Persistence of birth mode-dependent effects on gut microbiome composition, immune system stimulation and antimicrobial resistance during the first year of life

in ISME Communications (2021)

Caesarean section delivery (CSD) disrupts mother-to-neonate transmission of specific microbial strains and functional repertoires as well as linked immune system priming. Here we investigate whether ... [more ▼]

Caesarean section delivery (CSD) disrupts mother-to-neonate transmission of specific microbial strains and functional repertoires as well as linked immune system priming. Here we investigate whether differences in microbiome composition and impacts on host physiology persist at 1 year of age. We perform high-resolution, quantitative metagenomic analyses of the gut microbiomes of infants born by vaginal delivery (VD) or by CSD, from immediately after birth through to 1 year of life. Several microbial populations show distinct enrichments in CSD-born infants at 1 year of age including strains of Bacteroides caccae, Bifidobacterium bifidum and Ruminococcus gnavus, whereas others are present at higher levels in the VD group including Faecalibacterium prausnitizii, Bifidobacterium breve and Bifidobacterium kashiwanohense. The stimulation of healthy donor-derived primary human immune cells with LPS isolated from neonatal stool samples results in higher levels of tumour necrosis factor alpha (TNF-α) in the case of CSD extracts over time, compared to extracts from VD infants for which no such changes were observed during the first year of life. Functional analyses of the VD metagenomes at 1 year of age demonstrate a significant increase in the biosynthesis of the natural antibiotics, carbapenem and phenazine. Concurrently, we find antimicrobial resistance (AMR) genes against several classes of antibiotics in both VD and CSD. The abundance of AMR genes against synthetic (including semi-synthetic) agents such as phenicol, pleuromutilin and diaminopyrimidine are increased in CSD children at day 5 after birth. In addition, we find that mobile genetic elements, including phages, encode AMR genes such as glycopeptide, diaminopyrimidine and multidrug resistance genes. Our results demonstrate persistent effects at 1 year of life resulting from birth mode-dependent differences in earliest gut microbiome colonisation. [less ▲]

Small RNA profiling of low biomass samples: identification and removal of contaminants

in BMC Biology (2018), 16(52),

Background: Sequencing-based analyses of low-biomass samples are known to be prone to misinterpretation due to the potential presence of contaminating molecules derived from laboratory reagents and ... [more ▼]

Background: Sequencing-based analyses of low-biomass samples are known to be prone to misinterpretation due to the potential presence of contaminating molecules derived from laboratory reagents and environments. DNA contamination has been previously reported, however contamination with RNA is usually considered to be unlikely due to its inherent instability. Small RNAs (sRNAs) identified in tissues and bodily fluids such as blood plasma, have implications for physiology and pathology, and therefore the potential to act as disease biomarkers. Thus, the possibility for RNA contaminants demands a careful evaluation. Results: Here we report the presence of small RNA contaminants in widely used microRNA extraction kits and propose an approach for their depletion. We sequenced sRNAs extracted from human plasma samples and detected important levels of non-human (exogenous) sequences whose source could be traced to the microRNA extraction columns through a careful qPCR-based analysis of several laboratory reagents. Furthermore, we also detected the presence of artefactual sequences related to these contaminants in a range of published datasets, arguing for a re-evaluation of reports suggesting the presence of exogenous RNAs of microbial and dietary origins in blood plasma. To avoid artefacts in future experiments, we also devise several protocols of contaminant RNAs, define minimal amounts of starting material for artefact-free analyses, and confirm the reduction of contaminant levels for identification of bona fide sequences using ‘ultra-clean’ extraction kits. Conclusion: This is the first report of the presence of RNA molecules as contaminants in RNA extraction kits. The described protocols should be applied in the future to avoid confounding sRNA studies. [less ▲]

Can health indicators and psychosocial characteristics predict attrition in youth with overweight and obesity seeking ambulatory treatment? Data from a retrospective longitudinal study in a paediatric clinic in Luxembourg.

in BMJ Open (2017), 7(9),

ABSTRACT Objectives: The current study aimed to identify factors that could predict attrition in youth starting ambulatory treatment to control or lose weight. Design: retrospective longitudinal study ... [more ▼]

ABSTRACT Objectives: The current study aimed to identify factors that could predict attrition in youth starting ambulatory treatment to control or lose weight. Design: retrospective longitudinal study Setting: paediatric clinic: ambulatory treatment program Patients and measures: A youth sample (N=191; 89 boys; age 7-17 years) completed measures of demographic characteristics, health and psychosocial traits before starting an ambulatory weight management program. Anthropometric and biological markers related to obesity were also obtained. Test of mean differences and regression analyses were used to investigate the relationship between these variables and attrition after one year. Results: Chi-square and t-test results showed both psychosocial and health indicators differentiated between participants who continued attending the treatment program and those that dropped out. More specifically, youth that dropped out of treatment were significantly older, had higher BMI-Z scores, higher levels of insulin, triglycerides and HOMA-IR, reported poorer health and more conduct problems, and were more dissatisfied with themselves and their bodies before starting treatment. Results of regression analyses revealed that weight status (anthropometric and biological markers), age and body dissatisfaction predict attrition (overall prediction success 73%; prediction success for continued attendance 90/91%; prediction success for dropout 42/44%). Conclusion: Attrition, but especially the continued attendance in treatment, can be successfully predicted by age, weight status and body dissatisfaction. For patients who present with one or more risk factors, careful consideration is needed to decide which (combination of) in- or outpatient program may facilitate prolonged engagement of the patient and hence may be most effective in establishing weight loss. [less ▲]