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Li Q, Xie Y, Lin J, Li M, Gu Z, Xin T, Zhang Y, Lu Q, Guo Y, Xing Y, Wang W. Microglia Sing the Prelude of Neuroinflammation-Associated Depression. Mol Neurobiol 2025; 62:5311-5332. [PMID: 39535682 DOI: 10.1007/s12035-024-04575-w] [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: 06/14/2023] [Accepted: 10/21/2024] [Indexed: 11/16/2024]
Abstract
Major depressive disorder (MDD) is a psychiatric condition characterized by sadness and anhedonia and is closely linked to chronic low-grade neuroinflammation, which is primarily induced by microglia. Nonetheless, the mechanisms by which microglia elicit depressive symptoms remain uncertain. This review focuses on the mechanism linking microglia and depression encompassing the breakdown of the blood-brain barrier, the hypothalamic-pituitary-adrenal axis, the gut-brain axis, the vagus and sympathetic nervous systems, and the susceptibility influenced by epigenetic modifications on microglia. These pathways may lead to the alterations of microglia in cytokine levels, as well as increased oxidative stress. Simultaneously, many antidepressant treatments can alter the immune phenotype of microglia, while anti-inflammatory treatments can also have antidepressant effects. This framework linking microglia, neuroinflammation, and depression could serve as a reference for targeting microglia to treat depression.
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Affiliation(s)
- Qingqing Li
- Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, 209 Tongshan Rd, Xuzhou, 221004, Jiangsu, China
| | - Ying Xie
- Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, 209 Tongshan Rd, Xuzhou, 221004, Jiangsu, China
| | - Jinyi Lin
- Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, 209 Tongshan Rd, Xuzhou, 221004, Jiangsu, China
| | - Miaomiao Li
- Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, 209 Tongshan Rd, Xuzhou, 221004, Jiangsu, China
| | - Ziyan Gu
- Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, 209 Tongshan Rd, Xuzhou, 221004, Jiangsu, China
| | - Tianli Xin
- Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, 209 Tongshan Rd, Xuzhou, 221004, Jiangsu, China
| | - Yang Zhang
- Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, 209 Tongshan Rd, Xuzhou, 221004, Jiangsu, China
| | - Qixia Lu
- Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, 209 Tongshan Rd, Xuzhou, 221004, Jiangsu, China
| | - Yihui Guo
- Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, 209 Tongshan Rd, Xuzhou, 221004, Jiangsu, China
| | - Yanhong Xing
- Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, 209 Tongshan Rd, Xuzhou, 221004, Jiangsu, China.
| | - Wuyang Wang
- Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, 209 Tongshan Rd, Xuzhou, 221004, Jiangsu, China.
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2
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Alamán-Zárate MG, Rady BJ, Ledermann R, Shephard N, Evans CA, Dickman MJ, Turner RD, Rifflet A, Patel AV, Gomperts Boneca I, Poole PS, Bern M, Mesnage S. A software tool and strategy for peptidoglycomics, the high-resolution analysis of bacterial peptidoglycans via LC-MS/MS. Commun Chem 2025; 8:91. [PMID: 40133660 PMCID: PMC11937551 DOI: 10.1038/s42004-025-01490-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Accepted: 03/10/2025] [Indexed: 03/27/2025] Open
Abstract
Peptidoglycan is an essential component of the bacterial cell envelope-a mesh-like macromolecule that protects the bacterium from osmotic stress and its internal turgor pressure. The composition and architecture of peptidoglycan is heterogeneous and changes as bacteria grow, divide, and respond to their environment. Though peptidoglycan has long been studied via LC-MS/MS, the analysis of this data remains challenging as peptidoglycan's unusual composition and branching can't be handled by proteomics software. Here we describe user-friendly open-source tools and a web interface for building peptidoglycan databases, performing MS searches, and predicting the MS/MS fragmentation of muropeptides. We then use Rhizobium leguminosarum to describe a step-by-step strategy for the high-resolution analysis of peptidoglycan. The unprecedented detail of R. leguminosarum's peptidoglycan composition (>250 muropeptides) reveals even the subtlest remodelling between growth conditions. These new and easier to use tools enable more systematic analyses of peptidoglycan dynamics.
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Affiliation(s)
| | - Brooks J Rady
- Molecular Microbiology, School of Biosciences, University of Sheffield, Sheffield, UK
| | | | - Neil Shephard
- Research Software Engineer team, University of Sheffield, Sheffield, UK
| | - Caroline A Evans
- Department of Chemical and Biological Engineering, ChELSI Institute, University of Sheffield, Sheffield, UK
| | - Mark J Dickman
- Department of Chemical and Biological Engineering, ChELSI Institute, University of Sheffield, Sheffield, UK
| | - Robert D Turner
- Research Software Engineer team, University of Sheffield, Sheffield, UK
| | - Aline Rifflet
- Institut Pasteur, Université Paris Cité, INSERM U1306, CNRS UMR6047, Biology and genetics of the bacterial cell wall Unit, Paris, France
| | - Ankur V Patel
- Molecular Microbiology, School of Biosciences, University of Sheffield, Sheffield, UK
| | - Ivo Gomperts Boneca
- Institut Pasteur, Université Paris Cité, INSERM U1306, CNRS UMR6047, Biology and genetics of the bacterial cell wall Unit, Paris, France
| | | | | | - Stéphane Mesnage
- Molecular Microbiology, School of Biosciences, University of Sheffield, Sheffield, UK.
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3
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Martínez Sánchez I, Spielbauer J, Diaz Heijtz R. Maternal peptidoglycan overexposure during late pregnancy alters neurodevelopment and behavior in juvenile offspring. Brain Behav Immun 2025; 127:96-102. [PMID: 40058669 DOI: 10.1016/j.bbi.2025.03.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Revised: 02/19/2025] [Accepted: 03/06/2025] [Indexed: 03/16/2025] Open
Abstract
Emerging evidence suggests that maternal gut microbiota-derived metabolites and components influence fetal brain development and subsequent neurodevelopment. This study investigates the effects of maternal overexposure to muramyl dipeptide (MDP)-a bacterial peptidoglycan (PGN) motif recognized by Nod2 receptors-on offspring neurodevelopment and behavior. Time-mated C57BL/6J female mice received MDP via drinking water from gestational days 16-19. Nod2 activation in amniotic fluid was assessed using a Nod2 cell-based reporter assay, showing a significant increase in males 24 h after MDP exposure. Gene expression analysis revealed upregulation of PGN transporters in fetal brains, with males showing higher levels of Slc15a1/PepT1, Slc15a2/PepT2, and Slc46a2. No changes in inflammatory or microglia-related markers were found. Behavioral assessments during the juvenile period revealed sex-specific effects: prenatally exposed males showed reduced social interaction, while females exhibited reduced novelty-induced locomotion and impaired social recognition. These behavioral changes were linked to altered expression of synaptic (Dlg4, Ppp1r9b, Darpp-32) and microglial (Trem-2, Cx3cr1) genes in the prefrontal cortex. Our findings underscore the sex-specific effects of maternal PGN overexposure on offspring neurodevelopment, highlighting the potential role of the maternal microbiome in the neurobiology of neurodevelopmental disorders, even in the absence of infection or robust inflammation.
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Affiliation(s)
| | - Julia Spielbauer
- Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden
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Faraji N, Payami B, Ebadpour N, Gorji A. Vagus nerve stimulation and gut microbiota interactions: A novel therapeutic avenue for neuropsychiatric disorders. Neurosci Biobehav Rev 2025; 169:105990. [PMID: 39716559 DOI: 10.1016/j.neubiorev.2024.105990] [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] [Received: 11/18/2024] [Accepted: 12/19/2024] [Indexed: 12/25/2024]
Abstract
The rising prevalence of treatment-resistant neuropsychiatric disorders underscores the need for innovative and effective treatment strategies. The gut microbiota (GM) plays a pivotal role in the progression of these diseases, influencing the brain and mental health through the gut-brain axis (GBA). The vagus nerve plays a significant role in the GBA, making it a key area of focus for potential novel therapeutic interventions. Vagus nerve stimulation (VNS) was introduced and approved as a treatment for refractory forms of some neuropsychological disorders, such as depression and epilepsy. Considering its impact on several brain regions that play a vital part in mood, motivation, affection, and cognitive function, the VNS has shown significant therapeutic potential for treating a variety of neuropsychiatric disorders. Using VNS to target the bidirectional communication pathways linking the GM and the VN could present an exciting and novel approach to treating neuropsychological disorders. Imbalances in the GM, such as dysbiosis, can impair the communication pathways between the gut and the brain, contributing to the development of neuropsychological disorders. VNS shows potential for modulating these interconnected systems, helping to restore balance. Interestingly, the composition of the GM may also influence the effectiveness of VNS, as it has the potential to modify the brain's response to this therapeutic approach. This study provides a comprehensive analysis of a relatively unexplored but noteworthy interaction between VNS and GM in the treatment of neuropsychiatric disorders. In addition, we discussed the mechanisms, therapeutic potential, and clinical implications of VNS on the GBA across neuropsychiatric disorders.
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Affiliation(s)
- Navid Faraji
- Student research committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Bahareh Payami
- Student research committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Negar Ebadpour
- Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ali Gorji
- Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Epilepsy Research Center, Department of Neurosurgery, Münster University, Germany; Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran.
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5
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Armbruster M, Forsythe P. The Perinatal Microbiota-Gut-Brain Axis: Implications for Postpartum Depression. Neuroimmunomodulation 2025; 32:67-82. [PMID: 39837281 DOI: 10.1159/000543691] [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: 10/28/2024] [Accepted: 01/17/2025] [Indexed: 01/23/2025] Open
Abstract
BACKGROUND Pregnancy and childbirth are accompanied by widespread maternal physiological adaptations and hormonal shifts that have been suggested to result in a period of vulnerability for the development of mood disorders such as postpartum depression (PPD). There is also evidence of peripartum changes in the composition of the gut microbiota, but the potential contribution of intestinal microbes to the adaptations, or subsequent vulnerabilities, during this period are unknown. SUMMARY Here, we outline key pathways involved in peripartum adaptations including GABAergic signaling, oxytocin, and immunomodulation that are also associated with susceptibility to mood disorders and present evidence that these pathways are modulated by gut microbes. We also discuss the therapeutic potential of the microbiota-gut-brain axis in PPD and identify future directions for research to help realize this potential. KEY MESSAGES Peripartum adaptations are associated with shifts in gut microbial composition. Disruption of GABAergic, oxytocin, and immunomodulatory pathways may contribute to vulnerability of mood disorders including PPD. These key adaptive pathways are modulated by intestinal microbes suggesting a role for the gut microbiota in determining susceptibility to PPD. More research is needed to confirm relationship between gut microbes and PPD and to gain the mechanistic understanding required to realize the therapeutic potential of microbiota-gut-brain axis in this mood disorder.
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Affiliation(s)
- Marie Armbruster
- Pulmonary Division, Department of Medicine, Alberta Respiratory Centre, University of Alberta, Edmonton, Alberta, Canada
| | - Paul Forsythe
- Pulmonary Division, Department of Medicine, Alberta Respiratory Centre, University of Alberta, Edmonton, Alberta, Canada
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Morin C, Faure F, Mollet J, Guenoun D, Heydari-Olya A, Sautet I, Diao S, Faivre V, Pansiot J, Tabet L, Hua J, Schwendimann L, Mokhtari A, Martin-Rosique R, Chadi S, Laforge M, Demené C, Delahaye-Duriez A, Diaz-Heijtz R, Fleiss B, Matrot B, Auger S, Tanter M, Van Steenwinckel J, Gressens P, Bokobza C. C-section and systemic inflammation synergize to disrupt the neonatal gut microbiota and brain development in a model of prematurity. Brain Behav Immun 2025; 123:824-837. [PMID: 39442636 DOI: 10.1016/j.bbi.2024.10.023] [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: 10/31/2023] [Revised: 10/07/2024] [Accepted: 10/20/2024] [Indexed: 10/25/2024] Open
Abstract
Infants born very preterm (below 28 weeks of gestation) are at high risk of developing neurodevelopmental disorders, such as intellectual deficiency, autism spectrum disorders, and attention deficit. Preterm birth often occurs in the context of perinatal systemic inflammation due to chorioamnionitis and postnatal sepsis. In addition, C-section is often performed for very preterm neonates to avoid hypoxia during a vaginal delivery. We have developed and characterized a mouse model based on intraperitoneal injections of IL-1β between postnatal days one and five to reproduce perinatal systemic inflammation. This model replicates several neuropathological, brain imaging, and behavioral deficits observed in preterm infants. We hypothesized that C-sections could synergize with systemic inflammation to induce more severe brain abnormalities. We observed that C-sections significantly exacerbated the deleterious effects of IL-1β on reduced gut microbial diversity, increased levels of circulating peptidoglycans, abnormal microglia/macrophage reactivity, impaired myelination, and reduced functional connectivity in the brain relative to vaginal delivery plus intraperitoneal saline. These data demonstrate the deleterious synergistic effects of C-section and neonatal systemic inflammation on brain maldevelopment and malfunction, two conditions frequently observed in very preterm infants, who are at high risk of developing neurodevelopmental disorders.
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Affiliation(s)
- Cécile Morin
- Université Paris Cité, Inserm, NeuroDiderot, F-75019 Paris, France; Department of Obstetrics and Gynecology, AP-HP, Robert Debré Hospital, 75019 Paris, France
| | - Flora Faure
- Physics for Medicine Paris, Inserm, ESPCI Paris-PSL, CNRS, 75015 Paris, France
| | - Julie Mollet
- Université Paris Cité, Inserm, NeuroDiderot, F-75019 Paris, France
| | - David Guenoun
- Université Paris Cité, Inserm, NeuroDiderot, F-75019 Paris, France; Department of Pharmacy, AP-HP, Robert Debré Hospital, 75019 Paris, France
| | | | - Irvin Sautet
- Université Paris Cité, Inserm, NeuroDiderot, F-75019 Paris, France
| | - Sihao Diao
- Université Paris Cité, Inserm, NeuroDiderot, F-75019 Paris, France; Fudan University, Department of Neonatology, Children's Hospital of Fudan University, 201102 Shanghai, China
| | - Valérie Faivre
- Université Paris Cité, Inserm, NeuroDiderot, F-75019 Paris, France
| | - Julien Pansiot
- Université Paris Cité, Inserm, NeuroDiderot, F-75019 Paris, France
| | - Lara Tabet
- Université Paris Cité, Inserm, NeuroDiderot, F-75019 Paris, France
| | - Jennifer Hua
- Université Paris Cité, Inserm, NeuroDiderot, F-75019 Paris, France
| | | | - Amazigh Mokhtari
- Université Paris Cité, Inserm, NeuroDiderot, F-75019 Paris, France
| | - Rebeca Martin-Rosique
- INRAE, Université Paris-Saclay, AgroParisTech, UMR1319 Micalis Institute, 78352 Jouy-en-Josas, France
| | - Sead Chadi
- INRAE, Université Paris-Saclay, AgroParisTech, UMR1319 Micalis Institute, 78352 Jouy-en-Josas, France
| | - Mireille Laforge
- Université Paris Cité, Inserm, NeuroDiderot, F-75019 Paris, France
| | - Charlie Demené
- Physics for Medicine Paris, Inserm, ESPCI Paris-PSL, CNRS, 75015 Paris, France
| | - Andrée Delahaye-Duriez
- Université Paris Cité, Inserm, NeuroDiderot, F-75019 Paris, France; UFR Santé Médecine et Biologie Humaine, Université Sorbonne Paris Nord, 93000 Bobigny, France; Unité Fonctionnelle de Médecine Génomique et Génétique Clinique, Hôpital Jean Verdier, Hôpitaux Universitaires Paris Seine Saint-Denis, Assistance Publique des Hôpitaux de Paris, 93140 Bondy, France
| | | | - Bobbi Fleiss
- School of Health and Biomedical Sciences, STEM College, RMIT University, Bundoora, Melbourne, Victoria 3083, Australia
| | - Boris Matrot
- Université Paris Cité, Inserm, NeuroDiderot, F-75019 Paris, France
| | - Sandrine Auger
- INRAE, Université Paris-Saclay, AgroParisTech, UMR1319 Micalis Institute, 78352 Jouy-en-Josas, France
| | - Mickael Tanter
- Physics for Medicine Paris, Inserm, ESPCI Paris-PSL, CNRS, 75015 Paris, France
| | | | - Pierre Gressens
- Université Paris Cité, Inserm, NeuroDiderot, F-75019 Paris, France
| | - Cindy Bokobza
- Université Paris Cité, Inserm, NeuroDiderot, F-75019 Paris, France.
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Zeiher C, Kuhrt H, Rifflet A, Winter K, Boon L, Stassart RM, Nutma E, Middeldorp J, Strating IM, Boneca IG, Bechmann I, Laman JD. Peptidoglycan accumulates in distinct brain regions and cell types over lifetime but is absent in newborns. Brain Behav Immun 2025; 123:799-812. [PMID: 39442638 DOI: 10.1016/j.bbi.2024.10.024] [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: 05/03/2024] [Revised: 09/28/2024] [Accepted: 10/20/2024] [Indexed: 10/25/2024] Open
Abstract
Peptidoglycan (PGN) is a large complex polymer critical to structure and function of all bacterial species. Intact PGN and its fragments are inflammatory, contributing to infectious and autoimmune disease. Recent studies show that PGN physiologically contributes to immune setpoints, and importantly also to mouse brain development and behavior. However, for the human brain, it remains unknown whether PGN and its fragments differentially gain access to distinct brain regions, which cell types accumulate it, and whether PGN brain load varies with age. Therefore, we investigated human postmortem brain samples of donors with an extensive age range, from newborns to nonagenarians. We examined two monoclonal antibodies against PGN which were validated using dot blot analysis, competition assays and immunofluorescence experiments on bacteria sacculi, which jointly showed specific detection of Gram-positive PGN. As positive reference tissue, brain tissue from sepsis patients, and human liver were used, both showing the expected high PGN levels. In adult brain tissue of different age (34- to 94-year-old) and sex, we detected PGN signals in seven different brain regions, with highest loads in the occipital cortex, hippocampal formation, frontal cortex, the periventricular region and the olfactory bulb. Age-dependent increase of signals was not evident by microscopic observations and only weak correlation was found by statistical analysis in this cohort. PGN was found intracellularly in the cytoplasm surrounding the cell nucleus in astrocytes, oligodendrocytes, neurons, and endothelial cells, but not in macrophages like microglia. PGN was absent in brain tissues of three human newborns (stillbirth to four weeks old). For comparison, three brain regions from non-human primates of varying age (newborn to 21 years) were immunohistochemically stained. The highest PGN-load was observed in brain tissue from 18- to 21-year-old macaques. This first systematic evaluation of PGN in human postmortem brain suggests that PGN accumulates during lifetime until it reaches a plateau by homeostatic turnover and highlights the ubiquitous presence of PGN in human brain tissues, and their ability to participate in physiological as well as pathological processes throughout life.
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Affiliation(s)
- Carolin Zeiher
- Institute of Anatomy, University of Leipzig, Leipzig, Germany.
| | - Heidrun Kuhrt
- Institute of Anatomy, University of Leipzig, Leipzig, Germany
| | - Aline Rifflet
- Institute Pasteur, Université Paris Cité, INSERM U1306, Biology and Genetics of the Bacterial Cell Wall Unit, F-75015 Paris, France
| | - Karsten Winter
- Institute of Anatomy, University of Leipzig, Leipzig, Germany
| | | | | | - Erik Nutma
- Biomedical Primate Research Centre (BPRC), Department of Neurobiology and Aging, Rijswijk, Netherlands (The)
| | - Jinte Middeldorp
- Biomedical Primate Research Centre (BPRC), Department of Neurobiology and Aging, Rijswijk, Netherlands (The)
| | - Inge M Strating
- University Groningen, University Medical Center Groningen (UMCG), Dept. Pathology & Medical Biology, and MS Center Noord Nederland (MSCNN), Groningen, Netherlands (The)
| | - Ivo G Boneca
- Institute Pasteur, Université Paris Cité, INSERM U1306, Biology and Genetics of the Bacterial Cell Wall Unit, F-75015 Paris, France.
| | - Ingo Bechmann
- Institute of Anatomy, University of Leipzig, Leipzig, Germany.
| | - Jon D Laman
- University Groningen, University Medical Center Groningen (UMCG), Dept. Pathology & Medical Biology, and MS Center Noord Nederland (MSCNN), Groningen, Netherlands (The).
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8
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Priego-Parra BA, Remes-Troche JM. Bidirectional relationship between gastrointestinal cancer and depression: The key is in the microbiota-gut-brain axis. World J Gastroenterol 2024; 30:5104-5110. [PMID: 39735265 PMCID: PMC11612697 DOI: 10.3748/wjg.v30.i48.5104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Revised: 10/23/2024] [Accepted: 11/04/2024] [Indexed: 11/29/2024] Open
Abstract
In this Editorial, we review the recent publication in the World Journal of Gastroenterology, which explores the complex relationship between depression and gastric cancer and offers perspectives. Key topics discussed include the microbiota-gut-brain axis, dysbiosis, and the influence of microbial metabolites in homeostasis. Additionally, we address toxic stress caused by hypothalamic-pituitary-adrenal axis dysregulation, psychological assessments, and future research directions. Our Editorial aims to expand the understanding of the bidirectional relationship between depression and gastrointestinal cancer.
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Affiliation(s)
- Bryan Adrian Priego-Parra
- Digestive Physiology and Gastrointestinal Motility Laboratory, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz 91700, Mexico
| | - Jose Maria Remes-Troche
- Digestive Physiology and Gastrointestinal Motility Laboratory, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz 91700, Mexico
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9
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Momeni N, Mousavi SN, Chiti H, Heidarzadeh S. A maternal sweet diet is associated with the gut dysbiosis in the first trimester of pregnancy. BMC Nutr 2024; 10:162. [PMID: 39695908 DOI: 10.1186/s40795-024-00972-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2024] [Accepted: 12/08/2024] [Indexed: 12/20/2024] Open
Abstract
BACKGROUND The composition of maternal gut phylum in each trimester of pregnancy has been associated with fetal development, separately. Diet is a main effective factor on the gut composition of phylum. However, associations between dietary glycemic index (GI), load (GL) and total antioxidant capacity (TAC) not studied with the gut population of phylum in mothers at the first trimester of pregnancy. MATERIALS AND METHODS Ninety healthy pregnant women aged 18-40 yrs, in the first trimester, were participated. Stool samples were gathered in a fasting state. Population of dominant phylum was determined after DNA extraction based on the 16SrRNA expression, as a housekeeping gene. Dietary intake was collected by a validated food frequency questionnaire and dietary indices were computed. RESULTS The Proteobacteria population was significantly higher in the gut of pregnant mothers than the other phylum (p < 0.001). Participants in the highest level of dietary GI had lower Bacteroidetes (p < 0.001) and Actinobacteria (p = 0.04) in their gut compared to the lowest level. Participants in the lowest level of dietary GL had higher Bacteroidetes (p < 0.001) and lower proteobacteria (p = 0.04) in their gut than the highest level. Dietary selenium showed a significant negative effect on the Firmicutes (p = 0.04) and Proteobacteria (p = 0.04), however positively affected the Actinobacteria (p = 0.01) population. Dietary zinc and manganese showed a negative effect on the Firmicutes population (p = 0.01 and p = 0.003). Zinc and vitamin E showed a negative effect on the Proteobacteria population (p = 0.04 and p = 0.03). CONCLUSIONS A maternal diet with high GI and GL have been associated with the gut dysbiosis, however dietary intake of selenium, zinc, manganese and vitamin E act in favor of the intestinal eubiosis in the first trimester of pregnancy.
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Affiliation(s)
- Navid Momeni
- Zanjan Metabolic Diseases Research Center, Health and Metabolic Diseases Research Institute, Zanjan University of Medical Sciences, Parvin Etesami St, Azadi Square, Zanjan, Iran
| | - Seyedeh Neda Mousavi
- Zanjan Metabolic Diseases Research Center, Health and Metabolic Diseases Research Institute, Zanjan University of Medical Sciences, Parvin Etesami St, Azadi Square, Zanjan, Iran.
- Department of Nutrition, School of Public Health, Zanjan University of Medical Sciences, Zanjan, Iran.
| | - Hossein Chiti
- Zanjan Metabolic Diseases Research Center, Health and Metabolic Diseases Research Institute, Zanjan University of Medical Sciences, Parvin Etesami St, Azadi Square, Zanjan, Iran.
| | - Siamak Heidarzadeh
- Department of Microbiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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10
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González-García S, Hamdan-Partida A, Pérez-Ramos J, Aguirre-Garrido JF, Bustos-Hamdan A, Bustos-Martínez J. Comparison of the bacterial microbiome in the pharynx and nasal cavity of persistent, intermittent carriers and non-carriers of Staphylococcus aureus. J Med Microbiol 2024; 73:001940. [PMID: 39629792 PMCID: PMC11616445 DOI: 10.1099/jmm.0.001940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Accepted: 11/13/2024] [Indexed: 12/08/2024] Open
Abstract
Introduction. Staphylococcus aureus is a bacterium that colonizes various human sites. The pharynx has been considered as a site of little clinical relevance and little studied. Recently, it has been reported that S. aureus can colonize more the pharynx than the nose. In addition, S. aureus can persist in these sites for prolonged periods of time.Hypothesis. The composition of the pharyngeal and nasal microbiome will differ between persistent, intermittent carriers and non-carriers of S. aureus.Aim. Determine whether the pharyngeal and nasal microbiome is different between carriers and non-carriers of S. aureus.Methodology. S. aureus carriers were monitored by means of pharyngeal and nasal exudates of apparently healthy adult university students for 3 months. Samples from individuals of the same carrier type were pooled, and DNA was extracted and the 16S rRNA was sequenced. The sequences were analysed in MOTHUR v.1.48.0 software, by analysing the percentages of relative abundance in the STAMP 2.1.3 program, in addition to the predictive analysis of metabolic pathways in PICRUSt2.Results. A greater colonization of S. aureus was found in the pharynx than in the nose. The microbiomes of S. aureus carriers and non-carriers do not show significant differences. The main microbiome difference found was between pharyngeal and nasal microbiomes. No significant differences were found in the abundance of the genus Staphylococcus in pharyngeal and nasal S. aureus carriers and non-carriers. The nasal microbiome was found to have more variation compared to the pharyngeal microbiome, which appears to be more stable between individuals and pools. Predictive analysis of metabolic pathways showed a greater presence of Staphylococcus-associated pathways in the nose than in the pharynx.Conclusion. S. aureus can colonize and persist in the pharynx in equal or greater proportion than in the nose. No statistically significant differences were found in the microbiome of the pharyngeal and nasal carriers and non-carriers of S. aureus, but the pharyngeal and nasal microbiomes are different independent of the type of S. aureus carrier or non-carrier. Therefore, the microbiome apparently does not influence the persistence of S. aureus.
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Affiliation(s)
- Samuel González-García
- Doctorado en Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana, Mexico City, Mexico
| | - Aida Hamdan-Partida
- Departamento de Atención a la Salud, UAM Xochimilco, Calzada del Hueso 1100, Colonia Villa Quietud, Alcaldía Coyoacán, C.P. 04960, CDMX, Mexico
| | - Julia Pérez-Ramos
- Departamento de Sistemas Biológicos, UAM Xochimilco, Calzada del Hueso 1100, Colonia Villa Quietud, Alcaldía Coyoacán, C.P. 04960, CDMX, Mexico
| | - José Félix Aguirre-Garrido
- Departamento de Ciencias Ambientales, UAM Lerma, Av. de las Garzas 10E, l Panteón 52005, Municipio Lerma de Villada, Estado de México, Mexico
| | - Anaíd Bustos-Hamdan
- Departamento de Atención a la Salud, UAM Xochimilco, Calzada del Hueso 1100, Colonia Villa Quietud, Alcaldía Coyoacán, C.P. 04960, CDMX, Mexico
| | - Jaime Bustos-Martínez
- Departamento de Atención a la Salud, UAM Xochimilco, Calzada del Hueso 1100, Colonia Villa Quietud, Alcaldía Coyoacán, C.P. 04960, CDMX, Mexico
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11
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Fallah A, Sedighian H, Kachuei R, Fooladi AAI. Human microbiome in post-acute COVID-19 syndrome (PACS). CURRENT RESEARCH IN MICROBIAL SCIENCES 2024; 8:100324. [PMID: 39717208 PMCID: PMC11665312 DOI: 10.1016/j.crmicr.2024.100324] [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] [Indexed: 12/25/2024] Open
Abstract
The global COVID-19 pandemic, which began in 2019, is still ongoing. SARS-CoV-2, also known as the severe acute respiratory syndrome coronavirus 2, is the causative agent. Diarrhea, nausea, and vomiting are common GI symptoms observed in a significant number of COVID-19 patients. Additionally, the respiratory and GI tracts express high level of transmembrane protease serine 2 (TMPRSS2) and angiotensin-converting enzyme-2 (ACE2), making them primary sites for human microbiota and targets for SARS-CoV-2 infection. A growing body of research indicates that individuals with COVID-19 and post-acute COVID-19 syndrome (PACS) exhibit considerable alterations in their microbiome. In various human disorders, including diabetes, obesity, cancer, ulcerative colitis, Crohn's disease, and several viral infections, the microbiota play a significant immunomodulatory role. In this review, we investigate the potential therapeutic implications of the interactions between host microbiota and COVID-19. Microbiota-derived metabolites and components serve as primary mediators of microbiota-host interactions, influencing host immunity. We discuss the various mechanisms through which these metabolites or components produced by the microbiota impact the host's immune response to SARS-CoV-2 infection. Additionally, we address confounding factors in microbiome studies. Finally, we examine and discuss about a range of potential microbiota-based prophylactic measures and treatments for COVID-19 and PACS, as well as their effects on clinical outcomes and disease severity.
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Affiliation(s)
- Arezoo Fallah
- Department of Bacteriology and Virology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Hamid Sedighian
- Applied Microbiology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Reza Kachuei
- Molecular Biology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Abbas Ali Imani Fooladi
- Applied Microbiology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
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12
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Siegler Lathrop T, Perego S, Bastiaanssen TFS, van Hemert S, Chronakis IS, Diaz Heijtz R. Multispecies probiotic intake during pregnancy modulates neurodevelopmental trajectories of offspring: Aiming towards precision microbial intervention. Brain Behav Immun 2024; 122:547-554. [PMID: 39197545 DOI: 10.1016/j.bbi.2024.08.050] [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: 04/23/2024] [Revised: 08/15/2024] [Accepted: 08/24/2024] [Indexed: 09/01/2024] Open
Abstract
Recent research highlights the pivotal role of the maternal gut microbiome during pregnancy in shaping offspring neurodevelopment. In this study, we investigated the impact of maternal intake of a multispecies probiotic formulation during a critical prenatal window (from gestational day 6 until birth) on neurodevelopmental trajectories in mice. Our findings demonstrate significant and persistent benefits in emotional behavior, gut microbiota composition, and expression of tight junction-related genes, particularly in male offspring, who exhibited heightened sensitivity to the probiotic intervention compared to females. Additionally, we observed elevated gene expression levels of the anti-inflammatory cytokine IL-10 and the oxytocin receptor (Oxtr) in the prefrontal cortex (PFC) of exposed juvenile offspring; however, these changes persisted only in the adult male offspring. Furthermore, the sustained increase in the expression of the proton-coupled oligopeptide transporter 1 (PepT1), which is involved in the transport of bacterial peptidoglycan motifs, in the PFC of exposed male offspring suggests a potential mechanistic pathway underlying the observed sex-dependent effects on behavior and gene expression. These results underscore the potential of prenatal multispecies probiotic interventions to promote long-term neurodevelopmental outcomes, with implications for precision microbial reconstitution aimed at promoting healthy neurodevelopment and behavior.
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Affiliation(s)
- Tatiana Siegler Lathrop
- Technical University of Denmark, DTU-Food, Research Group for Food Production Engineering, Laboratory of Nano-BioScience, Denmark
| | - Sarah Perego
- Department of Neuroscience, Karolinska Institutet, Stockholm Sweden
| | | | - Saskia van Hemert
- Wageningen Bioveterinary Research, Wageningen University & Research, the Netherlands
| | - Ioannis S Chronakis
- Technical University of Denmark, DTU-Food, Research Group for Food Production Engineering, Laboratory of Nano-BioScience, Denmark
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13
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Spielbauer J, Glotfelty EJ, Sarlus H, Harris RA, Diaz Heijtz R, Karlsson TE. Bacterial peptidoglycan signalling in microglia: Activation by MDP via the NF-κB/MAPK pathway. Brain Behav Immun 2024; 121:43-55. [PMID: 38971207 DOI: 10.1016/j.bbi.2024.06.027] [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: 02/23/2024] [Revised: 06/26/2024] [Accepted: 06/28/2024] [Indexed: 07/08/2024] Open
Abstract
Bacterial peptidoglycan (PGN) fragments are commonly studied in the context of bacterial infections. However, PGN fragments recently gained recognition as signalling molecules from the commensal gut microbiota in the healthy host. Here we focus on the minimal bioactive PGN motif muramyl dipeptide (MDP), found in both Gram-positive and Gram-negative commensal bacteria, which signals through the Nod2 receptor. MDP from the gut microbiota translocates to the brain and is associated with changes in neurodevelopment and behaviour, yet there is limited knowledge about the underlying mechanisms. In this study we demonstrate that physiologically relevant doses of MDP induce rapid changes in microglial gene expression and lead to cytokine and chemokine secretion. In immortalised microglial (IMG) cells, C-C Motif Chemokine Ligand 5 (CCL5/RANTES) expression is acutely sensitive to the lowest physiologically prevalent dose (0.1 µg/ml) of MDP. As CCL5 plays an important role in memory formation and synaptic plasticity, microglial CCL5 might be the missing link in elucidating MDP-induced alterations in synaptic gene expression. We observed that a higher physiological dose of MDP elevates the expression of cytokines TNF-α and IL-1β, indicating a transition toward a pro-inflammatory phenotype in IMG cells, which was validated in primary microglial cultures. Furthermore, MDP induces the translocation of NF-κB subunit p65 into the nucleus, which is blocked by MAPK p38 inhibitor SB202190, suggesting that an interplay of both the NF-κB and MAPK pathways is responsible for the MDP-specific microglial phenotype. These findings underscore the significance of different MDP levels in shaping microglial function in the CNS and indicate MDP as a potential mediator for early inflammatory processes in the brain. It also positions microglia as an important target in the gut microbiota-brain-axis pathway through PGN signalling.
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Affiliation(s)
- Julia Spielbauer
- Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden.
| | - Elliot J Glotfelty
- Drug Design & Development Section, Translational Gerontology Branch, Intramural Research Program National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
| | - Heela Sarlus
- Department of Clinical Neuroscience, Karolinska Institutet, Centre for Molecular Medicine, Karolinska Hospital at Solna, 171 77 Stockholm, Sweden
| | - Robert A Harris
- Department of Clinical Neuroscience, Karolinska Institutet, Centre for Molecular Medicine, Karolinska Hospital at Solna, 171 77 Stockholm, Sweden
| | | | - Tobias E Karlsson
- Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden.
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14
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Vaia Y, Bruschi F, Tagi VM, Tosi M, Montanari C, Zuccotti G, Tonduti D, Verduci E. Microbiota gut-brain axis: implications for pediatric-onset leukodystrophies. Front Nutr 2024; 11:1417981. [PMID: 39070252 PMCID: PMC11272617 DOI: 10.3389/fnut.2024.1417981] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 07/02/2024] [Indexed: 07/30/2024] Open
Abstract
Neurodegenerative disorders are a group of diseases characterized by progressive degeneration of the nervous system, leading to a gradual loss of previously acquired motor, sensory and/or cognitive functions. Leukodystrophies are amongst the most frequent childhood-onset neurodegenerative diseases and primarily affect the white matter of the brain, often resulting in neuro-motor disability. Notably, gastrointestinal (GI) symptoms and complications, such as gastroesophageal reflux disease (GERD) and dysphagia, significantly impact patients' quality of life, highlighting the need for comprehensive management strategies. Gut dysbiosis, characterized by microbial imbalance, has been implicated in various GI disorders and neurodegenerative diseases. This narrative review explores the intricate relationship between GI symptoms, Gut Microbiota (GM), and neurodegeneration. Emerging evidence underscores the profound influence of GM on neurological functions via the microbiota gut-brain axis. Animal models have demonstrated alterations in GM composition associated with neuroinflammation and neurodegeneration. Our single-centre experience reveals a high prevalence of GI symptoms in leukodystrophy population, emphasizing the importance of gastroenterological assessment and nutritional intervention in affected children. The bidirectional relationship between GI disorders and neurodegeneration suggests a potential role of gut dysbiosis in disease progression. Prospective studies investigating the GM in leukodystrophies are essential to understand the role of gut-brain axis dysfunction in disease progression and identify novel therapeutic targets. In conclusion, elucidating the interplay between GI disorders, GM, and neurodegeneration holds promise for precision treatments aimed at improving patient outcomes and quality of life.
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Affiliation(s)
- Ylenia Vaia
- C.O.A.L.A. (Center for Diagnosis and Treatment of Leukodystrophies), Unit of Pediatric Neurology, V. Buzzi Children’s Hospital, Milan, Italy
- Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy
| | - Fabio Bruschi
- C.O.A.L.A. (Center for Diagnosis and Treatment of Leukodystrophies), Unit of Pediatric Neurology, V. Buzzi Children’s Hospital, Milan, Italy
- Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy
| | - Veronica Maria Tagi
- Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy
- Department of Pediatrics, V. Buzzi Children's Hospital, Milan, Italy
| | - Martina Tosi
- Department of Pediatrics, V. Buzzi Children's Hospital, Milan, Italy
- Department of Health Sciences, University of Milan, Milan, Italy
| | - Chiara Montanari
- Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy
- Department of Pediatrics, V. Buzzi Children's Hospital, Milan, Italy
| | - Gianvincenzo Zuccotti
- Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy
- Department of Pediatrics, V. Buzzi Children's Hospital, Milan, Italy
| | - Davide Tonduti
- C.O.A.L.A. (Center for Diagnosis and Treatment of Leukodystrophies), Unit of Pediatric Neurology, V. Buzzi Children’s Hospital, Milan, Italy
- Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy
| | - Elvira Verduci
- Department of Health Sciences, University of Milan, Milan, Italy
- Metabolic Diseases Unit, Department of Pediatrics, V. Buzzi Children’s Hospital, University of Milan, Milan, Italy
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15
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He P, Yu L, Tian F, Chen W, Zhang H, Zhai Q. Effects of Probiotics on Preterm Infant Gut Microbiota Across Populations: A Systematic Review and Meta-Analysis. Adv Nutr 2024; 15:100233. [PMID: 38908894 PMCID: PMC11251410 DOI: 10.1016/j.advnut.2024.100233] [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] [Received: 01/10/2024] [Revised: 04/13/2024] [Accepted: 04/17/2024] [Indexed: 06/24/2024] Open
Abstract
Microbiota in early life is closely associated with the health of infants, especially premature ones. Probiotics are important drivers of gut microbiota development in preterm infants; however, there is no consensus regarding the characteristics of specific microbiota in preterm infants receiving probiotics. In this study, we performed a meta-analysis of 5 microbiome data sets (1816 stool samples from 706 preterm infants) to compare the gut microbiota of preterm infants exposed to probiotics with that of preterm infants not exposed to probiotics across populations. Despite study-specific variations, we found consistent differences in gut microbial composition and predicted functional pathways between the control and probiotic groups across different cohorts of preterm infants. The enrichment of Acinetobacter, Bifidobacterium, and Lactobacillus spp and the depletion of the potentially pathogenic bacteria Finegoldia, Veillonella, and Klebsiella spp. were the most consistent changes in the gut microbiota of preterm infants supplemented with probiotics. Probiotics drove microbiome transition into multiple preterm gut community types, and notably, preterm gut community type 3 had the highest α-diversity, with enrichment of Bifidobacterium and Bacteroides spp. At the functional level, the major predicted microbial pathways involved in peptidoglycan biosynthesis consistently increased in preterm infants supplemented with probiotics; in contrast, the crucial pathways associated with heme biosynthesis consistently decreased. Interestingly, Bifidobacterium sp. rather than Lactobacillus sp. gradually became dominant in gut microbiota of preterm infants using mixed probiotics, although both probiotic strains were administered at the same dosage. Taken together, our meta-analysis suggests that probiotics contribute to reshaping the microbial ecosystem of preterm infants at both the taxonomic and functional levels of the bacterial community. More standardized and relevant studies may contribute to better understanding the crosstalk among probiotics, the gut microbiota, and subsequent disease risk, which could help to give timely nutritional feeding guidance to preterm infants. This systematic review and meta-analysis was registered at PROSPERO (https://www.crd.york.ac.uk/PROSPERO/) as CRD42023447901.
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Affiliation(s)
- Pandi He
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu, China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China.
| | - Leilei Yu
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu, China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China.
| | - Fengwei Tian
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu, China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China.
| | - Wei Chen
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu, China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China; National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, Jiangsu, China.
| | - Hao Zhang
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu, China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China.
| | - Qixiao Zhai
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu, China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China.
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16
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Duve K, Petakh P, Kamyshnyi O. COVID-19-associated encephalopathy: connection between neuroinflammation and microbiota-gut-brain axis. Front Microbiol 2024; 15:1406874. [PMID: 38863751 PMCID: PMC11165208 DOI: 10.3389/fmicb.2024.1406874] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Accepted: 05/16/2024] [Indexed: 06/13/2024] Open
Abstract
While neurological complications of COVID-19, such as encephalopathy, are relatively rare, their potential significant impact on long-term morbidity is substantial, especially given the large number of infected patients. Two proposed hypotheses for the pathogenesis of this condition are hypoxia and the uncontrolled release of proinflammatory cytokines. The gut microbiota plays an important role in regulating immune homeostasis and overall gut health, including its effects on brain health through various pathways collectively termed the gut-brain axis. Recent studies have shown that COVID-19 patients exhibit gut dysbiosis, but how this dysbiosis can affect inflammation in the central nervous system (CNS) remains unclear. In this context, we discuss how dysbiosis could contribute to neuroinflammation and provide recent data on the features of neuroinflammation in COVID-19 patients.
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Affiliation(s)
- Khrystyna Duve
- Department of Neurology, I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine
| | - Pavlo Petakh
- Department of Biochemistry and Pharmacology, Uzhhorod National University, Uzhhorod, Ukraine
- Department of Microbiology, Virology, and Immunology, I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine
| | - Oleksandr Kamyshnyi
- Department of Biochemistry and Pharmacology, Uzhhorod National University, Uzhhorod, Ukraine
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17
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Aburto MR, Cryan JF. Gastrointestinal and brain barriers: unlocking gates of communication across the microbiota-gut-brain axis. Nat Rev Gastroenterol Hepatol 2024; 21:222-247. [PMID: 38355758 DOI: 10.1038/s41575-023-00890-0] [Citation(s) in RCA: 64] [Impact Index Per Article: 64.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/20/2023] [Indexed: 02/16/2024]
Abstract
Crosstalk between gut and brain has long been appreciated in health and disease, and the gut microbiota is a key player in communication between these two distant organs. Yet, the mechanisms through which the microbiota influences development and function of the gut-brain axis remain largely unknown. Barriers present in the gut and brain are specialized cellular interfaces that maintain strict homeostasis of different compartments across this axis. These barriers include the gut epithelial barrier, the blood-brain barrier and the blood-cerebrospinal fluid barrier. Barriers are ideally positioned to receive and communicate gut microbial signals constituting a gateway for gut-microbiota-brain communication. In this Review, we focus on how modulation of these barriers by the gut microbiota can constitute an important channel of communication across the gut-brain axis. Moreover, barrier malfunction upon alterations in gut microbial composition could form the basis of various conditions, including often comorbid neurological and gastrointestinal disorders. Thus, we should focus on unravelling the molecular and cellular basis of this communication and move from simplistic framing as 'leaky gut'. A mechanistic understanding of gut microbiota modulation of barriers, especially during critical windows of development, could be key to understanding the aetiology of gastrointestinal and neurological disorders.
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Affiliation(s)
- María R Aburto
- APC Microbiome Ireland, University College Cork, Cork, Ireland.
- Department of Anatomy and Neuroscience, School of Medicine, University College Cork, Cork, Ireland.
| | - John F Cryan
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Department of Anatomy and Neuroscience, School of Medicine, University College Cork, Cork, Ireland
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18
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Joo MK, Lee JW, Woo JH, Kim HJ, Kim DH, Choi JH. Regulation of colonic neuropeptide Y expression by the gut microbiome in patients with ulcerative colitis and its association with anxiety- and depression-like behavior in mice. Gut Microbes 2024; 16:2319844. [PMID: 38404132 PMCID: PMC10900276 DOI: 10.1080/19490976.2024.2319844] [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: 05/25/2023] [Accepted: 02/13/2024] [Indexed: 02/27/2024] Open
Abstract
Patients with inflammatory bowel disease (IBD), including ulcerative colitis (UC), show an increased incidence of anxiety and depression; however, the association between UC-associated psychiatric disorders and the gut microbiota is unclear. This study aimed to examine whether gut microbiota from patients with UC can alter colonic gene expression, leading to anxiety- and depression-like behavior in mice receiving fecal microbiota transplantation (FMT). RNA sequencing transcriptome analyses revealed a difference in colonic gene expression between mice receiving FMT from patients with UC (UC-FMT mice) and those receiving FMT from healthy controls (HC-FMT mice). Gene ontology analysis revealed the downregulation of neuropeptide signaling pathways, including neuropeptide Y (NPY) expression, in the colons of UC-FMT mice. The protein levels of NPY also decreased in the colon and plasma of UC-FMT mice compared to those in HC-FMT mice. The oral administration of Enterococcus mundtii (EM), a bacterium isolated from the feces of patients with UC, reduced NPY expression in the colons of mice and induced intestinal inflammation, anxiety, and depression-like behavior. Reduced NPY protein levels were also observed in the plasma and hippocampus of EM-treated mice. Intraperitoneal administration of NPY significantly alleviated anxiety- and depressive-like behaviors induced by EM in mice. Capsular polysaccharide in EM was associated with EM-induced NPY downregulation in the colon. Analysis of Gene Expression Omnibus datasets showed markedly reduced NPY expression in the inflamed colons of patients with UC compared with that in the colons of healthy controls. In summary, EM-induced reduction in the colonic expression of NPY may be associated with a decrease in hippocampal NPY and anxiety- and depression-like behavior in mice.
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Affiliation(s)
- Min-Kyung Joo
- Department of Biomedical and Pharmaceutical Sciences, Kyung Hee University, Seoul, Korea
- College of Pharmacy, Kyung Hee University, Seoul, Korea
| | - Jae-Won Lee
- Department of Biomedical and Pharmaceutical Sciences, Kyung Hee University, Seoul, Korea
- College of Pharmacy, Kyung Hee University, Seoul, Korea
| | - Jeong-Hwa Woo
- College of Pharmacy, Kyung Hee University, Seoul, Korea
| | - Hyo-Jong Kim
- Department of Internal Medicine, School of Medicine, Kyung Hee University, Seoul, Korea
| | - Dong-Hyun Kim
- Department of Biomedical and Pharmaceutical Sciences, Kyung Hee University, Seoul, Korea
- College of Pharmacy, Kyung Hee University, Seoul, Korea
| | - Jung-Hye Choi
- Department of Biomedical and Pharmaceutical Sciences, Kyung Hee University, Seoul, Korea
- College of Pharmacy, Kyung Hee University, Seoul, Korea
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19
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Liu Y, Yang W, Xue J, Chen J, Liu S, Zhang S, Zhang X, Gu X, Dong Y, Qiu P. Neuroinflammation: The central enabler of postoperative cognitive dysfunction. Biomed Pharmacother 2023; 167:115582. [PMID: 37748409 DOI: 10.1016/j.biopha.2023.115582] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 09/21/2023] [Accepted: 09/22/2023] [Indexed: 09/27/2023] Open
Abstract
The proportion of advanced age patients undergoing surgical procedures is on the rise owing to advancements in surgical and anesthesia technologies as well as an overall aging population. As a complication of anesthesia and surgery, older patients frequently suffer from postoperative cognitive dysfunction (POCD), which may persist for weeks, months or even longer. POCD is a complex pathological process involving multiple pathogenic factors, and its mechanism is yet unclear. Potential theories include inflammation, deposition of pathogenic proteins, imbalance of neurotransmitters, and chronic stress. The identification, prevention, and treatment of POCD are still in the exploratory stages owing to the absence of standardized diagnostic criteria. Undoubtedly, comprehending the development of POCD remains crucial in overcoming the illness. Neuroinflammation is the leading hypothesis and a crucial component of the pathological network of POCD and may have complex interactions with other mechanisms. In this review, we discuss the possible ways in which surgery and anesthesia cause neuroinflammation and investigate the connection between neuroinflammation and the development of POCD. Understanding these mechanisms may likely ensure that future treatment options of POCD are more effective.
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Affiliation(s)
- Yang Liu
- Department of Oncology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning province, China
| | - Wei Yang
- Department of Infectious Disease, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning province, China
| | - Jinqi Xue
- Department of Oncology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning province, China
| | - Juntong Chen
- Zhejiang University School of Medicine, Hangzhou 311121, Zhejiang province, China
| | - Shiqing Liu
- Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Shijie Zhang
- Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Xiaohui Zhang
- Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Xi Gu
- Department of Oncology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning province, China.
| | - Youjing Dong
- Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China.
| | - Peng Qiu
- Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China.
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20
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Kim J, Kim Y, La J, Park WH, Kim HJ, Park SH, Ku KB, Kang BH, Lim J, Kwon MS, Lee HK. Supplementation with a high-glucose drink stimulates anti-tumor immune responses to glioblastoma via gut microbiota modulation. Cell Rep 2023; 42:113220. [PMID: 37804509 DOI: 10.1016/j.celrep.2023.113220] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 08/22/2023] [Accepted: 09/20/2023] [Indexed: 10/09/2023] Open
Abstract
A high-sugar diet induces lifestyle-associated metabolic diseases, such as obesity and diabetes, which may underlie the pro-tumor effects of a high-sugar diet. We supply GL261 syngeneic glioblastoma (GBM) mice with a short-term high-glucose drink (HGD) and find an increased survival rate with no evidence of metabolic disease. Modulation of the gut microbiota through HGD supplementation is critical for enhancing the anti-tumor immune response. Single-cell RNA sequencing shows that gut microbiota modulation by HGD supplementation increases the T cell-mediated anti-tumor immune response in GBM mice. We find that the cytotoxic CD4+ T cell population in GBM is increased due to synergy with anti-programmed cell death protein 1 (anti-PD-1) immune checkpoint inhibitors, but this effect depends upon HGD supplementation. Thus, we determine that HGD supplementation enhances anti-tumor immune responses in GBM mice through gut microbiota modulation and suggest that the role of HGD supplementation in GBM should be re-examined.
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Affiliation(s)
- Jaeho Kim
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea
| | - Yumin Kim
- Department of Biological Sciences, KAIST, Daejeon 34141, Republic of Korea
| | - Jeongwoo La
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea
| | - Won Hyung Park
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea
| | - Hyun-Jin Kim
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea
| | - Sang Hee Park
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea
| | - Keun Bon Ku
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea; Department of Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea
| | - Byeong Hoon Kang
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea
| | - Juhee Lim
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea
| | - Myoung Seung Kwon
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea
| | - Heung Kyu Lee
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea; Department of Biological Sciences, KAIST, Daejeon 34141, Republic of Korea.
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21
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Wang Q, Yang Q, Liu X. The microbiota-gut-brain axis and neurodevelopmental disorders. Protein Cell 2023; 14:762-775. [PMID: 37166201 PMCID: PMC10599644 DOI: 10.1093/procel/pwad026] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Accepted: 04/27/2023] [Indexed: 05/12/2023] Open
Abstract
The gut microbiota has been found to interact with the brain through the microbiota-gut-brain axis, regulating various physiological processes. In recent years, the impacts of the gut microbiota on neurodevelopment through this axis have been increasingly appreciated. The gut microbiota is commonly considered to regulate neurodevelopment through three pathways, the immune pathway, the neuronal pathway, and the endocrine/systemic pathway, with overlaps and crosstalks in between. Accumulating studies have identified the role of the microbiota-gut-brain axis in neurodevelopmental disorders including autism spectrum disorder, attention deficit hyperactivity disorder, and Rett Syndrome. Numerous researchers have examined the physiological and pathophysiological mechanisms influenced by the gut microbiota in neurodevelopmental disorders (NDDs). This review aims to provide a comprehensive overview of advancements in research pertaining to the microbiota-gut-brain axis in NDDs. Furthermore, we analyzed both the current state of research progress and discuss future perspectives in this field.
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Affiliation(s)
- Qinwen Wang
- State Key Laboratory of Reproductive Medicine and offspring Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China
- Department of Pathogen Biology-Microbiology Division, Key Laboratory of Pathogen of Jiangsu Province Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing 211166, China
| | - Qianyue Yang
- State Key Laboratory of Reproductive Medicine and offspring Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China
- Department of Pathogen Biology-Microbiology Division, Key Laboratory of Pathogen of Jiangsu Province Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing 211166, China
| | - Xingyin Liu
- State Key Laboratory of Reproductive Medicine and offspring Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China
- Department of Pathogen Biology-Microbiology Division, Key Laboratory of Pathogen of Jiangsu Province Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing 211166, China
- The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Nanjing 211166, China
- Department of Microbiota Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 211166, China
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22
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Xu W, Rustenhoven J, Nelson CA, Dykstra T, Ferreiro A, Papadopoulos Z, Burnham CAD, Dantas G, Fremont DH, Kipnis J. A novel immune modulator IM33 mediates a glia-gut-neuronal axis that controls lifespan. Neuron 2023; 111:3244-3254.e8. [PMID: 37582366 PMCID: PMC10592285 DOI: 10.1016/j.neuron.2023.07.010] [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: 11/18/2022] [Revised: 05/19/2023] [Accepted: 07/18/2023] [Indexed: 08/17/2023]
Abstract
Aging is a complex process involving various systems and behavioral changes. Altered immune regulation, dysbiosis, oxidative stress, and sleep decline are common features of aging, but their interconnection is poorly understood. Using Drosophila, we discover that IM33, a novel immune modulator, and its mammalian homolog, secretory leukocyte protease inhibitor (SLPI), are upregulated in old flies and old mice, respectively. Knockdown of IM33 in glia elevates the gut reactive oxygen species (ROS) level and alters gut microbiota composition, including increased Lactiplantibacillus plantarum abundance, leading to a shortened lifespan. Additionally, dysbiosis induces sleep fragmentation through the activation of insulin-producing cells in the brain, which is mediated by the binding of Lactiplantibacillus plantarum-produced DAP-type peptidoglycan to the peptidoglycan recognition protein LE (PGRP-LE) receptor. Therefore, IM33 plays a role in the glia-microbiota-neuronal axis, connecting neuroinflammation, dysbiosis, and sleep decline during aging. Identifying molecular mediators of these processes could lead to the development of innovative strategies for extending lifespan.
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Affiliation(s)
- Wangchao Xu
- Brain Immunology and Glia (BIG) Center, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Department of Pathology and Immunology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA.
| | - Justin Rustenhoven
- Brain Immunology and Glia (BIG) Center, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Department of Pathology and Immunology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Department of Pharmacology and Clinical Pharmacology, The University of Auckland, Auckland, New Zealand; Centre for Brain Research, The University of Auckland, Auckland, New Zealand
| | - Christopher A Nelson
- Department of Pathology and Immunology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA
| | - Taitea Dykstra
- Brain Immunology and Glia (BIG) Center, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Department of Pathology and Immunology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA
| | - Aura Ferreiro
- The Edison Family Center for Genome Sciences and Systems Biology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, USA
| | - Zachary Papadopoulos
- Brain Immunology and Glia (BIG) Center, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Department of Pathology and Immunology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Neuroscience Graduate Program, School of Medicine, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA
| | - Carey-Ann D Burnham
- Department of Pathology and Immunology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA
| | - Gautam Dantas
- Department of Pathology and Immunology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; The Edison Family Center for Genome Sciences and Systems Biology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, USA; Department of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA
| | - Daved H Fremont
- Department of Pathology and Immunology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Department of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA; Department of Biochemistry & Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA
| | - Jonathan Kipnis
- Brain Immunology and Glia (BIG) Center, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Department of Pathology and Immunology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Neuroscience Graduate Program, School of Medicine, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA.
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23
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Plummer AM, Matos YL, Lin HC, Ryman SG, Birg A, Quinn DK, Parada AN, Vakhtin AA. Gut-brain pathogenesis of post-acute COVID-19 neurocognitive symptoms. Front Neurosci 2023; 17:1232480. [PMID: 37841680 PMCID: PMC10568482 DOI: 10.3389/fnins.2023.1232480] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Accepted: 09/01/2023] [Indexed: 10/17/2023] Open
Abstract
Approximately one third of non-hospitalized coronavirus disease of 2019 (COVID-19) patients report chronic symptoms after recovering from the acute stage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Some of the most persistent and common complaints of this post-acute COVID-19 syndrome (PACS) are cognitive in nature, described subjectively as "brain fog" and also objectively measured as deficits in executive function, working memory, attention, and processing speed. The mechanisms of these chronic cognitive sequelae are currently not understood. SARS-CoV-2 inflicts damage to cerebral blood vessels and the intestinal wall by binding to angiotensin-converting enzyme 2 (ACE2) receptors and also by evoking production of high levels of systemic cytokines, compromising the brain's neurovascular unit, degrading the intestinal barrier, and potentially increasing the permeability of both to harmful substances. Such substances are hypothesized to be produced in the gut by pathogenic microbiota that, given the profound effects COVID-19 has on the gastrointestinal system, may fourish as a result of intestinal post-COVID-19 dysbiosis. COVID-19 may therefore create a scenario in which neurotoxic and neuroinflammatory substances readily proliferate from the gut lumen and encounter a weakened neurovascular unit, gaining access to the brain and subsequently producing cognitive deficits. Here, we review this proposed PACS pathogenesis along the gut-brain axis, while also identifying specific methodologies that are currently available to experimentally measure each individual component of the model.
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Affiliation(s)
- Allison M. Plummer
- School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, United States
| | - Yvette L. Matos
- The Mind Research Network/Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM, United States
| | - Henry C. Lin
- Division of Gastroenterology and Hepatology, University of New Mexico, Albuquerque, NM, United States
- Section of Gastroenterology, New Mexico Veterans Affairs Health Care System, Albuquerque, NM, United States
| | - Sephira G. Ryman
- The Mind Research Network/Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM, United States
- Nene and Jamie Koch Comprehensive Movement Disorder Center, Department of Neurology, University of New Mexico, Albuquerque, NM, United States
| | - Aleksandr Birg
- Division of Gastroenterology and Hepatology, University of New Mexico, Albuquerque, NM, United States
- Section of Gastroenterology, New Mexico Veterans Affairs Health Care System, Albuquerque, NM, United States
| | - Davin K. Quinn
- Department of Psychiatry and Behavioral Sciences, University of New Mexico School of Medicine, Albuquerque, NM, United States
| | - Alisha N. Parada
- Division of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM, United States
| | - Andrei A. Vakhtin
- The Mind Research Network/Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM, United States
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24
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He Z, Liu R, Wang M, Wang Q, Zheng J, Ding J, Wen J, Fahey AG, Zhao G. Combined effect of microbially derived cecal SCFA and host genetics on feed efficiency in broiler chickens. MICROBIOME 2023; 11:198. [PMID: 37653442 PMCID: PMC10472625 DOI: 10.1186/s40168-023-01627-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Accepted: 07/18/2023] [Indexed: 09/02/2023]
Abstract
BACKGROUND Improving feed efficiency is the most important goal for modern animal production. The regulatory mechanisms of controlling feed efficiency traits are extremely complex and include the functions related to host genetics and gut microbiota. Short-chain fatty acids (SCFAs), as significant metabolites of microbiota, could be used to refine the combined effect of host genetics and gut microbiota. However, the association of SCFAs with the gut microbiota and host genetics for regulating feed efficiency is far from understood. RESULTS In this study, 464 broilers were housed for RFI measuring and examining the host genome sequence. And 300 broilers were examined for cecal microbial data and SCFA concentration. Genome-wide association studies (GWAS) showed that four out of seven SCFAs had significant associations with genome variants. One locus (chr4: 29414391-29417189), located near or inside the genes MAML3, SETD7, and MGST2, was significantly associated with propionate and had a modest effect on feed efficiency traits and the microbiota. The genetic effect of the top SNP explained 8.43% variance of propionate. Individuals with genotype AA had significantly different propionate concentrations (0.074 vs. 0.131 μg/mg), feed efficiency (FCR: 1.658 vs. 1.685), and relative abundance of 14 taxa compared to those with the GG genotype. Christensenellaceae and Christensenellaceae_R-7_group were associated with feed efficiency, propionate concentration, the top SNP genotypes, and lipid metabolism. Individuals with a higher cecal abundance of these taxa showed better feed efficiency and lower concentrations of caecal SCFAs. CONCLUSION Our study provides strong evidence of the pathway that host genome variants affect the cecal SCFA by influencing caecal microbiota and then regulating feed efficiency. The cecal taxa Christensenellaceae and Christensenellaceae_R-7_group were identified as representative taxa contributing to the combined effect of host genetics and SCFAs on chicken feed efficiency. These findings provided strong evidence of the combined effect of host genetics and gut microbial SCFAs in regulating feed efficiency traits. Video Abstract.
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Affiliation(s)
- Zhengxiao He
- State Key Laboratory of Animal Nutrition; Key Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
- School of Agriculture and Food Science, University College Dublin, Dublin, Ireland
| | - Ranran Liu
- State Key Laboratory of Animal Nutrition; Key Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
| | - Mengjie Wang
- State Key Laboratory of Animal Nutrition; Key Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
| | - Qiao Wang
- State Key Laboratory of Animal Nutrition; Key Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
| | - Jumei Zheng
- State Key Laboratory of Animal Nutrition; Key Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
| | - Jiqiang Ding
- State Key Laboratory of Animal Nutrition; Key Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
| | - Jie Wen
- State Key Laboratory of Animal Nutrition; Key Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
| | - Alan G Fahey
- School of Agriculture and Food Science, University College Dublin, Dublin, Ireland.
| | - Guiping Zhao
- State Key Laboratory of Animal Nutrition; Key Laboratory of Animal (Poultry) Genetics Breeding and Reproduction, Ministry of Agriculture, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.
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25
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Li L, Yang J, Liu T, Shi Y. Role of the gut-microbiota-metabolite-brain axis in the pathogenesis of preterm brain injury. Biomed Pharmacother 2023; 165:115243. [PMID: 37517290 DOI: 10.1016/j.biopha.2023.115243] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 07/09/2023] [Accepted: 07/25/2023] [Indexed: 08/01/2023] Open
Abstract
Brain injury, a common complication in preterm infants, includes the destruction of the key structural and functional connections of the brain and causes neurodevelopmental disorders; it has high morbidity and mortality rates. The exact mechanism underlying brain injury in preterm infants is unclear. Intestinal flora plays a vital role in brain development and the maturation of the immune system in infants; however, detailed understanding of the gut microbiota-metabolite-brain axis in preterm infants is lacking. In this review, we summarise the key mechanisms by which the intestinal microbiota contribute to neurodevelopment and brain injury in preterm infants, with special emphasis on the influence of microorganisms and their metabolites on the regulation of neurocognitive development and neurodevelopmental risks related to preterm birth, infection and neonatal necrotising enterocolitis (NEC). This review provides support for the development and application of novel therapeutic strategies, including probiotics, prebiotics, synbiotics, and faecal bacteria transplantation targeting at brain injury in preterm infants.
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Affiliation(s)
- Ling Li
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 110004, China.
| | - Jiahui Yang
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 110004, China.
| | - Tianjing Liu
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 110004, China.
| | - Yongyan Shi
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 110004, China.
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26
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Joo MK, Ma X, Yoo JW, Shin YJ, Kim HJ, Kim DH. Patient-derived Enterococcus mundtii and its capsular polysaccharides cause depression through the downregulation of NF-κB-involved serotonin and BDNF expression. Microbes Infect 2023; 25:105116. [PMID: 36758891 DOI: 10.1016/j.micinf.2023.105116] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2022] [Revised: 12/09/2022] [Accepted: 01/28/2023] [Indexed: 02/10/2023]
Abstract
The genus Enterococcus is commonly overpopulated in patients with depression compared to healthy control in the feces. Therefore, we isolated Enterococcus faecalis, Enterococcus durans, Enterococcus gallinarum, Enterococcus faecium, and Enterococcus mundtii from the feces of patients with comorbid inflammatory bowel disease with depression and examined their roles in depression in vivo and in vitro. Of these Enterococci, E. mundtii NK1516 most potently induced NF-κB-activated TNF-α and IL-6 expression in BV2 microglia cells. NK1516 also caused the most potent depression-like behaviors in the absence of sickness behaviors, neuroinflammation, downregulated brain-derived neurotrophic factor (BDNF), and serotonin (5-HT) levels in the hippocampus of mice. Furthermore, E. mundtii NK1516 reduced the mRNA expression of Htr1a in the hippocampus. Its capsular polysaccharide (CP), but not cytoplasmic components, also caused depression-like behaviors and reduced BDNF and serotonin levels in the hippocampus. Conversely, this was not observed with E. mundtii ATCC882, a well-known probiotic, or its CP. Orally gavaged fluorescence isothiocyanate (FITC)-conjugated NK1516 CP was detected in the hippocampus of mice. The NK1516 genome exhibited unique CP biosynthesis-related genes (capD, wbjC, WecB, vioB), unlike that of ATCC882. These findings suggest that E. mundtii may be a risk factor for depression.
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Affiliation(s)
- Min-Kyung Joo
- Neurobiota Research Center and Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Seoul 02447, South Korea.
| | - Xiaoyang Ma
- Neurobiota Research Center and Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Seoul 02447, South Korea.
| | - Jong-Wook Yoo
- Neurobiota Research Center and Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Seoul 02447, South Korea.
| | - Yoon-Jung Shin
- Neurobiota Research Center and Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Seoul 02447, South Korea.
| | - Hyo-Jong Kim
- Department of Internal Medicine, Kyung Hee University School of Medicine, Kyung Hee University, Seoul 02447, South Korea.
| | - Dong-Hyun Kim
- Neurobiota Research Center and Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Seoul 02447, South Korea.
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27
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Mann B, Crawford JC, Reddy K, Lott J, Youn YH, Gao G, Guy C, Chou CH, Darnell D, Trivedi S, Bomme P, Loughran AJ, Thomas PG, Han YG, Tuomanen EI. Bacterial TLR2/6 Ligands Block Ciliogenesis, Derepress Hedgehog Signaling, and Expand the Neocortex. mBio 2023; 14:e0051023. [PMID: 37052506 PMCID: PMC10294647 DOI: 10.1128/mbio.00510-23] [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: 02/27/2023] [Accepted: 03/21/2023] [Indexed: 04/14/2023] Open
Abstract
Microbial components have a range of direct effects on the fetal brain. However, little is known about the cellular targets and molecular mechanisms that mediate these effects. Neural progenitor cells (NPCs) control the size and architecture of the brain and understanding the mechanisms regulating NPCs is crucial to understanding brain developmental disorders. We identify ventricular radial glia (vRG), the primary NPC, as the target of bacterial cell wall (BCW) generated during the antibiotic treatment of maternal pneumonia. BCW enhanced proliferative potential of vRGs by shortening the cell cycle and increasing self-renewal. Expanded vRGs propagated to increase neuronal output in all cortical layers. Remarkably, Toll-like receptor 2 (TLR2), which recognizes BCW, localized at the base of primary cilia in vRGs and the BCW-TLR2 interaction suppressed ciliogenesis leading to derepression of Hedgehog (HH) signaling and expansion of vRGs. We also show that TLR6 is an essential partner of TLR2 in this process. Surprisingly, TLR6 alone was required to set the number of cortical neurons under healthy conditions. These findings suggest that an endogenous signal from TLRs suppresses cortical expansion during normal development of the neocortex and that BCW antagonizes that signal through the TLR2/cilia/HH signaling axis changing brain structure and function. IMPORTANCE Fetal brain development in early gestation can be impacted by transplacental infection, altered metabolites from the maternal microbiome, or maternal immune activation. It is less well understood how maternal microbial subcomponents that cross the placenta, such as bacterial cell wall (BCW), directly interact with fetal neural progenitors and neurons and affect development. This scenario plays out in the clinic when BCW debris released during antibiotic therapy of maternal infection traffics to the fetal brain. This study identifies the direct interaction of BCW with TLR2/6 present on the primary cilium, the signaling hub on fetal neural progenitor cells (NPCs). NPCs control the size and architecture of the brain and understanding the mechanisms regulating NPCs is crucial to understanding brain developmental disorders. Within a window of vulnerability before the appearance of fetal immune cells, the BCW-TLR2/6 interaction results in the inhibition of ciliogenesis, derepression of Sonic Hedgehog signaling, excess proliferation of neural progenitors, and abnormal cortical architecture. In the first example of TLR signaling linked to Sonic Hedgehog, BCW/TLR2/6 appears to act during fetal brain morphogenesis to play a role in setting the total cell number in the neocortex.
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Affiliation(s)
- Beth Mann
- Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
| | - Jeremy Chase Crawford
- Department of Immunology, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
| | - Kavya Reddy
- Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
| | - Josi Lott
- Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
| | - Yong Ha Youn
- Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
| | - Geli Gao
- Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
| | - Cliff Guy
- Department of Immunology, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
| | - Ching-Heng Chou
- Department of Immunology, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
| | - Daniel Darnell
- Hartwell Center for Bioinformatics and Biotechnology, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
| | - Sanchit Trivedi
- Hartwell Center for Bioinformatics and Biotechnology, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
| | - Perrine Bomme
- Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
| | - Allister J. Loughran
- Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
| | - Paul G. Thomas
- Department of Immunology, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
| | - Young-Goo Han
- Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
| | - Elaine I. Tuomanen
- Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
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28
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Hitache Z, Al-Dalali S, Pei H, Cao X. Review of the Health Benefits of Cereals and Pseudocereals on Human Gut Microbiota. FOOD BIOPROCESS TECH 2023. [DOI: 10.1007/s11947-023-03069-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/05/2023]
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29
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Damiani F, Cornuti S, Tognini P. The gut-brain connection: Exploring the influence of the gut microbiota on neuroplasticity and neurodevelopmental disorders. Neuropharmacology 2023; 231:109491. [PMID: 36924923 DOI: 10.1016/j.neuropharm.2023.109491] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Revised: 02/22/2023] [Accepted: 03/05/2023] [Indexed: 03/17/2023]
Abstract
Neuroplasticity refers to the ability of brain circuits to reorganize and change the properties of the network, resulting in alterations in brain function and behavior. It is traditionally believed that neuroplasticity is influenced by external stimuli, learning, and experience. Intriguingly, there is new evidence suggesting that endogenous signals from the body's periphery may play a role. The gut microbiota, a diverse community of microorganisms living in harmony with their host, may be able to influence plasticity through its modulation of the gut-brain axis. Interestingly, the maturation of the gut microbiota coincides with critical periods of neurodevelopment, during which neural circuits are highly plastic and potentially vulnerable. As such, dysbiosis (an imbalance in the gut microbiota composition) during early life may contribute to the disruption of normal developmental trajectories, leading to neurodevelopmental disorders. This review aims to examine the ways in which the gut microbiota can affect neuroplasticity. It will also discuss recent research linking gastrointestinal issues and bacterial dysbiosis to various neurodevelopmental disorders and their potential impact on neurological outcomes.
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Affiliation(s)
| | - Sara Cornuti
- Laboratory of Biology, Scuola Normale Superiore, Pisa, Italy
| | - Paola Tognini
- Laboratory of Biology, Scuola Normale Superiore, Pisa, Italy; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
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30
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Kwan JMC, Qiao Y. Mechanistic Insights into the Activities of Major Families of Enzymes in Bacterial Peptidoglycan Assembly and Breakdown. Chembiochem 2023; 24:e202200693. [PMID: 36715567 DOI: 10.1002/cbic.202200693] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Revised: 01/28/2023] [Accepted: 01/30/2023] [Indexed: 01/31/2023]
Abstract
Serving as an exoskeletal scaffold, peptidoglycan is a polymeric macromolecule that is essential and conserved across all bacteria, yet is absent in mammalian cells; this has made bacterial peptidoglycan a well-established excellent antibiotic target. In addition, soluble peptidoglycan fragments derived from bacteria are increasingly recognised as key signalling molecules in mediating diverse intra- and inter-species communication in nature, including in gut microbiota-host crosstalk. Each bacterial species encodes multiple redundant enzymes for key enzymatic activities involved in peptidoglycan assembly and breakdown. In this review, we discuss recent findings on the biochemical activities of major peptidoglycan enzymes, including peptidoglycan glycosyltransferases (PGT) and transpeptidases (TPs) in the final stage of peptidoglycan assembly, as well as peptidoglycan glycosidases, lytic transglycosylase (LTs), amidases, endopeptidases (EPs) and carboxypeptidases (CPs) in peptidoglycan turnover and metabolism. Biochemical characterisation of these enzymes provides valuable insights into their substrate specificity, regulation mechanisms and potential modes of inhibition.
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Affiliation(s)
- Jeric Mun Chung Kwan
- School of Chemistry, Chemical Engineering and Biotechnology (CCEB), 21 Nanyang Link, Singapore, 637371, Singapore.,LKC School of Medicine, Nanyang Technological University (NTU) Singapore, 11 Mandalay Road, Singapore, Singapore, 208232, Singapore
| | - Yuan Qiao
- School of Chemistry, Chemical Engineering and Biotechnology (CCEB), Nanyang Technological University (NTU), Singapore, 21 Nanyang Link, Singapore, 637371, Singapore
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Lai Y, Dhingra R, Zhang Z, Ball LM, Zylka MJ, Lu K. Toward Elucidating the Human Gut Microbiota-Brain Axis: Molecules, Biochemistry, and Implications for Health and Diseases. Biochemistry 2022; 61:2806-2821. [PMID: 34910469 PMCID: PMC10857864 DOI: 10.1021/acs.biochem.1c00656] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
In recent years, a substantial amount of data have supported an active role of gut microbiota in mediating mammalian brain function and health. Mining gut microbiota and their metabolites for neuroprotection is enticing but requires that the fundamental biochemical details underlying such microbiota-brain crosstalk be deciphered. While a neuronal gut-brain axis (through the vagus nerve) is not disputable, accumulating studies also point to a humoral route (via blood/lymphatic circulation) by which innumerable microbial molecular cues translocate from local gut epithelia to circulation with potentials to further cross the blood-brain barrier and reach the brain. In this Perspective, we review a realm of gut microbial molecules to evaluate their fate, function, and neuroactivities in vivo as mediated by microbiota. We turn to seminal studies of neurophysiology and neurologic disease models for the elucidation of biochemical pathways that link microbiota to gut-brain signaling. In addition, we discuss opportunities and challenges for advancing the microbiota-brain axis field while calling for high-throughput discovery of microbial molecules and studies for resolving the interspecies, interorgan, and interclass interaction among these neuroactive microbial molecules.
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Affiliation(s)
- Yunjia Lai
- Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Campus Box 7431, Chapel Hill, North Carolina 27599, United States
| | - Radhika Dhingra
- Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Campus Box 7431, Chapel Hill, North Carolina 27599, United States
- Institute of Environmental Health Solutions, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
| | - Zhenfa Zhang
- Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Campus Box 7431, Chapel Hill, North Carolina 27599, United States
| | - Louise M Ball
- Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Campus Box 7431, Chapel Hill, North Carolina 27599, United States
| | - Mark J Zylka
- UNC Neuroscience Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
- Carolina Institute for Developmental Disabilities, The University of North Carolina at Chapel Hill, Carrboro, North Carolina 27510, United States
- Department of Cell and Molecular Physiology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
| | - Kun Lu
- Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Campus Box 7431, Chapel Hill, North Carolina 27599, United States
- Curriculum in Toxicology and Environmental Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
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Han W, Wang N, Han M, Ban M, Sun T, Xu J. Reviewing the role of gut microbiota in the pathogenesis of depression and exploring new therapeutic options. Front Neurosci 2022; 16:1029495. [PMID: 36570854 PMCID: PMC9772619 DOI: 10.3389/fnins.2022.1029495] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Accepted: 11/24/2022] [Indexed: 12/14/2022] Open
Abstract
The relationship between gut microbiota (GM) and mental health is one of the focuses of psychobiology research. In recent years, the microbial-gut-brain axis (MGBA) concept has gradually formed about this bidirectional communication between gut and brain. But how the GM is involved in regulating brain function and how they affect emotional disorders these mechanisms are tenuous and limited to animal research, and often controversial. Therefore, in this review, we attempt to summarize and categorize the latest advances in current research on the mechanisms of GM and depression to provide valid information for future diagnoses and therapy of mental disorders. Finally, we introduced some antidepressant regimens that can help restore gut dysbiosis, including classic antidepressants, Chinese materia medica (CMM), diet, and exogenous strains. These studies provide further insight into GM's role and potential pathways in emotion-related diseases, which holds essential possible clinical outcomes for people with depression or related psychiatric disorders. Future research should focus on clarifying the causal role of GM in disease and developing microbial targets, applying these findings to the prevention and treatment of depression.
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Affiliation(s)
- Wenjie Han
- Department of Breast Medicine, Liaoning Cancer Hospital, Cancer Hospital of China Medical University, Shenyang, China,Department of Pharmacology, Liaoning Cancer Hospital, Cancer Hospital of China Medical University, Shenyang, China
| | - Na Wang
- Department of Breast Medicine, Liaoning Cancer Hospital, Cancer Hospital of China Medical University, Shenyang, China,Department of Pharmacology, Liaoning Cancer Hospital, Cancer Hospital of China Medical University, Shenyang, China
| | - Mengzhen Han
- Department of Breast Medicine, Liaoning Cancer Hospital, Cancer Hospital of China Medical University, Shenyang, China,Department of Pharmacology, Liaoning Cancer Hospital, Cancer Hospital of China Medical University, Shenyang, China
| | - Meng Ban
- Liaoning Microhealth Biotechnology Co., Ltd., Shenyang, China
| | - Tao Sun
- Department of Breast Medicine, Liaoning Cancer Hospital, Cancer Hospital of China Medical University, Shenyang, China,Department of Breast Medicine, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital, Shenyang, China
| | - Junnan Xu
- Department of Breast Medicine, Liaoning Cancer Hospital, Cancer Hospital of China Medical University, Shenyang, China,Department of Pharmacology, Liaoning Cancer Hospital, Cancer Hospital of China Medical University, Shenyang, China,Department of Breast Medicine, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital, Shenyang, China,*Correspondence: Junnan Xu,
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Alloo J, Leleu I, Grangette C, Pied S. Parasite infections, neuroinflammation, and potential contributions of gut microbiota. Front Immunol 2022; 13:1024998. [PMID: 36569929 PMCID: PMC9772015 DOI: 10.3389/fimmu.2022.1024998] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Accepted: 11/21/2022] [Indexed: 12/12/2022] Open
Abstract
Many parasitic diseases (including cerebral malaria, human African trypanosomiasis, cerebral toxoplasmosis, neurocysticercosis and neuroschistosomiasis) feature acute or chronic brain inflammation processes, which are often associated with deregulation of glial cell activity and disruption of the brain blood barrier's intactness. The inflammatory responses of astrocytes and microglia during parasite infection are strongly influenced by a variety of environmental factors. Although it has recently been shown that the gut microbiota influences the physiology and immunomodulation of the central nervous system in neurodegenerative diseases like Alzheimer's disease and Parkinson's, the putative link in parasite-induced neuroinflammatory diseases has not been well characterized. Likewise, the central nervous system can influence the gut microbiota. In parasite infections, the gut microbiota is strongly perturbed and might influence the severity of the central nervous system inflammation response through changes in the production of bacterial metabolites. Here, we review the roles of astrocytes and microglial cells in the neuropathophysiological processes induced by parasite infections and their possible regulation by the gut microbiota.
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Affiliation(s)
| | | | | | - Sylviane Pied
- Center for Infection and Immunity of Lille-CIIL, Centre National de la Recherche Scientifique-CNRS UMR 9017-Institut National de la Recherche Scientifique et Médicale-Inserm U1019, Institut Pasteur de Lille, Univ. Lille, Lille, France
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Ajeeb TT, Gonzalez E, Solomons NW, Koski KG. Human milk microbial species are associated with infant head-circumference during early and late lactation in Guatemalan mother-infant dyads. Front Microbiol 2022; 13:908845. [PMID: 36466698 PMCID: PMC9709448 DOI: 10.3389/fmicb.2022.908845] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 10/10/2022] [Indexed: 08/27/2023] Open
Abstract
Human milk contains abundant commensal bacteria that colonize and establish the infant's gut microbiome but the association between the milk microbiome and head circumference during infancy has not been explored. For this cross-sectional study, head-circumference-for-age-z-scores (HCAZ) of vaginally delivered breastfed infants were collected from 62 unrelated Mam-Mayan mothers living in eight remote rural communities in the Western Highlands of Guatemala during two stages of lactation, 'early' (6-46 days postpartum, n = 29) or 'late' (109-184 days postpartum, n = 33). At each stage of lactation, infants were divided into HCAZ ≥ -1 SD (early: n = 18; late: n = 14) and HCAZ < -1 SD (early: n = 11; late: n = 19). Milk microbiome communities were assessed using 16S ribosomal RNA gene sequencing and DESeq2 was used to compare the differential abundance (DA) of human milk microbiota with infant HCAZ subgroups at both stages of lactations. A total of 503 ESVs annotated 256 putative species across the 64 human milk samples. Alpha-diversity using Chao index uncovered a difference in microbial community richness between HCAZ ≥ -1 SD and HCAZ < -1 SD groups at late lactation (p = 0.045) but not at early lactation. In contrast, Canonical Analysis of Principal Coordinates identified significant differences between HCAZ ≥ -1 SD and HCAZ < -1 SD at both stages of lactation (p = 0.003); moreover, 26 milk microbial taxa differed in relative abundance (FDR < 0.05) between HCAZ ≥ -1 SD and HCAZ < -1 SD, with 13 differentially abundant at each lactation stage. Most species in the HCAZ ≥ -1 SD group were Streptococcus species from the Firmicutes phylum which are considered human colonizers associated with human milk whereas the HCAZ < -1 SD group at late lactation had more differentially abundant taxa associated with environmentally and 'potentially opportunistic' species belonging to the Actinobacteria genus. These findings suggest possible associations between brain growth of breastfed infants and the milk microbiome during lactation. Importantly, these data provide the first evidence of cross talk between the human milk microbiome and the infant brain that requires further investigation.
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Affiliation(s)
- Tamara T. Ajeeb
- School of Human Nutrition, McGill University, Montréal, QC, Canada
- Department of Clinical Nutrition, College of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Emmanuel Gonzalez
- Canadian Centre for Computational Genomics, McGill Genome Centre, Montréal, QC, Canada
- Department of Human Genetics, McGill University, Montréal, QC, Canada
- Gerald Bronfman Department of Oncology, McGill University, Montréal, QC, Canada
| | - Noel W. Solomons
- Center for Studies of Sensory Impairment, Aging and Metabolism (CeSSIAM), Guatemala City, Guatemala
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Sun Y, Deng G, Fan J, Feng F, Ge Q, Song Y, Kang X. Associations of air PM 2.5 level with gut microbiota in Chinese Han preschoolers and effect modification by oxytocin receptor gene polymorphism. ENVIRONMENTAL RESEARCH 2022; 214:114123. [PMID: 35995218 DOI: 10.1016/j.envres.2022.114123] [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: 09/26/2021] [Revised: 07/13/2022] [Accepted: 08/13/2022] [Indexed: 06/15/2023]
Abstract
Variations in the single nucleotide polymorphisms (SNPs) of the oxytocin receptors (OXTR) indicate individual differences in stress response, social behavior, and psychopathology, but very few paper mentioned OXTR as part of the mechanism linking exposure to air pollution and poor social interactions. The authors investigated the moderating role of Oxytocin receptor (OXTR) rs53576 polymorphism in the relationship between PM2.5 level and gut microbiota in children, in an attempt to provide some reference for the evidence linking biological and environmental factors to children brain development. The study included 86 healthy Chinese preschoolers (50 males, 36 females) from two campuses of a kindergarten with different air PM2.5 levels. Atmospheric PM2.5 values released by air quality monitoring stations where the two campuses are located were collected for 30 days. The genotypes of OXTR rs53576 were determined by PCR and restriction fragment length polymorphism. The gut microbiota situation was evaluated by determining urinary concentrations of short-chain fatty acids. Urinary levels of cortisone and cortisol were determined to assess the impact of air pollution on the HPA axis. Urinary 2'-Deoxy-7,8-dihydro-8-oxoguanosine and 8-oxo-7,8-dihydroguanosine were measured to evaluate the oxidative stress state. The genotype distribution frequency of rs53576 polymorphism was consistent with Hardy-Weinberg equilibrium. The average urinary concentrations of cortisone, cortisol and 8-OHdG in high pollution campus preschoolers were significantly higher than those in low pollution campus preschoolers, while situations were opposite for acetic acid, propionic acid, isobutyric acid, butyric acid and valeric acid. The interaction between OXTR rs53576 and air pollution had a significant effect on urinary acetic acid. Allele G of rs53576 may be a risk factor for gut microbiota disorder caused by air pollution, and children with GA/GG genotype may be more susceptible than those with AA genotype.
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Affiliation(s)
- Ying Sun
- Key Laboratory of Child Development and Learning Science, Ministry of Education, School of Biological Science & Medical Engineering, Southeast University, Nanjing, 210096, China
| | - Guozhe Deng
- Key Laboratory of Child Development and Learning Science, Ministry of Education, School of Biological Science & Medical Engineering, Southeast University, Nanjing, 210096, China
| | - Jinhui Fan
- Key Laboratory of Child Development and Learning Science, Ministry of Education, School of Biological Science & Medical Engineering, Southeast University, Nanjing, 210096, China
| | - Fulin Feng
- Key Laboratory of Child Development and Learning Science, Ministry of Education, School of Biological Science & Medical Engineering, Southeast University, Nanjing, 210096, China
| | - Qinyu Ge
- State Key Laboratory of Bioelectronics, School of Biological Science & Medical Engineering, Southeast University, Nanjing, 210096, China
| | - Yuan Song
- Division of Child Care, Suzhou Municipal Hospital, Suzhou, 215000, China
| | - Xuejun Kang
- Key Laboratory of Child Development and Learning Science, Ministry of Education, School of Biological Science & Medical Engineering, Southeast University, Nanjing, 210096, China.
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Carrico AW, Cherenack EM, Rubin LH, McIntosh R, Ghanooni D, Chavez JV, Klatt NR, Paul RH. Through the Looking-Glass: Psychoneuroimmunology and the Microbiome-Gut-Brain Axis in the Modern Antiretroviral Therapy Era. Psychosom Med 2022; 84:984-994. [PMID: 36044613 PMCID: PMC9553251 DOI: 10.1097/psy.0000000000001133] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 08/18/2022] [Indexed: 11/26/2022]
Abstract
OBJECTIVE Depression, substance use disorders, and other neuropsychiatric comorbidities are common in people with HIV (PWH), but the underlying mechanisms are not sufficiently understood. HIV-induced damage to the gastrointestinal tract potentiates residual immune dysregulation in PWH receiving effective antiretroviral therapy. However, few studies among PWH have examined the relevance of microbiome-gut-brain axis: bidirectional crosstalk between the gastrointestinal tract, immune system, and central nervous system. METHODS A narrative review was conducted to integrate findings from 159 articles relevant to psychoneuroimmunology (PNI) and microbiome-gut-brain axis research in PWH. RESULTS Early PNI studies demonstrated that neuroendocrine signaling via the hypothalamic-pituitary-adrenal axis and autonomic nervous system could partially account for the associations of psychological factors with clinical HIV progression. This review highlights the need for PNI studies examining the mechanistic relevance of the gut microbiota for residual immune dysregulation, tryptophan catabolism, and oxytocin release as key biological determinants of neuropsychiatric comorbidities in PWH (i.e., body-to-mind pathways). It also underscores the continued relevance of neuroendocrine signaling via the hypothalamic-pituitary-adrenal axis, autonomic nervous system, and oxytocin release in modifying microbiome-gut-brain axis functioning (i.e., mind-to-body pathways). CONCLUSIONS Advancing our understanding of PNI and microbiome-gut-brain axis pathways relevant to depression, substance use disorders, and other neuropsychiatric comorbidities in PWH can guide the development of novel biobehavioral interventions to optimize health outcomes. Recommendations are provided for biobehavioral and neurobehavioral research investigating bidirectional PNI and microbiome-gut-brain axis pathways among PWH in the modern antiretroviral therapy era.
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Affiliation(s)
- Adam W Carrico
- From the Department of Public Health Sciences (Carrico, Cherenack, Ghanooni, Chavez), University of Miami Miller School of Medicine, Miami, Florida; Departments of Neurology (Rubin) and Psychiatry and Behavioral Sciences (Rubin), Johns Hopkins University School of Medicine; Department of Epidemiology (Rubin), Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland; Department of Psychology (McIntosh), University of Miami College of Arts and Sciences, Coral Gables, Florida; Department of Surgery (Klatt), University of Minnesota School of Medicine, Minneapolis, Minnesota; and Department of Psychological Sciences (Paul), University of Missouri St. Louis, St. Louis, Missouri
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Rebeaud J, Peter B, Pot C. How Microbiota-Derived Metabolites Link the Gut to the Brain during Neuroinflammation. Int J Mol Sci 2022; 23:ijms231710128. [PMID: 36077526 PMCID: PMC9456539 DOI: 10.3390/ijms231710128] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Revised: 08/29/2022] [Accepted: 09/01/2022] [Indexed: 11/16/2022] Open
Abstract
Microbiota-derived metabolites are important molecules connecting the gut to the brain. Over the last decade, several studies have highlighted the importance of gut-derived metabolites in the development of multiple sclerosis (MS). Indeed, microbiota-derived metabolites modulate the immune system and affect demyelination. Here, we discuss the current knowledge about microbiota-derived metabolites implications in MS and in different mouse models of neuroinflammation. We focus on the main families of microbial metabolites that play a role during neuroinflammation. A better understanding of the role of those metabolites may lead to new therapeutical avenues to treat neuroinflammatory diseases targeting the gut–brain axis.
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Nandwana V, Nandwana NK, Das Y, Saito M, Panda T, Das S, Almaguel F, Hosmane NS, Das BC. The Role of Microbiome in Brain Development and Neurodegenerative Diseases. Molecules 2022; 27:3402. [PMID: 35684340 PMCID: PMC9182002 DOI: 10.3390/molecules27113402] [Citation(s) in RCA: 54] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Revised: 05/18/2022] [Accepted: 05/23/2022] [Indexed: 12/13/2022] Open
Abstract
Hundreds of billions of commensal microorganisms live in and on our bodies, most of which colonize the gut shortly after birth and stay there for the rest of our lives. In animal models, bidirectional communications between the central nervous system and gut microbiota (Gut-Brain Axis) have been extensively studied, and it is clear that changes in microbiota composition play a vital role in the pathogenesis of various neurodevelopmental and neurodegenerative disorders, such as Autism Spectrum Disorder, Alzheimer's disease, Parkinson's disease, Multiple Sclerosis, Amyotrophic Lateral Sclerosis, anxiety, stress, and so on. The makeup of the microbiome is impacted by a variety of factors, such as genetics, health status, method of delivery, environment, nutrition, and exercise, and the present understanding of the role of gut microbiota and its metabolites in the preservation of brain functioning and the development of the aforementioned neurological illnesses is summarized in this review article. Furthermore, we discuss current breakthroughs in the use of probiotics, prebiotics, and synbiotics to address neurological illnesses. Moreover, we also discussed the role of boron-based diet in memory, boron and microbiome relation, boron as anti-inflammatory agents, and boron in neurodegenerative diseases. In addition, in the coming years, boron reagents will play a significant role to improve dysbiosis and will open new areas for researchers.
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Affiliation(s)
- Varsha Nandwana
- Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY 11201, USA; (V.N.); (N.K.N.); (T.P.); (S.D.)
| | - Nitesh K. Nandwana
- Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY 11201, USA; (V.N.); (N.K.N.); (T.P.); (S.D.)
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Yogarupa Das
- Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA; (Y.D.); (M.S.)
| | - Mariko Saito
- Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA; (Y.D.); (M.S.)
| | - Tanisha Panda
- Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY 11201, USA; (V.N.); (N.K.N.); (T.P.); (S.D.)
| | - Sasmita Das
- Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY 11201, USA; (V.N.); (N.K.N.); (T.P.); (S.D.)
| | - Frankis Almaguel
- School of Medicine, Loma Linda University Health, Loma Linda, CA 92350, USA;
| | - Narayan S. Hosmane
- Department of Chemistry and Biochemistry, Northern Illinois University, DeKalb, IL 60115, USA;
| | - Bhaskar C. Das
- Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY 11201, USA; (V.N.); (N.K.N.); (T.P.); (S.D.)
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
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Li C, Liang Y, Qiao Y. Messengers From the Gut: Gut Microbiota-Derived Metabolites on Host Regulation. Front Microbiol 2022; 13:863407. [PMID: 35531300 PMCID: PMC9073088 DOI: 10.3389/fmicb.2022.863407] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Accepted: 03/28/2022] [Indexed: 12/12/2022] Open
Abstract
The human gut is the natural habitat for trillions of microorganisms, known as the gut microbiota, which play indispensable roles in maintaining host health. Defining the underlying mechanistic basis of the gut microbiota-host interactions has important implications for treating microbiota-associated diseases. At the fundamental level, the gut microbiota encodes a myriad of microbial enzymes that can modify various dietary precursors and host metabolites and synthesize, de novo, unique microbiota-derived metabolites that traverse from the host gut into the blood circulation. These gut microbiota-derived metabolites serve as key effector molecules to elicit host responses. In this review, we summarize recent studies in the understanding of the major classes of gut microbiota-derived metabolites, including short-chain fatty acids (SCFAs), bile acids (BAs) and peptidoglycan fragments (PGNs) on their regulatory effects on host functions. Elucidation of the structures and biological activities of such gut microbiota-derived metabolites in the host represents an exciting and critical area of research.
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40
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Mitrea L, Nemeş SA, Szabo K, Teleky BE, Vodnar DC. Guts Imbalance Imbalances the Brain: A Review of Gut Microbiota Association With Neurological and Psychiatric Disorders. Front Med (Lausanne) 2022; 9:813204. [PMID: 35433746 PMCID: PMC9009523 DOI: 10.3389/fmed.2022.813204] [Citation(s) in RCA: 98] [Impact Index Per Article: 32.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Accepted: 02/23/2022] [Indexed: 12/12/2022] Open
Abstract
Over the last 10 years, there has been a growing interest in the relationship between gut microbiota, the brain, and neurologic-associated affections. As multiple preclinical and clinical research studies highlight gut microbiota’s potential to modulate the general state of health state, it goes without saying that gut microbiota plays a significant role in neurogenesis, mental and cognitive development, emotions, and behaviors, and in the progression of neuropsychiatric illnesses. Gut microbiota produces important biologic products that, through the gut-brain axis, are directly connected with the appearance and evolution of neurological and psychiatric disorders such as depression, anxiety, bipolar disorder, autism, schizophrenia, Parkinson’s disease, Alzheimer’s disease, dementia, multiple sclerosis, and epilepsy. This study reviews recent research on the link between gut microbiota and the brain, and microbiome’s role in shaping the development of the most common neurological and psychiatric illnesses. Moreover, special attention is paid to the use of probiotic formulations as a potential non-invasive therapeutic opportunity for prevention and management of neuropsychiatric-associated affections.
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Affiliation(s)
- Laura Mitrea
- Institute of Life Sciences, University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca, Cluj-Napoca, Romania.,Faculty of Food Science and Technology, University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca, Cluj-Napoca, Romania
| | - Silvia-Amalia Nemeş
- Institute of Life Sciences, University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca, Cluj-Napoca, Romania.,Faculty of Food Science and Technology, University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca, Cluj-Napoca, Romania
| | - Katalin Szabo
- Institute of Life Sciences, University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca, Cluj-Napoca, Romania
| | - Bernadette-Emőke Teleky
- Institute of Life Sciences, University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca, Cluj-Napoca, Romania
| | - Dan-Cristian Vodnar
- Institute of Life Sciences, University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca, Cluj-Napoca, Romania.,Faculty of Food Science and Technology, University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca, Cluj-Napoca, Romania
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41
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Abstract
Peptidoglycans from gut microbiota modulate appetite through hypothalamic circuits.
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Affiliation(s)
- Antoine Adamantidis
- Zentrum für Experimentelle Neurologie, Department of Neurology, Inselspital University Hospital Bern, Bern, Switzerland.,Department of Biomedical Research, University of Bern, Bern, Switzerland
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42
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Ren X, Guo S, Guan X, Kang Y, Liu J, Yang X. Immunological Classification of Tumor Types and Advances in Precision Combination Immunotherapy. Front Immunol 2022; 13:790113. [PMID: 35296094 PMCID: PMC8918549 DOI: 10.3389/fimmu.2022.790113] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Accepted: 01/28/2022] [Indexed: 12/13/2022] Open
Abstract
Immunity is an important physiological function acquired throughout evolution as a defense system against the invasion of pathogenic microorganisms. The immune system also eliminates senescent cells and maintains homeostasis, monitoring cell mutations and preventing tumor development via the action of the immune cells and molecules. Immunotherapy often relies on the interaction of immune cells with the tumor microenvironment (TME). Based on the distribution of the number of lymphocytes (CD3 and CD8) in the center and edge of the tumor and the expression level of B7-H1/PD-L1, tumors are divided into hot tumors, cold tumors, and intermediate tumors (including immune-suppressed and isolated). This review focuses on the advances in precision combination immunotherapy, which has been widely explored in recent years, and its application in different tumor types.
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Affiliation(s)
- Xiufang Ren
- Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Songyi Guo
- Department of Neurosurgery, The First Hospital of China Medical University, Shenyang, China
| | - Xiaojiao Guan
- Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Ye Kang
- Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Jiamei Liu
- Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xianghong Yang
- Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, China
- *Correspondence: Xianghong Yang,
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43
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Sohrabi M, Sahu B, Kaur H, Hasler WA, Prakash A, Combs CK. Gastrointestinal Changes and Alzheimer's Disease. Curr Alzheimer Res 2022; 19:335-350. [PMID: 35718965 PMCID: PMC10497313 DOI: 10.2174/1567205019666220617121255] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 02/08/2022] [Accepted: 03/06/2022] [Indexed: 11/22/2022]
Abstract
BACKGROUND There is a well-described mechanism of communication between the brain and gastrointestinal system in which both organs influence the function of the other. This bi-directional communication suggests that disease in either organ may affect function in the other. OBJECTIVE To assess whether the evidence supports gastrointestinal system inflammatory or degenerative pathophysiology as a characteristic of Alzheimer's disease (AD). METHODS A review of both rodent and human studies implicating gastrointestinal changes in AD was performed. RESULTS Numerous studies indicate that AD changes are not unique to the brain but also occur at various levels of the gastrointestinal tract involving both immune and neuronal changes. In addition, it appears that numerous conditions and diseases affecting regions of the tract may communicate to the brain to influence disease. CONCLUSION Gastrointestinal changes represent an overlooked aspect of AD, representing a more system influence of this disease.
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Affiliation(s)
- Mona Sohrabi
- Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58202-9037, USA
| | - Bijayani Sahu
- Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58202-9037, USA
| | - Harpreet Kaur
- Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58202-9037, USA
| | - Wendie A Hasler
- Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58202-9037, USA
| | - Atish Prakash
- Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58202-9037, USA
| | - Colin K Combs
- Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58202-9037, USA
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44
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Dallabernardina P, Benazzi V, Laman JD, Seeberger PH, Loeffler FF. Automated glycan assembly of peptidoglycan backbone fragments. Org Biomol Chem 2021; 19:9829-9832. [PMID: 34734957 DOI: 10.1039/d1ob01987b] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
We report the automated glycan assembly (AGA) of different oligosaccharide fragments of the bacterial peptidoglycan (PGN) backbone. Iterative addition on a solid support of an acetyl glucosamine and a new muramic acid building block is followed by cleavage from the solid support and final deprotection providing 10 oligosaccharides up to six units.
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Affiliation(s)
- Pietro Dallabernardina
- Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Muehlenberg 1, 14476 Potsdam, Germany.
| | - Valentina Benazzi
- Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Muehlenberg 1, 14476 Potsdam, Germany. .,University of Pavia, Department of Organic Chemistry, V.le Torquato Taramelli, 10, 27100 Pavia, Italy
| | - Jon D Laman
- Department of Pathology & Medical Biology, University Medical Center Groningen, Groningen, The Netherlands
| | - Peter H Seeberger
- Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Muehlenberg 1, 14476 Potsdam, Germany. .,Freie Universität Berlin, Institute of Chemistry and Biochemistry, Arnimallee 22, 14195 Berlin, Germany
| | - Felix F Loeffler
- Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Muehlenberg 1, 14476 Potsdam, Germany.
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45
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Heijtz RD, Gonzalez-Santana A, Laman JD. Young microbiota rejuvenates the aging brain. NATURE AGING 2021; 1:625-627. [PMID: 37117768 DOI: 10.1038/s43587-021-00100-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/30/2023]
Affiliation(s)
- Rochellys Diaz Heijtz
- Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
- Institut National de la Santé et de la Recherche Médicale (INSERM) Unit 1239, University of Rouen Normandy, Rouen, France.
| | | | - Jon D Laman
- Department of Pathology and Medical Biology, University Medical Center Groningen (UMCG), Groningen, the Netherlands
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46
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Han H, Yi B, Zhong R, Wang M, Zhang S, Ma J, Yin Y, Yin J, Chen L, Zhang H. From gut microbiota to host appetite: gut microbiota-derived metabolites as key regulators. MICROBIOME 2021; 9:162. [PMID: 34284827 PMCID: PMC8293578 DOI: 10.1186/s40168-021-01093-y] [Citation(s) in RCA: 133] [Impact Index Per Article: 33.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Accepted: 05/11/2021] [Indexed: 05/25/2023]
Abstract
Feelings of hunger and satiety are the key determinants for maintaining the life of humans and animals. Disturbed appetite control may disrupt the metabolic health of the host and cause various metabolic disorders. A variety of factors have been implicated in appetite control, including gut microbiota, which develop the intricate interactions to manipulate the metabolic requirements and hedonic feelings. Gut microbial metabolites and components act as appetite-related signaling molecules to regulate appetite-related hormone secretion and the immune system, or act directly on hypothalamic neurons. Herein, we summarize the effects of gut microbiota on host appetite and consider the potential molecular mechanisms. Furthermore, we propose that the manipulation of gut microbiota represents a clinical therapeutic potential for lessening the development and consequence of appetite-related disorders. Video abstract.
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Affiliation(s)
- Hui Han
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
- Precision Livestock and Nutrition Unit, Gembloux Agro-Bio Tech, University of Liège, Passage de Déportés 2, 5030, Gembloux, Belgium
| | - Bao Yi
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
| | - Ruqing Zhong
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
| | - Mengyu Wang
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
| | - Shunfen Zhang
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
| | - Jie Ma
- College of Animal Science and Technology, Hunan Agricultural University, Changsha, 410128, China
| | - Yulong Yin
- College of Animal Science and Technology, Hunan Agricultural University, Changsha, 410128, China
- Key Laboratory of Agro-Ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan, 410125, China
| | - Jie Yin
- College of Animal Science and Technology, Hunan Agricultural University, Changsha, 410128, China.
| | - Liang Chen
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.
| | - Hongfu Zhang
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.
- College of Animal Science and Technology, Hunan Agricultural University, Changsha, 410128, China.
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47
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Qian XH, Song XX, Liu XL, Chen SD, Tang HD. Inflammatory pathways in Alzheimer's disease mediated by gut microbiota. Ageing Res Rev 2021; 68:101317. [PMID: 33711509 DOI: 10.1016/j.arr.2021.101317] [Citation(s) in RCA: 97] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Revised: 02/25/2021] [Accepted: 03/08/2021] [Indexed: 12/14/2022]
Abstract
In the past decade, numerous studies have demonstrated the close relationship between gut microbiota and the occurrence and development of Alzheimer's disease (AD). However, the specific mechanism is still unclear. Both the neuroinflammation and systemic inflammation serve as the key hubs to accelerate the process of AD by promoting pathology and damaging neuron. What's more, the gut microbiota is also crucial for the regulation of inflammation. Therefore, this review focused on the role of gut microbiota in AD through inflammatory pathways. Firstly, this review summarized the relationship and interaction among gut microbiota, inflammation, and AD. Secondly, the direct and indirect regulatory effects of gut microbiota on AD through inflammatory pathways were described. These effects were mainly mediated by the component of the gut microbiota (lipopolysaccharides (LPS) and amyloid peptides), the metabolites of bacteria (short-chain fatty acids, branched amino acids, and neurotransmitters) and functional by-products (bile acids). In addition, potential treatments (fecal microbiota transplantation, antibiotics, probiotics, prebiotics, and dietary interventions) for AD were also discussed through these mechanisms. Finally, according to the current research status, the key problems to be solved in the future studies were proposed.
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Affiliation(s)
- Xiao-Hang Qian
- Department of Neurology and Institute of Neurology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
| | - Xiao-Xuan Song
- Department of Neurology and Institute of Neurology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
| | - Xiao-Li Liu
- Department of Neurology, Shanghai Fengxian District Central Hospital, Shanghai Jiao Tong University Affiliated Sixth People's Hospital South Campus, Shanghai, 201406, China.
| | - Sheng-di Chen
- Department of Neurology and Institute of Neurology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
| | - Hui-Dong Tang
- Department of Neurology and Institute of Neurology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
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48
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Decoding the Role of Gut-Microbiome in the Food Addiction Paradigm. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18136825. [PMID: 34202073 PMCID: PMC8297196 DOI: 10.3390/ijerph18136825] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 06/22/2021] [Accepted: 06/23/2021] [Indexed: 12/12/2022]
Abstract
Eating behaviour is characterised by a solid balance between homeostatic and hedonic regulatory mechanisms at the central level and highly influenced by peripheral signals. Among these signals, those generated by the gut microbiota have achieved relevance in recent years. Despite this complex regulation, under certain circumstances eating behaviour can be deregulated becoming addictive. Although there is still an ongoing debate about the food addiction concept, studies agree that patients with eating addictive behaviour present similar symptoms to those experienced by drug addicts, by affecting central areas involved in the control of motivated behaviour. In this context, this review tries to summarise the main data regarding the role of the gut microbiome in eating behaviour and how a gut dysbiosis can be responsible for a maladaptive behaviour such as “food addiction”.
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49
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Nargeh H, Aliabadi F, Ajami M, Pazoki-Toroudi H. Role of Polyphenols on Gut Microbiota and the Ubiquitin-Proteasome System in Neurodegenerative Diseases. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2021; 69:6119-6144. [PMID: 34038102 DOI: 10.1021/acs.jafc.1c00923] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Today, neurodegenerative diseases have become a remarkable public health challenge due to their direct relation with aging. Accordingly, understanding the molecular and cellular mechanisms occurring in the pathogenesis of them is essential. Both protein aggregations as a result of the ubiquitin-proteasome system (UPS) inefficiency and gut microbiota alternation are the main pathogenic hallmarks. Polyphenols upregulating this system may decrease the developing rate of neurodegenerative diseases. Most of the dietary intake of polyphenols is converted into other microbial metabolites, which have completely different biological properties from the original polyphenols and should be thoroughly investigated. Herein, several prevalent neurodegenerative diseases are pinpointed to explain the role of gut microbiota alternations and the role of molecular changes, especially UPS down-regulation in their pathogenesis. Some of the most important polyphenols found in our diet are explained along with their microbial metabolites in the body.
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Affiliation(s)
- Hanieh Nargeh
- Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran 1417466191, Iran
| | - Fatemeh Aliabadi
- Physiology Research Center, Faculty of Medicine, Iran University of Medical Sciences, Tehran 14535, Iran
| | - Marjan Ajami
- Faculty of Nutrition Sciences & Food Technology, Shahid Beheshti University of Medical Sciences, 7th Floor, Bldg No. 2 SBUMS, Arabi Avenue, Daneshjoo Boulevard, Velenjak, Tehran 19839-63113, Iran
| | - Hamidreza Pazoki-Toroudi
- Physiology Research Center, Faculty of Medicine, Iran University of Medical Sciences, Tehran 14535, Iran
- Department of Physiology and Physiology Research Center, Faculty of Medicine, Iran University of Medical Sciences, Tehran 14535, Iran
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50
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Eitan S, Madison CA, Kuempel J. The self-serving benefits of being a good host: A role for our micro-inhabitants in shaping opioids' function. Neurosci Biobehav Rev 2021; 127:284-295. [PMID: 33894242 DOI: 10.1016/j.neubiorev.2021.04.019] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Revised: 04/07/2021] [Accepted: 04/18/2021] [Indexed: 02/07/2023]
Abstract
Opioids are highly efficacious in their ability to relieve pain, but they are liable for abuse, dependence, and addiction. Risk factors to develop opioid use disorders (OUD) include chronic stress, socio-environment, and preexisting major depressive disorders (MDD) and posttraumatic stress disorders (PTSD). Additionally, opioids reduce gut motility, induce loss of gut barrier function, and alter the composition of the trillions of microbes hosted in the gastrointestinal tract, known as the gut microbiota. The microbiota are significant contributors to the reciprocal communication between the central nervous system (CNS) and the gut, termed the gut-brain axis. They have strong influences on their host behaviors, including the ability to cope with stress, sociability, affect, mood, and anxiety. Thus, they are implicated in the etiology of MDD and PTSD. Here we review the latest studies demonstrating that intestinal flora can, directly and indirectly, by affecting sociability levels, responses to stress, and mental state, alter the responses to opioids. It suggests that microbiota can potentially be used to increase the resilience to develop analgesic tolerance and OUD.
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Affiliation(s)
- Shoshana Eitan
- Behavioral and Cellular Neuroscience, Department of Psychological and Brain Sciences, Texas A&M University, 4235 TAMU, College Station, TX, 77843, USA.
| | - Caitlin A Madison
- Behavioral and Cellular Neuroscience, Department of Psychological and Brain Sciences, Texas A&M University, 4235 TAMU, College Station, TX, 77843, USA
| | - Jacob Kuempel
- Behavioral and Cellular Neuroscience, Department of Psychological and Brain Sciences, Texas A&M University, 4235 TAMU, College Station, TX, 77843, USA
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