Gut-Lung Dysbiosis Accompanied by Diabetes Mellitus Leads to Pulmonary Fibrotic Change through the NF-κB Signaling Pathway

Wang, Guang; Hu, Yuxuan; He, Meiyao; Xie, Yunhai; Su, Wei Yi; Long, Denglu; Zhao, Ran; Wang, Jingyun; Dai, Chenyang; Li, Haiyang; Si, Zhen-Peng; Cheng, Xin; Li, Rui-Man; Li, Zhijie; Yang, Xuesong

doi:10.1016/j.ajpath.2021.02.019

Cited by 31 publications

(18 citation statements)

References 73 publications

(59 reference statements)

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“…Diabetes is characterized by considerable morbidity and mortality, mainly from cardiovascular and renal complications, and it is well known that diabetes predisposes to a variety of infectious diseases, including pneumonia [30]. Studies have also shown that the lungs can be a target of diabetic complication where related pathologic findings include inflammatory cell infiltration and increased fibrosis [31,32]. In a study using mice with DM, it was reported that DM-related dysbiosis of gut-lung axis activates the NF-κB signaling pathway that leads to fibrotic changes in the lung tissue [31].…”

Section: Discussionmentioning

confidence: 99%

“…Studies have also shown that the lungs can be a target of diabetic complication where related pathologic findings include inflammatory cell infiltration and increased fibrosis [31,32]. In a study using mice with DM, it was reported that DM-related dysbiosis of gut-lung axis activates the NF-κB signaling pathway that leads to fibrotic changes in the lung tissue [31]. However, there are few studies on DM and airway dysbiosis and therefore further research on the respiratory microbiome and the pathologic changes in the airway would be necessary to better understand the impact of DM on the respiratory microbiome [33].…”

Section: Discussionmentioning

confidence: 99%

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Metataxonomic investigation of the microbial community in the trachea and oropharynx of healthy controls and diabetic patients using endotracheal tubes

et al. 2021

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Background Although the study of respiratory microbiota has been an active field of research, obtaining the appropriate respiratory samples for healthy controls remains to be a challenge. As such, this study aims to evaluate the use of endotracheal tube washing as a viable control for sputum samples. Methods A total of 14 subjects, including 8 healthy respiratory controls and 6 diabetic patients without any respiratory disease, were enrolled in this study, during which the endotracheal tubes used in their scheduled routine surgery were collected. Pre-operative oral gargles were also collected from non-diabetic subjects. Results 16S amplicon sequencing revealed similar taxa composition in endotracheal tube washings and oral gargles in the healthy control subjects, although the relative abundance of 11 genus level operational taxonomic units was significantly different between the two sample sources. The diabetic subjects showed relatively lower diversity than those of non-diabetic subjects. The proportion range of the most abundant taxa detected in each endotracheal tube washings were 10.1–33.2%. Conclusion Endotracheal tube washing fluid may provide healthy control samples for upper respiratory investigations without incurring any additional risk to the subject.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Metataxonomic investigation of the microbial community in the trachea and oropharynx of healthy controls and diabetic patients using endotracheal tubes

et al. 2021

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“…The sections were counter-stained with 4′-6-diamidino-2-phenylindole (DAPI, 5 μg/mL, Life Tech, USA) to reveal the nuclei and finally photographed by an Olympus IX51 microscope (Olympus, Tokyo, Japan). The immunofluorescent intensity was quantitative measured as previously described [ 37 , 38 ]. The results were analyzed using IPP 5.0 or image J software.…”

Section: Methodsmentioning

confidence: 99%

NF-κB activation impedes the transdifferentiation of hypertrophic chondrocytes at the growth plate of mouse embryos in diabetic pregnancy

Liu

Fan

et al. 2021

Journal of Orthopaedic Translation

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Background Diabetes mellitus could cause numerous complications and health problems including abnormality of endochondral bone formation during embryogenesis. However, the underlying mechanisms still remain obscure. Methods Streptozotoci (STZ) was injected to induce pregestational diabetes mellitus (PGDM) mouse model. The femurs of E18.5 mouse embryos from control and PGDM groups were harvested. Morphological staining was implemented to determine the abnormality of the bone development. The expressions of the key genes participating in osteogenesis (e.g., Sox9, Runx2, and Osterix), the NF-κB signaling molecules (e.g., P50, P65, IκBα), and the corresponding regulatory factors (e.g., Bmp2, phospho-p38) were evaluated by immunofluorescence, quantitative PCR and western blot. Finally, in vitro chondrocyte differentiation model was employed to verify the role of NF-κB on the expressions of chondro-osteogenic markers. Results Alcian blue/alizarin red double staining and H&E staining demonstrated the restriction of skeletal development and relatively extended hypertrophic zone at growth plate in E18.5 STZ-induced diabetic mouse embryos compared to the control. Immunofluorescent staining and qPCR showed that Sox9 expression increased, while Runx2 and Osterix expressions decreased in the growth plate of the offspring of PGDM mice. Immunofluorescence of P65 manifested the activation of NF-κB signaling in growth plate in PGDM mouse embryos. Furthermore, the relatively extended hypertrophic zone was also observed in the growth plate of the NF-κB-activated transgenic mice, as well as the activated p65 up-regulated the expression of Bmp2 and p-p38. In ATDC5 cells, we could observe the high glucose up-regulated the P50 and P65 expressions and down-regulated IκBα expression, but the high glucose-activated NF-κB signaling could be reversed by addition of Bay (inhibitor of NF-κB signaling). The expression changes of Bmp2, Sox9 and Runx2 in presence of high glucose were resumed too. Conclusion Our data revealed that NF-κB signaling was involved in mediation effects of dysfunctional trans-differentiation of hypertrophic chondrocytes in the embryonic growth plate induced by maternal diabetic mellitus.

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“…The lung microbiome has been reported to change in different conditions including metabolic diseases [ 79 ], asthma [ 80 ], COPD [ 81 ], pulmonary cystic fibrosis [ 82 ], and cancer [ 83 ]. During infections, these changes can be produced by the entry of a pathogen, an increase of pathobionts, loss of commensals or keystone taxa [ 55 , 56 ].…”

Section: Human Microbiome and Its Importance In Health And Diseasementioning

confidence: 99%

The Microbiome as Part of the Contemporary View of Tuberculosis Disease

et al. 2022

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The study of the microbiome has changed our overall perspective on health and disease. Although studies of the lung microbiome have lagged behind those on the gastrointestinal microbiome, there is now evidence that the lung microbiome is a rich, dynamic ecosystem. Tuberculosis is one of the oldest human diseases, it is primarily a respiratory infectious disease caused by strains from the Mycobacterium tuberculosis Complex. Even today, during the COVID-19 pandemic, it remains one of the principal causes of morbidity and mortality worldwide. Tuberculosis disease manifests itself as a dynamic spectrum that ranges from asymptomatic latent infection to life-threatening active disease. The review aims to provide an overview of the microbiome in the tuberculosis setting, both in patients’ and animal models. We discuss the relevance of the microbiome and its dysbiosis, and how, probably through its interaction with the immune system, it is a significant factor in tuberculosis’s susceptibility, establishment, and severity.

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Gut-Lung Dysbiosis Accompanied by Diabetes Mellitus Leads to Pulmonary Fibrotic Change through the NF-κB Signaling Pathway

Cited by 31 publications

References 73 publications

Metataxonomic investigation of the microbial community in the trachea and oropharynx of healthy controls and diabetic patients using endotracheal tubes

Metataxonomic investigation of the microbial community in the trachea and oropharynx of healthy controls and diabetic patients using endotracheal tubes

NF-κB activation impedes the transdifferentiation of hypertrophic chondrocytes at the growth plate of mouse embryos in diabetic pregnancy

The Microbiome as Part of the Contemporary View of Tuberculosis Disease

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