Specific synbiotics in early life protect against diet-induced obesity in adult mice

Aims: The metabolic state of human adults is associated with their gut microbiome. The symbiosis between host and microbiome is initiated at birth, and early life microbiome perturbation can disturb health throughout life. Here, we determined how beneficial microbiome interventions in early life affect metabolic health in adulthood. Methods: Postnatal diets were supplemented with either prebiotics (scGOS/lcFOS) or synbiotics (scGOS/lcFOS with Bifidobacterium breve M-16V) until post-natal (PN) day 42 in a well-established rodent model for nutritional programming. Mice were subsequently challenged with a high-fat Western-style diet (WSD) for 8 weeks. Body weight and composition were monitored, as was gut microbiota composition at PN21, 42 and 98. Markers of glucose homeostasis, lipid metabolism and host transcriptomics of 6 target tissues were determined in adulthood (PN98). Results: Early life synbiotics protected mice against WSD-induced excessive fat accumulation throughout life, replicable in 2 independent European animal facilities. Adult insulin sensitivity and dyslipidaemia were improved and most pronounced changes in gene expression were observed in the ileum. We observed subtle changes in faecal microbiota composition, both in early life and in adulthood, including increased abundance of Bifidobacterium. Microbiota transplantation using samples collected from synbiotics-supplemented adolescent mice at PN42 to age-matched germ-free recipients did not transfer the beneficial phenotype, indicating that synbiotics-modified microbiota at PN42 is not sufficient to transfer long-lasting protection of metabolic health status. Conclusion: Together, these findings show the potential and importance of timing of synbiotic interventions in early life during crucial microbiota development as a preventive measure to lower the risk of obesity and improve metabolic health throughout life

Early-life fecal microbiome and metabolome dynamics in response to an intervention with infant formula containing specific prebiotics and postbiotics

This study examined fecal metabolome dynamics to gain greater functional insights into the interactions between nutrition and the activity of the developing gut microbiota in healthy term-born infants. The fecal samples used here originate from a randomized, controlled, double-blind clinical study that assessed the efficacy of infant formula with prebiotics and postbiotics (experimental arm) compared with a standard infant formula (control arm). A group of exclusively breast-fed term infants was used as a reference arm. First, conventional targeted physiological and microbial measurements were performed, which showed differences in fecal Bifidobacterium levels and corresponding activity (e.g., lactate levels). Next, the overall fecal microbiota composition was determined by 16S rRNA gene amplicon sequencing. The microbiota composition profiles showed several bacterial groups in the experimental arm to be significantly different from the control arm and mostly closer to the levels observed in the reference arm. Finally, we applied an untargeted UPLC-MS/MS approach to examine changes in the fecal metabolome. Fecal metabolome profiles showed the most distinct separation, up to 404 significantly different metabolites, between the study arms. Our data reveal that infant formula with specific prebiotics and postbiotics may trigger responses in the intestinal microbiota composition that brings the ensuing fecal metabolite profile of formula-fed infants closer toward those observed in breast-fed infants. Furthermore, our results demonstrate a clear need for establishing an infant gut metabolome reference database to translate these metabolite profile dynamics into functional and physiologically relevant responses. NEW & NOTEWORTHY Untargeted metabolomics techniques can provide a ???snapshot??? of an ecosystem in response to environmental stimuli, such as nutritional interventions. Our analyses of fecal samples from infants demonstrate the potential of phenotyping by metabolomics while deciphering the complex interactions of early-life nutrition and gut microbiome development

Effects of a postbiotic and prebiotic mixture on suckling rats' microbiota and immunity

Human milk serves as a model for infant formula providing nutritional solutions for infants not able to receive enough mother's milk. Infant formulas aim to mimic the composition and functionality of human milk by providing ingredients reflecting those of the latest human milk insights, such as prebiotics, probiotics and postbiotics. The aim of this study was to examine the effects of the supplementation with a postbiotic (LactofidusTM) and its combination with the prebiotics short-chain galactooligosaccharides (scGOS) and long-chain fructooligosaccharides (lcFOS) in a preclinical model of healthy suckling rats. Pups were supplemented daily with LactofidusTM (POST group) and/or scGOS/lcFOS (P+P and PRE groups, respectively). Body weight and fecal consistency were analyzed. At the end of the study, immunoglobulin (Ig) profile, intestinal gene expression, microbiota composition and short chain fatty acid (SCFA) proportion were quantified. The supplementation with all nutritional interventions modulated the Ig profile, but the prebiotic mixture and the postbiotic induced differential effects: whereas scGOS/lcFOS induced softer feces and modulated microbiota composition and SCFA profile, Lactofidus upregulated Toll-like receptors gene expression. The use of the combination of scGOS/lcFOS and Lactofidus showed the effects observed for the oligosaccharides separately, as well as showing a synergistic impact on animal growth. Thus, the combined use of both products seems to be a good strategy to modulate immune and microbial features in early life. View Full-Text Keywords: postbiotic; prebiotic; suckling rats; Lactofidus; scGOS/lcFOS; microbiota; SCF

Influence of timing of maternal antibiotic administration during caesarean section on infant microbial colonisation:a randomised controlled trial

OBJECTIVE: Revised guidelines for caesarean section (CS) advise maternal antibiotic administration prior to skin incision instead of after umbilical cord clamping, unintentionally exposing the infant to antibiotics antenatally. We aimed to investigate if timing of intrapartum antibiotics contributes to the impairment of microbiota colonisation in CS born infants. DESIGN: In this randomised controlled trial, women delivering via CS received antibiotics prior to skin incision (n=20) or after umbilical cord clamping (n=20). A third control group of vaginally delivering women (n=23) was included. Faecal microbiota was determined from all infants at 1, 7 and 28 days after birth and at 3 years by 16S rRNA gene sequencing and whole-metagenome shotgun sequencing. RESULTS: Compared with vaginally born infants, profound differences were found in microbial diversity and composition in both CS groups in the first month of life. A decreased abundance in species belonging to the genera Bacteroides and Bifidobacterium was found with a concurrent increase in members belonging to the phylum Proteobacteria. These differences could not be observed at 3 years of age. No statistically significant differences were observed in taxonomic and functional composition of the microbiome between both CS groups at any of the time points. CONCLUSION: We confirmed that microbiome colonisation is strongly affected by CS delivery. Our findings suggest that maternal antibiotic administration prior to CS does not result in a second hit on the compromised microbiome. Future, larger studies should confirm that antenatal antibiotic exposure in CS born infants does not aggravate colonisation impairment and impact long-term health

Faecal Microbiota Composition in Adults Is Associated with the FUT2 Gene Determining the Secretor Status

Peer reviewe

Microbial DNA fingerprinting of human fingerprints: dynamic colonization of fingertip microflora challenges human host inferences for forensic purposes

Human fingertip microflora is transferred to touched objects and may provide forensically relevant information on individual hosts, such as on geographic origins, if endogenous microbial skin species/strains would be retrievable from physical fingerprints and would carry geographically restricted DNA diversity. We tested the suitability of physical fingerprints for revealing human host information, with geographic inference as example, via microbial DNA fingerprinting. We showed that the transient exogenous fingertip microflora is frequently different from the resident endogenous bacteria of the same individuals. In only 54% of the experiments, the DNA analysis of the transient fingertip microflora allowed the detection of defined, but often not the major, elements of the resident microflora. Although we found microbial persistency in certain individuals, time-wise variation of transient and resident microflora within individuals was also observed when resampling fingerprints after 3 weeks. While microbial species differed considerably in their frequency spectrum between fingerprint samples from volunteers in Europe and southern Asia, there was no clear geographic distinction between Staphylococcus strains in a cluster analysis, although bacterial genotypes did not overlap between both continental regions. Our results, though limited in quantity, clearly demonstrate that the dynamic fingerprint microflora challenges human host inferences for forensic purposes including geographic ones. Overall, our results suggest that human fingerprint microflora is too dynamic to allow for forensic marker developments for retrieving human information

Fat, fibre and cancer risk in African Americans and rural Africans

Rates of colon cancer are much higher in African Americans (65: 100,000) than in rural South Africans (Peer reviewe

Fat, fibre and cancer risk in African Americans and rural Africans

Rates of colon cancer are much higher in African Americans (65: 100,000) than in rural South Africans (Peer reviewe

Metaproteomic and 16S rRNA Gene Sequencing Analysis of the Infant Fecal Microbiome

A metaproteomic analysis was conducted on the fecal microbiome of eight infants to characterize global protein and pathway expression. Although mass spectrometry-based proteomics is now a routine tool, analysis of the microbiome presents specific technical challenges, including the complexity and dynamic range of member taxa, the need for well-annotated metagenomic databases, and high inter-protein sequence redundancy and similarity. In this study, an approach was developed for assessment of biological phenotype and metabolic status, as a functional complement to DNA sequence analysis. Fecal samples were prepared and analysed by tandem mass spectrometry and a homology-based meta-clustering strategy was used to combine peptides from multiple species into representative proteins. In total, 15,250 unique peptides were sequenced and assigned to 2154 metaclusters, which were then assigned to pathways and functional groups. Differences were noted in several pathways, consistent with the dominant genera observed in different subjects. Although this study was not powered to draw conclusions from the comparisons, the results obtained demonstrate the applicability of this approach and provide the methods needed for performing semi-quantitative comparisons of human fecal microbiome composition, physiology and metabolism, as well as a more detailed assessment of microbial composition in comparison to 16S rRNA gene sequencing.</p