702 results on '"Catherine, Stanton"'
Search Results
2. Feed your microbes to deal with stress: a psychobiotic diet impacts microbial stability and perceived stress in a healthy adult population
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Kirsten Berding, Thomaz F. S. Bastiaanssen, Gerard M. Moloney, Serena Boscaini, Conall R. Strain, Andrea Anesi, Caitriona Long-Smith, Fulvio Mattivi, Catherine Stanton, Gerard Clarke, Timothy G. Dinan, and John F. Cryan
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psychobiotic diet ,intervention study ,perceived stress ,3-hydroxykynurenine ,metabolomics ,5-hydroxyindole-3-acetic acid ,Cellular and Molecular Neuroscience ,Psychiatry and Mental health ,perceived stress, microbiota, metabolomics ,tryptophan ,tryptophan metabolism ,microbiota ,Settore CHIM/10 - CHIMICA DEGLI ALIMENTI ,Molecular Biology - Abstract
The impact of diet on the microbiota composition and the role of diet in supporting optimal mental health have received much attention in the last decade. However, whether whole dietary approaches can exert psychobiotic effects is largely understudied. Thus, we investigated the influence of a psychobiotic diet (high in prebiotic and fermented foods) on the microbial profile and function as well as on mental health outcomes in a healthy human population. Forty-five adults were randomized into either a psychobiotic (n = 24) or control (n = 21) diet for 4 weeks. Fecal microbiota composition and function was characterized using shotgun sequencing. Stress, overall health and diet were assessed using validated questionnaires. Metabolic profiling of plasma, urine and fecal samples was performed. Intervention with a psychobiotic diet resulted in reductions of perceived stress (32% in diet vs. 17% in control group), but not between groups. Similarly, biological marker of stress were not affected. Additionally, higher adherence to the diet resulted in stronger decreases in perceived stress. While the dietary intervention elicited only subtle changes in microbial composition and function, significant changes in the level of 40 specific fecal lipids and urinary tryptophan metabolites were observed. Lastly, microbial volatility was linked to greater changes in perceived stress scores in those on the psychobiotic diet. These results highlight that dietary approaches can be used to reduce perceived stress in a human cohort. Using microbiota-targeted diets to positively modulate gut-brain communication holds possibilities for the reduction of stress and stress-associated disorders, but additional research is warranted to investigate underlying mechanisms, including the role of the microbiota.
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- 2023
3. Bifidobacterium longum subsp. infantis FJSYZ1M3 ameliorates DSS-induced colitis by maintaining the intestinal barrier, regulating inflammatory cytokines, and modifying gut microbiota
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Mingjie Li, Jiuhong Ding, Catherine Stanton, R. Paul Ross, Jianxin Zhao, Bo Yang, and Wei Chen
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General Medicine ,Food Science - Abstract
B. longum subsp. infantis FJSYZ1M3 could significantly alleviate the symptoms of colitis by reducing the damage of the intestinal barrier, regulating the inflammatory cytokines, up-regulating butyric acid, and relieving gut microbiota disturbance.
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- 2023
4. Exploiting lactic acid bacteria for colorectal cancer: a recent update
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Yang Chen, Bo Yang, Jianxin Zhao, R. Paul Ross, Catherine Stanton, Hao Zhang, and Wei Chen
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General Medicine ,Industrial and Manufacturing Engineering ,Food Science - Abstract
Colorectal cancer (CRC) is the third most common cancer in the world. Currently, chemotherapy and radiotherapy used to treat CRC exhibit many side effects, hence, it is an urgent need to design effective therapies to prevent and treat CRC. Lactic acid bacteria (LAB) can regulate gut microbiota, intestinal immunity, and intestinal mechanical barrier, which is becoming a hot product for the prevention and treatment of CRC, whereas comprehensive reviews of their anti-CRC mechanisms are limited. This review systematically reveals the latest incidence, mortality, risk factors, and molecular mechanisms of CRC, then summarizes the roles of probiotics in alleviating CRC in animal and clinical studies and critically reviews the possible mechanisms by which these interventions exert their activities. It then shows the limitations in mechanisms and clinical studies, and the suggestions for future research are also put forward, which will play an important role in guiding and promoting the basic and clinical research of remising CRC by LAB and the development of LAB products.
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- 2022
5. Bifidobacterium breve CCFM1078 Alleviates Collagen-Induced Arthritis in Rats via Modulating the Gut Microbiota and Repairing the Intestinal Barrier Damage
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Bowen Li, Mengfan Ding, Xiaoming Liu, Jianxin Zhao, R. Paul Ross, Catherine Stanton, Bo Yang, and Wei Chen
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General Chemistry ,General Agricultural and Biological Sciences - Published
- 2022
6. Corrigendum to: Naturally Derived Polyphenols Protect Against Corticosterone-Induced Changes in Primary Cortical Neurons
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Francisco Donoso, Valerie T Ramírez, Anna V Golubeva, Gerard Moloney, Catherine Stanton, Timothy G Dinan, and John F Cryan
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Pharmacology ,Psychiatry and Mental health ,Pharmacology (medical) - Published
- 2023
7. Sex, pain, and the microbiome: The relationship between baseline gut microbiota composition, gender and somatic pain in healthy individuals
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Valentina, Caputi, Thomaz F S, Bastiaanssen, Veronica, Peterson, Jahangir, Sajjad, Luuk P, Simons, Amy, Murphy, Catherine, Stanton, Brian, McNamara, George D, Shorten, John F, Cryan, and Siobhain M, O'Mahony
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Behavioral Neuroscience ,Endocrine and Autonomic Systems ,Immunology - Abstract
Relative to men, women present with pain conditions more commonly. Although consistent differences exist between men and women in terms of physiological pain sensitivity, the underlying mechanisms are incompletely understood and yet could inform the development of effective sex specific treatments for pain. The gut microbiota can modulate nervous system functioning, including pain signaling pathways. We hypothesized that the gut microbiota and critical components of the gut-brain axis might influence electrical pain thresholds. Further, we hypothesized that sex, menstrual cycle, and hormonal contraceptive use might account for inter-sex differences in pain perception.Healthy, non-obese males (N = 15) and females (N = 16), (nine of whom were using hormonal contraceptives), were recruited. Male subjects were invited to undergo testing once, whereas females were invited three times across the menstrual cycle, based on self-reported early follicular (EF), late follicular (LF), or mid-luteal (ML) phase. On test days, electrical stimulation on the right ankle was performed; salivary cortisol levels were measured in the morning; levels of lipopolysaccharide-binding protein (LBP), soluble CD14 (sCD14), pro-inflammatory cytokines were assessed in plasma, and microbiota composition and short-chain fatty acids (SCFAs) levels were determined in fecal samples.We observed that the pain tolerance threshold/pain sensation threshold (PTT/PST) ratio was significantly lesser in women than men, but not PST or PTT alone. Further, hormonal contraceptive use was associated with increased LBP levels (LFML phase), whilst sCD14 levels or inflammatory cytokines were not affected. Interestingly, in women, hormonal contraceptive use was associated with an increase in the relative abundance of Erysipelatoclostridium, and the relative abundances of certain bacterial genera correlated positively with pain sensation thresholds (Prevotella and Megasphera) during the LF phase and cortisol awakening response (Anaerofustis) during the ML phase. In comparison with men, women displayed overall stronger associations between i) SCFAs data, ii) cortisol data, iii) inflammatory cytokines and PTT and PST.Our findings support the hypothesis that the gut microbiota may be one of the factors determining the physiological inter-sex differences in pain perception. Further research is needed to investigate the molecular mechanisms by which specific sex hormones and gut microbes modulate pain signaling pathways, but this study highlights the possibilities for innovative individual targeted therapies for pain management.
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- 2022
8. Modulation of the gut microbiome with nisin
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Catherine O’Reilly, Ghjuvan M. Grimaud, Mairéad Coakley, Paula M. O’Connor, Harsh Mathur, Veronica L. Peterson, Ciara M. O’Donovan, Peadar G. Lawlor, Paul D. Cotter, Catherine Stanton, Mary C. Rea, Colin Hill, and R. Paul Ross
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Multidisciplinary - Abstract
Nisin is a broad spectrum bacteriocin used extensively as a food preservative that was identified in Lactococcus lactis nearly a century ago. We show that orally-ingested nisin survives transit through the porcine gastrointestinal tract intact (as evidenced by activity and molecular weight determination) where it impacts both the composition and functioning of the microbiota. Specifically, nisin treatment caused a reversible decrease in Gram positive bacteria, resulting in a reshaping of the Firmicutes and a corresponding relative increase in Gram negative Proteobacteria. These changes were mirrored by the modification in relative abundance of pathways involved in acetate, butyrate (decreased) and propionate (increased) synthesis which correlated with overall reductions in short chain fatty acid levels in stool. These reversible changes that occur as a result of nisin ingestion demonstrate the potential of bacteriocins like nisin to shape mammalian microbiomes and impact on the functionality of the community.
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- 2023
9. A longitudinal study of fatty acid profiles, macronutrient levels, and plasmin activity in human milk
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Fanyu Meng, Therese Uniacke-Lowe, Elisa Lanfranchi, Grainne Meehan, Carol-Anne O'Shea, Theresa Dennehy, Anthony C. Ryan, Catherine Stanton, and Alan L. Kelly
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Nutrition and Dietetics ,Endocrinology, Diabetes and Metabolism ,Food Science - Abstract
IntroductionHuman milk provides nutrients essential for infant growth and health, levels of which are dynamic during lactation.MethodsIn this study, changes in macronutrients, fatty acids, and plasmin activities over the first six months of lactation in term milk were studied.ResultsThere was a significant influence of lactation stage on levels of protein and plasmin activities, but not on levels of fat and carbohydrate in term milk. Concerning fatty acids in term milk, levels of caproic acid and α-linolenic acid increased significantly (p < 0.05), whereas those of arachidonic acid and docosahexaenoic acid decreased, in the six months after birth. Significant impacts of maternal pre-pregnancy BMI and infant gender on fatty acid profiles were also found. Multivariate statistical analysis showed that protein level, plasmin activity, and several fatty acids (α-linolenic acid, lignoceric acid, and docasadienoic acid) contributed strongly to discrimination of milk from different lactational stages.DiscussionThe study demonstrates that not all but some fatty acids were influenced by lactation, whereas protein and protease levels showed clear decreasing trends during lactation, which may help in understanding the nutritional requirements of infants.
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- 2023
10. Altered oral microbiome in Sudanese Toombak smokeless tobacco users carries a newly emerging risk of squamous cell carcinoma development and progression
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Amel Sami, Imad Elimairi, C. Anthony Ryan, Catherine Stanton, Dhrati Patangia, and R. Paul Ross
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Multidisciplinary - Abstract
There are an estimated 6–10 million smokeless tobacco (Toombak) users in Sudan, the majority being males. Toombak is known to be a carcinogenic product that is likely to modify the oral microbiome spatiality into a high-risk potential for the development and progression of oral cancer, but previous studies are lacking in this field. Here, we endeavour for the first time the exploration of the oral microbiome in key mucosal areas of the oral cavity and assess the microbiome variations in premalignant and oral squamous cell carcinoma (OSCC) samples from both users and non-users of Toombak. 16S rRNA sequencing was performed on DNA obtained from pooled saliva, oral mucosa and supragingival plaque from 78 Sudanese users and non-users of Toombak, aged between 20 and 70 years. In 32 of the pooled saliva samples, the mycobiome (fungal) environment was analysed through ITS sequencing. Then, 46 formalin-fixed paraffin-embedded samples of premalignant and OSCC samples were collected, and their associated microbiomes sequenced. The oral Sudanese microbiome was found to be enriched in Streptococcaceae, but Staphylococcaceae were significantly more abundant amongst Toombak users. Genera enriched in the oral cavity of Toombak users included Corynebacterium_1 and Cardiobacterium while in non-users, Prevotella, Lactobacillus and Bifidobacterium were prominent. Aspergillus was the most abundant fungus in the mouths of Toombak users with a marked loss of Candida. The genus Corynebacterium_1 was abundant in the buccal, floor of the mouth and saliva microbiomes as well as in oral cancer samples from Toombak users indicating a possible role for this genus in the early stages of oral cancer development. An oral cancer microbiome that favours poor survival and metastasis in those who use Toombak also emerged that includes the genera Stenotrophomonas and Schlegelella. Those utilising Toombak carry an altered oral microbiome that may be an additional risk factor for this products carcinogenicity to the oral structures. These significant microbiome modulations are a newly emerging key driving factor in oral cancer development and progression in Toombak users while it is also shown that Toombak users carry an oral cancer microbiome that may increase the potential for a poorer prognosis.
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- 2023
11. Microbial metabolites as modulators of the infant gut microbiome and host-microbial interactions in early life
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Henrik M. Roager, Catherine Stanton, and Lindsay J. Hall
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Microbiology (medical) ,Infectious Diseases ,Health ,Microbiota ,Host ,Metabolites ,Gastroenterology ,Metabolomics ,Infants ,Microbiology ,Diet - Abstract
The development of infant gut microbiome is a pivotal process affecting the ecology and function of the microbiome, as well as host health. While the establishment of the infant microbiome has been of interest for decades, the focus on gut microbial metabolism and the resulting small molecules (metabolites) has been rather limited. However, technological and computational advances are now enabling researchers to profile the plethora of metabolites in the infant gut, allowing for improved understanding of how gut microbial-derived metabolites drive microbiome community structuring and host-microbial interactions. Here, we review the current knowledge on development of the infant gut microbiota and metabolism within the first year of life, and discuss how these microbial metabolites are key for enhancing our basic understanding of interactions during the early life developmental window.
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- 2023
12. The gut microbiome in social anxiety disorder: evidence of altered composition and function
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Mary I. Butler, Thomaz F. S. Bastiaanssen, Caitriona Long-Smith, Sabrina Morkl, Kirsten Berding, Nathaniel L. Ritz, Conall Strain, Dhrati Patangia, Shriram Patel, Catherine Stanton, Siobhain M. O’Mahony, John F. Cryan, Gerard Clarke, and Timothy G. Dinan
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Cellular and Molecular Neuroscience ,Psychiatry and Mental health ,Biological Psychiatry - Abstract
The microbiome-gut-brain axis plays a role in anxiety, the stress response and social development, and is of growing interest in neuropsychiatric conditions. The gut microbiota shows compositional alterations in a variety of psychiatric disorders including depression, generalised anxiety disorder (GAD), autism spectrum disorder (ASD) and schizophrenia but studies investigating the gut microbiome in social anxiety disorder (SAD) are very limited. Using whole-genome shotgun analysis of 49 faecal samples (31 cases and 18 sex- and age-matched controls), we analysed compositional and functional differences in the gut microbiome of patients with SAD in comparison to healthy controls. Overall microbiota composition, as measured by beta-diversity, was found to be different between the SAD and control groups and several taxonomic differences were seen at a genus- and species-level. The relative abundance of the genera Anaeromassillibacillus and Gordonibacter were elevated in SAD, while Parasuterella was enriched in healthy controls. At a species-level, Anaeromassilibacillus sp An250 was found to be more abundant in SAD patients while Parasutterella excrementihominis was higher in controls. No differences were seen in alpha diversity. In relation to functional differences, the gut metabolic module ‘aspartate degradation I’ was elevated in SAD patients. In conclusion, the gut microbiome of patients with SAD differs in composition and function to that of healthy controls. Larger, longitudinal studies are warranted to validate these preliminary results and explore the clinical implications of these microbiome changes.
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- 2023
13. Efficacy of Bifidobacterium longum alone or in multi-strain probiotic formulations during early life and beyond
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Susan Mills, Bo Yang, Graeme J. Smith, Catherine Stanton, and R. Paul Ross
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Microbiology (medical) ,Infectious Diseases ,Gastroenterology ,Microbiology - Published
- 2023
14. Gut microbiota insights into human adaption to high-plateau diet
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Yina Huang, Jinxin Liu, Hein Min Tun, Catherine Stanton, Tingtao Chen, Hani El‐Nezami, Hua Wei, Mingfu Wang, and Qinglong Wu
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Article - Abstract
[Image: see text]
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- 2023
15. Nisin E is a novel nisin variant produced by multiple Streptococcus equinus strains
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Ivan Sugrue, Daragh Hill, Paula M. O’Connor, Li Day, Catherine Stanton, Colin Hill, and R. Paul Ross
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Microbiology (medical) ,Streptococcus equinus ,antimicrobial peptide ,Bacteriocin ,streptococcus equinus ,Microbiology ,Biotherapeutic ,Lantibiotic ,lantibiotic ,bacteriocin ,biotherapeutic ,Virology ,nisin ,Antimicrobial peptide ,Nisin - Abstract
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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- 2023
16. Vertical transfer of antibiotics and antibiotic resistant strains across the mother/baby axis
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Catherine Stanton, Eugene M. Dempsey, C. Anthony Ryan, Dhrati Patangia, and R. Paul Ross
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Microbiology (medical) ,Gene Transfer, Horizontal ,medicine.drug_class ,Offspring ,Antibiotics ,Mothers ,Biology ,Microbiology ,Vertical transfer ,03 medical and health sciences ,Antibiotic resistance ,Drug Resistance, Multiple, Bacterial ,Virology ,medicine ,Humans ,030304 developmental biology ,0303 health sciences ,Bacteria ,030306 microbiology ,Transmission (medicine) ,Infant, Newborn ,Antibiotic exposure ,Infant ,biology.organism_classification ,Anti-Bacterial Agents ,Infectious Diseases ,Horizontal gene transfer ,Immunology ,Female - Abstract
Antibiotic resistance is a health and socioeconomic crisis recognized as a serious threat affecting humans worldwide. Overuse of antibiotics enhances the spread of multidrug-resistant bacteria, causing drug-resistant infections which can be difficult to treat. This resistance, mostly of the acquired type, is thus a major clinical issue. Acquired resistance can occur by horizontal transfer of genes between bacteria (community settings), by vertical transmission that can occur between mother and her offspring at birth and during lactation, or spontaneously due to antibiotic exposure. While there have been multiple studies about the horizontal transfer of antibiotic-resistance genes, not many studies have been conducted to study their vertical transmission. Vertical transmission is of importance as the early bacterial colonization of infants has an impact on their health and immune programming throughout life. This review discusses some possible mechanisms of mother-to-infant transmission of antibiotics and antibiotic-resistant strains and addresses the knowledge gaps for further studies.
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- 2022
17. Dietary-Induced Bacterial Metabolites Reduce Inflammation and Inflammation-Associated Cancer via Vitamin D Pathway
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Caitlin O’Mahony, Adam Clooney, Siobhan F. Clarke, Mònica Aguilera, Aisling Gavin, Donjete Simnica, Mary Ahern, Aine Fanning, Maurice Stanley, Raul Cabrera Rubio, Elaine Patterson, Tatiana Marques, Rebecca Wall, Aileen Houston, Amr Mahmoud, Michael W. Bennett, Catherine Stanton, Marcus J. Claesson, Paul D. Cotter, Fergus Shanahan, Susan A. Joyce, and Silvia Melgar
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Inorganic Chemistry ,Organic Chemistry ,General Medicine ,Physical and Theoretical Chemistry ,colitis ,colitis-associated cancer ,high-fat diet ,bile acids ,vitamin D ,proliferation ,inflammation ,Molecular Biology ,Spectroscopy ,Catalysis ,Computer Science Applications - Abstract
Environmental factors, including westernised diets and alterations to the gut microbiota, are considered risk factors for inflammatory bowel diseases (IBD). The mechanisms underpinning diet-microbiota-host interactions are poorly understood in IBD. We present evidence that feeding a lard-based high-fat (HF) diet can protect mice from developing DSS-induced acute and chronic colitis and colitis-associated cancer (CAC) by significantly reducing tumour burden/incidence, immune cell infiltration, cytokine profile, and cell proliferation. We show that HF protection was associated with increased gut microbial diversity and a significant reduction in Proteobacteria and an increase in Firmicutes and Clostridium cluster XIVa abundance. Microbial functionality was modulated in terms of signalling fatty acids and bile acids (BA). Faecal secondary BAs were significantly induced to include moieties that can activate the vitamin D receptor (VDR), a nuclear receptor richly represented in the intestine and colon. Indeed, colonic VDR downstream target genes were upregulated in HF-fed mice and in combinatorial lipid-BAs-treated intestinal HT29 epithelial cells. Collectively, our data indicate that HF diet protects against colitis and CAC risk through gut microbiota and BA metabolites modulating vitamin D targeting pathways. Our data highlights the complex relationship between dietary fat-induced alterations of microbiota-host interactions in IBD/CAC pathophysiology.
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- 2023
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18. The Mycobiome of Toombak
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Amel Sami, Imad Elimairi, C. Anthony Ryan, Dhrati Patangia, R. Paul Ross, and Catherine Stanton
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History ,Polymers and Plastics ,Business and International Management ,Industrial and Manufacturing Engineering - Published
- 2023
19. Clinical implications of preterm infant gut microbiome development
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David B. Healy, C. Anthony Ryan, R. Paul Ross, Catherine Stanton, and Eugene M. Dempsey
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Microbiology (medical) ,Immunology ,Genetics ,Cell Biology ,Applied Microbiology and Biotechnology ,Microbiology - Published
- 2021
20. Bifidobacterium longum Ameliorates Dextran Sulfate Sodium-Induced Colitis by Producing Conjugated Linoleic Acid, Protecting Intestinal Mechanical Barrier, Restoring Unbalanced Gut Microbiota, and Regulating the Toll-Like Receptor-4/Nuclear Factor-κB Signaling Pathway
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Jiuhong Ding, Jianxin Zhao, Catherine Stanton, R. Paul Ross, Yang Chen, Wei Chen, Bo Yang, Haiqin Chen, and Hao Zhang
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Toll-like receptor ,Bifidobacterium longum ,biology ,Conjugated linoleic acid ,food and beverages ,General Chemistry ,Gut flora ,Pharmacology ,medicine.disease ,biology.organism_classification ,digestive system ,chemistry.chemical_compound ,fluids and secretions ,Downregulation and upregulation ,chemistry ,medicine ,TLR4 ,Tumor necrosis factor alpha ,Colitis ,General Agricultural and Biological Sciences - Abstract
This study aimed to explore the effects and differences of conjugated linoleic acid (CLA)-producing Bifidobacterium longum on the alleviation of dextran sulfate sodium (DSS)-induced colitis and to explore its patterns. Different B. longum strains were administered at 109 cfu/day 7 days before DSS treatment. B. longum CCFM681 significantly increased goblet cells, mucin2 (MUC2), claudin-3, α-catenin1, and ZO-1, but neither B. longum CCFM760 nor B. longum CCFM642 had those protective effects. Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were downregulated, while IL-10 was upregulated by B. longum CCFM681 but neither by B. longum CCFM760 nor by B. longum CCFM642. Moreover, B. longum CCFM681 treatment inhibited the toll-like receptor-4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway. Furthermore, B. longum CCFM681 treatment rebalanced gut microbiota via regulating the diversity and key microorganisms. Colonic CLA concentrations in mice fed with B. longum CCFM681 were significantly higher than that of DSS-exposed mice, while those in B. longum CCFM760 and B. longum CCFM642 groups showed insignificant difference compared with the DSS group. Moreover, CLA showed a significantly positive correlation with the effectiveness of relieving colitis. B. longum CCFM681 alleviated colitis by protecting the intestinal mechanical barrier, modulating the gut microbiota, and inhibiting the TLR4/NF-κB pathway and associated pro-inflammatory cytokines. These results will help the clinical trials of probiotics and the development of functional products for colitis.
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- 2021
21. The contrasting human gut microbiota in early and late life and implications for host health and disease
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Kenneth J. O’Riordan, John F. Cryan, Chris I R Gill, Susan Mills, Emeran A. Mayer, Catherine Stanton, O. Skillington, Daniele Del Rio, R.P. Ross, and A. Gupta
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Nutrition and Dietetics ,Human gut ,Host (biology) ,Immunology ,Medicine (miscellaneous) ,Disease ,Biology ,digestive system ,Biochemistry ,Food Science - Abstract
The gut microbiota plays a significant role in health and development from birth and continues to affect several processes throughout life and into old age. During both infancy and old age, the trajectory of the gut microbiota changes with contrasting consequences at both stages for the host. The infant gut is unstable, and colonization is influenced by a variety of perinatal and postnatal factors. Many of these factors can contribute to an altered microbiota profile in infancy which can be associated with negative consequences later in life such as allergies, obesity, and neuropsychiatric disorders. The late-life gut microbiota is influenced by physiological changes within the host, illness, diet and lifestyle that impact its composition and functionality. Indeed, reduced microbial diversity, loss of beneficial microorganisms and increased pathobionts are key signatures of the elderly microbiome. Such changes have been associated with degenerative diseases including inflammaging, Alzheimer’s disease, Parkinson’s disease, and increased risk of infection with Clostridioides difficile. Here, we examine early- and late-life factors that contribute to contrasting gut microbiota disturbances and the consequences associated with these disruptions. Finally, we provide compelling evidence of nutritional and probiotic/prebiotic interventions that may help alleviate the effects of gut microbiota changes into old age.
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- 2021
22. A randomized, double blind, parallel, placebo‐controlled study to investigate the efficacy of Lactobacillus paracasei N1115 in gut development of young children
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R.P. Ross, Andrea M. Doolan, Feng Lili, Shijie Wang, Xun Yiping, Yuling Xue, Catherine Stanton, Zhang Dong, Hong Zhu, and Grace Ahern
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medicine.medical_specialty ,Lactobacillus paracasei ,Placebo-controlled study ,Placebo ,Gastroenterology ,law.invention ,Probiotic ,law ,Internal medicine ,Lactobacillus ,medicine ,TX341-641 ,Microbiome ,short‐chain fatty acid ,Feces ,Original Research ,fecal microbiota ,biology ,business.industry ,Nutrition. Foods and food supply ,biology.organism_classification ,Lactobacillus paracasei N1115 ,Clinical trial ,caesarean section ,business ,probiotic ,Food Science - Abstract
In this clinical trial, the safety and effectiveness of Lactobacillus paracasei N1115 (LP N1115) were investigated as a potential probiotic to enhance gut development in young children born by caesarean section. Infants and young children between the ages of 6 months and 3 years were administered with a probiotic consisting of LP N1115 strain (n = 30) or placebo supplement (n = 30) over an 8 weeks intervention. And the stool consistency, bowel habits, salivary cortisol, fecal microbiota, and short‐chain fatty acid metabolism were investigated. Efficacy data were obtained from 58 participants who completed the study. Overall, the placebo functioned similarly to LP N1115 group in relation to stool consistency, gastrointestinal symptoms, salivary cortisol, and short‐chain fatty acids. However, the scoring data relating to the 6–18 months subgroup receiving LP N1115 remained stable over 8 weeks in comparison to placebo. Analysis of the fecal microbiota using 16S rRNA amplicon sequencing revealed that the phyla Firmicutes represented 62% of the microbial relative abundance in the feces of the subjects during the intervening period. No significant changes in alpha‐ or beta‐diversity were noted between the placebo and LP N1115 groups overtime and at each time point. Differential abundance analysis indicated an increase in Lactobacillus in LP N1115 group at weeks 4 (p, A randomized, double‐blind, parallel, placebo‐controlled study on Lactobacillus paracasei N1115 (LP N1115) was investigated as a probiotic to enhance gut development in young children born by caesarean section. Infants and young children between the ages of 6 months and 3 years were administered with a probiotic consisting of LP N1115 strain (n = 30) or placebo supplement (n = 30) over an 8 weeks intervention. The study results would seem to indicate that efficacy of LP N1115 supplementation at an early age may be effective in enhancing the gut development.
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- 2021
23. Different Effects of Different Lactobacillus acidophilus Strains on DSS-Induced Colitis
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Zheng Huang, Lei Gong, Yan Jin, Catherine Stanton, Reynolds Paul Ross, Jianxin Zhao, Bo Yang, and Wei Chen
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Inflammation ,Organic Chemistry ,General Medicine ,Gut microbiota ,Escherichia-coli ,Signature ,Catalysis ,Dextran sulfate sodium ,Computer Science Applications ,Metastasis ,Inorganic Chemistry ,Metabolism ,Induced ulcerative-colitis ,Lactobacillus acidophilus ,colitis ,cytokines ,gut microbiota ,SCFAs ,Colorectal carcinogenesis ,Physical and Theoretical Chemistry ,Molecular Biology ,Spectroscopy ,Receptor - Abstract
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.
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- 2022
- Full Text
- View/download PDF
24. Effects of
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Bingyong, Mao, Zhujun, He, Yang, Chen, Catherine, Stanton, Reynolds Paul, Ross, Jianxin, Zhao, Wei, Chen, and Bo, Yang
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In breast milk, 2'-Fucosyllactose (2'FL) is the most abundant breast milk oligosaccharide and can selectively promote the proliferation of bifidobacteria. This study aimed to explore the effect of ifidobacterial with different utilization capacities of 2'FL on the intestinal microecology of mice. Furthermore, the effects of ifidobacterial with different 2'FL utilization capabilities on mice gut microbiota under the competitive pressure of 2'FL as a carbon source were explored. Compared with the control group, 2'FL
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- 2022
25. Different Effects of Different
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Zheng, Huang, Lei, Gong, Yan, Jin, Catherine, Stanton, Reynolds Paul, Ross, Jianxin, Zhao, Bo, Yang, and Wei, Chen
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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
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- 2022
26. Samantha Thimmaya v Lancashire NHS Foundation Trust v Mr Firas Jamil
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Catherine Stanton
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Plaintiff ,Civil Procedure Rules ,Malpractice ,Medicine (miscellaneous) ,Foundation (evidence) ,State Medicine ,Clinical negligence ,Expert witness ,Order (business) ,Law ,Humans ,Sociology ,Expert Testimony - Abstract
In Samantha Thimmaya v Lancashire NHS Trust v Mr Firas Jamal (Thimmaya), Mr Jamil, an expert witness acting for the Claimant in a clinical negligence action, was ordered to pay part of the Defendant’s costs, amounting to over £88,000. The court determined that his conduct as an expert had been ‘improper, unreasonable, or negligent’, thus enabling the court to make a third-party costs order against him. Although the case must have raised alarm amongst medical experts, the facts of the case show that it concerned a very unusual set of circumstances. Additionally, the more recent case of Walker and Walker v Tui UK Ltd v Dr Timothy Leigh (Walker), also discussed below, suggests that the threshold to be applied in determining whether costs orders should be made against experts will be higher than that applied in Thimmaya. Both cases serve as a reminder of the duties owed by experts to the court.
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- 2021
27. Crosstalk between sIgA-Coated Bacteria in Infant Gut and Early-Life Health
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R. Paul Ross, Jianxin Zhao, Bo Yang, Wei Chen, Mengfan Ding, Hao Zhang, and Catherine Stanton
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Microbiology (medical) ,chemical and pharmacologic phenomena ,Gut flora ,digestive system ,Microbiology ,03 medical and health sciences ,fluids and secretions ,Immune system ,stomatognathic system ,Virology ,Humans ,Microbiome ,Intestinal Mucosa ,030304 developmental biology ,0303 health sciences ,Innate immune system ,Bacteria ,biology ,030306 microbiology ,Transmission (medicine) ,Infant ,food and beverages ,biology.organism_classification ,Acquired immune system ,Infectious Disease Transmission, Vertical ,Gastrointestinal Microbiome ,Infectious Diseases ,Bacterial Translocation ,Immunoglobulin A, Secretory ,Immunology ,biology.protein ,Flagellin - Abstract
Gut microbiota transmission from mother to offspring has attracted much interest in recent years. The gut microbiota in the infant plays a potentially significant role in modulating and maintaining the development of infant immunity. Secretory immunoglobulin A (sIgA), the major immunoglobulin in the intestine, can target polysaccharides and flagellin on the bacterial surface, resulting in sIgA-coated bacteria. The presentation of specific bacteria coated with sIgA may be a signal of disease and provide novel insights into the relationship between infant microbiota and disease. Here, we review the composition of sIgA-coated bacteria in the adult intestine, human milk, and the infant intestine, as well as the factors that influence the development of gut microbiota in early life. Then, we highlight the diseases that are related to variations in sIgA-coated bacteria in the infant and adult intestine. Furthermore, we discuss the possibility that sIgA-coated bacteria could play a role in mediating both innate and adaptive immune responses. Finally, we propose directions for future research to promote our understanding within this field.
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- 2021
28. Metataxonomic Mapping of the Microbial Diversity of Irish and Eastern Mediterranean Cheeses
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Eleni Kamilari, Dimitrios Tsaltas, Catherine Stanton, and R. Paul Ross
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Genome ,Health (social science) ,Spoilage ,Bacteria ,Communities ,Strains ,Plant Science ,Health Professions (miscellaneous) ,Microbiology ,Scale ,Milk ,Lactis ,Sequence ,cheese ,microbiome ,16S rDNA ,ITS loci ,high throughput sequencing ,ripened cheeses ,biomarkers ,lactic acid bacteria ,starter cultures ,metataxonomic sequencing ,Clostridium-perfringens ,Food Science - Abstract
The distinct sensorial characteristics of local cheeses influence consumer preferences, and make an essential contribution to the local economy. Microbial diversity in cheese is among the fundamental contributors to sensorial and qualitative characteristics. However, knowledge regarding the existence of microbial patterns associated with regional production practices in ripened cheeses remains limited. The present research was conducted to test the hypothesis that the background metagenome of cheeses could be used as a marker of their origin. We compared Irish versus Eastern Mediterranean cheeses—namely Greek and Cypriot—using High Throughput Sequencing (HTS). The study identified a significantly distinct separation among cheeses originating from the three different countries, in terms of the total microbial community composition. The use of machine learning and biomarkers discovery algorithms defined key microbes that differentiate each geographic region. Finally, the development of interaction networks revealed that the key species developed mostly negative interactions with the other members of the communities, highlighting their dominance in the community. The findings of the present research demonstrate that metagenome could indeed be used as a biological marker of the origin of mature cheeses, and could provide further insight into the dynamics of microbial community composition in ripened cheeses.
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- 2022
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29. Microbiota-assisted therapy for systemic inflammatory arthritis: advances and mechanistic insights
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Bowen Li, Bo Yang, Xiaoming Liu, Jianxin Zhao, R. Paul Ross, Catherine Stanton, Hao Zhang, and Wei Chen
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Pharmacology ,Cellular and Molecular Neuroscience ,Microbiota ,Arthritis, Psoriatic ,Humans ,Molecular Medicine ,Cell Biology ,Molecular Biology ,Gastrointestinal Microbiome - Abstract
Research on the influence of gut microbiota on systemic inflammatory arthritis has exploded in the past decade. Gut microbiota changes may be a crucial regulatory component in systemic inflammatory arthritis. As a result of advancements in the field, microbiota-assisted therapy has evolved, but this discipline is still in its infancy. Consequently, we review the limitations of current systemic inflammatory arthritis treatment, analyze the connection between the microbiota and arthritis, and summarize the research progress of microbiota regulating systemic inflammatory arthritis and the further development aspects of microbiota-assisted therapy. Finally, the partial mechanisms of microbiota-assisted therapy of systemic inflammatory arthritis are being discussed. In general, this review summarizes the current progress, challenges, and prospects of microbiota-assisted therapy for systemic inflammatory arthritis and points out the direction for the development of microbiota-assisted therapy in the future.
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- 2022
30. Sudanese Toombak smokeless tobacco users harbour significantly altered long–term cortisol body production
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Amel Sami, Imad Elimairi, C. Anthony Ryan, R. Paul Ross, and Catherine Stanton
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Pharmacology ,Endocrinology ,Organic Chemistry ,Clinical Biochemistry ,Molecular Biology ,Biochemistry - Published
- 2023
31. Linoleate Isomerase Complex Contributes to Metabolism and Remission of DSS-Induced Colitis in Mice of Lactobacillus plantarum ZS2058
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Hui Qi, Catherine Stanton, Bo Yang, Jianxin Zhao, Hao Zhang, Haiqin Chen, Yang Chen, R. Paul Ross, He Gao, and Wei Chen
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Antioxidant ,biology ,Conjugated linoleic acid ,Linoleic acid ,medicine.medical_treatment ,Lipid metabolism ,General Chemistry ,Metabolism ,biology.organism_classification ,Linoleate isomerase ,chemistry.chemical_compound ,chemistry ,Biochemistry ,Lactobacillus ,medicine ,General Agricultural and Biological Sciences ,Lactobacillus plantarum - Abstract
A linoleate isomerase complex including myosin-cross-reactive antigen, short-chain dehydrogenase/oxidoreductase, and acetoacetate decarboxylase has been confirmed as the pivotal factor for conjugated linoleic acid (CLA) production in Lactobacillus plantarum. However, its role in the metabolism and health-associated benefits of Lactobacillus remain unclear. In the current study, the mild type, knockout, and complemented mutants of the linoleate isomerase complex of L. plantarum ZS2058 were used to investigate those putative effects. The metabonomic results showed that a linoleate isomerase complex could significantly influence the glycol-metabolism, lipid metabolism, and antioxidant compounds. Especially, with the stress of linoleic acid, linoleate isomerase complex knockout mutants induced the increase of several antioxidant compounds, such as glutamic acid, glycine, l-cysteine, glycerol, and l-sorbosone. Moreover, the linoleate isomerase complex played a pivotal role in ameliorating DSS-induced colitis. The knockout mutants showed effects similar to those in the DSS group, whereas complementation of the corresponding gene in the knockout mutants could restore the anti-inflammatory activity, wherein the integrity of a mucus layer was repaired, the level of pro-inflammatory cytokines decreased, and the amount of anti-inflammatory cytokines increased significantly. All the results indicated that the linoleate isomerase complex plays a key role in CLA production and metabolism as well as the health-associated benefits of L. plantarum ZS2058. These results are conducive to promote clinical trials and product development of probiotics for colitis.
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- 2021
32. Critical windows of early-life microbiota disruption on behaviour, neuroimmune function, and neurodevelopment
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Caoimhe M.K. Lynch, Caitlin S.M. Cowan, Thomaz F.S. Bastiaanssen, Gerard M. Moloney, Nigel Theune, Marcel van de Wouw, Eva Florensa Zanuy, Ana Paula Ventura-Silva, Martin G. Codagnone, Francisca Villalobos-Manríquez, Matilde Segalla, Fatma Koc, Catherine Stanton, Paul Ross, Timothy G. Dinan, Gerard Clarke, and John F. Cryan
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Behavioral Neuroscience ,Endocrine and Autonomic Systems ,Immunology - Abstract
Numerous studies have emphasised the importance of the gut microbiota during early life and its role in modulating neurodevelopment and behaviour. Epidemiological studies have shown that early-life antibiotic exposure can increase an individual's risk of developing immune and metabolic diseases. Moreover, preclinical studies have shown that long-term antibiotic-induced microbial disruption in early life can have enduring effects on physiology, brain function and behaviour. However, these studies have not investigated the impact of targeted antibiotic-induced microbiota depletion during critical developmental windows and how this may be related to neurodevelopmental outcomes. Here, we addressed this gap by administering a broad-spectrum oral antibiotic cocktail (ampicillin, gentamicin, vancomycin, and imipenem) to mice during one of three putative critical windows: the postnatal (PN; P2-9), pre-weaning (PreWean; P12-18), or post-weaning (Wean; P21-27) developmental periods and assessed the effects on physiology and behaviour in later life. Our results demonstrate that targeted microbiota disruption during early life has enduring effects into adolescence on the structure and function of the caecal microbiome, especially for antibiotic exposure during the weaning period. Further, we show that microbial disruption in early life selectively alters circulating immune cells and modifies neurophysiology in adolescence, including altered myelin-related gene expression in the prefrontal cortex and altered microglial morphology in the basolateral amygdala. We also observed sex and time-dependent effects of microbiota depletion on anxiety-related behavioural outcomes in adolescence and adulthood. Antibiotic-induced microbial disruption had limited and subtle effects on social behaviour and did not have any significant effects on depressive-like behaviour, short-term working, or recognition memory. Overall, this study highlights the importance of the gut microbiota during critical windows of development and the subtle but long-term effects that microbiota-targeted perturbations can have on brain physiology and behaviour.
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- 2022
33. Long-term dietary intake from infancy to late adolescence is associated with gut microbiota composition in young adulthood
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Gerard Clarke, Catherine Stanton, Katriona Lyons, Kirsten Berding, John F. Cryan, Ute Nöthlings, Kolade Oluwagbemigun, Aoife N O'Donovan, Matthias Schmid, and Ute Alexy
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Adult ,DNA, Bacterial ,0301 basic medicine ,Aging ,Adolescent ,carbohydrate intake ,030106 microbiology ,Medicine (miscellaneous) ,Physiology ,Biology ,Gut flora ,Diet Records ,AcademicSubjects/MED00160 ,Feces ,AcademicSubjects/MED00060 ,03 medical and health sciences ,Nutritional Epidemiology and Public Health ,RNA, Ribosomal, 16S ,DONALD study ,3-day weighed dietary records ,Dietary Carbohydrates ,Humans ,Microbiome ,Young adult ,Child ,Nutrition and Dietetics ,Bacteria ,long-term diet ,Infant ,Anthropometry ,Carbohydrate ,biology.organism_classification ,Gastrointestinal Microbiome ,RNA, Bacterial ,Original Research Communications ,030104 developmental biology ,Child, Preschool ,gut microbiota composition ,Phascolarctobacterium ,Desulfovibrio ,Composition (visual arts) ,Child Nutritional Physiological Phenomena ,Dialister - Abstract
Background Gut microbiota composition as influenced by long-term diet may be associated with the risk of adult chronic diseases. Thus, establishing the relation of long-term diet, particularly starting from early life, with adult microbiota composition would be an important research advance. Objective We aimed to investigate the association of long-term intake of energy, carbohydrate, fiber, protein, and fat from infancy to late adolescence with microbiota composition in adulthood. Methods Within the prospective DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study, we sampled stool 1 or 2 times within 1 y from 128 adults (median age: 29 y). Microbiota composition was profiled by 16S ribosomal RNA sequencing. Annual dietary records from age 1 to 18 y were retrieved. We estimated trajectories of energy, energy-adjusted carbohydrate, fiber, protein, and fat intake with multilevel models, producing predicted intake at age 1 y and rates of change in intake. A multivariate, zero-inflated, logistic-normal model was used to model the association between intake trajectories and the composition of 158 genera in single-sampled individuals. Associations found in this model were confirmed in double-sampled individuals using a zero-inflated Beta regression model. Results Adjusting for covariates and temporal differences in microbiota composition, long-term carbohydrate intake was associated with 3 genera. Specifically, carbohydrate intake at age 1 y was negatively associated with Phascolarctobacterium [coefficient = −4.31; false discovery rate (FDR)–adjusted P = 0.006] and positively associated with Dialister (coefficient = 3.06; FDR-adjusted P = 0.003), and the rate of change in carbohydrate intake was positively associated with Desulfovibrio (coefficient = 13.16; FDR-adjusted P = 0.00039). Energy and other macronutrients were not associated with any genus. Conclusions This work links long-term carbohydrate intake to microbiota composition. Considering the associations of high carbohydrate intake and microbiota composition with some diseases, these findings could inform the development of gut microbiota–targeted dietary recommendations for disease prevention.
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- 2021
34. A New Argument for No-Fault Compensation in Health Care: The Introduction of Artificial Intelligence Systems
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Søren Holm, Benjamin Bartlett, and Catherine Stanton
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Artificial intelligence ,Health (social science) ,No-fault compensation ,Computer science ,0603 philosophy, ethics and religion ,Fault (power engineering) ,Health informatics ,03 medical and health sciences ,0302 clinical medicine ,Argument ,Health care ,Humans ,030212 general & internal medicine ,Product liability ,Tort ,business.industry ,Health Policy ,Compensation (psychology) ,Malpractice ,Deep learning ,Liability, Legal ,06 humanities and the arts ,Issues, ethics and legal aspects ,Philosophy of medicine ,Clinical negligence ,Compensation and Redress ,Original Article ,060301 applied ethics ,business ,Delivery of Health Care - Abstract
Artificial intelligence (AI) systems advising healthcare professionals will be widely introduced into healthcare settings within the next 5–10 years. This paper considers how this will sit with tort/negligence based legal approaches to compensation for medical error. It argues that the introduction of AI systems will provide an additional argument pointing towards no-fault compensation as the better legal solution to compensation for medical error in modern health care systems. The paper falls into four parts. The first part rehearses the main arguments for and against no-fault compensation. The second explains why it is likely that AI systems will be widely introduced. The third part analyses why it is difficult to fit AI systems into fault-based compensation systems while the final part suggests how no-fault compensation could provide a possible solution to such challenges.
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- 2021
35. Dose–Response Efficacy and Mechanisms of Orally Administered Bifidobacterium breve CCFM683 on IMQ-Induced Psoriasis in Mice
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Xinqi Chen, Yang Chen, Catherine Stanton, Reynolds Paul Ross, Jianxin Zhao, Wei Chen, and Bo Yang
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Nutrition and Dietetics ,Bifidobacterium breve ,psoriasis ,gut microbiota ,dose–response efficacy ,bile acids ,FXR/NF-κB pathway ,Food Science - Abstract
This study aimed to investigate the dose–response effect of Bifidobacteriumbreve CCFM683 on relieving psoriasis and its underlying patterns. Specifically, the expression of keratin 16, keratin 17, and involucrin were substantially decreased by administration of 109 CFU and 1010 CFU per day. Moreover, interleukin (IL)-17 and TNF-α levels were substantially decreased by 109 and 1010 CFU/day. Furthermore, the gut microbiota in mice treated with 109 or 1010 CFU/day was rebalanced by improving the diversity, regulating microbe interactions, increasing Lachnoclostridium, and decreasing Oscillibacter. Moreover, the concentrations of colonic bile acids were positively correlated with the effectiveness of the strain in relieving psoriasis. The gavage dose should be more than 108.42 CFU/day to improve psoriasis according to the dose–effect curve. In conclusion, CCFM683 supplementation alleviated psoriasis in a dose-dependent manner by recovering microbiota, promoting bile acid production, regulating the FXR/NF-κB pathway, diminishing proinflammatory cytokines, regulating keratinocytes, and maintaining the epidermal barrier function. These results may help guide probiotic product development and clinical trials in psoriasis.
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- 2023
36. Uncovering the Biotechnological Importance of Geotrichum candidum
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Eleni Kamilari, Catherine Stanton, F. Jerry Reen, and R. Paul Ross
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Health (social science) ,Plant Science ,Health Professions (miscellaneous) ,Microbiology ,Food Science - Abstract
Fungi make a fundamental contribution to several biotechnological processes, including brewing, winemaking, and the production of enzymes, organic acids, alcohols, antibiotics, and pharmaceuticals. The present review explores the biotechnological importance of the filamentous yeast-like fungus Geotrichum candidum, a ubiquitous species known for its use as a starter in the dairy industry. To uncover G. candidum’s biotechnological role, we performed a search for related work through the scientific indexing internet services, Web of Science and Google Scholar. The following query was used: Geotrichum candidum, producing about 6500 scientific papers from 2017 to 2022. From these, approximately 150 that were associated with industrial applications of G. candidum were selected. Our analysis revealed that apart from its role as a starter in the dairy and brewing industries, this species has been administered as a probiotic nutritional supplement in fish, indicating improvements in developmental and immunological parameters. Strains of this species produce a plethora of biotechnologically important enzymes, including cellulases, β-glucanases, xylanases, lipases, proteases, and α-amylases. Moreover, strains that produce antimicrobial compounds and that are capable of bioremediation were identified. The findings of the present review demonstrate the importance of G. candidum for agrifood- and bio-industries and provide further insights into its potential future biotechnological roles.
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- 2023
37. Protocol for a prospective cohort study exploring the gut microbiota of infants with congenital heart disease undergoing cardiopulmonary bypass (the GuMiBear study)
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Claire Magner, Dominic Jenkins, Fatma Koc, Mong Hoi Tan, Molly O’Toole, Jordan Boyle, Niamh Maguire, Sophie Duignan, Kiera Murphy, Paul Ross, Catherine Stanton, and Colin J McMahon
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General Medicine - Abstract
IntroductionThe gut microbiota develops from birth and matures significantly during the first 24 months of life, playing a major role in infant health and development. The composition of the gut microbiota is influenced by several factors including mode of delivery, gestational age, feed type and treatment with antibiotics. Alterations in the pattern of gut microbiota development and composition can be associated with illness and compromised health outcomes.Infants diagnosed with ‘congenital heart disease’ (CHD) often require surgery involving cardiopulmonary bypass (CPB) early in life. The impact of this type of surgery on the integrity of the gut microbiome is poorly understood. In addition, these infants are at significant risk of developing the potentially devastating intestinal condition necrotising enterocolitis.Methods and analysisThis study will employ a prospective cohort study methodology to investigate the gut microbiota and urine metabolome of infants with CHD undergoing surgery involving CPB. Stool and urine samples, demographic and clinical data will be collected from eligible infants based at the National Centre for Paediatric Cardiac Surgery in Ireland. Shotgun metagenome sequencing will be performed on stool samples and urine metabolomic analysis will identify metabolic biomarkers. The impact of the underlying diagnosis, surgery involving CPB, and the influence of environmental factors will be explored. Data from healthy age-matched infants from the INFANTMET study will serve as a control for this study.Ethics and disseminationThis study has received full ethical approval from the Clinical Research Ethics Committee of Children’s Health Ireland, GEN/826/20.
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- 2023
38. Bifidobacterium pseudocatenulatum Ameliorates DSS-Induced Colitis by Maintaining Intestinal Mechanical Barrier, Blocking Proinflammatory Cytokines, Inhibiting TLR4/NF-κB Signaling, and Altering Gut Microbiota
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Hao Zhang, Yang Chen, Jianxin Zhao, R. Paul Ross, Bo Yang, Catherine Stanton, and Wei Chen
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0106 biological sciences ,biology ,Tight junction ,Chemistry ,010401 analytical chemistry ,Bifidobacterium pseudocatenulatum ,General Chemistry ,Gut flora ,Pharmacology ,medicine.disease ,biology.organism_classification ,Sutterella ,01 natural sciences ,0104 chemical sciences ,Proinflammatory cytokine ,medicine ,TLR4 ,Colitis ,Bacteroides ,General Agricultural and Biological Sciences ,010606 plant biology & botany - Abstract
This study was designed to explore the effects and discrepancy of different CLA-producing Bifidobacterium pseudocatenulatum on relieving colitis and to investigate the potential mechanisms. B. pseudocatenulatum MY40C and CCFM680 were administered to mice with DSS-induced colitis. The content of tight junction proteins and mucin2 was significantly upregulated. TNF-α and IL-6 were downregulated, while IL-10 and PPAR-γ were upregulated. TLR4/NF-κB pathway activation was significantly inhibited. Moreover, each treated strain increased Allobaculum and decreased Sutterella, Bacteroides, and Oscillospira. The colonic conjugated linoleic acid (CLA) concentrations were significantly and positively correlated with the effectiveness of strain in relieving colitis. In conclusion, MY40C and CCFM680 supplementation alleviated DSS-induced colitis by protecting intestinal mechanical barrier, modulating gut microbiota, blocking proinflammatory cytokines, and inhibiting TLR4/NF-κB pathway. These results are conducive to promote clinical trials and product development of probiotics for colitis.
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- 2021
39. Lactobacillus rhamnosusFJSYC4-1 andLactobacillus reuteriFGSZY33L6 alleviate metabolic syndromeviagut microbiota regulation
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R. Paul Ross, Wei Chen, Fuli Zheng, Catherine Stanton, Jianxin Zhao, Hao Zhang, Bo Yang, and Zhi Wang
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biology ,food and beverages ,General Medicine ,Gut flora ,medicine.disease ,biology.organism_classification ,Lactobacillus reuteri ,Microbiology ,law.invention ,Probiotic ,Insulin resistance ,Lactobacillus rhamnosus ,law ,Lactobacillus ,medicine ,medicine.symptom ,Metabolic syndrome ,Weight gain ,Food Science - Abstract
Metabolic syndrome, which includes a series of metabolic disorders such as hyperglycemia, hyperlipidemia, insulin resistance and obesity, has become a catastrophic disease worldwide. Accordingly, probiotic intervention is a new strategy to alleviate metabolic syndrome, which can adjust the gut microbiota to a certain extent. The aim of the current work was to explore the alleviation of metabolic syndrome by Lactobacillus reuteri and L. rhamnosus. Two L. reuteri and two L. rhamnosus strains were administered to mice with a high-fat diet for 12 weeks. All Lactobacillus strains tested significantly slowed weight gain in the mice. Among four strains, L. reuteri FGSZY33L6 and L. rhamnosus FJSYC4-1 showed the strongest ability to relieve blood glucose disorders, blood lipid disorders, tissue damage, and particularly gut microbiota disorders. Thus, our findings indicate that these strains can regulate the gut microbiota and produce short-chain fatty acids (SCFAs), which can induce satiety hormones, inhibit food intake and increase satiety, and thus improve metabolic syndrome.
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- 2021
40. The ultra-structural, metabolomic and metagenomic characterisation of the sudanese smokeless tobacco ‘Toombak’
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Amel Sami, C. Anthony Ryan, I. Elimairi, Dhrati Patangia, Claire Watkins, R. Paul Ross, and Catherine Stanton
- Subjects
Firmicutes ,Health, Toxicology and Mutagenesis ,Toxicology ,Actinobacteria ,Sudan ,RA1190-1270 ,Virgibacillus ,Tobacco-specific nitrosamines ,Food science ,Toombak ,ComputingMethodologies_COMPUTERGRAPHICS ,biology ,Chemistry ,pH ,Staphylococcus gallinarum ,Regular Article ,biology.organism_classification ,Heavy metal ,Smokeless tobacco ,Nicotiana rustica ,Toxicology. Poisons ,Metabolome ,Antibiotic transport ,Microbiome ,Scanning electron microscopy ,Composition - Abstract
Graphical abstract, Highlights • Toombak, a form of moist smokeless tobacco from Sudan is placed as a dip in the oral cavity most commonly used by males. • The microbiome of Toombak predominantly consists of the phyla, Firmicutes and Actinobacteria while abundant species include Corynebacterium casei, Atopostipes suicloacalis and Oceanobacillus chironomi. • High concentrations of iron, volatile aldehydes and tobacco specific nitrosamines were found in Toombak and can lead to toxicity. • Toombak has a non-homogenous abrasive surface with a high sodium level in the ready to buy form that can damage the oral mucosa. • New measures must be taken in Sudan to limit harmful compounds in Toombak., Toombak is a smokeless tobacco produced from the Nicotiana rustica tobacco plant from Sudan. Pre-prepared and ready to buy Toombak samples were analysed using mass spectrometry (heavy metals), gas and liquid chromatography (metabolomics), 16S rRNA metagenomic sequencing (microbiome) and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt), scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX) and pH analysis. Chromium, cobalt, and copper were high in the pre-prepared form of Toombak while iron, tobacco specific nitrosamines (TSNAs), formaldehyde and acetaldehyde were high in both types. Firmicutes and Actinobacteria dominated Toombak. Samples of ready to buy Toombak showed inter-variational differences depending on place of purchase. We found Virgibacillus were increased in the pre-prepared form while Corynebacterium casei, Atopococus tabaci, Atopostipes suicloacalis, Oceanobacillus chironomi and Staphylococcus gallinarum were the most abundant species in the ready to buy forms. PICRUSt analysis highlighted increased activity of metal transport systems in the ready to buy samples as well as an antibiotic transport system. SEM-EDX highlighted large non-homogenous, irregular particles with increased sodium, while pH of samples was in the alkaline range. The final composition of Toombak is affected by its method of preparation and the end product has the potential to impart many negative consequences on the health of its users. TSNA levels observed in Toombak were some of the highest in the world while the micro-environment of Toombak supports a distinct microbiota profile.
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- 2021
41. Effects of the short-term administration of Pediococcus pentosaceus on physiological characteristics, inflammation, and intestinal microecology in mice
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Wei Chen, Jianxin Zhao, Catherine Stanton, Jie Jiang, R. Paul Ross, Cui Shumao, Hao Zhang, Bowen Li, and Bo Yang
- Subjects
0301 basic medicine ,Operon ,030106 microbiology ,food and beverages ,Inflammation ,General Medicine ,Biology ,Gut flora ,biology.organism_classification ,Microecology ,PEDIOCOCCUS PENTOSACEUS ,law.invention ,Microbiology ,03 medical and health sciences ,Probiotic ,030104 developmental biology ,Beneficial bacteria ,Bacteriocin ,law ,medicine ,medicine.symptom ,Food Science - Abstract
The role of Pediococcus pentosaceus in the gastrointestinne has received considerable attention in recent decades. This study aimed to investigate the effects of the short-term administration of P. pentosaceus on physiological characteristics, inflammation, and intestinal microecology in mice. In this study, 90 male C57BL/6J mice were divided into 15 groups, with 14 groups treated with a daily intragastric administration of different genotypes of P. pentosaceus. After three weeks of intragastric administration P. pentosaceus had a mild effect on mice. It could be seen that different P. pentosaceus strains had different effects on the gut microbiota and intestinal microecology. P. pentosaceus VCQYC5144M12 possessing an Enterolysin A operon may have been harmful, activating the expression of inflammatory factors, while P. pentosaceus DYNDL69M8 consisting of only a pediocin-like operon increased the abundance of beneficial bacteria and increased the content of acetic acid. The presence of various genotypes of bacteriocin may have been the explanation for variations among strains. This may provide theoretical support for further exploring the probiotic effect and patterns of P. pentosaceus.
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- 2021
42. Characterization of CRISPR-Cas systems in Bifidobacterium breve
- Author
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Xiao Han, Xingya Zhou, Zhangming Pei, Catherine Stanton, R. Paul Ross, Jianxin Zhao, Hao Zhang, Bo Yang, and Wei Chen
- Subjects
General Medicine - Abstract
The clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated protein (Cas) system is an important adaptive immune system for bacteria to resist foreign DNA infection, which has been widely used in genotyping and gene editing. To provide a theoretical basis for the application of the CRISPR-Cas system in Bifidobacterium breve , the occurrence and diversity of CRISPR-Cas systems were analysed in 150 B. breve strains. Specifically, 47 % (71/150) of B. breve genomes possessed the CRISPR-Cas system, and type I-C CRISPR-Cas system was the most widely distributed among those strains. The spacer sequences present in B. breve can be used as a genotyping marker. Additionally, the phage assembly-related proteins were important targets of the type I-C CRISPR-Cas system in B. breve , and the protospacer adjacent motif sequences were further characterized in B. breve type I-C system as 5′-TTC-3′. All these results might provide a molecular basis for the development of endogenous genome editing tools in B. breve .
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- 2022
43. Characterization of CRISPR-Cas systems in
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Xiao, Han, Xingya, Zhou, Zhangming, Pei, Catherine, Stanton, R Paul, Ross, Jianxin, Zhao, Hao, Zhang, Bo, Yang, and Wei, Chen
- Subjects
DNA ,Sequence Analysis, DNA ,Bifidobacterium breve ,CRISPR-Cas Systems - Abstract
The clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated protein (Cas) system is an important adaptive immune system for bacteria to resist foreign DNA infection, which has been widely used in genotyping and gene editing. To provide a theoretical basis for the application of the CRISPR-Cas system in
- Published
- 2022
44. Impact of Food Origin Lactiplantibacillus plantarum Strains on the Human Intestinal Microbiota in an in vitro System
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Natalia Garcia-Gonzalez, Joan Colom Comas, Hugh M. B. Harris, Conall Strain, Catherine Stanton, Colin Hill, Aldo Corsetti, and Cormac G. M. Gahan
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Microbiology (medical) ,fluids and secretions ,gut microbiota ,Lactiplantibacillus plantarum ,fecal fermentation ,ex vivo model ,short-chain fatty acid ,food and beverages ,Microbiology - Abstract
We have previously isolated and characterized food-dwelling strains of Lactiplantibacillus (Lpb.) plantarum that are consumed naturally as part of the microbiota of table olives and raw milk cheeses. Despite being consumed at relatively high levels, the impact of such strains on the human gut microbiota is currently unclear. In the current study we evaluated the potential impact of food-dominant Lpb. plantarum strains on the human gut microbiota using a continuous fecal fermentation system. Daily inoculation of Lpb. plantarum strains led to significant, detectable levels in the fecal fermentation system. We examined the impact of the presence of Lpb. plantarum on the microbiota derived from two separate donors. For one donor, Lpb. plantarum increased alpha diversity and beta diversity. This was reflected in significant alterations in abundance of the unclassified genera, dominated by Enterobacteriaceae_unclass and Ruminococcaceae_unclass. The microbiota of the other donor was relatively unaffected following introduction of the Lpb. plantarum strains. Overall, the work describes the response of the human microbiota to the introduction of high levels of food-dominant Lpb. plantarum strains and indicates that the response may reflect interindividual differences between donor samples.
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- 2022
45. The human milk microbiome aligns with lactation stage and not birth mode
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Katriona E. Lyons, Carol-Anne O.’ Shea, Ghjuvan Grimaud, C. Anthony Ryan, Eugene Dempsey, Alan L. Kelly, R. Paul Ross, and Catherine Stanton
- Subjects
Multidisciplinary - Abstract
We analysed the human milk microbiome in a cohort of 80 lactating women and followed the dynamics in taxa over the course of lactation from birth to 6 months. Two hundred and thirty one milk samples were collected from full-term lactating women at 1, 4, 8 and 24 weeks following birth and analysed for microbiota composition using 16S rRNA sequencing. A significant decrease in milk microbiota diversity was observed throughout the first 6 months of lactation, with the greatest difference seen between week 8 and week 24. Nine genera predominated in milk over lactation from week 1 to week 24, comprising of Staphylococcus, Streptococcus, Pseudomonas, Acinetobacter, Bifidobacterium, Mesorhizobium, Brevundimonas, Flavobacterium, and Rhodococcus; however, fluctuations in these core genera were apparent over time. There was a significant effect of stage of lactation on the microbiome, while no effect of birth mode, infant sex and maternal BMI was observed throughout lactation. Streptococcus had the highest mean relative abundance at week 1 and 24 (17.3% and 24% respectively), whereas Pseudomonas predominated at week 4 (22%) and week 8 (19%). Bifidobacterium and Lactobacillus had the highest mean relative abundance at week 4 (5% and 1.4% respectively), and occurred at a relative abundance of ≤ 1% at all other time points. A decrease in milk microbiota diversity throughout lactation was also observed. This study concluded that lactation stage was the primary driving factor in milk microbiota compositional changes over lactation from birth to 6 months, while mode of delivery was not a factor driving compositional changes throughout human lactation.
- Published
- 2022
46. The road not taken: host genetics in shaping intergenerational microbiomes
- Author
-
Shuqin Zeng, Shaopu Wang, R. Paul Ross, and Catherine Stanton
- Subjects
Microbiota ,Genetics ,Animals ,Humans ,Gastrointestinal Microbiome - Abstract
The early-life gut microbiome is linked to human phenotypes as an imbalanced microbiome of this period is implicated in diseases throughout life. Several determinants of early-life gut microbiome are explored, however, mechanisms of acquisition, colonization, and stability of early-life gut microbiome and their interindividual variability remain elusive. Host genetics play a vital role to shape the gut microbiome and interact with it to modulate individual phenotypes in human studies and animal models. Given the microbial linkage between host generations, we discuss the current state of roles of host genetics in forming intergenerational microbiomes associated with mothers, offspring, and those vertically transmitted, providing a basis for taking into account host genetics in future early-life microbiome research. We further expand our discussion to the bidirectional interactions between host gene expression and microbiome in human health.
- Published
- 2022
47. Fermented Foods, Health and the Gut Microbiome
- Author
-
Natasha K. Leeuwendaal, Catherine Stanton, Paul W. O’Toole, and Tom P. Beresford
- Subjects
carbohydrates (lipids) ,Nutrition and Dietetics ,digestive, oral, and skin physiology ,Fermentation ,food and beverages ,Humans ,Fermented Foods ,Food Science ,Diet ,Gastrointestinal Microbiome - Abstract
Fermented foods have been a part of human diet for almost 10,000 years, and their level of diversity in the 21st century is substantial. The health benefits of fermented foods have been intensively investigated; identification of bioactive peptides and microbial metabolites in fermented foods that can positively affect human health has consolidated this interest. Each fermented food typically hosts a distinct population of microorganisms. Once ingested, nutrients and microorganisms from fermented foods may survive to interact with the gut microbiome, which can now be resolved at the species and strain level by metagenomics. Transient or long-term colonization of the gut by fermented food strains or impacts of fermented foods on indigenous gut microbes can therefore be determined. This review considers the primary food fermentation pathways and microorganisms involved, the potential health benefits, and the ability of these foodstuffs to impact the gut microbiome once ingested either through compounds produced during the fermentation process or through interactions with microorganisms from the fermented food that are capable of surviving in the gastro-intestinal transit. This review clearly shows that fermented foods can affect the gut microbiome in both the short and long term, and should be considered an important element of the human diet.
- Published
- 2022
48. Enduring Behavioral Effects Induced by Birth by Caesarean Section in the Mouse
- Author
-
Silvia Arboleya, S. Beers, Karen A. Scott, Orla O'Sullivan, Jan Knol, Rachel D. Moloney, Shugui Wang, Alan E. Hoban, Ana Paula Ventura-Silva, Catherine Stanton, Paul W. O'Toole, Ingrid B. Renes, Kieran Rea, Roman M. Stilling, Paul Cherry, Elaine Patterson, Livia H. Morais, Yuliya E. Borre, Sahar El Aidy, Angela Moya-Pérez, Ana M. Sequeira, Anna V. Golubeva, Thomaz F.S. Bastiaanssen, Gerard M. Moloney, John F. Cryan, Timothy G. Dinan, R. Paul Ross, Paul D. Cotter, and Host-Microbe Interactions
- Subjects
0301 basic medicine ,medicine.medical_treatment ,ved/biology.organism_classification_rank.species ,Gut–brain axis ,Physiology ,Gut flora ,microbiota gut-brain axis ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Feces ,Mice ,0302 clinical medicine ,Immune system ,Pregnancy ,medicine ,microbiota ,Animals ,Caesarean section ,Microbiome ,MolEco ,Bifidobacterium ,VLAG ,Bifidobacterium breve ,biology ,ved/biology ,Cesarean Section ,behavior ,gut-brain axis ,Prebiotic ,biology.organism_classification ,Gastrointestinal Microbiome ,Disease Models, Animal ,030104 developmental biology ,probiotics ,Female ,Nervous System Diseases ,General Agricultural and Biological Sciences ,prebiotics ,030217 neurology & neurosurgery ,co-housing - Abstract
Birth by Caesarean (C)-section impacts early gut microbiota colonization and is associated with an increased risk of developing immune and metabolic disorders. Moreover, alterations of the microbiome have been shown to affect neurodevelopmental trajectories. However, the long-term effects of C-section on neurobehavioral processes remain unknown. Here, we demonstrated that birth by C-section results in marked but transient changes in microbiome composition in the mouse, in particular, the abundance of Bifidobacterium spp. was depleted in early life. Mice born by C-section had enduring social, cognitive, and anxiety deficits in early life and adulthood. Interestingly, we found that these specific behavioral alterations induced by the mode of birth were also partially corrected by co-housing with vaginally born mice. Finally, we showed that supplementation from birth with a Bifidobacterium breve strain, or with a dietary prebiotic mixture that stimulates the growth of bifidobacteria, reverses selective behavioral alterations in C-section mice. Taken together, our data link the gut microbiota to behavioral alterations in C-section-born mice and suggest the possibility of developing adjunctive microbiota-targeted therapies that may help to avert long-term negative consequences on behavior associated with C-section birth mode.
- Published
- 2020
49. The public health rationale for increasing dietary fibre: Health benefits with a focus on gut microbiota
- Author
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Conall R. Strain, R.P. Ross, Susan Mills, Catherine Stanton, and Fatma Koc
- Subjects
medicine.medical_specialty ,Focus (computing) ,Nutrition and Dietetics ,biology ,Public health ,Environmental health ,medicine ,Dietary fibre ,Medicine (miscellaneous) ,Gut flora ,Health benefits ,biology.organism_classification - Published
- 2020
50. Investigating the potential of fish oil as a nutraceutical in an animal model of early life stress
- Author
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R. Paul Ross, Sian Egerton, John F. Cryan, Snehal Gite, Sarah C. Culloty, Fiona Fouhy, Ted Dinan, Jason Whooley, Patrick Fitzgerald, Catherine Stanton, and Francisco Donoso
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Elevated plus maze ,Gut–brain axis ,Medicine (miscellaneous) ,Butyrate ,Biology ,Open field ,03 medical and health sciences ,chemistry.chemical_compound ,Fish Oils ,0302 clinical medicine ,Adverse Childhood Experiences ,Corticosterone ,Internal medicine ,medicine ,Animals ,Fluoxetine ,030109 nutrition & dietetics ,Nutrition and Dietetics ,Behavior, Animal ,Maternal Deprivation ,General Neuroscience ,General Medicine ,Fish oil ,Rats ,Disease Models, Animal ,Endocrinology ,chemistry ,Dietary Supplements ,Stress, Psychological ,030217 neurology & neurosurgery ,medicine.drug ,Behavioural despair test - Abstract
Background: Early life stress is a key predisposing factor for depression and anxiety disorders. Selective serotonin re-uptake inhibitors (SSRI) are frequently used as the first line of pharmacology treatment for depression but have several negative qualities, i.e. a delay or absence of effectiveness and negative side-effects. Therefore, there is a growing need for new nutraceutical-based strategies to blunt the effects of adverse-life events.Objectives: This study aimed to use the maternal separation model in rats to test the efficacy of fish oil dietary supplementation, on its own and in conjunction with the SSRI anti-depressant fluoxetine, as a treatment for depressive and anxiety-like symptoms associated with early life stress.Methods: Behavioural tests (open field test, elevated plus maze test and forced swim test) and biochemical markers (corticosterone, BDNF, brain fatty acids and short chain fatty acids) were used to analyse the effects of the dietary treatments. Gut microbial communities and relating metabolites (SCFA) were analysed to investigate possible changes in the microbiota-gut-brain axis.Results: Maternally separated rats showed depressive-like behaviours in the forced swim and open field tests. These behaviours were prevented significantly by fluoxetine administration and in part by fish oil supplementation. Associated biochemical changes reported include altered brain fatty acids, significantly lower plasma corticosterone levels (AUC) and reduced brain stem serotonin turnover, compared to untreated, maternally separated (MS) rats. Untreated MS animals had significantly lower ratios of SCFA producers such as Caldicoprobacteraceae, Streptococcaceae, Rothia, Lachnospiraceae_NC2004_group, and Ruminococcus_2, along with significantly reduced levels of total SCFA compared to non-separated animals. Compared to untreated MS animals, animals fed fish oil had significantly higher Bacteroidetes and Prevotellaceae and reduced levels of butyrate, while fluoxetine treatment resulted in significantly higher levels of Neochlamydia, Lachnoclostridium, Acetitomaculum and Stenotrophomonas and, acetate and propionate.Conclusion: Despite the limitations in extrapolating from animal behavioural data and the notable differences in pharmacokinetics between rodents and humans, the results of this study provide a further advancement into the understanding of some of the complex systems within which nutraceuticals and pharmaceuticals effect the microbiota-gut-brain axis.
- Published
- 2020
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