Publications by authors named "Kirsten Berding"

18 Publications

  • Page 1 of 1

Acute stress increases monocyte levels and modulates receptor expression in healthy females.

Brain Behav Immun 2021 May 9;94:463-468. Epub 2021 Mar 9.

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

There has been a growing recognition of the involvement of the immune system in stress-related disorders. Acute stress leads to the activation of neuroendocrine systems, which in turn orchestrate a large-scale redistribution of innate immune cells, such as monocytes. Even though acute stress/monocyte interactions have been well-characterized in mice, this is not the case for humans. As such, this study aimed to investigate whether acute stress modulates blood monocyte levels in a subtype-dependent manner and whether the receptor expression of stress-related receptors is affected in humans. Blood was collected from healthy female volunteers at baseline and 1 h after the socially evaluated cold pressor test, after which blood monocyte levels and receptor expression were assessed by flow cytometry. Our results reveal a stress-induced increase in blood monocyte levels, which was independent of monocyte subtypes. Furthermore, colony stimulating factor 1 receptor (CSF-1R) and CD29 receptor expression was increased, while CD62L showed a trend towards increased expression. These results provide novel insights into how acute stress affects the innate immune system.
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http://dx.doi.org/10.1016/j.bbi.2021.03.005DOI Listing
May 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

Mining microbes for mental health: Determining the role of microbial metabolic pathways in human brain health and disease.

Neurosci Biobehav Rev 2021 Mar 3;125:698-761. Epub 2021 Mar 3.

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

There is increasing knowledge regarding the role of the microbiome in modulating the brain and behaviour. Indeed, the actions of microbial metabolites are key for appropriate gut-brain communication in humans. Among these metabolites, short-chain fatty acids, tryptophan, and bile acid metabolites/pathways show strong preclinical evidence for involvement in various aspects of brain function and behaviour. With the identification of neuroactive gut-brain modules, new predictive tools can be applied to existing datasets. We identified 278 studies relating to the human microbiota-gut-brain axis which included sequencing data. This spanned across psychiatric and neurological disorders with a small number also focused on normal behavioural development. With a consistent bioinformatics pipeline, thirty-five of these datasets were reanalysed from publicly available raw sequencing files and the remainder summarised and collated. Among the reanalysed studies, we uncovered evidence of disease-related alterations in microbial metabolic pathways in Alzheimer's Disease, schizophrenia, anxiety and depression. Amongst studies that could not be reanalysed, many sequencing and technical limitations hindered the discovery of specific biomarkers of microbes or metabolites conserved across studies. Future studies are warranted to confirm our findings. We also propose guidelines for future human microbiome analysis to increase reproducibility and consistency within the field.
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http://dx.doi.org/10.1016/j.neubiorev.2021.02.044DOI Listing
March 2021

Going with the grain: Fiber, cognition, and the microbiota-gut-brain-axis.

Exp Biol Med (Maywood) 2021 Apr 28;246(7):796-811. Epub 2021 Feb 28.

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

Healthy dietary intake has been acknowledged for decades as one of the main contributors to health. More recently, the field of nutritional psychiatry has progressed our understanding regarding the importance of nutrition in supporting mental health and cognitive function. Thereby, individual nutrients, including omega-3 fatty acids and polyphenols, have been recognized to be key drivers in this relationship. With the progress in appreciating the influence of dietary fiber on health, increasingly research is focusing on deciphering its role in brain processes. However, while the importance of dietary fiber in gastrointestinal and metabolic health is well established, leading to the development of associated health claims, the evidence is not conclusive enough to support similar claims regarding cognitive function. Albeit the increasing knowledge of the impact of dietary fiber on mental health, only a few human studies have begun to shed light onto the underexplored connection between dietary fiber and cognition. Moreover, the microbiota-gut-brain axis has emerged as a key conduit for the effects of nutrition on the brain, especially fibers, that are acted on by specific bacteria to produce a variety of health-promoting metabolites. These metabolites (including short chain fatty acids) as well as the vagus nerve, the immune system, gut hormones, or the kynurenine pathway have been proposed as underlying mechanisms of the microbiota-brain crosstalk. In this minireview, we summarize the evidence available from human studies on the association between dietary fiber intake and cognitive function. We provide an overview of potential underlying mechanisms and discuss remaining questions that need to be answered in future studies. While this field is moving at a fast pace and holds promise for future important discoveries, especially data from human cohorts are required to further our understanding and drive the development of public health recommendations regarding dietary fiber in brain health.
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http://dx.doi.org/10.1177/1535370221995785DOI 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

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

Diet and depression: exploring the biological mechanisms of action.

Mol Psychiatry 2021 01 3;26(1):134-150. Epub 2020 Nov 3.

Deakin University, IMPACT (the Institute for Mental and Physical Health and Clinical Translation), Food & Mood Centre, Geelong, VIC, Australia.

The field of nutritional psychiatry has generated observational and efficacy data supporting a role for healthy dietary patterns in depression onset and symptom management. To guide future clinical trials and targeted dietary therapies, this review provides an overview of what is currently known regarding underlying mechanisms of action by which diet may influence mental and brain health. The mechanisms of action associating diet with health outcomes are complex, multifaceted, interacting, and not restricted to any one biological pathway. Numerous pathways were identified through which diet could plausibly affect mental health. These include modulation of pathways involved in inflammation, oxidative stress, epigenetics, mitochondrial dysfunction, the gut microbiota, tryptophan-kynurenine metabolism, the HPA axis, neurogenesis and BDNF, epigenetics, and obesity. However, the nascent nature of the nutritional psychiatry field to date means that the existing literature identified in this review is largely comprised of preclinical animal studies. To fully identify and elucidate complex mechanisms of action, intervention studies that assess markers related to these pathways within clinically diagnosed human populations are needed.
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http://dx.doi.org/10.1038/s41380-020-00925-xDOI Listing
January 2021

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

Recipe for a Healthy Gut: Intake of Unpasteurised Milk Is Associated with Increased Abundance in the Human Gut Microbiome.

Nutrients 2020 May 19;12(5). Epub 2020 May 19.

APC Microbiome Ireland, University College Cork, T12 YN60 Cork, Ireland.

Introduction: The gut microbiota plays a role in gut-brain communication and can influence psychological functioning. Diet is one of the major determinants of gut microbiota composition. The impact of unpasteurised dairy products on the microbiota is unknown. In this observational study, we investigated the effect of a dietary change involving intake of unpasteurised dairy on gut microbiome composition and psychological status in participants undertaking a residential 12-week cookery course on an organic farm.

Methods: Twenty-four participants completed the study. The majority of food consumed during their stay originated from the organic farm itself and included unpasteurised milk and dairy products. At the beginning and end of the course, participants provided faecal samples and completed self-report questionnaires on a variety of parameters including mood, anxiety and sleep. Nutrient intake was monitored with a food frequency questionnaire. Gut microbiota analysis was performed with 16S rRNA gene sequencing. Additionally, faecal short chain fatty acids (SCFAs) were measured.

Results: Relative abundance of the genus increased significantly between pre- and post-course time points. This increase was associated with participants intake of unpasteurised milk and dairy products. An increase in the faecal SCFA, valerate, was observed along with an increase in the functional richness of the microbiome profile, as determined by measuring the predictive neuroactive potential using a gut-brain module approach.

Conclusions: While concerns in relation to safety need to be considered, intake of unpasteurised milk and dairy products appear to be associated with the growth of the probiotic bacterial genus, , in the human gut. More research is needed on the effect of dietary changes on gut microbiome composition, in particular in relation to the promotion of bacterial genera, such as , which are recognised as being beneficial for a range of physical and mental health outcomes.
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http://dx.doi.org/10.3390/nu12051468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285075PMC
May 2020

Dietary Patterns Impact Temporal Dynamics of Fecal Microbiota Composition in Children With Autism Spectrum Disorder.

Front Nutr 2019 10;6:193. Epub 2020 Jan 10.

Division of Nutritional Sciences, University of Illinois, Urbana, IL, United States.

Environmental factors such as diet are known influencers on gastrointestinal (GI) microbiota variability and some diseases are associated with microbial stability. Whether microbial variability is related to symptoms of Autism Spectrum Disorder (ASD) and how diet impacts microbial stability in ASD is unknown. Herein, temporal variability in stool microbiota in relation to dietary habits in 2-7 years-old children with ASD (ASD, = 26) and unaffected controls (CONT, = 32) was investigated. Fecal samples were collected at baseline, 6-weeks and 6-months. Bacterial composition was assessed using 16S rRNA sequencing. Short fatty acid (SCFA) concentrations were analyzed by gas chromatography. Nutrient intake was assessed using a 3-day food diary and dietary patterns (DP) were empirically derived from a food frequency questionnaire. Social deficit scores (SOCDEF) were assessed using the Pervasive Developmental Disorder Behavior Inventory-Screening Version (PDDBI-SV). GI symptoms were assessed using the GI severity index. Overall, temporal variability in microbial structure, and membership did not differ between the groups. In children with ASD, abundances of , Streptophyta, , varied significantly, and concentrations of all SCFAs decreased over time. Variability in community membership was negatively correlated with median SOCDEF scores. Additionally, Clostridiales, , and were components of a more stable microbiota community in children with ASD. DP1, characterized by vegetables, starchy vegetables, legumes, nuts and seeds, fruit, grains, juice and dairy, was associated with changes in species diversity, abundance of , and and concentrations of propionate, butyrate, isobutyrate and isovalerate in children with ASD. DP2 characterized by fried, protein and starchy foods, "Kid's meals," condiments, and snacks was associated with variations in microbiota structure, abundance of , and and changes in all SCFA concentrations. However, no association between microbial stability and SOCDEF or GI severity scores were observed. In conclusion, microbiota composition varies over time in children with ASD, might be related to social deficit scores and can be impacted by diet. Future studies investigating the physiological effect of the changes in specific microbial taxa and metabolites are needed to delineate the impact on ASD symptomology.
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http://dx.doi.org/10.3389/fnut.2019.00193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6968728PMC
January 2020

Analysis of gut microbiome, nutrition and immune status in autism spectrum disorder: a case-control study in Ecuador.

Gut Microbes 2020 05 18;11(3):453-464. Epub 2019 Sep 18.

Centro de Investigación Traslacional, Universidad de las Américas , Quito, Ecuador.

Most studies on autism spectrum disorder (ASD) risk factors have been conducted in developed countries where ethnicity and environment are different than in developing countries. We compared nutritional status, immune response and microbiota composition in mestizo children with ASD with matched controls in Ecuador. Twenty-five cases and 35 controls were matched by age, sex and school location. The prevalence of under- and overweight was higher in children with ASD. Nutritional differences were accompanied by abnormal food habits and more frequent gastrointestinal symptoms in children with ASD. Also, greater serum concentrations of TGF-β1 were observed in children with ASD. Finally, there was greater alpha diversity and abundance of (2 OTUs), and different species of in ASD children.
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http://dx.doi.org/10.1080/19490976.2019.1662260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524316PMC
May 2020

Diet Can Impact Microbiota Composition in Children With Autism Spectrum Disorder.

Front Neurosci 2018 31;12:515. Epub 2018 Jul 31.

Division of Nutritional Sciences, University of Illinois, Urbana, IL, United States.

Diet is one of the most influential environmental factors in determining the composition of the gastrointestinal microbiota. Microbial dysbiosis in children with Autism Spectrum Disorder (ASD) and the impact of some bacterial taxa on symptoms of ASD has been recognized. Children with ASD are often described as picky eaters with low intake of fiber-rich foods, including fruits and vegetables. However, the impact of diet on the microbiota composition in children with ASD is largely unknown. Herein, fecal samples, 3 day food diaries and the Youth and Adolescence Food Frequency questionnaire (YAQ) were collected from children with ASD (ASD; = 26) and unaffected controls (CONT; = 32). Children's ASD symptoms were determined using the Pervasive Developmental Disorder Behavior Inventory Screening Version (PDDBI-SV). Differences in the microbiota composition at the phyla, order, family, and genus level between ASD and CONT were observed. Microbiota composition of children with ASD was investigated in relation to feeding behavior, nutrient and food group intake as well as dietary patterns derived from the YAQ. In children with ASD, two distinct dietary patterns (DP) were associated with unique microbial profiles. DP1, characterized by higher intakes of vegetables, legumes, nuts and seeds, fruit, refined carbohydrates, and starchy vegetables, but lower intakes of sweets, was associated with lower abundance of , and . DP2, characterized by low intakes of vegetables, legumes, nuts and seeds and starchy vegetables, was associated with higher and and lower , as well as higher levels of propionate, isobutyrate, valerate, and isovalerate. Peptostreptococcaceae and predicted social deficit scores in children with ASD as measured by the PDDBI-SV. Diet-associated microbial profiles were related to GI symptoms, but no significant interaction between nutrition and microbiota in predicting social deficit scores were observed. In conclusion, dietary patterns associated with fecal microbiota composition and VFA concentrations in children with ASD were identified. Future studies using a larger sample size and measuring other behaviors associated with ASD are needed to investigate whether dietary intake may be a modifiable moderator of ASD symptoms.
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http://dx.doi.org/10.3389/fnins.2018.00515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6079226PMC
July 2018

Fecal microbiome composition and stability in 4- to 8-year old children is associated with dietary patterns and nutrient intake.

J Nutr Biochem 2018 06 20;56:165-174. Epub 2018 Mar 20.

Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, 61801; Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, 61801. Electronic address:

How long-term dietary intake shapes microbiota composition and stability in young children is poorly understood. Herein, the temporal variability in stool microbiota composition in relation to habitual dietary patterns of 4- to 8-year-old children (n=22) was investigated. Fecal samples were collected at baseline, 6 weeks and 6 months. Bacterial composition and volatile fatty acids were assessed by 16S rRNA sequencing and gas-chromatography, respectively. Nutrient intake was assessed using 3-day food diaries and dietary patterns were empirically derived from a food frequency questionnaire. Using a factor loading of >0.45 for a food group to be a major contributor to the overall dietary pattern, two dietary patterns were found to be associated with distinct microbiome composition. Dietary Pattern 1 (DP1), characterized by intake of fish, protein foods, refined carbohydrates, vegetables, fruit, juice and sweetened beverages, kid's meals and snacks and sweets, was associated with higher relative abundance of Bacteroidetes, Bacteroides and Ruminococcus and lower abundance of Bifidobacterium, Prevotella, Blautia and Roseburia. Dietary Pattern 2 (DP2), characterized by intake of grains, dairy and legumes, nuts and seeds, was associated with higher relative abundance of Cyanobacteria and Phascolarctobacterium and lower abundance of Dorea and Eubacterium. Fruit and starchy foods were present in both patterns, but were more associated with DP1 and DP2, respectively. Temporal stability of microbiota over a 6-month period was associated with baseline dietary patterns. Understanding how dietary intake contributes to microbiota composition and stability in early life in important for dietary recommendations and designing clinical interventions for microbiota-associated diseases.
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http://dx.doi.org/10.1016/j.jnutbio.2018.01.002DOI Listing
June 2018

Serum cortisol mediates the relationship between fecal Ruminococcus and brain N-acetylaspartate in the young pig.

Gut Microbes 2017 11 18;8(6):589-600. Epub 2017 Aug 18.

a Piglet Nutrition & Cognition Laboratory , University of Illinois , Urbana , IL , USA.

A dynamic relationship between the gut microbiota and brain is pivotal in neonatal development. Dysbiosis of the microbiome may result in altered neurodevelopment; however, it is unclear which specific members of microbiota are most influential and what factors might mediate the relationship between the gut and the brain. Twenty-four vaginally-derived male piglets were subjected to magnetic resonance spectroscopy at 30 d of age. Ascending colon contents, feces, and blood were collected and analyzed for volatile fatty acids, microbiota relative abundance by 16s rRNA, and serum metabolites, respectively. A mediation analysis was performed to assess the mediatory effect of serum biomarkers on the relationship between microbiota and neurometabolites. Results indicated fecal Ruminococcus and Butyricimonas predicted brain N-acetylaspartate (NAA). Analysis of serum biomarkers indicated Ruminococcus independently predicted serum serotonin and cortisol. A 3-step mediation indicated: i) Ruminococcus negatively predicted NAA, ii) Ruminococcus negatively predicted cortisol, and iii) a significant indirect effect (i.e., the effect of fecal Ruminococcus through cortisol on NAA) was observed and the direct effect became insignificant. Thus, serum cortisol fully mediated the relationship between fecal Ruminococcus and brain NAA. Using magnetic resonance spectroscopy, this study used a statistical mediation analysis and provides a novel perspective into the potential underlying mechanisms through which the microbiota may shape brain development. This is the first study to link Ruminococcus, cortisol, and NAA in vivo, and these findings are substantiated by previous literature indicating these factors may be influential in the etiology of neurodevelopmental disorders.
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http://dx.doi.org/10.1080/19490976.2017.1353849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5730385PMC
November 2017

Microbiome and nutrition in autism spectrum disorder: current knowledge and research needs.

Nutr Rev 2016 12;74(12):723-736

K. Berding and S.M. Donovan are with the Division of Nutritional Sciences, University of Illinois, Urbana, Illinois, USA; S.M. Donovan is with the Department of Food Science and Human Nutrition, University of Illinois, Urbana, Illinois, USA.

Autism spectrum disorder (ASD) is the fastest growing neurodevelopmental disorder in the United States. Besides genetic risks, environmental factors have been suggested to contribute to the increase in ASD diagnosis over the past decade. Several studies have reported abnormalities in microbiota composition and differences in microbial metabolites in children with ASD. Gastrointestinal discomfort is commonly reported in children with ASD. Additionally, food selectivity and picky eating patterns are commonly reported. A number of mechanisms underlying the interaction between nutrition, the gut microbiota, and ASD symptoms via the microbiota-gut-brain axis have been proposed, including immune, hormonal, or neuronal pathways. Here, the current evidence base regarding the gut environment and nutritional status of children with ASD is reviewed. Potential underlying mechanisms of the microbiota-gut-brain axis in ASD and the interplay between nutrition, microbiota, and ASD symptoms are also reviewed. Future studies investigating the microbiota in the context of dietary intake are needed to increase understanding of the interplay between diet and the gut microbiota in ASD and to identify potential dietary, probiotic, or prebiotic intervention strategies.
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http://dx.doi.org/10.1093/nutrit/nuw048DOI Listing
December 2016

Prebiotics and Bioactive Milk Fractions Affect Gut Development, Microbiota, and Neurotransmitter Expression in Piglets.

J Pediatr Gastroenterol Nutr 2016 12;63(6):688-697

*Division of Nutritional Sciences †Department of Food Science and Human Nutrition ‡Piglet Nutrition and Cognition Laboratory, Department of Animal Sciences §Neuroscience Program, University of Illinois, Urbana-Champaign ||Mead Johnson Pediatric Nutrition Institute, Evansville, IN.

Objective: This study tested the hypothesis that the addition of prebiotics and 2 functional milk ingredients to infant formula would maintain normal growth and gut development, and modify microbiota composition and neurotransmitter gene expression in neonatal piglets.

Methods: Two-day-old male piglets (n = 24) were fed formula (CONT) or formula with polydextrose (1.2 g/100 g diet), galactooligosaccharides (3.5 g/100 g diet), bovine lactoferrin (0.3 g/100 g diet), and milk fat globule membrane-10 (2.5 g/100 g diet) (TEST) for 30 days. On study day 31, intestinal samples, ileal and colonic contents, and feces were collected. Intestinal histomorphology, disaccharidase activity, serotonin (5'HT), vasoactive intestinal peptide (VIP), and tyrosine hydroxylase (TH) were measured. Gut microbiota composition was assessed by pyrosequencing of the V3-V5 regions of 16S rRNA and quantitative polymerase chain reaction.

Results: Body weight of piglets on TEST was greater (P ≤ 0.05) than CONT on days 17 to 30. Both groups displayed growth patterns within the range observed for sow-reared pigs. TEST piglets had greater jejunal lactase (P = 0.03) and higher (P = 0.003) ileal VIP expression. TEST piglets tended to have greater (P = 0.09) sucrase activity, longer (P = 0.08) ileal villi, and greater (P = 0.06) duodenal TH expression. Microbial communities of TEST piglets differed from CONT in ascending colon (AC, P = 0.001) and feces (P ≤ 0.05). CONT piglets had greater relative abundances of Mogibacterium, Collinsella, Klebsiella, Escherichia/Shigella, Eubacterium, and Roseburia compared with TEST piglets in AC. In feces, CONT piglets harbored lower (P ≤ 0.05) proportions of Parabacteroides, Clostridium IV, Lutispora, and Sutterella than TEST piglets.

Conclusions: A mixture of bioactive ingredients improved weight gain and gut maturation, modulated colonic and fecal microbial composition, and reduced the proportions of opportunistic pathogens.
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http://dx.doi.org/10.1097/MPG.0000000000001200DOI Listing
December 2016

Dietary Prebiotics, Milk Fat Globule Membrane, and Lactoferrin Affects Structural Neurodevelopment in the Young Piglet.

Front Pediatr 2016 4;4. Epub 2016 Feb 4.

Piglet Nutrition and Cognition Laboratory, Department of Animal Sciences, University of Illinois, Urbana, IL, USA; Neuroscience Program, University of Illinois, Urbana, IL, USA; Division of Nutritional Sciences, University of Illinois, Urbana, IL, USA.

Introduction: Milk fat globule membrane (MFGM) and lactoferrin have been identified as two components that have potential to affect neurodevelopment. While concentrations of some MFGM constituents in infant formulas are within human milk range, they may not be present at optimal or clinically effective levels. However, lactoferrin levels of infant formulas are consistently reported to be lower than human milk. This study sought to provide a novel combination of prebiotics, bovine-derived MFGM, and lactoferrin and assess their influence on neurodevelopment.

Methods: Twenty-four male piglets were provided either TEST (n = 12) or CONT (n = 12) diet from 2 to 31 days of age. Piglets underwent spatial T-maze assessment starting at 17 days of age, were subjected to magnetic resonance imaging at 30 days of age, and were euthanized for tissue collection at 31 days of age.

Results: Diffusion tensor imaging revealed differences in radial (P = 0.032) and mean (P = 0.028) diffusivities in the internal capsule, where CONT piglets had higher rates of diffusion compared with TEST piglets. Voxel-based morphometry indicated larger (P < 0.05) differences in cortical gray and white matter concentrations, with CONT piglets having larger tissue clusters in these regions compared with TEST piglets. In the spatial T-maze assessment, CONT piglets exhibited shorter latency to choice compared with TEST piglets on day 2 of acquisition and days 3 and 4 of reversal.

Conclusion: Observed differences in microstructure maturation of the internal capsule and cortical tissue concentrations suggest that piglets provided TEST diet were more advanced developmentally than piglets provided CONT diet. Therefore, supplementation of infant formula with prebiotics, MFGM, and lactoferrin may support neurodevelopment in human infants.
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http://dx.doi.org/10.3389/fped.2016.00004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4740374PMC
February 2016

Responses of Preterm Pigs to an Oral Fluid Supplement During Parenteral Nutrition.

JPEN J Parenter Enteral Nutr 2016 09 9;40(7):934-43. Epub 2015 Mar 9.

Health and Sport Science, University of Memphis, Memphis, Tennessee, USA

Background: Nutrients and electrolytes in amniotic fluid swallowed by fetuses are important for growth and development. Yet, preterm infants requiring parenteral nutrition (PN) receive minimal or no oral inputs. With the limited availability of amniotic fluid, we evaluated the responses of preterm pigs receiving PN to an oral fluid supplement (OFS) based on the electrolyte and nutrient composition of amniotic fluid.

Materials And Methods: Preterm pigs (92% of term) received a combination of PN (6 mL/kg-h) and 4 mL/kg-h of supplemental fluid as an experimental OFS (n = 9), lactated Ringer's either enterally (n = 10) or intravenously (n = 8). Outcome measures after 96 hours were weight gain, blood chemistry, organ weights, and small intestine mass and brush-border membrane carbohydrases.

Results: The OFS did not improve weight gain compared with providing lactated Ringer's orally or intravenously, or increase serum urea nitrogen values, but resulted in higher serum total and low-density lipoprotein cholesterol, as well as improved glucoregulation and heavier intestines, livers, kidneys, and brains and lighter lungs.

Conclusions: Providing supplemental fluid and electrolytes during PN either intravenously or orally increases weight gain after preterm birth. An oral fluid supplement based on amniotic fluid may accelerate development and maturation of organs critical for extrauterine life after preterm birth and may enhance neurodevelopment.
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Source
http://dx.doi.org/10.1177/0148607115574746DOI Listing
September 2016