scholarly journals Alterations of lung microbiota in a mouse model of LPS-induced lung injury

2015 ◽  
Vol 309 (1) ◽  
pp. L76-L83 ◽  
Author(s):  
Valeriy Poroyko ◽  
Fanyong Meng ◽  
Angelo Meliton ◽  
Taras Afonyushkin ◽  
Alexander Ulanov ◽  
...  
Keyword(s):  
Lung Injury ◽  
Mouse Model ◽  
Lung Inflammation ◽  
Diversity Index ◽  
Bacterial Load ◽  
Rrna Gene ◽  
Barrier Dysfunction ◽  
Intratracheal Administration ◽  
Significant Difference ◽  
Community Complexity

Acute lung injury (ALI) and the more severe acute respiratory distress syndrome are common responses to a variety of infectious and noninfectious insults. We used a mouse model of ALI induced by intratracheal administration of sterile bacterial wall lipopolysaccharide (LPS) to investigate the changes in innate lung microbiota and study microbial community reaction to lung inflammation and barrier dysfunction induced by endotoxin insult. One group of C57BL/6J mice received LPS via intratracheal injection ( n = 6), and another received sterile water ( n = 7). Bronchoalveolar lavage (BAL) was performed at 72 h after treatment. Bacterial DNA was extracted and used for qPCR and 16S rRNA gene-tag (V3–V4) sequencing (Illumina). The bacterial load in BAL from ALI mice was increased fivefold ( P = 0.03). The community complexity remained unchanged (Simpson index, P = 0.7); the Shannon diversity index indicated the increase of community evenness in response to ALI ( P = 0.07). Principal coordinate analysis and analysis of similarity (ANOSIM) test ( P = 0.005) revealed a significant difference between microbiota of control and ALI groups. Bacteria from families Xanthomonadaceae and Brucellaceae increased their abundance in the ALI group as determined by Metastats test ( P < 0.02). In concordance with the 16s-tag data, Stenotrohomonas maltophilia ( Xanthomonadaceae) and Ochrobactrum anthropi ( Brucellaceae) were isolated from lungs of mice from both groups. Metabolic profiling of BAL detected the presence of bacterial substrates suitable for both isolates. Additionally, microbiota from LPS-treated mice intensified IL-6-induced lung inflammation in naive mice. We conclude that the morbid transformation of ALI microbiota was attributed to the set of inborn opportunistic pathogens thriving in the environment of inflamed lung, rather than the external infectious agents.

scholarly journals miR-34b-5p inhibition attenuates lung inflammation and apoptosis in an LPS-induced acute lung injury mouse model by targeting progranulin

2018 ◽  
Vol 233 (9) ◽  
pp. 6615-6631 ◽  
Author(s):  
Wang Xie ◽  
Qingchun Lu ◽  
Kailing Wang ◽  
Jingjing Lu ◽  
Xia Gu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Mouse Model ◽  
Lung Inflammation

scholarly journals Inhibition of Pyk2 blocks lung inflammation and injury in a mouse model of acute lung injury

2012 ◽  
Vol 13 (1) ◽  
pp. 4 ◽  
Author(s):  
Yingli Duan ◽  
Jonathan Learoyd ◽  
Angelo Y Meliton ◽  
Alan R Leff ◽  
Xiangdong Zhu
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Mouse Model ◽  
Lung Inflammation

scholarly journals Influence of intramuscular depot-medroxyprogesterone acetate initiation on vaginal microbiota in the postpartum period

2020 ◽  
Author(s):  
Bridget M Whitney ◽  
Sujatha Srinivasan ◽  
Kenneth Tapia ◽  
Eric Munene Muriuki ◽  
Bhavna H Chohan ◽  
...  
Keyword(s):  
Bacterial Community ◽  
Medroxyprogesterone Acetate ◽  
High Throughput Sequencing ◽  
Bacterial Community Composition ◽  
Bacterial Load ◽  
Alpha Diversity ◽  
Rrna Gene ◽  
Nugent Score ◽  
Depot Medroxyprogesterone Acetate ◽  
Significant Difference

Abstract Background The vaginal microbiome plays a key role in women’s reproductive health. Use of exogenous hormones, such as intramuscular depot-medroxyprogesterone acetate (DMPA-IM), may alter the composition of vaginal bacterial community. Methods Vaginal swabs were collected from postpartum Kenyan women initiating DMPA-IM or non-hormonal contraception (non-HC). Bacterial vaginosis was assessed by Nugent score (Nugent-BV) and bacterial community composition was evaluated using broad-range 16S rRNA gene PCR with high-throughput sequencing. Changes in Nugent score, alpha diversity (Shannon diversity index), and total bacterial load between contraceptive groups from enrollment to three-months post-initiation were estimated using multivariable linear mixed effects regression. Results Among 54 HIV-negative women, 33 choosing DMPA-IM and 21 choosing non-HC, Nugent-BV was more common among DMPA-IM users at enrollment. At follow-up, Nugent score had decreased significantly among DMPA-IM users (Δ=-1.89 (95%CI:-3.53, -0.25; p=0.02) while alpha diversity remained stable (Δ=0.03, 95%CI:-0.24, 0.30; p=0.83). Conversely, Nugent score remained relatively stable among non-HC users (Δ=-0.73, 95%CI:-2.18, 0.73; p=0.33) while alpha diversity decreased (Δ=-0.34, 95%CI:-0.67, -0.001; p=0.05). Total bacterial load decreased slightly in DMPA-IM users and increased slightly among non-HC users, resulting in a significant difference in change between the contraceptive groups (difference=-0.64 log10 gene copies/swab, 95%CI:-1.19, -0.08; p=0.02). While significant changes in Nugent score and alpha diversity were observed within contraceptive groups, changes between groups were not significantly different. Conclusions Postpartum vaginal bacterial diversity did not change in DMPA-IM users despite a reduction in Nugent-BV, but decreased significantly among women using non-HC. Choice of contraception may influence Lactobacillus recovery in postpartum women.

scholarly journals Applying fecal microbiota transplantation (FMT) to treat recurrent Clostridium difficile infections (rCDI) in children

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4663 ◽  
Author(s):  
Shaaz Fareed ◽  
Neha Sarode ◽  
Frank J. Stewart ◽  
Aneeq Malik ◽  
Elham Laghaie ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Adverse Effects ◽  
Gut Microbiome ◽  
Pediatric Patients ◽  
Fecal Microbiota Transplantation ◽  
Diversity Index ◽  
Microbial Community Composition ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Significant Difference

Background Fecal Microbiota Transplantation (FMT) is an innovative means of treating recurrent Clostridium difficile infection (rCDI), through restoration of gut floral balance. However, there is a lack of data concerning the efficacy of FMT and its impact on the gut microbiome among pediatric patients. This study analyzes clinical outcomes and microbial community composition among 15 pediatric patients treated for rCDI via FMT. Methods This is a prospective, observational, pilot study of 15 children ≤18 years, who presented for rCDI and who met inclusion criteria for FMT at a pediatric hospital and pediatric gastroenterology clinic. Past medical history and demographics were recorded at enrollment and subsequent follow-up. Specimens of the donors’ and the patients’ pre-FMT and post-FMT fecal specimen were collected and used to assess microbiome composition via 16S rRNA gene sequencing. Results FMT successfully prevented rCDI episodes for minimum of 3 months post-FMT in all patients, with no major adverse effects. Three patients reported continued GI bleeding; however, all three also had underlying Inflammatory Bowel Disease (IBD). Our analyses confirm a significant difference between pre-and post-FMT gut microbiome profiles (Shannon diversity index), whereas no significant difference was observed between post-FMT and donor microbiome profiles. At the phyla level, post-FMT profiles showed significantly increased levels of Bacteroidetes and significantly decreased levels of Proteobacteria. Subjects with underlying IBD showed no difference in their pre-and post-FMT profiles. Conclusion The low rate of recurrence or re-infection by C. difficile, coupled with minimal adverse effects post-FMT, suggests that FMT is a viable therapeutic means to treat pediatric rCDI. Post-FMT microbiomes are different from pre-FMT microbiomes, and similar to those of healthy donors, suggesting successful establishment of a healthier microbiome.

Inhibition Of Pyk2 Blocks Lung Inflammation And Injury In A Mouse Model Of Acute Lung Injury

2010 ◽  
Author(s):  
Yingli Duan ◽  
Jonathan Learoyd ◽  
Angelo Y. Meliton ◽  
Alan R. Leff ◽  
Xiangdong Zhu
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Mouse Model ◽  
Lung Inflammation

Abstract 20051: Divergent Actions of Circulating Angiopoietin-2 on Vascular Inflammation and Leak in a Mouse Model of Acute Lung Injury

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Kenny Schlosser ◽  
Mohamad Taha ◽  
Yupu Deng ◽  
Shirley H Mei ◽  
Duncan J Stewart
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Mouse Model ◽  
Lung Inflammation ◽  
Partial Agonist ◽  
Vascular Inflammation ◽  
Vascular Leak ◽  
Angiopoietin 2 ◽  
Circulating Levels

Introduction: Angiopoietin-2 (Angpt2) is a partial agonist/antagonist of the vascular-stabilizing endothelial Tie2 receptor. In both animal models and patients with acute lung injury (ALI), Angpt2 circulating levels are elevated; however, it remains unclear whether these elevated levels contribute to, or protect against, the lung inflammation and vascular leak associated with ALI. Objective: To evaluate the biological consequences of elevated circulating Angpt2 levels in a mouse model of endotoxin-induced ALI. Methods and Results: Transgenic mice (Angpt2OVR) with elevated circulating levels of human (h)Angpt2, via conditional hepatocyte-specific overexpression, were examined at several timepoints (from 3 h to 72 h) following lipopolysaccharide (LPS)-induced ALI (n=7-14 mice/genotype group/timepoint). Bronchoalveolar lavage (BAL) neutrophil and inflammatory cytokine levels were significantly higher (P<0.05) in Angpt2OVR versus littermate controls at 48 h and 6 h post LPS, respectively. In contrast, vascular leak, evidenced by decreased BAL IgM and albumin levels at 24 and 48 h, was attenuated in Angpt2OVR mice. Systemic Angpt2 overexpression showed no net detriment or benefit for survival following LPS-induced injury (n=37-38 mice/group). Tail vein injection of an anti-hAngpt2-neutralizing aptamer (versus non-functional scrambled-sequence control; n=12-13 mice/group), reversed the pro-inflammatory and anti-leak effects observed at 48 h in LPS-injured Angpt2OVR mice. Transcript profiling, via PCR array, was also conducted to probe the effects of Angpt2 neutralization on the lung tissue expression of 84 genes involved in vascular biology. Angpt2 neutralization via aptamer caused alterations in multiple genes linked to angiogenesis, vascular tone, inflammation, apoptosis, cell adhesion, coagulation, and platelet activation (P<0.05 versus scrambled control, n=4/group). Conclusions: Angpt2 exerts differential effects on lung inflammation and permeability under pathological conditions in vivo. These data establish novel context-dependent actions of Angpt2, and suggest elevated circulating levels may help regulate multiple pathways necessary to fine-tune the vascular response to lung injury.

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