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      COPD and Gut–Lung Axis: How Microbiota and Host Inflammasome Influence COPD and Related Therapeutics

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          Abstract

          The exact pathogenesis of chronic obstructive pulmonary disease (COPD) remains largely unknown. While current management strategies are effective at stabilizing the disease or relief the symptoms, new approaches are required to target underlying disease process and reverse lung function deterioration. Recent research showed that pneumonia bacteria is critical in disease progression and gut microbiome is likely perturbed in COPD, which is usually accompanied by a decreased intestinal microbial diversity and a disturbance in immune system, contributing to a chronic inflammation. The cross-talk between gut microbes and lungs, termed as the “gut-lung axis,” is known to impact immune response and homeostasis in the airway. Although the gut and respiratory microbiota exhibit compositional differences, the gut and lung showed similarities in the origin of epithelia of both gastrointestinal and respiratory tracts, the anatomical structure, and early-life microbial colonization. Evidence showed that respiratory infection might be prevented, or at least dampened by regulating gut microbial ecosystem; thus, a promising yet understudied area of COPD management is nutrition-based preventive strategies. COPD patient is often deficient in nutrient such as antioxidant, vitamins, and fiber intake. However, further larger-scale randomized clinical trials (RCTs) are required to establish the role of these nutrition-based diet in COPD management. In this review, we highlight the important and complex interaction of microbiota and immune response on gut-lung axis. Further research into the modification and improvement of the gut microbiota and new interventions through diet, probiotics, vitamins, and fecal microbiota transplantation is extreme critical to provide new preventive therapies for COPD.

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          Most cited references94

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          A human gut microbial gene catalogue established by metagenomic sequencing.

          To understand the impact of gut microbes on human health and well-being it is crucial to assess their genetic potential. Here we describe the Illumina-based metagenomic sequencing, assembly and characterization of 3.3 million non-redundant microbial genes, derived from 576.7 gigabases of sequence, from faecal samples of 124 European individuals. The gene set, approximately 150 times larger than the human gene complement, contains an overwhelming majority of the prevalent (more frequent) microbial genes of the cohort and probably includes a large proportion of the prevalent human intestinal microbial genes. The genes are largely shared among individuals of the cohort. Over 99% of the genes are bacterial, indicating that the entire cohort harbours between 1,000 and 1,150 prevalent bacterial species and each individual at least 160 such species, which are also largely shared. We define and describe the minimal gut metagenome and the minimal gut bacterial genome in terms of functions present in all individuals and most bacteria, respectively.
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            Revised Estimates for the Number of Human and Bacteria Cells in the Body

            Reported values in the literature on the number of cells in the body differ by orders of magnitude and are very seldom supported by any measurements or calculations. Here, we integrate the most up-to-date information on the number of human and bacterial cells in the body. We estimate the total number of bacteria in the 70 kg "reference man" to be 3.8·1013. For human cells, we identify the dominant role of the hematopoietic lineage to the total count (≈90%) and revise past estimates to 3.0·1013 human cells. Our analysis also updates the widely-cited 10:1 ratio, showing that the number of bacteria in the body is actually of the same order as the number of human cells, and their total mass is about 0.2 kg.
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              The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation

              The NLRP3 inflammasome is a critical component of the innate immune system that mediates caspase-1 activation and the secretion of proinflammatory cytokines IL-1β/IL-18 in response to microbial infection and cellular damage. However, the aberrant activation of the NLRP3 inflammasome has been linked with several inflammatory disorders, which include cryopyrin-associated periodic syndromes, Alzheimer’s disease, diabetes, and atherosclerosis. The NLRP3 inflammasome is activated by diverse stimuli, and multiple molecular and cellular events, including ionic flux, mitochondrial dysfunction, and the production of reactive oxygen species, and lysosomal damage have been shown to trigger its activation. How NLRP3 responds to those signaling events and initiates the assembly of the NLRP3 inflammasome is not fully understood. In this review, we summarize our current understanding of the mechanisms of NLRP3 inflammasome activation by multiple signaling events, and its regulation by post-translational modifications and interacting partners of NLRP3.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                01 April 2022
                2022
                : 13
                : 868086
                Affiliations
                [1] 1Department of Respiratory and Critical Care Medicine, Shanghai Putuo District Liqun Hospital , Shanghai, China
                [2] 2Department of Science and Education, Shanghai Putuo District Liqun Hospital , Shanghai, China
                [3] 3Department of Clinical Laboratory, Shanghai Putuo District Liqun Hospital , Shanghai, China
                Author notes

                Edited by: Joanna Jackowska, Poznan University of Medical Sciences, Poland

                Reviewed by: Izabela Galvao, Royal Prince Alfred Hospital, Australia

                *Correspondence: Yunfeng Zhang, yunfengzhang910@ 123456hotmail.com

                These authors have contributed equally to this work

                This article was submitted to Microorganisms in Vertebrate Digestive Systems, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2022.868086
                9012580
                35432269
                a6fae989-00eb-4507-9f77-370964469538
                Copyright © 2022 Qu, Cheng, Wang, Mu and Zhang.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 02 February 2022
                : 14 March 2022
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 94, Pages: 9, Words: 8225
                Funding
                Funded by: Scientific and Technological Innovation Foundation of Health Commission of Putuo District of China
                Award ID: ptkwws202118
                Funded by: Improvement Project of Specialized Diseases of Putuo District of China
                Award ID: 2020tszb05
                Categories
                Microbiology
                Mini Review

                Microbiology & Virology
                chronic obstructive pulmonary disease,copd,gut-lung axis,microbiota,nutrition

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