Publications by authors named "Catherine Stanton"

281 Publications

Development of gut microbiota and bifidobacterial communities of neonates in the first 6 weeks and their inheritance from mother.

Gut Microbes 2021 Jan-Dec;13(1):1-13

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China.

Microbiota especially play an important role in adjusting and maintaining homeostatic balance within the infant intestine. The aim of this study was to elucidate the relationship between maternal and infant gut microbiota and identify the species that may transfer from mother to infant over the first 42 days of the infant's life. Nineteen mother-infant-pair fecal samples were collected and the diversity and composition of the total bacterial and communities were analyzed via 16S rDNA and bifidobacterial gene high throughput sequencing. The results revealed that the relative abundance of was significantly higher in the infant gut while and were at lower relative abundance in 7-day and 42-day infant fecal samples compared to the maternal samples. The maternal gut has more . In the infant group, and relative abundance increased while subsp. decreased from days 7 to 42. Additionally, subsp. isolated from FGZ16 and FGZ35 may have transferred from mother to infant and colonized the infant gut. The results of the current study provide insight toward the infant gut microbiota composition and structure during the first 42 days and may help guide supplementation strategies in mothers and infants.
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http://dx.doi.org/10.1080/19490976.2021.1908100DOI Listing
April 2021

The gut microbiome influences the bioavailability of olanzapine in rats.

EBioMedicine 2021 Apr 1;66:103307. Epub 2021 Apr 1.

APC Microbiome Ireland, University College Cork, Cork, Ireland; School of Pharmacy, University College Cork, Cavanagh Pharmacy Building, Cork, Ireland. Electronic address:

Background: The role of the gut microbiome in the biotransformation of drugs has recently come under scrutiny. It remains unclear whether the gut microbiome directly influences the extent of drug absorbed after oral administration and thus potentially alters clinical pharmacokinetics.

Methods: In this study, we evaluated whether changes in the gut microbiota of male Sprague Dawley rats, as a result of either antibiotic or probiotic administration, influenced the oral bioavailability of two commonly prescribed antipsychotics, olanzapine and risperidone.

Findings: The bioavailability of olanzapine, was significantly increased (1.8-fold) in rats that had undergone antibiotic-induced depletion of gut microbiota, whereas the bioavailability of risperidone was unchanged. There was no direct effect of microbiota depletion on the expression of major CYP450 enzymes involved in the metabolism of either drug. However, the expression of UGT1A3 in the duodenum was significantly downregulated. The reduction in faecal enzymatic activity, observed during and after antibiotic administration, did not alter the ex vivo metabolism of olanzapine or risperidone. The relative abundance of Alistipes significantly correlated with the AUC of olanzapine but not risperidone.

Interpretation: Alistipes may play a role in the observed alterations in olanzapine pharmacokinetics. The gut microbiome might be an important variable determining the systemic bioavailability of orally administered olanzapine. Additional research exploring the potential implication of the gut microbiota on the clinical pharmacokinetics of olanzapine in humans is warranted.

Funding: This research is supported by APC Microbiome Ireland, a research centre funded by Science Foundation Ireland (SFI), through the Irish Government's National Development Plan (grant no. 12/RC/2273 P2) and by Nature Research-Yakult (The Global Grants for Gut Health; Ref No. 626891).
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http://dx.doi.org/10.1016/j.ebiom.2021.103307DOI Listing
April 2021

A New Argument for No-Fault Compensation in Health Care: The Introduction of Artificial Intelligence Systems.

Health Care Anal 2021 Mar 21. Epub 2021 Mar 21.

Department of Law, School of Social Sciences, The University of Manchester, Manchester, U.K.

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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http://dx.doi.org/10.1007/s10728-021-00430-4DOI Listing
March 2021

Diet and the Microbiota-Gut-Brain Axis: Sowing the Seeds of Good Mental Health.

Adv Nutr 2021 Mar 9. Epub 2021 Mar 9.

APC Microbiome Ireland, Cork, Ireland.

Over the past decade, the gut microbiota has emerged as a key component in regulating brain processes and behavior. Diet is one of the major factors involved in shaping the gut microbiota composition across the lifespan. However, whether and how diet can affect the brain via its effects on the microbiota is only now beginning to receive attention. Several mechanisms for gut-to-brain communication have been identified, including microbial metabolites, immune, neuronal, and metabolic pathways, some of which could be prone to dietary modulation. Animal studies investigating the potential of nutritional interventions on the microbiota-gut-brain axis have led to advancements in our understanding of the role of diet in this bidirectional communication. In this review, we summarize the current state of the literature triangulating diet, microbiota, and host behavior/brain processes and discuss potential underlying mechanisms. Additionally, determinants of the responsiveness to a dietary intervention and evidence for the microbiota as an underlying modulator of the effect of diet on brain health are outlined. In particular, we emphasize the understudied use of whole-dietary approaches in this endeavor and the need for greater evidence from clinical populations. While promising results are reported, additional data, specifically from clinical cohorts, are required to provide evidence-based recommendations for the development of microbiota-targeted, whole-dietary strategies to improve brain and mental health.
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http://dx.doi.org/10.1093/advances/nmaa181DOI Listing
March 2021

Measuring Conjugated Linoleic Acid (CLA) Production by Bifidobacteria.

Methods Mol Biol 2021 ;2278:87-100

Teagasc Food Research Centre, Moorepark, Fermoy, Co. Cork, Ireland.

The biological significance of conjugated fatty acids (CFAs) has been linked to positive health effects based on biomedical, in vitro, and clinical studies. Of note, conjugated linoleic acids (CLAs) are the most widely characterized fatty acids as geometric isomers cis-9,trans-11 and trans-10,cis-12 CLA occur naturally in ruminant fats, dairy products, and hydrogenated oils. Concerning CLAs, it is known that bacterial biohydrogenation, a process whereby ruminal bacteria or starter cultures of lactic acid bacteria have the ability to synthesize CLA by altering the chemical structure of essential fatty acids via enzymatic mechanisms, produces a multitude of isomers with desirable properties. Bifidobacterium species are classed as food grade microorganisms and some of these strains harness molecular determinants that are responsible for the bioconversion of free fatty acids to CLAs. However, molecular mechanisms have yet to be fully elucidated. Reports pertaining to CLAs have been attributed to suppressing tumor growth, delaying the onset of diabetes mellitus and reducing body fat in obese individuals. Given the increased attention for their bioactive properties, we describe in this chapter the qualitative and quantitative methods used to identify and quantify CLA isomers produced by bifidobacterial strains in supplemented broth media. These approaches enable rapid detection of potential CLA producing strains and accurate measurement of fatty acids in biological matrices.
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http://dx.doi.org/10.1007/978-1-0716-1274-3_8DOI Listing
April 2021

Crosstalk between sIgA-Coated Bacteria in Infant Gut and Early-Life Health.

Trends Microbiol 2021 Feb 15. Epub 2021 Feb 15.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China; National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, Jiangsu, China. Electronic address:

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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http://dx.doi.org/10.1016/j.tim.2021.01.012DOI Listing
February 2021

Priming for Life: Early Life Nutrition and the Microbiota-Gut-Brain Axis.

Nutrients 2021 Jan 28;13(2). Epub 2021 Jan 28.

APC Microbiome Ireland, Biosciences Institute, University College Cork, Cork T12 YT20, Ireland.

Microbes colonize the human body during the first moments of life and coexist with the host throughout the lifespan. Intestinal microbiota and their metabolites aid in the programming of important bodily systems such as the immune and the central nervous system during critical temporal windows of development, with possible structural and functional implications throughout the lifespan. These critical developmental windows perinatally (during the first 1000 days) are susceptible timepoints for insults that can endure long lasting effects on the microbiota-gut-brain axis. Environmental and parental factors like host genetics, mental health, nutrition, delivery and feeding mode, exposure to antibiotics, immune activation and microbiota composition antenatally, are all factors that are able to modulate the microbiota composition of mother and infant and may thus regulate important bodily functions. Among all these factors, early life nutrition plays a pivotal role in perinatal programming and in the modulation of offspring microbiota from birth throughout lifespan. This review aims to present current data on the impact of early life nutrition and microbiota priming of important bodily systems and all the factors influencing the microbial coexistence with the host during early life development.
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http://dx.doi.org/10.3390/nu13020423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912058PMC
January 2021

Ameliorates DSS-Induced Colitis by Maintaining Intestinal Mechanical Barrier, Blocking Proinflammatory Cytokines, Inhibiting TLR4/NF-κB Signaling, and Altering Gut Microbiota.

J Agric Food Chem 2021 Feb 29;69(5):1496-1512. Epub 2021 Jan 29.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China.

This study was designed to explore the effects and discrepancy of different CLA-producing on relieving colitis and to investigate the potential mechanisms. 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 and decreased , and . 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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http://dx.doi.org/10.1021/acs.jafc.0c06329DOI Listing
February 2021

Effects of the short-term administration of on physiological characteristics, inflammation, and intestinal microecology in mice.

Food Funct 2021 Mar;12(4):1695-1707

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China and School of Food Science and Technology, Jiangnan University, Wuxi, China. and National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, China.

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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http://dx.doi.org/10.1039/d0fo02948cDOI Listing
March 2021

A time-lagged association between the gut microbiome, nestling weight and nestling survival in wild great tits.

J Anim Ecol 2021 Apr 9;90(4):989-1003. Epub 2021 Feb 9.

School of Biological, Earth and Environmental Sciences, University College Cork, Cork, Ireland.

Natal body mass is a key predictor of viability and fitness in many animals. While variation in body mass and therefore juvenile viability may be explained by genetic and environmental factors, emerging evidence points to the gut microbiota as an important factor influencing host health. The gut microbiota is known to change during development, but it remains unclear whether the microbiome predicts fitness, and if it does, at which developmental stage it affects fitness traits. We collected data on two traits associated with fitness in wild nestling great tits Parus major: weight and survival to fledging. We characterised the gut microbiome using 16S rRNA sequencing from nestling faeces and investigated temporal associations between the gut microbiome and fitness traits across development at Day-8 (D8) and Day-15 (D15) post-hatching. We also explored whether particular microbial taxa were 'indicator species' that reflected whether nestlings survived or not. There was no link between mass and microbial diversity on D8 or D15. However, we detected a time-lagged relationship where weight at D15 was negatively associated with the microbial diversity at D8, controlling for weight at D8, therefore reflecting relative weight gain over the intervening period. Indicator species analysis revealed that specificity values were high and fidelity values were low, suggesting that indicator taxa were primarily detected within either the survived or not survived groups, but not always detected in birds that either survived or died. Therefore these indicator taxa may be sufficient, but not necessary for determining either survival or mortality, perhaps owing to functional overlap in microbiota. We highlight that measuring microbiome-fitness relationships at just one time point may be misleading, especially early in life. Instead, microbial-host fitness effects may be best investigated longitudinally to detect critical development windows for key microbiota and host traits associated with neonatal weight. Our findings should inform future hypothesis testing to pinpoint which features of the gut microbial community impact on host fitness, and when during development this occurs. Such confirmatory research will shed light on population level processes and could have the potential to support conservation.
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http://dx.doi.org/10.1111/1365-2656.13428DOI Listing
April 2021

Long-term dietary intake from infancy to late adolescence is associated with gut microbiota composition in young adulthood.

Am J Clin Nutr 2021 03;113(3):647-656

Unit of Nutritional Epidemiology, Department of Nutrition and Food Sciences, University of Bonn, Bonn, Germany.

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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http://dx.doi.org/10.1093/ajcn/nqaa340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948843PMC
March 2021

A multicentre analysis of Clostridium difficile in persons with Cystic Fibrosis demonstrates that carriage may be transient and highly variable with respect to strain and level.

J Infect 2021 Mar 11;82(3):363-370. Epub 2021 Jan 11.

Cork Adult Cystic Fibrosis Centre, University College Cork, Cork University Hospital, Wilton, Cork, Ireland. Electronic address:

Purpose: Clostridium difficile has been reported to occur in the gastrointestinal tract of 50% of Cystic Fibrosis (CF) subjects, however, clinical C. difficile infection (CDI) is a rare occurrence in this cohort despite the presence of toxigenic and hypervirulent ribotypes. Here, we present the first longitudinal, multicentre analysis of C. difficile prevalence among adult CF subjects.

Methodology: Faecal samples were collected from adults with CF (selected based on confirmed Pseudomonas aeruginosa pulmonary colonisation) from Ireland, UK and Belgium as part of the CFMATTERS clinical research trial (grant No. 603038) and from non-CF controls. Faecal samples were collected on enrolment, at three monthly intervals, during pulmonary exacerbation and three months post exacerbation. C. difficile was isolated from faecal samples by ethanol shocking followed by culturing on cycloserine cefoxitin egg yolk agar. Isolates were characterised in terms of ribotype, toxin type and antibiotic susceptibility to antibiotics routinely used in the treatment of CDI (metronidazole and vancomycin) and those implicated in induction of CDI (ciprofloxacin and moxifloxacin).

Results: Prevalence of C. difficile among CF subjects in the three sites was similar ranging from 47% to 50% at baseline, while the healthy control cohort had a carriage rate of 7.1%. Including subjects who were positive for C. difficile at any time point there was a higher carriage rate of 71.4%, 66.7% and 63.2% in Ireland, UK, and Belgium, respectively. Ribotyping of 80 isolates from 45 CF persons, over multiple time points revealed 23 distinct ribotypes with two ribotypes (046 and 078) shared by all centres. The proportion of toxigenic isolates varied across the sites, ranging from 66.7% in Ireland to 52.9% in Belgium and 100% in the UK. Antibiotic susceptibility rates to vancomycin, metronidazole, ciprofloxacin and moxifloxacin was 100%, 97.5%, 1.3% and 63.8%, respectively.

Conclusions: This study demonstrates the highest carriage rate of C. difficile to date in a CF cohort. Longitudinal data show that C. difficile can be a transient inhabitant of the CF gut, changing both in terms of strain and excretion rates.
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http://dx.doi.org/10.1016/j.jinf.2020.12.027DOI Listing
March 2021

The Sporobiota of the Human Gut.

Gut Microbes 2021 Jan-Dec;13(1):1-17

Food Biosciences Department, Teagasc Food Research Centre , Moorepark, Fermoy, Co. Cork, Ireland.

The human gut microbiome is a diverse and complex ecosystem that plays a critical role in health and disease. The composition of the gut microbiome has been well studied across all stages of life. In recent years, studies have investigated the production of endospores by specific members of the gut microbiome. An endospore is a tough, dormant structure formed by members of the Firmicutes phylum, which allows for greater resistance to otherwise inhospitable conditions. This innate resistance has consequences for human health and disease, as well as in biotechnology. In particular, the formation of endospores is strongly linked to antibiotic resistance and the spread of antibiotic resistance genes, also known as the resistome. The term sporobiota has been used to define the spore-forming cohort of a microbial community. In this review, we present an overview of the current knowledge of the sporobiota in the human gut. We discuss the development of the sporobiota in the infant gut and the perinatal factors that may have an effect on vertical transmission from mother to infant. Finally, we examine the sporobiota of critically important food sources for the developing infant, breast milk and powdered infant formula.
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http://dx.doi.org/10.1080/19490976.2020.1863134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801112PMC
January 2021

Effect of storage, temperature, and extraction kit on the phylogenetic composition detected in the human milk microbiota.

Microbiologyopen 2021 01 29;10(1):e1127. Epub 2020 Dec 29.

Teagasc Food Research Centre, Moorepark, Fermoy, Co., Cork, Ireland.

Human milk is considered the optimum feeding regime for newborns and is a source of bacteria for the developing infant gastrointestinal tract. However, as with all low biomass samples, standardization across variabilities such as sample collection, storage, and extraction methods is needed to eliminate discrepancies in microbial composition across studies. The aim of this study was to investigate how different storage methods, temperatures, preservatives, and extraction kits influence the human milk microbiome, compared to fresh samples. Breast milk samples were processed via six different methods: fresh (Method 1), frozen at -80°C (Method 2), treated with RNAlater and stored at 4°C or -80°C (Methods 3 and 4), and treated with Milk Preservation Solution at room temperature (Methods 5 and 6). Methods 1-5 were extracted using PowerFood Microbial DNA Isolation kit (Mobio), and Method 6 was extracted using Milk DNA Preservation and Isolation kit (Norgen BioTek). At genus level, the most abundant genera were shared across Methods 1-5. Samples frozen at -80°C had fewest significant changes while samples treated and extracted using Milk Preservation and Isolation kit had the most significant changes when compared to fresh samples. Diversity analysis indicated that variation in microbiota composition was related to the method and extraction kit used. This study highlighted that, when extraction from fresh milk samples is not an option, freezing at -80°C is the next best option to preserve the integrity of the milk microbiome. Furthermore, our results demonstrate that choice of extraction kit had a profound impact on the microbiota populations detected in milk.
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http://dx.doi.org/10.1002/mbo3.1127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841076PMC
January 2021

Short communication: Genotype-phenotype association analysis revealed different utilization ability of 2'-fucosyllactose in Bifidobacterium genus.

J Dairy Sci 2021 Feb 23;104(2):1518-1523. Epub 2020 Dec 23.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China; National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, Jiangsu 214122, China; Beijing Innovation Center of Food Nutrition and Human Health, Beijing Technology and Business University (BTBU), Beijing 100048, China.

The oligosaccharide 2'-fucosyllactose (2'FL) in human breast milk selectively promotes the proliferation of bifidobacteria. One hundred fifty-one Bifidobacterium strains were evaluated for their capacity to utilize 2'FL based on the combination of phenotype and genotype association analysis. Through genotype analysis, 37 strains were predicted to have the ability to use 2'FL, including Bifidobacteriumbifidum, Bifidobacteriumbreve, Bifidobacteriumlongum ssp. longum, Bifidobacteriumlongum ssp. infantis, and Bifidobacteriumdentium, whereas Bifidobacteriumadolescentis, Bifidobacteriumanimalis, Bifidobacteriumpseudocatenulatum, and Bifidobacteriumangulatum could not use 2'FL. For in vitro utilization, there were noteworthy differences for 2'FL usage among different species, which were 100% consistent with genotype prediction. The results indicated that 2'FL utilization ability differed even within the same species, and Bifidobacterium followed the currently well-known pathway to utilize 2'FL, which could provide guidance to develop personalized prebiotics for different bifidobacteria via gene-trait matching analysis.
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http://dx.doi.org/10.3168/jds.2020-19013DOI Listing
February 2021

Bifidobacterium longum counters the effects of obesity: Partial successful translation from rodent to human.

EBioMedicine 2021 Jan 18;63:103176. Epub 2020 Dec 18.

APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.

Background: The human gut microbiota has emerged as a key factor in the development of obesity. Certain probiotic strains have shown anti-obesity effects. The objective of this study was to investigate whether Bifidobacterium longum APC1472 has anti-obesity effects in high-fat diet (HFD)-induced obese mice and whether B. longum APC1472 supplementation reduces body-mass index (BMI) in healthy overweight/obese individuals as the primary outcome. B. longum APC1472 effects on waist-to-hip ratio (W/H ratio) and on obesity-associated plasma biomarkers were analysed as secondary outcomes.

Methods: B. longum APC1472 was administered to HFD-fed C57BL/6 mice in drinking water for 16 weeks. In the human intervention trial, participants received B. longum APC1472 or placebo supplementation for 12 weeks, during which primary and secondary outcomes were measured at the beginning and end of the intervention.

Findings: B. longum APC1472 supplementation was associated with decreased bodyweight, fat depots accumulation and increased glucose tolerance in HFD-fed mice. While, in healthy overweight/obese adults, the supplementation of B. longum APC1472 strain did not change primary outcomes of BMI (0.03, 95% CI [-0.4, 0.3]) or W/H ratio (0.003, 95% CI [-0.01, 0.01]), a positive effect on the secondary outcome of fasting blood glucose levels was found (-0.299, 95% CI [-0.44, -0.09]).

Interpretation: This study shows a positive translational effect of B. longum APC1472 on fasting blood glucose from a preclinical mouse model of obesity to a human intervention study in otherwise healthy overweight and obese individuals. This highlights the promising potential of B. longum APC1472 to be developed as a valuable supplement in reducing specific markers of obesity.

Funding: This research was funded in part by Science Foundation Ireland in the form of a Research Centre grant (SFI/12/RC/2273) to APC Microbiome Ireland and by a research grant from Cremo S.A.
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http://dx.doi.org/10.1016/j.ebiom.2020.103176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838052PMC
January 2021

GG soluble mediators ameliorate early life stress-induced visceral hypersensitivity and changes in spinal cord gene expression.

Neuronal Signal 2020 Dec 23;4(4):NS20200007. Epub 2020 Nov 23.

APC Microbiome Ireland, University College Cork, Cork, Ireland.

Visceral hypersensitivity is a hallmark of many functional and stress-related gastrointestinal disorders, and there is growing evidence that the gut microbiota may play a role in its pathophysiology. It has previously been shown that early life stress-induced visceral sensitivity is reduced by various probiotic strains of bacteria (including Lactobacillus rhamnosus GG (LGG)) alone or in combination with prebiotic fibres in rat models. However, the exact mechanisms underpinning such effects remain unresolved. Here, we investigated if soluble mediators derived from LGG can mimic the bacteria's effects on visceral hypersensitivity and the microbiota-gut-brain axis. Rats were exposed to maternal separation (MS) from postnatal days 2-12. From weaning onwards both non-separated (NS) and MS offspring were provided drinking water with or without supplementation of standardized preparations of the LGG soluble mediators (LSM). Our results show that MS led to increased visceral sensitivity and exaggerated corticosterone plasma levels following restraint stress in adulthood, and both of these effects were ameliorated through LSM supplementation. Differential regulation of various genes in the spinal cord of MS versus NS rats was observed, 41 of which were reversed by LSM supplementation. At the microbiota composition level MS led to changes in beta diversity and abundance of specific bacteria including , which were ameliorated by LSM. These findings support probiotic soluble mediators as potential interventions in the reduction of symptoms of visceral hypersensitivity.
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http://dx.doi.org/10.1042/NS20200007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726314PMC
December 2020

Volatility as a Concept to Understand the Impact of Stress on the Microbiome.

Psychoneuroendocrinology 2021 Feb 8;124:105047. Epub 2020 Dec 8.

Department of Anatomy & Neuroscience, University College Cork, Ireland; APC Microbiome Ireland, University College Cork, Ireland. Electronic address:

The microbiome-gut-brain-axis is a complex phenomenon spanning several dynamic systems in the body which can be parsed at a molecular, cellular, physiological and ecological level. A growing body of evidence indicates that this axis is particularly sensitive to the effects of stress and that it may be relevant to stress resilience and susceptibility. Although stress-induced changes in the composition of the microbiome have been reported, the degree of compositional change over time, which we define as volatility, has not been the subject of in-depth scrutiny. Using a chronic psychosocial stress paradigm in male mice, we report that the volatility of the microbiome significantly correlated with several readouts of the stress response, including behaviour and corticosterone response. We then validated these findings in a second independent group of stressed mice. Additionally, we assessed the relationship between volatility and stress parameters in a cohort of health volunteers who were undergoing academic exams and report similar observations. Finally, we found inter-species similarities in the microbiome stress response on a functional level. Our research highlights the effects of stress on the dynamic microbiome and underscores the informative value of volatility as a parameter that should be considered in all future analyses of the microbiome.
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http://dx.doi.org/10.1016/j.psyneuen.2020.105047DOI Listing
February 2021

Diet induces parallel changes to the gut microbiota and problem solving performance in a wild bird.

Sci Rep 2020 11 27;10(1):20783. Epub 2020 Nov 27.

School of Biological, Earth and Environmental Sciences, University College Cork, Distillery Fields, North Mall, Cork, Ireland.

The microbial community in the gut is influenced by environmental factors, especially diet, which can moderate host behaviour through the microbiome-gut-brain axis. However, the ecological relevance of microbiome-mediated behavioural plasticity in wild animals is unknown. We presented wild-caught great tits (Parus major) with a problem-solving task and showed that performance was weakly associated with variation in the gut microbiome. We then manipulated the gut microbiome by feeding birds one of two diets that differed in their relative levels of fat, protein and fibre content: an insect diet (low content), or a seed diet (high content). Microbial communities were less diverse among individuals given the insect compared to those on the seed diet. Individuals were less likely to problem-solve after being given the insect diet, and the same microbiota metrics that were altered as a consequence of diet were also those that correlated with variation in problem solving performance. Although the effect on problem-solving behaviour could have been caused by motivational or nutritional differences between our treatments, our results nevertheless raise the possibility that dietary induced changes in the gut microbiota could be an important mechanism underlying individual behavioural plasticity in wild populations.
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http://dx.doi.org/10.1038/s41598-020-77256-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699645PMC
November 2020

Dietary vitamin A supplementation prevents early obesogenic diet-induced microbiota, neuronal and cognitive alterations.

Int J Obes (Lond) 2021 Mar 22;45(3):588-598. Epub 2020 Nov 22.

Université de Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, UFR de Pharmacie, 146 Rue Léo Saignat, 33076, Bordeaux Cedex, France.

Background: Early consumption of obesogenic diets, rich in saturated fat and added sugar, is associated with a plethora of biological dysfunctions, at both peripheral and brain levels. Obesity is also linked to decreased vitamin A bioavailability, an essential molecule for brain plasticity and memory function.

Methods: Here we investigated in mice whether dietary vitamin A supplementation (VAS) could prevent some of the metabolic, microbiota, neuronal and cognitive alterations induced by obesogenic, high-fat and high-sugar diet (HFSD) exposure from weaning to adulthood, i.e. covering periadolescent period.

Results: As expected, VAS was effective in enhancing peripheral vitamin A levels as well as hippocampal retinoic acid levels, the active metabolite of vitamin A, regardless of the diet. VAS attenuated HFSD-induced excessive weight gain, without affecting metabolic changes, and prevented alterations of gut microbiota α-diversity. In HFSD-fed mice, VAS prevented recognition memory deficits but had no effect on aversive memory enhancement. Interestingly, VAS alleviated both HFSD-induced higher neuronal activation and lower glucocorticoid receptor phosphorylation in the hippocampus after training.

Conclusion: Dietary VAS was protective against the deleterious effects of early obesogenic diet consumption on hippocampal function, possibly through modulation of the gut-brain axis.
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http://dx.doi.org/10.1038/s41366-020-00723-zDOI Listing
March 2021

Lactobacillus plantarum relieves diarrhea caused by enterotoxin-producing Escherichia coli through inflammation modulation and gut microbiota regulation.

Food Funct 2020 Dec 21;11(12):10362-10374. Epub 2020 Nov 21.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China.

Lactobacillus plantarum can relieve diarrhea caused by enterotoxigenic Escherichia coli (ETEC), but the remission mechanism has not been fully explained. This study compares the ability of four Lactobacillus plantarum strains from different niches to alleviate diarrhea caused by ETEC infection and explores their potential remission manner. The results showed that Lactobacillus plantarum CCFM1143 had the most obvious protective effect on diarrhea caused by ETEC. FGDLZ1M5, FCQNA30M6 and CCFM1143 reduced tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and interleukin (IL)-6 as well as jejunal injury. Moreover, FCQNA30M6 and CCFM1143 increased the aquaporin AQP3, and CCFM1143 increased interleukin (IL)-10 and decreased heat-stable enterotoxin (ST), while FGDLZ1M5 reduced the toll-like receptor (TLR4). The gut microbiota analysis demonstrated that ETEC increased Proteus and Pseudomonas and reduced Bifidobacterium, Odoribacter, Allobaculum and Blautia. A supplement of Lactobacillus plantarum could reconstruct the unbalanced gut microbiota. Furthermore, CCFM1143 significantly increased butyric acid, acetic acid, propionic acid and isobutyric acid, while FGDLZ1M5 only increased butyric acid. In summary, Lactobacillus plantarum alleviated ETEC-induced diarrhea by regulating the inflammatory cytokines, rebalancing the gut microbiota and modulating short-chain fatty acids (SCFAs) generation, which could provide the foundation and support for subsequent clinical trials and probiotic products.
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http://dx.doi.org/10.1039/d0fo02670kDOI Listing
December 2020

Enduring neurobehavioral effects induced by microbiota depletion during the adolescent period.

Transl Psychiatry 2020 11 6;10(1):382. Epub 2020 Nov 6.

APC Microbiome Ireland, University College Cork, Cork, Ireland.

The gut microbiota is an essential regulator of many aspects of host physiology. Disruption of gut microbial communities affects gut-brain communication which ultimately can manifest as changes in brain function and behaviour. Transient changes in gut microbial composition can be induced by various intrinsic and extrinsic factors, however, it is possible that enduring shifts in the microbiota composition can be achieved by perturbation at a timepoint when the gut microbiota has not fully matured or is generally unstable, such as during early life or ageing. In this study, we investigated the effects of 3-week microbiota depletion with antibiotic treatment during the adolescent period and in adulthood. Following a washout period to restore the gut microbiota, behavioural and molecular hallmarks of gut-brain communication were investigated. Our data revealed that transient microbiota depletion had long-lasting effects on microbiota composition and increased anxiety-like behaviour in mice exposed to antibiotic treatment during adolescence but not in adulthood. Similarly, gene expression in the amygdala was more severely affected in mice treated during adolescence. Taken together these data highlight the vulnerability of the gut microbiota during the critical adolescent period and the long-lasting impact manipulations of the microbiota can have on gene expression and behaviour in adulthood.
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http://dx.doi.org/10.1038/s41398-020-01073-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648059PMC
November 2020

The Role of the Microbiome in Oral Squamous Cell Carcinoma with Insight into the Microbiome-Treatment Axis.

Int J Mol Sci 2020 Oct 29;21(21). Epub 2020 Oct 29.

Department of Paediatrics and Child Health, University College Cork, Cork T12 DFK4, Ireland.

Oral squamous cell carcinoma (OSCC) is one of the leading presentations of head and neck cancer (HNC). The first part of this review will describe the highlights of the oral microbiome in health and normal development while demonstrating how both the oral and gut microbiome can map OSCC development, progression, treatment and the potential side effects associated with its management. We then scope the dynamics of the various microorganisms of the oral cavity, including bacteria, mycoplasma, fungi, archaea and viruses, and describe the characteristic roles they may play in OSCC development. We also highlight how the human immunodeficiency viruses (HIV) may impinge on the host microbiome and increase the burden of oral premalignant lesions and OSCC in patients with HIV. Finally, we summarise current insights into the microbiome-treatment axis pertaining to OSCC, and show how the microbiome is affected by radiotherapy, chemotherapy, immunotherapy and also how these therapies are affected by the state of the microbiome, potentially determining the success or failure of some of these treatments.
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http://dx.doi.org/10.3390/ijms21218061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662318PMC
October 2020

A specific dietary fibre supplementation improves cognitive performance-an exploratory randomised, placebo-controlled, crossover study.

Psychopharmacology (Berl) 2021 Jan 20;238(1):149-163. Epub 2020 Sep 20.

APC Microbiome Ireland, University College Cork, Cork, Ireland.

Rationale: The impact of the microbiota on the gut-brain axis is increasingly appreciated. A growing body of literature demonstrates that use of dietary fibre and prebiotics can manipulate the microbiota and affect host health. However, the influence on cognition and acute stress response is less well understood.

Objectives: The objective of this study was to investigate the efficacy of a dietary fibre, polydextrose (PDX), in improving cognitive performance and acute stress responses through manipulation of the gut microbiota in a healthy population.

Methods: In this double-blind, randomised, placebo-controlled, crossover design study, 18 healthy female participants received 12.5 g Litesse®Ultra (> 90% PDX polymer) or maltodextrin for 4 weeks. Cognitive performance, mood, acute stress responses, microbiota composition, and inflammatory markers were assessed pre- and post-intervention.

Results: PDX improved cognitive flexibility as evidenced by the decrease in the number of errors made in the Intra-Extra Dimensional Set Shift (IED) task. A better performance in sustained attention was observed through higher number of correct responses and rejections in the Rapid Visual Information Processing (RVP) task. Although there was no change in microbial diversity, abundance of Ruminiclostridium 5 significantly increased after PDX supplementation compared with placebo. PDX supplementation attenuated the increase of adhesion receptor CD62L on classical monocytes observed in the placebo group.

Conclusions: Supplementation with the PDX resulted in a modest improvement in cognitive performance. The results indicate that PDX could benefit gut-to-brain communication and modulate behavioural responses.
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http://dx.doi.org/10.1007/s00213-020-05665-yDOI Listing
January 2021

Enduring Behavioral Effects Induced by Birth by Caesarean Section in the Mouse.

Curr Biol 2020 Oct 20;30(19):3761-3774.e6. Epub 2020 Aug 20.

APC Microbiome Ireland, University College Cork, Cork T12 YT20, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork T12 XF62, Ireland. Electronic address:

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.
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http://dx.doi.org/10.1016/j.cub.2020.07.044DOI Listing
October 2020

A good start in life is important-perinatal factors dictate early microbiota development and longer term maturation.

FEMS Microbiol Rev 2020 11;44(6):763-781

APC Microbiome Ireland, Cork, Ireland, P12 YT20.

Maternal health status is vital for the development of the offspring of humans, including physiological health and psychological functions. The complex and diverse microbial ecosystem residing within humans contributes critically to these intergenerational impacts. Perinatal factors, including maternal nutrition, antibiotic use and maternal stress, alter the maternal gut microbiota during pregnancy, which can be transmitted to the offspring. In addition, gestational age at birth and mode of delivery are indicated frequently to modulate the acquisition and development of gut microbiota in early life. The early-life gut microbiota engages in a range of host biological processes, particularly immunity, cognitive neurodevelopment and metabolism. The perturbed early-life gut microbiota increases the risk for disease in early and later life, highlighting the importance of understanding relationships of perinatal factors with early-life microbial composition and functions. In this review, we present an overview of the crucial perinatal factors and summarise updated knowledge of early-life microbiota, as well as how the perinatal factors shape gut microbiota in short and long terms. We further discuss the clinical consequences of perturbations of early-life gut microbiota and potential therapeutic interventions with probiotics/live biotherapeutics.
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http://dx.doi.org/10.1093/femsre/fuaa030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685781PMC
November 2020

Extensive bacteriocin gene shuffling in the Streptococcus bovis/Streptococcus equinus complex reveals gallocin D with activity against vancomycin resistant enterococci.

Sci Rep 2020 08 10;10(1):13431. Epub 2020 Aug 10.

APC Microbiome Ireland, Cork, Ireland.

Streptococcus gallolyticus LL009 produces gallocin D, a narrow spectrum two component bacteriocin with potent activity against vancomycin-resistant enterococci. Gallocin D is distinct from gallocin A, a separate two component bacteriocin produced by S. gallolyticus. Although the gene clusters encoding gallocin A and gallocin D have a high degree of gene synteny, the structural genes are highly variable and appear to have undergone gene shuffling with other streptococcal species. Gallocin D was analysed in laboratory-based experiments. The mature peptides are 3,343 ± 1 Da and 3,019 ± 1 Da and could be readily synthesized and display activity against a vancomycin resistant Enterococcus strain EC300 with a MIC value of 1.56 µM. Importantly, these bacteriocins could contribute to the ability of S. gallolyticus to colonize the colon where they have been associated with colorectal cancer.
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http://dx.doi.org/10.1038/s41598-020-70328-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417737PMC
August 2020

Is there evidence for bacterial transfer via the placenta and any role in the colonization of the infant gut? - a systematic review.

Crit Rev Microbiol 2020 Sep 10;46(5):493-507. Epub 2020 Aug 10.

Human Nutrition, School of Medicine, Dentistry, and Nursing, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow Royal Infirmary, Glasgow, UK.

With the important role of the gut microbiome in health and disease, it is crucial to understand key factors that establish the microbial community, including gut colonization during infancy. It has been suggested that the first bacterial exposure is via a placental microbiome. However, despite many publications, the robustness of the evidence for the placental microbiome and transfer of bacteria from the placenta to the infant gut is unclear and hence the concept disputed. Therefore, we conducted a systematic review of the evidence for the role of the placental, amniotic fluid and cord blood microbiome in healthy mothers in the colonization of the infant gut. Most of the papers which were fully assessed considered placental tissue, but some studied amniotic fluid or cord blood. Great variability in methodology was observed especially regarding sample storage conditions, DNA/RNA extraction, and microbiome characterization. No study clearly considered transfer of the normal placental microbiome to the infant gut. Moreover, some studies in the review and others published subsequently reported little evidence for a placental microbiome in comparison to negative controls. In conclusion, current data are limited and provide no conclusive evidence that there is a normal placental microbiome which has any role in colonization of infant gut.
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http://dx.doi.org/10.1080/1040841X.2020.1800587DOI Listing
September 2020

Investigating the potential of fish oil as a nutraceutical in an animal model of early life stress.

Nutr Neurosci 2020 Jul 31:1-23. Epub 2020 Jul 31.

APC Microbiome Ireland, Cork, Ireland.

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. 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. 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. 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. 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.
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http://dx.doi.org/10.1080/1028415X.2020.1753322DOI Listing
July 2020

Diversity of Gut Microbiota and Bifidobacterial Community of Chinese Subjects of Different Ages and from Different Regions.

Microorganisms 2020 Jul 24;8(8). Epub 2020 Jul 24.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China.

Gut microbiota composition and functionality are closely linked to host health. In this study, the fecal microbiota and bifidobacterial communities of 111 healthy volunteers from four regions of China of varying age profiles (Child, 1-5 years; Young, 18-50 years; Elder, 60-80 years; Longevity, ≥90 years) were investigated via high-throughput sequencing. Canonical analysis revealed that the gut microbiota, as well as bifidobacteria profiles of the subjects, clustered according to their regions and age. Eight genera were shared among all subjects, however, certain genera distributed differently in subjects grouped by region and age. was enriched in samples from Zhongxiang, unclassified and were enriched in the Longevity group, and was enriched in Child. Within , was the most abundant species in almost all samples except for Child, in which was the most abundant. Additionally, the abundances of and were lower in Child. In conclusion, our results suggest that geography and age affect the structure of the gut microbiota, as well as composition, and this variation may greatly associate with the metabolic and immune changes that occur during the process of aging.
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http://dx.doi.org/10.3390/microorganisms8081108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464982PMC
July 2020