Effect of Antibiotic-induced Intestinal Dysbacteriosis on Bronchopulmonary Dysplasia and Related Mechanisms

Abstract BackgroundThe modification of the gut microbiota by antibiotics may influence the disease susceptibility and immunological responses. Infants in the neonatal intensive care unit (NICU) subjected to frequent antibiotics and oxygen therapies, which may give rise to the local and systemic inflammatory reactions and progression of bronchopulmonary dysplasia (BPD). This study aimed to investigate the role of intestinal dysbacteriosis by antibiotic therapy before hyperoxia exposure in the progression of BPD.MethodsMice had been exposed to hyperoxia (85% O2) since postnatal day 3 until day 16 for the BPD model establishment, treated with antibiotics from postnatal day 2 until day 8. Treated mice and appropriate controls were harvested on postnatal day 10 for 16S rRNA gene sequencing, or postnatal day 17 for assessment of alveolar morphometry and macrophages differentiation.ResultsAntibiotic-induced intestinal dysbacteriosis before hyperoxia exposure gave rise to deterioration of BPD evidenced by reduced survival rates and alveolarization, moreover, antibiotic-induced intestinal dysbacteriosis resulted in increased iNOS and decreased Arg-1 levels in lung homogenates.ConclusionBroad-spectrum antibiotic-induced intestinal dysbacteriosis may participate in BPD pathogenesis via alteration of the macrophage polarization status. Manipulating the gut microbiota may potentially intervene the therapy of BPD.

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Effect of antibiotic-induced intestinal dysbacteriosis on bronchopulmonary dysplasia and related mechanisms

Journal of Translational Medicine ◽

10.1186/s12967-021-02794-6 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Xiao Ran ◽

Yu He ◽

Qing Ai ◽

Yuan Shi

Keyword(s):

Gut Microbiota ◽

Bronchopulmonary Dysplasia ◽

Macrophage Polarization ◽

Survival Rates ◽

Rrna Gene ◽

M2 Macrophage ◽

Inflammatory Reactions ◽

M1 Macrophage ◽

Hyperoxia Exposure ◽

Intestinal Dysbacteriosis

Abstract Background Modification of the gut microbiota by antibiotics may influence the disease susceptibility and immunological responses. Infants in the neonatal intensive care unit (NICU) subjected to frequent antibiotics and oxygen therapies, which may give rise to local and systemic inflammatory reactions and progression of bronchopulmonary dysplasia (BPD). This study aimed to investigate the role of intestinal dysbacteriosis by antibiotic therapy before hyperoxia exposure in the progression of BPD. Methods Mice had been exposed to hyperoxia (85% O2) since postnatal day 3 until day 16 for the BPD model establishment, treated with antibiotics from postnatal day 2 until day 8. Treated mice and appropriate controls were harvested on postnatal day 2 or 10 for 16S rRNA gene sequencing, or postnatal day 17 for assessment of alveolar morphometry and macrophages differentiation. Results Antibiotic-induced intestinal dysbacteriosis before hyperoxia exposure gave rise to deterioration of BPD evidenced by reduced survival rates and alveolarization. Moreover, antibiotic-induced intestinal dysbacteriosis resulted in increased M1 macrophage maker (iNOS) and decreased M2 macrophage maker (Arg-1) levels in lung homogenates. Conclusion Broad-spectrum antibiotic-induced intestinal dysbacteriosis may participate in BPD pathogenesis via alteration of the macrophage polarization status. Manipulating the gut microbiota may potentially intervene the therapy of BPD.

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Neonatal intensive care unit (NICU) exposures exert a sustained influence on the progression of gut microbiota and metabolome in the first year of life

Scientific Reports ◽

10.1038/s41598-020-80278-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Polly Soo Xi Yap ◽

Chun Wie Chong ◽

Azanna Ahmad Kamar ◽

Ivan Kok Seng Yap ◽

Yao Mun Choo ◽

...

Keyword(s):

Gut Microbiota ◽

Preterm Infants ◽

Neonatal Intensive Care ◽

Early Time ◽

16S Rrna Gene Sequencing ◽

Resonance Spectroscopy ◽

Rrna Gene ◽

Microbial Composition ◽

Term Infants ◽

Rrna Gene Sequencing

AbstractEmerging evidence has shown a link between the perturbations and development of the gut microbiota in infants with their immediate and long-term health. To better understand the assembly of the gut microbiota in preterm infants, faecal samples were longitudinally collected from the preterm (n = 19) and term (n = 20) infants from birth until month 12. 16S rRNA gene sequencing (n = 141) and metabolomics profiling (n = 141) using nuclear magnetic resonance spectroscopy identified significant differences between groups in various time points. A panel of amino acid metabolites and central metabolism intermediates significantly correlated with the relative abundances of 8 species of bacteria were identified in the preterm group. In contrast, faecal metabolites of term infants had significantly higher levels of metabolites which are commonly found in milk such as fucose and β-hydroxybutyrate. We demonstrated that the early-life factors such as gestational age, birth weight and NICU exposures, exerted a sustained effect to the dynamics of gut microbial composition and metabolism of the neonates up to one year of age. Thus, our findings suggest that intervention at this early time could provide ‘metabolic rescue’ to preterm infants from aberrant initial gut microbial colonisation and succession.

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Changes in the Composition of the Gut Microbiota and the Blood Transcriptome in Preterm Infants at Less than 29 Weeks Gestation Diagnosed with Bronchopulmonary Dysplasia

mSystems ◽

10.1128/msystems.00484-19 ◽

2019 ◽

Vol 4 (5) ◽

Cited By ~ 5

Author(s):

Feargal J. Ryan ◽

Damian P. Drew ◽

Chloe Douglas ◽

Lex E. X. Leong ◽

Max Moldovan ◽

...

Keyword(s):

Gene Expression ◽

Gut Microbiota ◽

Preterm Infants ◽

Bronchopulmonary Dysplasia ◽

Gene Sequencing ◽

16S Rrna Gene Sequencing ◽

Rrna Gene ◽

Immune Gene ◽

Immune Gene Expression ◽

Rrna Gene Sequencing

ABSTRACT Bronchopulmonary dysplasia (BPD) is a common chronic lung condition in preterm infants that results in abnormal lung development and leads to considerable morbidity and mortality, making BPD one of the most common complications of preterm birth. We employed RNA sequencing and 16S rRNA gene sequencing to profile gene expression in blood and the composition of the fecal microbiota in infants born at <29 weeks gestational age and diagnosed with BPD in comparison to those of preterm infants that were not diagnosed with BPD. 16S rRNA gene sequencing, performed longitudinally on 255 fecal samples collected from 50 infants in the first months of life, identified significant differences in the relative levels of abundance of Klebsiella, Salmonella, Escherichia/Shigella, and Bifidobacterium in the BPD infants in a manner that was birth mode dependent. Transcriptome sequencing (RNA-Seq) analysis revealed that more than 400 genes were upregulated in infants with BPD. Genes upregulated in BPD infants were significantly enriched for functions related to red blood cell development and oxygen transport, while several immune-related pathways were downregulated. We also identified a gene expression signature consistent with an enrichment of immunosuppressive CD71+ early erythroid cells in infants with BPD. Intriguingly, genes that were correlated in their expression with the relative abundances of specific taxa in the microbiota were significantly enriched for roles in the immune system, suggesting that changes in the microbiota might influence immune gene expression systemically. IMPORTANCE Bronchopulmonary dysplasia (BPD) is a serious inflammatory condition of the lung and is the most common complication associated with preterm birth. A large body of evidence now suggests that the gut microbiota can influence immunity and inflammation systemically; however, the role of the gut microbiota in BPD has not been evaluated to date. Here, we report that there are significant differences in the gut microbiota of infants born at <29 weeks gestation and subsequently diagnosed with BPD, which are particularly pronounced when infants are stratified by birth mode. We also show that erythroid and immune gene expression levels are significantly altered in BPD infants. Interestingly, we identified an association between the composition of the microbiota and immune gene expression in blood in early life. Together, these findings suggest that the composition of the microbiota may influence the risk of developing BPD and, more generally, may shape systemic immune gene expression.

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Diversity, Composition and Functional Inference of Gut Microbiota in Indian Cabbage white Pieris canidia (Lepidoptera: Pieridae)

Life ◽

10.3390/life10110254 ◽

2020 ◽

Vol 10 (11) ◽

pp. 254

Author(s):

Ying Wang ◽

Jianqing Zhu ◽

Jie Fang ◽

Li Shen ◽

Shuojia Ma ◽

...

Keyword(s):

Gut Microbiota ◽

16S Rrna Gene Sequencing ◽

Adult Survival ◽

Rrna Gene ◽

Life Stages ◽

Microbial Composition ◽

Significant Difference ◽

Functional Inference ◽

Rrna Gene Sequencing ◽

Insect Fitness

We characterized the gut microbial composition and relative abundance of gut bacteria in the larvae and adults of Pieris canidia by 16S rRNA gene sequencing. The gut microbiota structure was similar across the life stages and sexes. The comparative functional analysis on P. canidia bacterial communities with PICRUSt showed the enrichment of several pathways including those for energy metabolism, immune system, digestive system, xenobiotics biodegradation, transport, cell growth and death. The parameters often used as a proxy of insect fitness (development time, pupation rate, emergence rate, adult survival rate and weight of 5th instars larvae) showed a significant difference between treatment group and untreated group and point to potential fitness advantages with the gut microbiomes in P. canidia. These data provide an overall view of the bacterial community across the life stages and sexes in P. canidia.

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Gut microbiota markers associated with obesity and overweight in Italian adults

Scientific Reports ◽

10.1038/s41598-021-84928-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Vanessa Palmas ◽

Silvia Pisanu ◽

Veronica Madau ◽

Emanuela Casula ◽

Andrea Deledda ◽

...

Keyword(s):

Gut Microbiota ◽

Relative Abundance ◽

Smoking Status ◽

16S Rrna Gene Sequencing ◽

Normal Weight ◽

Activity Level ◽

Rrna Gene ◽

Illumina Platform ◽

Obesity And Overweight ◽

Rrna Gene Sequencing

AbstractIn the present study, we characterized the distinctive signatures of the gut microbiota (GM) from overweight/obese patients (OB), and normal-weight controls (NW), both of Sardinian origin. Fecal bacterial composition of 46 OB patients (BMI = 36.6 ± 6.0; F/M = 40/6) was analyzed and compared to that of 46 NW subjects (BMI = 21.6 ± 2.1; F/M = 41/5), matched for sex, age and smoking status, by using 16S rRNA gene sequencing on MiSeq Illumina platform. The gut microbial community of OB patients exhibited a significant decrease in the relative abundance of several Bacteroidetes taxa (i.e. Flavobacteriaceae, Porphyromonadaceae, Sphingobacteriaceae, Flavobacterium, Rikenella spp., Pedobacter spp., Parabacteroides spp., Bacteroides spp.) when compared to NW; instead, several Firmicutes taxa were significantly increased in the same subjects (Lachnospiraceae, Gemellaceae, Paenibacillaceae, Streptococcaceae, Thermicanaceae, Gemella, Mitsuokella, Streptococcus, Acidaminococcus spp., Eubacterium spp., Ruminococcus spp., Megamonas spp., Streptococcus, Thermicanus, Megasphaera spp. and Veillonella spp.). Correlation analysis indicated that body fatness and waist circumference negatively correlated with Bacteroidetes taxa, while Firmicutes taxa positively correlated with body fat and negatively with muscle mass and/or physical activity level. Furthermore, the relative abundance of several bacterial taxa belonging to Enterobacteriaceae family, known to exhibit endotoxic activity, was increased in the OB group compared to NW. The results extend our knowledge on the GM profiles in Italian OB, identifying novel taxa linking obesity and intestine.

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Gut microbiota accelerates cisplatin-induced acute liver injury associated with robust inflammation and oxidative stress in mice

Journal of Translational Medicine ◽

10.1186/s12967-021-02814-5 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Shenhai Gong ◽

Yinglin Feng ◽

Yunong Zeng ◽

Huanrui Zhang ◽

Meiping Pan ◽

...

Keyword(s):

Oxidative Stress ◽

16S Rrna ◽

Gut Microbiota ◽

Gene Sequencing ◽

16S Rrna Gene Sequencing ◽

Rrna Gene ◽

Metabolomic Analysis ◽

Rrna Gene Sequencing ◽

And Oxidative Stress

Abstract Background Gut microbiota has been reported to be disrupted by cisplatin, as well as to modulate chemotherapy toxicity. However, the precise role of intestinal microbiota in the pathogenesis of cisplatin hepatotoxicity remains unknown. Methods We compared the composition and function of gut microbiota between mice treated with and without cisplatin using 16S rRNA gene sequencing and via metabolomic analysis. For understanding the causative relationship between gut dysbiosis and cisplatin hepatotoxicity, antibiotics were administered to deplete gut microbiota and faecal microbiota transplantation (FMT) was performed before cisplatin treatment. Results 16S rRNA gene sequencing and metabolomic analysis showed that cisplatin administration caused gut microbiota dysbiosis in mice. Gut microbiota ablation by antibiotic exposure protected against the hepatotoxicity induced by cisplatin. Interestingly, mice treated with antibiotics dampened the mitogen-activated protein kinase pathway activation and promoted nuclear factor erythroid 2-related factor 2 nuclear translocation, resulting in decreased levels of both inflammation and oxidative stress in the liver. FMT also confirmed the role of microbiota in individual susceptibility to cisplatin-induced hepatotoxicity. Conclusions This study elucidated the mechanism by which gut microbiota mediates cisplatin hepatotoxicity through enhanced inflammatory response and oxidative stress. This knowledge may help develop novel therapeutic approaches that involve targeting the composition and metabolites of microbiota.

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Comparison between 16S rRNA and shotgun sequencing data for the taxonomic characterization of the gut microbiota

Scientific Reports ◽

10.1038/s41598-021-82726-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Francesco Durazzi ◽

Claudia Sala ◽

Gastone Castellani ◽

Gerardo Manfreda ◽

Daniel Remondini ◽

...

Keyword(s):

16S Rrna ◽

Gut Microbiota ◽

16S Rrna Gene ◽

Gene Sequencing ◽

16S Rrna Gene Sequencing ◽

Shotgun Sequencing ◽

Rrna Gene ◽

Metagenomic Sequencing ◽

Experimental Conditions ◽

Rrna Gene Sequencing

AbstractIn this paper we compared taxonomic results obtained by metataxonomics (16S rRNA gene sequencing) and metagenomics (whole shotgun metagenomic sequencing) to investigate their reliability for bacteria profiling, studying the chicken gut as a model system. The experimental conditions included two compartments of gastrointestinal tracts and two sampling times. We compared the relative abundance distributions obtained with the two sequencing strategies and then tested their capability to distinguish the experimental conditions. The results showed that 16S rRNA gene sequencing detects only part of the gut microbiota community revealed by shotgun sequencing. Specifically, when a sufficient number of reads is available, Shotgun sequencing has more power to identify less abundant taxa than 16S sequencing. Finally, we showed that the less abundant genera detected only by shotgun sequencing are biologically meaningful, being able to discriminate between the experimental conditions as much as the more abundant genera detected by both sequencing strategies.

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Infant Gut Microbiota Associated with Fine Motor Skills

Nutrients ◽

10.3390/nu13051673 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1673

Author(s):

Inmaculada Acuña ◽

Tomás Cerdó ◽

Alicia Ruiz ◽

Francisco J. Torres-Espínola ◽

Ana López-Moreno ◽

...

Keyword(s):

Gut Microbiota ◽

Infant Development ◽

16S Rrna Gene Sequencing ◽

Fine Motor ◽

Rrna Gene ◽

Neurodevelopmental Outcomes ◽

Gut Colonization ◽

Healthy Infants ◽

Behavioural Characteristics ◽

Rrna Gene Sequencing

BACKGROUND: During early life, dynamic gut colonization and brain development co-occur with potential cross-talk mechanisms affecting behaviour. METHODS: We used 16S rRNA gene sequencing to examine the associations between gut microbiota and neurodevelopmental outcomes assessed by the Bayley Scales of Infant Development III in 71 full-term healthy infants at 18 months of age. We hypothesized that children would differ in gut microbial diversity, enterotypes obtained by Dirichlet multinomial mixture analysis and specific taxa based on their behavioural characteristics. RESULTS: In children dichotomized by behavioural trait performance in above- and below-median groups, weighted Unifrac b-diversity exhibited significant differences in fine motor (FM) activity. Dirichlet multinomial mixture modelling identified two enterotypes strongly associated with FM outcomes. When controlling for maternal pre-gestational BMI and breastfeeding for up to 3 months, the examination of signature taxa in FM groups showed that Turicibacter and Parabacteroides were highly abundant in the below-median FM group, while Collinsella, Coprococcus, Enterococcus, Fusobacterium, Holdemanella, Propionibacterium, Roseburia, Veillonella, an unassigned genus within Veillonellaceae and, interestingly, probiotic Bifidobacterium and Lactobacillus were more abundant in the above-median FM group. CONCLUSIONS: Our results suggest an association between enterotypes and specific genera with FM activity and may represent an opportunity for probiotic interventions relevant to treatment for motor disorders.

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Effects of Psychotropics on the Microbiome in Patients With Depression and Anxiety: Considerations in a Naturalistic Clinical Setting

The International Journal of Neuropsychopharmacology ◽

10.1093/ijnp/pyaa070 ◽

2020 ◽

Author(s):

Yoshihiro Tomizawa ◽

Shunya Kurokawa ◽

Daiki Ishii ◽

Katsuma Miyaho ◽

Chiharu Ishii ◽

...

Keyword(s):

Gut Microbiota ◽

Microbial Diversity ◽

Depressive Disorders ◽

Alpha Diversity ◽

16S Rrna Gene Sequencing ◽

Shannon Index ◽

Rrna Gene ◽

Depression And Anxiety ◽

The Impact ◽

Whole Tree

Abstract Background The antibacterial effects of psychotropics may be part of their pharmacological effects when treating depression. However, limited studies have focused on gut microbiota in relation to prescribed medication. Method We longitudinally investigated the relationship between patients’ prescribed medications and intestinal bacterial diversity in a naturalistic treatment course for patients with major depressive disorders and anxiety disorders. Patients were recruited and their stool was collected at 3 time points during their usual psychiatric treatments. Gut microbiota were analyzed using 16S rRNA gene sequencing. We examined the impact of psychotropics (i.e., antidepressants, anxiolytics, antipsychotics) on their gut microbial diversity and functions. Results We collected 246 stool samples from 40 patients. Despite no differences in microbial diversity between medication groups at the baseline, over the course of treatment, phylogenic diversity whole-tree diversity decreased in patients on antipsychotics compared with patients without (P = .027), and beta diversity followed this trend. Based on a fixed-effect model, antipsychotics predicted microbial diversity; the higher doses correlated with less diversity based on the Shannon index and phylogenic diversity whole tree (estimate = −0.00254, SE = 0.000595, P < .0001; estimate = −0.02644, SE = 0.00833, P = .002, respectively). Conclusion Antipsychotics may play a role in decreasing the alpha diversity of the gut microbiome among patients with depression and anxiety, and our results indicate a relationship with medication dosage. Future studies are warranted and should consider patients’ types and doses of antipsychotics in order to further elucidate the mechanisms of gut-brain interactions in psychiatric disorders.

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The Effects of Genetic Relatedness on the Preterm Infant Gut Microbiota

Microorganisms ◽

10.3390/microorganisms9020278 ◽

2021 ◽

Vol 9 (2) ◽

pp. 278

Author(s):

Shen Jean Lim ◽

Miriam Aguilar-Lopez ◽

Christine Wetzel ◽

Samia V. O. Dutra ◽

Vanessa Bray ◽

...

Keyword(s):

Gut Microbiota ◽

Preterm Infant ◽

Neonatal Intensive Care ◽

Genetic Relatedness ◽

Bovine Milk ◽

Alpha Diversity ◽

Neonatal Intensive Care Units ◽

Rrna Gene ◽

Microbial Composition ◽

Operational Taxonomic Units

The preterm infant gut microbiota is influenced by environmental, endogenous, maternal, and genetic factors. Although siblings share similar gut microbial composition, it is not known how genetic relatedness affects alpha diversity and specific taxa abundances in preterm infants. We analyzed the 16S rRNA gene content of stool samples, ≤ and >3 weeks postnatal age, and clinical data from preterm multiplets and singletons at two Neonatal Intensive Care Units (NICUs), Tampa General Hospital (TGH; FL, USA) and Carle Hospital (IL, USA). Weeks on bovine milk-based fortifier (BMF) and weight gain velocity were significant predictors of alpha diversity. Alpha diversity between siblings were significantly correlated, particularly at ≤3 weeks postnatal age and in the TGH NICU, after controlling for clinical factors. Siblings shared higher gut microbial composition similarity compared to unrelated individuals. After residualizing against clinical covariates, 30 common operational taxonomic units were correlated between siblings across time points. These belonged to the bacterial classes Actinobacteria, Bacilli, Bacteroidia, Clostridia, Erysipelotrichia, and Negativicutes. Besides the influence of BMF and weight variables on the gut microbial diversity, our study identified gut microbial similarities between siblings that suggest genetic or shared maternal and environmental effects on the preterm infant gut microbiota.

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