A synbiotic intervention modulates meta-omics signatures of gut redox potential and acidity in elective caesarean born infants.

Background The compromised gut microbiome that results from C-section birth has been hypothesized as a risk factor for the development of non-communicable diseases (NCD). In a double-blind randomized controlled study, 153 infants born by elective C-section received an infant formula supplemented with either synbiotic, prebiotics, or unsupplemented from birth until 4 months old. Vaginally born infants were included as a reference group. Stool samples were collected from day 3 till week 22. Multi-omics were deployed to investigate the impact of mode of delivery and nutrition on the development of the infant gut microbiome, and uncover putative biological mechanisms underlying the role of a compromised microbiome as a risk factor for NCD. Results As early as day 3, infants born vaginally presented a hypoxic and acidic gut environment characterized by an enrichment of strict anaerobes (Bifidobacteriaceae). Infants born by C-section presented the hallmark of a compromised microbiome driven by an enrichment of Enterobacteriaceae. This was associated with meta-omics signatures characteristic of a microbiome adapted to a more oxygen-rich gut environment, enriched with genes associated with reactive oxygen species metabolism and lipopolysaccharide biosynthesis, and depleted in genes involved in the metabolism of milk carbohydrates. The synbiotic formula modulated expression of microbial genes involved in (oligo)saccharide metabolism, which emulates the eco-physiological gut environment observed in vaginally born infants. The resulting hypoxic and acidic milieu prevented the establishment of a compromised microbiome. Conclusions This study deciphers the putative functional hallmarks of a compromised microbiome acquired during C-section birth, and the impact of nutrition that may counteract disturbed microbiome development. Trial registration The study was registered in the Dutch Trial Register (Number: 2838 ) on 4th April 2011

Cost-effectiveness analysis study of HPV testing as a primary cervical cancer screening in Thailand

Objectives: The aim of this study is to compare the cost and benefit of four different cervical cancer screening strategies involving primary HPV 16/18 genotyping, hrHPV testing alone and cytology for detecting CIN2+. Methods: Economical analysis using Markov modeling approach to combine the epidemiological data from current population-based study of The National Cancer Institute of Thailand. A cohort of 100,000 hypothetical female population age 30–65 years was simulated in each strategy. The compared strategies are HPV 16/18 genotyping with reflexed cytology, hrHPV testing alone followed by colposcopy, Papanicolaou standard cytology and liquid based cytology followed by colposcopy. The interval of screening was 5 years' interval. The main outcomes were defined as a number of CIN2+ cases and cost per 100,000 women screening over 35 years. Results: Model predictions indicated that, the most cost-effectiveness strategy is hrHPV testing alone by reducing cost and also increase CIN2+ detection rate. It identify an additional 130 cases and decrease cost by 46,950,840 THB (1,394,441 USD) per 100,000 women screened when compared to HPV 16/18 genotyping. Compared with cytology, hrHPV testing decrease cost by 51,279,781 THB (1,523,011 USD) and detected more 506 cases of CIN2+. From sensitivity analysis, the cost of HPV testing, cost of colposcopy, incidence of HPV infection and sensitivity of cytology may affect the results. (1 USD = 33.67 Baht). Conclusion: The results of this cost-effectiveness analysis support the full scale implementation of HPV testing as a primary cervical cancer screening in Thailand

The epidemiologic and economic impact of a quadrivalent human papillomavirus vaccine in Thailand.

BackgroundThe human papillomavirus (HPV) vaccine was introduced into Thailand's national immunization program in 2017 for 11-12 year old school girls. The objectives of this study were to examine the epidemiological consequences and cost-effectiveness of a routine quadrivalent HPV (4vHPV) vaccination and the routine 4vHPV vaccination plus 5-year catch-up vaccination by comparing with cervical cancer screening only (no vaccination) in Thailand.MethodA transmission dynamic model was used to assess the cost-effectiveness of the routine 4vHPV vaccination and the routine 4vHPV vaccination plus catch-up vaccination, compared with no vaccination (screening only) in Thai population. The vaccination coverage rate assumptions were 95% in 11-12-year-old girls for the routine vaccination and 70% in 13-24 year-old females for the 5-year catch-up vaccination. Vaccination costs, direct medical costs of HPV-related diseases, and the number of quality of life years (QALYs) gained were calculated for over a 100-year time horizon with discount rate of 3%.ResultThe model indicated that the routine 4vHPV vaccination and the routine plus catch-up 4vHPV vaccination strategies could prevent approximately 434,130 and 472,502 cumulative cases of cervical cancer, 182,234 and 199,068 cumulative deaths from cervical cancer and 12,708,349 and 13,641,398 cumulative cases of HPV 6/11 related genital warts, respectively, when compared with no vaccination over 100 years. The estimated cost per QALY gained (ICER) when compared to no vaccination in Thailand was 8,370 THB/QALY for the routine vaccination and 9,650 THB/QALY for the routine with catch-up vaccination strategy.ConclusionConsidering the recommended threshold of 160,000 THB/QALY for Thailand, the implementation of the routine 4vHPV vaccination either alone or plus the catch-up vaccination was cost-effective as compared to the cervical cancer screening only

Effect of Synbiotic on the Gut Microbiota of Cesarean Delivered Infants : A Randomized, Double-blind, Multicenter Study

We determined the effect of short-chain galacto-oligosaccharides (scGOS), long-chain fructo-oligosaccharides (lcFOS) and Bifidobacterium breve M-16V on the gut microbiota of cesarean-born infants. Infants were randomized to receive a standard formula (control), the same with scGOS/lcFOS and B. breve M-16V (synbiotic), or with scGOS/lcFOS (prebiotic) from birth until week 16, 30 subjects born vaginally were included as a reference group. Synbiotic supplementation resulted in a higher bifidobacteria proportion from day 3/5 (P<0.0001) until week 8 (P=0.041), a reduction of Enterobacteriaceae from day 3/5 (P=0.002) till week 12 (P=0.016) compared to controls. This was accompanied with a lower fecal pH and higher acetate. In the synbiotic group, B. breve M-16V was detected 6 weeks postintervention in 38.7% of the infants. This synbiotic concept supported the early modulation of Bifidobacterium in C-section born infants that was associated with the emulation of the gut physiological environment observed in vaginally delivered infants.</p

A synbiotic intervention modulates meta-omics signatures of gut redox potential and acidity in elective caesarean born infants

The compromised gut microbiome that results from C-section birth has been hypothesized as a risk factor for the development of non-communicable diseases (NCD). In a double-blind randomized controlled study, 153 infants born by elective C-section received an infant formula supplemented with either synbiotic, prebiotics, or unsupplemented from birth until 4 months old. Vaginally born infants were included as a reference group. Stool samples were collected from day 3 till week 22. Multi-omics were deployed to investigate the impact of mode of delivery and nutrition on the development of the infant gut microbiome, and uncover putative biological mechanisms underlying the role of a compromised microbiome as a risk factor for NCD. Results: As early as day 3, infants born vaginally presented a hypoxic and acidic gut environment characterized by an enrichment of strict anaerobes (Bifidobacteriaceae). Infants born by C-section presented the hallmark of a compromised microbiome driven by an enrichment of Enterobacteriaceae. This was associated with meta-omics signatures characteristic of a microbiome adapted to a more oxygen-rich gut environment, enriched with genes associated with reactive oxygen species metabolism and lipopolysaccharide biosynthesis, and depleted in genes involved in the metabolism of milk carbohydrates. The synbiotic formula modulated expression of microbial genes involved in (oligo)saccharide metabolism, which emulates the eco-physiological gut environment observed in vaginally born infants. The resulting hypoxic and acidic milieu prevented the establishment of a compromised microbiome. Conclusions: This study deciphers the putative functional hallmarks of a compromised microbiome acquired during C-section birth, and the impact of nutrition that may counteract disturbed microbiome development

A synbiotic intervention modulates meta-omics signatures of gut redox potential and acidity in elective caesarean born infants

The compromised gut microbiome that results from C-section birth has been hypothesized as a risk factor for the development of non-communicable diseases (NCD). In a double-blind randomized controlled study, 153 infants born by elective C-section received an infant formula supplemented with either synbiotic, prebiotics, or unsupplemented from birth until 4 months old. Vaginally born infants were included as a reference group. Stool samples were collected from day 3 till week 22. Multi-omics were deployed to investigate the impact of mode of delivery and nutrition on the development of the infant gut microbiome, and uncover putative biological mechanisms underlying the role of a compromised microbiome as a risk factor for NCD. Results: As early as day 3, infants born vaginally presented a hypoxic and acidic gut environment characterized by an enrichment of strict anaerobes (Bifidobacteriaceae). Infants born by C-section presented the hallmark of a compromised microbiome driven by an enrichment of Enterobacteriaceae. This was associated with meta-omics signatures characteristic of a microbiome adapted to a more oxygen-rich gut environment, enriched with genes associated with reactive oxygen species metabolism and lipopolysaccharide biosynthesis, and depleted in genes involved in the metabolism of milk carbohydrates. The synbiotic formula modulated expression of microbial genes involved in (oligo)saccharide metabolism, which emulates the eco-physiological gut environment observed in vaginally born infants. The resulting hypoxic and acidic milieu prevented the establishment of a compromised microbiome. Conclusions: This study deciphers the putative functional hallmarks of a compromised microbiome acquired during C-section birth, and the impact of nutrition that may counteract disturbed microbiome development

Data for: "A synbiotic intervention modulates meta-omics signatures of gut redox potential and acidity in elective caesarean born infants"

Supplementary datasets published to support the paper, "A synbiotic intervention modulates meta-omics signatures of gut redox potential and acidity in elective caesarean born infants". Table 1 contains information on the number of subjects per group and number of 16S rRNA samples per group and time point, Table 2 contains 16S rRNA sequencing outputs, Table 3 contains Permutational Multivariate Analysis of Variance (PERMANOVA) tests, Table 4 contains 16S rRNA Family data (Mean and SD) per group and time point, Table 5 contains 16S rRNA Genus data (Mean and SD) per group and time point, and Table 6 provides 16S rRNA Species data (Mean and SD) per group and time point. Table 7-9 contain non-parametric Mann-Whitney U tests performed at each time point on each pair of study group combination at family level (Table 7), genus level (Table 8), and species level (table 9). Table 10 contains categorization of bacterial families into functional groups (anaerobic/aerobic metabolism and Lactic Acid Bacteria). Table 11 contains KEGG functional annotation and Table 12 contains SEED functional annotation. Raw 16S rRNA data are available at https://www.ebi.ac.uk using accession number PRJEB44790. Shotgun Metagenomics and Metatranscriptomics data are available at https://www.ncbi.nlm.nih.gov under accession number PRJNA726032