scholarly journals P673 Microbial diversity in newly diagnosed treatment naïve Inflammatory Bowel Disease patients

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S594-S595
Author(s):  
S Ellul ◽  
P Rausch ◽  
A Pisani ◽  
C Bang ◽  
P Ellul ◽  
...  
Keyword(s):  
Species Richness ◽  
Beta Diversity ◽  
Pathogenic Bacteria ◽  
Bacterial Species ◽  
Alpha Diversity ◽  
Rrna Gene ◽  
Healthy Controls ◽  
Newly Diagnosed ◽  
Treatment Naïve ◽  
Stool Samples

Abstract Background The role of microbiome with the alteration between commensal and pathogenic bacteria, has been linked to IBD. Meanwhile Escherichia coli Nissle 1917, Lactobacillus rhamnosus GG (LGG) and faecal transplantation are used in IBD. The aim of this study was to prospectively determine faecal microbiota composition of newly diagnosed treatment naïve IBD patients. Methods Patients diagnosed with IBD between January 2018-September 2019 were recruited. Clinical data was collected and patients asked to submit stool samples for microbiome analysis. Stool samples from a control population were recruited and analysed via the bacterial 16s rRNA gene sequencing on illumine MiSeq. Results 100 IBD patients (CD: n=46, UC: n=53 & IBDU: n=1) and 97 controls with specific inclusion and exclusion criteria collected. IBD patients were noted to display reduced average species richness and community evenness compared to healthy controls (Alpha- Diversity) (Figure 1). Beta-diversity between microbial communities of healthy individuals and IBD patients was significantly different, but no observed separation between the two types of IBD was noted (Figure 2). 11 ASVs were abundant in CD patients including: ASV-70 – Lactobacillus gasseri, Klebsiella uncl., Candidatus-saccharibacteria, ASV-157 - Acteroides clarus and ASV 249- Parasutterella uncl. In UC cohort, 10 ASVs were abundant including: ASV 6-Escherichia/Shigella uncl., ASB-41-Sutterella wadsworthensis, ASV 44- Bacteroides faecis and Actinobacteria. An association between UC and ASV 313 (Faecalibacteria) was present. In the microbiome of healthy controls, 20 ASVs were abundant, including: ASV-14 G-Alistipes uncl., ASV 20-(Akkermansia muciniphila),(bacterium belonging to the phylum Verrucomicrobia), ASV 321 (Clostridia uncl.), ASV 96 (Rumminococcaceae uncl.), Alistepes uncl. (ASV 61), Subdoligranulum uncl. (ASV 453) and the unclassifiable bacteria. A higher amount of Verrucomicrobia was present in the healthy group as opposed to the IBD. Conclusion ASV 249- Parasutterella unlc., was indicative of CD associated microbiome through the indicator species analysis. Typical microbiome changes in IBD patients include increased abundance of the pro-inflammatory species with a reduction in anti-inflammatory bacterial species, with a noticeable reduction in alpha and beta diversity. In the local cohort, a particular change in the local α- and β diversity was noted to be present between healthy controls and IBD cohort. This could be a potential way in which targeted therapeutic approaches using specific dosage and durations of probiotic or faecal transplant can be used to alter faecal microbiome using specific bacteria present in healthy controls and with elimination of potentially harmful bacteria in IBD patients. Figure 1: Alpha diversity between different Groups using Chao1 species richness and Simpson 1-D Figure 2: Beta diversity between different groups using Bray-Curtis dissimilarity, Jaccard distance.

Alterations of gut microbiome in autoimmune hepatitis

Gut ◽  
2019 ◽  
Vol 69 (3) ◽  
pp. 569-577 ◽  
Author(s):  
Yiran Wei ◽  
Yanmei Li ◽  
Li Yan ◽  
Chunyan Sun ◽  
Qi Miao ◽  
...  
Keyword(s):  
Autoimmune Hepatitis ◽  
Gut Microbiome ◽  
Alpha Diversity ◽  
Disease Status ◽  
16S Rrna Gene Sequencing ◽  
Rrna Gene ◽  
Healthy Controls ◽  
Microbial Composition ◽  
Cross Sectional ◽  
Treatment Naïve

ObjectiveThe significance of the liver-microbiome axis has been increasingly recognised as a major modulator of autoimmunity. The aim of this study was to take advantage of a large well-defined corticosteroids treatment-naïve group of patients with autoimmune hepatitis (AIH) to rigorously characterise gut dysbiosis compared with healthy controls.DesignWe performed a cross-sectional study of individuals with AIH (n=91) and matched healthy controls (n=98) by 16S rRNA gene sequencing. An independent cohort of 28 patients and 34 controls was analysed to validate the results. All the patients were collected before corticosteroids therapy.ResultsThe gut microbiome of steroid treatment-naïve AIH was characterised with lower alpha-diversity (Shannon and observed operational taxonomic units, both p<0.01) and distinct overall microbial composition compared with healthy controls (p=0.002). Depletion of obligate anaerobes and expansion of potential pathobionts including Veillonella were associated with disease status. Of note, Veillonella dispar, the most strongly disease-associated taxa (p=8.85E–8), positively correlated with serum level of aspartate aminotransferase and liver inflammation. Furthermore, the combination of four patients with AIH-associated genera distinguished AIH from controls with an area under curves of approximately 0.8 in both exploration and validation cohorts. In addition, multiple predicted functional modules were altered in the AIH gut microbiome, including lipopolysaccharide biosynthesis as well as metabolism of amino acids that can be processed by bacteria to produce immunomodulatory metabolites.ConclusionOur study establishes compositional and functional alterations of gut microbiome in AIH and suggests the potential for using gut microbiota as non-invasive biomarkers to assess disease activity.

scholarly journals Comparative analysis of cutaneous bacterial communities of farmed Rana dybowskii after gentamycin bath

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8430
Author(s):  
Jia Bie ◽  
Qing Tong ◽  
Xiaoning Liu ◽  
Xianhao Zhang ◽  
Hongbin Wang
Keyword(s):  
Bacterial Community ◽  
Beta Diversity ◽  
Pathogenic Bacteria ◽  
High Throughput Sequencing ◽  
Recovery Period ◽  
Alpha Diversity ◽  
Community Diversity ◽  
Control Group ◽  
Rrna Gene ◽  
Rana Dybowskii

Introduction Pathogenic bacteria limit the success of Rana dybowskii breeding. Gentamicin is used to treat R. dybowskii disease. To understand the effects of gentamicin on the composition and structure of the cutaneous bacterial community of R. dybowskii, three groups (control, gentamicin and recovery) were established in this study. Materials & Methods The V3–V4 hypervariable region of the 16S rRNA gene was analyzed in samples by high-throughput sequencing. Alpha diversity and beta diversity were evaluated to compare the cutaneous bacterial community diversity. Results A total of 1,159,668 valid sequences and 3,132 operational taxonomic units (OTUs) were obtained from these three experimental groups. The number of OTUs obtained in the control group, gentamicin group and recovery group were 2,194, 2,288, and 2,047, respectively, and the number of shared OTUs was 1,313. The alpha diversity of the cutaneous bacterial community was not significantly affected by gentamicin, while beta diversity was significantly affected. Discussion & Conclusions The effect of a gentamicin bath on relative species abundance was greater than the effect on the species composition. The changes in Proteobacteria, Acinetobacter, and Chryseobacterium were significant, and reductions were observed after the recovery period. Six potentially pathogenic genera were detected, including Aeromonas, Citrobacter, Chryseobacterium, Pseudomonas, Staphylococcus, and Streptococcus. Among them, Aeromonas and Chryseobacterium were significantly inhibited by the gentamicin bath. The results of this study provide a theoretical basis for the application of gentamicin in R. dybowskii breeding.

scholarly journals Gut microbial differences in breast and prostate cancer cases from two randomised controlled trials compared to matched cancer-free controls

2021 ◽  
pp. 1-10
Author(s):  
K.S. Smith ◽  
A.D. Frugé ◽  
W. van der Pol ◽  
N.E. Caston ◽  
C.D. Morrow ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Beta Diversity ◽  
Alpha Diversity ◽  
Rrna Gene ◽  
Faecal Microbiota ◽  
Treatment Naïve ◽  
Unweighted Unifrac ◽  
Breast And Prostate Cancer ◽  
Randomised Controlled

Implicated in several chronic diseases, the gastrointestinal microbiome is hypothesised to influence carcinogenesis. We compared faecal microbiota of newly diagnosed treatment-naïve overweight and obese cancer patients and matched controls. Cases were enrolled in presurgical weight-loss trials for breast (NCT02224807) and prostate (NCT01886677) cancers and had a body mass index (BMI) ≥25 kg/m2. Cancer-free controls were matched 1:1 by age (±5 years), race, gender, and BMI (±5 kg/m2). All participants provided faecal samples; isolated bacterial DNA were PCR amplified at the V4 region of the 16S rRNA gene and analysed using the QIIME pipeline. Tests compared cases versus controls, then separately by gender. Microbial alpha-diversity and beta-diversity were assessed, and relative abundance of Operational Taxonomic Units (OTU’s) were compared at the genus level, with false discovery rate (FDR) correction. 22 overweight and obese cancer patients were matched with 22 cancer-free controls, with an average BMI of 30.5±4.3 kg/m2, age 54.4±5.3 years, and 54.5% were black. Fourteen matches were made between breast cancer cases and healthy female controls, and 8 matches were made with prostate cancer cases and healthy male controls. Comparison of all cases and controls revealed no differences in alpha diversity, though prostate cancer patients had higher Chao1 (P=0.006) and Observed Species (P=0.036) than cancer-free males. Beta-diversity metrics were significantly different between cases and controls (P<0.03 for all tests in whole sample and in men), though only unweighted Unifrac was different in women (P=0.005). Kruskal Wallis tests indicated significant differences among 16 genera in all matches, 9 in female, and 51 in male. This study suggests the faecal microbiota of treatment-naive breast and prostate cancer patients differs from controls, though larger samples are needed to substantiate these findings. Trial registration: NIH Clinical Trials, NCT01886677, NCT02224807, registered 26 June 2013, 25 Aug 2014 (respectively) – retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT01886677 ; https://clinicaltrials.gov/ct2/show/NCT02224807

scholarly journals Salivary Microbial Dysbiosis Is Associated With Peri-Implantitis: A Case-Control Study in a Brazilian Population

2022 ◽  
Vol 11 ◽  
Author(s):  
Debora Pallos ◽  
Vanessa Sousa ◽  
Magda Feres ◽  
Belen Retamal-Valdes ◽  
Tsute Chen ◽  
...  
Keyword(s):  
Beta Diversity ◽  
Bacterial Species ◽  
Hypervariable Region ◽  
Alpha Diversity ◽  
Rrna Gene ◽  
Microbial Composition ◽  
Microbiome Composition ◽  
Ion Torrent Pgm ◽  
Microbial Dysbiosis ◽  
Haemophilus Parainfluenzae

Background and ObjectivesThe aim of this study was to examine the salivary microbiome in healthy peri-implant sites and those with peri-implantitis.MethodsSaliva samples were collected from 21 participants with healthy peri-implant sites and 21 participants with peri-implantitis. The V4 hypervariable region of the 16S rRNA gene was sequenced using the Ion Torrent PGM System (Ion 318™ Chip v2 400). The NGS analysis and composition of the salivary microbiome were determined by taxonomy assignment. Downstream bioinformatic analyses were performed in QIIME (v 1.9.1).ResultsClinical differences according to peri-implant condition status were found. Alpha diversity metrics revealed that the bacterial communities of participants with healthy peri-implant sites tended to have a richer microbial composition than individuals with peri-implantitis. In terms of beta diversity, bleeding on probing (BoP) may influence the microbial diversity. However, no clear partitioning was noted between the salivary microbiome of volunteers with healthy peri-implant sites or volunteers with peri-implantitis. The highest relative abundance of Stenotrophomonas, Enterococcus and Leuconostoc genus, and Faecalibacterium prausnitzii, Haemophilus parainfluenzae, Prevotella copri, Bacteroides vulgatus, and Bacteroides stercoris bacterial species was found in participants with peri-implantitis when compared with those with healthy peri-implant sites.ConclusionDifferences in salivary microbiome composition were observed between patients with healthy peri-implant sites and those with peri-implantitis. BoP could affect the diversity (beta diversity) of the salivary microbiome.

scholarly journals Effect of Bovine MFGM and LF in Infant Formula on Gut Microbiome and Metabolome at Four Months of Age

2021 ◽  
Author(s):  
Maciej Chichlowski ◽  
Nicholas Bokulich ◽  
Cheryl L Harris ◽  
Jennifer L Wampler ◽  
Fei Li ◽  
...  
Keyword(s):  
Infant Formula ◽  
Beta Diversity ◽  
Milk Fat ◽  
Alpha Diversity ◽  
Illumina Miseq ◽  
Rrna Gene ◽  
Term Infants ◽  
Linear Discriminant ◽  
Alpha And Beta Diversity ◽  
Metabolite Profiles

Abstract Background Milk fat globule membrane (MFGM) and lactoferrin (LF) are human milk bioactive components demonstrated to support gastrointestinal (GI) and immune development. Significantly fewer diarrhea and respiratory-associated adverse events through 18 months of age were previously reported in healthy term infants fed a cow's milk-based infant formula with added source of bovine MFGM and bovine LF through 12 months of age. Objectives To compare microbiota and metabolite profiles in a subset of study participants. Methods Stool samples were collected at Baseline (10–14 days of age) and Day 120 (MFGM + LF: 26, Control: 33). Bacterial community profiling was performed via16S rRNA gene sequencing (Illumina MiSeq) and alpha and beta diversity were analyzed (QIIME 2). Differentially abundant taxa were determined using Linear discriminant analysis effect size (LefSE) and visualized (Metacoder). Untargeted stool metabolites were analyzed (HPLC/mass spectroscopy) and expressed as the fold-change between group means (Control: MFGM + LF ratio). Results Alpha diversity increased significantly in both groups from baseline to 4 months. Subtle group differences in beta diversity were demonstrated at 4 months (Jaccard distance; R2 = 0.01, P = 0.042). Specifically, Bacteroides uniformis and Bacteroides plebeius were more abundant in the MFGM + LF group at 4 months. Metabolite profile differences for MFGM + LF vs Control included: lower fecal medium chain fatty acids, deoxycarnitine, and glycochenodeoxycholate, and some higher fecal carbohydrates and steroids (P &lt; 0.05). After applying multiple test correction, the differences in stool metabolomics were not significant. Conclusions Addition of bovine MFGM and LF in infant formula was associated with subtle differences in stool microbiome and metabolome by four months of age, including increased prevalence of Bacteroides species. Stool metabolite profiles may be consistent with altered microbial metabolism. Trial registration:  https://clinicaltrials.gov/ct2/show/NCT02274883).

scholarly journals Strongyloides stercoralis Infestation in a Child: How a Nematode Can Affect Gut Microbiota

2021 ◽  
Vol 22 (4) ◽  
pp. 2131
Author(s):  
Stefania Pane ◽  
Anna Sacco ◽  
Andrea Iorio ◽  
Lorenza Romani ◽  
Lorenza Putignani
Keyword(s):  
Gut Microbiota ◽  
Bacterial Species ◽  
Alpha Diversity ◽  
Strongyloides Stercoralis ◽  
Pulmonary Involvement ◽  
Diversity Indices ◽  
Parasite Infection ◽  
Intestinal Nematode ◽  
Immune Mediated ◽  
Stool Samples

Background: Strongyloidiasis is a neglected tropical disease caused by the intestinal nematode Strongyloides stercoralis and characterized by gastrointestinal and pulmonary involvement. We report a pediatric case of strongyloidiasis to underline the response of the host microbiota to the perturbation induced by the nematode. Methods: We performed a 16S rRNA-metagenomic analysis of the gut microbiota of a 7-year-old female during and after S. stercolaris infection, investigating three time-point of stool samples’ ecology: T0- during parasite infection, T1- a month after parasite infection, and T2- two months after parasite infection. Targeted-metagenomics were used to investigate ecology and to predict the functional pathways of the gut microbiota. Results: an increase in the alpha-diversity indices in T0-T1 samples was observed compared to T2 and healthy controls (CTRLs). Beta-diversity analysis showed a shift in the relative abundance of specific gut bacterial species from T0 to T2 samples. Moreover, the functional prediction of the targeted-metagenomics profiles suggested an enrichment of microbial glycan and carbohydrate metabolisms in the T0 sample compared with CTRLs. Conclusions: The herein report reinforces the literature suggestion of a putative direct or immune-mediated ability of S. stercolaris to promote the increase in bacterial diversity.

scholarly journals Detection of Food Spoilage and Pathogenic Bacteria Based on Ligation Detection Reaction Coupled to Flow-Through Hybridization on Membranes

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
K. Böhme ◽  
P. Cremonesi ◽  
M. Severgnini ◽  
Tomás G. Villa ◽  
I. C. Fernández-No ◽  
...  
Keyword(s):  
Pathogenic Bacteria ◽  
Bacterial Species ◽  
Cost Effective ◽  
Rrna Gene ◽  
Bacterial Identification ◽  
Dot Blot ◽  
Culture Collections ◽  
Ligation Detection Reaction ◽  
Flow Through ◽  
Food Safety And Quality

Traditional culturing methods are still commonly applied for bacterial identification in the food control sector, despite being time and labor intensive. Microarray technologies represent an interesting alternative. However, they require higher costs and technical expertise, making them still inappropriate for microbial routine analysis. The present study describes the development of an efficient method for bacterial identification based on flow-through reverse dot-blot (FT-RDB) hybridization on membranes, coupled to the high specific ligation detection reaction (LDR). First, the methodology was optimized by testing different types of ligase enzymes, labeling, and membranes. Furthermore, specific oligonucleotide probes were designed based on the 16S rRNA gene, using the bioinformatic tool Oligonucleotide Retrieving for Molecular Applications (ORMA). Four probes were selected and synthesized, being specific forAeromonasspp.,Pseudomonasspp.,Shewanellaspp., andMorganella morganii, respectively. For the validation of the probes, 16 reference strains from type culture collections were tested by LDR and FT-RDB hybridization using universal arrays spotted onto membranes. In conclusion, the described methodology could be applied for the rapid, accurate, and cost-effective identification of bacterial species, exhibiting special relevance in food safety and quality.

scholarly journals AB1232 ORAL DYSBIOSIS REFLECTS THE IMMUNOLOGICAL ALTERATION OF RA REGARDING TO ACPA AND HLA DRB1*SE: NAGASAKI ISLAND STUDY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1907.2-1907
Author(s):  
Y. Tsuji ◽  
M. Tamai ◽  
S. Morimoto ◽  
D. Sasaki ◽  
M. Nagayoshi ◽  
...  
Keyword(s):  
Beta Diversity ◽  
Healthy Subjects ◽  
Microbial Community Composition ◽  
Alpha Diversity ◽  
Enzyme Linked Immunosorbent Assay ◽  
Rrna Gene ◽  
Oral Microbiota ◽  
Unifrac Distance ◽  
Alpha And Beta Diversity ◽  
The Difference

Background:Anti-citrullinated protein antibody (ACPA) production is observed in several organs even prior to the onset of rheumatoid arthritis (RA), and oral mucosa is considered to be one of the important tissues. The presence of HLA-DRB1*SE closely associates with ACPA production. Saliva is considered to reflect the oral microbiota including periodontal disease. Alteration of oral microbiota of RA becomes to be normalized by DMARDs treatment, however, the interaction of HLA-DRB1*SE, ACPA and oral microbiota of RA patients remains to be elucidated.Objectives:The Nagasaki Island Study, which had started in 2014 collaborating with Goto City, is intended for research of the preclinical stage of RA, including ACPA/HLA genotype screening and ultrasound and magnetic resonance imaging examinations in high-risk subjects. Using the samples accumulated in this cohort, we have tried to investigate the difference of oral microbiota among RA patients and healthy subjects regarding to ACPA and HLA-DRB1*SE.Methods:Blood and salivary samples were obtained from 1422 subjects out of 4276 who have participated in the Nagasaki Island Study from 2016 to 2018. ACPA positivity was 1.7 % in total. Some of RA patients resided in Goto City participated in the Nagasaki Island Study. At this point, we selected 291 subjects, who were ACPA positive non-RA healthy subjects (n=22) and patients with RA (n=33, 11 subjects were ACPA positive and 22 ACPA negative respectively) as the case, age and gender matched ACPA negative non-RA healthy subjects (n=236) as the control. ACPA was measured by an enzyme-linked immunosorbent assay, and HLA genotyping was quantified by next-generation sequencing (Ref.1). The operational taxonomic unit (OUT) analysis using 16S rRNA gene sequencing were performed. The richness of microbial diversity within-subject (alpha diversity) was scaled via Shannon entropy. The dissimilarity between microbial community composition was calculated using Bray-Curtis distance as a scale, and differences between groups (beta diversity) were tested by permutational multivariate analysis of variance (PERMANOVA). In addition, UniFrac distance calculated in consideration of the distance on the phylogenetic tree were performed.Results:Median age 70 y.o., % Female 58.8 %. Among RA and non-RA subjects, not alpha diversity but beta diversity was statistically significance (p=0.022, small in RA). In RA subjects, both alpha and beta diversity is small (p<0.0001), especially significant in ACPA positive RA (Figure 1). Amongt RA subjects, presence of HLA-DRB1*SE did not show the difference but the tendency of being small of alpha diversity (p=0.29).Conclusion:Our study has suggested for the first time the association of oral microbiota alteration with the presence of ACPA and HLA-DRB1*SE. Oral dysbiosis may reflect the immunological status of patients with RA.References:[1]Kawaguchi S, et al. Methods Mol Biol 2018;1802: 22Disclosure of Interests:None declared

scholarly journals Association of Broiler Litter Microbiome Composition and Campylobacter Isolation

2021 ◽  
Vol 8 ◽  
Author(s):  
Robert Valeris-Chacin ◽  
Maria Pieters ◽  
Haejin Hwang ◽  
Timothy J. Johnson ◽  
Randall S. Singer
Keyword(s):  
Beta Diversity ◽  
Conditional Logistic Regression ◽  
Statistical Significance ◽  
Alpha Diversity ◽  
Rrna Gene ◽  
Campylobacter Coli ◽  
Broiler Litter ◽  
Logistic Regression Models ◽  
Microbiome Composition ◽  
Broiler House

Infection with Campylobacter species is one of the leading causes of bacterial diarrhea in humans in the US. Chickens, which become colonized on the farm, are important reservoirs of this bacterium. Campylobacter can establish itself in the broiler house via a variety of sources, can survive in the litter of the house, and possibly persist over successive flock cycles. However, the role of the broiler litter microbiome on Campylobacter persistence is not clear. A matched case-control study was conducted to determine whether the broiler litter microbiome composition was associated with Campylobacter isolation within the broiler house. Flocks were classified as cases when either Campylobacter jejuni or Campylobacter coli was isolated in boot sock samples, or as controls otherwise. Case and control flocks were matched at the broiler house level. Composite broiler litter samples were collected and used for DNA extraction and 16S rRNA gene V4 region sequencing. Reads were processed using the DADA2 pipeline to obtain a table of amplicon sequence variants. Alpha diversity and differential bacterial relative abundance were used as predictors of Campylobacter isolation status in conditional logistic regression models adjusting for flock age and sampling season. Beta diversity distances were used as regressors in stratified PERMANOVA with Campylobacter isolation status as predictor, and broiler house as stratum. When Campylobacter was isolated in boot socks, broiler litter microbiome richness and evenness were lower and higher, respectively, without reaching statistical significance. Campylobacter isolation status significantly explained a small proportion of the beta diversity (genus-level Aitchison dissimilarity distance). Clostridium and Anaerostipes were positively associated with Campylobacter isolation status, whereas Bifidobacterium, Anaerosporobacter, and Stenotrophomonas were negatively associated. Our results suggest the presence of bacterial interactions between Campylobacter and the broiler litter microbiome. The negative association of Campylobacter with Bifidobacterium, Anaerosporobacter, and Stenotrophomonas in litter could be potentially exploited as a pre-harvest control strategy.

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.

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