scholarly journals Predicting Hyperoxia-Induced Lung Injury from Associated Intestinal and Lung Dysbiosis in Neonatal Mice

Neonatology ◽  
2021 ◽  
pp. 106-116
Author(s):  
Chung-Ming Chen ◽  
Hsiu-Chu Chou ◽  
Yu-Chen S.H. Yang ◽  
Emily Chia-Yu Su ◽  
Yun-Ru Liu
Keyword(s):  
Lung Injury ◽  
Intestinal Microbiota ◽  
Bacterial Translocation ◽  
Left Lung ◽  
Intestinal Barrier ◽  
Intestinal Bacteria ◽  
Machine Learning Algorithms ◽  
Neonatal Mice ◽  
The Right ◽  
Neonatal Hyperoxia

Background: Preclinical studies have demonstrated that hyperoxia disrupts the intestinal barrier, changes the intestinal bacterial composition, and injures the lungs of newborn animals. Objectives: The aim of the study was to investigate the effects of hyperoxia on the lung and intestinal microbiota and the communication between intestinal and lung microbiota and to develop a predictive model for the identification of hyperoxia-induced lung injury from intestinal and lung microbiota based on machine learning algorithms in neonatal mice. Methods: Neonatal C57BL/6N mice were reared in either room air or hyperoxia (85% O2) from postnatal days 1–7. On postnatal day 7, lung and intestinal microbiota were sampled from the left lung and lower gastrointestinal tract for 16S ribosomal RNA gene sequencing. Tissue from the right lung and terminal ileum were harvested for Western blot and histology analysis. Results: Hyperoxia induced intestinal injury, decreased intestinal tight junction expression, and impaired lung alveolarization and angiogenesis in neonatal mice. Hyperoxia also altered intestinal and lung microbiota and promoted bacterial translocation from the intestine to the lung as evidenced by the presence of intestinal bacteria in the lungs of hyperoxia-exposed neonatal mice. The relative abundance of these bacterial taxa was significantly positively correlated with the increased lung cytokines. Conclusions: Neonatal hyperoxia induced intestinal and lung dysbiosis and promoted bacterial translocation from the intestine to the lung. Further studies are needed to clarify the pathophysiology of bacterial translocation to the lung.

scholarly journals Predicting Hyperoxia-Induced Lung Injury from Associated Intestinal and Lung Dysbiosis in Neonatal Mice

2020 ◽  
Author(s):  
Chung-Ming Chen ◽  
Hsiu-Chu Chou ◽  
Yu-Chen Yang ◽  
Emily Chia-Yu Su
Keyword(s):  
Lung Injury ◽  
Intestinal Microbiota ◽  
Bacterial Translocation ◽  
Prediction Models ◽  
Left Lung ◽  
Area Under The Curve ◽  
Intestinal Barrier ◽  
Machine Learning Algorithms ◽  
Neonatal Mice ◽  
Neonatal Hyperoxia

Abstract Background: Newborns with respiratory disorders often require supplemental oxygen. Preclinical studies have demonstrated that hyperoxia disrupts the intestinal barrier, impairs intestinal function, and injures the lungs of newborn animals. The effects of neonatal hyperoxia on intestinal and lung microbiota and the role of the intestinal microbiota in the pathogenesis of hyperoxia-induced lung injury have not been investigated.Results: In this study, we evaluated the effect of neonatal hyperoxia on intestine and lung microbiota alterations in neonatal C57BL/6N mice reared in either room air (RA) or hyperoxia (85% O2) from postnatal days 1 to 7. On postnatal day 7, lung and intestinal microbiota were sampled from the left lung and lower gastrointestinal tract for 16S ribosomal RNA gene sequencing. Tissue from the right lung and terminal ileum were harvested for Western blot and histology analysis. Hyperoxia decreased body weight, induced intestinal injury, decreased intestinal tight junction expression, impaired lung alveolarization and angiogenesis, and increased lung cytokines in neonatal mice. Hyperoxia also altered intestinal and lung microbiota and promoted bacterial translocation from the intestine to the lung as evidenced by the presence of intestinal bacteria in the lungs of hyperoxia-exposed neonatal mice. The relative abundance of these bacterial taxa was significantly positively correlated with lung cytokines. Intestinal and lung microbiota combined with cytokines were incorporated into machine learning algorithms to develop prediction models for the classification of RA- or hyperoxia-reared mice. The experiment results demonstrated that a Bayes network achieved the best predictive performance, attaining accuracy, sensitivity, specificity, and area under the curve values of 94.4%, 88.9%, 100%, and 0.963, respectively. Selected discriminative features included lung cytokines (interleukin-1β, macrophage inflammatory protein-2, and tumor necrosis factor-α), lung microbiota (Ruminococcaceae_UCG-010, CAG-56, and Enterobacter), and intestinal microbiota (Peptococcaceae_ge, Muribaculum, Enterobacter, and Ruminococcaceae_UCG-010). Conclusions: Neonatal hyperoxia exposure during the first week of life induced intestinal and lung dysbiosis and promoted bacterial translocation from the intestine to the lung. These findings suggest that changes in the composition of the intestinal microbiota contribute to hyperoxia-induced lung injury and that the combination of intestinal and lung microbiota may indicate hyperoxia-induced lung injury in neonatal mice.

scholarly journals Impact of Early Life Antibiotic Exposure and Neonatal Hyperoxia on the Murine Microbiome and Lung Injury

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Melissa H. Althouse ◽  
Christopher Stewart ◽  
Weiwu Jiang ◽  
Bhagavatula Moorthy ◽  
Krithika Lingappan
Keyword(s):  
Lung Injury ◽  
Beta Diversity ◽  
Alpha Diversity ◽  
Intestinal Microbiome ◽  
Rrna Gene ◽  
Antibiotic Exposure ◽  
Neonatal Mice ◽  
Intestinal Dysbiosis ◽  
Neonatal Hyperoxia

Abstract Cross talk between the intestinal microbiome and the lung and its role in lung health remains unknown. Perinatal exposure to antibiotics disrupts the neonatal microbiome and may have an impact on the preterm lung. We hypothesized that perinatal antibiotic exposure leads to long-term intestinal dysbiosis and increased alveolar simplification in a murine hyperoxia model. Pregnant C57BL/6 wild type dams and neonatal mice were treated with antibiotics before and/or immediately after delivery. Control mice received phosphate-buffered saline (PBS). Neonatal mice were exposed to 95% oxygen for 4 days or room air. Microbiome analysis was performed using 16S rRNA gene sequencing. Pulmonary alveolarization and vascularization were analyzed at postnatal day (PND) 21. Perinatal antibiotic exposure modified intestinal beta diversity but not alpha diversity in neonatal mice. Neonatal hyperoxia exposure altered intestinal beta diversity and relative abundance of commensal bacteria in antibiotic treated mice. Hyperoxia disrupted pulmonary alveolarization and vascularization at PND 21; however, there were no differences in the degree of lung injury in antibiotic treated mice compared to vehicle treated controls. Our study suggests that exposure to both hyperoxia and antibiotics early in life may cause long-term alterations in the intestinal microbiome, but intestinal dysbiosis may not significantly influence neonatal hyperoxic lung injury.

scholarly journals Intestinal Barrier Dysfunction, Bacterial Translocation and Inflammation: Deathly Triad in Sepsis

2021 ◽  
Author(s):  
Bercis Imge Ucar ◽  
Gulberk Ucar
Keyword(s):  
Bacterial Translocation ◽  
Current Knowledge ◽  
Intestinal Barrier ◽  
Intestinal Bacteria ◽  
Mucosal Barrier ◽  
High Morbidity ◽  
Barrier Dysfunction ◽  
Intestinal Barrier Dysfunction ◽  
Gut Mucosa ◽  
Sepsis Detection

Sepsis, as a complex entity, comprises multiple pathophysiological mechanisms which bring about high morbidity and mortality. The previous studies showed that the gastrointestinal tract is damaged during sepsis, and its main symptoms include increased permeability, bacterial translocation (BT), and malabsorption. BT is the invasion of indigenous intestinal bacteria via the gut mucosa to other tissues. It occurs in pathological conditions such as disruption of the intestine’s ecological balance and mucosal barrier permeability, immunosuppression, and oxidative stress through transcellular/paracellular pathways and initiate an excessive systemic inflammatory response. Thereby, recent clinical and preclinical studies focus on the association between sepsis and intestinal barrier dysfunction. This chapter overviews the current knowledge about the molecular basis of BT of the intestine, its role in the progress of sepsis, detection of BT, and actual therapeutic approaches.

scholarly journals Role of the Intestinal Microbiome, Intestinal Barrier and Psychobiotics in Depression

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 927
Author(s):  
Paulina Trzeciak ◽  
Mariola Herbet
Keyword(s):  
Immune System ◽  
Intestinal Microbiota ◽  
Intestinal Barrier ◽  
Intestinal Bacteria ◽  
Intestinal Microbiome ◽  
Stress Reactions ◽  
Treatment Of Depression ◽  
Increased Activity ◽  
Excessive Activation

The intestinal microbiota plays an important role in the pathophysiology of depression. As determined, the microbiota influences the shaping and modulation of the functioning of the gut–brain axis. The intestinal microbiota has a significant impact on processes related to neurotransmitter synthesis, the myelination of neurons in the prefrontal cortex, and is also involved in the development of the amygdala and hippocampus. Intestinal bacteria are also a source of vitamins, the deficiency of which is believed to be related to the response to antidepressant therapy and may lead to exacerbation of depressive symptoms. Additionally, it is known that, in periods of excessive activation of stress reactions, the immune system also plays an important role, negatively affecting the tightness of the intestinal barrier and intestinal microflora. In this review, we have summarized the role of the gut microbiota, its metabolites, and diet in susceptibility to depression. We also describe abnormalities in the functioning of the intestinal barrier caused by increased activity of the immune system in response to stressors. Moreover, the presented study discusses the role of psychobiotics in the prevention and treatment of depression through their influence on the intestinal barrier, immune processes, and functioning of the nervous system.

scholarly journals TRANSLOCATION OF INTESTINAL MICROFLORA IN CIRRHOSIS

2020 ◽  
Vol 4 (2) ◽  
pp. 143-150
Author(s):  
D. I. Haurylenka ◽  
◽  
N. N. Silivontchik ◽  
Keyword(s):  
Bacterial Translocation ◽  
Bacterial Infections ◽  
Intestinal Microflora ◽  
Intestinal Barrier ◽  
Intestinal Bacteria ◽  
Cochrane Collaboration ◽  
Russian Language ◽  
Intestinal Lumen ◽  
Future Research ◽  
Inflammatory Status

Background. Understanding of intestinal bacteria-host interaction physiology as well as bacterial translocation characteristics at the initial stages and in advanced cirrhosis emphasizes the importance of approaches minimizing the migration of microorganisms and their components from the intestinal lumen. Objective – to provide a brief review of publications highlighting the problem of bacterial intestinal translocation as the main mechanism for the development of bacterial infections and pro-inflammatory status in patients with liver cirrhosis. Material and methods. We performed the study and analysis of English- and Russian-language articles over the past 30 years contained in the following databases: PubMed, Cochrane Collaboration, UpToDate. The key words were: «intestinal microflora translocation», «bacterial translocation», «translocation markers». Results. Contemporary views on changes of the intestinal barrier and those of innate and adaptive immunity systems in liver diseases are considered. Data on possibility and signifcance of detecting bacterial translocation are presented.Current methods used for gut microbiome analysis as well as some areas for future research are discussed. Conclusion. A validated marker/markers is required to study bacterial translocation in cirrhosis.

scholarly journals The Multi-Component Causes of Late Neonatal Sepsis—Can We Regulate Them?

Nutrients ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 243
Author(s):  
Magdalena Pilarczyk-Zurek ◽  
Grzegorz Majka ◽  
Beata Skowron ◽  
Agnieszka Baranowska ◽  
Monika Piwowar ◽  
...  
Keyword(s):  
Bacterial Translocation ◽  
Neonatal Sepsis ◽  
Neonatal Intensive Care ◽  
Late Onset ◽  
Intraperitoneal Administration ◽  
Intestinal Barrier ◽  
Oral Intake ◽  
Intestinal Bacteria ◽  
Stress Factors ◽  
Rat Pups

Elucidating the mechanisms of bacterial translocation is crucial for the prevention and treatment of neonatal sepsis. In the present study, we aimed to evaluate the potential of lactoferrin to inhibit the development of late-onset blood infection in neonates. Our investigation evaluates the role of key stress factors leading to the translocation of intestinal bacteria into the bloodstream and, consequently, the development of life-threatening sepsis. Three stress factors, namely weaning, intraperitoneal administration of Gram-positive cocci and oral intake of Gram-negative rods, were found to act synergistically. We developed a novel model of rat pups sepsis induced by bacterial translocation and observed the inhibition of this process by supplementation of various forms of lactoferrin: iron-depleted (apolactoferrin), iron-saturated (hololactoferrin) and manganese-saturated lactoferrin. Additionally, lactoferrin saturated with manganese significantly increases the Lactobacillus bacterial population, which contributes to the fortification of the intestinal barrier and inhibits the translocation phenomenon. The acquired knowledge can be used to limit the development of sepsis in newborns in hospital neonatal intensive care units.

Role of damage to intestinal barrier in development of psoriasis

2021 ◽  
pp. 34-37
Author(s):  
I. N. Ekimov ◽  
O. V. Pravdina
Keyword(s):  
Intestinal Permeability ◽  
Intestinal Microbiota ◽  
Ussing Chamber ◽  
Intestinal Barrier ◽  
Intestinal Bacteria ◽  
Intestinal Wall ◽  
Diagnostic Significance ◽  
Fatty Acid Binding ◽  
Barrier Permeability

Disorders of interstitial barrier permeability as one of the promising mechanisms of psoriasis formation and development is a trend of the last decades. In the analysis of modern works devoted to the evaluation of the role of intestinal barrier damage in the development of psoriasis, several ways of assessing intestinal permeability have been noted (including measurement of transepithelial electrical responses using a Ussing chamber, measurement of excretion of orally injected molecules, determination of dynamics and kinetics of LPS intestinal bacteria, immunohistochemical confocal analysis of uniform Z-sections perpendicular to the epithelial cell surface, etc.). However, most authors emphasize the diagnostic significance and availability of biomarker detection. Among the described biomarkers, claudin-3, fecal zonulin, α1-antitrypsin, calprotectin and intestinal fatty acid binding protein (I-FABP) are the most valuable. Through these methods of assessing intestinal permeability and the results of their studies, a number of authors practically prove the correlation between the violation of the intestinal microbiota, intestinal barrier permeability and the development of psoriasis, as well as its severity. This aspect is promising to the therapy of patients with psoriasis, which includes correction of intestinal microbiota and intestinal wall permeability.

Evaluation of perilla ketone-induced unilateral lung injury using external gamma scanning

1994 ◽  
Vol 76 (1) ◽  
pp. 138-145 ◽  
Author(s):  
V. J. Abernathy ◽  
N. A. Pou ◽  
R. E. Parker ◽  
R. J. Roselli
Keyword(s):  
Lung Injury ◽  
Left Lung ◽  
Lung Water ◽  
Lung Weight ◽  
Permeability Changes ◽  
Before And After ◽  
Water Volumes ◽  
The Right ◽  
And Control ◽  
Gamma Scanning

We used a modified external gamma scanning technique to quantitate right and left lung permeability changes to iodinated sheep albumin before and after perilla ketone (PK)-mediated unilateral lung injury in seven anesthetized sheep. Three portable gamma scintillation probes containing 2-in. NaI crystals detected radioactivities of 51Cr-labeled red blood cells and 125I-labeled albumin over the right and left lungs and blood, respectively. Radioactivities were monitored for 1 h before and 3 h after infusion of 25 mg/kg PK into a single lung. Calculation of normalized slope index (NSI) (Roselli and Riddle, J. Appl. Physiol. 67: 2343–2350, 1989) over the 30-min interval before PK and over the 60- to 90-min interval after PK for each lung revealed a four- to five-fold NSI increase in lungs receiving PK (0.00237 +/- 0.00065 to 0.0109 +/- 0.0016 min-1) and no increase in contralateral control lungs (0.00214 +/- 0.00065 to 0.00201 +/- 0.00032 min-1). Observed changes in NSI were consistent with postmortem evaluations of each lung. Lungs receiving PK had significantly higher wet-to-dry lung weight ratios and extravascular lung water volumes than contralateral control lungs. Measured bloodless wet-to-dry lung weight ratios were 5.68 +/- 0.39 and 3.27 +/- 0.27 (P < 0.05) for PK and control lungs, respectively.

Unilateral Acid Aspiration Augments the Effects of Ventilator Lung Injury in the Contralateral Lung

2013 ◽  
Vol 119 (3) ◽  
pp. 642-651 ◽  
Author(s):  
Maria Amigoni ◽  
Giacomo Bellani ◽  
Vanessa Zambelli ◽  
Margherita Scanziani ◽  
Francesca Farina ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Left Lung ◽  
Inflammatory Cells ◽  
Lung Compliance ◽  
Polymorphonuclear Cells ◽  
Acid Aspiration ◽  
Injured Lung ◽  
The Right

Abstract Background: Mechanical ventilation is necessary during acute respiratory distress syndrome, but it promotes lung injury because of the excessive stretch applied to the aerated parenchyma. The authors’ hypothesis was that after a regional lung injury, the noxious effect of mechanical ventilation on the remaining aerated parenchyma would be more pronounced. Methods: Mice, instilled with hydrochloric acid (HCl) in the right lung, was assigned to one of the following groups: mechanical ventilation with tidal volumes (VT) 25 ml/kg (HCl-VILI25, n = 12), or VT 15 ml/kg (HCl-VILI15, n = 9), or spontaneous breathing (HCl-SB, n = 14). Healthy mice were ventilated with VT 25 ml/kg (VILI25, n = 11). Arterial oxygenation, lung compliance, bronchoalveolar lavage inflammatory cells, albumin, and cytokines concentration were measured. Results: After 7 h, oxygenation and lung compliance resulted lower in HCl-VILI25 than in VILI25 (P &lt; 0.05, 210 ± 54 vs. 479 ± 83 mmHg, and 32 ± 3.5 vs. 45 ± 4.1 µl/cm H2O, mean ± SD, respectively). After right lung injury, the left lung of HCl-VILI25 group received a greater fraction of the VT than the VILI25 group, despite an identical global VT. The number of total and polymorphonuclear cells in bronchoalveolar lavage resulted significantly higher in HCl-VILI25, compared with the other groups, in not only the right lung, but also in the left lung. The albumin content in the left lung resulted higher in HCl-VILI25 than in VILI25 (224 ± 85 vs. 33 ± 6 µg/ml; P &lt; 0.05). Cytokines levels did not differ between groups. Conclusion: Aggressive mechanical ventilation aggravates the preexisting lung injury, which is noxious for the contralateral, not previously injured lung, possibly because of a regional redistribution of VT.

scholarly journals Bifidobacteria may be beneficial to intestinal microbiota and reduction of bacterial translocation in mice following ischaemia and reperfusion injury

2012 ◽  
Vol 109 (11) ◽  
pp. 1990-1998 ◽  
Author(s):  
Honggang Wang ◽  
Wei Zhang ◽  
Lugen Zuo ◽  
Weiming Zhu ◽  
Bin Wang ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Intestinal Microbiota ◽  
Bacterial Translocation ◽  
Cell Apoptosis ◽  
Intestinal Barrier ◽  
Peroral Administration ◽  
Barrier Dysfunction ◽  
Mesenteric Lymph Nodes ◽  
Ischaemia And Reperfusion ◽  
Epithelial Cell Apoptosis

The aim of the present study was to determine the effect of peroral bifidobacteria on the intestinal microbiota, barrier function and bacterial translocation (BT) in a mouse model of ischaemia and reperfusion (I/R) injury. A total of twenty-four male BALB/c mice were randomly allocated into three groups: (1) sham-operated, (2) I/R and (3) I/R injury and bifidobacteria pretreatment (109colony-forming units/d). Bifidobacteria were administered daily intragastrically for 2 weeks before induction of I/R. Subsequently, samples of caecal content, intestinal mucosa, ileal segments, blood, mesenteric lymph nodes (MLN) and distant organs (liver, spleen and kidney) were prepared for examination. In the I/R model, barrier dysfunction (caecal microbiota dysbiosis, disruption of tight junction (TJ), increased epithelial cell apoptosis, disruption of mucosa and multiple erosions) in the intestine was observed, associated with increased BT to extraintestinal sites. The ratio of BT to MLN and distant organs in mice exposed to I/R injury was 62·5 %, which was significantly higher than the sham-operated group. However, pretreatment of animals with bifidobacteria prevented I/R-induced BT, reduced pro-inflammatory cytokine release, the levels of endotoxin, intestinal epithelial cell apoptosis, disruption of TJ and increased the concentration of SCFA, resulting in recovered microbiota and mucosal integrity. Bifidobacteria may be beneficial in reducing BT in I/R injury of mice. Therefore, peroral administration of bifidobacteria is a potential strategy to prevent I/R-induced BT and intestinal barrier dysfunction.

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