The Role of Lung and Gut Microbiota in the Pathology of Asthma

Barcik, Weronika; Boutin, Rozlyn C.T.; Sokołowska, Milena; Finlay, B. Brett

doi:10.1016/j.immuni.2020.01.007

Cited by 351 publications

(249 citation statements)

References 188 publications

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“…Therefore, intestinal endogenous bacterial infection is an important reason of ALI. In addition, studies on the relationship between pulmonary microbiome and disease are also increasing [44][45][46][47][48][49]. The studies found that healthy lungs also have microbiome [50], and the state of pulmonary microbiome changes with the severity of the disease [51,52].…”

Section: Introductionmentioning

confidence: 99%

Adipose-derived mesenchymal stem cells attenuate acute lung injury and improve the gut microbiota in septic rats

et al. 2020

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Background We hypothesized that adipose-derived mesenchymal stem cells (ADMSCs) may ameliorate sepsis-induced acute lung injury (ALI) and change microorganism populations in the gut microbiota, such as that of Firmicutes and Bacteroidetes. Methods A total of 60 male adult Sprague-Dawley (SD) rats were separated into three groups: the sham control (SC) group, the sepsis induced by cecal ligation and puncture (CLP) group, and the ADMSC treatment (CLP-ADMSCs) group, in which rats underwent the CLP procedure and then received 1 × 106 ADMSCs. Rats were sacrificed 24 h after the SC or CLP procedures. To study the role of ADMSCs during ALI caused by sepsis and examine the impact of ADMSCs on the gut microbiome composition, rat lungs were histologically evaluated using hematoxylin and eosin (H&E) staining, serum levels of pro-inflammatory factors were detected using enzyme-linked immunosorbent assay (ELISA), and fecal samples were collected and analyzed using 16S rDNA sequencing. Results The serum levels of inflammatory cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-6, were significantly increased in rats after the CLP procedure, but were significantly decreased in rats treated with ADMSCs. Histological evaluation of the rat lungs yielded results consistent with the changes in IL-6 levels among all groups. Treatment with ADMSCs significantly increased the diversity of the gut microbiota in rats with sepsis. The principal coordinates analysis (PCoA) results showed that there was a significant difference between the gut microbiota of the CLP-ADMSCs group and that of the CLP group. In rats with sepsis, the proportion of Escherichia–Shigella (P = 0.01) related to lipopolysaccharide production increased, and the proportion of Akkermansia (P = 0.02) related to the regulation of intestinal mucosal thickness and the maintenance of intestinal barrier function decreased. These changes in the gut microbiota break the energy balance, aggravate inflammatory reactions, reduce intestinal barrier functions, and promote the translocation of intestinal bacteria. Intervention with ADMSCs increased the proportion of beneficial bacteria, reduced the proportion of harmful bacteria, and normalized the gut microbiota. Conclusions Therapeutically administered ADMSCs ameliorate CLP-induced ALI and improves gut microbiota, which provides a potential therapeutic mechanism for ADMSCs in the treatment of sepsis.

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Section: Introductionmentioning

confidence: 99%

Adipose-derived mesenchymal stem cells attenuate acute lung injury and improve the gut microbiota in septic rats

et al. 2020

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“…The distal ileum and colon contain a million to billion fold more bacteria per gram of organ weight in the distal ileum and colon as compared to the healthy lung (45). Many groups have strongly supported the role of the lung microbiome in influencing ARDS, sepsis and other lung disease outcomes (4,12,13,38). This may be due to a greater microbial biomass within context of diseased lungs (where favorable growth conditions may exist) and due to gut bacterial translocation to the lung in critical illness [reviewed in (32,55)].…”

Section: Discussionmentioning

confidence: 99%

Lung Immune Tone Regulation by the Gut-Lung Immune Axis: Short-chain Fatty Acid Receptors FFAR2 and FFAR3, and IL-1β Expression Profiling in Mouse and Human Lung

Liu

Tian

Maruyama

et al. 2020

Preprint

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Microbial metabolites produced by the gut microbiome, such as short-chain fatty acids (SCFA), can influence both local intestinal and distant lung physiology and response to injury. However, how lung immune activity is regulated by SCFAs is unknown. We examined fresh human lung tissue and observed the presence of SCFAs with large inter-individual and even intra-lobe variability. In vitro, SCFAs were capable of modifying the metabolic programming in both resting and LPS-exposed alveolar macrophages (AM). Additionally, since we hypothesized that lung immune tone could be defined through priming of the inflammasome (aka signal 1), we interrogated naïve mouse lungs for pro-IL-1β message and localized its presence within the alveolar space in situ, specifically in AM subsets, and in close proximity to alveolar type 2 epithelial (AT2) cells. We established that metabolically active gut microbiota, that produce SCFAs, can transmit LPS and SCFAs to the lung (potential sources of signal 1), and thereby could regulate lung immune tone and metabolic programming. To understand how murine lung cells sensed and upregulated IL-1β in response to gut-microbiome factors, we determined that in vitro, AM and AT2 cells expressed SCFA receptors, FFAR2, FFAR3, and IL-1β but with different expression patterns and LPS-inducibility. Finally, we observed that IL-1β, FFAR2 and FFAR3 were expressed both in isolated human AM and AT2 cells ex-vivo, but in fresh human lung sections in situ, only AM expressed IL-1β at rest and after LPS challenge. Together, this translational study using mouse and human lung tissue and cells supports an important role for the gut microbiome and SCFAs in regulating lung immune tone.

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“…Regarding the homeostatic situation, research in recent years has revealed that in contrast to the older view of the lungs as sterile organs, a lung microbiota is present in the lower airways which exerts significant effects in health and disease, although it is not as abundant as in the gut (29)(30)(31)(32). The term "microbiota" refers to all the microorganisms present, namely bacteria, fungi, protozoans, and viruses (29), but here we will only consider the role of bacteria.…”

Section: Nk Cells In the Lungsmentioning

confidence: 99%

“…Everything that disturbs this balance, such as some medications and particularly antibiotics, increases in nutrients (high fat diet, low fiber diet), cigarette smoke, infectious agents, chronic inflammation, can disturb the gut as well as the lung microbiota and lead to a state of dysbiosis, characterized by an increased number of airway bacteria and a change in its composition. The dysbiosis is profoundly linked to several severe lung diseases [asthma, chronic obstructive pulmonary disease (COPD), infections, cancer] (29)(30)(31)(32)(33)(34)(35).…”

Section: Nk Cells In the Lungsmentioning

confidence: 99%

Airway Natural Killer Cells and Bacteria in Health and Disease

2020

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Natural killer (NK) cells are innate lymphoid cells at the interface between innate and adaptive immunity and mostly studied for their important roles in viral infections and malignant tumors. They can kill diseased cells and produce cytokines and chemokines, thereby shaping the adaptive immune response. Nowadays, NK cells are considered as a strong weapon for cancer immunotherapy and can for example be transduced to express tumor-specific chimeric antigen receptors or harnessed with therapeutic antibodies such as the so-called NK engagers. Whereas a large body of literature exists about the antiviral and antitumoral properties of NK cells, their potential role in bacterial infections is not that well delineated. Furthermore, NK cells are much more heterogeneous than previously thought and have tissue-characteristic features and phenotypes. This review gives an overview of airway NK cells and their position within the immunological army dressed against bacterial infections in the upper and predominantly the lower respiratory tracts. Whereas it appears that in several infections, NK cells play a non-redundant and protective role, they can likewise act as rather detrimental. The use of mouse models and the difficulty of access to human airway tissues for ethical reasons might partly explain the divergent results. However, new methods are appearing that are likely to reduce the heterogeneity between studies and to give a more coherent picture in this field.

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The Role of Lung and Gut Microbiota in the Pathology of Asthma

Cited by 351 publications

References 188 publications

Adipose-derived mesenchymal stem cells attenuate acute lung injury and improve the gut microbiota in septic rats

Adipose-derived mesenchymal stem cells attenuate acute lung injury and improve the gut microbiota in septic rats

Lung Immune Tone Regulation by the Gut-Lung Immune Axis: Short-chain Fatty Acid Receptors FFAR2 and FFAR3, and IL-1β Expression Profiling in Mouse and Human Lung

Airway Natural Killer Cells and Bacteria in Health and Disease

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