IRIS Collection

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    Envisioning emerging frontiers on human gut microbiota and its applications
    (Wiley, 2020-09) Ventura, Marco; Milani, Christian; Turroni, Francesca; van Sinderen, Douwe; European Commission; Fondazione Cariparma; Science Foundation Ireland; GenProbio
    The human gut microbiota is involved in multiple health-influencing host interactions during the host's entire life span. Microbes colonize the infant gut instantaneously after birth and subsequently the founding and interactive progress of this early gut microbiota is considered to be driven and modulated by different host- and microbe-associated forces. A rising number of studies propose that the composition of the human gut microbiota in the early stages of life impact on the human health conditions at later stages of life. This notion has powered research aimed at detailed investigations of the infant gut microbiota composition. Nevertheless, the molecular mechanisms supporting the gut microbiome functionality and the interaction of the early gut microbes with the human host remain largely unknown.
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    Bifidobacterium breve UCC2003 induces a distinct global transcriptomic program in neonatal murine intestinal epithelial cells
    (Elsevier, 2020-07) Kiu, Raymond; Treveil, Agatha; Harnisch, Lukas C.; Caim, Shabhonam; Leclaire, Charlotte; van Sinderen, Douwe; Korcsmaros, Tamas; Hall, Lindsay J.; Norwich Bioscience Institutes (NBI) Computing infrastructure for Science (CiS) group; Wellcome Trust; Gut Microbes and Health; Genomics for Food security; Norwich Research Park Biosciences; Science Foundation Ireland
    The underlying health-driving mechanisms of Bifidobacterium during early life are not well understood, particularly how this microbiota member may modulate the intestinal barrier via programming of intestinal epithelial cells (IECs). We investigated the impact of Bifidobacterium breve UCC2003 on the transcriptome of neonatal murine IECs. Small IECs from two-week-old neonatal mice administered B. breve UCC2003 or PBS (control) were subjected to global RNA sequencing, and differentially expressed genes, pathways, and affected cell types were determined. We observed extensive regulation of the IEC transcriptome with ∼4,000 genes significantly up-regulated, including key genes linked with epithelial barrier function. Enrichment of cell differentiation pathways was observed, along with an overrepresentation of stem cell marker genes, indicating an increase in the regenerative potential of the epithelial layer. In conclusion, B. breve UCC2003 plays a central role in driving intestinal epithelium homeostatic development during early life and suggests future avenues for next-stage clinical studies.
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    Human milk oligosaccharides: shaping the infant gut microbiota and supporting health
    (Elsevier, 2020-09) Walsh, Clodagh; Lane, Jonathan A.; van Sinderen, Douwe; Hickey, Rita M.; H and H Group; Science Foundation Ireland
    Human milk oligosaccharides (HMO) are complex sugars which are found in breast milk at significant concentrations and with unique structural diversity. These sugars are the fourth most abundant component of human milk after water, lipids, and lactose and yet provide no direct nutritional value to the infant. Recent research has highlighted that HMOs have various functional roles to play in infant development. These sugars act as prebiotics by promoting growth of beneficial intestinal bacteria thereby generating short-chain fatty acids which are critical for gut health. HMOs also directly modulate host-epithelial immune responses and can selectively reduce binding of pathogenic bacteria and viruses to the gut epithelium preventing the emergence of a disease. This review covers current knowledge related to the functional biology of HMOs and their associated impact on infant gut health.
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    From lab bench to formulated ingredient: characterization, production, and commercialization of human milk oligosaccharides
    (Elsevier, 2020-09) Walsh, Clodagh; Lane, Jonathan A.; van Sinderen, Douwe; Hickey, Rita M.; H & H Group; Science Foundation Ireland
    Human milk oligosaccharides (HMOs) are known to positively influence infant health. Extensive variation exists in the levels, diversity, and complexity of oligosaccharides in the milk of a lactating mother. Until recently, limited availability of HMOs hampered their use in clinical applications. Most HMOs are unique to human milk, and have proven difficult and expensive to isolate and synthesize. Added to that, analysis of these complex glycans in milk samples requires state-of-the-art analytical instruments and associated technologies. The current review provides a critical overview of methods used in HMO analysis, and highlights the importance of understanding the factors which influence their composition and structural diversity. We also discuss recently employed strategies to overcome the availability of HMOs at industrial scale including microbial metabolic engineering and chemoenzymatic techniques. Finally, we examine how these recent advancements have opened up new avenues for future research and nutraceutical applications.
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    Exploring species-level infant gut bacterial biodiversity by meta-analysis and formulation of an optimized cultivation medium
    (Nature Research, 2022-10) Alessandri, Giulia; Fontana, Federico; Mancabelli, Leonardo; Lugli, Gabriele Andrea; Tarracchini, Chiara; Argentini, Chiara; Longhi, Giulia; Viappiani, Alice; Milani, Christian; Turroni, Francesca; van Sinderen, Douwe; Ventura, Marco; GenProbio srl; Università degli Studi di Parma; Science Foundation Ireland; Fondazione Cariparma; Ministero della Salute
    In vitro gut cultivation models provide host-uncoupled, fast, and cost-efficient solutions to investigate the effects of intrinsic and extrinsic factors impacting on both composition and functionality of the intestinal microbial ecosystem. However, to ensure the maintenance and survival of gut microbial players and preserve their functions, these systems require close monitoring of several variables, including oxygen concentration, pH, and temperature, as well as the use of a culture medium satisfying the microbial nutritional requirements. In this context, in order to identify the macro- and micro-nutrients necessary for in vitro cultivation of the infant gut microbiota, a meta-analysis based on 1669 publicly available shotgun metagenomic samples corresponding to fecal samples of healthy, full-term infants aged from a few days to three years was performed to define the predominant species characterizing the "infant-like" gut microbial ecosystem. A subsequent comparison of growth performances was made using infant fecal samples that contained the most abundant bacterial taxa of the infant gut microbiota, when cultivated on 18 different culture media. This growth analysis was performed by means of flow cytometry-based bacterial cell enumeration and shallow shotgun sequencing, which allowed the formulation of an optimized growth medium, i.e., Infant Gut Super Medium (IGSM), which maintains and sustains the infant gut microbial biodiversity under in vitro growth conditions. Furthermore, this formulation was used to evaluate the in vitro effect of two drugs commonly used in pediatrics, i.e., acetaminophen and simethicone, on the taxonomic composition of the infant gut microbiota.