whether Der p1 is present in human gut and to assess its effect on gut barrier function and inflammation. DESIGN Colonic biopsies, gut fluid, serum and stool were collected from healthy adults during endoscopy. Der p1 was measured by ELISA. Effect of HDM was assessed on gut permeability, tight-junction and mucin expression, and cytokine production, in presence or absence of cysteine protease inhibitors or serine protease inhibitors. In vivo effect of HDM was examined in mice given oral HDM or protease-neutralised HDM. Role of HDM in low-grade inflammation was studied in patients with IBS. RESULTS HDM Der p1 was detected in the human gut. In colonic biopsies from healthy patients, HDM increased epithelial permeability (p<0.001), reduced expression of tight-junction proteins and mucus barrier. These effects were associated with increased tumour necrosis factor (TNF)-α and interleukin (IL)-10 production and were abolished by cysteine-protease inhibitor (p<0.01). HDM effects did not require Th2 immunity. Results were confirmed in vivo in mice. In patients with IBS, HDM further deteriorated gut barrier function, induced TNF-α but failed to induce IL-10 secretion (p<0.001). CONCLUSIONS HDM, a ubiquitous environmental factor, is present in the human gut where it directly affects gut function through its proteolytic activity. HDM may be an important trigger of gut dysfunction and warrants further investigation.
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Affiliation(s)
- Meri K Tulic
- Université de Nice Sophia-Antipolis, EA 6302 Immune Tolerance (TIM), Nice, France The International Inflammation 'in-FLAME' Network, Worldwide Universities Network
| | - Mylene Vivinus-Nébot
- Université de Nice Sophia-Antipolis, EA 6302 Immune Tolerance (TIM), Nice, France Department of Immunology, Hôpital Archet 1, CHU de Nice, Université de Nice Sophia-Antipolis, Nice, France
| | - Akila Rekima
- Université de Nice Sophia-Antipolis, EA 6302 Immune Tolerance (TIM), Nice, France
| | - Samara Rabelo Medeiros
- Université de Nice Sophia-Antipolis, EA 6302 Immune Tolerance (TIM), Nice, France Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Chrystelle Bonnart
- INSERM U1043, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France CNRS, U5282, Toulouse, France Université de Toulouse, Site Paul Sabatier (UPS), Toulouse, France
| | - Haining Shi
- Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Charlestown, Massachusetts, USA
| | - Allan Walker
- Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Charlestown, Massachusetts, USA
| | - Raffaella Dainese
- Université de Nice Sophia-Antipolis, EA 6302 Immune Tolerance (TIM), Nice, France Department of Gastroenterology and Nutrition, Hôpital Archet 2, CHU de Nice, Université de Nice Sophia-Antipolis, Nice, France
| | - Julien Boyer
- Université de Nice Sophia-Antipolis, EA 6302 Immune Tolerance (TIM), Nice, France Department of Gastroenterology and Nutrition, Hôpital Archet 2, CHU de Nice, Université de Nice Sophia-Antipolis, Nice, France
| | - Nathalie Vergnolle
- INSERM U1043, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France CNRS, U5282, Toulouse, France Université de Toulouse, Site Paul Sabatier (UPS), Toulouse, France
| | - Thierry Piche
- Université de Nice Sophia-Antipolis, EA 6302 Immune Tolerance (TIM), Nice, France Department of Gastroenterology and Nutrition, Hôpital Archet 2, CHU de Nice, Université de Nice Sophia-Antipolis, Nice, France
| | - Valérie Verhasselt
- Université de Nice Sophia-Antipolis, EA 6302 Immune Tolerance (TIM), Nice, France The International Inflammation 'in-FLAME' Network, Worldwide Universities Network
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Rodriguez-Roisin R, Bartolome SD, Huchon G, Krowka MJ. Inflammatory bowel diseases, chronic liver diseases and the lung. Eur Respir J 2016; 47:638-50. [PMID: 26797027 DOI: 10.1183/13993003.00647-2015] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2015] [Accepted: 11/12/2015] [Indexed: 12/12/2022]
Abstract
This review is devoted to the distinct associations of inflammatory bowel diseases (IBD) and chronic liver disorders with chronic airway diseases, namely chronic obstructive pulmonary disease and bronchial asthma, and other chronic respiratory disorders in the adult population. While there is strong evidence for the association of chronic airway diseases with IBD, the data are much weaker for the interplay between lung and liver multimorbidities. The association of IBD, encompassing Crohn's disease and ulcerative colitis, with pulmonary disorders is underlined by their heterogeneous respiratory manifestations and impact on chronic airway diseases. The potential relationship between the two most prevalent liver-induced pulmonary vascular entities, i.e. portopulmonary hypertension and hepatopulmonary syndrome, and also between liver disease and other chronic respiratory diseases is also approached. Abnormal lung function tests in liver diseases are described and the role of increased serum bilirubin levels on chronic respiratory problems are considered.
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Affiliation(s)
- Roberto Rodriguez-Roisin
- Servei de Pneumologia (Institut del Tòrax), Hospital Clínic, Institut Biomédic August Pi i Sunyer (IDIBAPS), Ciber Enfermedades Respiratorias (CIBERES), Universitat de Barcelona, Barcelona, Spain
| | - Sonja D Bartolome
- Pulmonary and Critical Care Medicine, UT Southwestern Medical Center, Dallas, TX, USA
| | - Gérard Huchon
- Service de Pneumologie, Université Paris 5, Paris, France
| | - Michael J Krowka
- Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA
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DeChristopher LR, Uribarri J, Tucker KL. Intake of high fructose corn syrup sweetened soft drinks is associated with prevalent chronic bronchitis in U.S. Adults, ages 20-55 y. Nutr J 2015; 14:107. [PMID: 26474970 PMCID: PMC4609055 DOI: 10.1186/s12937-015-0097-x] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2015] [Accepted: 10/07/2015] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND High fructose corn syrup (HFCS) sweetened soft drink intake has been linked with asthma in US high-schoolers. Intake of beverages with excess free fructose (EFF), including apple juice, and HFCS sweetened fruit drinks and soft drinks, has been associated with asthma in children. One hypothesis for this association is that underlying fructose malabsorption and fructose reactivity in the GI may contribute to in situ formation of enFruAGEs. EnFruAGEs may be an overlooked source of advanced glycation end-products (AGE) that contribute to lung disease. AGE/ RAGEs are elevated in COPD lungs. EFF intake has increased in recent decades, and intakes may exceed dosages associated with adult fructose malabsorption in subsets of the population. Intestinal dysfunction has been shown to be elevated in COPD patients. The objective of this study was to investigate the association between HFCS sweetened soft drink intake and chronic bronchitis (CB), a common manifestation of COPD, in adults. METHODS DESIGN In this cross sectional analysis, the outcome variable was self-reported existing chronic bronchitis or history of CB. Exposure variable was non-diet soda. Rao Scott Ҳ(2) was used for prevalence differences and logistic regression for associations, adjusted for age, sex, race-ethnicity, BMI, smoking, exposure to in-home smoking, pre-diabetes, diabetes, SES, total energy and total fruits and beverages consumption. SETTING Data are from the National Health and Nutrition Examination Survey 2003-2006. SUBJECTS 2801 adults aged 20-55 y. RESULTS There was a statistically significant correlation between intake of non-diet soft drinks and greater prevalence and odds of chronic bronchitis (p < 0.05). Independent of all covariates, intake of non-diet soda ≥5 times a week (vs. non/low non-diet soda) was associated with nearly twice the likelihood of having chronic bronchitis (OR = 1.80; p = 0.047; 95% CI 1.01-3.20). CONCLUSIONS HFCS sweetened soft drink intake is correlated with chronic bronchitis in US adults aged 20-55 y, after adjusting for covariates, including smoking. Results support the hypothesis that underlying fructose malabsorption and fructose reactivity in the GI may contribute to chronic bronchitis, perhaps through in situ formation of enFruAGEs, which may contribute to lung disease. Longitudinal and biochemical research is needed to confirm and clarify the mechanisms involved.
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Affiliation(s)
- Luanne Robalo DeChristopher
- Biochemistry, Molecular Biology, NY Medical College, Valhalla, NY, USA.
- , P.O. Box 5542, Eugene, OR, 97405, USA.
| | - Jaime Uribarri
- Department of Medicine, the Icahn School of Medicine, New York, NY, USA
| | - Katherine L Tucker
- Department of Clinical Laboratory and Nutritional Sciences, University of Massachusetts, Lowell, MA, USA
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Mortaz E, Adcock IM, Ricciardolo FLM, Varahram M, Jamaati H, Velayati AA, Folkerts G, Garssen J. Anti-Inflammatory Effects of Lactobacillus Rahmnosus and Bifidobacterium Breve on Cigarette Smoke Activated Human Macrophages. PLoS One 2015; 10:e0136455. [PMID: 26317628 PMCID: PMC4552661 DOI: 10.1371/journal.pone.0136455] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2015] [Accepted: 08/03/2015] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Chronic obstructive pulmonary disease (COPD) is a major global health problem with cigarette smoke (CS) as the main risk factor for its development. Airway inflammation in COPD involves the increased expression of inflammatory mediators such as CXCL-8 and IL-1β which are important mediators for neutrophil recruitment. Macrophages are an important source of these mediators in COPD. Lactobacillus rhamnosus (L. rhamnosus) and Befidobacterium breve (B. breve) attenuate the development of 'allergic asthma' in animals but their effects in COPD are unknown. OBJECTIVE To determine the anti-inflammatory effects of L. rhamnosus and B. breve on CS and Toll-like receptor (TLR) activation. DESIGN We stimulated the human macrophage cell line THP-1 with CS extract in the presence and absence of L. rhamnosus and B. breve and measured the expression and release of inflammatory mediators by RT-qPCR and ELISA respectively. An activity assay and Western blotting were used to examine NF-κB activation. RESULTS Both L. rhamnosus and B. breve were efficiently phagocytized by human macrophages. L. rhamnosus and B. breve significantly suppressed the ability of CS to induce the expression of IL-1β, IL-6, IL-10, IL-23, TNFα, CXCL-8 and HMGB1 release (all p<0.05) in human THP-1 macrophages. Similar suppression of TLR4- and TLR9-induced CXCL8 expression was also observed (p<0.05). The effect of L. rhamnosus and B. breve on inflammatory mediator release was associated with the suppression of CS-induced NF-κB activation (p<0.05). CONCLUSIONS This data indicate that these probiotics may be useful anti-inflammatory agents in CS-associated disease such as COPD.
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Affiliation(s)
- Esmaeil Mortaz
- Cell and Molecular Biology Group, Airways Disease Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, Dovehouse Street, London, United Kingdom
- Chronic respiratory research center, National Research and Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Department of Immunology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ian M. Adcock
- Cell and Molecular Biology Group, Airways Disease Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, Dovehouse Street, London, United Kingdom
| | | | - Mohammad Varahram
- Mycobacteriology Research Center (MRC) National Research Institute of Tuberculosis and lung diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamidreza Jamaati
- Chronic respiratory research center, National Research and Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Akbar Velayati
- Mycobacteriology Research Center (MRC) National Research Institute of Tuberculosis and lung diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Gert Folkerts
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands
| | - Johan Garssen
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands
- Nutricia Research Centre for Specialized Nutrition, Utrecht, The Netherlands
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Alterations of the Murine Gut Microbiome with Age and Allergic Airway Disease. J Immunol Res 2015; 2015:892568. [PMID: 26090504 PMCID: PMC4451525 DOI: 10.1155/2015/892568] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2015] [Accepted: 04/16/2015] [Indexed: 12/13/2022] Open
Abstract
The gut microbiota plays an important role in the development of asthma. With advanced age the microbiome and the immune system are changing and, currently, little is known about how these two factors contribute to the development of allergic asthma in the elderly. In this study we investigated the associations between the intestinal microbiome and allergic airway disease in young and old mice that were sensitized and challenged with house dust mite (HDM). After challenge, the animals were sacrificed, blood serum was collected for cytokine analysis, and the lungs were processed for histopathology. Fecal pellets were excised from the colon and subjected to 16S rRNA analysis. The microbial community structure changed with age and allergy development, where alterations in fecal communities from young to old mice resembled those after HDM challenge. Allergic mice had induced serum levels of IL-17A and old mice developed a greater allergic airway response compared to young mice. This study demonstrates that the intestinal bacterial community structure differs with age, possibly contributing to the exaggerated pulmonary inflammatory response in old mice. Furthermore, our results show that the composition of the gut microbiota changes with pulmonary allergy, indicating bidirectional gut-lung communications.
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