Differential flora in the microenvironment of lung tumor and paired adjacent normal tissues

2020 ◽  
Vol 41 (8) ◽  
pp. 1094-1103
Author(s):  
Qixing Mao ◽  
Weidong Ma ◽  
Zhongqiu Wang ◽  
Yingkuan Liang ◽  
Te Zhang ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Lung Tumor ◽  
Lung Carcinogenesis ◽  
Microbial Composition ◽  
Lung Cancer Patients ◽  
Normal Tissues ◽  
Β Diversity ◽  
Tumor Tissues ◽  
Α Diversity ◽  
Significant Difference

Abstract Recent evidence demonstrates the existence of diversified microbiota in the lung. However, the effect of lung carcinogenesis on the flora in lung microenvironment has yet not been well investigated. In this study, we surveyed the microbial composition and diversity in lung tumor and paired adjacent normal tissues obtained from 55 lung cancer patients to test whether any specific tumor-associated microbial features in lung microenvironment can be identified. Compared with non-malignant adjacent tissues, the tumor samples showed significantly lower community richness (α diversity), but no significant difference in overall microbiome dissimilarity (β diversity). Strong intrasubject correlations were observed between tumor sample and its paired non-malignant adjacent tissues. In addition, correlation network analysis found more significant taxa–taxa correlations (adjusted q-value < 0.05) in tumor microenvironment than non-malignant adjacent tissues. At taxa level, we found Propionibacterium genus were significantly reduced in tumor tissues compared with non-malignant adjacent tissues. In summary, the microbiota in tumor tissues showed the lower richness, higher taxa–taxa interaction, and reduction of potential pro-inflammatory microbial genera compared with non-malignant tissues, suggesting the potential link between the tumor microbiota and the altered tumor microenvironment for the further investigation.

scholarly journals Comprehensive analysis of PD-L1 expression, tumor-infiltrating lymphocytes, and tumor microenvironment in LUAD: differences between Asians and Caucasians

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Fenglong Bie ◽  
He Tian ◽  
Nan Sun ◽  
Ruochuan Zang ◽  
Moyan Zhang ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Infiltrating Lymphocytes ◽  
The Cancer Genome Atlas ◽  
Normal Tissues ◽  
Asian Patients ◽  
Expression Of Genes ◽  
Tumor Tissues ◽  
Significant Difference ◽  
Cancer Genome Atlas ◽  
Infiltrating Lymphocytes

Abstract Backgrounds The characteristics of programmed cell death protein-1 (PD-L1) expression, tumor-infiltrating lymphocytes (TILs), and tumor microenvironment (TME) in lung adenocarcinoma (LUAD) patients are closely related to immunotherapy, and there are differences between Asians and Caucasians. Methods Acquire the transcriptome data of the Cancer Genome Atlas and Chinese LUAD patients. R software was used to analyze the differential expression of genes, prognosis, and gene function. Use CIBERSORT for TIL-related analysis and ESTIMATE for TME-related analysis. Results The expression of PD-L1 in tumor tissues of Caucasian LUAD patients was lower than that in normal tissues, while there was no significant difference in Asians. There was no statistical difference between PD-L1 expression and prognosis. The composition of TILs between Caucasian and Asian LUAD patients was quite different. There was no correlation between TILs and prognosis in Caucasians. However, the higher content of resting mast cells indicated a better prognosis in Asians. The Caucasian patients with higher immune and estimate scores had a better prognosis (p = 0.021, p = 0.025). However, the Asian patients with a higher estimate score had a worse prognosis (p = 0.024). The high expression of COL5A2 (p = 0.046, p = 0.027) and NOX4 (p = 0.020, p = 0.019) were both associated with the poor prognosis in Caucasians and Asians. Conclusion There are many differences in the characteristics of PD-L1 expression, TILs, and TME between Caucasian and Asian LUAD patients. This provides a certain hint for the selection of specific immunotherapy strategies separately for Caucasian and Asian LUAD patients.

scholarly journals Gut microbiome as a response marker for pancreatic enzyme replacement therapy in a porcine model of exocrine pancreas insufficiency

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Sabrina Ritz ◽  
Daniela Hahn ◽  
Haleluya T. Wami ◽  
Karin Tegelkamp ◽  
Ulrich Dobrindt ◽  
...  
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Gut Microbiome ◽  
Pancreatic Enzyme ◽  
Microbial Composition ◽  
Enzyme Replacement ◽  
Β Diversity ◽  
Healthy State ◽  
Α Diversity ◽  
Pancreatic Enzyme Replacement Therapy

Abstract Background Exocrine pancreatic insufficiency (EPI) is characterized by the loss of active pancreatic enzymes and a resulting severely reduced food digestion. EPI therapy requires orally applied pancreatic enzyme replacement. The gut microbiome is a known mediator of intestinal diseases and may influence the outcome of EPI and the effects of a pancreatic enzyme replacement therapy (PERT). Here, we analyzed the effects of EPI and PERT on the gut microbiome in the model of pancreatic duct ligated minipigs. Results The microbial community composition in pig feces was analyzed by next generation sequencing of 16S rRNA amplicons. The data were evaluated for α- and β-diversity changes and changes at the different Operational Taxonomic Unit (OTU) levels by Shannon–Wiener and inverse Simpson index calculation as well as by Principal Coordinates Analysis based on Bray–Curtis dissimilarity. Microbial α-diversity was reduced after EPI induction and reverted to nearly healthy state after PERT. Analysis of microbial composition and β-diversity showed distinctive clusters of the three study groups and a change towards a composition comparable to healthy animals upon PERT. The relative abundance of possible pathobionts like Escherichia/Shigella, Acinetobacter or Stenotrophomonas was reduced by PERT. Conclusion These data demonstrate that EPI-induced dysbiosis could be reverted by PERT to a nearly healthy state. Elevated α-diversity and the reduction of bacterial overgrowth after PERT promises benefits for EPI patients. Non-invasive microbiome studies may be useful for EPI therapy monitoring and as marker for response to PERT.

scholarly journals Capturing the Differences between Humoral Immunity in the Normal and Tumor Environments from Repertoire-Seq of B-Cell Receptors Using Supervised Machine Learning

2017 ◽  
Author(s):  
Hiroki Konishi ◽  
Daisuke Komura ◽  
Hiroto Katoh ◽  
Shinichiro Atsumi ◽  
Hirotomo Koda ◽  
...  
Keyword(s):  
Machine Learning ◽  
Tumor Microenvironment ◽  
B Cell ◽  
Supervised Machine Learning ◽  
B Cell Receptors ◽  
Rna Sequences ◽  
Cell Receptors ◽  
Tumor Microenvironments ◽  
Normal Tissues ◽  
Tumor Tissues

ABSTRACTThe recent success of immunotherapy in treating tumors has attracted increasing interest in research related to the adaptive immune system in the tumor microenvironment. Recent advances in next-generation sequencing technology enabled the sequencing of whole T-cell receptors (TCRs) and B-cell receptors (BCRs)/immunoglobulins (Igs) in the tumor microenvironment. Since BCRs/Igs in tumor tissues have high affinities for tumor-specific antigens, the patterns of their amino acid sequences and other sequence-independent features such as the number of somatic hypermutations (SHMs) may differ between the normal and tumor microenvironments. However, given the high diversity of BCRs/Igs and the rarity of recurrent sequences among individuals, it is far more difficult to capture such differences in BCR/Ig sequences than in TCR sequences. The aim of this study was to explore the possibility of discriminating BCRs/Igs in tumor and in normal tissues, by capturing these differences using supervised machine learning methods applied to RNA sequences of BCRs/Igs.RNA sequences of BCRs/Igs were obtained from matched normal and tumor specimens from 90 gastric cancer patients. BCR/Ig-features obtained in Rep-Seq were used to classify individual BCR/Ig sequences into normal or tumor classes. Different machine learning models using various features were constructed as well as gradient boosting machine (GBM) classifier combining these models. The results demonstrated that BCR/Ig sequences between normal and tumor microenvironments exhibit their differences. Next, by using a GBM trained to classify individual BCR/Ig sequences, we tried to classify sets of BCR/Ig sequences into normal or tumor classes. As a result, an area under the curve (AUC) value of 0.826 was achieved, suggesting that BCR/Ig repertoires have distinct sequence-level features in normal and tumor tissues.To the best of our knowledge, this is the first study to show that BCR/Ig sequences derived from tumor and normal tissues have globally distinct patterns, and that these tissues can be effectively differentiated using BCR/Ig repertoires.

scholarly journals Methyl DNA phosphate adduct formation in lung tumor tissue and adjacent normal tissue of lung cancer patients

2019 ◽  
Vol 40 (11) ◽  
pp. 1387-1394 ◽  
Author(s):  
Bin Ma ◽  
Peter W Villalta ◽  
J Bradley Hochalter ◽  
Irina Stepanov ◽  
Stephen S Hecht
Keyword(s):  
Lung Cancer ◽  
Dna Adducts ◽  
Human Lung ◽  
Lung Tumor ◽  
Normal Lung ◽  
Lung Cancer Patients ◽  
Normal Tissues ◽  
Phosphate Backbone ◽  
Limit Of Quantitation ◽  
Methylating Carcinogens

Abstract The formation of methyl DNA adducts is a critical step in carcinogenesis initiated by the exposure to methylating carcinogens. Methyl DNA phosphate adducts, formed by methylation of the oxygen atoms of the DNA phosphate backbone, have been detected in animals treated with methylating carcinogens. However, detection of these adducts in human tissues has not been reported. We developed an ultrasensitive liquid chromatography–nanoelectrospray ionization–high resolution tandem mass spectrometry method for detecting methyl DNA phosphate adducts. Using 50 μg of human lung DNA, a limit of quantitation of two adducts/1010 nucleobases was achieved. Twenty-two structurally unique methyl DNA phosphate adducts were detected in human lung DNA. The adduct levels were measured in both tumor and adjacent normal tissues from 30 patients with lung cancer, including 13 current smokers and 17 current non-smokers, as confirmed by measurements of urinary cotinine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol. Levels of total methyl DNA phosphate adducts in normal lung tissues were higher in smokers than non-smokers, with an average of 13 and 8 adducts/109 nucleobases, respectively. Methyl DNA phosphate adducts were also detected in lung tissues from untreated rats with steady-state levels of 5–7 adducts/109 nucleobases over a period of 70 weeks. This is the first study to report the detection of methyl DNA phosphate adducts in human lung tissues. The results provide new insights toward using these DNA adducts as potential biomarkers to study human exposure to environmental methylating carcinogens.

scholarly journals The Dynamics of Respiratory Microbiota during Mechanical Ventilation in Patients with Pneumonia

2020 ◽  
Vol 9 (3) ◽  
pp. 638 ◽  
Author(s):  
Seongji Woo ◽  
So-Yeong Park ◽  
Youngmi Kim ◽  
Jin Pyeong Jeon ◽  
Jae Jun Lee ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Intensive Care ◽  
Clinical Outcomes ◽  
Extubation Failure ◽  
Shannon Index ◽  
Β Diversity ◽  
Α Diversity ◽  
Significant Difference ◽  
Respiratory Microbiome ◽  
Successful Extubation

Bacterial pneumonia is a major cause of mechanical ventilation in intensive care units. We hypothesized that the presence of particular microbiota in endotracheal tube aspirates during the course of intubation was associated with clinical outcomes such as extubation failure or 28-day mortality. Sixty mechanically ventilated ICU (intensive care unit) patients (41 patients with pneumonia and 19 patients without pneumonia) were included, and tracheal aspirates were obtained on days 1, 3, and 7. Gene sequencing of 16S rRNA was used to measure the composition of the respiratory microbiome. A total of 216 endotracheal aspirates were obtained from 60 patients. A total of 22 patients were successfully extubatedwithin3 weeks, and 12 patients died within 28days. Microbiota profiles differed significantly between the pneumonia group and the non-pneumonia group (Adonis, p < 0.01). While α diversity (Shannon index) significantly decreased between day 1 and day 7 in the successful extubation group, it did not decrease in the failed extubation group among intubated patients with pneumonia. There was a significant difference in the change of βdiversity between the successful extubation group and the failed extubation group for Bray-Curtis distances (p < 0.001). At the genus level, Rothia, Streptococcus, and Prevotella correlated with the change of β diversity. A low relative abundance of Streptococci at the time of intubation was strongly associated with 28-day mortality. The dynamics of respiratory microbiome were associated with clinical outcomes such as extubation failure and mortality. Further large prospective studies are needed to test the predictive value of endotracheal aspirates in intubated patients.

scholarly journals Soil Bacterial and Fungal Composition and Diversity Responses to Seasonal Deer Grazing in a Subalpine Meadow

Diversity ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 84
Author(s):  
Andéole Niyongabo Turatsinze ◽  
Baotian Kang ◽  
Tianqi Zhu ◽  
Fujiang Hou ◽  
Saman Bowatte
Keyword(s):  
Relative Abundance ◽  
Soil Microbial Communities ◽  
Gansu Province ◽  
Total Carbon ◽  
Mountain Range ◽  
Microbial Composition ◽  
Soil Microbial ◽  
Β Diversity ◽  
Α Diversity ◽  
Soil Bacterial

Soil microbial composition and diversity are widely recognized for their role in ecological functioning. This study examined the differences of soil microbial communities between two seasonally grazed grasslands. The study area was in the Gansu red deer farm located on the Qilian Mountain range in the Gansu province of northwestern China. This farm adopted a seasonal rotation grazing system whereby grasslands at higher altitudes are grazed in summer (SG), whilst grasslands at lower altitudes are grazed in winter (WG). The soil bacterial and fungal communities were examined by Illumina MiSeq sequencing. We found that soil water content (SWC), organic carbon (OC), total carbon (TC), and total nitrogen (TN) were significantly higher, whereas the C/N ratio was significantly lower in SG than WG pastures. The α-diversity of bacteria was greater than that of fungi in both pastures, while both bacterial and fungal α-diversity were not significantly different between the pastures. The bacterial β-diversity was significantly different between the pastures, but fungal β-diversity was not. The bacterial phylum Actinobacteria and fungal phylum Ascomycota were dominant in both pastures. The relative abundance of Actinobacteria in soil was significantly higher in WG pastures, whereas the relative abundance of Proteobacteria in soil was significantly higher in SG pastures. Significant correlations between bacterial and fungal phyla and soil properties were observed, but this varied between the two grasslands. This study showed that distinct microbial community structures developed in two pastures within the same geographic location that were grazed in different seasons.

scholarly journals The Influence of Maternal Unhealthy Diet On Maturation of Offspring Gut Microbiota in Rat

2021 ◽  
Author(s):  
Kyoko Hasebe ◽  
Michael D Kendig ◽  
Nadeem O Kaakoush ◽  
Aynaz Tajaddini ◽  
R Frederick Westbrook ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Maternal Diet ◽  
Female Offspring ◽  
Developmental Trajectory ◽  
The Other ◽  
Interactive Effects ◽  
Female Rats ◽  
Microbial Composition ◽  
Β Diversity ◽  
Α Diversity

Abstract Background: Despite well-known effects of diet on gut microbiota diversity, relatively little is known about how maternal diet quality shapes the longitudinal maturation of gut microbiota in offspring. To investigate, we fed female rats standard chow (Chow) or a western-style, high-choice cafeteria diet (Caf) prior to and during mating, gestation and lactation. At weaning (3 weeks), male and female offspring were either maintained on their mother’s diet (ChowChow, CafCaf groups) or switched to the other diet (ChowCaf, CafChow). Fecal microbial composition was assessed in dams and longitudinally in offspring at 3, 7 and 14 weeks of age.Results: The effect of maternal diet on maturation of offspring gut microbiota was assessed by α- and β-diversities, Deseq2/LEfSe, and SourceTracker analyses. Weanling gut microbiota composition was characterised by reduced α- and β-diversity profiles that clustered away from dams and older siblings. After weaning, offspring gut microbiota came to resemble an adult-like gut microbiota, with increased α-diversity and reduced dissimilarity of β-diversity. Similarly, Deseq2/LEfSe analyses found fewer numbers of altered operational taxonomic units (OTUs) between groups from weaning to adulthood. SourceTracker analyses indicated a greater overall contribution of Caf mothers’ microbial community (up to 20%) to that of their offspring than the contribution of Chow mothers (up to 8%). Groups maintained on the maternal diet (ChowChow, CafCaf), versus those switched to the other diet (ChowCaf, CafChow) post-weaning significantly differed from each other at 14 weeks (Permutational Multivariate Analysis of Variance), indicating interactive effects of maternal and post-weaning diet on offspring gut microbiota maturation. Nevertheless, this developmental trajectory was unaffected by sex and appeared consistent between ChowChow, CafCaf, ChowCaf and CafChow groups. Conclusions: Introducing solid food at weaning triggered the maturation of offspring gut microbiota to an adult-like profile in rats, in line with previous human studies. Postweaning Caf diet exposure had the largest impact on offspring gut microbiome, but this was modulated by maternal diet history. An unhealthy maternal Caf diet did not alter the developmental trajectory of offspring gut microbiota towards an adult-like profile, insofar as it did not prevent the age-associated increase in α-diversity and reduction in β-diversity dissimilarity.

scholarly journals The Gut Microbiome of Heart Failure With Preserved Ejection Fraction

2021 ◽  
Author(s):  
Anna L. Beale ◽  
Joanne A. O’Donnell ◽  
Michael E. Nakai ◽  
Shane Nanayakkara ◽  
Donna Vizi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Short Chain ◽  
Preserved Ejection Fraction ◽  
Β Diversity ◽  
Α Diversity ◽  
Significant Difference

Background Risk factors for heart failure with preserved ejection fraction (HFpEF) include hypertension, age, sex, and obesity. Emerging evidence suggests that the gut microbiota independently contributes to each one of these risk factors, potentially mediated via gut microbial‐derived metabolites such as short‐chain fatty acids. In this study, we determined whether the gut microbiota were associated with HFpEF and its risk factors. Methods and Results We recruited 26 patients with HFpEF and 67 control participants from 2 independent communities. Patients with HFpEF were diagnosed by exercise right heart catheterization. We assessed the gut microbiome by bacterial 16S rRNA sequencing and food intake by the food frequency questionnaire. There was a significant difference in α‐diversity (eg, number of microbes) and β‐diversity (eg, type and abundance of microbes) between both cohorts of controls and patients with HFpEF ( P =0.001). We did not find an association between β‐diversity and specific demographic or hemodynamic parameters or risk factors for HFpEF. The Firmicutes to Bacteroidetes ratio, a commonly used marker of gut dysbiosis, was lower, but not significantly so ( P =0.093), in the patients with HFpEF. Compared with controls, the gut microbiome of patients with HFpEF was depleted of bacteria that are short‐chain fatty acid producers. Consistent with this, participants with HFpEF consumed less dietary fiber (17.6±7.7 versus 23.2±8.8 g/day; P =0.016). Conclusions We demonstrate key changes in the gut microbiota in patients with HFpEF, including the depletion of bacteria that generate metabolites known to be important for cardiovascular homeostasis. Further studies are required to validate the role of these gut microbiota and metabolites in the pathophysiology of HFpEF.

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