Association Between Neonatal Gut Microbiome and Infant Wheeze

Background: Asthma is a chronic respiratory disease that affects 10% of children. Infant wheeze at 1 year and the subsequent development of asthma in early childhood has been associated with infant gut dysbiosis. However, little is known about the relationship between neonatal gut microbiome and the development of wheeze during the first 18 months of life. We hypothesize that the gut microbiome at birth and throughout the first 18 months of life is associated with infant wheeze. Project Methods: Stool samples were collected from infants at birth, 1, 3, and 12 months of age. The Illumina Miseq system was used to sequence the bacterial V4 region of 16S-rRNA gene. Mothur software was used for analysis. Statistical analysis was used to measure stool shannon diversity and evenness as they relate to timepoint and wheeze vs no wheeze groups. Results: The study population consisted of 28 infants (18 males and 10 females). 11% of participants reported they had been diagnosed with wheeze by a physician (n=3). Statistical analysis of shannon diversity showed no differences in the stool between participants who wheeze vs those who do not wheeze (p=0.78). No difference in stool evenness was detected between participants who reported wheeze vs no wheeze (p=0.71). However, this analysis includes multiple timepoints. Analysis of stool shannon diversity across timepoints did show a significant difference in stool microbiome (p=0.01). Conclusion: No differences in stool microbiome were found between infants who do not wheeze and those who do. Further studies can investigate a greater number of samples at each timepoint and relate these to objective measures such as pulmonary function tests. Understanding the association between infant gut dysbiosis and wheeze could have implications for predicting development of asthma in early childhood and potentially lead to targeted interventions.

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Gut microbiome profiling of a rural and urban South African cohort reveals biomarkers of a population in lifestyle transition

BMC Microbiology ◽

10.1186/s12866-020-02017-w ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

O. H. Oduaran ◽

F. B. Tamburini ◽

V. Sahibdeen ◽

R. Brewster ◽

F. X. Gómez-Olivé ◽

...

Keyword(s):

South African ◽

Gut Microbiome ◽

Geographical Location ◽

16S Rrna Gene Sequencing ◽

Overweight And Obesity ◽

Future Research ◽

Epidemiological Transition ◽

Rrna Gene ◽

Microbiome Composition ◽

Targeted Interventions

Abstract Background Comparisons of traditional hunter-gatherers and pre-agricultural communities in Africa with urban and suburban Western North American and European cohorts have clearly shown that diet, lifestyle and environment are associated with gut microbiome composition. Yet, little is known about the gut microbiome composition of most communities in the very diverse African continent. South Africa comprises a richly diverse ethnolinguistic population that is experiencing an ongoing epidemiological transition and concurrent spike in the prevalence of obesity, largely attributed to a shift towards more Westernized diets and increasingly inactive lifestyle practices. To characterize the microbiome of African adults living in more mainstream lifestyle settings and investigate associations between the microbiome and obesity, we conducted a pilot study, designed collaboratively with community leaders, in two South African cohorts representative of urban and transitioning rural populations. As the rate of overweight and obesity is particularly high in women, we collected single time-point stool samples from 170 HIV-negative women (51 at Soweto; 119 at Bushbuckridge), performed 16S rRNA gene sequencing on these samples and compared the data to concurrently collected anthropometric data. Results We found the overall gut microbiome of our cohorts to be reflective of their ongoing epidemiological transition. Specifically, we find that geographical location was more important for sample clustering than lean/obese status and observed a relatively higher abundance of the Melainabacteria, Vampirovibrio, a predatory bacterium, in Bushbuckridge. Also, Prevotella, despite its generally high prevalence in the cohorts, showed an association with obesity. In comparisons with benchmarked datasets representative of non-Western populations, relatively higher abundance values were observed in our dataset for Barnesiella (log2fold change (FC) = 4.5), Alistipes (log2FC = 3.9), Bacteroides (log2FC = 4.2), Parabacteroides (log2FC = 3.1) and Treponema (log2FC = 1.6), with the exception of Prevotella (log2FC = − 4.7). Conclusions Altogether, this work identifies putative microbial features associated with host health in a historically understudied community undergoing an epidemiological transition. Furthermore, we note the crucial role of community engagement to the success of a study in an African setting, the importance of more population-specific studies to inform targeted interventions as well as present a basic foundation for future research.

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Gut Dysbiosis With Bacilli Dominance and Accumulation of Fermentation Products Precedes Late-onset Sepsis in Preterm Infants

Clinical Infectious Diseases ◽

10.1093/cid/ciy882 ◽

2018 ◽

Vol 69 (2) ◽

pp. 268-277 ◽

Cited By ~ 21

Author(s):

S Graspeuntner ◽

S Waschina ◽

S Künzel ◽

N Twisselmann ◽

T K Rausch ◽

...

Keyword(s):

Preterm Infants ◽

Gut Microbiome ◽

Late Onset ◽

Anaerobic Bacteria ◽

Gene Profiling ◽

Rrna Gene ◽

Coagulase Negative Staphylococci ◽

Fermentation Products ◽

Gut Dysbiosis ◽

Late Onset Sepsis

Abstract Background Gut dysbiosis has been suggested as a major risk factor for the development of late-onset sepsis (LOS), a main cause of mortality and morbidity in preterm infants. We aimed to assess specific signatures of the gut microbiome, including metabolic profiles, in preterm infants <34 weeks of gestation preceding LOS. Methods In a single-center cohort, fecal samples from preterm infants were prospectively collected during the period of highest vulnerability for LOS (days 7, 14, and 21 of life). Following 16S rRNA gene profiling, we assessed microbial community function using microbial metabolic network modeling. Data were adjusted for gestational age and use of probiotics. Results We studied stool samples from 71 preterm infants with LOS and 164 unaffected controls (no LOS/necrotizing enterocolitis). In most cases, the bacteria isolated in diagnostic blood culture corresponded to the genera in the gut microbiome. LOS cases had a decelerated development of microbial diversity. Before onset of disease, LOS cases had specific gut microbiome signatures with higher abundance of Bacilli (specifically coagulase-negative Staphylococci) and a lack of anaerobic bacteria. In silico modeling of bacterial community metabolism suggested accumulation of the fermentation products ethanol and formic acid in LOS cases before the onset of disease. Conclusions Intestinal dysbiosis preceding LOS is characterized by an accumulation of Bacilli and their fermentation products and a paucity of anaerobic bacteria. Early microbiome and metabolic patterns may become a valuable biomarker to guide individualized prevention strategies of LOS in highly vulnerable populations.

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

PeerJ ◽

10.7717/peerj.4663 ◽

2018 ◽

Vol 6 ◽

pp. e4663 ◽

Cited By ~ 6

Author(s):

Shaaz Fareed ◽

Neha Sarode ◽

Frank J. Stewart ◽

Aneeq Malik ◽

Elham Laghaie ◽

...

Keyword(s):

Clostridium Difficile ◽

Adverse Effects ◽

Gut Microbiome ◽

Pediatric Patients ◽

Fecal Microbiota Transplantation ◽

Diversity Index ◽

Microbial Community Composition ◽

Fecal Microbiota ◽

Rrna Gene ◽

Significant Difference

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

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Gut Microbiome Profiling of a Rural and Urban South African Cohort Reveals Biomarkers of a Population in Lifestyle Transition

10.1101/2020.02.27.964023 ◽

2020 ◽

Cited By ~ 1

Author(s):

OH. Oduaran ◽

FB. Tamburini ◽

V. Sahibdeen ◽

R. Brewster ◽

FX. Gómez-Olivé ◽

...

Keyword(s):

South African ◽

Gut Microbiome ◽

16S Rrna Gene Sequencing ◽

Overweight And Obesity ◽

Future Research ◽

Epidemiological Transition ◽

Rrna Gene ◽

Microbiome Composition ◽

Targeted Interventions ◽

Rural And Urban

AbstractBackgroundComparisons of traditional hunter-gatherers and pre-agricultural communities in Africa with urban and suburban Western North American and European cohorts have clearly shown that diet, lifestyle and environment are associated with gut microbiome composition. Yet, little is known about the gut microbiome composition of most African adults. South Africa comprises a richly diverse ethnolinguistic population that is experiencing an ongoing epidemiological transition and concurrent spike in the prevalence of obesity, largely attributed to a shift towards more Westernized diets and increasingly inactive lifestyle practices. To better characterize the microbiome of African adults living in more mainstream lifestyle settings and to investigate associations between the microbiome and obesity, we conducted a pilot study in two South African cohorts that are representative of urban and rural populations. The study was designed collaboratively with community leaders. As the rate of overweight and obesity is particularly high in women, we collected single time-point stool samples from 170 HIV-negative women (51 at Soweto; 119 at Bushbuckridge), performed 16S rRNA gene sequencing on these samples and compared the data to concurrently collected anthropometric data.ResultsWe found the overall gut microbiome of our cohorts to be reflective of their ongoing epidemiological transition. Specifically, our results show a relatively higher than expected abundance of Western gut-associated taxa such as Barnesiella and the presence of Bifidobacteria and Bacteroides together with the more traditionally non-Western gut-associated Prevotella, Treponema and Succinivibrio. Interestingly, we observed a relatively higher abundance of the Melainabacteria, Vampirovibrio, a predatory bacterium, in the rural cohort. We also found Prevotella, despite its generally high prevalence relative to all taxa present in the cohort, to be associated with obesity.ConclusionsAltogether, this work identifies putative microbial features associated with host health in a historically understudied community. Furthermore, we note the crucial role of community engagement to the success of a study in an African setting, the importance of more population-specific studies to inform targeted interventions as well as present a basic foundation for future research in this regard.

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Insights into gut microbiome and its functional pathways in asthma patients through high-throughput sequencing

Future Microbiology ◽

10.2217/fmb-2020-0101 ◽

2021 ◽

Author(s):

Chunrong Huang ◽

Youchao Yu ◽

Wei Du ◽

Yahui Liu ◽

Ranran Dai ◽

...

Keyword(s):

Bladder Cancer ◽

Gut Microbiome ◽

High Throughput Sequencing ◽

Functional Genes ◽

Inhaled Corticosteroid ◽

Fecal Microbiome ◽

Gut Dysbiosis ◽

Significant Difference ◽

Asthma Patients ◽

Functional Pathways

Aim: To describe gut microbiome and functional genes of asthma. Patients & methods: Fecal microbiome in controls, asthma patients with and without inhaled corticosteroid (ICS) treatment was determined. Results: Patients with ICS had lower abundance of Alloprevotella, unclassified_f_Lachnospiraceae and Lachnospiraceae_NC2004_group, higher abundance of Sutterella and Sphingomonas than patients without ICS. In all the asthma patients, there are microbial differences in aging distribution, different gender and different asthmatic phenotypes. Asthma patients without ICS treatment had more microbial genes related to geraniol degradation, ethylbenzene degradation and bladder cancer than controls; 15 pathways showed significant difference between asthma patients with and without ICS treatment. Conclusion: We found gut dysbiosis in asthma and different functional pathways associated with both asthma and ICS.

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Salivary Cystatin S in Children With Early Childhood Caries in Comparison With Caries-free Children; Statistical Analysis and Machine Learning

10.21203/rs.3.rs-620613/v1 ◽

2021 ◽

Author(s):

Maryam Koopaie ◽

Mahsa Salamati ◽

Roshanak Montazeri ◽

Mansour Davoudi ◽

Sajad Kolahdooz

Keyword(s):

Machine Learning ◽

Early Childhood ◽

Statistical Analysis ◽

Free Group ◽

Roc Curve ◽

Early Childhood Caries ◽

Control Group ◽

Whole Saliva ◽

Significant Difference ◽

Childhood Caries

Abstract Background: Early childhood caries is the most common infectious disease in childhood, with a high prevalence in developing countries. Recognition of the factors affecting early childhood caries and its pathophysiology, allows better control of disease. Cystatin S as one of the salivary proteins, has an important role in pellicle formation, tooth re-mineralization and protection. The aim of the present study is to assess salivary cystatin S levels and demographic data in early childhood caries children in comparison with caries-free ones using statistical analysis and machine learning methods. Methods: A cross-sectional case-control study was undertaken on 20 cases of early childhood caries and 20 caries-free children as a control group. Unstimulated whole saliva samples by suction method was collected. Cystatin S concentrations were determined using human cystatin S ELISA kit. A checklist was collected for each participant about the demographic characteristics, oral health status and dietary habits by interviewing parents. The regression and receiver operating characteristic (ROC) curve analysis was done to evaluate the potential role of cystatin S salivary level and demographic using machine learning and statistical analysis.Results: The mean value of salivary cystatin S concentration in early childhood caries group was 191.55±81.90 (ng/ml) and in caries-free group was 370.06±128.87 (ng/ml). T-test analysis showed that there is a statistically significant difference between early childhood caries and caries-free group in salivary cystatin S level (p: 0.032). Investigation of area under the curve and accuracy of ROC curve revealed that logistic regression model based on the salivary cystatin S levels and birth weight had most and acceptable potential for discriminating of early childhood caries from caries-free controls. After that the machine learning models and finally salivary cystatin S levels had more capability for differentiation of early childhood caries from caries-free controls.Conclusion: Salivary cystatin S in caries-free children was higher than the children with early childhood caries. Therefore, cystatin S protein can be used as a biomarker for early prediction of early childhood caries, furthermore cystatin S is a protective factor against dental caries.

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Investigation of the impact of commonly used medications on the oral microbiome of individuals living without major chronic conditions

PLoS ONE ◽

10.1371/journal.pone.0261032 ◽

2021 ◽

Vol 16 (12) ◽

pp. e0261032

Author(s):

Vanessa DeClercq ◽

Jacob T. Nearing ◽

Morgan G. I. Langille

Keyword(s):

Thyroid Hormones ◽

Relative Abundance ◽

Beta Diversity ◽

Chronic Conditions ◽

Oral Microbiome ◽

Rrna Gene ◽

Oral Microbiota ◽

Shannon Diversity ◽

Significant Difference ◽

The Impact

Background Commonly used medications produce changes in the gut microbiota, however, the impact of these medications on the composition of the oral microbiota is understudied. Methods Saliva samples were obtained from 846 females and 368 males aged 35–69 years from a Canadian population cohort, the Atlantic Partnership for Tomorrow’s Health (PATH). Samples were analyzed by 16S rRNA gene sequencing and differences in microbial community compositions between nonusers, single-, and multi-drug users as well as the 3 most commonly used medications (thyroid hormones, statins, and proton pump inhibitors (PPI)) were examined. Results Twenty-six percent of participants were taking 1 medication and 21% were reported taking 2 or more medications. Alpha diversity indices of Shannon diversity, Evenness, Richness, and Faith’s phylogenetic diversity were similar among groups, likewise beta diversity as measured by Bray-Curtis dissimilarity (R2 = 0.0029, P = 0.053) and weighted UniFrac distances (R2 = 0.0028, P = 0.161) were non-significant although close to our alpha value threshold (P = 0.05). After controlling for covariates (sex, age, BMI), six genera (Saprospiraceae uncultured, Bacillus, Johnsonella, Actinobacillus, Stenotrophomonas, and Mycoplasma) were significantly different from non-medication users. Thyroid hormones, HMG-CoA reductase inhibitors (statins) and PPI were the most reported medications. Shannon diversity differed significantly among those taking no medication and those taking only thyroid hormones, however, there were no significant difference in other measures of alpha- or beta diversity with single thyroid hormone, statin, or PPI use. Compared to participants taking no medications, the relative abundance of eight genera differed significantly in participants taking thyroid hormones, six genera differed in participants taking statins, and no significant differences were observed with participants taking PPI. Conclusion The results from this study show negligible effect of commonly used medications on microbial diversity and small differences in the relative abundance of specific taxa, suggesting a minimal influence of commonly used medication on the salivary microbiome of individuals living without major chronic conditions.

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Salivary cystatin S levels in children with early childhood caries in comparison with caries-free children; statistical analysis and machine learning

BMC Oral Health ◽

10.1186/s12903-021-02016-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Maryam Koopaie ◽

Mahsa Salamati ◽

Roshanak Montazeri ◽

Mansour Davoudi ◽

Sajad Kolahdooz

Keyword(s):

Machine Learning ◽

Early Childhood ◽

Statistical Analysis ◽

Roc Curve ◽

Early Childhood Caries ◽

Learning Methods ◽

Machine Learning Methods ◽

Whole Saliva ◽

Significant Difference ◽

Childhood Caries

Abstract Background Early childhood caries is the most common infectious disease in childhood, with a high prevalence in developing countries. The assessment of the variables that influence early childhood caries as well as its pathophysiology leads to improved control of this disease. Cystatin S, as one of the salivary proteins, has an essential role in pellicle formation, tooth re-mineralization, and protection. The present study aims to assess salivary cystatin S levels and demographic data in early childhood caries in comparison with caries-free ones using statistical analysis and machine learning methods. Methods A cross-sectional, case–control study was undertaken on 20 cases of early childhood caries and 20 caries-free children as a control. Unstimulated whole saliva samples were collected by suction. Cystatin S concentrations in samples were determined using human cystatin S ELISA kit. The checklist was collected from participants about demographic characteristics, oral health status, and dietary habits by interviewing parents. Regression and receiver operating characteristic (ROC) curve analysis were done to evaluate the potential role of cystatin S salivary level and demographic using statistical analysis and machine learning. Results The mean value of salivary cystatin S concentration in the early childhood caries group was 191.55 ± 81.90 (ng/ml) and in the caries-free group was 370.06 ± 128.87 (ng/ml). T-test analysis showed a statistically significant difference between early childhood caries and caries-free groups in salivary cystatin S levels (p = 0.032). Investigation of the area under the curve (AUC) and accuracy of the ROC curve revealed that the logistic regression model based on salivary cystatin S levels and birth weight had the most and acceptable potential for discriminating of early childhood caries from caries-free controls. Furthermore, using salivary cystatin S levels enhanced the capability of machine learning methods to differentiate early childhood caries from caries-free controls. Conclusion Salivary cystatin S levels in caries-free children were higher than the children with early childhood caries. Results of the present study suggest that considering clinical examination, demographic and socioeconomic factors, along with the salivary cystatin S levels, could be usefull for early diagnosis ofearly childhood caries in high-risk children; furthermore, cystatin S is a protective factor against dental caries.

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Abnormalities in Gut Microbiota and Metabolism in Patients With Chronic Spontaneous Urticaria

Frontiers in Immunology ◽

10.3389/fimmu.2021.691304 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xin Wang ◽

Wanyu Yi ◽

Liting He ◽

Shuaihantian Luo ◽

Jiaqi Wang ◽

...

Keyword(s):

Correlation Analysis ◽

Gut Microbiota ◽

Gut Microbiome ◽

Gene Sequencing ◽

16S Rrna Gene Sequencing ◽

Chronic Spontaneous Urticaria ◽

Rrna Gene ◽

Α Diversity ◽

Significant Difference ◽

Rrna Gene Sequencing

BackgroundIncreasing evidence suggests that the gut microbiome plays a role in the pathogenesis of allergy and autoimmunity. The association between abnormalities in the gut microbiota and chronic spontaneous urticaria (CSU) remains largely undefined.MethodsFecal samples were obtained from 39 patients with CSU and 40 healthy controls (HCs). 16S ribosomal RNA (rRNA) gene sequencing (39 patients with CSU and 40 HCs) and untargeted metabolomics (12 patients with CSU and 12 HCs) were performed to analyze the compositional and metabolic alterations of the gut microbiome in CSU patients and HCs.ResultsThe 16S rRNA gene sequencing results showed a significant difference in the β-diversity of the gut microbiota, presented as the Jaccard distance, between CSU patients and HCs. No significant differences were found in the α-diversity of the gut microbiota between patients and HCs. At the phylum level, the major bacteria in the gut microbiome of patients with CSU were Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. At the genus level, Lactobacillus, Turicibacter, and Lachnobacterium were significantly increased and Phascolarctobacterium was decreased in patients with CSU. PICRUSt and correlation analysis indicated that Lactobacillus, Turicibacter, and Phascolarctobacterium were positively related to G protein-coupled receptors. Metabolomic analysis showed that α-mangostin and glycyrrhizic acid were upregulated and that 3-indolepropionic acid, xanthine, and isobutyric acid were downregulated in patients with CSU. Correlation analysis between the intestinal microbiota and metabolites suggested that there was a positive correlation between Lachnobacterium and α-mangostin.ConclusionsThis study suggests that disturbances in the gut microbiome composition and metabolites and their crosstalk or interaction may participate in the pathogenesis of CSU.

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Gut microbiome composition in the Hispanic Community Health Study/Study of Latinos is shaped by geographic relocation, environmental factors, and obesity

Genome Biology ◽

10.1186/s13059-019-1831-z ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 14

Author(s):

Robert C. Kaplan ◽

Zheng Wang ◽

Mykhaylo Usyk ◽

Daniela Sotres-Alvarez ◽

Martha L. Daviglus ◽

...

Keyword(s):

Community Health ◽

Gut Microbiome ◽

Alpha Diversity ◽

Amplicon Sequencing ◽

Shannon Index ◽

Health Study ◽

Rrna Gene ◽

Cross Sectional ◽

Hispanic Community ◽

The Usa

Abstract Background Hispanics living in the USA may have unrecognized potential birthplace and lifestyle influences on the gut microbiome. We report a cross-sectional analysis of 1674 participants from four centers of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), aged 18 to 74 years old at recruitment. Results Amplicon sequencing of 16S rRNA gene V4 and fungal ITS1 fragments from self-collected stool samples indicate that the host microbiome is determined by sociodemographic and migration-related variables. Those who relocate from Latin America to the USA at an early age have reductions in Prevotella to Bacteroides ratios that persist across the life course. Shannon index of alpha diversity in fungi and bacteria is low in those who relocate to the USA in early life. In contrast, those who relocate to the USA during adulthood, over 45 years old, have high bacterial and fungal diversity and high Prevotella to Bacteroides ratios, compared to USA-born and childhood arrivals. Low bacterial diversity is associated in turn with obesity. Contrasting with prior studies, our study of the Latino population shows increasing Prevotella to Bacteroides ratio with greater obesity. Taxa within Acidaminococcus, Megasphaera, Ruminococcaceae, Coriobacteriaceae, Clostridiales, Christensenellaceae, YS2 (Cyanobacteria), and Victivallaceae are significantly associated with both obesity and earlier exposure to the USA, while Oscillospira and Anaerotruncus show paradoxical associations with both obesity and late-life introduction to the USA. Conclusions Our analysis of the gut microbiome of Latinos demonstrates unique features that might be responsible for health disparities affecting Hispanics living in the USA.

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