APC Microbiome Institute- Journal Articles

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    The microbiome of deep-sea fish reveals new microbial species and a sparsity of antibiotic resistance genes
    (Taylor & Francis, 2021-01) Collins, Fergus W. J.; Walsh, Calum J.; Gomez-Sala, Beatriz; Guijarro-Garcia, Elena; Stokes, David; Jakobsdottir, Klara B.; Kristjansson, Kristján; Burns, Finlay; Cotter, Paul D.; Rea, Mary C.; Hill, Colin; Ross, R. Paul; Science Foundation Ireland
    Adaptation to life in the deep-sea can be dramatic, with fish displaying behaviors and appearances unlike those seen in any other aquatic habitat. However, the extent of which adaptations may have developed at a microbial scale is not as clear. Shotgun metagenomic sequencing of the intestinal microbiome of 32 species of deep-sea fish from across the Atlantic Ocean revealed that many of the associated microbes differ extensively from those previously identified in reference databases. 111 individual metagenome-assembled genomes (MAGs) were constructed representing individual microbial species from the microbiomes of these fish, many of which are potentially novel bacterial taxa and provide a window into the microbial diversity in this underexplored environment. These MAGs also demonstrate how these microbes have adapted to deep-sea life by encoding a greater capacity for several cellular processes such as protein folding and DNA replication that can be inhibited by high pressure. Another intriguing feature was the almost complete lack of genes responsible for acquired resistance to known antibiotics in many of the samples. This highlights that deep-sea fish microbiomes may represent one of few animal-associated microbiomes with little influence from human activity. The ability of the microbes in these samples to bioluminesce is lower than expected given predictions that this trait has an important role in their life cycle at these depths. The study highlights the uniqueness, complexity and adaptation of microbial communities living in one of the largest and harshest environments on Earth.
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    Dose-response efficacy and mechanisms of orally administered CLA-producing Bifidobacterium breve CCFM683 on DSS-induced colitis in mice
    (Elsevier, 2020-12) Chen, Yang; Jin, Yan; Stanton, Catherine; Ross, R. Paul; Wang, Zhi; Zhao, Jianxin; Zhang, Hao; Yang, Bo; Chen, Wei; National Natural Science Foundation of China; National First-Class Discipline Program of Food Science and Technology; Fundamental Research Funds for the Central Universities; Postgraduate Research & Practice Innovation Program of Jiangsu Province; Wuxi Young Talent Foundation; Collaborative Innovationcenter of Food Safety and Quality Control in Jiangsu Province
    This study designed to explore the dose-effect relationship of CCFM683 in relieving colitis and investigate the mechanisms involved. Specifically, the concentration of mucin2, goblet cells and tight junction proteins were significantly up-regulated by 1010 and 109 cfu/day CCFM683. Moreover, interleukin (IL)-1 beta and IL-6 were significantly down-regulated by 1010 and 109 cfu/day CCFM683. Furthermore, gut microbiota in mice treated with 1010 and 109 cfu/day CCFM683 were rebalanced via improving the unbalanced interaction, regulating the diversity, increasing Bifidobacterium and decreasing Bacteroides and Sutterella. Moreover, the colonic conjugated linoleic acid (CLA) concentration was significantly positive correlated with the effectiveness of the strain in relieving colitis. The gavage dose of CCFM683 should be more than 108.65 cfu/day in mice for improving colitis according to dose-effect curve. In conclusion, CCFM683 supplementation alleviated colitis in a dose-dependent manner by improving intestinal epithelial barriers, protecting the intestinal mucus layer, restoring gut micro biota, and down-regulating the inflammatory cytokines.
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    Antiproliferation activity and mechanism of c9, t11, c15-CLNA and t9, t11, c15-CLNA from Lactobacillus plantarum ZS2058 on colon cancer cells
    (MDPI AG, 2020-03) Ren, Qing; Yang, Bo; Zhu, Guangzhen; Wang, Shunyu; Fu, Chengli; Zhang, Hao; Ross, R. Paul; Stanton, Catherine; Chen, Haiqin; Chen, Wei; National Natural Science Foundation of China; Fundamental Research Funds for the Central Universities; National First-Class Discipline Program of Food Science and Technology; Collaborative Innovationcenter of Food Safety and Quality Control in Jiangsu Province
    Conjugated linolenic acid (CLNA) is a type of ω-3 fatty acid which has been proven to have a series of benefits. However, there is no study about the function of Lactobacillus-derived CLNA isomer. Lactobacillus plantarum ZS2058 has been proven to manifest comprehensive functions and can produce CLNA. To investigate the specific functions of CLNA produced by this probiotic bacterium, two different conjugated a-linolenic acid (CLNA) isomers were successfully isolated. These isoforms, CLNA1 (c9, t11, c15-CLNA, purity 97.48%) and CLNA2 (c9, t11, t15-CLNA, purity 99.00%), both showed the ability to inhibit the growth of three types of colon cancer cells in a time- and concentration-dependent manner. In addition, the expression of MDA in Caco-2 cells was increased by CLNA1 or CLNA2, which indicated that lipid peroxidation was related to the antiproliferation activity of CLNAs. An examination of the key protein of pyroptosis showed that CLNA1 induced the cleavage of caspase-1 and gasdermin-D, while CLNA2 induced the cleavage of caspase-4, 5 and gasdermin-D. The addition of relative inhibitors could alleviate the pyroptosis by CLNAs. CLNA1 and CLNA2 showed no effect on caspase-3, 7, 9 and PARP-1, which were key proteins associated with apoptosis. No sub-diploid apoptotic peak appeared in the result of PI single staining test. In conclusion, CLNA1 activated caspase-1 and induced Caco-2 cell pyroptosis, whereas CLNA2 induced pyroptosis through the caspase-4/5-mediated pathway. The inhibition of Caco-2 cells by the two isomers was not related to apoptosis. This is the first study on the function of Lactobacillus-derived CLNA isomer. The inhibition pathway of Lactobacillus-derived CLNA isomer on colon cancer cells were proved.
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    Nisin E is a novel nisin variant produced by multiple Streptococcus equinus strains
    (MDPI, 2023-02) Sugrue, Ivan; Hill, Daragh; O'Connor, Paula M.; Day, Li; Stanton, Catherine; Hill, Colin; Ross, R. Paul; Teagasc; JPI Food Processing for Health Longlife Project; Science Foundation Ireland
    Nisin A, the prototypical lantibiotic, is an antimicrobial peptide currently utilised as a food preservative, with potential for therapeutic applications. Here, we describe nisin E, a novel nisin variant produced by two Streptococcus equinus strains, APC4007 and APC4008, isolated from sheep milk. Shotgun whole genome sequencing and analysis revealed biosynthetic gene clusters similar to nisin U, with a unique rearrangement of the core peptide encoding gene within the cluster. The 3100.8 Da peptide by MALDI-TOF mass spectrometry, is 75% identical to nisin A, with 10 differences, including 2 deletions: Ser29 and Ile30, and 8 substitutions: Ile4Lys, Gly18Thr, Asn20Pro, Met21Ile, His27Gly, Val32Phe, Ser33Gly, and Lys34Asn. Nisin E producing strains inhibited species of Lactobacillus, Bacillus, and Clostridiodes and were immune to nisin U. Sequence alignment identified putative promoter sequences across the nisin producer genera, allowing for the prediction of genes in Streptococcus to be potentially regulated by nisin. S. equinus pangenome BLAST analyses detected 6 nisin E operons across 44 publicly available genomes. An additional 20 genomes contained a subset of nisin E transport/immunity and regulatory genes (nseFEGRK), without adjacent peptide production genes. These genes suggest that nisin E response mechanisms, distinct from the canonical nisin immunity and resistance operons, are widespread across the S. equinus species. The discovery of this new nisin variant and its immunity determinants in S. equinus suggests a central role for nisin in the competitive nature of the species.
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    Different effects of different Lactobacillus acidophilus strains on DSS-induced colitis
    (MDPI, 2022-12) Huang, Zheng; Gong, Lei; Jin, Yan; Stanton, Catherine; Ross, R. Paul; Zhao, Jianxin; Yang, Bo; Chen, Wei; National Natural Science Foundation of China; 111 project; Collaborative Innovationcenter of Food Safety and Quality Control in Jiangsu Province
    Inflammatory bowel disease (IBD) is a worldwide chronic intestinal inflammatory immune-related disease. In this study, mice with dextran sulfate sodium (DSS)-induced colitis were used to evaluate the effect of Lactobacillus acidophilus on colitis. The results revealed that L. acidophilus CCFM137 and FAHWH11L56 show potential for relieving colitis symptoms, while L. acidophilus FGSYC48L79 did not show a protective effect. Moreover, L. acidophilus NCFM and FAHWH11L56 showed similar effects on various indicators of DSS-induced colitis, increasing the IL-10 and IL-17 in the colon, and modifying the CCL2/CCR2 axis and CCL3/CCR1 axis. For L. acidophilus CCFM137, its effects on colitis were different from the above two strains. Moreover, L. acidophilus FGSYC48L79 had negative effects on colitis by increasing the abundance of harmful bacteria in the gut microbiota and may promote the signaling of chemokines and their receptors. This may be related to its special genome compared to the other strains.