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Fortmann I, Welp A, Hoffmann N, Faust K, Silwedel C, Retzmann J, Gembicki M, Köstlin-Gille N, Häfke A, Zemlin M, Marissen J, Bossung V, Soler Wenglein J, Scharf JL, Weichert J, Müller A, Ricklefs I, Rody A, Pirr S, Boutin S, Rupp J, Brinkmann F, Heideking M, Stichtenoth G, Göpel W, Herting E, Hanke K, Härtel C. Perinatal Antibiotic Exposure and Respiratory Outcomes in Children Born Preterm. JAMA Netw Open 2025; 8:e259647. [PMID: 40354053 PMCID: PMC12070239 DOI: 10.1001/jamanetworkopen.2025.9647] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2024] [Accepted: 03/07/2025] [Indexed: 05/14/2025] Open
Abstract
Importance Animal models suggest a link between early antibiotic exposure and obstructive airway disease, but corresponding data for premature infants are lacking. Objective To investigate whether repeated perinatal antibiotic exposure in preterm neonates with very low birth weight (VLBW) is associated with obstructive airway disease at early school age. Design, Setting, and Participants In this population-based, multicenter cohort study, VLBW preterm neonates (22 weeks 0 days' to 36 weeks 6 days' gestation with birth weight <1500 g) were enrolled in 58 German Neonatal Network (GNN) centers from January 2009 to March 2017 and received a standardized follow-up at 5 to 7 years of age. To assess the sequential outcomes of antibiotic exposures, the post hoc analysis was restricted to participants born by cesarean delivery. Data were analyzed from May 2024 to February 2025. Exposure Perinatal antibiotic exposure, defined by an antibiotic risk score (ARS). Main Outcome and Measures The primary end point was the forced expiratory volume in 1 second (FEV1) z score at 5 to 7 years of age. The low-risk (ARS I) group was exclusively exposed to surgical antimicrobial prophylaxis (SAP) given to the mother before cesarean delivery. The intermediate-risk (ARS II) group was exposed to maternal SAP and postnatal antibiotic treatment of the neonate, while the high-risk (ARS III) group was additionally exposed to antenatal maternal treatment. Secondary outcomes included forced vital capacity (FVC) z score and childhood asthma episodes. Univariate and linear regression models were used to analyze outcome measures. Results Of 3820 VLBW preterm-born children with follow-up at age 5 to 7 years (median gestational age, 28.4 weeks [IQR, 26.6-30.3 weeks]; 1948 [51.0%] male; 1382 [36.2%] from a multiple birth), 3109 (81.4%) were born by cesarean delivery. Of these children, 292 (9.4%) were classified into ARS I, 1329 (42.7%) into ARS II, and 1488 (47.9%) into ARS III. Higher ARS levels were associated with lower FEV1 z scores at early school age (ARS II vs I: β, -0.31 [95% CI, -0.59 to -0.02]; P = .03; ARS III vs II: β, -0.27 [95% CI, -0.46 to -0.08]; P = .006). In the secondary analysis, a higher exposure level (ARS III vs II) was associated with impaired FVC z scores (β, -0.23; 95% CI, -0.43 to -0.03; P = .02) and an increased risk of early childhood asthma episodes (odds ratio, 1.91; 95% CI, 1.32-2.76; P = .001). Conclusions and Relevance In this GNN cohort study, multiple episodes of perinatal antibiotic exposure were associated with impaired lung function in preterm-born children at early school age. Early identification of high-risk neonates may enable targeted strategies to support respiratory health and optimize long-term outcomes.
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Affiliation(s)
- Ingmar Fortmann
- Department of Pediatrics, University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
- German Center for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Lübeck and Borstel, Germany
| | - Amrei Welp
- Department of Gynecology and Obstetrics, University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Nele Hoffmann
- Department of Pediatrics, University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Kirstin Faust
- Department of Pediatrics, University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Christine Silwedel
- Department of Pediatrics, University Hospital of Würzburg, Würzburg, Germany
| | - Jana Retzmann
- Department of Pediatrics, University Hospital of Würzburg, Würzburg, Germany
| | - Michael Gembicki
- Department of Gynecology and Obstetrics, University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | | | - Anna Häfke
- Department of Pediatrics, University Hospital of Würzburg, Würzburg, Germany
| | - Michael Zemlin
- Department of Pediatrics, University Hospital of Saarland, Homburg, Germany
| | - Janina Marissen
- Department of Pediatrics, University Hospital of Würzburg, Würzburg, Germany
| | - Verena Bossung
- Department of Obstetrics, University Hospital Zürich, Zürich, Switzerland
| | - Janina Soler Wenglein
- Department of Pediatrics, Protestant Hospital of the Bethel Foundation, University Medical Center OWL, Bielefeld University, Bielefeld, Germany
- Medical School, Bielefeld University, Bielefeld, Germany
- Department of Human Medicine, Faculty of Medicine, Witten/Herdecke University, Witten, Germany
| | - Jan-Lennard Scharf
- Department of Gynecology and Obstetrics, University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Jan Weichert
- Department of Gynecology and Obstetrics, University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Andreas Müller
- Department of Pediatrics, University Hospital of Bonn, Bonn, Germany
| | - Isabell Ricklefs
- Department of Pediatrics, University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
- Airway Research Center North (ARCN), German Center for Lung Research (DZL), Lübeck, Germany
| | - Achim Rody
- Department of Gynecology and Obstetrics, University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Sabine Pirr
- Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany
| | - Sebastien Boutin
- German Center for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Lübeck and Borstel, Germany
- Airway Research Center North (ARCN), German Center for Lung Research (DZL), Lübeck, Germany
- Institute of Medical Microbiology, University of Lübeck and University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Jan Rupp
- German Center for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Lübeck and Borstel, Germany
- Institute of Medical Microbiology, University of Lübeck and University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
- Infectious Disease Clinic, University of Lübeck and University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Folke Brinkmann
- Department of Pediatrics, University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
- Airway Research Center North (ARCN), German Center for Lung Research (DZL), Lübeck, Germany
| | - Martin Heideking
- Department of Pediatrics, University Hospital of Tübingen, Tübingen, Germany
| | - Guido Stichtenoth
- Department of Pediatrics, University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Wolfgang Göpel
- Department of Pediatrics, University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Egbert Herting
- Department of Pediatrics, University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Kathrin Hanke
- Department of Pediatrics, University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Christoph Härtel
- Department of Pediatrics, University Hospital of Würzburg, Würzburg, Germany
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Bellocchi C, Volkmann ER. Advancing Gastrointestinal Microbiota Research in Systemic Sclerosis: Lessons Learned from Prior Research and Opportunities to Accelerate Discovery. Rheum Dis Clin North Am 2025; 51:213-231. [PMID: 40246439 DOI: 10.1016/j.rdc.2025.01.002] [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] [Indexed: 04/19/2025]
Abstract
Dysbiosis is a feature of patients with systemic sclerosis (SSc). While a causal relationship between the gastrointestinal (GI) microbiota and SSc pathogenesis has not been established, alterations in the GI microbiota are appreciated early in the SSc disease course. Moreover, recent research has illuminated specific microbial signatures that define SSc phenotypes. This review summarizes new research on the GI microbiome in SSc with a focus on technical advancements and the emerging study of the GI metabolome. This review also addresses diverse modalities for manipulating the GI microbiome with the hope of developing preventative treatment strategies to avert progression of SSc.
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Affiliation(s)
- Chiara Bellocchi
- Department of Clinical Sciences and Community Health, University of Milan, Dipartimento di Eccellenza 2023-2027, Milan, Italy; Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Via Pace 9, Milano 20122, Italy
| | - Elizabeth R Volkmann
- Department of Medicine, University of California, Los Angeles, David Geffen School of Medicine, USA.
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Guo W, Hong E, Ma H, Wang J, Wang Q. Effect of the gut microbiome, skin microbiome, plasma metabolome, white blood cells subtype, immune cells, inflammatory proteins, and inflammatory cytokines on asthma: a two-sample Mendelian randomized study and mediation analysis. Front Immunol 2025; 16:1436888. [PMID: 40191192 PMCID: PMC11968350 DOI: 10.3389/fimmu.2025.1436888] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Accepted: 03/03/2025] [Indexed: 04/09/2025] Open
Abstract
Background Asthma is a chronic inflammatory disorder arising from incompletely understood heterogenic gene-environment interactions. This study aims to investigate causal relationships among gut microbiota, skin microbiota, plasma metabolomics, white blood cells subtype, immune cells, inflammatory proteins, inflammatory cytokines, and asthma. Methods First, two-sample Mendelian randomization analysis was used to identify causal relationships. The summary statistics of 412 gut microbiota traits (N = 7 738), 150 skin microbiota traits (N = 579), 1 400 plasma metabolite traits (N = 8 299), white blood cells subtype counts (N = 746 667), 731 immune cell traits (N = 3 669), 91 circulating inflammatory proteins (N = 14 744), 41 inflammatory cytokine traits (N = 8 293), and asthma traits (N = 244 562) were obtained from publicly available genome-wide association studies. Inverse-variance weighted regression was used as the primary Mendelian randomization method. A series of sensitivity analyses was performed to test the robustness of causal estimates. Subsequently, mediation analysis was performed to identify the pathway from gut or skin microbiota to asthma mediated by plasma metabolites, immune cells, and inflammatory proteins. Results Mendelian randomization revealed the causal effects of 31 gut bacterial features (abundances of 19 bacterial pathways and 12 microbiota), 10 skin bacterial features, 108 plasma metabolites (81 metabolites and 27 ratios), 81 immune cells, five circulating inflammatory proteins, and three inflammatory cytokines and asthma. Moreover, the mediation analysis results supported the mediating effects of one plasma metabolite, five immunophenotypes, and one inflammatory protein on the gut or skin microbiota in asthma pathogenesis. Conclusion The findings of this study support a causal relationship among gut microbiota, skin microbiota, plasma metabolites, immune cells, inflammatory proteins, inflammatory cytokines, and asthma. Mediating pathways through which the above factors may affect asthma were proposed. The biomarkers and mediation pathways identified in this work provide new insights into the mechanism of asthma and contribute to its prevention and treatment.
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Affiliation(s)
- Wenqian Guo
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
- National Institute of Traditional Chinese Medicine Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Er Hong
- Department of Respiratory Medicine, Ningbo Hospital of Traditional Chinese Medicine, Zhejiang University of Chinese Medicine, Ningbo, China
| | - Han Ma
- National Institute of Traditional Chinese Medicine Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, China
- The Second Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
| | - Ji Wang
- National Institute of Traditional Chinese Medicine Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Qi Wang
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
- National Institute of Traditional Chinese Medicine Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, China
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Pattaroni C, Marsland BJ, Harris NL. Early-Life Host-Microbial Interactions and Asthma Development: A Lifelong Impact? Immunol Rev 2025; 330:e70019. [PMID: 40099971 PMCID: PMC11917194 DOI: 10.1111/imr.70019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Revised: 02/19/2025] [Accepted: 02/28/2025] [Indexed: 03/20/2025]
Abstract
Childhood is a multifactorial disease, and recent research highlights the influence of early-life microbial communities in shaping disease risk. This review explores the roles of the gut and respiratory microbiota in asthma development, emphasizing the importance of early microbial exposure. The gut microbiota has been particularly well studied, with certain taxa like Faecalibacterium and Bifidobacterium linked to asthma protection, whereas short-chain fatty acids produced by gut microbes support immune tolerance through the gut-lung axis. In contrast, the respiratory microbiota, though low in biomass, shows consistent associations between early bacterial colonization by Streptococcus, Moraxella, and Haemophilus and increased asthma risk. The review also addresses the emerging roles of the skin microbiota and environmental fungi in asthma, though findings remain inconsistent. Timing is a critical factor, with early-life disruptions, such as antibiotic use, potentially leading to increased asthma risk. Despite significant advances, there are still unresolved questions about the long-term consequences of early microbial perturbations, particularly regarding whether microbial dysbiosis is a cause or consequence of asthma. This review integrates current findings, highlighting the need for deeper investigation into cross-organ interactions and early microbial exposures to understand childhood asthma pathophysiology.
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Affiliation(s)
- Céline Pattaroni
- Department of Immunology, School of Translational MedicineMonash UniversityMelbourneVictoriaAustralia
| | - Benjamin J. Marsland
- Department of Immunology, School of Translational MedicineMonash UniversityMelbourneVictoriaAustralia
| | - Nicola L. Harris
- Department of Immunology, School of Translational MedicineMonash UniversityMelbourneVictoriaAustralia
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Yin Y, Yang T, Tian Z, Shi C, Yan C, Li H, Du Y, Li G. Progress in the investigation of the Firmicutes/Bacteroidetes ratio as a potential pathogenic factor in ulcerative colitis. J Med Microbiol 2025; 74. [PMID: 39886918 DOI: 10.1099/jmm.0.001966] [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] [Indexed: 02/01/2025] Open
Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that presents significant challenges in terms of treatment owing to a pronounced likelihood of recurrence and an elevated risk of cancer development, thereby imposing substantial risks on affected individuals. The gut microbiota of Firmicutes and Bacteroidetes (F/B) can affect diseases associated with IBD, which is also a risk factor for breast cancer. This review discusses the hazards associated with UC, highlights the existing disparities in UC-associated gut microbiome research, explores the concept of the F/B ratio and scrutinizes its correlation with UC. Moreover, the differences in the F/B ratios between healthy individuals and those with UC were thoroughly examined. These findings suggest that an elevated F/B ratio may promote the occurrence and progression of UC. Consequently, the F/B ratio may play a significant role in UC by influencing gut microbiota composition and inflammatory responses, suggesting that future research should focus on this ratio as a potential biomarker for disease progression and therapeutic targets in managing UC.
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Affiliation(s)
- Yu Yin
- The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130117, PR China
| | - Tiezheng Yang
- The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130117, PR China
| | - Ziyue Tian
- Hainan Provincial People's Hospital, Haikou 570100, PR China
| | - Chong Shi
- The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130117, PR China
| | - Chengqiu Yan
- The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130117, PR China
| | - Hui Li
- The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130117, PR China
| | - Yu Du
- The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130117, PR China
| | - Guofeng Li
- Shenzhen Bao'an Authentic TCM Therapy Hospital, Shenzhen 518000, PR China
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Kabil A, Nayyar N, Brassard J, Li Y, Chopra S, Hughes MR, McNagny KM. Microbial intestinal dysbiosis drives long-term allergic susceptibility by sculpting an ILC2-B1 cell-innate IgE axis. J Allergy Clin Immunol 2024; 154:1260-1276.e9. [PMID: 39134158 DOI: 10.1016/j.jaci.2024.07.023] [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: 02/27/2024] [Revised: 07/16/2024] [Accepted: 07/19/2024] [Indexed: 09/05/2024]
Abstract
BACKGROUND The abundance and diversity of intestinal commensal bacteria influence systemic immunity with impact on disease susceptibility and severity. For example, loss of short chain fatty acid (SCFA)-fermenting bacteria in early life (humans and mice) is associated with enhanced type 2 immune responses in peripheral tissues including the lung. OBJECTIVE Our goal was to reveal the microbiome-dependent cellular and molecular mechanisms driving enhanced susceptibility to type 2 allergic lung disease. METHODS We used low-dose vancomycin to selectively deplete SCFA-fermenting bacteria in wild-type mice. We then examined the frequency and activation status of innate and adaptive immune cell lineages with and without SCFA supplementation. Finally, we used ILC2-deficient and signal transducer and activator of transcription 6 (STAT6)-deficient transgenic mouse strains to delineate the cellular and cytokine pathways leading to enhanced allergic disease susceptibility. RESULTS Mice with vancomycin-induced dysbiosis exhibited a 2-fold increase in lung ILC2 primed to produce elevated levels of IL-2, -5, and -13. In addition, upon IL-33 inhalation, mouse lung ILC2 displayed a novel ability to produce high levels of IL-4. These expanded and primed ILC2s drove B1 cell expansion and IL-4-dependent production of IgE that in turn led to exacerbated allergic inflammation. Importantly, these enhanced lung inflammatory phenotypes in mice with vancomycin-induced dysbiosis were reversed by administration of dietary SCFA (specifically butyrate). CONCLUSION SCFAs regulate an ILC2-B1 cell-IgE axis. Early-life administration of vancomycin, an antibiotic known to deplete SCFA-fermenting gut bacteria, primes and amplifies this axis and leads to lifelong enhanced susceptibility to type 2 allergic lung disease.
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Affiliation(s)
- Ahmed Kabil
- School of Biomedical Engineering, University of British Columbia, Vancouver, British Columbia, Canada
| | - Natalia Nayyar
- School of Biomedical Engineering, University of British Columbia, Vancouver, British Columbia, Canada
| | - Julyanne Brassard
- School of Biomedical Engineering, University of British Columbia, Vancouver, British Columbia, Canada
| | - Yicong Li
- School of Biomedical Engineering, University of British Columbia, Vancouver, British Columbia, Canada
| | - Sameeksha Chopra
- School of Biomedical Engineering, University of British Columbia, Vancouver, British Columbia, Canada
| | - Michael R Hughes
- School of Biomedical Engineering, University of British Columbia, Vancouver, British Columbia, Canada.
| | - Kelly M McNagny
- School of Biomedical Engineering, University of British Columbia, Vancouver, British Columbia, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada; Center for Heart Lung Innovation, St Paul's Hospital, Vancouver, British Columbia, Canada.
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Dai DLY, Petersen C, Turvey SE. Reduce, reinforce, and replenish: safeguarding the early-life microbiota to reduce intergenerational health disparities. Front Public Health 2024; 12:1455503. [PMID: 39507672 PMCID: PMC11537995 DOI: 10.3389/fpubh.2024.1455503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Accepted: 10/02/2024] [Indexed: 11/08/2024] Open
Abstract
Socioeconomic (SE) disparity and health inequity are closely intertwined and associated with cross-generational increases in the rates of multiple chronic non-communicable diseases (NCDs) in North America and beyond. Coinciding with this social trend is an observed loss of biodiversity within the community of colonizing microbes that live in and on our bodies. Researchers have rightfully pointed to the microbiota as a key modifiable factor with the potential to ease existing health inequities. Although a number of studies have connected the adult microbiome to socioeconomic determinants and health outcomes, few studies have investigated the role of the infant microbiome in perpetuating these outcomes across generations. It is an essential and important question as the infant microbiota is highly sensitive to external forces, and observed shifts during this critical window often portend long-term outcomes of health and disease. While this is often studied in the context of direct modulators, such as delivery mode, family size, antibiotic exposure, and breastfeeding, many of these factors are tied to underlying socioeconomic and/or cross-generational factors. Exploring cross-generational socioeconomic and health inequities through the lens of the infant microbiome may provide valuable avenues to break these intergenerational cycles. In this review, we will focus on the impact of social inequality in infant microbiome development and discuss the benefits of prioritizing and restoring early-life microbiota maturation for reducing intergenerational health disparities.
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Affiliation(s)
| | | | - Stuart E. Turvey
- Department of Pediatrics, BC Children’s Hospital, University of British Columbia, Vancouver, BC, Canada
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Suárez-Martínez C, Santaella-Pascual M, Yagüe-Guirao G, García-Marcos L, Ros G, Martínez-Graciá C. The Early Appearance of Asthma and Its Relationship with Gut Microbiota: A Narrative Review. Microorganisms 2024; 12:1471. [PMID: 39065238 PMCID: PMC11278858 DOI: 10.3390/microorganisms12071471] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Revised: 07/12/2024] [Accepted: 07/15/2024] [Indexed: 07/28/2024] Open
Abstract
Asthma is, worldwide, the most frequent non-communicable disease affecting both children and adults, with high morbidity and relatively low mortality, compared to other chronic diseases. In recent decades, the prevalence of asthma has increased in the pediatric population, and, in general, the risk of developing asthma and asthma-like symptoms is higher in children during the first years of life. The "gut-lung axis" concept explains how the gut microbiota influences lung immune function, acting both directly, by stimulating the innate immune system, and indirectly, through the metabolites it generates. Thus, the process of intestinal microbial colonization of the newborn is crucial for his/her future health, and the alterations that might generate dysbiosis during the first 100 days of life are most influential in promoting hypersensitivity diseases. That is why this period is termed the "critical window". This paper reviews the published evidence on the numerous factors that can act by modifying the profile of the intestinal microbiota of the infant, thereby promoting or inhibiting the risk of asthma later in life. The following factors are specifically addressed in depth here: diet during pregnancy, maternal adherence to a Mediterranean diet, mode of delivery, exposure to antibiotics, and type of infant feeding during the first three months of life.
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Affiliation(s)
- Clara Suárez-Martínez
- Biomedical Research Institute of Murcia (IMIB-Arrixaca), 30120 Murcia, Spain; (C.S.-M.); (G.Y.-G.); (G.R.)
- Food Science and Nutrition Department, Veterinary Faculty, Regional Campus of International Excellence Campus Mare Nostrum, University of Murcia, 30100 Murcia, Spain
| | - Marina Santaella-Pascual
- Biomedical Research Institute of Murcia (IMIB-Arrixaca), 30120 Murcia, Spain; (C.S.-M.); (G.Y.-G.); (G.R.)
- Food Science and Nutrition Department, Veterinary Faculty, Regional Campus of International Excellence Campus Mare Nostrum, University of Murcia, 30100 Murcia, Spain
| | - Genoveva Yagüe-Guirao
- Biomedical Research Institute of Murcia (IMIB-Arrixaca), 30120 Murcia, Spain; (C.S.-M.); (G.Y.-G.); (G.R.)
- Microbiology Service, Virgen de La Arrixaca University Clinical Hospital, Regional Campus of International Excellence Campus Mare Nostrum, University of Murcia, 30120 Murcia, Spain
| | - Luis García-Marcos
- Biomedical Research Institute of Murcia (IMIB-Arrixaca), 30120 Murcia, Spain; (C.S.-M.); (G.Y.-G.); (G.R.)
- Pediatric Allergy and Pulmonology Units, Virgen de La Arrixaca University Clinical Hospital, Regional Campus of International Excellence Campus Mare Nostrum, University of Murcia, 30120 Murcia, Spain
- Network of Asthma and Adverse and Allergic Reactions (ARADyAL), 28029 Madrid, Spain
| | - Gaspar Ros
- Biomedical Research Institute of Murcia (IMIB-Arrixaca), 30120 Murcia, Spain; (C.S.-M.); (G.Y.-G.); (G.R.)
- Food Science and Nutrition Department, Veterinary Faculty, Regional Campus of International Excellence Campus Mare Nostrum, University of Murcia, 30100 Murcia, Spain
| | - Carmen Martínez-Graciá
- Biomedical Research Institute of Murcia (IMIB-Arrixaca), 30120 Murcia, Spain; (C.S.-M.); (G.Y.-G.); (G.R.)
- Food Science and Nutrition Department, Veterinary Faculty, Regional Campus of International Excellence Campus Mare Nostrum, University of Murcia, 30100 Murcia, Spain
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Song X, Liang J, Lin S, Xie Y, Ke C, Ao D, Lu J, Chen X, He Y, Liu X, Li W. Gut-lung axis and asthma: A historical review on mechanism and future perspective. Clin Transl Allergy 2024; 14:e12356. [PMID: 38687096 PMCID: PMC11060082 DOI: 10.1002/clt2.12356] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Revised: 03/24/2024] [Accepted: 04/17/2024] [Indexed: 05/02/2024] Open
Abstract
BACKGROUND Gut microbiota are closely related to the development and regulation of the host immune system by regulating the maturation of immune cells and the resistance to pathogens, which affects the host immunity. Early use of antibiotics disrupts the homeostasis of gut microbiota and increases the risk of asthma. Gut microbiota actively interact with the host immune system via the gut-lung axis, a bidirectional communication pathway between the gut and lung. The manipulation of gut microbiota through probiotics, helminth therapy, and fecal microbiota transplantation (FMT) to combat asthma has become a hot research topic. BODY: This review mainly describes the current immune pathogenesis of asthma, gut microbiota and the role of the gut-lung axis in asthma. Moreover, the potential of manipulating the gut microbiota and its metabolites as a treatment strategy for asthma has been discussed. CONCLUSION The gut-lung axis has a bidirectional effect on asthma. Gut microecology imbalance contributes to asthma through bacterial structural components and metabolites. Asthma, in turn, can also cause intestinal damage through inflammation throughout the body. The manipulation of gut microbiota through probiotics, helminth therapy, and FMT can inform the treatment strategies for asthma by regulating the maturation of immune cells and the resistance to pathogens.
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Affiliation(s)
- Xiu‐Ling Song
- Department of PediatricsAffiliated Hospital of Guangdong Medical UniversityZhanjiangChina
| | - Juan Liang
- Department of PediatricsAffiliated Hospital of Guangdong Medical UniversityZhanjiangChina
| | - Shao‐Zhu Lin
- Department of PediatricsAffiliated Hospital of Guangdong Medical UniversityZhanjiangChina
| | - Yu‐Wei Xie
- Department of PediatricsAffiliated Hospital of Guangdong Medical UniversityZhanjiangChina
| | - Chuang‐Hong Ke
- Department of PediatricsAffiliated Hospital of Guangdong Medical UniversityZhanjiangChina
| | - Dang Ao
- Department of PediatricsAffiliated Hospital of Guangdong Medical UniversityZhanjiangChina
| | - Jun Lu
- Department of PediatricsAffiliated Hospital of Guangdong Medical UniversityZhanjiangChina
| | - Xue‐Mei Chen
- Department of PediatricsAffiliated Hospital of Guangdong Medical UniversityZhanjiangChina
| | - Ying‐Zhi He
- Department of PediatricsAffiliated Hospital of Guangdong Medical UniversityZhanjiangChina
| | - Xiao‐Hua Liu
- Department of PediatricsAffiliated Hospital of Guangdong Medical UniversityZhanjiangChina
| | - Wen Li
- Department of PediatricsAffiliated Hospital of Guangdong Medical UniversityZhanjiangChina
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Yang CH, Li XY, Lv JJ, Hou MJ, Zhang RH, Guo H, Feng C. Temporal Trends of Asthma Among Children in the Western Pacific Region From 1990 to 2045: Longitudinal Observational Study. JMIR Public Health Surveill 2024; 10:e55327. [PMID: 38483459 PMCID: PMC10979332 DOI: 10.2196/55327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2023] [Revised: 12/19/2023] [Accepted: 01/23/2024] [Indexed: 04/01/2024] Open
Abstract
BACKGROUND Asthma has become one of the most common chronic conditions worldwide, especially among children. Recent findings show that the prevalence of childhood asthma has increased by 12.6% over the past 30 years, with >262 million people currently affected globally. The reasons for the growing asthma epidemic remain complex and multifactorial. OBJECTIVE This study aims to provide an up-to-date analysis of the changing global and regional asthma prevalence, mortality, disability, and risk factors among children aged <20 years by leveraging the latest data from the Global Burden of Disease Study 2019. Findings from this study can help inform priority areas for intervention to alleviate the rising burden of childhood asthma globally. METHODS The study used data from the Global Burden of Disease Study 2019, concentrating on children aged 0 to 14 years with asthma. We conducted an in-depth analysis of asthma, including its age-standardized prevalence, incidence, mortality, and disability-adjusted life years (DALYs), across diverse demographics, such as region, age, sex, and sociodemographic index, spanning 1990 to 2019. We also projected the future burden of the disease. RESULTS Overall, in the Western Pacific Region, the age-standardized prevalence rate of asthma among children increased slightly, from 3898.4 cases per 100,000 people in 1990 to 3924 per 100,000 in 2019. The age-standardized incidence rate of asthma also increased slightly, from 979.2 to 994.9 per 100,000. In contrast, the age-standardized death rate of asthma decreased from 0.9 to 0.4 per 100,000 and the age-standardized DALY rate decreased from 234.9 to 189.7 per 100,000. At the country level, Japan experienced a considerable decrease in the age-standardized prevalence rate of asthma among children, from 6669.1 per 100,000 in 1990 to 5071.5 per 100,000 in 2019. Regarding DALYs, Japan exhibited a notable reduction, from 300.6 to 207.6 per 100,000. Malaysia also experienced a DALY rate reduction, from 188.4 to 163.3 per 100,000 between 1990 and 2019. We project that the burden of disease in countries other than Japan and the Philippines will remain relatively stable up to 2045. CONCLUSIONS The study indicates an increase in the prevalence and incidence of pediatric asthma, coupled with a decrease in mortality and DALYs in the Western Pacific Region between 1990 and 2019. These intricate phenomena appear to result from a combination of lifestyle shifts, environmental influences, and barriers to health care access. The findings highlight that nations such as Japan have achieved notable success in managing asthma. Overall, the study identified areas of improvement in view of persistent disease burden, underscoring the need for comprehensive collaborative efforts to mitigate the impact of pediatric asthma throughout the region.
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Affiliation(s)
- Cheng-Hao Yang
- Department of General Surgery, School of Medicine, Shanghai Putuo People's Hospital, Tongji University, Shanghai, China
| | - Xin-Yu Li
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jia-Jie Lv
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Meng-Jie Hou
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ru-Hong Zhang
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hong Guo
- Department of Gynecology and Obstetrics, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Chu Feng
- Department of General Surgery, School of Medicine, Shanghai Putuo People's Hospital, Tongji University, Shanghai, China
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11
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Puiu R, Motoc NS, Lucaciu S, Ruta MV, Rajnoveanu RM, Todea DA, Man MA. The Role of Lung Microbiome in Fibrotic Interstitial Lung Disease-A Systematic Review. Biomolecules 2024; 14:247. [PMID: 38540667 PMCID: PMC10968628 DOI: 10.3390/biom14030247] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Revised: 02/11/2024] [Accepted: 02/13/2024] [Indexed: 07/23/2024] Open
Abstract
Interstitial Lung Disease (ILD) involves lung disorders marked by chronic inflammation and fibrosis. ILDs include pathologies like idiopathic pulmonary fibrosis (IPF), connective tissue disease-associated ILD (CTD-ILD), hypersensitivity pneumonitis (HP) or sarcoidosis. Existing data covers pathogenesis, diagnosis (especially using high-resolution computed tomography), and treatments like antifibrotic agents. Despite progress, ILD diagnosis and management remains challenging with significant morbidity and mortality. Recent focus is on Progressive Fibrosing ILD (PF-ILD), characterized by worsening symptoms and fibrosis on HRCT. Prevalence is around 30%, excluding IPF, with a poor prognosis. Early diagnosis is crucial for optimizing outcomes in PF-ILD individuals. The lung microbiome comprises all the microorganisms that are in the respiratory tract. Relatively recent research try to evaluate its role in respiratory disease. Healthy lungs have a diverse microbial community. An imbalance in bacterial composition, changes in bacterial metabolic activities, or changes in bacterial distribution within the lung termed dysbiosis is linked to conditions like COPD, asthma and ILDs. We conducted a systematic review of three important scientific data base using a focused search strategy to see how the lung microbiome is involved in the progression of ILDs. Results showed that some differences in the composition and quality of the lung microbiome exist in ILDs that show progressive fibrosing phenotype. The results seem to suggest that the lung microbiota could be involved in ILD progression, but more studies showing its exact pathophysiological mechanisms are needed.
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Affiliation(s)
- Ruxandra Puiu
- Department of Medical Sciences, Pulmonology, Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania or (R.P.); (S.L.); (D.A.T.); (M.A.M.)
| | - Nicoleta Stefania Motoc
- Department of Medical Sciences, Pulmonology, Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania or (R.P.); (S.L.); (D.A.T.); (M.A.M.)
| | - Sergiu Lucaciu
- Department of Medical Sciences, Pulmonology, Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania or (R.P.); (S.L.); (D.A.T.); (M.A.M.)
| | - Maria Victoria Ruta
- I Department of Pulmonology, “Leon Daniello” Clinical Hospital of Pulmonology, 400371 Cluj-Napoca, Romania;
| | - Ruxandra-Mioara Rajnoveanu
- Department of Palliative Medicine, Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
| | - Doina Adina Todea
- Department of Medical Sciences, Pulmonology, Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania or (R.P.); (S.L.); (D.A.T.); (M.A.M.)
| | - Milena Adina Man
- Department of Medical Sciences, Pulmonology, Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania or (R.P.); (S.L.); (D.A.T.); (M.A.M.)
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Kong J, Yang F, Zong Y, Wang M, Jiang S, Ma Z, Li Z, Li W, Cai Y, Zhang H, Zhao X, Wang J. Early-life antibiotic exposure promotes house dust mite-induced allergic airway inflammation by impacting gut microbiota and lung lipid metabolism. Int Immunopharmacol 2024; 128:111449. [PMID: 38199196 DOI: 10.1016/j.intimp.2023.111449] [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: 09/27/2023] [Revised: 12/04/2023] [Accepted: 12/22/2023] [Indexed: 01/12/2024]
Abstract
Asthma is a chronic inflammatory respiratory disease. Early-life antibiotic exposure is a unique risk factor for the incidence and severity of asthma later in life. Perturbations in microbial-metabolite-immune interaction caused by antibiotics are closely associated with the pathogenesis of allergy and asthma. We investigated the effect of early intervention with common oral antibiotics on later asthma exacerbations and found that different antibiotic exposures can amplify different types of immune responses induced by HDM. Cefixime (CFX) promoted a biased type 2 inflammation, azithromycin (AZM) enhanced Th17 immune response, and cefuroxime axetil (CFA) induced eosinophils recruitment. Moreover, early-life antibiotic exposure can have short- and long-term effects on the abundance, composition, and diversity of the gut microbiota. In the model of CFX-promoted type 2 airway inflammation, fecal metabolomics indicated abnormal lipid metabolism and T cell response. Lipidomic also suggested allergic airway inflammation amplified by CFX is closely associated with abnormal lipid metabolism in lung tissues. Moreover, abnormalities in lipid metabolism-related genes (LMRGs) were found to have cellular heterogeneity be associated with asthma severity by bioinformatics analysis.
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Affiliation(s)
- Jingwei Kong
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China; National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Fan Yang
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China; National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Yuhan Zong
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China; National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Manting Wang
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China; National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Shiyuan Jiang
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Zhaotian Ma
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Zhuqing Li
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China; National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Wenle Li
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China; National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Yuyang Cai
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China; National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Huixian Zhang
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Xiaoshan Zhao
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China; National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, China; School of Chinese Medicine, Southern Medical University, Guangzhou, China.
| | - Ji Wang
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China; National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, China.
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13
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Eladham MW, Selvakumar B, Saheb Sharif-Askari N, Saheb Sharif-Askari F, Ibrahim SM, Halwani R. Unraveling the gut-Lung axis: Exploring complex mechanisms in disease interplay. Heliyon 2024; 10:e24032. [PMID: 38268584 PMCID: PMC10806295 DOI: 10.1016/j.heliyon.2024.e24032] [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: 08/12/2023] [Revised: 12/18/2023] [Accepted: 01/02/2024] [Indexed: 01/26/2024] Open
Abstract
The link between gut and lung starts as early as during organogenesis. Even though they are anatomically distinct, essential bidirectional crosstalk via complex mechanisms supports GLA. Emerging studies have demonstrated the association of gut and lung diseases via multifaceted mechanisms. Advancements in omics and metagenomics technologies revealed a potential link between gut and lung microbiota, adding further complexity to GLA. Despite substantial studies on GLA in various disease models, mechanisms beyond microbial dysbiosis regulating the interplay between gut and lung tissues during disease conditions are not thoroughly reviewed. This review outlines disease specific GLA mechanisms, emphasizing research gaps with a focus on gut-to-lung direction based on current GLA literature. Moreover, the review discusses potential gut microbiota and their products like metabolites, immune modulators, and non-bacterial contributions as a basis for developing treatment strategies for lung diseases. Advanced experimental methods, modern diagnostic tools, and technological advancements are also highlighted as crucial areas for improvement in developing novel therapeutic approaches for GLA-related diseases. In conclusion, this review underscores the importance of exploring additional mechanisms within the GLA to gain a deeper understanding that could aid in preventing and treating a wide spectrum of lung diseases.
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Affiliation(s)
- Mariam Wed Eladham
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
| | - Balachandar Selvakumar
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
| | - Narjes Saheb Sharif-Askari
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
- Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Fatemeh Saheb Sharif-Askari
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
- Department of Pharmacy Practice and Pharmaceutics, College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates
| | | | - Rabih Halwani
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
- Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
- Prince Abdullah Ben Khaled Celiac Disease Research Chair, Department of Pediatrics, Faculty of Medicine, King Saud University, Saudi Arabia
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14
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Li Y, Rao G, Zhu G, Cheng C, Yuan L, Li C, Gao J, Tang J, Wang Z, Li W. Dysbiosis of lower respiratory tract microbiome are associated with proinflammatory states in non-small cell lung cancer patients. Thorac Cancer 2024; 15:111-121. [PMID: 38041547 PMCID: PMC10788479 DOI: 10.1111/1759-7714.15166] [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: 08/07/2023] [Revised: 11/02/2023] [Accepted: 11/03/2023] [Indexed: 12/03/2023] Open
Abstract
BACKGROUND The lung has a sophisticated microbiome, and respiratory illnesses are greatly influenced by the lung microbiota. Despite the fact that numerous studies have shown that lung cancer patients have a dysbiosis as compared to healthy people, more research is needed to explore the association between the microbiota dysbiosis and immune profile within the tumor microenvironment (TME). METHODS In this study, we performed metagenomic sequencing of tumor and normal tissues from 61 non-small cell lung cancer (NSCLC) patients and six patients with other lung diseases. In order to characterize the impact of the microbes in TME, the cytokine concentrations of 24 lung tumor and normal tissues were detected using a multiple cytokine panel. RESULTS Our results showed that tumors had lower microbiota diversity than the paired normal tissues, and the microbiota of NSCLC was enriched in Proteobacteria, Firmicutes, and Actinobacteria. In addition, proinflammatory cytokines such as IL-8, MIF, TNF- α, and so on, were significantly upregulated in tumor tissues. CONCLUSION We discovered a subset of bacteria linked to host inflammatory signaling pathways and, more precisely, to particular immune cells. We determined that lower airway microbiome dysbiosis may be linked to the disruption of the equilibrium of the immune system causing lung inflammation. The spread of lung cancer may be linked to specific bacteria.
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Affiliation(s)
- Yangqian Li
- Department of Respiratory and Critical Care Medicine, Institute of Respiratory Health, Frontiers Science Center for Disease‐related Molecular Network, West China HospitalSichuan UniversityChengduChina
| | - Guanhua Rao
- Genskey Medical Technology Co., LtdBeijingChina
| | - Guonian Zhu
- Department of Respiratory and Critical Care Medicine, Institute of Respiratory Health, Frontiers Science Center for Disease‐related Molecular Network, West China HospitalSichuan UniversityChengduChina
| | - Cheng Cheng
- Department of Respiratory and Critical Care Medicine, Institute of Respiratory Health, Frontiers Science Center for Disease‐related Molecular Network, West China HospitalSichuan UniversityChengduChina
| | - Lijuan Yuan
- Genskey Medical Technology Co., LtdBeijingChina
| | - Chengpin Li
- Department of Respiratory and Critical Care Medicine, Institute of Respiratory Health, Frontiers Science Center for Disease‐related Molecular Network, West China HospitalSichuan UniversityChengduChina
| | | | - Jun Tang
- Department of Respiratory and Critical Care Medicine, Institute of Respiratory Health, Frontiers Science Center for Disease‐related Molecular Network, West China HospitalSichuan UniversityChengduChina
| | - Zhoufeng Wang
- Department of Respiratory and Critical Care Medicine, Institute of Respiratory Health, Frontiers Science Center for Disease‐related Molecular Network, West China HospitalSichuan UniversityChengduChina
| | - Weimin Li
- Department of Respiratory and Critical Care Medicine, Institute of Respiratory Health, Frontiers Science Center for Disease‐related Molecular Network, West China HospitalSichuan UniversityChengduChina
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15
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Zhou P, Zou Z, Wu W, Zhang H, Wang S, Tu X, Huang W, Chen C, Zhu S, Weng Q, Zheng S. The gut-lung axis in critical illness: microbiome composition as a predictor of mortality at day 28 in mechanically ventilated patients. BMC Microbiol 2023; 23:399. [PMID: 38110878 PMCID: PMC10726596 DOI: 10.1186/s12866-023-03078-3] [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: 08/03/2023] [Accepted: 10/20/2023] [Indexed: 12/20/2023] Open
Abstract
BACKGROUND Microbial communities are of critical importance in the human host. The lung and gut microbial communities represent the most essential microbiota within the human body, collectively referred to as the gut-lung axis. However, the differentiation between these communities and their influence on clinical outcomes in critically ill patients remains uncertain. METHODS An observational cohort study was obtained in the intensive care unit (ICU) of an affiliated university hospital. Sequential samples were procured from two distinct anatomical sites, namely the respiratory and intestinal tracts, at two precisely defined time intervals: within 48 h and on day 7 following intubation. Subsequently, these samples underwent a comprehensive analysis to characterize microbial communities using 16S ribosomal RNA (rRNA) gene sequencing and to quantify concentrations of fecal short-chain fatty acids (SCFAs). The primary predictors in this investigation included lung and gut microbial diversity, along with indicator species. The primary outcome of interest was the survival status at 28 days following mechanical ventilation. RESULTS Sixty-two mechanically ventilated critically ill patients were included in this study. Compared to the survivors, the diversity of microorganisms was significantly lower in the deceased, with a significant contribution from the gut-originated fraction of lung microorganisms. Lower concentrations of fecal SCFAs were detected in the deceased. Multivariate Cox regression analysis revealed that not only lung microbial diversity but also the abundance of Enterococcaceae from the gut were correlated with day 28 mortality. CONCLUSION Critically ill patients exhibited lung and gut microbial dysbiosis after mechanical ventilation, as evidenced by a significant decrease in lung microbial diversity and the proliferation of Enterococcaceae in the gut. Levels of fecal SCFAs in the deceased served as a marker of imbalance between commensal and pathogenic flora in the gut. These findings emphasize the clinical significance of microbial profiling in predicting the prognosis of ICU patients.
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Affiliation(s)
- Piaopiao Zhou
- Department of Critical Care Medicine, Fujian Medical University Union Hospital, Fuzhou, China
| | - Zhiqiang Zou
- Department of Critical Care Medicine, Fujian Medical University Union Hospital, Fuzhou, China
| | - Wenwei Wu
- Department of Critical Care Medicine, Fujian Medical University Union Hospital, Fuzhou, China
| | - Hui Zhang
- Department of Critical Care Medicine, Fujian Medical University Union Hospital, Fuzhou, China
| | - Shuling Wang
- Department of Critical Care Medicine, Fujian Medical University Union Hospital, Fuzhou, China
| | - Xiaoyan Tu
- Department of Critical Care Medicine, Fujian Medical University Union Hospital, Fuzhou, China
| | - Weibin Huang
- Department of Critical Care Medicine, Fujian Medical University Union Hospital, Fuzhou, China
| | - Cunrong Chen
- Department of Critical Care Medicine, Fujian Medical University Union Hospital, Fuzhou, China
| | - Shuaijun Zhu
- Department of Critical Care Medicine, Fujian Medical University Union Hospital, Fuzhou, China
| | - Qinyong Weng
- Department of Critical Care Medicine, Fujian Medical University Union Hospital, Fuzhou, China.
| | - Shixiang Zheng
- Department of Critical Care Medicine, Fujian Medical University Union Hospital, Fuzhou, China.
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16
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Zhu Y, Ma G, Ren W, Hu Z, Zhou L, Zhang X, Zhao N, Zhang M, Yan L, Yu Q, Liu X, Chen J. Effect of oral probiotics on clinical efficacy and intestinal flora in elderly severe pneumonia patients. Medicine (Baltimore) 2023; 102:e36320. [PMID: 38050216 PMCID: PMC10695597 DOI: 10.1097/md.0000000000036320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Accepted: 11/03/2023] [Indexed: 12/06/2023] Open
Abstract
Complex microbial ecosystems in both gastrointestinal and respiratory systems have been found to have a significant impact on human health. Growing evidence has demonstrated that intestinal dysbiosis can increase vulnerability to pulmonary infections. However, changes in the composition and activity of the intestinal flora after probiotic supplementation may alter the disease state of the host. The effects of probiotics on the improvement of diseases, such as severe pneumonia (SP), in intensive care units (ICUs) remain controversial. We retrospectively included 88 patients diagnosed with severe pneumonia between April 2021 and June 2022. The patients were divided into 2 groups: a probiotic group (n = 40) and a control group (n = 48). In addition, changes in CRP, PCT, WBC, IL-6, Clostridium difficile toxin, and PSI pneumonia scores were assessed. Changes in the gut microbiome of the patients were assessed using amplicon sequencing. Compared to the control group, a significant reduction in the incidence of length of hospital stay was observed in the probiotic group, but there were no significant differences in the mortality rate, duration of fever, diarrhea, and constipation. After probiotic treatment, CRP, PCT, WBC, and PSI score were significantly lower than before, and better clinical efficacy was achieved in the probiotic group for the duration of antibiotic therapy. Gut microbiota analysis revealed that the abundance of opportunistic pathogens (e.g., Massilia) increased remarkably at the genus level in the control group, and a significant increase in Erysipelotrichaceae_ge was observed after probiotic intervention. The control group showed an increase in opportunistic pathogens (Citrobacter, Massilia) during the antibiotic treatment. Probiotics interventions inhibit the growth of opportunistic pathogens. In addition, we found that the population of butyrate-producing bacteria (e.g., Ruminococcaceae UCG-005) increased following probiotic treatment.
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Affiliation(s)
| | - Guannan Ma
- Key Laboratory of Digital Technology in Medical Diagnostics of Zhejiang Province, Hangzhou, China
- Beijing D.A. Medical Laboratory, Beijing, China
| | - Wei Ren
- Aerospace Center Hospital, Beijing, China
| | - Zhenyu Hu
- Aerospace Center Hospital, Beijing, China
| | - Ling Zhou
- Aerospace Center Hospital, Beijing, China
| | - Xin Zhang
- Aerospace Center Hospital, Beijing, China
| | - Na Zhao
- Aerospace Center Hospital, Beijing, China
| | | | - Lei Yan
- Aerospace Center Hospital, Beijing, China
| | - Qian Yu
- Key Laboratory of Digital Technology in Medical Diagnostics of Zhejiang Province, Hangzhou, China
- Beijing D.A. Medical Laboratory, Beijing, China
| | - Xuetong Liu
- Key Laboratory of Digital Technology in Medical Diagnostics of Zhejiang Province, Hangzhou, China
- Beijing D.A. Medical Laboratory, Beijing, China
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Liu Q, Zhang W, Pei Y, Tao H, Ma J, Li R, Zhang F, Wang L, Shen L, Liu Y, Jia X, Hu Y. Gut mycobiome as a potential non-invasive tool in early detection of lung adenocarcinoma: a cross-sectional study. BMC Med 2023; 21:409. [PMID: 37904139 PMCID: PMC10617124 DOI: 10.1186/s12916-023-03095-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Accepted: 09/26/2023] [Indexed: 11/01/2023] Open
Abstract
BACKGROUND The gut mycobiome of patients with lung adenocarcinoma (LUAD) remains unexplored. This study aimed to characterize the gut mycobiome in patients with LUAD and evaluate the potential of gut fungi as non-invasive biomarkers for early diagnosis. METHODS In total, 299 fecal samples from Beijing, Suzhou, and Hainan were collected prospectively. Using internal transcribed spacer 2 sequencing, we profiled the gut mycobiome. Five supervised machine learning algorithms were trained on fungal signatures to build an optimized prediction model for LUAD in a discovery cohort comprising 105 patients with LUAD and 61 healthy controls (HCs) from Beijing. Validation cohorts from Beijing, Suzhou, and Hainan comprising 44, 17, and 15 patients with LUAD and 26, 19, and 12 HCs, respectively, were used to evaluate efficacy. RESULTS Fungal biodiversity and richness increased in patients with LUAD. At the phylum level, the abundance of Ascomycota decreased, while that of Basidiomycota increased in patients with LUAD. Candida and Saccharomyces were the dominant genera, with a reduction in Candida and an increase in Saccharomyces, Aspergillus, and Apiotrichum in patients with LUAD. Nineteen operational taxonomic unit markers were selected, and excellent performance in predicting LUAD was achieved (area under the curve (AUC) = 0.9350) using a random forest model with outcomes superior to those of four other algorithms. The AUCs of the Beijing, Suzhou, and Hainan validation cohorts were 0.9538, 0.9628, and 0.8833, respectively. CONCLUSIONS For the first time, the gut fungal profiles of patients with LUAD were shown to represent potential non-invasive biomarkers for early-stage diagnosis.
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Affiliation(s)
- Qingyan Liu
- Graduate School, Chinese People's Liberation Army Medical School, Beijing, China
- Department of Oncology, Fifth Medical Center of the Chinese People's Liberation Army General Hospital, 28 Fuxing Road, Haidian Distrist, Beijing, 100000, China
| | - Weidong Zhang
- Graduate School, Chinese People's Liberation Army Medical School, Beijing, China
- Department of Thoracic Surgery, First Medical Center of the Chinese People's Liberation Army General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100000, China
| | - Yanbin Pei
- Graduate School, Chinese People's Liberation Army Medical School, Beijing, China
| | - Haitao Tao
- Department of Oncology, Fifth Medical Center of the Chinese People's Liberation Army General Hospital, 28 Fuxing Road, Haidian Distrist, Beijing, 100000, China
| | - Junxun Ma
- Department of Oncology, Fifth Medical Center of the Chinese People's Liberation Army General Hospital, 28 Fuxing Road, Haidian Distrist, Beijing, 100000, China
| | - Rong Li
- Department of Health Medicine, Second Medical Center of the Chinese People's Liberation Army General Hospital, Beijing, China
| | - Fan Zhang
- Department of Oncology, Fifth Medical Center of the Chinese People's Liberation Army General Hospital, 28 Fuxing Road, Haidian Distrist, Beijing, 100000, China
| | - Lijie Wang
- Department of Oncology, Fifth Medical Center of the Chinese People's Liberation Army General Hospital, 28 Fuxing Road, Haidian Distrist, Beijing, 100000, China
| | - Leilei Shen
- Department of Thoracic Surgery, Hainan Medical Center of the Chinese People's Liberation Army General Hospital, Hainan, China
| | - Yang Liu
- Department of Thoracic Surgery, First Medical Center of the Chinese People's Liberation Army General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100000, China.
| | - Xiaodong Jia
- Department of Oncology, Fifth Medical Center of the Chinese People's Liberation Army General Hospital, 28 Fuxing Road, Haidian Distrist, Beijing, 100000, China.
| | - Yi Hu
- Department of Oncology, Fifth Medical Center of the Chinese People's Liberation Army General Hospital, 28 Fuxing Road, Haidian Distrist, Beijing, 100000, China.
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18
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Ni S, Yuan X, Cao Q, Chen Y, Peng X, Lin J, Li Y, Ma W, Gao S, Chen D. Gut microbiota regulate migration of lymphocytes from gut to lung. Microb Pathog 2023; 183:106311. [PMID: 37625662 DOI: 10.1016/j.micpath.2023.106311] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 06/10/2023] [Accepted: 08/18/2023] [Indexed: 08/27/2023]
Abstract
The community of microorganisms known as gut microbiota that lives in the intestine confers significant health benefits on its host, primarily in the form of immunological homeostasis regulation. Gut microbiota not only can shape immune responses in the gut but also in other organs. This review focus on the gut-lung axis. Aberrant gut microbiota development is associated with greater lung disease susceptibility and respiratory disease induced by a variety of pathogenic bacteria. They are known to cause changes in gut microbiota. Recent research has found that immune cells in the intestine migrate to distant lung to exert anti-infective effects. Moreover, evidence indicates that the gut microbiota and their metabolites influence intestinal immune cells. Therefore, we suspect that intestine-derived immune cells may play a significant role against pulmonary pathogenic infections by receiving instructions from gut microbiota.
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Affiliation(s)
- Silu Ni
- College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, Shaanxi, China.
| | - Xiulei Yuan
- College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, Shaanxi, China.
| | - Qihang Cao
- College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, Shaanxi, China.
| | - Yiming Chen
- College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, Shaanxi, China.
| | - Xingyu Peng
- College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, Shaanxi, China.
| | - Jingyi Lin
- College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, Shaanxi, China.
| | - Yanyan Li
- College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, Shaanxi, China.
| | - Wentao Ma
- College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, Shaanxi, China.
| | - Shikong Gao
- Shenmu Animal Husbandry Development Center, Shenmu, 719399, Shaanxi, China.
| | - Dekun Chen
- College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, Shaanxi, China.
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19
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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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20
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Borbet TC, Pawline MB, Li J, Ho ML, Yin YS, Zhang X, Novikova E, Jackson K, Mullins BJ, Ruiz VE, Hines MJ, Zhang XS, Müller A, Koralov SB, Blaser MJ. Disruption of the early-life microbiota alters Peyer's patch development and germinal center formation in gastrointestinal-associated lymphoid tissue. iScience 2023; 26:106810. [PMID: 37235047 PMCID: PMC10206152 DOI: 10.1016/j.isci.2023.106810] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 03/17/2023] [Accepted: 05/01/2023] [Indexed: 05/28/2023] Open
Abstract
During postnatal development, both the maturing microbiome and the host immune system are susceptible to environmental perturbations such as antibiotic use. The impact of timing in which antibiotic exposure occurs was investigated by treating mice from days 5-9 with amoxicillin or azithromycin, two of the most commonly prescribed medications in children. Both early-life antibiotic regimens disrupted Peyer's patch development and immune cell abundance, with a sustained decrease in germinal center formation and diminished intestinal immunoglobulin A (IgA) production. These effects were less pronounced in adult mice. Through comparative analysis of microbial taxa, Bifidobacterium longum abundance was found to be associated with germinal center frequency. When re-introduced to antibiotic-exposed mice, B. longum partially rescued the immunological deficits. These findings suggest that early-life antibiotic use affects the development of intestinal IgA-producing B cell functions and that probiotic strains could be used to restore normal development after antibiotic exposure.
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Affiliation(s)
- Timothy C. Borbet
- Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
| | - Miranda B. Pawline
- Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
| | - Jackie Li
- Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
| | - Melody L. Ho
- Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
| | - Yue Sandra Yin
- Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
- Center for Advanced Biotechnology and Medicine, Rutgers University, New Brunswick, NJ 08854, USA
| | - Xiaozhou Zhang
- Institute of Molecular Cancer Research, University of Zurich, Zurich 8057, Switzerland
| | - Ekaterina Novikova
- Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
| | - Katelyn Jackson
- Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
- Department of Biological Sciences, Mississippi State University, Mississippi State, MS 39762, USA
| | - Briana J. Mullins
- Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
| | - Victoria E. Ruiz
- Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
| | - Marcus J. Hines
- Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
| | - Xue-Song Zhang
- Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
- Center for Advanced Biotechnology and Medicine, Rutgers University, New Brunswick, NJ 08854, USA
| | - Anne Müller
- Institute of Molecular Cancer Research, University of Zurich, Zurich 8057, Switzerland
| | - Sergei B. Koralov
- Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
| | - Martin J. Blaser
- Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
- Center for Advanced Biotechnology and Medicine, Rutgers University, New Brunswick, NJ 08854, USA
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21
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Shi H, Zhao T, Geng R, Sun L, Fan H. The associations between gut microbiota and chronic respiratory diseases: a Mendelian randomization study. Front Microbiol 2023; 14:1200937. [PMID: 37333634 PMCID: PMC10272395 DOI: 10.3389/fmicb.2023.1200937] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Accepted: 05/16/2023] [Indexed: 06/20/2023] Open
Abstract
Introduction Growing evidence indicates that variations in the composition of the gut microbiota are linked to the onset and progression of chronic respiratory diseases (CRDs), albeit the causal relationship between the two remains unclear. Methods We conducted a comprehensive two-sample Mendelian randomization (MR) analysis to investigate the relationship between gut microbiota and five main CRDs, including chronic obstructive pulmonary disease (COPD), asthma, idiopathic pulmonary fibrosis (IPF), sarcoidosis, and pneumoconiosis. For MR analysis, the inverse variance weighted (IVW) method was utilized as the primary method. The MR-Egger, weighted median, and MR-PRESSO statistical methods were used as a supplement. To detect heterogeneity and pleiotropy, the Cochrane and Rucker Q test, MR-Egger intercept test, and MR-PRESSO global test were then implemented. The leave-one-out strategy was also applied to assess the consistency of the MR results. Results Based on substantial genetic data obtained from genome-wide association studies (GWAS) comprising 3,504,473 European participants, our study offers evidence that several gut microbial taxa, including 14 probable microbial taxa (specifically, 5, 3, 2, 3 and 1 for COPD, asthma, IPF, sarcoidosis, and pneumoconiosis, respectively) and 33 possible microbial taxa (specifically, 6, 7, 8, 7 and 5 for COPD, asthma, IPF, sarcoidosis, and pneumoconiosis, respectively) play significant roles in the formation of CRDs. Discussion This work implies causal relationships between the gut microbiota and CRDs, thereby shedding new light on the gut microbiota-mediated prevention of CRDs.
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Affiliation(s)
- Hanyu Shi
- Department of Internal Medicine, Hospital of the First Mobile Corps of the Chinese People’s Armed Police Force, Dingzhou, Hebei, China
| | - Tong Zhao
- Department of Internal Medicine, Hospital of the First Mobile Corps of the Chinese People’s Armed Police Force, Dingzhou, Hebei, China
| | - RuiHui Geng
- Department of Internal Medicine, Hospital of the First Mobile Corps of the Chinese People’s Armed Police Force, Dingzhou, Hebei, China
| | - Liang Sun
- Department of Pulmonary and Critical Care, Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin, China
| | - Haojun Fan
- Institute of Disaster and Emergency Medicine, Tianjin University, Tianjin, China
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22
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Narayana JK, Aliberti S, Mac Aogáin M, Jaggi TK, Ali NABM, Ivan FX, Cheng HS, Yip YS, Vos MIG, Low ZS, Lee JXT, Amati F, Gramegna A, Wong SH, Sung JJY, Tan NS, Tsaneva-Atanasova K, Blasi F, Chotirmall SH. Microbial Dysregulation of the Gut-Lung Axis in Bronchiectasis. Am J Respir Crit Care Med 2023; 207:908-920. [PMID: 36288294 PMCID: PMC10111978 DOI: 10.1164/rccm.202205-0893oc] [Citation(s) in RCA: 38] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 10/26/2022] [Indexed: 11/16/2022] Open
Abstract
Rationale: Emerging data support the existence of a microbial "gut-lung" axis that remains unexplored in bronchiectasis. Methods: Prospective and concurrent sampling of gut (stool) and lung (sputum) was performed in a cohort of n = 57 individuals with bronchiectasis and subjected to bacteriome (16S rRNA) and mycobiome (18S Internal Transcribed Spacer) sequencing (total, 228 microbiomes). Shotgun metagenomics was performed in a subset (n = 15; 30 microbiomes). Data from gut and lung compartments were integrated by weighted similarity network fusion, clustered, and subjected to co-occurrence analysis to evaluate gut-lung networks. Murine experiments were undertaken to validate specific Pseudomonas-driven gut-lung interactions. Results: Microbial communities in stable bronchiectasis demonstrate a significant gut-lung interaction. Multibiome integration followed by unsupervised clustering reveals two patient clusters, differing by gut-lung interactions and with contrasting clinical phenotypes. A high gut-lung interaction cluster, characterized by lung Pseudomonas, gut Bacteroides, and gut Saccharomyces, is associated with increased exacerbations and greater radiological and overall bronchiectasis severity, whereas the low gut-lung interaction cluster demonstrates an overrepresentation of lung commensals, including Prevotella, Fusobacterium, and Porphyromonas with gut Candida. The lung Pseudomonas-gut Bacteroides relationship, observed in the high gut-lung interaction bronchiectasis cluster, was validated in a murine model of lung Pseudomonas aeruginosa infection. This interaction was abrogated after antibiotic (imipenem) pretreatment in mice confirming the relevance and therapeutic potential of targeting the gut microbiome to influence the gut-lung axis. Metagenomics in a subset of individuals with bronchiectasis corroborated our findings from targeted analyses. Conclusions: A dysregulated gut-lung axis, driven by lung Pseudomonas, associates with poorer clinical outcomes in bronchiectasis.
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Affiliation(s)
| | - Stefano Aliberti
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Respiratory Unit, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Micheál Mac Aogáin
- Biochemical Genetics Laboratory, Department of Biochemistry, St. James’s Hospital, Dublin, Ireland
- Clinical Biochemistry Unit, School of Medicine, Trinity College Dublin, Dublin, Ireland
| | | | | | | | | | | | | | | | | | - Francesco Amati
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Respiratory Unit, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Andrea Gramegna
- Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Respiratory Unit and Cystic Fibrosis Adult Center, Milan, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Sunny H. Wong
- Lee Kong Chian School of Medicine and
- Department of Gastroenterology and
| | - Joseph J. Y. Sung
- Lee Kong Chian School of Medicine and
- Department of Gastroenterology and
| | - Nguan Soon Tan
- Lee Kong Chian School of Medicine and
- School of Biological Sciences, Nanyang Technological University, Singapore, Singapore
| | - Krasimira Tsaneva-Atanasova
- Department of Mathematics and Statistics and
- Living Systems Institute, University of Exeter, Exeter, United Kingdom
| | - Francesco Blasi
- Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Respiratory Unit and Cystic Fibrosis Adult Center, Milan, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Sanjay H. Chotirmall
- Lee Kong Chian School of Medicine and
- Department of Respiratory and Critical Care Medicine, Tan Tock Seng Hospital, Singapore, Singapore; and
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23
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Xiang Q, Yan X, Lin X, Zheng H, Wang L, Wan J, Zhao W, Zhang W. Intestinal Microflora Altered by Vancomycin Exposure in Early Life Up-regulates Type 2 Innate Lymphocyte and Aggravates Airway Inflammation in Asthmatic Mice. Inflammation 2023; 46:509-521. [PMID: 36526899 DOI: 10.1007/s10753-022-01748-4] [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: 02/05/2022] [Revised: 09/02/2022] [Accepted: 09/27/2022] [Indexed: 12/23/2022]
Abstract
Allergic asthma is a chronic inflammatory disease primarily mediated by Th2 immune mechanisms. Exposure to antibiotics during early life is associated with an increased risk of allergic asthma, although the exact mechanism is not fully understood. In this study, mice were randomly divided into a normal saline control group (NS group), an OVA-induced asthma group (OVA group), a vancomycin treatment control group (VAN.NS group), and a vancomycin treatment the OVA-induced asthma group (VAN.OVA group). The results showed that vancomycin altered dominant species in experimental mice. The phylum level histogram showed that Bacteroides abundance was increased, and Firmicutes abundance was decreased in the OVA group. Airway inflammation and airway hyperresponsiveness (AHR) were aggravated in the vancomycin-exposed group. Enzyme-linked immunosorbent assay (ELISA) showed that the serum levels of IL-5, IL-13, and IL-33 in the OVA group were higher than those in the NS group, especially in the VAN.OVA group. The expression of GATA binding protein-3(GATA3) and retinoid acid receptor-related orphan receptor alpha (RORa) increased in the OVA group, even more so in the VAN.OVA group. Group 2 innate lymphoid cells (ILC2s) in the lung detected by flow cytometry was increased in OVA mice more than those in control mice, with a more remarkable increase in the VAN.OVA. Our results demonstrated that vancomycin used in early life could alter the intestinal microecology of mice, which, in turn, aggravates airway inflammation and upregulate type 2 innate lymphocytes.
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Affiliation(s)
- Qiangwei Xiang
- Department of Pediatric Allergy and Immunology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Xueyuan West Road 109, Wenzhou, 325027, China
| | - Xiumei Yan
- Department of Pediatric Gastroenterology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China
| | - Xixi Lin
- Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China
| | - Hang Zheng
- Department of Pediatric Allergy and Immunology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Xueyuan West Road 109, Wenzhou, 325027, China
| | - Like Wang
- Department of Pediatric Allergy and Immunology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Xueyuan West Road 109, Wenzhou, 325027, China
| | - Jinyi Wan
- Department of Pediatric Allergy and Immunology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Xueyuan West Road 109, Wenzhou, 325027, China
| | - Wei Zhao
- The Second Clinical Medical College, Wenzhou Medical University, 270 West Xueyuan Road, Zhejiang Province, Wenzhou, 325027, China.
- Department of Allergy and Immunology for Clinical Operation, Department of Pediatrics, Virginia Commonwealth University, Richmond, VA, 23298, USA.
| | - Weixi Zhang
- Department of Pediatric Allergy and Immunology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Xueyuan West Road 109, Wenzhou, 325027, China.
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24
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Harshaw C, Kojima S, Wellman CL, Demas GE, Morrow AL, Taft DH, Kenkel WM, Leffel JK, Alberts JR. Maternal antibiotics disrupt microbiome, behavior, and temperature regulation in unexposed infant mice. Dev Psychobiol 2022; 64:e22289. [PMID: 35748626 PMCID: PMC9236156 DOI: 10.1002/dev.22289] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 04/21/2022] [Accepted: 05/12/2022] [Indexed: 12/31/2022]
Abstract
Maternal antibiotic (ABx) exposure can significantly perturb the transfer of microbiota from mother to offspring, resulting in dysbiosis of potential relevance to neurodevelopmental disorders such as autism spectrum disorder (ASD). Studies in rodent models have found long-term neurobehavioral effects in offspring of ABx-treated dams, but ASD-relevant behavior during the early preweaning period has thus far been neglected. Here, we exposed C57BL/6J mouse dams to ABx (5 mg/ml neomycin, 1.25 μg/ml pimaricin, .075% v/v acetic acid) dissolved in drinking water from gestational day 12 through offspring postnatal day 14. A number of ASD-relevant behaviors were assayed in offspring, including ultrasonic vocalization (USV) production during maternal separation, group huddling in response to cold challenge, and olfactory-guided home orientation. In addition, we obtained measures of thermoregulatory competence in pups during and following behavioral testing. We found a number of behavioral differences in offspring of ABx-treated dams (e.g., modulation of USVs by pup weight, activity while huddling) and provide evidence that some of these behavioral effects can be related to thermoregulatory deficiencies, particularly at younger ages. Our results suggest not only that ABx can disrupt microbiomes, thermoregulation, and behavior, but that metabolic effects may confound the interpretation of behavioral differences observed after early-life ABx exposure.
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Affiliation(s)
| | - Sayuri Kojima
- Department of Psychological & Brain Sciences, Indiana University, Bloomington, IN
| | - Cara L. Wellman
- Department of Psychological & Brain Sciences, Indiana University, Bloomington, IN
| | | | - Ardythe L. Morrow
- Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Diana Hazard Taft
- Department of Food Science and Technology, University of California, Davis, Davis, CA
| | - William M. Kenkel
- Department of Psychological and Brain Sciences, University of Delaware, Newark, DE
| | - Joseph K. Leffel
- Department of Psychological & Brain Sciences, Indiana University, Bloomington, IN
| | - Jeffrey R. Alberts
- Department of Psychological & Brain Sciences, Indiana University, Bloomington, IN
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25
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Saeed NK, Al-Beltagi M, Bediwy AS, El-Sawaf Y, Toema O. Gut microbiota in various childhood disorders: Implication and indications. World J Gastroenterol 2022; 28:1875-1901. [PMID: 35664966 PMCID: PMC9150060 DOI: 10.3748/wjg.v28.i18.1875] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 03/08/2022] [Accepted: 03/27/2022] [Indexed: 02/06/2023] Open
Abstract
Gut microbiota has a significant role in gut development, maturation, and immune system differentiation. It exerts considerable effects on the child's physical and mental development. The gut microbiota composition and structure depend on many host and microbial factors. The host factors include age, genetic pool, general health, dietary factors, medication use, the intestine's pH, peristalsis, and transit time, mucus secretions, mucous immunoglobulin, and tissue oxidation-reduction potentials. The microbial factors include nutrient availability, bacterial cooperation or antagonism, and bacterial adhesion. Each part of the gut has its microbiota due to its specific characteristics. The gut microbiota interacts with different body parts, affecting the pathogenesis of many local and systemic diseases. Dysbiosis is a common finding in many childhood disorders such as autism, failure to thrive, nutritional disorders, coeliac disease, Necrotizing Enterocolitis, helicobacter pylori infection, functional gastrointestinal disorders of childhood, inflammatory bowel diseases, and many other gastrointestinal disorders. Dysbiosis is also observed in allergic conditions like atopic dermatitis, allergic rhinitis, and asthma. Dysbiosis can also impact the development and the progression of immune disorders and cardiac disorders, including heart failure. Probiotic supplements could provide some help in managing these disorders. However, we are still in need of more studies. In this narrative review, we will shed some light on the role of microbiota in the development and management of common childhood disorders.
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Affiliation(s)
- Nermin Kamal Saeed
- Medical Microbiology Section, Department of Pathology, Salmaniya Medical Complex, Ministry of Health, Manama 12, Bahrain
- Microbiology Section, Department of Pathology, Irish Royal College of Surgeon, Busaiteen 15503, Bahrain
| | - Mohammed Al-Beltagi
- Department of Pediatrics, University Medical Center, Arabian Gulf University, Dr. Sulaiman Al Habib Medical Group, Manama 26671, Bahrain
- Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta 31511, Egypt
| | - Adel Salah Bediwy
- Department of Chest Disease, Faculty of Medicine, Tanta University, Tanta 31527, Egypt
- Department of Pulmonology, University Medical Center, Arabian Gulf University, Dr. Sulaiman Al Habib Medical Group, Manama 26671, Bahrain
| | - Yasser El-Sawaf
- Department of Tropical Medicine, Faculty of Medicine, Tanta University, Tanta 31527, Egypt
- Department of Gastroenterology, University Medical Center, Arabian Gulf University, Dr. Sulaiman Al-Habib Medical Group, Manama 26671, Bahrain
| | - Osama Toema
- Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta 31511, Egypt
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26
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Vandenplas Y. Breastfeeding and its risk factors. J Pediatr (Rio J) 2022; 98:219-220. [PMID: 35120884 PMCID: PMC9432162 DOI: 10.1016/j.jped.2021.12.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Accepted: 12/30/2021] [Indexed: 11/25/2022] Open
Affiliation(s)
- Yvan Vandenplas
- Vrije Universiteit Brussel (VUB), UZ Brussel, KidZ Health Castle, Belgium.
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27
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Meng R, Dong W, Gao J, Lu C, Zhang C, Liao Q, Chen L, Wu H, Hu J, Wei W, Jiang Z. Clostridium, Bacteroides and Prevotella associates with increased fecal metabolites Trans-4-Hydroxy-L-proline and Genistein in active pulmonary tuberculosis patients during anti-tuberculosis chemotherapy with isoniazid-rifampin-pyrazinamide-ethambutol (HRZE). Indian J Microbiol 2022; 62:374-383. [PMID: 35974910 PMCID: PMC9375812 DOI: 10.1007/s12088-022-01003-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Accepted: 01/18/2022] [Indexed: 11/28/2022] Open
Abstract
Purpose To investigated the changes of gut microbiome and fecal metabolome during anti-tuberculosis chemotherapy with isoniazid (H)-rifampin (R)-pyrazinamide (Z)-ethambutol (E). Patients and methods (1) In this study, we recruited 168 stool specimens from 49 healthy volunteers without M. tuberculosis (Mtb), 30 healthy volunteers with latently infected by Mtb, 41 patients with active tuberculosis (ATB), 28 patients with 2-month HRZE treatment and 20 patients with 2-month HRZE followed by 4-month HR treatment. (2) We used 16S rRNA sequencing and an untargeted Liquid Chromatograph Mass Spectrometer-based metabolomics to investigate the changes of gut microbiome and the alteration of fecal metabolome, respectively, during anti-TB chemotherapy. Results Mtb infection can reduce the diversity of intestinal flora of ATB patients and change their taxonomic composition, while the diversity of intestinal flora of ATB patients were restored during anti-TB chemotherapy. Especially, family Veillonellacea and Bateroidaceae and their genera Veillonella and Bacteroides significantly increased in the gut microbiota during anti-TB chemotherapy. Additionally, Mtb infection dynamically regulates fecal metabolism in ATB patients during anti-TB chemotherapy. Interestingly, the altered abundance of fecal metabolites correlated with the altered gut microbiota, especially the change of gut Clostridium, Bacteroides and Prevotella was closely related to the change of fecal metabolites such as Trans-4-Hydroxy-L-proline and Genistein caused by Mtb infection or anti-TB chemotherapy. Conclusion Anti-TB chemotherapy with HRZE can disrupt both gut microbiotas and metabolome in ATB patients. Some specific genera and metabolites are depleted or enriched during anti-TB chemotherapy. Therefore, revealing potential relevance between gut microbiota and anti-TB chemotherapy will provide potential biomarkers for evaluating the therapeutic efficacy in ATB patients. Supplementary Information The online version contains supplementary material available at 10.1007/s12088-022-01003-2.
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Affiliation(s)
- Ruijie Meng
- Department of Microbiology and Immunology, College of Basic Medicine and Public Hygiene, Jinan University, GuangZhou, 510632 China
| | - Wenya Dong
- Department of Microbiology and Immunology, College of Basic Medicine and Public Hygiene, Jinan University, GuangZhou, 510632 China
- Department of Clinical Laboratory, Guangdong Women and Children Hospital, Guangzhou, 511443 China
| | - Jie Gao
- Department of Microbiology and Immunology, College of Basic Medicine and Public Hygiene, Jinan University, GuangZhou, 510632 China
| | - Chunrong Lu
- Shenzhen Center for Chronic Disease Control, Shenzhen, 518102 China
| | - Chenchen Zhang
- Center for Tuberculosis Control of Guangdong Province, Key laboratory of translational medicine of Guangdong, Guangzhou, 510630 China
| | - Qinghua Liao
- Center for Tuberculosis Control of Guangdong Province, Key laboratory of translational medicine of Guangdong, Guangzhou, 510630 China
| | - Liang Chen
- Center for Tuberculosis Control of Guangdong Province, Key laboratory of translational medicine of Guangdong, Guangzhou, 510630 China
| | - Huizhong Wu
- Center for Tuberculosis Control of Guangdong Province, Key laboratory of translational medicine of Guangdong, Guangzhou, 510630 China
| | - Jiwen Hu
- Medical Laboratory of Shenzhen Luohu Hospital Group, Shenzhen, 518112 China
| | - Wenjing Wei
- Center for Tuberculosis Control of Guangdong Province, Key laboratory of translational medicine of Guangdong, Guangzhou, 510630 China
| | - Zhenyou Jiang
- Department of Microbiology and Immunology, College of Basic Medicine and Public Hygiene, Jinan University, GuangZhou, 510632 China
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Atta AH, Atta SA, Nasr SM, Mouneir SM. Current perspective on veterinary drug and chemical residues in food of animal origin. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2022; 29:15282-15302. [PMID: 34981398 DOI: 10.1007/s11356-021-18239-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 12/16/2021] [Indexed: 06/14/2023]
Abstract
The marked increase in the demand for animal protein of high quality necessitates protecting animals from infectious diseases. This requires increasing the use of veterinary therapeutics. The overuse and misuse of veterinary products can cause a risk to human health either as short-term or long-term health problems. However, the biggest problem is the emergence of resistant strains of bacteria or parasites. This is in addition to economic losses due to the discarding of polluted milk or condemnation of affected carcasses. This paper discusses three key points: possible sources of drug and chemical residues, human health problems, and the possible method of control and prevention of veterinary drug residues in animal products.
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Affiliation(s)
- Attia H Atta
- Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt.
| | - Shimaa A Atta
- Immunology Department, Theodor Bilharz Research Institute, Giza, 12411, Egypt
| | - Soad M Nasr
- Department of Parasitology & Animal Diseases, National Research Centre, 33 Bohouth St., Dokki, Giza, 12622, Egypt
| | - Samar M Mouneir
- Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt
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29
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Guo J, Chang X, Chen L, Liu X, Jia S, Chen Y, Feng Q, Liu L, Wang S, Cui Y. Dynamic changes in the intestinal microbial community of two time-aged soils under combined cadmium and ciprofloxacin contaminated conditions. THE SCIENCE OF THE TOTAL ENVIRONMENT 2022; 806:150558. [PMID: 34624797 DOI: 10.1016/j.scitotenv.2021.150558] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Revised: 09/16/2021] [Accepted: 09/20/2021] [Indexed: 06/13/2023]
Abstract
The effects of combined contaminated soils containing cadmium (Cd) and ciprofloxacin (CIP) on the human gut microbiota are demonstrated using an in vitro test. Uncontaminated soil samples were artificially polluted with Cd and CIP using three different treatments (CK: 0 mg·kg-1; CIPI: 5 mg·kg-1, CIPII: 25 mg·kg-1, and Cd: 80 mg·kg-1). An experiment was performed to investigate the effect of Cd and CIP on the human colon microbiota using two aging times (D30: Day 30; D60: Day 60), and then the method of high-throughput 16S rRNA gene sequencing was used. In this study, we observed five phyla: Proteobacteria, Firmicutes, Synergistetes, Bacteroidetes, and Actinobacteria in colon microbial community. In addition, our results indicated that the relative abundances of the gut bacteria varied at the phylum level. Nevertheless, a slight decline in the relative abundance of Bacteroidetes among all the sets (compared to the D30-CK + Cd set) was revealed, and the lowest decline percentage of 90% was observed in the D60-CIPI + Cd set. Our results validated that the relative abundance of Rhodococcus increased with an increase in the CIP concentration in D30. In addition, this may disrupt normal physiological functions of the intestine after exposure to contaminated soil via the mouth. This study provides a theoretical basis for human risk assessment of oral exposure to Cd and CIP contaminated soils.
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Affiliation(s)
- Jianbo Guo
- College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 101408, China
| | - Xuhui Chang
- College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 101408, China
| | - Long Chen
- College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 101408, China
| | - Xiaotong Liu
- College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 101408, China
| | - Shugang Jia
- Guangxi Geographical Indication Crops Research Center of Big Data Mining and Experimental Engineering Technology, Key Laboratory of Environment Change and Resources Use in Beibu Gulf, Nanning Normal University, Nanning 530001, China
| | - Yang Chen
- College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 101408, China
| | - Qinzhong Feng
- College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 101408, China
| | - Liyuan Liu
- College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 101408, China
| | - Shuping Wang
- College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 101408, China.
| | - Yanshan Cui
- College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 101408, China.
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Rastogi S, Mohanty S, Sharma S, Tripathi P. Possible role of gut microbes and host's immune response in gut-lung homeostasis. Front Immunol 2022; 13:954339. [PMID: 36275735 PMCID: PMC9581402 DOI: 10.3389/fimmu.2022.954339] [Citation(s) in RCA: 48] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Accepted: 09/07/2022] [Indexed: 02/05/2023] Open
Abstract
The vast diversity of microbial communities reside in various locations of the human body, and they are collectively named as the 'Human Microbiota.' The majority of those microbes are found in the gastrointestinal and respiratory tracts. The microorganisms present in the gastrointestinal and the respiratory tracts are called the gut microbiota and the airway microbiota, respectively. These microbial communities are known to affect both the metabolic functions and the immune responses of the host. Among multiple factors determining the composition of gut microbiota, diet has played a pivotal role. The gut microbes possess enzymatic machinery for assimilating dietary fibers and releasing different metabolites, primarily short-chain fatty acids (SCFAs). The SCFAs modulate the immune responses of not only the gut but other distal mucosal sites as well, such as the lungs. Dysbiosis in normal gut flora is one of the factors involved in the development of asthma and other respiratory disorders. Of note, several human and murine studies have indicated significant cross-talk between gut microbiota and lung immunity, known as the gut-lung axis. Here, in this review, we summarize the recent state of the field concerning the effect of dietary metabolites, particularly SCFAs, on the "gut-lung axis" as well as discuss its impact on lung health. Moreover, we have highlighted the role of the "gut-lung axis" in SARS-CoV-2 mediated inflammation. Also, to analyze the global research progress on the gut-lung axis and to identify the knowledge gap in this field, we have also utilized the bibliographic tools Dimension database and VOS viewer analysis software. Through network mapping and visualization analysis, we can predict the present research trend and the possibility to explore new directions.
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Affiliation(s)
- Sonakshi Rastogi
- Food Drug and Chemical Toxicology Division, Council of Scientific and Industrial Research (CSIR)-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, India
| | - Sneha Mohanty
- Food Drug and Chemical Toxicology Division, Council of Scientific and Industrial Research (CSIR)-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, India
| | - Sapna Sharma
- Institute of Biosciences and Biotechnology, Shri Ramswaroop Memorial University, Barabanki, Uttar Pradesh, India
- *Correspondence: Prabhanshu Tripathi, ; Sapna Sharma,
| | - Prabhanshu Tripathi
- Food Drug and Chemical Toxicology Division, Council of Scientific and Industrial Research (CSIR)-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, India
- *Correspondence: Prabhanshu Tripathi, ; Sapna Sharma,
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31
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Aan FJ, Glibetic N, Montoya-Uribe V, Matter ML. COVID-19 and the Microbiome: The Gut-Lung Connection. COMPREHENSIVE GUT MICROBIOTA 2022. [PMCID: PMC8131000 DOI: 10.1016/b978-0-12-819265-8.00048-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Wang WW, Mao B, Liu Y, Gu SY, Lu HW, Bai JW, Liang S, Yang JW, Li JX, Su X, Hu HY, Wang C, Xu JF. Altered fecal microbiome and metabolome in adult patients with non-cystic fibrosis bronchiectasis. Respir Res 2022; 23:317. [PMCID: PMC9675243 DOI: 10.1186/s12931-022-02229-w] [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: 08/11/2022] [Accepted: 10/30/2022] [Indexed: 11/21/2022] Open
Abstract
Background Emerging experimental and epidemiological evidence highlights a crucial cross-talk between the intestinal flora and the lungs, termed the “gut-lung axis”. However, the function of the gut microbiota in bronchiectasis remains undefined. In this study, we aimed to perform a multi-omics-based approach to identify the gut microbiome and metabolic profiles in patients with bronchiectasis. Methods Fecal samples collected from non-CF bronchiectasis patients (BE group, n = 61) and healthy volunteers (HC group, n = 37) were analyzed by 16 S ribosomal RNA (rRNA) sequencing. The BE group was divided into two groups based on their clinical status: acute exacerbation (AE group, n = 31) and stable phase (SP group, n = 30). Further, metabolome (lipid chromatography-mass spectrometry, LC-MS) analyses were conducted in randomly selected patients (n = 29) and healthy volunteers (n = 31). Results Decreased fecal microbial diversity and differential microbial and metabolic compositions were observed in bronchiectasis patients. Correlation analyses indicated associations between the differential genera and clinical parameters such as bronchiectasis severity index (BSI). Disease-associated gut microbiota was screened out, with eight genera exhibited high accuracy in distinguishing SP patients from HCs in the discovery cohort and validation cohort using a random forest model. Further correlation networks were applied to illustrate the relations connecting disease-associated genera and metabolites. Conclusion The study uncovered the relationships among the decreased fecal microbial diversity, differential microbial and metabolic compositions in bronchiectasis patients by performing a multi-omics-based approach. It is the first study to characterize the gut microbiome and metabolome in bronchiectasis, and to uncover the gut microbiota’s potentiality as biomarkers for bronchiectasis. Trial registration: This study is registered with ClinicalTrials.gov, number NCT04490447. Supplementary Information The online version contains supplementary material available at 10.1186/s12931-022-02229-w.
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Affiliation(s)
- Wen-Wen Wang
- grid.24516.340000000123704535Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Institute of Respiratory Medicine, Tongji University School of Medicine, 200433 Shanghai, China
| | - Bei Mao
- grid.24516.340000000123704535Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Institute of Respiratory Medicine, Tongji University School of Medicine, 200433 Shanghai, China
| | - Yang Liu
- grid.24516.340000000123704535Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Institute of Respiratory Medicine, Tongji University School of Medicine, 200433 Shanghai, China
| | - Shu-Yi Gu
- grid.24516.340000000123704535Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Institute of Respiratory Medicine, Tongji University School of Medicine, 200433 Shanghai, China
| | - Hai-Wen Lu
- grid.24516.340000000123704535Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Institute of Respiratory Medicine, Tongji University School of Medicine, 200433 Shanghai, China
| | - Jiu-Wu Bai
- grid.24516.340000000123704535Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Institute of Respiratory Medicine, Tongji University School of Medicine, 200433 Shanghai, China
| | - Shuo Liang
- grid.24516.340000000123704535Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Institute of Respiratory Medicine, Tongji University School of Medicine, 200433 Shanghai, China
| | - Jia-Wei Yang
- grid.24516.340000000123704535Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Institute of Respiratory Medicine, Tongji University School of Medicine, 200433 Shanghai, China
| | - Jian-Xiong Li
- grid.24516.340000000123704535Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Institute of Respiratory Medicine, Tongji University School of Medicine, 200433 Shanghai, China
| | - Xiao Su
- grid.429007.80000 0004 0627 2381Unit of Respiratory Infection and Immunity, Institute Pasteur of Shanghai, Chinese Academy of Sciences, 200031 Shanghai, China
| | - Hai-Yang Hu
- grid.254147.10000 0000 9776 7793State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 211198 Nanjing, China
| | - Chen Wang
- grid.254147.10000 0000 9776 7793State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 211198 Nanjing, China
| | - Jin-Fu Xu
- grid.24516.340000000123704535Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Institute of Respiratory Medicine, Tongji University School of Medicine, 200433 Shanghai, China
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33
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Shi CY, Yu CH, Yu WY, Ying HZ. Gut-Lung Microbiota in Chronic Pulmonary Diseases: Evolution, Pathogenesis, and Therapeutics. THE CANADIAN JOURNAL OF INFECTIOUS DISEASES & MEDICAL MICROBIOLOGY = JOURNAL CANADIEN DES MALADIES INFECTIEUSES ET DE LA MICROBIOLOGIE MEDICALE 2021; 2021:9278441. [PMID: 34900069 PMCID: PMC8664551 DOI: 10.1155/2021/9278441] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/19/2021] [Accepted: 11/20/2021] [Indexed: 12/17/2022]
Abstract
The microbiota colonized in the human body has a symbiotic relationship with human body and forms a different microecosystem, which affects human immunity, metabolism, endocrine, and other physiological processes. The imbalance of microbiota is usually linked to the aberrant immune responses and inflammation, which eventually promotes the occurrence and development of respiratory diseases. Patients with chronic respiratory diseases, including asthma, COPD, bronchiectasis, and idiopathic pulmonary fibrosis, often have alteration of the composition and function of intestinal and lung microbiota. Gut microbiota affects respiratory immunity and barrier function through the lung-gut microbiota, resulting in altered prognosis of chronic respiratory diseases. In turn, lung dysbiosis promotes aggravation of lung diseases and causes intestinal dysfunction through persistent activation of lymphoid cells in the body. Recent advances in next-generation sequencing technology have disclosed the pivotal roles of lung-gut microbiota in the pathogenesis of chronic respiratory diseases. This review focuses on the association between the gut-lung dysbiosis and respiratory diseases pathogenesis. In addition, potential therapeutic modalities, such as probiotics and fecal microbiota transplantation, are also evaluated for the prevention of chronic respiratory diseases.
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Affiliation(s)
- Chang Yi Shi
- Zhejiang Provincial Laboratory of Experimental Animal's & Nonclinical Laboratory Studies, Hangzhou Medical College, Hangzhou, China
| | - Chen Huan Yu
- Institute of Cancer and Basic Medicine, Chinese Academy of Sciences, Hangzhou, China
- Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China
| | - Wen Ying Yu
- Zhejiang Provincial Laboratory of Experimental Animal's & Nonclinical Laboratory Studies, Hangzhou Medical College, Hangzhou, China
| | - Hua Zhong Ying
- Zhejiang Provincial Laboratory of Experimental Animal's & Nonclinical Laboratory Studies, Hangzhou Medical College, Hangzhou, China
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34
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The influence of early-life microbial exposures on long-term respiratory health. Paediatr Respir Rev 2021; 40:15-23. [PMID: 34140238 DOI: 10.1016/j.prrv.2021.05.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Accepted: 05/20/2021] [Indexed: 11/21/2022]
Abstract
Host-microbiome interactions exert a profound influence on human physiology and health outcomes. In particular, certain characteristics of commensal microbiota during a critical period in early life are essential for the establishment of immune tone and metabolic control. An increasing body of evidence suggests that early life exposures that disrupt these interactions can substantially influence life-long risks for respiratory disease. Here, we explore how such early life exposures, including antibiotic exposure, maternal diet, preterm birth, mode of delivery, breastfeeding, and environmental variables shape the infant microbiome, and the mechanisms by such changes can in turn impact respiratory health.
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Baradaran Ghavami S, Pourhamzeh M, Farmani M, Keshavarz H, Shahrokh S, Shpichka A, Asadzadeh Aghdaei H, Hakemi-Vala M, Hossein-khannazer N, Timashev P, Vosough M. Cross-talk between immune system and microbiota in COVID-19. Expert Rev Gastroenterol Hepatol 2021; 15:1281-1294. [PMID: 34654347 PMCID: PMC8567289 DOI: 10.1080/17474124.2021.1991311] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 10/06/2021] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Human gut microbiota plays a crucial role in providing protective responses against pathogens, particularly by regulating immune system homeostasis. There is a reciprocal interaction between the gut and lung microbiota, called the gut-lung axis (GLA). Any alteration in the gut microbiota or their metabolites can cause immune dysregulation, which can impair the antiviral activity of the immune system against respiratory viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. AREAS COVERED This narrative review mainly outlines emerging data on the mechanisms underlying the interactions between the immune system and intestinal microbial dysbiosis, which is caused by an imbalance in the levels of essential metabolites. The authors will also discuss the role of probiotics in restoring the balance of the gut microbiota and modulation of cytokine storm. EXPERT OPINION Microbiota-derived signals regulate the immune system and protect different tissues during severe viral respiratory infections. The GLA's equilibration could help manage the mortality and morbidity rates associated with SARS-CoV-2 infection.
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Affiliation(s)
- Shaghayegh Baradaran Ghavami
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Thran, Iran
| | - Mahsa Pourhamzeh
- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
- Division of Neuroscience, Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Maryam Farmani
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Thran, Iran
| | - Hediye Keshavarz
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Thran, Iran
| | - Shabnam Shahrokh
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Thran, Iran
| | - Anastasia Shpichka
- Institute for Regenerative Medicine, Sechenov First Moscow State Medical University, Moscow, Russia
- World-Class Research Center “Digital Biodesign and Personalized Healthcare”, Sechenov First Moscow State Medical University, Moscow, Russia
- Chemistry Department, Lomonosov Moscow State University, Moscow, Russia
| | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Thran, Iran
| | - Mojdeh Hakemi-Vala
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nikoo Hossein-khannazer
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Thran, Iran
| | - Peter Timashev
- Institute for Regenerative Medicine, Sechenov First Moscow State Medical University, Moscow, Russia
- World-Class Research Center “Digital Biodesign and Personalized Healthcare”, Sechenov First Moscow State Medical University, Moscow, Russia
- Chemistry Department, Lomonosov Moscow State University, Moscow, Russia
| | - Massoud Vosough
- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
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Abdelgawad AS, Lal CV, Ambalavanan N, Willis KA. Toll-like receptors: shapers of the pulmonary microbiome? Am J Physiol Lung Cell Mol Physiol 2021; 321:L553-L554. [PMID: 34346777 DOI: 10.1152/ajplung.00279.2021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Affiliation(s)
- Ahmed S Abdelgawad
- Department of Pediatrics, Division of Neonatology, School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama
| | - C Vivek Lal
- Department of Pediatrics, Division of Neonatology, School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama
| | - Namasivayam Ambalavanan
- Department of Pediatrics, Division of Neonatology, School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama
| | - Kent A Willis
- Department of Pediatrics, Division of Neonatology, School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama
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37
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Luo M, Zhou DD, Shang A, Gan RY, Li HB. Influences of food contaminants and additives on gut microbiota as well as protective effects of dietary bioactive compounds. Trends Food Sci Technol 2021. [DOI: 10.1016/j.tifs.2021.05.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Dhudasia MB, Spergel JM, Puopolo KM, Koebnick C, Bryan M, Grundmeier RW, Gerber JS, Lorch SA, Quarshie WO, Zaoutis T, Mukhopadhyay S. Intrapartum Group B Streptococcal Prophylaxis and Childhood Allergic Disorders. Pediatrics 2021; 147:peds.2020-012187. [PMID: 33833072 PMCID: PMC8085997 DOI: 10.1542/peds.2020-012187] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/03/2021] [Indexed: 12/31/2022] Open
Abstract
OBJECTIVES To determine if maternal intrapartum group B Streptococcus (GBS) antibiotic prophylaxis is associated with increased risk of childhood asthma, eczema, food allergy, or allergic rhinitis. METHODS Retrospective cohort study of 14 046 children. GBS prophylaxis was defined as administration of intravenous penicillin, ampicillin, cefazolin, clindamycin, or vancomycin to the mother, ≥4 hours before delivery. Composite primary outcome was asthma, eczema, or food allergy diagnosis within 5 years of age, identified by diagnosis codes and appropriate medication prescription. Allergic rhinitis was defined by using diagnostic codes only and analyzed as a separate outcome. Analysis was a priori stratified by delivery mode and conducted by using Cox proportional hazards model adjusted for multiple confounders and covariates. Secondary analyses, restricted to children retained in cohort at 5 years' age, were conducted by using multivariate logistic regression. RESULTS GBS prophylaxis was not associated with increased incidence of composite outcome among infants delivered vaginally (hazard ratio: 1.13, 95% confidence interval [CI]: 0.95-1.33) or by cesarean delivery (hazard ratio: 1.08, 95% CI: 0.88-1.32). At 5 years of age, among 10 404 children retained in the study, GBS prophylaxis was not associated with the composite outcome in vaginal (odds ratio: 1.21, 95% CI: 0.96-1.52) or cesarean delivery (odds ratio: 1.17, 95% CI: 0.88-1.56) cohorts. Outcomes of asthma, eczema, food allergy, separately, and allergic rhinitis were also not associated with GBS prophylaxis. CONCLUSIONS Intrapartum GBS prophylaxis was not associated with subsequent diagnosis of asthma, eczema, food allergy, or allergic rhinitis in the first 5 years of age.
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Affiliation(s)
- Miren B. Dhudasia
- Divisions of Neonatology,,Center for Pediatric Clinical Effectiveness, and
| | - Jonathan M. Spergel
- Allergy-Immunology, and,Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania Philadelphia, Pennsylvania
| | - Karen M. Puopolo
- Divisions of Neonatology,,Center for Pediatric Clinical Effectiveness, and,Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania Philadelphia, Pennsylvania
| | - Corinna Koebnick
- Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, California; and
| | | | - Robert W. Grundmeier
- Department of Biomedical and Health Informatics, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania;,Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania Philadelphia, Pennsylvania
| | - Jeffrey S. Gerber
- Infectious Diseases,,Center for Pediatric Clinical Effectiveness, and,Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania Philadelphia, Pennsylvania
| | - Scott A. Lorch
- Divisions of Neonatology,,Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania Philadelphia, Pennsylvania
| | - William O. Quarshie
- Department of Biomedical and Health Informatics, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Theoklis Zaoutis
- Center for Pediatric Clinical Effectiveness, and,Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania Philadelphia, Pennsylvania
| | - Sagori Mukhopadhyay
- Divisions of Neonatology, .,Center for Pediatric Clinical Effectiveness, and.,Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania Philadelphia, Pennsylvania
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39
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Coker MO, Laue HE, Hoen AG, Hilliard M, Dade E, Li Z, Palys T, Morrison HG, Baker E, Karagas MR, Madan JC. Infant Feeding Alters the Longitudinal Impact of Birth Mode on the Development of the Gut Microbiota in the First Year of Life. Front Microbiol 2021; 12:642197. [PMID: 33897650 PMCID: PMC8059768 DOI: 10.3389/fmicb.2021.642197] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Accepted: 02/22/2021] [Indexed: 12/15/2022] Open
Abstract
Cesarean-delivered (CD) infants harbor a distinct gut microbiome from vaginally delivered (VD) infants, however, during infancy, the most important driver of infant gut microbial colonization is infant feeding. Earlier studies have shown that breastfeeding is associated with higher levels of health-promoting bacteria such and Bifidobacterium and Bacteroides via modulation of the immune system, and production of metabolites. As the infant gut matures and solid foods are introduced, it is unclear whether longer duration of breast feeding restore loss of beneficial taxa within the intestinal microbiota of operatively delivered infants. Within the New Hampshire Birth Cohort Study, we evaluated the longitudinal effect of delivery mode and infant feeding on the taxonomic composition and functional capacity of developing gut microbiota in the First year of life. Microbiota of 500 stool samples collected between 6 weeks and 12 months of age (from 229 infants) were characterized by 16S ribosomal RNA sequencing. Shotgun metagenomic sequencing was also performed on 350 samples collected at either 6 weeks or 12 months of age. Among infant participants, 28% were cesarean-delivered (CD) infants and most (95%) initiated breastfeeding within the first six months of life, with 26% exclusively breastfed and 69% mixed-fed (breast milk and formula), in addition to complementary foods by age 1. Alpha (within-sample) diversity was significantly lower in CD infants compared to vaginally delivered (VD) infants (P < 0.05) throughout the study period. Bacterial community composition clustering by both delivery mode and feeding duration at 1 year of age revealed that CD infants who were breast fed for < 6 months were more dissimilar to VD infants than CD infants who breast fed for ≥ 6 months. We observed that breastfeeding modified the longitudinal impact of delivery mode on the taxonomic composition of the microbiota by 1 year of age, with an observed increase in abundance of Bacteroides fragilis and Lactobacillus with longer duration of breastfeeding among CD infants while there was an increase in Faecalibacterium for VD infants. Our findings confirm that duration of breastfeeding plays a critical role in restoring a health-promoting microbiome, call for further investigations regarding the association between breast milk exposure and health outcomes in early life.
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Affiliation(s)
- Modupe O. Coker
- Department of Epidemiology, The Geisel School of Medicine at Dartmouth, Hanover, NH, United States
- School of Dental Medicine, School of Public Health at Rutgers, Newark, NJ, United States
| | - Hannah E. Laue
- Department of Epidemiology, The Geisel School of Medicine at Dartmouth, Hanover, NH, United States
| | - Anne G. Hoen
- Department of Epidemiology, The Geisel School of Medicine at Dartmouth, Hanover, NH, United States
- Center for Molecular Epidemiology, The Geisel School of Medicine at Dartmouth, Hanover, NH, United States
- Children’s Environmental Health & Disease Prevention Research Center at Dartmouth, Hanover, NH, United States
| | - Margaret Hilliard
- Department of Epidemiology, The Geisel School of Medicine at Dartmouth, Hanover, NH, United States
| | - Erika Dade
- Department of Epidemiology, The Geisel School of Medicine at Dartmouth, Hanover, NH, United States
| | - Zhigang Li
- Department of Biostatistics, University of Florida, Gainsville, FL, United States
| | - Thomas Palys
- Children’s Environmental Health & Disease Prevention Research Center at Dartmouth, Hanover, NH, United States
| | - Hilary G. Morrison
- Marine Biological Laboratory, Josephine Bay Paul Center, Woods Hole, MA, United States
| | - Emily Baker
- Department of Pediatrics, Children’s Hospital at Dartmouth, Lebanon, NH, United States
| | - Margaret R. Karagas
- Department of Epidemiology, The Geisel School of Medicine at Dartmouth, Hanover, NH, United States
- Center for Molecular Epidemiology, The Geisel School of Medicine at Dartmouth, Hanover, NH, United States
- Children’s Environmental Health & Disease Prevention Research Center at Dartmouth, Hanover, NH, United States
| | - Juliette C. Madan
- Department of Epidemiology, The Geisel School of Medicine at Dartmouth, Hanover, NH, United States
- Children’s Environmental Health & Disease Prevention Research Center at Dartmouth, Hanover, NH, United States
- Department of Pediatrics, Children’s Hospital at Dartmouth, Lebanon, NH, United States
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Cait A, Messing M, Cait J, Canals Hernaez D, McNagny KM. Antibiotic Treatment in an Animal Model of Inflammatory Lung Disease. Methods Mol Biol 2021; 2223:281-293. [PMID: 33226601 DOI: 10.1007/978-1-0716-1001-5_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Allergic disease is on the rise and yet the underlying cause and risk factors are not fully understood. While lifesaving in many circumstances, the use of antibiotics and the subsequent disruption of the microbiome are positively correlated with the development of allergies. Here, we describe the use of the antibiotic vancomycin in combination with the papain-induced mouse model of allergic disease that allows for the assessment of microbiome perturbations and the impact on allergy development.
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Affiliation(s)
- Alissa Cait
- Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada
| | - Melina Messing
- Division of Experimental Medicine, Faculty of Medicine, University of British Columbia, The Biomedical Research Centre, Vancouver, BC, Canada
| | - Jessica Cait
- Division of Experimental Medicine, Faculty of Medicine, University of British Columbia, The Biomedical Research Centre, Vancouver, BC, Canada
| | - Diana Canals Hernaez
- Departments of Biomedical Engineering and Medical Genetics, University of British Columbia, Vancouver, BC, Canada
| | - Kelly M McNagny
- Division of Experimental Medicine, Faculty of Medicine, University of British Columbia, The Biomedical Research Centre, Vancouver, BC, Canada. .,Departments of Biomedical Engineering and Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
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Acevedo N, Alashkar Alhamwe B, Caraballo L, Ding M, Ferrante A, Garn H, Garssen J, Hii CS, Irvine J, Llinás-Caballero K, López JF, Miethe S, Perveen K, Pogge von Strandmann E, Sokolowska M, Potaczek DP, van Esch BCAM. Perinatal and Early-Life Nutrition, Epigenetics, and Allergy. Nutrients 2021; 13:724. [PMID: 33668787 PMCID: PMC7996340 DOI: 10.3390/nu13030724] [Citation(s) in RCA: 87] [Impact Index Per Article: 21.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 02/08/2021] [Accepted: 02/12/2021] [Indexed: 02/08/2023] Open
Abstract
Epidemiological studies have shown a dramatic increase in the incidence and the prevalence of allergic diseases over the last several decades. Environmental triggers including risk factors (e.g., pollution), the loss of rural living conditions (e.g., farming conditions), and nutritional status (e.g., maternal, breastfeeding) are considered major contributors to this increase. The influences of these environmental factors are thought to be mediated by epigenetic mechanisms which are heritable, reversible, and biologically relevant biochemical modifications of the chromatin carrying the genetic information without changing the nucleotide sequence of the genome. An important feature characterizing epigenetically-mediated processes is the existence of a time frame where the induced effects are the strongest and therefore most crucial. This period between conception, pregnancy, and the first years of life (e.g., first 1000 days) is considered the optimal time for environmental factors, such as nutrition, to exert their beneficial epigenetic effects. In the current review, we discussed the impact of the exposure to bacteria, viruses, parasites, fungal components, microbiome metabolites, and specific nutritional components (e.g., polyunsaturated fatty acids (PUFA), vitamins, plant- and animal-derived microRNAs, breast milk) on the epigenetic patterns related to allergic manifestations. We gave insight into the epigenetic signature of bioactive milk components and the effects of specific nutrition on neonatal T cell development. Several lines of evidence suggest that atypical metabolic reprogramming induced by extrinsic factors such as allergens, viruses, pollutants, diet, or microbiome might drive cellular metabolic dysfunctions and defective immune responses in allergic disease. Therefore, we described the current knowledge on the relationship between immunometabolism and allergy mediated by epigenetic mechanisms. The knowledge as presented will give insight into epigenetic changes and the potential of maternal and post-natal nutrition on the development of allergic disease.
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Affiliation(s)
- Nathalie Acevedo
- Institute for Immunological Research, University of Cartagena, Cartagena 130014, Colombia; (N.A.); (L.C.); (K.L.-C.); (J.F.L.)
| | - Bilal Alashkar Alhamwe
- Institute of Tumor Immunology, Clinic for Hematology, Oncology and Immunology, Center for Tumor Biology and Immunology, Philipps University Marburg, 35043 Marburg, Germany; (B.A.A.); (E.P.v.S.)
- College of Pharmacy, International University for Science and Technology (IUST), Daraa 15, Syria
| | - Luis Caraballo
- Institute for Immunological Research, University of Cartagena, Cartagena 130014, Colombia; (N.A.); (L.C.); (K.L.-C.); (J.F.L.)
| | - Mei Ding
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, 7265 Davos, Switzerland; (M.D.); (M.S.)
- Christine Kühne-Center for Allergy Research and Education, 7265 Davos, Switzerland
- Department of Allergology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
| | - Antonio Ferrante
- Department of Immunopathology, SA Pathology at the Women’s and Children’s Hospital, North Adelaide, SA 5006, Australia; (A.F.); (C.S.H.); (J.I.); (K.P.)
- Adelaide School of Medicine and the Robinson Research Institute, University of Adelaide, Adelaide, SA 5005, Australia
- School of Biological Sciences, University of Adelaide, Adelaide, SA 5005, Australia
| | - Holger Garn
- Translational Inflammation Research Division & Core Facility for Single Cell Multiomics, Medical Faculty, Philipps University Marburg, Member of the German Center for Lung Research (DZL) and the Universities of Giessen and Marburg Lung Center, 35043 Marburg, Germany; (H.G.); (S.M.)
| | - Johan Garssen
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands;
- Danone Nutricia Research, 3584 CT Utrecht, The Netherlands
| | - Charles S. Hii
- Department of Immunopathology, SA Pathology at the Women’s and Children’s Hospital, North Adelaide, SA 5006, Australia; (A.F.); (C.S.H.); (J.I.); (K.P.)
- Adelaide School of Medicine and the Robinson Research Institute, University of Adelaide, Adelaide, SA 5005, Australia
| | - James Irvine
- Department of Immunopathology, SA Pathology at the Women’s and Children’s Hospital, North Adelaide, SA 5006, Australia; (A.F.); (C.S.H.); (J.I.); (K.P.)
- Adelaide School of Medicine and the Robinson Research Institute, University of Adelaide, Adelaide, SA 5005, Australia
| | - Kevin Llinás-Caballero
- Institute for Immunological Research, University of Cartagena, Cartagena 130014, Colombia; (N.A.); (L.C.); (K.L.-C.); (J.F.L.)
| | - Juan Felipe López
- Institute for Immunological Research, University of Cartagena, Cartagena 130014, Colombia; (N.A.); (L.C.); (K.L.-C.); (J.F.L.)
| | - Sarah Miethe
- Translational Inflammation Research Division & Core Facility for Single Cell Multiomics, Medical Faculty, Philipps University Marburg, Member of the German Center for Lung Research (DZL) and the Universities of Giessen and Marburg Lung Center, 35043 Marburg, Germany; (H.G.); (S.M.)
| | - Khalida Perveen
- Department of Immunopathology, SA Pathology at the Women’s and Children’s Hospital, North Adelaide, SA 5006, Australia; (A.F.); (C.S.H.); (J.I.); (K.P.)
- Adelaide School of Medicine and the Robinson Research Institute, University of Adelaide, Adelaide, SA 5005, Australia
| | - Elke Pogge von Strandmann
- Institute of Tumor Immunology, Clinic for Hematology, Oncology and Immunology, Center for Tumor Biology and Immunology, Philipps University Marburg, 35043 Marburg, Germany; (B.A.A.); (E.P.v.S.)
| | - Milena Sokolowska
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, 7265 Davos, Switzerland; (M.D.); (M.S.)
- Christine Kühne-Center for Allergy Research and Education, 7265 Davos, Switzerland
| | - Daniel P. Potaczek
- Translational Inflammation Research Division & Core Facility for Single Cell Multiomics, Medical Faculty, Philipps University Marburg, Member of the German Center for Lung Research (DZL) and the Universities of Giessen and Marburg Lung Center, 35043 Marburg, Germany; (H.G.); (S.M.)
| | - Betty C. A. M. van Esch
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands;
- Danone Nutricia Research, 3584 CT Utrecht, The Netherlands
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Chioma OS, Hesse LE, Chapman A, Drake WP. Role of the Microbiome in Interstitial Lung Diseases. Front Med (Lausanne) 2021; 8:595522. [PMID: 33604346 PMCID: PMC7885795 DOI: 10.3389/fmed.2021.595522] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2020] [Accepted: 01/06/2021] [Indexed: 12/14/2022] Open
Abstract
There are trillions of microorganisms in the human body, consisting of bacteria, viruses, fungi, and archaea; these collectively make up the microbiome. Recent studies suggest that the microbiome may serve as a biomarker for disease, a therapeutic target, or provide an explanation for pathophysiology in lung diseases. Studies describing the impact of the microorganisms found in the respiratory tract on lung health have been published and are discussed here in the context of interstitial lung diseases. Additionally, epidemiological and experimental evidence highlights the importance of cross-talk between the gut microbiota and the lungs, called the gut–lung axis. The gut-lung axis postulates that alterations in gut microbial communities may have a profound effect on lung disease. Dysbiosis in the microbial community of the gut is linked with changes in immune responses, homeostasis in the airways, and inflammatory conditions in the gastrointestinal tract itself. In this review, we summarize studies describing the role of the microbiome in interstitial lung disease and discuss the implications of these findings on the diagnosis and treatment of these diseases. This paper describes the impact of the microbial communities on the pathogenesis of lung diseases by assessing recent original research and identifying remaining gaps in knowledge.
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Affiliation(s)
- Ozioma S Chioma
- Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United States
| | - Laura E Hesse
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN, United States
| | - Austin Chapman
- Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United States
| | - Wonder P Drake
- Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United States.,Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN, United States
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Zhou A, Lei Y, Tang L, Hu S, Yang M, Wu L, Yang S, Tang B. Gut Microbiota: the Emerging Link to Lung Homeostasis and Disease. J Bacteriol 2021; 203:e00454-20. [PMID: 33077630 PMCID: PMC7847545 DOI: 10.1128/jb.00454-20] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The gut microbiota plays a crucial role in the development of the immune system and confers benefits or disease susceptibility to the host. Emerging studies have indicated the gut microbiota could affect pulmonary health and disease through cross talk between the gut microbiota and the lungs. Gut microbiota dysbiosis could lead to acute or chronic lung disease, such as asthma, tuberculosis, and lung cancer. In addition, the composition of the gut microbiota may be associated with different lung diseases, the prevalence of which also varies by age. Modulation of the gut microbiota through short-chain fatty acids, probiotics, and micronutrients may present potential therapeutic strategies to protect against lung diseases. In this review, we will provide an overview of the cross-talk between the gut microbiota and the lungs, as well as elucidate the underlying pathogenesis and/or potential therapeutic strategies of some lung diseases from the point of view of the gut microbiota.
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Affiliation(s)
- An Zhou
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Yuanyuan Lei
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Li Tang
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Shiping Hu
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Min Yang
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Lingyi Wu
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Shiming Yang
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Bo Tang
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
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Liu SK, Ma LB, Yuan Y, Ji XY, Sun WJ, Duan JX, Zeng QP, Wasti B, Xiao B, Zheng JF, Chen P, Xiang XD. Alanylglutamine Relieved Asthma Symptoms by Regulating Gut Microbiota and the Derived Metabolites in Mice. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2020; 2020:7101407. [PMID: 33456673 PMCID: PMC7785351 DOI: 10.1155/2020/7101407] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Revised: 11/26/2020] [Accepted: 12/04/2020] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Allergic asthma is a chronic inflammatory disease, which seriously affects the life quality of patients, especially children. Alanylglutamine is a nutritional supplement with potential protective and anti-inflammatory effects, but its function in allergic asthma remains elusive. In this study, we focused on the investigations of the roles and functional mechanism of Alanylglutamine in asthma. METHODS Ovalbumin (OVA) induction was utilized to establish a mouse asthma model. 16S rDNA sequencing was performed to compare the diversity of intestinal microorganisms under different treatments. Gas chromatography was utilized to screen the intestinal microbe-short-chain fatty acids in the stool. The lung tissue was extracted to determine signaling pathways, including AMPK, NF-κB, mTOR, STAT3, IKKβ, TGF-β, and IL-1β through Western blot or RT-qPCR. RESULTS It was observed that Alanylglutamine reduced the cytokine in OVA-induced allergic asthma mice. H&E staining showed obvious pneumonia symptoms in the asthma group, while Alanylglutamine alleviated the inflammatory infiltration. Alanylglutamine reversed gut microbiota compositions in OVA-induced allergic asthma mice and enhanced the butyric acid level. The protective role of Alanylglutamine may be associated with the gut microbiota-butyric acid-GPR43 pathway in asthma mice. In contrast to the OVA group, Alanylglutamine activated the protein expression of P-AMPK/AMPK and inhibited the protein expression of P-mTOR/mTOR, P-P65/P65, P-STAT3/STAT3, P-IKKβ/IKKβ, TGF-β, and IL-1β, with similar effects from butyric acid. CONCLUSION The results indicated that Alanylglutamine might be beneficial for asthma, and its effect was achieved through the regulation on microbiota and the derived metabolites. The therapeutic effects might be associated with AMPK, NF-κB, mTOR, and STAT3 signaling pathways. These findings will help identify effective therapeutic direction to alleviate allergic inflammation of the lungs and airways.
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Affiliation(s)
- Shao-Kun Liu
- Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
- Research Unit of Respiratory Disease, Central South University, Changsha, Hunan 410011, China
- Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan 410011, China
| | - Li-Bing Ma
- Department of Respiratory Medicine, The Affiliated Hospital of Guilin Medical University, Guilin 541001, China
- Institute of Respiratory Diseases, Guilin Medical University, Guilin 541001, China
| | - Yu Yuan
- Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
- Research Unit of Respiratory Disease, Central South University, Changsha, Hunan 410011, China
- Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan 410011, China
| | - Xiao-Ying Ji
- Department of Respiratory Medicine, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518106, China
| | - Wen-Jin Sun
- Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
- Research Unit of Respiratory Disease, Central South University, Changsha, Hunan 410011, China
- Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan 410011, China
| | - Jia-Xi Duan
- Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
- Research Unit of Respiratory Disease, Central South University, Changsha, Hunan 410011, China
- Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan 410011, China
| | - Qing-Ping Zeng
- Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
- Research Unit of Respiratory Disease, Central South University, Changsha, Hunan 410011, China
- Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan 410011, China
| | - Binaya Wasti
- Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
- Research Unit of Respiratory Disease, Central South University, Changsha, Hunan 410011, China
- Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan 410011, China
| | - Bing Xiao
- Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
- Research Unit of Respiratory Disease, Central South University, Changsha, Hunan 410011, China
- Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan 410011, China
| | - Jian-Fei Zheng
- Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
- Research Unit of Respiratory Disease, Central South University, Changsha, Hunan 410011, China
- Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan 410011, China
| | - Ping Chen
- Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
- Research Unit of Respiratory Disease, Central South University, Changsha, Hunan 410011, China
- Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan 410011, China
| | - Xu-Dong Xiang
- Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
- Research Unit of Respiratory Disease, Central South University, Changsha, Hunan 410011, China
- Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan 410011, China
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Li X, Tan CP, Liu YF, Xu YJ. Interactions between Food Hazards and Intestinal Barrier: Impact on Foodborne Diseases. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2020; 68:14728-14738. [PMID: 33289375 DOI: 10.1021/acs.jafc.0c07378] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
The intestine is an important digestive organ of the human body, and its barrier is the guardian of the body from the external environment. The impairment of the intestinal barrier is believed to be an important determinant in various foodborne diseases. Food hazards can lead to the occurrence of many foodborne diseases represented by inflammation. Therefore, understanding the mechanisms of the impact of the food hazards on intestinal barriers is essential for promoting human health. This review examined the relationship between food hazards and the intestinal barrier in three aspects: apoptosis, imbalance of gut microbiota, and pro-inflammatory cytokines. The mechanism of dysfunctional gut microbiota caused by food hazards was also discussed. This review discusses the interaction among food hazards, intestinal barrier, and foodborne diseases and, thus, offers a new thought to deal with foodborne disease.
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Affiliation(s)
- Xue Li
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, National Engineering Research Center for Functional Food, National Engineering Laboratory for Cereal Fermentation Technology, Collaborative Innovation Center of Food Safety and Quality Control, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu 214122, People's Republic of China
| | - Chin-Ping Tan
- Department of Food Technology, Faculty of Food Science and Technology, University Putra Malaysia, Selangor 410500, Malaysia
| | - Yuan-Fa Liu
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, National Engineering Research Center for Functional Food, National Engineering Laboratory for Cereal Fermentation Technology, Collaborative Innovation Center of Food Safety and Quality Control, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu 214122, People's Republic of China
| | - Yong-Jiang Xu
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, National Engineering Research Center for Functional Food, National Engineering Laboratory for Cereal Fermentation Technology, Collaborative Innovation Center of Food Safety and Quality Control, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu 214122, People's Republic of China
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The Gut Microbiota and Respiratory Diseases: New Evidence. J Immunol Res 2020; 2020:2340670. [PMID: 32802893 PMCID: PMC7415116 DOI: 10.1155/2020/2340670] [Citation(s) in RCA: 137] [Impact Index Per Article: 27.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Revised: 06/13/2020] [Accepted: 06/18/2020] [Indexed: 12/14/2022] Open
Abstract
Human body surfaces, such as the skin, intestines, and respiratory and urogenital tracts, are colonized by a large number of microorganisms, including bacteria, fungi, and viruses, with the gut being the most densely and extensively colonized organ. The microbiome plays an essential role in immune system development and tissue homeostasis. Gut microbiota dysbiosis not only modulates the immune responses of the gastrointestinal (GI) tract but also impacts the immunity of distal organs, such as the lung, further affecting lung health and respiratory diseases. Here, we review the recent evidence of the correlations and underlying mechanisms of the relationship between the gut microbiota and common respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), lung cancer, and respiratory infection, and probiotic development as a therapeutic intervention for these diseases.
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Belleggia L, Aquilanti L, Ferrocino I, Milanović V, Garofalo C, Clementi F, Cocolin L, Mozzon M, Foligni R, Haouet MN, Scuota S, Framboas M, Osimani A. Discovering microbiota and volatile compounds of surströmming, the traditional Swedish sour herring. Food Microbiol 2020; 91:103503. [PMID: 32539969 DOI: 10.1016/j.fm.2020.103503] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Revised: 04/01/2020] [Accepted: 04/01/2020] [Indexed: 12/31/2022]
Abstract
In this study, the microbiota of ready-to-eat surströmming from three Swedish producers were studied using a combined approach. The pH values of the samples ranged between 6.67 ± 0.01 and 6.98 ± 0.01, whereas their aw values were between 0.911 ± 0.001 and 0.940 ± 0.001. The acetic acid concentration was between 0.289 ± 0.009 g/100 g and 0.556 ± 0.036 g/100 g. Very low concentrations of lactic acid were measured. Viable counting revealed the presence of mesophilic aerobes, mesophilic lactobacilli and lactococci as well as halophilic lactobacilli and lactococci, coagulase-negative staphylococci, halophilic aerobes and anaerobes. Negligible counts for Enterobacteriaceae, Pseudomonadaceae and total eumycetes were observed, whereas no sulfite-reducing anaerobes were detected. Listeria monocytogenes and Salmonella spp. were absent in all samples. Multiplex real-time PCR revealed the absence of the bont/A, bont/B, bont/E, bont/F, and 4gyrB (CP) genes, which encode botulinic toxins, in all the samples analyzed. Metagenomic sequencing revealed the presence of a core microbiota dominated by Halanaerobium praevalens, Alkalibacterium gilvum, Carnobacterium spp., Tetragenococcus halophilus, Clostridiisalibacter spp. and Porphyromonadaceae. Psychrobacter celer, Ruminococcaceae, Marinilactibacillus psychrotolerans, Streptococcus infantis and Salinivibrio costicola were detected as minor OTUs. GC-MS analysis of volatile components revealed the massive presence of trimethylamine and sulphur compounds. Moreover, 1,2,4-trithiolane, phenols, ketones, aldehydes, alcohols, esters and long chain aliphatic hydrocarbons were also detected. The data obtained allowed pro-technological bacteria, which are well-adapted to saline environments, to be discovered for the first time. Further analyses are needed to better clarify the extent of the contribution of either the microbiota or autolytic enzymes of the fish flesh in the aroma definition.
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Affiliation(s)
- Luca Belleggia
- Dipartimento di Scienze Agrarie, Alimentari ed Ambientali, Università Politecnica delle Marche, via Brecce Bianche, 60131, Ancona, Italy
| | - Lucia Aquilanti
- Dipartimento di Scienze Agrarie, Alimentari ed Ambientali, Università Politecnica delle Marche, via Brecce Bianche, 60131, Ancona, Italy
| | - Ilario Ferrocino
- Department of Agricultural, Forest, and Food Science, University of Turin, Largo Paolo Braccini 2, 10095, Grugliasco, Torino, Italy.
| | - Vesna Milanović
- Dipartimento di Scienze Agrarie, Alimentari ed Ambientali, Università Politecnica delle Marche, via Brecce Bianche, 60131, Ancona, Italy
| | - Cristiana Garofalo
- Dipartimento di Scienze Agrarie, Alimentari ed Ambientali, Università Politecnica delle Marche, via Brecce Bianche, 60131, Ancona, Italy
| | - Francesca Clementi
- Dipartimento di Scienze Agrarie, Alimentari ed Ambientali, Università Politecnica delle Marche, via Brecce Bianche, 60131, Ancona, Italy
| | - Luca Cocolin
- Department of Agricultural, Forest, and Food Science, University of Turin, Largo Paolo Braccini 2, 10095, Grugliasco, Torino, Italy
| | - Massimo Mozzon
- Dipartimento di Scienze Agrarie, Alimentari ed Ambientali, Università Politecnica delle Marche, via Brecce Bianche, 60131, Ancona, Italy
| | - Roberta Foligni
- Dipartimento di Scienze Agrarie, Alimentari ed Ambientali, Università Politecnica delle Marche, via Brecce Bianche, 60131, Ancona, Italy
| | - M Naceur Haouet
- Istituto Zooprofilattico Sperimentale dell'Umbria e delle Marche, via Salvemini, Perugia, Italy
| | - Stefania Scuota
- Istituto Zooprofilattico Sperimentale dell'Umbria e delle Marche, via Salvemini, Perugia, Italy
| | - Marisa Framboas
- Istituto Zooprofilattico Sperimentale dell'Umbria e delle Marche, via Salvemini, Perugia, Italy
| | - Andrea Osimani
- Dipartimento di Scienze Agrarie, Alimentari ed Ambientali, Università Politecnica delle Marche, via Brecce Bianche, 60131, Ancona, Italy.
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Hufnagl K, Pali-Schöll I, Roth-Walter F, Jensen-Jarolim E. Dysbiosis of the gut and lung microbiome has a role in asthma. Semin Immunopathol 2020; 42:75-93. [PMID: 32072252 PMCID: PMC7066092 DOI: 10.1007/s00281-019-00775-y] [Citation(s) in RCA: 233] [Impact Index Per Article: 46.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Accepted: 12/15/2019] [Indexed: 02/07/2023]
Abstract
Worldwide 300 million children and adults are affected by asthma. The development of asthma is influenced by environmental and other exogenous factors synergizing with genetic predisposition, and shaping the lung microbiome especially during birth and in very early life. The healthy lung microbial composition is characterized by a prevalence of bacteria belonging to the phyla Bacteroidetes, Actinobacteria, and Firmicutes. However, viral respiratory infections are associated with an abundance of Proteobacteria with genera Haemophilus and Moraxella in young children and adult asthmatics. This dysbiosis supports the activation of inflammatory pathways and contributes to bronchoconstriction and bronchial hyperresponsiveness. Exogenous factors can affect the natural lung microbiota composition positively (farming environment) or negatively (allergens, air pollutants). It is evident that also gut microbiota dysbiosis has a high influence on asthma pathogenesis. Antibiotics, antiulcer medications, and other drugs severely impair gut as well as lung microbiota. Resulting dysbiosis and reduced microbial diversity dysregulate the bidirectional crosstalk across the gut-lung axis, resulting in hypersensitivity and hyperreactivity to respiratory and food allergens. Efforts are undertaken to reconstitute the microbiota and immune balance by probiotics and engineered bacteria, but results from human studies do not yet support their efficacy in asthma prevention or treatment. Overall, dysbiosis of gut and lung seem to be critical causes of the increased emergence of asthma.
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Affiliation(s)
- Karin Hufnagl
- The Interuniversity Messerli Research Institute, Medical University Vienna and University of Veterinary Medicine Vienna, Vienna, Austria
| | - Isabella Pali-Schöll
- The Interuniversity Messerli Research Institute, Medical University Vienna and University of Veterinary Medicine Vienna, Vienna, Austria
| | - Franziska Roth-Walter
- The Interuniversity Messerli Research Institute, Medical University Vienna and University of Veterinary Medicine Vienna, Vienna, Austria
| | - Erika Jensen-Jarolim
- The Interuniversity Messerli Research Institute, Medical University Vienna and University of Veterinary Medicine Vienna, Vienna, Austria.
- Center for Pathophysiology, Infectiology and Immunology, Institute of Pathophysiology and Allergy Research, Medical University Vienna, Währinger G. 18-20, 1090, Vienna, Austria.
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Perioperative Prophylactic Antibiotics in 1,250 Orbital Surgeries. Ophthalmic Plast Reconstr Surg 2020; 36:385-389. [DOI: 10.1097/iop.0000000000001565] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Ponzo V, Ferrocino I, Zarovska A, Amenta MB, Leone F, Monzeglio C, Rosato R, Pellegrini M, Gambino R, Cassader M, Ghigo E, Cocolin L, Bo S. The microbiota composition of the offspring of patients with gestational diabetes mellitus (GDM). PLoS One 2019; 14:e0226545. [PMID: 31841548 PMCID: PMC6913919 DOI: 10.1371/journal.pone.0226545] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Accepted: 11/23/2019] [Indexed: 02/07/2023] Open
Abstract
The microbiota composition of the offspring of women with gestational diabetes mellitus (GDM), a common pregnancy complication, is still little known. We investigated whether the GDM offspring gut microbiota composition is associated with the maternal nutritional habits, metabolic variables or pregnancy outcomes. Furthermore, we compared the GDM offspring microbiota to the microbiota of normoglycemic-mother offspring. Fecal samples of 29 GDM infants were collected during the first week of life and assessed by 16S amplicon-based sequencing. The offspring's microbiota showed significantly lower α-diversity than the corresponding mothers. Earlier maternal nutritional habits were more strongly associated with the offspring microbiota (maternal oligosaccharide positively with infant Ruminococcus, maternal saturated fat intake inversely with infant Rikenellaceae and Ruminococcus) than last-trimester maternal habits. Principal coordinate analysis showed a separation of the infant microbiota according to the type of feeding (breastfeeding vs formula-feeding), displaying in breast-fed infants a higher abundance of Bifidobacterium. A few Bacteroides and Blautia oligotypes were shared by the GDM mothers and their offspring, suggesting a maternal microbial imprinting. Finally, GDM infants showed higher relative abundance of pro-inflammatory taxa than infants from healthy women. In conclusion, many maternal conditions impact on the microbiota composition of GDM offspring whose microbiota showed increased abundance of pro-inflammatory taxa.
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Affiliation(s)
- Valentina Ponzo
- Department of Medical Sciences, University of Turin, Turin, Italy
| | - Ilario Ferrocino
- Department of Agricultural, Forestry, and Food Science, University of Turin, Turin, Italy
| | - Adriana Zarovska
- Department of Medical Sciences, University of Turin, Turin, Italy
| | | | - Filomena Leone
- Clinical Nutrition Unit, S. Anna Hospital, Città della Salute e della Scienza, Turin, Italy
| | - Clara Monzeglio
- Gynecology and Obstetrics Unit, S. Anna Hospital, Città della Salute e della Scienza, Turin, Italy
| | - Rosalba Rosato
- Department of Psychology, University of Turin, Turin, Italy
| | | | - Roberto Gambino
- Department of Medical Sciences, University of Turin, Turin, Italy
| | | | - Ezio Ghigo
- Department of Medical Sciences, University of Turin, Turin, Italy
| | - Luca Cocolin
- Department of Agricultural, Forestry, and Food Science, University of Turin, Turin, Italy
| | - Simona Bo
- Department of Medical Sciences, University of Turin, Turin, Italy
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