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Zimmermann P, Kurth S, Giannoukos S, Stocker M, Bokulich NA. NapBiome trial: Targeting gut microbiota to improve sleep rhythm and developmental and behavioural outcomes in early childhood in a birth cohort in Switzerland - a study protocol. BMJ Open 2025; 15:e092938. [PMID: 40032396 PMCID: PMC11877202 DOI: 10.1136/bmjopen-2024-092938] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Accepted: 02/08/2025] [Indexed: 03/05/2025] Open
Abstract
INTRODUCTION The gut-brain axis plays a crucial role in the regulation and development of psychological and physical processes. The first year of life is a critical period for the development of the gut microbiome, which parallels important milestones in establishing sleep rhythm and brain development. Growing evidence suggests that the gut microbiome influences sleep, cognition and early neurodevelopment. For term-born and preterm-born infants, difficulties in sleep regulation may have consequences on health. Identifying effective interventions on the gut-brain axis in early life is likely to have long-term implications for the health and development of at-risk infants. METHODS AND ANALYSES In this multicentre, four-group, double-blinded, placebo (PLC)-controlled randomised trial with a factorial design, 120 preterm-born and 260 term-born infants will be included. The study will investigate whether the administration of daily synbiotics or PLC for a duration of 3 months improves sleep patterns and neurodevelopmental outcomes up to 2 years of age. The trial will also: (1) determine the association between gut microbiota, sleep patterns and health outcomes in children up to 2 years of age; and (2) leverage the interactions between gut microbiota, brain and sleep to develop new intervention strategies for at-risk infants. ETHICS AND DISSEMINATION The NapBiome trial has received ethical approval by the Committee of Northwestern and Central Switzerland and Canton Vaud, Switzerland (#2024-01681). Outcomes will be disseminated through publication and will be presented at scientific conferences. Metagenomic data will be shared through the European Nucleotide Archive. TRIAL REGISTRATION NUMBER The US National Institutes of Health NCT06396689.
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Affiliation(s)
- Petra Zimmermann
- Department of Community Health and Department of Paediatrics, Fribourg Hospital, University of Fribourg, Fribourg, Switzerland
- Department of Paediatrics, The University of Melbourne, Melbourne, Victoria, Australia
| | - Salome Kurth
- Department of Psychology, University of Fribourg, Fribourg, Switzerland
| | - Stamatios Giannoukos
- Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland
| | - Martin Stocker
- Neonatology, Children's Hospital Lucerne, Lucerne, Switzerland
| | - Nicholas A Bokulich
- Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland
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Wilmes L, Caputi V, Bastiaanssen TF, Collins JM, Crispie F, Cotter PD, Dinan TG, Cryan JF, Clarke G, O'Mahony SM. Sex specific gut-microbiota signatures of resilient and comorbid gut-brain phenotypes induced by early life stress. Neurobiol Stress 2024; 33:100686. [PMID: 39583744 PMCID: PMC11582825 DOI: 10.1016/j.ynstr.2024.100686] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Revised: 10/23/2024] [Accepted: 11/02/2024] [Indexed: 11/26/2024] Open
Abstract
Background Alterations in gut-brain axis communication pathways and the gut microbiota ecosystem caused by early life stress have been extensively described as critical players in the pathophysiology of stress-induced disorders. However, the extent to which stress-induced gut microbiota alterations manifest in early life and contribute to the sex-specific susceptibility to distinct gut-brain phenotypes in adulthood has yet to be defined. Methods Male and female Sprague-Dawley rat offspring underwent maternal separation (3h/day from postnatal day 2-12). Faecal samples were collected before weaning for gut microbiota 16S rRNA sequencing and metabolomic analysis. Visceral pain sensitivity and negative valence behaviours were assessed in adulthood using colorectal distension and the forced swim test respectively. Behavioural data were processed in a two-step cluster analysis to identify groupings within the dataset. Multi-omics analysis was carried out to investigate if the microbial signatures following early life stress were already defined according to the membership of the adult behavioural phenotypes. Results Maternal separation resulted in increased visceral hypersensitivity while showing a trend for a sex-dependent increase in negative valence behaviour in adulthood. The cluster analysis revealed four clusters within the dataset representing distinct pathophysiological domains reminiscent of the behavioural consequences of early-life stress: 1. resilient, 2. pain, 3. immobile and 4. comorbid. The early life gut microbiota of each of these clusters show distinct alterations in terms of diversity, genus level differential abundance, and functional modules. Multi-omic integrations points towards a role for different metabolic pathways underlying each cluster-specific phenotype. Conclusion Our study is the first to identify distinct phenotypes defined by susceptibility or resilience to gut-brain dysfunction induced by early life stress. The gut microbiota in early life shows sex-dependent alterations in each cluster that precede specific behavioural phenotypes in adulthood. Future research is warranted to determine the causal relationship between early-life stress-induced changes in the gut microbiota and to understand the trajectory leading to the manifestation of different behavioural phenotypes in adulthood.
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Affiliation(s)
- Lars Wilmes
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
- Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland
| | - Valentina Caputi
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
| | - Thomaz F.S. Bastiaanssen
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
| | - James M. Collins
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
| | - Fiona Crispie
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland
| | - Paul D. Cotter
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland
| | - Timothy G. Dinan
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland
| | - John F. Cryan
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
| | - Gerard Clarke
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
- Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland
| | - Siobhain M. O'Mahony
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
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Oh J, Woo HG, Kim HJ, Park J, Lee M, Rahmati M, Rhee SY, Min C, Koyanagi A, Smith L, Fond G, Boyer L, Kim MS, Shin JI, Lee SW, Yon DK. Prenatal and infant exposure to antibiotics and subsequent risk of neuropsychiatric disorders in children: A nationwide birth cohort study in South Korea. Psychiatry Res 2024; 340:116117. [PMID: 39128166 DOI: 10.1016/j.psychres.2024.116117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Revised: 06/17/2024] [Accepted: 07/29/2024] [Indexed: 08/13/2024]
Abstract
We aimed to assess the association between antibiotic exposure in fetal and postnatal life (within six months after birth) and the risk of neuropsychiatric disorders in childhood. A nationwide, population-based birth cohort study(infants, n = 3,163,206; paired mothers, n = 2,322,735) was conducted in South Korea, with a mean follow-up duration of 6.8 years, using estimates of hazard ratio [HR] and 95 % confidence intervals (CIs). Following propensity score matching including the baseline variables, antibiotic exposure in both fetal (HR,1.07 [95 % CI, 1.05-1.08]) and postnatal life (1.05 [1.03-1.07]) was associated with an increased risk of overall childhood neuropsychiatric disorders. A synergistic effect was observed with prenatal and postnatal exposures (1.12 [1.09-1.15]). The risk increases with the increasing number and duration of prescriptions. Significant associations were found for both common (1.06 [1.05-1.08]) and severe outcomes (1.17 [1.09-1.26]), especially for intellectual disability (1.12 [1.07-1.17]), ADHD (1.10 [1.07-1.13]), anxiety (1.06 [1.02-1.11]), mood (1.06 [1.00-1.12]), and autism (1.03 [1.01-1.07]). When comparing siblings with different exposure statuses to consider familial factors, prenatal and postnatal exposure risk increased to 10 % (95 % CI, 6-12) and 12 % (7-17), respectively. Similar results were observed in the unmatched and health screening cohort, which considers maternal obesity, smoking, and breastfeeding. Based on these findings, clinicians may consider potential long-term risks when assessing the risk-benefit of early-life antibiotic prescription.
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Affiliation(s)
- Jiyeon Oh
- Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea
| | - Ho Geol Woo
- Department of Neurology, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea
| | - Hyeon Jin Kim
- Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea; Department of Regulatory Science, Kyung Hee University, Seoul, South Korea
| | - Jaeyu Park
- Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea; Department of Regulatory Science, Kyung Hee University, Seoul, South Korea
| | - Myeongcheol Lee
- Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea; Department of Regulatory Science, Kyung Hee University, Seoul, South Korea
| | - Masoud Rahmati
- CEReSS-Health Service Research and Quality of Life Center, Assistance Publique-Hôpitaux de Marseille, Aix-Marseille University, Marseille, France; Department of Physical Education and Sport Sciences, Faculty of Literature and Human Sciences, Lorestan University, Khoramabad, Iran; Department of Physical Education and Sport Sciences, Faculty of Literature and Humanities, Vali-E-Asr University of Rafsanjan, Rafsanjan, Iran
| | - Sang Youl Rhee
- Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea; Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, Seoul, South Korea
| | - Chanyang Min
- Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea
| | - Ai Koyanagi
- Research and Development Unit, Parc Sanitari Sant Joan de Deu, Barcelona, Spain
| | - Lee Smith
- Centre for Health, Performance and Wellbeing, Anglia Ruskin University, Cambridge, UK
| | - Guillaume Fond
- CEReSS-Health Service Research and Quality of Life Center, Assistance Publique-Hôpitaux de Marseille, Aix-Marseille University, Marseille, France
| | - Laurent Boyer
- CEReSS-Health Service Research and Quality of Life Center, Assistance Publique-Hôpitaux de Marseille, Aix-Marseille University, Marseille, France
| | - Min Seo Kim
- Medical and Population Genetics and Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Jae Il Shin
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, South Korea; Severance Underwood Meta-Research Center, Institute of Convergence Science, Yonsei University, Seoul, South Korea
| | - Seung Won Lee
- Department of Precision Medicine, Sungkyunkwan University School of Medicine, Suwon, South Korea
| | - Dong Keon Yon
- Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea; Department of Regulatory Science, Kyung Hee University, Seoul, South Korea; Department of Pediatrics, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea.
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Willemsen Y, Ou Y, Belzer C, Arias Vásquez A, Smidt H, Beijers R, de Weerth C. A longitudinal study of the gut microbiota during the first three years of life: Links with problem behavior and executive functions at preschool age. Dev Psychopathol 2024; 36:2032-2048. [PMID: 37994488 DOI: 10.1017/s0954579423001402] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2023]
Abstract
Early life is a sensitive period when microbiota-gut-brain interactions may have important impact on development. This study investigated the associations of the gut microbiota in the first three years of life (two, six, and 12 weeks, and one and three years) with problem behavior and executive functions in N = 64 three-year-old children. Higher relative abundance of Streptococcus at the age of two weeks, as well as its trajectory over time (including ages two, six and 12 weeks, and one and three years), was related to worse executive functions. Higher relative abundance of [Ruminococcus] torques group at the age of three years, as well as its trajectory from one to three years, was associated with less internalizing behavior. Besides, several robust age-specific associations were identified: higher Bifidobacterium relative abundance (age three years) was associated with more internalizing and externalizing issues; higher Blautia relative abundance (age three years) was linked to less internalizing behavior; and increased relative abundance of an unidentified Enterobacteriaceae genus (age two weeks) was related to more externalizing behavior. Our findings provide important longitudinal evidence that early-life gut microbiota may be linked to behavioral and cognitive development in low-risk children.
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Affiliation(s)
- Yvonne Willemsen
- Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Yangwenshan Ou
- Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands
- Laboratory of Microbiology, Wageningen University & Research, Wageningen, The Netherlands
| | - Clara Belzer
- Laboratory of Microbiology, Wageningen University & Research, Wageningen, The Netherlands
| | - Alejandro Arias Vásquez
- Department of Psychiatry and Human Genetics, Donders Center for Medical Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Hauke Smidt
- Laboratory of Microbiology, Wageningen University & Research, Wageningen, The Netherlands
| | - Roseriet Beijers
- Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands
- Behavioral Science Institute, Radboud University, Nijmegen, The Netherlands
| | - Carolina de Weerth
- Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands
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Cho NA, Giesbrecht GF, Dewey D, Reimer RA. Early Life Surgency, but not Effortful Control or Negative Affectivity, Is a Mediating Variable Between Maternal Pre-Pregnancy Body Mass Index and Childhood Obesity Risk. Dev Psychobiol 2024; 66:e22517. [PMID: 38924077 DOI: 10.1002/dev.22517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Revised: 05/24/2024] [Accepted: 05/27/2024] [Indexed: 06/28/2024]
Abstract
Maternal gestational obesity is related to risk of obesity in the child. This risk may be in part mediated by altered child temperament, which can affect mother-child interactions, including feeding and soothing behaviors that affect obesity risk. Our objective was to examine the association between maternal pre-pregnancy BMI and child zBMI and determine if child temperament, specifically positive Affectivity/Surgency, mediates this association. Using conditional process modeling, we analyzed data from 408 mother-child dyads enrolled in the Alberta Pregnancy Outcomes and Nutrition (APrON) study. Child temperament was assessed at 3 years of age via a parent report measure, the Child Behavior Questionnaire (CBQ), and child zBMI was calculated from in-person measurements of child height and weight at 4-5 years of age. Bivariate correlations showed that there was a significant positive correlation between zBMI and Surgency (r = 0.11, p = 0.03), and zBMI was also correlated with maternal pre-pregnancy BMI (r = 0.12, p = 0.02). Multivariable regression revealed that maternal pre-pregnancy BMI (adjusted β = 0.15, 95% confidence interval [CI]; 0.00-0.05, p = 0.02) and Surgency scores (adjusted β = 0.14, 95% CI; 0.02-0.28, p = 0.03) were associated with higher child zBMI at 4-5 years of age. Mediation analysis showed that Surgency mediated the association between pre-pregnancy BMI and child zBMI. Our models controlled for maternal gestational weight gain, gestational diabetes, socioeconomic status, maternal anxiety and depression, and gestational age at birth. Overall, maternal pre-pregnancy BMI was positively associated with child zBMI, and this association was mediated by higher child Surgency scores.
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Affiliation(s)
- Nicole A Cho
- Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada
| | - Gerald F Giesbrecht
- Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
- Department of Psychology, University of Calgary, Calgary, Alberta, Canada
- Alberta Children's Hospital Research Institute (ACHRI), University of Calgary, Calgary, Alberta, Canada
- Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Deborah Dewey
- Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
- Alberta Children's Hospital Research Institute (ACHRI), University of Calgary, Calgary, Alberta, Canada
- Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
- Hotchkiss Brain Institute (HBI), University of Calgary, Calgary, Alberta, Canada
| | - Raylene A Reimer
- Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada
- Alberta Children's Hospital Research Institute (ACHRI), University of Calgary, Calgary, Alberta, Canada
- Department of Biochemistry & Molecular Biology, Cumming School of Medicine, Calgary, Alberta, Canada
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Sealschott S, Pickler R, Fortney C, Bailey M, Loman B. Gut Microbiota and Symptom Expression and Severity in Neonatal Abstinence Syndrome. Biol Res Nurs 2024; 26:460-468. [PMID: 38528812 DOI: 10.1177/10998004241242102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/27/2024]
Abstract
Problem: Neonatal abstinence syndrome (NAS) affecting neonates with fetal exposure to opioids, is defined by expression and severity of symptoms. The pathophysiology behind symptoms variability is lacking. The study aims were to examine (a) differences in gut microbiota of neonates with and without NAS, (b) the relationships between gut microbiota and symptom expression and NAS severity, and (c) the changes in the neonate gut microbiota diversity during the course of NAS treatment. Methods: A cross-sectional observational design was used to examine differences in microbiota and a longitudinal, repeated measures approach was used to determine relationships between gut microbiota and NAS symptoms. Symptom data were collected using the Finnegan Neonatal Abstinence Scoring Tool and the Neonatal Pain Agitation and Sedation Scale. Stool samples were collected for microbiome analyses with 16S rRNA microbiome sequencing. Results: Differences in alpha and beta diversity between neonates with and without NAS were seen. Relative abundance results revealed 18 taxa were different in neonates with NAS compared to neonates without NAS. No differences were found in alpha or beta diversity in neonates with NAS between enrollment and hospital discharge. There was increased abundance of Escherichia-Shigella and Bacteriodes genera related to higher symptom scores. Discussion: Differences in alpha and beta diversity between neonates with and without NAS may be due to differences in birth mode and type of feeding. The findings of specific increased bacteria related to increased symptoms in the neonates with NAS may also be influenced by birth mode and type of feeding.
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Affiliation(s)
| | - Rita Pickler
- The Ohio State University College of Nursing, Columbus, OH, USA
| | | | - Michael Bailey
- The Ohio State University College of Nursing, Columbus, OH, USA
- Center for Microbial Pathogenesis, Columbus, The Research Institute at Nationwide Children's Hospital, OH, USA
| | - Brett Loman
- University of Illinois Urbana-Champaign, Urbana, IL, USA
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Otaru N, Kourouma L, Pugin B, Constancias F, Braegger C, Mansuy IM, Lacroix C. Transgenerational effects of early life stress on the fecal microbiota in mice. Commun Biol 2024; 7:670. [PMID: 38822061 PMCID: PMC11143345 DOI: 10.1038/s42003-024-06279-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Accepted: 05/02/2024] [Indexed: 06/02/2024] Open
Abstract
Stress in early life can affect the progeny and increase the risk to develop psychiatric and cardiometabolic diseases across generations. The cross-generational effects of early life stress have been modeled in mice and demonstrated to be associated with epigenetic factors in the germline. While stress is known to affect gut microbial features, whether its effects can persist across life and be passed to the progeny is not well defined. Here we show that early postnatal stress in mice shifts the fecal microbial composition (binary Jaccard index) throughout life, including abundance of eight amplicon sequencing variants (ASVs). Further effects on fecal microbial composition, structure (weighted Jaccard index), and abundance of 16 ASVs are detected in the progeny across two generations. These effects are not accompanied by changes in bacterial metabolites in any generation. These results suggest that changes in the fecal microbial community induced by early life traumatic stress can be perpetuated from exposed parent to the offspring.
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Affiliation(s)
- Nize Otaru
- Nutrition Research Unit, University Children's Hospital Zürich, Zürich, Switzerland
- Department of Health Sciences and Technology, Laboratory of Food Biotechnology, ETH Zürich, Zürich, Switzerland
| | - Lola Kourouma
- Department of Health Science and Technology of the ETH Zurich, Laboratory of Neuroepigenetics, Brain Research Institute, Medical Faculty of the University of Zurich, and Institute for Neuroscience, Zurich, Switzerland
- Center for Neuroscience Zürich, ETH and University Zürich, Zurich, Switzerland
| | - Benoit Pugin
- Department of Health Sciences and Technology, Laboratory of Food Biotechnology, ETH Zürich, Zürich, Switzerland
| | - Florentin Constancias
- Department of Health Sciences and Technology, Laboratory of Food Biotechnology, ETH Zürich, Zürich, Switzerland
| | - Christian Braegger
- Nutrition Research Unit, University Children's Hospital Zürich, Zürich, Switzerland
| | - Isabelle M Mansuy
- Department of Health Science and Technology of the ETH Zurich, Laboratory of Neuroepigenetics, Brain Research Institute, Medical Faculty of the University of Zurich, and Institute for Neuroscience, Zurich, Switzerland.
- Center for Neuroscience Zürich, ETH and University Zürich, Zurich, Switzerland.
| | - Christophe Lacroix
- Department of Health Sciences and Technology, Laboratory of Food Biotechnology, ETH Zürich, Zürich, Switzerland.
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Porru S, Esplugues A, Llop S, Delgado-Saborit JM. The effects of heavy metal exposure on brain and gut microbiota: A systematic review of animal studies. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2024; 348:123732. [PMID: 38462196 DOI: 10.1016/j.envpol.2024.123732] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 02/12/2024] [Accepted: 03/05/2024] [Indexed: 03/12/2024]
Abstract
The gut-brain axis is a crucial interface between the central nervous system and the gut microbiota. Recent evidence shows that exposure to environmental contaminants, such as heavy metals, can cause dysbiosis in gut microbiota, which may affect the gut-brain communication, impacting aspects of brain function and behavior. This systematic review of the literature aims to evaluate whether deleterious effects on brain function due to heavy metal exposure could be mediated by changes in the gut microbiota profile. Animal studies involving exposure to heavy metals and a comparison with a control group that evaluated neuropsychological outcomes and/or molecular outcomes along with the analysis of microbiota composition were reviewed. The authors independently assessed studies for inclusion, extracted data and assessed risk of bias using the protocol of Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) for preclinical studies. A search in 3 databases yielded 16 eligible studies focused on lead (n = 10), cadmium (n = 1), mercury (n = 3), manganese (n = 1), and combined exposure of lead and manganese (n = 1). The animal species were rats (n = 7), mice (n = 4), zebrafish (n = 3), carp (n = 1) and fruit fly (n = 1). Heavy metals were found to adversely affect cognitive function, behavior, and neuronal morphology. Moreover, heavy metal exposure was associated with changes in the abundance of specific bacterial phyla, such as Firmicutes and Proteobacteria, which play crucial roles in gut health. In some studies, these alterations were correlated with learning and memory impairments and mood disorders. The interplay of heavy metals, gut microbiota, and brain suggests that heavy metals can induce direct brain alterations and indirect effects through the microbiota, contributing to neurotoxicity and the development of neuropsychological disorders. However, the small number of papers under review makes it difficult to draw definitive conclusions. Further research is warranted to unravel the underlying mechanisms and evaluate the translational implications for human health.
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Affiliation(s)
- Simona Porru
- Department of Medicine, Faculty of Health Sciences. Universitat Jaume I, Avenida de Vicent Sos Baynat s/n, 12071, Castellón de la Plana, Spain
| | - Ana Esplugues
- Faculty of Nursing and Podiatry, Universitat de València, C/Menendez Pelayo S/n, 46010, València, Spain; Epidemiology and Environmental Health Joint Research Unit, FISABIO-Universitat Jaume I-Universitat de Valencia, Av. Catalunya 21, 46020, València, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Av. Monforte de Lemos, 3-5. Pabellón 11, 28029, Madrid, Spain
| | - Sabrina Llop
- Epidemiology and Environmental Health Joint Research Unit, FISABIO-Universitat Jaume I-Universitat de Valencia, Av. Catalunya 21, 46020, València, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Av. Monforte de Lemos, 3-5. Pabellón 11, 28029, Madrid, Spain
| | - Juana María Delgado-Saborit
- Department of Medicine, Faculty of Health Sciences. Universitat Jaume I, Avenida de Vicent Sos Baynat s/n, 12071, Castellón de la Plana, Spain; Epidemiology and Environmental Health Joint Research Unit, FISABIO-Universitat Jaume I-Universitat de Valencia, Av. Catalunya 21, 46020, València, Spain.
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Li N, Xiao X, Zhang H, Bai Z, Li M, Sun J, Dong Y, Zhu W, Fei Z, Sun X, Xiao P, Gao Y, Zhou D. Sterile soil mitigates the intergenerational loss of gut microbial diversity and anxiety-like behavior induced by antibiotics in mice. Brain Behav Immun 2024; 115:179-190. [PMID: 37848098 DOI: 10.1016/j.bbi.2023.10.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2023] [Revised: 10/10/2023] [Accepted: 10/14/2023] [Indexed: 10/19/2023] Open
Abstract
The decline in gut microbial diversity in modern humans is closely associated with the rising prevalence of various diseases. It is imperative to investigate the underlying causes of gut microbial loss and restoring methods. Although the impact of non-perinatal antibiotic use on gut microbiota has been recognized, its intergenerational effects remain unexplored. Our previous research has highlighted soil in the farm environment as a key factor for gut microbiome health by restoring gut microbial diversity and balance. In this study, we investigated the intergenerational consequences of antibiotic exposure and the therapeutic potential of sterile soil. We treated C57BL/6 mice with vancomycin and streptomycin for 2 weeks continuously, followed by a 4-8 week withdrawal period before breeding. The process was repeated across 3 generations. Half of the mice in each generation received an oral sterile soil intervention. We assessed gut microbial diversity, anxiety behavior, microglial reactivity, and gut barrier integrity across generations. Antibiotic exposure led to a decrease in gut microbial diversity over generations, along with aggravated anxiety behavior, microgliosis, and altered intestinal tight junction protein expression. Oral sterile soil intervention restored gut microbial diversity in adult mice across generations, concomitantly rescuing abnormalities in behavior, microgliosis, and intestinal barrier integrity. In conclusion, this study simulated an important process of the progressive loss of gut microbiota diversity in modern humans and demonstrated the potential of sterile soil to reverse this process. This study provides a theoretical and experimental basis for research and interventions targeting multiple modern chronic diseases related to intestinal microorganisms.
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Affiliation(s)
- Na Li
- Key Laboratory of Child Development and Learning Science of Department of Education, Southeast University, Nanjing 210096, China
| | - Xiaoao Xiao
- Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Honglin Zhang
- College of Food Science, Nanjing Xiaozhuang University, Nanjing 211171, China
| | - Zhimao Bai
- Key Laboratory of Environmental Medicine Engineering of Ministry of Education, Southeast University, Nanjing 210009, China
| | - Mengjie Li
- Key Laboratory of Child Development and Learning Science of Department of Education, Southeast University, Nanjing 210096, China
| | - Jia Sun
- Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Yangyang Dong
- Key Laboratory of Child Development and Learning Science of Department of Education, Southeast University, Nanjing 210096, China
| | - Wenyong Zhu
- State Key Laboratory of Bioelectronics, Southeast University, Nanjing 210096, China
| | - Zhongjie Fei
- State Key Laboratory of Bioelectronics, Southeast University, Nanjing 210096, China
| | - Xiao Sun
- State Key Laboratory of Bioelectronics, Southeast University, Nanjing 210096, China
| | - Pengfeng Xiao
- State Key Laboratory of Bioelectronics, Southeast University, Nanjing 210096, China
| | - Yuanqing Gao
- Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
| | - Dongrui Zhou
- Key Laboratory of Child Development and Learning Science of Department of Education, Southeast University, Nanjing 210096, China.
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10
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Su T, Yin X, Ren J, Lang Y, Zhang W, Cui L. Causal relationship between gut microbiota and myasthenia gravis: a bidirectional mendelian randomization study. Cell Biosci 2023; 13:204. [PMID: 37936124 PMCID: PMC10629094 DOI: 10.1186/s13578-023-01163-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Accepted: 11/02/2023] [Indexed: 11/09/2023] Open
Abstract
BACKGROUND Observational studies have demonstrated an association between gut microbiota and myasthenia gravis; however, the causal relationship between the two still lacks clarity. Our goals are to ascertain the existence of a bidirectional causal relationship between gut microbiota composition and myasthenia gravis, and to investigate how gut microbiota plays a role in reducing the risk of myasthenia gravis. METHODS We acquired gut microbiota data at the phylum, class, order, family, and genus levels from the MiBioGen consortium (N = 18,340) and myasthenia gravis data from the FinnGen Research Project (426 cases and 373,848 controls). In the two-sample Mendelian randomization analysis, we assessed the causal relationship between the gut microbiota and myasthenia gravis. We also conducted bidirectional MR analysis to determine the direction of causality. The inverse variance weighted, mendelian randomization-Egger, weighted median, simple mode, and weighted mode were used to test the causal relationship between the gut microbiota and severe myasthenia gravis. We used MR-Egger intercept and Cochran's Q test to assess for pleiotropy and heterogeneity, respectively. Furthermore, we utilized the MR-PRESSO method to evaluate horizontal pleiotropy and detect outliers. RESULTS In the forward analysis, the inverse-variance weighted method revealed that there is a positive correlation between the genus Lachnoclostridium (OR = 2.431,95%CI 1.047-5.647, p = 0.039) and the risk of myasthenia gravis. Additionally, the family Clostridiaceae1 (OR = 0.424,95%CI 0.202-0.889, p = 0.023), family Defluviitaleaceae (OR = 0.537,95%CI 0.290-0.995, p = 0.048), family Enterobacteriaceae (OR = 0.341,95%CI 0.135-0.865, p = 0.023), and an unknown genus (OR = 0.407,95%CI 0.209-0.793, p = 0.008) all demonstrated negative correlation with the risk of developing myasthenia gravis. Futhermore, reversed Mendelian randomization analysis proved a negative correlation between the risk of myasthenia gravis and genus Barnesiella (OR = 0.945,95%CI 0.906-0.985, p = 0.008). CONCLUSION Our research yielded evidence of a causality connection in both directions between gut microbiota and myasthenia gravis. We identified specific types of microbes associated with myasthenia gravis, which offers a fresh window into the pathogenesis of this disease and the possibility of developing treatment strategies. Nonetheless, more studies, both basic and clinical, are necessary to elucidate the precise role and therapeutic potential of the gut microbiota in the pathogenesis of myasthenia gravis.
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Affiliation(s)
- Tengfei Su
- Department of Neurology, the First Hospital of Jilin University, Changchun, China
| | - Xiang Yin
- Department of Neurology, the First Hospital of Jilin University, Changchun, China
| | - Jiaxin Ren
- Department of Neurology, the First Hospital of Jilin University, Changchun, China
| | - Yue Lang
- Department of Neurology, the First Hospital of Jilin University, Changchun, China
| | - Weiguanliu Zhang
- Department of Neurology, the First Hospital of Jilin University, Changchun, China
| | - Li Cui
- Department of Neurology, the First Hospital of Jilin University, Changchun, China.
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11
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Ju S, Shin Y, Han S, Kwon J, Choi TG, Kang I, Kim SS. The Gut-Brain Axis in Schizophrenia: The Implications of the Gut Microbiome and SCFA Production. Nutrients 2023; 15:4391. [PMID: 37892465 PMCID: PMC10610543 DOI: 10.3390/nu15204391] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 10/10/2023] [Accepted: 10/11/2023] [Indexed: 10/29/2023] Open
Abstract
Schizophrenia, a severe mental illness affecting about 1% of the population, manifests during young adulthood, leading to abnormal mental function and behavior. Its multifactorial etiology involves genetic factors, experiences of adversity, infection, and gene-environment interactions. Emerging research indicates that maternal infection or stress during pregnancy may also increase schizophrenia risk in offspring. Recent research on the gut-brain axis highlights the gut microbiome's potential influence on central nervous system (CNS) function and mental health, including schizophrenia. The gut microbiota, located in the digestive system, has a significant role to play in human physiology, affecting immune system development, vitamin synthesis, and protection against pathogenic bacteria. Disruptions to the gut microbiota, caused by diet, medication use, environmental pollutants, and stress, may lead to imbalances with far-reaching effects on CNS function and mental health. Of interest are short-chain fatty acids (SCFAs), metabolic byproducts produced by gut microbes during fermentation. SCFAs can cross the blood-brain barrier, influencing CNS activity, including microglia and cytokine modulation. The dysregulation of neurotransmitters produced by gut microbes may contribute to CNS disorders, including schizophrenia. This review explores the potential relationship between SCFAs, the gut microbiome, and schizophrenia. Our aim is to deepen the understanding of the gut-brain axis in schizophrenia and to elucidate its implications for future research and therapeutic approaches.
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Affiliation(s)
- Songhyun Ju
- Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea; (S.J.); (Y.S.); (S.H.); (J.K.)
- Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea;
- Biomedical Science Institute, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Yoonhwa Shin
- Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea; (S.J.); (Y.S.); (S.H.); (J.K.)
- Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea;
- Biomedical Science Institute, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Sunhee Han
- Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea; (S.J.); (Y.S.); (S.H.); (J.K.)
- Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea;
- Biomedical Science Institute, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Juhui Kwon
- Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea; (S.J.); (Y.S.); (S.H.); (J.K.)
- Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea;
- Biomedical Science Institute, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Tae Gyu Choi
- Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea;
| | - Insug Kang
- Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea; (S.J.); (Y.S.); (S.H.); (J.K.)
- Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea;
- Biomedical Science Institute, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Sung Soo Kim
- Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea; (S.J.); (Y.S.); (S.H.); (J.K.)
- Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea;
- Biomedical Science Institute, Kyung Hee University, Seoul 02447, Republic of Korea
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12
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Fowler SP, Gimeno Ruiz de Porras D, Swartz MD, Stigler Granados P, Heilbrun LP, Palmer RF. Daily Early-Life Exposures to Diet Soda and Aspartame Are Associated with Autism in Males: A Case-Control Study. Nutrients 2023; 15:3772. [PMID: 37686804 PMCID: PMC10490529 DOI: 10.3390/nu15173772] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Revised: 08/22/2023] [Accepted: 08/25/2023] [Indexed: 09/10/2023] Open
Abstract
Since its introduction, aspartame-the leading sweetener in U.S. diet sodas (DS)-has been reported to cause neurological problems in some users. In prospective studies, the offspring of mothers who consumed diet sodas/beverages (DSB) daily during pregnancy experienced increased health problems. We hypothesized that gestational/early-life exposure to ≥1 DS/day (DSearly) or equivalent aspartame (ASPearly: ≥177 mg/day) increases autism risk. The case-control Autism Tooth Fairy Study obtained retrospective dietary recalls for DSB and aspartame consumption during pregnancy/breastfeeding from the mothers of 235 offspring with autism spectrum disorder (ASD: cases) and 121 neurotypically developing offspring (controls). The exposure odds ratios (ORs) for DSearly and ASPearly were computed for autism, ASD, and the non-regressive conditions of each. Among males, the DSearly odds were tripled for autism (OR = 3.1; 95% CI: 1.02, 9.7) and non-regressive autism (OR = 3.5; 95% CI: 1.1, 11.1); the ASPearly odds were even higher: OR = 3.4 (95% CI: 1.1, 10.4) and 3.7 (95% CI: 1.2, 11.8), respectively (p < 0.05 for each). The ORs for non-regressive ASD in males were almost tripled but were not statistically significant: DSearly OR = 2.7 (95% CI: 0.9, 8.4); ASPearly OR = 2.9 (95% CI: 0.9, 8.8). No statistically significant associations were found in females. Our findings contribute to the growing literature raising concerns about potential offspring harm from maternal DSB/aspartame intake in pregnancy.
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Affiliation(s)
- Sharon Parten Fowler
- Department of Medicine, Joe R. & Teresa Lozano Long School of Medicine, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
| | - David Gimeno Ruiz de Porras
- Southwest Center for Occupational and Environmental Health, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health in San Antonio, The University of Texas Health Science Center at Houston, 7411 John Smith Drive, San Antonio, TX 78229, USA;
- Center for Research in Occupational Health, Universitat Pompeu Fabra, 08003 Barcelona, Spain
- CIBER of Epidemiology and Public Health, 28029 Madrid, Spain
| | - Michael D. Swartz
- Department of Biostatistics and Data Science, School of Public Health, The University of Texas Health Science Center at Houston, 1200 Pressler Street, Houston, TX 77030, USA;
| | - Paula Stigler Granados
- Divisions of Environmental Health and Global Health, School of Public Health, San Diego State University, 5500 Campanile Drive, San Diego, CA 92182, USA;
| | - Lynne Parsons Heilbrun
- Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health in San Antonio, The University of Texas Health Science Center at Houston, 7411 John Smith Drive, San Antonio, TX 78229, USA;
| | - Raymond F. Palmer
- Department of Family Practice and Community Medicine, Joe R. & Teresa Lozano Long School of Medicine, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA;
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13
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Zhang X, Huang Y, Lu Y, Mao F, Cao F. Associations of maternal antenatal bonding with neonatal meconium microbiota and the behavior temperament of infants: A prospective longitudinal study. J Psychiatr Res 2023; 163:159-165. [PMID: 37210834 DOI: 10.1016/j.jpsychires.2023.05.053] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2023] [Revised: 04/12/2023] [Accepted: 05/15/2023] [Indexed: 05/23/2023]
Abstract
Exposure to a poor intrauterine environment, such as maternal prenatal stress, has been linked to gut microbiota health in infants. Understanding the link between maternal prenatal bonding, early gut microbiota, and neuropsychological development may promote healthy development in early life. This study included 306 mother-child pairs. Women were assessed for maternal antenatal bonding using the Maternal Antenatal Attachment Scale in all three trimesters of pregnancy. Neonatal meconium samples were collected after birth. The behavioral temperament of infants was measured using the Very Short Form of the Infant Behavior Questionnaire-Revised at 6 months postpartum. Maternal prenatal bonding was negatively associated with the infants' relative abundance of Burkholderia and was positively associated with the relative abundance of Bifidobacterium, infant surgency and effortful control. The infant's relative abundance of Burkholderia mediates the association between maternal prenatal bonding and effortful control of the infant. This study provides new evidence about the long-term behavioral implications of a prenatally positive intrauterine environment in offspring microbiomes. The integration of maternal bonding assessment and intervention into prenatal healthcare and wellness models may modulate the establishment of gut microbiota in early life and long-term neuropsychological development in infants.
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Affiliation(s)
- Xuan Zhang
- School of Nursing and Rehabilitation, Shandong University, Jinan, Shandong Province, 250012, China
| | - Yongqi Huang
- School of Nursing and Rehabilitation, Shandong University, Jinan, Shandong Province, 250012, China
| | - Yane Lu
- School of Nursing and Rehabilitation, Shandong University, Jinan, Shandong Province, 250012, China
| | - Fangxiang Mao
- School of Nursing and Rehabilitation, Shandong University, Jinan, Shandong Province, 250012, China
| | - Fenglin Cao
- School of Nursing and Rehabilitation, Shandong University, Jinan, Shandong Province, 250012, China.
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14
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Zhang X, Huang Y, Lu Y, Mao F, Cao F. Associations of maternal antenatal bonding with neonatal meconium microbiota and the behavior temperament of infants: A prospective longitudinal study. J Psychiatr Res 2023; 163:159-165. [DOI: 2.doi: 10.1016/j.jpsychires.2023.05.053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/29/2025]
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15
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Mady EA, Doghish AS, El-Dakroury WA, Elkhawaga SY, Ismail A, El-Mahdy HA, Elsakka EGE, El-Husseiny HM. Impact of the mother's gut microbiota on infant microbiome and brain development. Neurosci Biobehav Rev 2023; 150:105195. [PMID: 37100161 DOI: 10.1016/j.neubiorev.2023.105195] [Citation(s) in RCA: 49] [Impact Index Per Article: 24.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 04/18/2023] [Accepted: 04/21/2023] [Indexed: 04/28/2023]
Abstract
The link between the gut microbiome and health has recently garnered considerable interest in its employment for medicinal purposes. Since the early microbiota exhibits more flexibility compared to that of adults, there is a considerable possibility that altering it will have significant consequences on human development. Like genetics, the human microbiota can be passed from mother to child. This provides information on early microbiota acquisition, future development, and prospective chances for intervention. The succession and acquisition of early-life microbiota, modifications of the maternal microbiota during pregnancy, delivery, and infancy, and new efforts to understand maternal-infant microbiota transmission are discussed in this article. We also examine the shaping of mother-to-infant microbial transmission, and we then explore possible paths for future research to advance our knowledge in this area.
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Affiliation(s)
- Eman A Mady
- Laboratory of Veterinary Physiology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai Cho, Fuchu-shi, Tokyo 183-8509, Japan; Department of Animal Hygiene, Behavior and Management, Faculty of Veterinary Medicine, Benha University, Moshtohor, Toukh, Elqaliobiya,13736, Egypt.
| | - Ahmed S Doghish
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt; Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt.
| | - Walaa A El-Dakroury
- Department of Pharmaceutics and industrial pharmacy, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt
| | - Samy Y Elkhawaga
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt
| | - Ahmed Ismail
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt.
| | - Hesham A El-Mahdy
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt
| | - Elsayed G E Elsakka
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt
| | - Hussein M El-Husseiny
- Cooperative Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai Cho, Fuchu-shi, Tokyo 183-8509, Japan.
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16
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Wang Y, Zhu J, Zou N, Zhang L, Wang Y, Zhang M, Wang C, Yang L. Pathogenesis from the microbial-gut-brain axis in white matter injury in preterm infants: A review. Front Integr Neurosci 2023; 17:1051689. [PMID: 37006416 PMCID: PMC10060642 DOI: 10.3389/fnint.2023.1051689] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Accepted: 03/06/2023] [Indexed: 03/18/2023] Open
Abstract
White matter injury (WMI) in premature infants is a unique form of brain injury and a common cause of chronic nervous system conditions such as cerebral palsy and neurobehavioral disorders. Very preterm infants who survive are at high risk of WMI. With developing research regarding the pathogenesis of premature WMI, the role of gut microbiota has attracted increasing attention in this field. As premature infants are a special group, early microbial colonization of the microbiome can affect brain development, and microbiome optimization can improve outcomes regarding nervous system development. As an important communication medium between the gut and the nervous system, intestinal microbes form a microbial-gut-brain axis. This axis affects the occurrence of WMI in premature infants via the metabolites produced by intestinal microorganisms, while also regulating cytokines and mediating oxidative stress. At the same time, deficiencies in the microbiota and their metabolites may exacerbate WMI in premature infants. This confers promise for probiotics and prebiotics as treatments for improving neurodevelopmental outcomes. Therefore, this review attempted to elucidate the potential mechanisms behind the communication of gut bacteria and the immature brain through the gut-brain axis, so as to provide a reference for further prevention and treatment of premature WMI.
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17
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Kondaveeti SN, Thekkekkara D, T LN, Manjula SN, Tausif YM, Babu A, Meheronnisha SK. A Deep Insight into the Correlation Between Gut Dysbiosis and Alzheimer’s Amyloidopathy. J Pharmacol Pharmacother 2023. [DOI: 10.1177/0976500x221150310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/24/2023] Open
Abstract
Background Recent research has shown a strong correlation between gut dysbiosis and Alzheimer’s disease (AD). Purpose To investigate the relationship between gut dysbiosis, immune system activation, and the onset of AD and to examine current breakthroughs in microbiota-targeted AD therapeutics. Methods A review of scientific literature was conducted to assess the correlation between gut dysbiosis and AD and the various factors associated. Results Gut dysbiosis produces an increase in harmful substances, such as bacterial amyloids, which makes the gut barrier and blood-brain barrier more permeable. This leads to the stimulation of immunological responses and an increase in cytokines such as interleukin-1β (IL-1β). As a result, gut dysbiosis accelerates the progression of AD. Conclusion The review highlights the connection between gut dysbiosis and AD and the potential for microbiota-targeted therapies in AD treatment. Pictorial Abstract
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Affiliation(s)
| | - Dithu Thekkekkara
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru, India
| | - Lakshmi Narayanan T
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru, India
| | - S. N. Manjula
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru, India
| | - Y Mohammed Tausif
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru, India
| | - Amrita Babu
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru, India
| | - SK Meheronnisha
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru, India
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Tartaglione AM, Villani A, Ajmone-Cat MA, Minghetti L, Ricceri L, Pazienza V, De Simone R, Calamandrei G. Maternal immune activation induces autism-like changes in behavior, neuroinflammatory profile and gut microbiota in mouse offspring of both sexes. Transl Psychiatry 2022; 12:384. [PMID: 36104346 PMCID: PMC9474453 DOI: 10.1038/s41398-022-02149-9] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 08/26/2022] [Accepted: 09/02/2022] [Indexed: 11/09/2022] Open
Abstract
Autism Spectrum Disorder (ASD) is a sex-biased neurodevelopmental disorder with a male to female prevalence of 4:1, characterized by persistent deficits in social communication and interaction and restricted-repetitive patterns of behavior, interests or activities. Microbiota alterations as well as signs of neuroinflammation have been also reported in ASD. The involvement of immune dysregulation in ASD is further supported by evidence suggesting that maternal immune activation (MIA), especially during early pregnancy, may be a risk factor for ASD. The present study was aimed at characterizing the effects of MIA on behavior, gut microbiota and neuroinflammation in the mouse offspring also considering the impact of MIA in the two sexes. MIA offspring exhibited significant ASD-like behavioral alterations (i.e., deficits in sociability and sensorimotor gating, perseverative behaviors). The analysis of microbiota revealed changes in specific microbial taxa that recapitulated those seen in ASD children. In addition, molecular analyses indicated sex-related differences in the neuroinflammatory responses triggered by MIA, with a more prominent effect in the cerebellum. Our data suggest that both sexes should be included in the experimental designs of preclinical studies in order to identify those mechanisms that confer different vulnerability to ASD to males and females.
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Affiliation(s)
- Anna Maria Tartaglione
- Centre for Behavioral Sciences and Mental Health, Italian National Institute of Health (ISS), Rome, Italy.
| | - Annacandida Villani
- grid.413503.00000 0004 1757 9135Gastroenterology Unit IRCCS “Casa Sollievo della Sofferenza”, Hospital San Giovanni Rotondo, Foggia, Italy
| | - Maria Antonietta Ajmone-Cat
- grid.416651.10000 0000 9120 6856National Centre for Drug Research and Evaluation, Italian National Institute of Health (ISS), Rome, Italy
| | - Luisa Minghetti
- grid.416651.10000 0000 9120 6856Research Coordination and Support Service, Italian National Institute of Health (ISS), Rome, Italy
| | - Laura Ricceri
- grid.416651.10000 0000 9120 6856Centre for Behavioral Sciences and Mental Health, Italian National Institute of Health (ISS), Rome, Italy
| | - Valerio Pazienza
- grid.413503.00000 0004 1757 9135Gastroenterology Unit IRCCS “Casa Sollievo della Sofferenza”, Hospital San Giovanni Rotondo, Foggia, Italy
| | - Roberta De Simone
- grid.416651.10000 0000 9120 6856National Centre for Drug Research and Evaluation, Italian National Institute of Health (ISS), Rome, Italy
| | - Gemma Calamandrei
- grid.416651.10000 0000 9120 6856Centre for Behavioral Sciences and Mental Health, Italian National Institute of Health (ISS), Rome, Italy
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Baniel A, Petrullo L, Mercer A, Reitsema L, Sams S, Beehner JC, Bergman TJ, Snyder-Mackler N, Lu A. Maternal effects on early-life gut microbiota maturation in a wild nonhuman primate. Curr Biol 2022; 32:4508-4520.e6. [PMID: 36099914 DOI: 10.1016/j.cub.2022.08.037] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 06/14/2022] [Accepted: 08/15/2022] [Indexed: 11/25/2022]
Abstract
Early-life microbial colonization is an important process shaping host physiology,1-3 immunity,4-6 and long-term health outcomes7-10 in humans. However, our understanding of this dynamic process remains poorly investigated in wild animals,11-13 where developmental mechanisms can be better understood within ecological and evolutionarily relevant contexts.11,12 Using one of the largest developmental datasets on a wild primate-the gelada (Theropithecus gelada)-we used 16S rRNA amplicon sequencing to characterize gut microbiota maturation during the first 3 years of life and assessed the role of maternal effects in shaping offspring microbiota assembly. In contrast to recent data on chimpanzees, postnatal microbial colonization in geladas was highly similar to humans:14 microbial alpha diversity increased rapidly following birth, followed by gradual changes in composition until weaning. Dietary changes associated with weaning (from milk- to plant-based diet) were the main drivers of shifts in taxonomic composition and microbial predicted functional pathways. Maternal effects were also an important factor influencing the offspring gut microbiota. During nursing (<12 months), offspring of experienced (multi-time) mothers exhibited faster functional microbial maturation, likely reflecting the general faster developmental pace of infants born to these mothers. Following weaning (>18 months), the composition of the juvenile microbiota tended to be more similar to the maternal microbiota than to the microbiota of other adult females, highlighting that maternal effects may persist even after nursing cessation.15,16 Together, our findings highlight the dynamic nature of early-life gut colonization and the role of maternal effects in shaping this trajectory in a wild primate.
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Affiliation(s)
- Alice Baniel
- Center for Evolution and Medicine, Arizona State University, E Tyler Mall, Tempe, AZ 85281, USA; School of Life Sciences, Arizona State University, E Tyler Mall, Tempe, AZ 85287, USA.
| | - Lauren Petrullo
- Department of Psychology, University of Michigan, Church St., Ann Arbor, MI 48109, USA
| | - Arianne Mercer
- Department of Psychology, University of Washington, Okanogan Ln., Seattle, WA 98195, USA
| | - Laurie Reitsema
- Department of Anthropology, University of Georgia, Jackson St., Athens, GA 30602, USA
| | - Sierra Sams
- Department of Psychology, University of Washington, Okanogan Ln., Seattle, WA 98195, USA
| | - Jacinta C Beehner
- Department of Psychology, University of Michigan, Church St., Ann Arbor, MI 48109, USA; Department of Anthropology, University of Michigan, S University Ave., Ann Arbor, MI 48109, USA
| | - Thore J Bergman
- Department of Psychology, University of Michigan, Church St., Ann Arbor, MI 48109, USA; Department of Ecology and Evolutionary Biology, University of Michigan, N University Ave., Ann Arbor, MI 48109, USA
| | - Noah Snyder-Mackler
- Center for Evolution and Medicine, Arizona State University, E Tyler Mall, Tempe, AZ 85281, USA; School of Life Sciences, Arizona State University, E Tyler Mall, Tempe, AZ 85287, USA; Department of Psychology, University of Washington, Okanogan Ln., Seattle, WA 98195, USA; School for Human Evolution and Social Change, Arizona State University, Cady Mall, Tempe, AZ 85287, USA.
| | - Amy Lu
- Department of Anthropology, Stony Brook University, Circle Rd., Stony Brook, NY 11794, USA.
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Caputi V, Bastiaanssen TFS, Peterson V, Sajjad J, Murphy A, Stanton C, McNamara B, Shorten GD, Cryan JF, O'Mahony SM. Sex, pain, and the microbiome: The relationship between baseline gut microbiota composition, gender and somatic pain in healthy individuals. Brain Behav Immun 2022; 104:191-204. [PMID: 35688340 DOI: 10.1016/j.bbi.2022.06.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 05/19/2022] [Accepted: 06/05/2022] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND AND AIM Relative to men, women present with pain conditions more commonly. Although consistent differences exist between men and women in terms of physiological pain sensitivity, the underlying mechanisms are incompletely understood and yet could inform the development of effective sex specific treatments for pain. The gut microbiota can modulate nervous system functioning, including pain signaling pathways. We hypothesized that the gut microbiota and critical components of the gut-brain axis might influence electrical pain thresholds. Further, we hypothesized that sex, menstrual cycle, and hormonal contraceptive use might account for inter-sex differences in pain perception. METHODS Healthy, non-obese males (N = 15) and females (N = 16), (nine of whom were using hormonal contraceptives), were recruited. Male subjects were invited to undergo testing once, whereas females were invited three times across the menstrual cycle, based on self-reported early follicular (EF), late follicular (LF), or mid-luteal (ML) phase. On test days, electrical stimulation on the right ankle was performed; salivary cortisol levels were measured in the morning; levels of lipopolysaccharide-binding protein (LBP), soluble CD14 (sCD14), pro-inflammatory cytokines were assessed in plasma, and microbiota composition and short-chain fatty acids (SCFAs) levels were determined in fecal samples. RESULTS We observed that the pain tolerance threshold/pain sensation threshold (PTT/PST) ratio was significantly lesser in women than men, but not PST or PTT alone. Further, hormonal contraceptive use was associated with increased LBP levels (LF & ML phase), whilst sCD14 levels or inflammatory cytokines were not affected. Interestingly, in women, hormonal contraceptive use was associated with an increase in the relative abundance of Erysipelatoclostridium, and the relative abundances of certain bacterial genera correlated positively with pain sensation thresholds (Prevotella and Megasphera) during the LF phase and cortisol awakening response (Anaerofustis) during the ML phase. In comparison with men, women displayed overall stronger associations between i) SCFAs data, ii) cortisol data, iii) inflammatory cytokines and PTT and PST. DISCUSSION AND CONCLUSION Our findings support the hypothesis that the gut microbiota may be one of the factors determining the physiological inter-sex differences in pain perception. Further research is needed to investigate the molecular mechanisms by which specific sex hormones and gut microbes modulate pain signaling pathways, but this study highlights the possibilities for innovative individual targeted therapies for pain management.
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Affiliation(s)
- Valentina Caputi
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
| | - Thomaz F S Bastiaanssen
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
| | | | - Jahangir Sajjad
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
| | - Amy Murphy
- Teagasc Food Research Centre, Moorepark, Co. Cork, Ireland
| | | | - Brian McNamara
- Department of Clinical Neurophysiology, Cork University Hospital, Co. Cork, Ireland
| | - George D Shorten
- Department of Anaesthesia and Intensive Care Medicine, University College Cork, Cork, Ireland
| | - John F Cryan
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
| | - Siobhain M O'Mahony
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.
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21
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González-Arancibia C, Collio V, Silva-Olivares F, Montaña-Collao P, Martínez-Pinto J, Julio-Pieper M, Sotomayor-Zárate R, Bravo JA. Early-Life Exposure to Non-Absorbable Broad-Spectrum Antibiotics Affects the Dopamine Mesocorticolimbic Pathway of Adult Rats in a Sex-Dependent Manner. Front Pharmacol 2022; 13:837652. [PMID: 35847016 PMCID: PMC9280042 DOI: 10.3389/fphar.2022.837652] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 06/02/2022] [Indexed: 11/13/2022] Open
Abstract
Gut microbiota with a stable, rich, and diverse composition is associated with adequate postnatal brain development. Colonization of the infant’s gut begins at birth when parturition exposes the newborn to a set of maternal bacteria, increasing richness and diversity until one to two first years of age when a microbiota composition is stable until old age. Conversely, alterations in gut microbiota by diet, stress, infection, and antibiotic exposure have been associated with several pathologies, including metabolic and neuropsychiatric diseases such as obesity, anxiety, depression, and drug addiction, among others. However, the consequences of early-life exposure to antibiotics (ELEA) on the dopamine (DA) mesocorticolimbic circuit are poorly studied. In this context, we administered oral non-absorbable broad-spectrum antibiotics to pregnant Sprague-Dawley dams during the perinatal period (from embryonic day 18 until postnatal day 7) and investigated their adult offspring (postnatal day 60) to assess methylphenidate-induced conditioned place preference (CPP) and locomotor activity, DA release, DA and 3,4-dihydroxyphenylacetic acid (DOPAC) content in ventral tegmental area (VTA), and expression of key proteins within the mesocorticolimbic system. Our results show that ELEA affect the rats conduct by increasing drug-seeking behavior and locomotor activity induced by methylphenidate of males and females, respectively, while reducing dopamine striatal release and VTA content of DOPAC in females. In addition, antibiotics increased protein levels of DA type 1 receptor in prefrontal cortex and VTA of female rats, and tyrosine hydroxylase in VTA of adult male and female rats. Altogether, these results suggest that ELEA alters the development of the microbiota-gut-brain axis affecting the reward system and the response to abuse drugs in adulthood.
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Affiliation(s)
- Camila González-Arancibia
- Laboratorio de Neuroquímica y Neurofarmacología, Centro de Neurobiología y Fisiopatología Integrativa (CENFI), Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile
- Grupo de NeuroGastroBioquímica, Instituto de Química, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile
- Programa de Doctorado en Ciencias Mención Neurociencias, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile
| | - Victoria Collio
- Laboratorio de Neuroquímica y Neurofarmacología, Centro de Neurobiología y Fisiopatología Integrativa (CENFI), Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile
- Programa de Doctorado en Ciencias Mención Neurociencias, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile
| | - Francisco Silva-Olivares
- Laboratorio de Neuroquímica y Neurofarmacología, Centro de Neurobiología y Fisiopatología Integrativa (CENFI), Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile
- Programa de Doctorado en Ciencias Mención Neurociencias, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile
| | - Paula Montaña-Collao
- Laboratorio de Neuroquímica y Neurofarmacología, Centro de Neurobiología y Fisiopatología Integrativa (CENFI), Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile
- Programa de Magíster en Ciencias Médicas, Mención Biología Celular y Molecular, Universidad de Valparaíso, Valparaíso, Chile
| | - Jonathan Martínez-Pinto
- Laboratorio de Neuroquímica y Neurofarmacología, Centro de Neurobiología y Fisiopatología Integrativa (CENFI), Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile
| | - Marcela Julio-Pieper
- Grupo de NeuroGastroBioquímica, Instituto de Química, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile
| | - Ramón Sotomayor-Zárate
- Laboratorio de Neuroquímica y Neurofarmacología, Centro de Neurobiología y Fisiopatología Integrativa (CENFI), Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile
- *Correspondence: Ramón Sotomayor-Zárate, ; Javier A. Bravo,
| | - Javier A. Bravo
- Grupo de NeuroGastroBioquímica, Instituto de Química, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile
- *Correspondence: Ramón Sotomayor-Zárate, ; Javier A. Bravo,
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22
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Shor EK, Brown SP, Freeman DA. Bacteria and Bellicosity: Photoperiodic Shifts in Gut Microbiota Drive Seasonal Aggressive Behavior in Male Siberian Hamsters. J Biol Rhythms 2022; 37:296-309. [PMID: 35502701 DOI: 10.1177/07487304221092105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
The existence of a microbiome-gut-brain axis has been established wherein gut microbiota significantly impacts host behavior and physiology, with increasing evidence suggesting a role for the gut microbiota in maintaining host homeostasis. Communication between the gut microbiota and the host is bidirectional, and shifts in the composition of the gut microbiota are dependent on both internal and external cues (host-derived signals, such as stress and immunity, and endocrine and environmental signals, such as photoperiod). Although there is host-driven seasonal variation in the composition of the microbiota, the mechanisms linking photoperiod, gut microbiota, and host behavior have not been characterized. The results of the present study suggest that seasonal changes in the gut microbiota drive seasonal changes in aggression. Implanting short-day Siberian hamsters (Phodopus sungorus) with fecal microbiota from long-day hamsters resulted in a reversal of seasonal aggression, whereby short-day hamsters displayed aggression levels typical of long-day hamsters. In addition, there are correlations between aggressive behavior and several bacterial taxa. These results implicate the gut microbiota as part of the photoperiodic mechanism regulating seasonal host behavior and contribute toward a more comprehensive understanding of the relationships between the microbiota, host, and environment.
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Affiliation(s)
- Elyan K Shor
- Department of Biological Sciences, Center for Biodiversity Research, The University of Memphis, Memphis, Tennessee, USA
| | - Shawn P Brown
- Department of Biological Sciences, Center for Biodiversity Research, The University of Memphis, Memphis, Tennessee, USA
| | - David A Freeman
- Department of Biological Sciences, Center for Biodiversity Research, The University of Memphis, Memphis, Tennessee, USA
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23
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Exploring the Gut Microbiome in Myasthenia Gravis. Nutrients 2022; 14:nu14081647. [PMID: 35458209 PMCID: PMC9027283 DOI: 10.3390/nu14081647] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 04/10/2022] [Accepted: 04/12/2022] [Indexed: 12/13/2022] Open
Abstract
The human gut microbiota is vital for maintaining human health in terms of immune system homeostasis. Perturbations in the composition and function of microbiota have been associated with several autoimmune disorders, including myasthenia gravis (MG), a neuromuscular condition associated with varying weakness and rapid fatigue of the skeletal muscles triggered by the host’s antibodies against the acetylcholine receptor (AChR) in the postsynaptic muscle membrane at the neuromuscular junction (NMJ). It is hypothesized that perturbation of the gut microbiota is associated with the pathogenesis of MG. The gut microbiota community profiles are usually generated using 16S rRNA gene sequencing. Compared to healthy individuals, MG participants had an altered gut microbiota’s relative abundance of bacterial taxa, particularly with a drop in Clostridium. The microbial diversity related to MG severity and the overall fecal short-chain fatty acids (SCFAs) were lower in MG subjects. Changes were also found in terms of serum biomarkers and fecal metabolites. A link was found between the bacterial Operational Taxonomic Unit (OTU), some metabolite biomarkers, and MG’s clinical symptoms. There were also variations in microbial and metabolic markers, which, in combination, could be used as an MG diagnostic tool, and interventions via fecal microbiota transplant (FMT) could affect MG development. Probiotics may influence MG by restoring the gut microbiome imbalance, aiding the prevention of MG, and lowering the risk of gut inflammation by normalizing serum biomarkers. Hence, this review will discuss how alterations of gut microbiome composition and function relate to MG and the benefits of gut modulation.
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24
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Linehan K, Dempsey EM, Ryan CA, Ross RP, Stanton C. First encounters of the microbial kind: perinatal factors direct infant gut microbiome establishment. MICROBIOME RESEARCH REPORTS 2022; 1:10. [PMID: 38045649 PMCID: PMC10688792 DOI: 10.20517/mrr.2021.09] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 12/28/2021] [Accepted: 01/11/2022] [Indexed: 12/05/2023]
Abstract
The human gut microbiome harbors a diverse range of microbes that play a fundamental role in the health and well-being of their host. The early-life microbiome has a major influence on human development and long-term health. Perinatal factors such as maternal nutrition, antibiotic use, gestational age and mode of delivery influence the initial colonization, development, and function of the neonatal gut microbiome. The perturbed early-life gut microbiome predisposes infants to diseases in early and later life. Understanding how perinatal factors guide and shape the composition of the early-life microbiome is essential to improving infant health. The following review provides a synopsis of perinatal factors with the most decisive influences on initial microbial colonization of the infant gut.
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Affiliation(s)
- Kevin Linehan
- Teagasc Food Research Centre, Moorepark, Fermoy, Co. Cork P61 C996, Ireland
- APC Microbiome Ireland, Biosciences Institute, University College Cork, Lee Maltings, Cork, Cork T12 YT20, Ireland
- School of Microbiology, University College Cork, Cork T12 YN60, Ireland
| | - Eugene M. Dempsey
- APC Microbiome Ireland, Biosciences Institute, University College Cork, Lee Maltings, Cork, Cork T12 YT20, Ireland
- Department of Paediatrics & Child Health and INFANT Centre, University College Cork, Cork T12 YN60, Ireland
| | - C. Anthony Ryan
- APC Microbiome Ireland, Biosciences Institute, University College Cork, Lee Maltings, Cork, Cork T12 YT20, Ireland
- Department of Paediatrics & Child Health and INFANT Centre, University College Cork, Cork T12 YN60, Ireland
| | - R. Paul Ross
- APC Microbiome Ireland, Biosciences Institute, University College Cork, Lee Maltings, Cork, Cork T12 YT20, Ireland
- School of Microbiology, University College Cork, Cork T12 YN60, Ireland
| | - Catherine Stanton
- Teagasc Food Research Centre, Moorepark, Fermoy, Co. Cork P61 C996, Ireland
- APC Microbiome Ireland, Biosciences Institute, University College Cork, Lee Maltings, Cork, Cork T12 YT20, Ireland
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25
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Egerton S, Donoso F, Fitzgerald P, Gite S, Fouhy F, Whooley J, Dinan TG, Cryan JF, Culloty SC, Ross RP, Stanton C. Investigating the potential of fish oil as a nutraceutical in an animal model of early life stress. Nutr Neurosci 2022; 25:356-378. [PMID: 32734823 DOI: 10.1080/1028415x.2020.1753322] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Background: Early life stress is a key predisposing factor for depression and anxiety disorders. Selective serotonin re-uptake inhibitors (SSRI) are frequently used as the first line of pharmacology treatment for depression but have several negative qualities, i.e. a delay or absence of effectiveness and negative side-effects. Therefore, there is a growing need for new nutraceutical-based strategies to blunt the effects of adverse-life events.Objectives: This study aimed to use the maternal separation model in rats to test the efficacy of fish oil dietary supplementation, on its own and in conjunction with the SSRI anti-depressant fluoxetine, as a treatment for depressive and anxiety-like symptoms associated with early life stress.Methods: Behavioural tests (open field test, elevated plus maze test and forced swim test) and biochemical markers (corticosterone, BDNF, brain fatty acids and short chain fatty acids) were used to analyse the effects of the dietary treatments. Gut microbial communities and relating metabolites (SCFA) were analysed to investigate possible changes in the microbiota-gut-brain axis.Results: Maternally separated rats showed depressive-like behaviours in the forced swim and open field tests. These behaviours were prevented significantly by fluoxetine administration and in part by fish oil supplementation. Associated biochemical changes reported include altered brain fatty acids, significantly lower plasma corticosterone levels (AUC) and reduced brain stem serotonin turnover, compared to untreated, maternally separated (MS) rats. Untreated MS animals had significantly lower ratios of SCFA producers such as Caldicoprobacteraceae, Streptococcaceae, Rothia, Lachnospiraceae_NC2004_group, and Ruminococcus_2, along with significantly reduced levels of total SCFA compared to non-separated animals. Compared to untreated MS animals, animals fed fish oil had significantly higher Bacteroidetes and Prevotellaceae and reduced levels of butyrate, while fluoxetine treatment resulted in significantly higher levels of Neochlamydia, Lachnoclostridium, Acetitomaculum and Stenotrophomonas and, acetate and propionate.Conclusion: Despite the limitations in extrapolating from animal behavioural data and the notable differences in pharmacokinetics between rodents and humans, the results of this study provide a further advancement into the understanding of some of the complex systems within which nutraceuticals and pharmaceuticals effect the microbiota-gut-brain axis.
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Affiliation(s)
- Sian Egerton
- School of Microbiology, University College Cork, Cork, Ireland
- School of Biological, Earth and Environmental Sciences, University College Cork, Cork, Ireland
- APC Microbiome Ireland, Cork, Ireland
| | - Francisco Donoso
- APC Microbiome Ireland, Cork, Ireland
- Department of Psychiatry and Neurobehavioral Science, University College Cork, Cork, Ireland
| | | | - Snehal Gite
- APC Microbiome Ireland, Cork, Ireland
- Biomarine Ingredients Ireland Ltd., Monaghan, Ireland
| | - Fiona Fouhy
- APC Microbiome Ireland, Cork, Ireland
- Teagasc Food Research Centre, Moorepark, Fermoy, County Cork, Ireland
| | - Jason Whooley
- Biomarine Ingredients Ireland Ltd., Monaghan, Ireland
| | - Ted G Dinan
- APC Microbiome Ireland, Cork, Ireland
- Department of Psychiatry and Neurobehavioral Science, University College Cork, Cork, Ireland
| | - John F Cryan
- APC Microbiome Ireland, Cork, Ireland
- Department of Anatomy & Neuroscience, University College Cork, Cork, Ireland
| | - Sarah C Culloty
- School of Biological, Earth and Environmental Sciences, University College Cork, Cork, Ireland
- Environmental Research Institute, University College Cork, Cork, Ireland
| | - R Paul Ross
- School of Microbiology, University College Cork, Cork, Ireland
- APC Microbiome Ireland, Cork, Ireland
| | - Catherine Stanton
- APC Microbiome Ireland, Cork, Ireland
- Department of Psychiatry and Neurobehavioral Science, University College Cork, Cork, Ireland
- Teagasc Food Research Centre, Moorepark, Fermoy, County Cork, Ireland
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Uniyal A, Tiwari V, Rani M, Tiwari V. Immune-microbiome interplay and its implications in neurodegenerative disorders. Metab Brain Dis 2022; 37:17-37. [PMID: 34357554 DOI: 10.1007/s11011-021-00807-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Accepted: 07/22/2021] [Indexed: 12/28/2022]
Abstract
The neurodegeneration and its related CNS pathologies need an urgent toolbox to minimize the global mental health burden. The neuroimmune system critically regulates the brain maturation and survival of neurons across the nervous system. The chronic manipulated immunological drive can accelerate the neuronal pathology hence promoting the burden of neurodegenerative disorders. The gut is home for trillions of microorganisms having a mutual relationship with the host system. The gut-brain axis is a unique biochemical pathway through which the gut residing microbes connects with the brain cells and regulates various physiological and pathological cascades. The gut microbiota and CNS communicate using a common language that synchronizes the tuning of immune cells. The intestinal gut microbial community has a profound role in the maturation of the immune system as well as the development of the nervous system. We have critically summarised the clinical and preclinical reports from the past a decade emphasising that the significant changes in gut microbiota can enhance the host susceptibility towards neurodegenerative disorders. In this review, we have discussed how the gut microbiota-mediated immune response inclines the host physiology towards neurodegeneration and indicated the gut microbiota as a potential future candidate for the management of neurodegenerative disorders.
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Affiliation(s)
- Ankit Uniyal
- Department of Pharmaceutical Engineering and Technology, Neuroscience and Pain Research Laboratory, Indian Institute of Technology (BHU), Varanasi, Uttar Pradesh, 221005, India
| | - Vineeta Tiwari
- Department of Pharmaceutical Engineering and Technology, Neuroscience and Pain Research Laboratory, Indian Institute of Technology (BHU), Varanasi, Uttar Pradesh, 221005, India
| | - Mousmi Rani
- Department of Pharmaceutical Engineering and Technology, Neuroscience and Pain Research Laboratory, Indian Institute of Technology (BHU), Varanasi, Uttar Pradesh, 221005, India
| | - Vinod Tiwari
- Department of Pharmaceutical Engineering and Technology, Neuroscience and Pain Research Laboratory, Indian Institute of Technology (BHU), Varanasi, Uttar Pradesh, 221005, India.
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Mikrobiota jelitowa a leki. Interakcje wpływające na skuteczność i bezpieczeństwo farmakoterapii. POSTEP HIG MED DOSW 2021. [DOI: 10.2478/ahem-2021-0009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Abstrakt
Mikrobiota jelitowa stanowi nieodłączny element organizmu umożliwiający jego prawidłowe funkcjonowanie. Dzięki mikroorganizmom jelitowym możliwa jest stymulacja układu odpornościowego, synteza witamin czy poprawa wchłaniania składników odżywczych. Jednak jej aktywność może również niekorzystnie działać na organizm, m.in. z powodu przetwarzania treści jelitowej. Opisywana w artykule interakcja mikrobiota–lek uwzględnia pozytywny i negatywny wpływ mikroorganizmów jelitowych na farmakoterapię poprzez bezpośrednie i pośrednie oddziaływanie na lek w organizmie. Ze względu na to, że mikrobiom stanowi nieodłączny element organizmu, ingerencja nawet w jego niewielką część może doprowadzić do wystąpienia daleko idących, czasami niespodziewanych skutków. Stąd w celu poprawy skuteczności i bezpieczeństwa farmakoterapii konieczne jest wyjaśnienie mechanizmów oddziaływania mikrobioty na lek w organizmie.
W artykule podsumowano obecną wiedzę na temat biologicznej aktywności mikrobioty jelitowej, a zwłaszcza oddziaływań mikrobiota–leki determinujących skuteczność i bezpieczeństwo farmakoterapii. Wyszukiwanie przeprowadzono we wrześniu 2020 r. w bazach danych PubMed, Scopus, Web of Science, Cochrane Library i powszechnie dostępnej literaturze z użyciem terminów: „mikrobiota jelitowa”, „mikrobiom”, „metabolizm leku”, „interakcje mikrobiota–lek”. W artykule omówiono interakcje między mikrobiotą a lekami m.in. z grupy antybiotyków, inhibitorów pompy protonowej, sulfonamidów, pochodnych kwasu 5-aminosalicylowego, niesteroidowych leków przeciwzapalnych, przeciwnowotworowych, statyn czy metforminą.
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28
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Mathis SP, Bodduluri SR, Haribabu B. Interrelationship between the 5-lipoxygenase pathway and microbial dysbiosis in the progression of Alzheimer's disease. Biochim Biophys Acta Mol Cell Biol Lipids 2021; 1866:158982. [PMID: 34062254 PMCID: PMC11522975 DOI: 10.1016/j.bbalip.2021.158982] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 05/11/2021] [Accepted: 05/17/2021] [Indexed: 02/08/2023]
Abstract
Alzheimer's disease (AD) is an age-related neurodegenerative disorder involving neurofibrillary tangles and amyloid plaques. The tau phosphorylation responsible for neurofibrillary tangles and amyloid deposition which causes plaques are both accelerated through the activity of 5-lipoxygenase (5-LO). In addition to these pathological pathways, 5-LO has also been linked to the neuro-inflammation associated with disease progression as well as to dysbiosis in the gut. Interestingly, gut dysbiosis itself has been correlated to AD development. Not only do gut metabolites have direct effects on the brain, but pro-inflammatory mediators such as LPS, BMAA and bacterial amyloids produced in the gut due to dysbiosis reach the brain causing increased neuro-inflammation. While microbial dysbiosis and 5-LO exert detrimental effects in the brain, the cause/effect relationship between these factors remain unknown. These issues may be addressed using mouse models of AD in the context of different knockout mice in the 5-LO pathway in specific pathogen-free, germ-free as well as gnotobiotic conditions.
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Affiliation(s)
- Steven P Mathis
- Department of Microbiology and Immunology, James Graham Brown Cancer Center and Center for Microbiomics, Inflammation and Pathogenicity, Louisville, KY 40202, United States of America; University of Louisville Health Sciences Center, Louisville, KY 40202, United States of America
| | - Sobha R Bodduluri
- Department of Microbiology and Immunology, James Graham Brown Cancer Center and Center for Microbiomics, Inflammation and Pathogenicity, Louisville, KY 40202, United States of America; University of Louisville Health Sciences Center, Louisville, KY 40202, United States of America
| | - Bodduluri Haribabu
- Department of Microbiology and Immunology, James Graham Brown Cancer Center and Center for Microbiomics, Inflammation and Pathogenicity, Louisville, KY 40202, United States of America; University of Louisville Health Sciences Center, Louisville, KY 40202, United States of America.
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29
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Brenner D, Shorten GD, O'Mahony SM. Postoperative pain and the gut microbiome. NEUROBIOLOGY OF PAIN 2021; 10:100070. [PMID: 34409198 PMCID: PMC8361255 DOI: 10.1016/j.ynpai.2021.100070] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 06/24/2021] [Accepted: 07/26/2021] [Indexed: 12/12/2022]
Abstract
Poorly controlled postoperative pain remains a major unresolved challenge globally. The gut microbiome impacts on inflammatory pain and neuropathic pain. Microbiota metabolites can regulate peripheral and central sensitisation. Stress is linked to both postoperative pain and an altered gut microbiome. In excess of 300 million surgical procedures are undertaken worldwide each year. Despite recognition of the prevalence of postoperative pain, and improvements in pain management techniques, poorly controlled postoperative pain remains a major unresolved challenge globally. An estimated 71% and 51% of patients experience moderate to severe pain after surgery in in-patient and outpatient settings, respectively. Inadequately controlled pain after surgery is associated with significant perioperative morbidity including myocardial infarction and pulmonary complications. As many as 20–56% of patients develop chronic pain after commonly performed procedures such as hernia repair, hysterectomy, and thoracotomy. Traditional analgesics and interventions are often ineffective or partially effective in the treatment of postoperative pain, resulting in a chronic pain condition with related socio-economic impacts and reduced quality of life for the patient. Such chronic pain which occurs after surgery is referred to as Persistent Post-Surgical Pain (PPSP). The complex ecosystem that is the gastrointestinal microbiota (including bacteria, fungi, viruses, phage) plays essential roles in the maintenance of the healthy state of the host. A disruption to the balance of this microbiome has been implicated not only in gastrointestinal disease but also neurological disorders including chronic pain. The influence of the gut microbiome is well documented in the context of visceral pain from the gastrointestinal tract while a greater understanding is emerging of the impact on inflammatory pain and neuropathic pain (both of which can occur during the perioperative period). The gut microbiome is an essential source for driving immune maturation and maintaining appropriate immune response. Given that inflammatory processes have been implicated in postoperative pain, aberrant microbiome profiles may play a role in the development of this type of pain. Furthermore, the microorganisms in our gut produce metabolites, neurotransmitters, and neuromodulators which interact with their receptors to regulate peripheral and central sensitisation associated with chronic pain. Microbiota-derived mediators can also regulate neuroinflammation, which is associated with activation of microglia as well as infiltration by immune cells, known to modulate the development and maintenance of central sensitisation. Moreover, risk factors for developing postoperative pain include anxiety, depression, and increased stress response. These central nervous system-related disorders have been associated with an altered gut microbiome and microbiome targeted intervention studies indicate improvements. Females are more likely to suffer from postoperative pain. As gonadal hormones are associated with a differential microbiome and pre-clinical studies show that male microbiome confers protection from inflammatory pain, it is possible that the composition of the microbiome and its by-products contribute to the increased risk for the development of postoperative pain. Very little evidence exists relating the microbiome to somatic pain. Here we discuss the potential role of the gut microbiome in the aetiology and pathophysiology of postoperative pain in the context of other somatic pain syndromes and what is known about microbe-neuron interactions. Investigations are needed to determine the specific role of the gut microbiome in this type of pain which may help inform the development of preventative interventions as well as management strategies to improve patient outcome.
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Affiliation(s)
- David Brenner
- Department of Anesthesia and Intensive Care Medicine, Cork University Hospital and University College Cork, Ireland
| | - George D Shorten
- Department of Anesthesia and Intensive Care Medicine, Cork University Hospital and University College Cork, Ireland
| | - Siobhain M O'Mahony
- APC Microbiome Ireland, University College Cork, Cork, Ireland.,Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
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Multi-Omics Analysis on Neurodevelopment in Preterm Neonates: A Protocol Paper. Nurs Res 2021; 70:462-468. [PMID: 34380978 DOI: 10.1097/nnr.0000000000000548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND The gut microbiome is an important determinant of health and disease in preterm infants. OBJECTIVES The objective of this paper is to share our current protocol for other neonatal intensive care units to potentially expand their existing protocols aiming to characterize the relationship between the intestinal microbiome and health outcomes in preterm infants. METHODS This prospective, longitudinal study planned to recruit 160 preterm infants born <32 weeks' gestational age or weighing <1,500 grams and admitted to one of two-level III/IV neonatal intensive care units. During the neonatal intensive care unit period, the primary measures included events of early life pain/stress, gut microbiome, host genetic variations, and neurobehavioral assessment. During follow-up visits, gut microbiome, pain sensitivity, and medical, growth, and developmental outcomes at 4-, 8-12-, and 18-24-month corrected age (CA) were measured. DISCUSSION As of February 14, 2020, 214 preterm infants have been recruited. We hypothesize that infants who experience greater levels of pain/stress will have altered gut microbiome, including potential adverse outcomes such as necrotizing enterocolitis (NEC) and host genetic variations, feeding intolerance, and/or neurodevelopmental impairments. These will differ from the intestinal microbiome of preterm infants that do not develop these adverse outcomes. To test this hypothesis, we will determine how alterations in the intestinal microbiome affect the risk of developing NEC, feeding intolerance, and neurodevelopmental impairments in preterm infants. In addition, we will examine the interaction between the intestinal microbiome and host genetics in the regulation of intestinal health and neurodevelopmental outcomes.
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31
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Mitochondria and Antibiotics: For Good or for Evil? Biomolecules 2021; 11:biom11071050. [PMID: 34356674 PMCID: PMC8301944 DOI: 10.3390/biom11071050] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Revised: 07/12/2021] [Accepted: 07/15/2021] [Indexed: 01/16/2023] Open
Abstract
The discovery and application of antibiotics in the common clinical practice has undeniably been one of the major medical advances in our times. Their use meant a drastic drop in infectious diseases-related mortality and contributed to prolonging human life expectancy worldwide. Nevertheless, antibiotics are considered by many a double-edged sword. Their extensive use in the past few years has given rise to a global problem: antibiotic resistance. This factor and the increasing evidence that a wide range of antibiotics can damage mammalian mitochondria, have driven a significant sector of the medical and scientific communities to advise against the use of antibiotics for purposes other to treating severe infections. Notwithstanding, a notorious number of recent studies support the use of these drugs to treat very diverse conditions, ranging from cancer to neurodegenerative or mitochondrial diseases. In this context, there is great controversy on whether the risks associated to antibiotics outweigh their promising beneficial features. The aim of this review is to provide insight in the topic, purpose for which the most relevant findings regarding antibiotic therapies have been discussed.
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32
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Niederle B. [Hygiene measures in antenatal care]. DER GYNAKOLOGE 2021; 54:399-411. [PMID: 33976454 PMCID: PMC8103136 DOI: 10.1007/s00129-021-04794-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Accepted: 03/24/2021] [Indexed: 10/26/2022]
Abstract
BACKGROUND The prevention of infections in the obstetric care of pregnant women is paramount, on the one hand with regard to pathogens of congenital infections and on the other hand due to the association of maternal infections with premature delivery. OBJECTIVES Which measures are recommended for effective prevention of bacterial and viral diseases relevant to obstetrics? MATERIALS AND METHODS Literature search on hygiene measures in terms of preventing transmission of infection. RESULTS The physiological vaginal flora of the pregnant woman is a fundamental factor in natural defence against infection. Its disruption-also through antimicrobial therapies-has a proven influence on the course of pregnancy (premature rupture of membranes, premature birth). It also leads to a disturbed intestinal microbiome in newborns, which has long-term consequences for their neurological, respiratory, metabolic and immunological development and increases mortality. The focus should therefore be on prevention-rather than therapy-of infectious diseases during pregnancy. This requires a detailed anamnesis, monitoring and updating of the vaccination status and, if necessary, clarification of the infection status by means of targeted serological tests. Then the gynecologist can give individual advice on preventive measures. This article provides specific recommendations on selected obstetrically relevant infections. CONCLUSIONS Focusing on hygiene measures to prevent infection in obstetrics can improve the health of both mother and child.
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Affiliation(s)
- Bernhard Niederle
- Klinik für Frauenheilkunde und Geburtshilfe, Klinikum Kempten und Immenstadt, Klinikverbund Allgäu, Robert-Weixler-Str. 50, 87439 Kempten, Deutschland
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33
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Ortega VA, Mercer EM, Giesbrecht GF, Arrieta MC. Evolutionary Significance of the Neuroendocrine Stress Axis on Vertebrate Immunity and the Influence of the Microbiome on Early-Life Stress Regulation and Health Outcomes. Front Microbiol 2021; 12:634539. [PMID: 33897639 PMCID: PMC8058197 DOI: 10.3389/fmicb.2021.634539] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2020] [Accepted: 03/15/2021] [Indexed: 12/12/2022] Open
Abstract
Stress is broadly defined as the non-specific biological response to changes in homeostatic demands and is mediated by the evolutionarily conserved neuroendocrine networks of the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic nervous system. Activation of these networks results in transient release of glucocorticoids (cortisol) and catecholamines (epinephrine) into circulation, as well as activation of sympathetic fibers innervating end organs. These interventions thus regulate numerous physiological processes, including energy metabolism, cardiovascular physiology, and immunity, thereby adapting to cope with the perceived stressors. The developmental trajectory of the stress-axis is influenced by a number of factors, including the gut microbiome, which is the community of microbes that colonizes the gastrointestinal tract immediately following birth. The gut microbiome communicates with the brain through the production of metabolites and microbially derived signals, which are essential to human stress response network development. Ecological perturbations to the gut microbiome during early life may result in the alteration of signals implicated in developmental programming during this critical window, predisposing individuals to numerous diseases later in life. The vulnerability of stress response networks to maladaptive development has been exemplified through animal models determining a causal role for gut microbial ecosystems in HPA axis activity, stress reactivity, and brain development. In this review, we explore the evolutionary significance of the stress-axis system for health maintenance and review recent findings that connect early-life microbiome disturbances to alterations in the development of stress response networks.
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Affiliation(s)
- Van A Ortega
- Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada.,International Microbiome Centre, Cumming School of Medicine, Health Sciences Centre, University of Calgary, Calgary, AB, Canada
| | - Emily M Mercer
- Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada.,International Microbiome Centre, Cumming School of Medicine, Health Sciences Centre, University of Calgary, Calgary, AB, Canada.,Department of Pediatrics, University of Calgary, Calgary, AB, Canada
| | - Gerald F Giesbrecht
- Department of Pediatrics, University of Calgary, Calgary, AB, Canada.,Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada.,Owerko Centre, The Alberta Children's Hospital Research Institute, Calgary, AB, Canada
| | - Marie-Claire Arrieta
- Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada.,International Microbiome Centre, Cumming School of Medicine, Health Sciences Centre, University of Calgary, Calgary, AB, Canada.,Department of Pediatrics, University of Calgary, Calgary, AB, Canada
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Saturio S, Nogacka AM, Suárez M, Fernández N, Mantecón L, Mancabelli L, Milani C, Ventura M, de los Reyes-Gavilán CG, Solís G, Arboleya S, Gueimonde M. Early-Life Development of the Bifidobacterial Community in the Infant Gut. Int J Mol Sci 2021; 22:ijms22073382. [PMID: 33806135 PMCID: PMC8036440 DOI: 10.3390/ijms22073382] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 03/19/2021] [Accepted: 03/22/2021] [Indexed: 12/30/2022] Open
Abstract
The establishment of the gut microbiota poses implications for short and long-term health. Bifidobacterium is an important taxon in early life, being one of the most abundant genera in the infant intestinal microbiota and carrying out key functions for maintaining host-homeostasis. Recent metagenomic studies have shown that different factors, such as gestational age, delivery mode, or feeding habits, affect the gut microbiota establishment at high phylogenetic levels. However, their impact on the specific bifidobacterial populations is not yet well understood. Here we studied the impact of these factors on the different Bifidobacterium species and subspecies at both the quantitative and qualitative levels. Fecal samples were taken from 85 neonates at 2, 10, 30, 90 days of life, and the relative proportions of the different bifidobacterial populations were assessed by 16S rRNA–23S rRNA internal transcribed spacer (ITS) region sequencing. Absolute levels of the main species were determined by q-PCR. Our results showed that the bifidobacterial population establishment is affected by gestational age, delivery mode, and infant feeding, as it is evidenced by qualitative and quantitative changes. These data underline the need for understanding the impact of perinatal factors on the gut microbiota also at low taxonomic levels, especially in the case of relevant microbial populations such as Bifidobacterium. The data obtained provide indications for the selection of the species best suited for the development of bifidobacteria-based products for different groups of neonates and will help to develop rational strategies for favoring a healthy early microbiota development when this process is challenged.
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Affiliation(s)
- Silvia Saturio
- Department of Microbiology and Biochemistry of Dairy Products, IPLA-CSIC, 33300 Villaviciosa, Spain; (S.S.); (A.M.N.); (C.G.d.l.R.-G.)
- Diet, Microbiota and Health Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain;
| | - Alicja M. Nogacka
- Department of Microbiology and Biochemistry of Dairy Products, IPLA-CSIC, 33300 Villaviciosa, Spain; (S.S.); (A.M.N.); (C.G.d.l.R.-G.)
- Diet, Microbiota and Health Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain;
| | - Marta Suárez
- Pediatrics Service, Hospital Universitario Central de Asturias, SESPA, 33011 Oviedo, Spain; (M.S.); (L.M.); (G.S.)
- Pediatrics Research Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain
| | - Nuria Fernández
- Diet, Microbiota and Health Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain;
- Pediatrics Service, Hospital de Cabueñes, SESPA, 33203 Gijón, Spain
| | - Laura Mantecón
- Pediatrics Service, Hospital Universitario Central de Asturias, SESPA, 33011 Oviedo, Spain; (M.S.); (L.M.); (G.S.)
- Pediatrics Research Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain
| | - Leonardo Mancabelli
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, 43121 Parma, Italy; (L.M.); (C.M.); (M.V.)
| | - Christian Milani
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, 43121 Parma, Italy; (L.M.); (C.M.); (M.V.)
| | - Marco Ventura
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, 43121 Parma, Italy; (L.M.); (C.M.); (M.V.)
| | - Clara G. de los Reyes-Gavilán
- Department of Microbiology and Biochemistry of Dairy Products, IPLA-CSIC, 33300 Villaviciosa, Spain; (S.S.); (A.M.N.); (C.G.d.l.R.-G.)
- Diet, Microbiota and Health Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain;
| | - Gonzalo Solís
- Pediatrics Service, Hospital Universitario Central de Asturias, SESPA, 33011 Oviedo, Spain; (M.S.); (L.M.); (G.S.)
- Pediatrics Research Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain
| | - Silvia Arboleya
- Department of Microbiology and Biochemistry of Dairy Products, IPLA-CSIC, 33300 Villaviciosa, Spain; (S.S.); (A.M.N.); (C.G.d.l.R.-G.)
- Diet, Microbiota and Health Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain;
- Correspondence: (S.A.); (M.G.); Tel.: +34-985-892-131 (S.A. & M.G.)
| | - Miguel Gueimonde
- Department of Microbiology and Biochemistry of Dairy Products, IPLA-CSIC, 33300 Villaviciosa, Spain; (S.S.); (A.M.N.); (C.G.d.l.R.-G.)
- Diet, Microbiota and Health Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain;
- Correspondence: (S.A.); (M.G.); Tel.: +34-985-892-131 (S.A. & M.G.)
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Integrative Review of Gut Microbiota and Expression of Symptoms Associated With Neonatal Abstinence Syndrome. Nurs Res 2021; 69:S66-S78. [PMID: 32555010 DOI: 10.1097/nnr.0000000000000452] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022]
Abstract
BACKGROUND Neonatal exposure and subsequent withdrawal from maternal substance use disorder are a growing problem and consequence of the current opioid epidemic. Neonatal abstinence syndrome (NAS) is defined by a specified cluster of symptoms with treatment guided by the expression and severity of these symptoms. The mechanisms or pathophysiology contributing to the development of NAS symptoms are not well known, but one factor that may influence NAS symptoms is the gut microbiota. OBJECTIVES The purpose of this integrative review was to examine evidence that might show if and how the gut microbiota influence expression and severity of symptoms similar to those seen in NAS. METHODS Using published guidelines, a review of research studies that focused on the gut microbiome and symptoms similar to those seen in NAS was conducted, using the Cochrane, EMBASE, and Scopus databases, from 2009 through 2019. RESULTS The review results included findings of aberrant microbial diversity, differences in microbial communities between study groups, and associations between specific taxa and symptoms. In studies involving interventions, there were reports of improved microbial diversity, community structure, and symptoms. DISCUSSION The review findings provide evidence that the gut microbiota may play a role in modifying variability in the expression and severity of symptoms associated with NAS. Future research should focus on examining the gut microbiota in infants with and without the syndrome as well as exploring the relationship between symptom expression and aberrant gut microbiota colonization in infants with NAS.
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Rahman Z, Dandekar MP. Crosstalk between gut microbiome and immunology in the management of ischemic brain injury. J Neuroimmunol 2021; 353:577498. [PMID: 33607506 DOI: 10.1016/j.jneuroim.2021.577498] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 12/30/2020] [Accepted: 01/21/2021] [Indexed: 02/06/2023]
Abstract
Ischemic brain injury is a serious neurological complication, which accrues an immense activation of neuroinflammatory responses. Several lines of research suggested the interconnection of gut microbiota perturbation with the activation of proinflammatory mediators. Intestinal microbial communities also interchange information with the brain through various afferent and efferent channels and microbial by-products. Herein, we discuss the different microelements of gut microbiota and its connection with the host immune system and how change in immune-microbial signatures correlates with the stroke incidence and post-injury neurological sequelae. The activated inflammatory cells increase the production of proinflammatory cytokines, chemokines, proteases and adhesive proteins that are involved in the systemic inflammation, blood brain barrier disruption, gut dysbiosis and aggravation of ischemic brain injury. We suggest that fine-tuning of commensal gut microbiota (eubiosis) may regulate the activation of CNS resident cells like microglial, astrocytes, mast cells and natural killer cells.
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Affiliation(s)
- Ziaur Rahman
- Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India
| | - Manoj P Dandekar
- Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India.
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Sohrabi M, Pecoraro HL, Combs CK. Gut Inflammation Induced by Dextran Sulfate Sodium Exacerbates Amyloid-β Plaque Deposition in the AppNL-G-F Mouse Model of Alzheimer's Disease. J Alzheimers Dis 2021; 79:1235-1255. [PMID: 33427741 PMCID: PMC8122495 DOI: 10.3233/jad-201099] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Although it is known that the brain communicates with the gastrointestinal (GI) tract via the well-established gut-brain axis, the influence exerted by chronic intestinal inflammation on brain changes in Alzheimer's disease (AD) is not fully understood. We hypothesized that increased gut inflammation would alter brain pathology of a mouse model of AD. OBJECTIVE Determine whether colitis exacerbates AD-related brain changes. METHODS To test this idea, 2% dextran sulfate sodium (DSS) was dissolved in the drinking water and fed ad libitum to male C57BL/6 wild type and AppNL-G-F mice at 6-10 months of age for two cycles of three days each. DSS is a negatively charged sulfated polysaccharide which results in bloody diarrhea and weight loss, changes similar to human inflammatory bowel disease (IBD). RESULTS Both wild type and AppNL-G-F mice developed an IBD-like condition. Brain histologic and biochemical assessments demonstrated increased insoluble Aβ1-40/42 levels along with the decreased microglial CD68 immunoreactivity in DSS treated AppNL-G-F mice compared to vehicle treated AppNL-G-F mice. CONCLUSION These data demonstrate that intestinal dysfunction is capable of altering plaque deposition and glial immunoreactivity in the brain. This study increases our knowledge of the impact of peripheral inflammation on Aβ deposition via an IBD-like model system.
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Affiliation(s)
- Mona Sohrabi
- Department of Biomedical Sciences, University of North Dakota School of Medicine & Health Sciences, Grand Forks, ND
| | - Heidi L. Pecoraro
- Veterinary Diagnostic Laboratory, North Dakota State University, Fargo ND
| | - Colin K. Combs
- Department of Biomedical Sciences, University of North Dakota School of Medicine & Health Sciences, Grand Forks, ND
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Luang-In V, Katisart T, Konsue A, Nudmamud-Thanoi S, Narbad A, Saengha W, Wangkahart E, Pumriw S, Samappito W, Ma NL. Psychobiotic Effects of Multi-Strain Probiotics Originated from Thai Fermented Foods in a Rat Model. Food Sci Anim Resour 2020; 40:1014-1032. [PMID: 33305285 PMCID: PMC7713776 DOI: 10.5851/kosfa.2020.e72] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 08/20/2020] [Accepted: 08/20/2020] [Indexed: 12/14/2022] Open
Abstract
This work aimed to investigate the psychobiotic effects of six bacterial strains on the mind and behavior of male Wistar rats. The probiotic (PRO) group (n=7) were rats pre-treated with antibiotics for 7 days followed by 14-day probiotic administration, antibiotics (ANT) group (n=7) were rats treated with antibiotics for 21 days without probiotics. The control (CON) group (n=7) were rats that received sham treatment for 21 days. The six bacterial strains with probiotic properties were mostly isolated from Thai fermented foods; Pedicoccus pentosaceus WS11, Lactobacillus plantarum SK321, L. fermentum SK324, L. brevis TRBC 3003, Bifidobacterium adolescentis TBRC 7154 and Lactococcus lactis subsp. lactis TBRC 375. The probiotics were freeze-dried into powder (6×109 CFU/5 g) and administered to the PRO group via oral gavage. Behavioral tests were performed. The PRO group displayed significantly reduced anxiety level and increased locomotor function using a marble burying test and open field test, respectively and significantly improved short-term memory performance using a novel object recognition test. Antibiotics significantly reduced microbial counts in rat feces in the ANT group by 100 fold compared to the PRO group. Probiotics significantly enhanced antioxidant enzymatic and non-enzymatic defenses in rat brains as assessed using catalase activity and ferric reducing antioxidant power assay, respectively. Probiotics also showed neuroprotective effects with less pyknotic cells and lower frequency of vacuolization in cerebral cortex. This multi-strain probiotic formulation from Thai fermented foods may offer a potential to develop psychobiotic-rich functional foods to modulate human mind and behaviors.
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Affiliation(s)
- Vijitra Luang-In
- Natural Antioxidant Innovation Research
Unit, Department of Biotechnology, Faculty of Technology, Mahasarakham
University, Khamriang, Kantarawichai, Maha Sarakham
44150, Thailand
| | - Teeraporn Katisart
- Department of Biology, Faculty of Science,
Mahasarakham University, Maha Sarakham 44150,
Thailand
| | - Ampa Konsue
- Applied Thai Traditional Medicine, Thai
Traditional Medicine Research Unit, Faculty of Medicine, Mahasarakham
University, Maha Sarakham 44000,
Thailand
| | - Sutisa Nudmamud-Thanoi
- Centre of Excellence in Medical
Biotechnology, Department of Anatomy, Faculty of Medical Science, Naresuan
University, Phitsanulok 65000,
Thailand
| | - Arjan Narbad
- Quadram Institute Bioscience, Norwich
Research Park, Colney, Norwich NR4 7UA,
UK
| | - Worachot Saengha
- Natural Antioxidant Innovation Research
Unit, Department of Biotechnology, Faculty of Technology, Mahasarakham
University, Khamriang, Kantarawichai, Maha Sarakham
44150, Thailand
| | - Eakapol Wangkahart
- Research Unit of Excellence for Tropical
Fisheries and Technology, Division of Fisheries, Department of Agricultural
Technology, Faculty of Technology, Mahasarakham University,
Khamriang, Kantarawichai, Maha Sarakham 44150,
Thailand
| | - Supaporn Pumriw
- Department of Food Technology, Faculty of
Agricultural Technology, Kalasin University, Mueang
Kalasin, Kalasin 46000, Thailand
| | - Wannee Samappito
- Department of Food Technology, Faculty of
Technology, Mahasarakham University, Khamriang,
Kantarawichai, Maha Sarakham 44150, Thailand
| | - Nyuk Ling Ma
- Faculty of Science and Marine Environment,
Universiti Malaysia Terengganu, Kuala Nerus,
Terengganu 21030, Malaysia
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Ragusa M, Santagati M, Mirabella F, Lauretta G, Cirnigliaro M, Brex D, Barbagallo C, Domini CN, Gulisano M, Barone R, Trovato L, Oliveri S, Mongelli G, Spitale A, Barbagallo D, Di Pietro C, Stefani S, Rizzo R, Purrello M. Potential Associations Among Alteration of Salivary miRNAs, Saliva Microbiome Structure, and Cognitive Impairments in Autistic Children. Int J Mol Sci 2020; 21:ijms21176203. [PMID: 32867322 PMCID: PMC7504581 DOI: 10.3390/ijms21176203] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Revised: 08/16/2020] [Accepted: 08/25/2020] [Indexed: 12/26/2022] Open
Abstract
Recent evidence has demonstrated that salivary molecules, as well as bacterial populations, can be perturbed by several pathological conditions, including neuro-psychiatric diseases. This relationship between brain functionality and saliva composition could be exploited to unveil new pathological mechanisms of elusive diseases, such as Autistic Spectrum Disorder (ASD). We performed a combined approach of miRNA expression profiling by NanoString technology, followed by validation experiments in qPCR, and 16S rRNA microbiome analysis on saliva from 53 ASD and 27 neurologically unaffected control (NUC) children. MiR-29a-3p and miR-141-3p were upregulated, while miR-16-5p, let-7b-5p, and miR-451a were downregulated in ASD compared to NUCs. Microbiome analysis on the same subjects revealed that Rothia, Filifactor, Actinobacillus, Weeksellaceae, Ralstonia, Pasteurellaceae, and Aggregatibacter increased their abundance in ASD patients, while Tannerella, Moryella and TM7-3 decreased. Variations of both miRNAs and microbes were statistically associated to different neuropsychological scores related to anomalies in social interaction and communication. Among miRNA/bacteria associations, the most relevant was the negative correlation between salivary miR-141-3p expression and Tannerella abundance. MiRNA and microbiome dysregulations found in the saliva of ASD children are potentially associated with cognitive impairments of the subjects. Furthermore, a potential cross-talking between circulating miRNAs and resident bacteria could occur in saliva of ASD.
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Affiliation(s)
- Marco Ragusa
- Department of Biomedical and Biotechnological Sciences, Section of Biology and Genetics G. Sichel, University of Catania, 95123 Catania, Italy; (M.R.); (F.M.); (G.L.); (M.C.); (D.B.); (C.B.); (D.B.); (C.D.P.)
- Oasi Research Institute—IRCCS, 94018 Troina, Italy
| | - Maria Santagati
- Department of Biomedical and Biotechnological Sciences, Section of Microbiology, University of Catania, 95123 Catania, Italy; (M.S.); (L.T.); (S.O.); (G.M.); (A.S.); (S.S.)
| | - Federica Mirabella
- Department of Biomedical and Biotechnological Sciences, Section of Biology and Genetics G. Sichel, University of Catania, 95123 Catania, Italy; (M.R.); (F.M.); (G.L.); (M.C.); (D.B.); (C.B.); (D.B.); (C.D.P.)
| | - Giovanni Lauretta
- Department of Biomedical and Biotechnological Sciences, Section of Biology and Genetics G. Sichel, University of Catania, 95123 Catania, Italy; (M.R.); (F.M.); (G.L.); (M.C.); (D.B.); (C.B.); (D.B.); (C.D.P.)
| | - Matilde Cirnigliaro
- Department of Biomedical and Biotechnological Sciences, Section of Biology and Genetics G. Sichel, University of Catania, 95123 Catania, Italy; (M.R.); (F.M.); (G.L.); (M.C.); (D.B.); (C.B.); (D.B.); (C.D.P.)
| | - Duilia Brex
- Department of Biomedical and Biotechnological Sciences, Section of Biology and Genetics G. Sichel, University of Catania, 95123 Catania, Italy; (M.R.); (F.M.); (G.L.); (M.C.); (D.B.); (C.B.); (D.B.); (C.D.P.)
| | - Cristina Barbagallo
- Department of Biomedical and Biotechnological Sciences, Section of Biology and Genetics G. Sichel, University of Catania, 95123 Catania, Italy; (M.R.); (F.M.); (G.L.); (M.C.); (D.B.); (C.B.); (D.B.); (C.D.P.)
| | - Carla Noemi Domini
- Department of Clinical and Experimental Medicine, Section of Child and Adolescent Psychiatry, University of Catania, 95123 Catania, Italy; (C.N.D.); (M.G.); (R.B.); (R.R.)
| | - Mariangela Gulisano
- Department of Clinical and Experimental Medicine, Section of Child and Adolescent Psychiatry, University of Catania, 95123 Catania, Italy; (C.N.D.); (M.G.); (R.B.); (R.R.)
| | - Rita Barone
- Department of Clinical and Experimental Medicine, Section of Child and Adolescent Psychiatry, University of Catania, 95123 Catania, Italy; (C.N.D.); (M.G.); (R.B.); (R.R.)
| | - Laura Trovato
- Department of Biomedical and Biotechnological Sciences, Section of Microbiology, University of Catania, 95123 Catania, Italy; (M.S.); (L.T.); (S.O.); (G.M.); (A.S.); (S.S.)
| | - Salvatore Oliveri
- Department of Biomedical and Biotechnological Sciences, Section of Microbiology, University of Catania, 95123 Catania, Italy; (M.S.); (L.T.); (S.O.); (G.M.); (A.S.); (S.S.)
| | - Gino Mongelli
- Department of Biomedical and Biotechnological Sciences, Section of Microbiology, University of Catania, 95123 Catania, Italy; (M.S.); (L.T.); (S.O.); (G.M.); (A.S.); (S.S.)
- Bio-nanotech Research and Innovation Tower (BRIT), University of Catania, 95123 Catania, Italy
| | - Ambra Spitale
- Department of Biomedical and Biotechnological Sciences, Section of Microbiology, University of Catania, 95123 Catania, Italy; (M.S.); (L.T.); (S.O.); (G.M.); (A.S.); (S.S.)
| | - Davide Barbagallo
- Department of Biomedical and Biotechnological Sciences, Section of Biology and Genetics G. Sichel, University of Catania, 95123 Catania, Italy; (M.R.); (F.M.); (G.L.); (M.C.); (D.B.); (C.B.); (D.B.); (C.D.P.)
| | - Cinzia Di Pietro
- Department of Biomedical and Biotechnological Sciences, Section of Biology and Genetics G. Sichel, University of Catania, 95123 Catania, Italy; (M.R.); (F.M.); (G.L.); (M.C.); (D.B.); (C.B.); (D.B.); (C.D.P.)
| | - Stefania Stefani
- Department of Biomedical and Biotechnological Sciences, Section of Microbiology, University of Catania, 95123 Catania, Italy; (M.S.); (L.T.); (S.O.); (G.M.); (A.S.); (S.S.)
| | - Renata Rizzo
- Department of Clinical and Experimental Medicine, Section of Child and Adolescent Psychiatry, University of Catania, 95123 Catania, Italy; (C.N.D.); (M.G.); (R.B.); (R.R.)
| | - Michele Purrello
- Department of Biomedical and Biotechnological Sciences, Section of Biology and Genetics G. Sichel, University of Catania, 95123 Catania, Italy; (M.R.); (F.M.); (G.L.); (M.C.); (D.B.); (C.B.); (D.B.); (C.D.P.)
- Correspondence:
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Impaired Hypothalamic Microglial Activation in Offspring of Antibiotic-Treated Pregnant/Lactating Rats Is Attenuated by Prebiotic Oligofructose Co-Administration. Microorganisms 2020; 8:microorganisms8071085. [PMID: 32708167 PMCID: PMC7409116 DOI: 10.3390/microorganisms8071085] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Revised: 07/16/2020] [Accepted: 07/20/2020] [Indexed: 12/26/2022] Open
Abstract
Microbial colonization of the gut early in life is crucial for the development of the immune and nervous systems, as well as influencing metabolism and weight gain. While early life exposure to antibiotics can cause microbial dysbiosis, prebiotics are non-digestible substrates that selectively promote the growth of beneficial gut microbiota. Our objective was to examine the effects of dietary prebiotic administration on the consequences of maternal antibiotic intake on offspring body weight, behavior, and neuroimmune responses later in life. Sprague-Dawley rat dams were given low-dose penicillin (LDP), prebiotic fiber (10% oligofructose), or both, during the third week of pregnancy and throughout lactation. Anxiety-like behavior, weight gain, body composition, cecal microbiota composition, and microglial responses to lipopolysaccharide (LPS) were assessed in offspring. Male and female prebiotic offspring had lower body weight compared to antibiotic offspring. Maternal antibiotic exposure resulted in lasting effects on select offspring microbiota including a lower relative abundance of Streptococcus, Lactococcus, and Eubacterium at 10 weeks of age. Maternal antibiotic use impaired microglial response to LPS in the hypothalamus compared to control, and this phenotype was reversed with prebiotic. Prebiotic fiber warrants further investigation as an adjunct to antibiotic use during pregnancy.
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Sarron E, Pérot M, Barbezier N, Delayre-Orthez C, Gay-Quéheillard J, Anton PM. Early exposure to food contaminants reshapes maturation of the human brain-gut-microbiota axis. World J Gastroenterol 2020; 26:3145-3169. [PMID: 32684732 PMCID: PMC7336325 DOI: 10.3748/wjg.v26.i23.3145] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Revised: 05/12/2020] [Accepted: 05/30/2020] [Indexed: 02/06/2023] Open
Abstract
Early childhood growth and development is conditioned by the consecutive events belonging to perinatal programming. This critical window of life will be very sensitive to any event altering programming of the main body functions. Programming of gut function, which is starting right after conception, relates to a very well-established series of cellular and molecular events associating all types of cells present in this organ, including neurons, endocrine and immune cells. At birth, this machinery continues to settle with the establishment of extra connection between enteric and other systemic systems and is partially under the control of gut microbiota activity, itself being under the densification and the diversification of microorganisms' population. As thus, any environmental factor interfering on this pre-established program may have a strong incidence on body functions. For all these reasons, pregnant women, fetuses and infants will be particularly susceptible to environmental factors and especially food contaminants. In this review, we will summarize the actual understanding of the consequences of repeated low-level exposure to major food contaminants on gut homeostasis settlement and on brain/gut axis communication considering the pivotal role played by the gut microbiota during the fetal and postnatal stages and the presumed consequences of these food toxicants on the individuals especially in relation with the risks of developing later in life non-communicable chronic diseases.
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Affiliation(s)
- Elodie Sarron
- Transformations and Agroressources (EA 7519), Institut Polytechnique UniLaSalle, Université d'Artois, Beauvais 60026, France
| | - Maxime Pérot
- Transformations and Agroressources (EA 7519), Institut Polytechnique UniLaSalle, Université d'Artois, Beauvais 60026, France
| | - Nicolas Barbezier
- Transformations and Agroressources (EA 7519), Institut Polytechnique UniLaSalle, Université d'Artois, Beauvais 60026, France
| | - Carine Delayre-Orthez
- Transformations and Agroressources (EA 7519), Institut Polytechnique UniLaSalle, Université d'Artois, Beauvais 60026, France
| | - Jérôme Gay-Quéheillard
- Périnatalité et risques Toxiques, UMR-I-01, Université de Picardie Jules Verne, Amiens 80000, France
| | - Pauline M Anton
- Transformations and Agroressources (EA 7519), Institut Polytechnique UniLaSalle, Université d'Artois, Beauvais 60026, France
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42
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Zwittink RD, van Zoeren-Grobben D, Renes IB, van Lingen RA, Norbruis OF, Martin R, Groot Jebbink LJ, Knol J, Belzer C. Dynamics of the bacterial gut microbiota in preterm and term infants after intravenous amoxicillin/ceftazidime treatment. BMC Pediatr 2020; 20:195. [PMID: 32380969 PMCID: PMC7204001 DOI: 10.1186/s12887-020-02067-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Accepted: 04/01/2020] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND It is important to understand the consequences of pre-emptive antibiotic treatment in neonates, as disturbances in microbiota development during this key developmental time window might affect early and later life health outcomes. Despite increasing knowledge regarding the detrimental effect of antibiotics on the gut microbiota, limited research focussed on antibiotic treatment duration. We determined the effect of short and long amoxicillin/ceftazidime administration on gut microbiota development during the immediate postnatal life of preterm and term infants. METHODS Faeces was collected from 63 (pre) term infants at postnatal weeks one, two, three, four and six. Infants received either no (control), short-term (ST) or long-term (LT) postpartum amoxicillin/ceftazidime treatment. RESULTS Compared to control infants, ST and LT infants' microbiota contained significantly higher abundance of Enterococcus during the first two postnatal weeks at the expense of Bifidobacterium and Streptococcus. Short and long antibiotic treatment both allowed for microbiota restoration within the first six postnatal weeks. However, Enterococcus and Bifidobacterium abundances were affected in fewer ST than LT infants. CONCLUSIONS Intravenous amoxicillin/ceftazidime administration affects intestinal microbiota composition by decreasing the relative abundance of Escherichia-Shigella and Streptococcus, while increasing the relative abundance of Enterococcus and Lactobacillus species during the first two postnatal weeks. Thriving of enterococci at the expense of bifidobacteria and streptococci should be considered as aspect of the cost-benefit determination for antibiotic prescription.
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Affiliation(s)
- Romy D Zwittink
- Laboratory of Microbiology, Wageningen University, Stippeneng 4, 6708WE, Wageningen, The Netherlands
| | | | | | - Richard A van Lingen
- Princess Amalia Dpt of Paediatrics, Dpt of Neonatology, Isala, Zwolle, The Netherlands
| | - Obbe F Norbruis
- Princess Amalia Dpt of Paediatrics, Dpt of Neonatology, Isala, Zwolle, The Netherlands
| | - Rocio Martin
- Danone Nutricia Research, Utrecht, The Netherlands
| | | | - Jan Knol
- Laboratory of Microbiology, Wageningen University, Stippeneng 4, 6708WE, Wageningen, The Netherlands.,Danone Nutricia Research, Utrecht, The Netherlands
| | - Clara Belzer
- Laboratory of Microbiology, Wageningen University, Stippeneng 4, 6708WE, Wageningen, The Netherlands.
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43
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Dugyala S, Ptacek TS, Simon JM, Li Y, Fröhlich F. Putative modulation of the gut microbiome by probiotics enhances preference for novelty in a preliminary double-blind placebo-controlled study in ferrets. Anim Microbiome 2020; 2. [PMID: 32490353 PMCID: PMC7266289 DOI: 10.1186/s42523-020-00030-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Background Increasing evidence suggests a causal relationship between the gut microbiome and psychiatric illnesses. In particular, autism spectrum disorder is associated with gastrointestinal symptoms and alterations in the gut microbiome. Administration of probiotics is a commonly used strategy by caregivers of people with neurodevelopmental illness. However, evidence for successful improvement in gut microbiome and (behavioral) symptoms has been lacking. Results Here, we use a novel ferret model of maternal immune activation to show that high-dose probiotic administration in a placebo-controlled study design causes changes in the gut microbiome in the form of a transient increase in the administered bacterial species. In contrast, we found no differences in baseline microbiome composition or changes induced by probiotic administration between animals exposed in utero to maternal immune activation and control animals. However, the relative presence of several bacterial species correlated with an increased preference for novelty (object and conspecific). Intriguingly, several of the hits in this screen are species that have previously emerged in the literature as being associated with autism and anxiety. Conclusions Together, our results suggest that high-dose probiotic interventions may be beneficial for the adjunct treatment of psychiatric illnesses. Placebo-controlled clinical trials in humans are urgently needed.
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Affiliation(s)
- Supritha Dugyala
- Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
| | - Travis S Ptacek
- UNC Neuroscience Center, University of North Carolina, Chapel Hill, NC, USA.,Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, NC, USA
| | - Jeremy M Simon
- UNC Neuroscience Center, University of North Carolina, Chapel Hill, NC, USA.,Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, NC, USA.,Department of Genetics, University of North Carolina, Chapel Hill, NC, USA
| | - Yuhui Li
- Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
| | - Flavio Fröhlich
- UNC Neuroscience Center, University of North Carolina, Chapel Hill, NC, USA.,Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.,Carolina Center for Neurostimulation, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.,Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.,Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.,Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, 115 Mason Farm Rd. NRB 4109F, Chapel Hill, NC 27599, USA
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44
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Fournier A, Mondillon L, Luminet O, Canini F, Mathieu N, Gauchez AS, Dantzer C, Bonaz B, Pellissier S. Interoceptive Abilities in Inflammatory Bowel Diseases and Irritable Bowel Syndrome. Front Psychiatry 2020; 11:229. [PMID: 32300314 PMCID: PMC7142209 DOI: 10.3389/fpsyt.2020.00229] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Accepted: 03/10/2020] [Indexed: 12/12/2022] Open
Abstract
Alexithymia is usually described by three main dimensions difficulty identifying feelings (DIF), difficulty describing feelings (DDF), and externally oriented thinking (EOT). The most commonly used questionnaire investigating alexithymia, the Toronto Alexithymia Scale (TAS-20), supports this three-factor structure. One important assumption is that alexithymia severity is associated to vulnerability to somatic diseases, among them gastrointestinal disorders. However, the association between alexithymia and gastrointestinal disorders is not systematic, thus questioning the role of alexithymia as a vulnerability factor for those illnesses. A recent factor analysis suggested another four-factor structure for the TAS-20: difficulties in awareness of feelings (DAF), difficulties in interoceptive abilities (DIA), externally oriented thinking (EOT), and poor affective sharing (PAS). We assume that DIA and DAF might be more relevant to investigate the association between alexithymia and gastrointestinal disorders. The rationale is that DIA and DAF reflect impairments in emotion regulation that could contribute to an inappropriate autonomic and HPA axis homeostasis in irritable bowel syndrome (IBS), ulcerative colitis (UC), or Crohn's disease (CD). The aim of this study was to investigate whether DIA and DAF are associated with the presence of IBS, UC or CD, while checking for anxiety, depression, parasympathetic (vagus nerve) activity and cortisol levels. We recruited control participants (n=26), and patients in remission who were diagnosed with IBS (n=24), UC (n=18), or CD (n=21). Participants completed questionnaires to assess anxiety, depression, and alexithymia. A blood sample and an electrocardiogram were used to measure the level of cortisol and parasympathetic activity, respectively. Logistic regressions with the four-factor structure of the TAS-20 revealed that DIA was a significant predictor of IBS (W(1)=6.27, p=.01). Conversely, DIA and DAF were not significant predictors in CD and UC patients. However, low cortisol level was a significant predictor of UC (W(1)=4.67, p=.035). Additional logistic regressions based on the original 3-factor structure of TAS-20 (DIF, DDF, and EOT) showed that only DDF was a significant predictor of CD [W(1)=6.16, p < .001]. The present study suggests that DIA is an important dimension for assessing potential risk for gastrointestinal diseases, in particular for IBS.
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Affiliation(s)
- Alicia Fournier
- Université de Bourgogne, Laboratoire Psy-DREPI, Dijon, France
- MSHE Claude-Nicolas Ledoux, USR3124, Behaviors, Risk and Health, Besançon, France
| | - Laurie Mondillon
- Université Clermont Auvergne, CNRS, Laboratoire de Psychologie Sociale et Cognitive, Team on Physiological and Psychosocial Stress, Well-being Physiological and Psychosocial Stress, Clermont-Ferrand, France
| | - Olivier Luminet
- Research Institute for Psychological Sciences, Université catholique de Louvain, Louvain-La-Neuve, Belgium
- Fund for Scientific Research (FRS-FNRS), Brussels, Belgium
| | - Fréderic Canini
- Unité de Neurophysiologie du Stress, Institut de Recherche Biomédicale des Armées (IRBA), Brétigny sur Orge, France
- École du Val de Grâce, Paris, France
| | - Nicolas Mathieu
- Service d’Hépato-Gastroentérology, Centre Hospitalier Universitaire de Grenoble, Grenoble, France
| | - Anne Sophie Gauchez
- Institut de Biologie et Pathologie, Centre Hospitalier Universitaire de Grenoble, Grenoble, France
| | - Cécile Dantzer
- Université de Bordeaux, Laboratoire de Psychologie, Bordeaux, France
| | - Bruno Bonaz
- Service d’Hépato-Gastroentérology, Centre Hospitalier Universitaire de Grenoble, Grenoble, France
- Université Grenoble Alpes, Grenoble Institute of Neurosciences, Grenoble, France
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Evrensel A, Ünsalver BÖ, Ceylan ME. Immune-Kynurenine Pathways and the Gut Microbiota-Brain Axis in Anxiety Disorders. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1191:155-167. [PMID: 32002928 DOI: 10.1007/978-981-32-9705-0_10] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Anxiety disorders are a complex set of illnesses in which genetic factors, particularly stress, play a role in the etiopathogenesis. In recent years, inflammation and intestinal microbiota have also been included in this complex network of relationships. The functions associated with tryptophan catabolism and serotonin biosynthesis have long been associated with anxiety disorders. Tryptophan catabolism progresses toward the path of the kynurenine in the presence of stress and inflammation. The catabolism of kynurenine is a pathway in which many enzymes play a role and a large number of catabolites with neuroactive properties occur. The body's serotonin biosynthesis is primarily performed by enterochromaffin cells located in the intestines. A change in the intestinal microbiota composition (dysbiosis) directly affects the serotonin biosynthesis. Stress, unhealthy nutrition, and the use of antibiotics cause dysbiosis. In the light of this new perspective, the role of dysbiosis-induced inflammation and kynurenine pathway catabolites activated sequentially come into prominence in the etiopathogenesis of anxiety disorders.
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Affiliation(s)
- Alper Evrensel
- Department of Psychiatry, Uskudar University, Umraniye, Istanbul, Turkey.
| | - Barış Önen Ünsalver
- Vocational School of Health Services, Department of Medical Documentation and Secretariat, Uskudar University, Istanbul, Turkey
| | - Mehmet Emin Ceylan
- Departments of Psychology and Philosophy, Uskudar University, Istanbul, Turkey
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Ren CC, Sylvia KE, Munley KM, Deyoe JE, Henderson SG, Vu MP, Demas GE. Photoperiod modulates the gut microbiome and aggressive behavior in Siberian hamsters. ACTA ACUST UNITED AC 2020; 223:jeb.212548. [PMID: 31862850 DOI: 10.1242/jeb.212548] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Accepted: 12/19/2019] [Indexed: 12/14/2022]
Abstract
Seasonally breeding animals undergo shifts in physiology and behavior in response to changes in photoperiod (day length). Interestingly, some species, such as Siberian hamsters (Phodopus sungorus), are more aggressive during the short-day photoperiods of the non-breeding season, despite gonadal regression. While our previous data suggest that Siberian hamsters employ a 'seasonal switch' from gonadal to adrenal regulation of aggression during short-day photoperiods, there is emerging evidence that the gut microbiome, an environment of symbiotic bacteria within the gastrointestinal tract, may also change seasonally and modulate social behaviors. The goal of this study was to compare seasonal shifts in the gut microbiome, circulating levels of adrenal dehydroepiandrosterone (DHEA) and aggression in male and female Siberian hamsters. Hamsters were housed in either long-day (LD) or short-day (SD) photoperiods for 9 weeks. Fecal samples were collected and behaviors were recorded following 3, 6 and 9 weeks of housing, and circulating DHEA was measured at week 9. SD females that were responsive to changes in photoperiod (SD-R), but not SD-R males, displayed increased aggression following 9 weeks of treatment. SD-R males and females also exhibited distinct changes in the relative abundance of gut bacterial phyla and families, yet showed no change in circulating DHEA. The relative abundance of some bacterial families (e.g. Anaeroplasmataceae in females) was associated with aggression in SD-R but not LD or SD non-responder (SD-NR) hamsters after 9 weeks of treatment. Collectively, this study provides insight into the complex role of the microbiome in regulating social behavior in seasonally breeding species.
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Affiliation(s)
- Clarissa C Ren
- Department of Biology and Center for the Integrative Study of Animal Behavior, Indiana University, Bloomington, IN 47405, USA
| | - Kristyn E Sylvia
- Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
| | - Kathleen M Munley
- Department of Biology and Center for the Integrative Study of Animal Behavior, Indiana University, Bloomington, IN 47405, USA
| | - Jessica E Deyoe
- Department of Biology and Center for the Integrative Study of Animal Behavior, Indiana University, Bloomington, IN 47405, USA
| | - Sarah G Henderson
- Department of Biology and Center for the Integrative Study of Animal Behavior, Indiana University, Bloomington, IN 47405, USA
| | - Michael P Vu
- Department of Biology and Center for the Integrative Study of Animal Behavior, Indiana University, Bloomington, IN 47405, USA
| | - Gregory E Demas
- Department of Biology and Center for the Integrative Study of Animal Behavior, Indiana University, Bloomington, IN 47405, USA
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47
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The Evolving Microbiome from Pregnancy to Early Infancy: A Comprehensive Review. Nutrients 2020; 12:nu12010133. [PMID: 31906588 PMCID: PMC7019214 DOI: 10.3390/nu12010133] [Citation(s) in RCA: 85] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2019] [Revised: 12/20/2019] [Accepted: 12/20/2019] [Indexed: 12/12/2022] Open
Abstract
Pregnancy induces a number of immunological, hormonal, and metabolic changes that are necessary for the mother to adapt her body to this new physiological situation. The microbiome of the mother, the placenta and the fetus influence the fetus growth and undoubtedly plays a major role in the adequate development of the newborn infant. Hence, the microbiome modulates the inflammatory mechanisms related to physiological and pathological processes that are involved in the perinatal progress through different mechanisms. The present review summarizes the actual knowledge related to physiological changes in the microbiota occurring in the mother, the fetus, and the child, both during neonatal period and beyond. In addition, we approach some specific pathological situations during the perinatal periods, as well as the influence of the type of delivery and feeding.
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48
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Golofast B, Vales K. The connection between microbiome and schizophrenia. Neurosci Biobehav Rev 2019; 108:712-731. [PMID: 31821833 DOI: 10.1016/j.neubiorev.2019.12.011] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Revised: 12/01/2019] [Accepted: 12/06/2019] [Indexed: 12/15/2022]
Abstract
There has been an accumulation of knowledge about the human microbiome, some detailed investigations of the gastrointestinal microbiota and its functions, and the highlighting of complex interactions between the gut, the gut microbiota, and the central nervous system. That assumes the involvement of the microbiome in the pathogenesis of various CNS diseases, including schizophrenia. Given this information and the fact, that the gut microbiota is sensitive to internal and environmental influences, we have speculated that among the factors that influence the formation and composition of gut microbiota during life, possible key elements in the schizophrenia development chain are hidden where gut microbiota is a linking component. This article aims to describe and understand the developmental relationships between intestinal microbiota and the risk of developing schizophrenia.
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Affiliation(s)
- Bogdana Golofast
- National Institute of Mental Health, Topolova 748, 250 67 Klecany, Prague East, Czech Republic; Third Faculty of Medicine, Charles University, Ruská 87, 100 00 Prague 10, Czech Republic.
| | - Karel Vales
- National Institute of Mental Health, Topolova 748, 250 67 Klecany, Prague East, Czech Republic
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49
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Lavebratt C, Yang LL, Giacobini M, Forsell Y, Schalling M, Partonen T, Gissler M. Early exposure to antibiotic drugs and risk for psychiatric disorders: a population-based study. Transl Psychiatry 2019; 9:317. [PMID: 31772217 PMCID: PMC6879739 DOI: 10.1038/s41398-019-0653-9] [Citation(s) in RCA: 67] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Revised: 10/21/2019] [Accepted: 11/04/2019] [Indexed: 12/12/2022] Open
Abstract
Early life exposure to infection, anti-infectives and altered immune activity have been associated with elevated risk of some psychiatric disorders. However, the risk from exposure in fetal life has been proposed to be confounded by familial factors. The hypothesis of this study is that antibiotic drug exposure during the fetal period and the first two postnatal years is associated with risk for later development of psychiatric disorders in children. All births in Finland between 1996 and 2012, 1 million births, were studied for antibiotic drug exposure: mothers during pregnancy and the children the first two postnatal years. The children were followed up for a wide spectrum of psychiatric diagnoses and psychotropic drug treatment until 2014. Cox proportional hazards modeling was used to estimate effects of antibiotic drug exposure on offspring psychiatric disorders. Modestly (10-50%) increased risks were found on later childhood development of sleep disorders, ADHD, conduct disorder, mood and anxiety disorders, and other behavioral and emotional disorders with childhood onset (ICD-10 F98), supported by increased risks also for childhood psychotropic medication. The prenatal exposure effects detected were not explained by explored familial confounding, nor by registered maternal infections. To conclude, this longitudinal nation-wide study shows that early life antibiotic drug exposure is associated with an increased risk for childhood development of psychopathology. Given the high occurrence of early-life antibiotic exposure, these findings are of public health relevance. Whether the associations reflect effects of the antibiotic drug use or of the targeted infections remains to be explored further.
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Affiliation(s)
- Catharina Lavebratt
- Karolinska Institutet, Department of Molecular Medicine and Surgery (MMK), Stockholm, Sweden. .,Karolinska University Hospital Solna, Center for Molecular Medicine, Stockholm, Sweden.
| | - Liu L. Yang
- 0000 0004 1937 0626grid.4714.6Karolinska Institutet, Department of Molecular Medicine and Surgery (MMK), Stockholm, Sweden ,0000 0000 9241 5705grid.24381.3cKarolinska University Hospital Solna, Center for Molecular Medicine, Stockholm, Sweden
| | - MaiBritt Giacobini
- 0000 0004 1937 0626grid.4714.6Karolinska Institutet, Department of Molecular Medicine and Surgery (MMK), Stockholm, Sweden ,PRIMA Child and Adult Psychiatry, Stockholm, Sweden
| | - Yvonne Forsell
- 0000 0004 1937 0626grid.4714.6Karolinska Institutet, Department of Public Health Sciences, Stockholm, Sweden
| | - Martin Schalling
- 0000 0004 1937 0626grid.4714.6Karolinska Institutet, Department of Molecular Medicine and Surgery (MMK), Stockholm, Sweden ,0000 0000 9241 5705grid.24381.3cKarolinska University Hospital Solna, Center for Molecular Medicine, Stockholm, Sweden
| | - Timo Partonen
- 0000 0001 1013 0499grid.14758.3fNational Institute for Health and Welfare (THL), Department of Public Health Solutions, Helsinki, Finland
| | - Mika Gissler
- 0000 0001 1013 0499grid.14758.3fNational Institute for Health and Welfare (THL), Department of Public Health Solutions, Helsinki, Finland ,0000 0004 1937 0626grid.4714.6Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden ,0000 0001 2097 1371grid.1374.1University of Turku, Research Centre for Child Psychiatry, Turku, Finland
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An infection of Enterobacter ludwigii affects development and causes age-dependent neurodegeneration in Drosophila melanogaster. INVERTEBRATE NEUROSCIENCE 2019; 19:13. [PMID: 31641932 DOI: 10.1007/s10158-019-0233-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/02/2019] [Accepted: 10/10/2019] [Indexed: 02/06/2023]
Abstract
The effects of teeth-blackening bacteria Enterobacter ludwigii on the physiological system were investigated using the model organism Drosophila melanogaster. The bacteria were mixed with the fly food, and its effect was checked on the growth, development and behaviour of Drosophila. Microbes generate reactive oxygen species (ROS) within the haemolymph of the larvae once it enters into the body. The increased amount of ROS was evidenced by the NBT assay and using 2',7'-dichlorofluorescin diacetate dye, which indicates the mitochondrial ROS. The increased amount of ROS resulted in a number of abnormal nuclei within the gut. Besides that larvae walking became sluggish in comparison with wild type although the larvae crawling path did not change much. Flies hatched from the infectious larvae have the posterior scutellar bristle absent from the thorax and abnormal mechanosensory hairs in the eye, and they undergo time-dependent neurodegeneration as evidenced by the geotrophic and phototrophic assays. To decipher the mechanism of neurodegeneration, flies were checked for the presence of four important bioamines: tyramine, cadaverine, putrescine and histamine. Out of these four, histamine was found to be absent in infected flies. Histamine is a key molecule required for the functioning of the photoreceptor as well as mechanoreceptors. The mechanism via which mouth infectious bacteria E. ludwigii can affect the development and cause age-dependent neurodegeneration is explained in this paper.
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