APC Microbiome Ireland - Journal Articles
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Item Prebiotic administration modulates gut microbiota and faecal short-chain fatty acid concentrations but does not prevent chronic intermittent hypoxia-induced apnoea and hypertension in adult rats(Elsevier, 2020) O'Connor, Karen M.; Lucking, Eric F.; Bastiaanssen, Thomaz F. S.; Peterson, Veronica L.; Crispie, Fiona; Cotter, Paul D.; Clarke, Gerard; Cryan, John F.; O'Halloran, Ken D.; Science Foundation IrelandBackground: Evidence is accruing to suggest that microbiota-gut-brain signalling plays a regulatory role in cardiorespiratory physiology. Chronic intermittent hypoxia (CIH), modelling human sleep apnoea, affects gut microbiota composition and elicits cardiorespiratory morbidity. We investigated if treatment with prebiotics ameliorates cardiorespiratory dysfunction in CIH-exposed rats. Methods: Adult male rats were exposed to CIH (96 cycles/day, 6.0% O2 at nadir) for 14 consecutive days with and without prebiotic supplementation (fructo- and galacto-oligosaccharides) beginning two weeks prior to gas exposures. Findings: CIH increased apnoea index and caused hypertension. CIH exposure had modest effects on the gut microbiota, decreasing the relative abundance of Lactobacilli species, but had no effect on microbial functional characteristics. Faecal short-chain fatty acid (SCFA) concentrations, plasma and brainstem pro-inflammatory cytokine concentrations and brainstem neurochemistry were unaffected by exposure to CIH. Prebiotic administration modulated gut microbiota composition and diversity, altering gut-metabolic (GMMs) and gut-brain (GBMs) modules and increased faecal acetic and propionic acid concentrations, but did not prevent adverse CIH-induced cardiorespiratory phenotypes. Interpretation: CIH-induced cardiorespiratory dysfunction is not dependant upon changes in microbial functional characteristics and decreased faecal SCFA concentrations. Prebiotic-related modulation of microbial function and resultant increases in faecal SCFAs were not sufficient to prevent CIH-induced apnoea and hypertension in our model. Our results do not exclude the potential for microbiota-gut-brain axis involvement in OSA-related cardiorespiratory morbidity, but they demonstrate that in a relatively mild model of CIH, sufficient to evoke classic cardiorespiratory dysfunction, such changes are not obligatory for the development of morbidity, but may become relevant in the elaboration and maintenance of cardiorespiratory morbidity with progressive disease. Funding: Department of Physiology and APC Microbiome Ireland, University College Cork, Ireland. APC Microbiome Ireland is funded byScience Foundation Ireland, through the Government’s National Development Plan.Item Isolation and characterization of a novel lytic Parabacteroides distasonis bacteriophage φPDS1 from the human gut(Taylor & Francis, 2024) Cortés-Martín, Adrián; Denise, Rémi; Guerin, Emma; Stockdale, Stephen R.; Draper, Lorraine A.; Ross, R. Paul; Shkoporov, Andrey N.; Hill, Colin; Science Foundation IrelandThe human gut microbiome plays a significant role in health and disease. The viral component (virome) is predominantly composed of bacteriophages (phages) and has received significantly less attention in comparison to the bacteriome. This knowledge gap is largely due to challenges associated with the isolation and characterization of novel gut phages, and bioinformatic hurdles such as the lack of a universal phage marker gene and the absence of sufficient numbers of homologs in viral databases. Here, we describe the isolation from human feces of a novel lytic phage with siphovirus morphology, φPDS1, infecting Parabacteroides distasonis APCS2/PD, and classified within a newly proposed Sagittacolavirus genus. In silico and biological characterization of this phage is presented in this study. Key to the isolation of φPDS1 was the antibiotic-driven selective enrichment of the bacterial host in a fecal fermenter. Despite producing plaques and lacking genes associated with lysogeny, φPDS1 demonstrates the ability to coexist in liquid culture for multiple days without affecting the abundance of its host. Multiple studies have shown that changes in Parabacteroides distasonis abundance can be linked to various disease states, rendering this novel phage-host pair and their interactions of particular interest.Item Emerging issues in probiotic safety: 2023 perspectives(Taylor & Francis, 2023) Merenstein, Daniel; Pot, Bruno; Leyer, Gregory; Ouwehand, Arthur C.; Preidis, Geoffrey A.; Elkins, Christopher A.; Hill, Colin; Lewis, Zachery T.; Shane, Andi L.; Zmora, Niv; Petrova, Mariya I.; Collado, Maria Carmen; Morelli, Lorenzo; Montoya, Gina A.; Szajewska, Hania; Tancredi, Daniel J.; Sanders, Mary EllenProbiotics are used for both generally healthy consumers and in clinical settings. However, theoretical and proven adverse events from probiotic consumption exist. New probiotic strains and products, as well as expanding use of probiotics into vulnerable populations, warrants concise, and actionable recommendations on how to work toward their safe and effective use. The International Scientific Association for Probiotics and Prebiotics convened a meeting to discuss and produce evidence-based recommendations on potential acute and long-term risks, risks to vulnerable populations, the importance for probiotic product quality to match the needs of vulnerable populations, and the need for adverse event reporting related to probiotic use. The importance of whole genome sequencing, which enables determination of virulence, toxin, and antibiotic resistance genes, as well as clear assignment of species and strain identity, is emphasized. We present recommendations to guide the scientific and medical community on judging probiotic safety.Item Harnessing the endogenous Type I-C CRISPR-Cas system for genome editing in Bifidobacterium breve(American Society for Microbiology, 2024-02-06) Han, Xiao; Chang, Lulu; Chen, Haiqin; Zhao, Jianxin; Tian, Fengwei; Ross, R. Paul; Stanton, Catherine; van Sinderen, Douwe; Chen, Wei; Yang, Bo; Dudley, Edward G.; National Key Research and Development Program of China; National Natural Science Foundation of China; Project 211; Collaborative Innovationcenter of Food Safety and Quality Control in Jiangsu ProvinceBifidobacterium breve, one of the main bifidobacterial species colonizing the human gastrointestinal tract in early life, has received extensive attention for its purported beneficial effects on human health. However, exploration of the mode of action of such beneficial effects exerted by B. breve is cumbersome due to the lack of effective genetic tools, which limits its synthetic biology application. The widespread presence of CRISPR-Cas systems in the B. breve genome makes endogenous CRISPR-based gene editing toolkits a promising tool. This study revealed that Type I-C CRISPR-Cas systems in B. breve can be divided into two groups based on the amino acid sequences encoded by cas gene clusters. Deletion of the gene coding uracil phosphoribosyl-transferase (upp) was achieved in five B. breve strains from both groups using this system. In addition, translational termination of uracil phosphoribosyl-transferase was successfully achieved in B. breve FJSWX38M7 by single-base substitution of the upp gene and insertion of three stop codons. The gene encoding linoleic acid isomerase (bbi) in B. breve, being a characteristic trait, was deleted after plasmid curing, which rendered it unable to convert linoleic acid into conjugated linoleic acid, demonstrating the feasibility of successive editing. This study expands the toolkit for gene manipulation in B. breve and provides a new approach toward functional genome editing and analysis of B. breve strains.Item Linking human milk oligosaccharide metabolism and early life gut microbiota: bifidobacteria and beyond(American Society for Microbiology, 2024-01-11) Lordan, Cathy; Roche, Aoife K.; Delsing, Dianne; Nauta, Arjen; Groeneveld, Andre; MacSharry, John; Cotter, Paul D.; van Sinderen, Douwe; Rey, Federico; FrieslandCampinaHuman milk oligosaccharides (HMOs) are complex, multi-functional glycans present in human breast milk. They represent an intricate mix of heterogeneous structures which reach the infant intestine in an intact form as they resist gastrointestinal digestion. Therefore, they confer a multitude of benefits, directly and/or indirectly, to the developing neonate. Certain bifidobacterial species, being among the earliest gut colonizers of breast-fed infants, have an adapted functional capacity to metabolize various HMO structures. This ability is typically observed in infant-associated bifidobacteria, as opposed to bifidobacteria associated with a mature microbiota. In recent years, information has been gleaned regarding how these infant-associated bifidobacteria as well as certain other taxa are able to assimilate HMOs, including the mechanistic strategies enabling their acquisition and consumption. Additionally, complex metabolic interactions occur between microbes facilitated by HMOs, including the utilization of breakdown products released from HMO degradation. Interest in HMO-mediated changes in microbial composition and function has been the focal point of numerous studies, in recent times fueled by the availability of individual biosynthetic HMOs, some of which are now commonly included in infant formula. In this review, we outline the main HMO assimilatory and catabolic strategies employed by infant-associated bifidobacteria, discuss other taxa that exhibit breast milk glycan degradation capacity, and cover HMO-supported cross-feeding interactions and related metabolites that have been described thus far.