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Chen Y, Chen X, Lin S, Huang S, Li L, Hong M, Li J, Ma L, Ma J. Effects of psychological stress on inflammatory bowel disease via affecting the microbiota-gut-brain axis. Chin Med J (Engl) 2025; 138:664-677. [PMID: 39965932 PMCID: PMC11925421 DOI: 10.1097/cm9.0000000000003389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2024] [Indexed: 02/20/2025] Open
Abstract
ABSTRACT Inflammatory bowel disease (IBD) is an idiopathic intestinal inflammatory condition with chronic and relapsing manifestations and is characterized by a disturbance in the interplay between the intestinal microbiota, the gut, and the brain. The microbiota-gut-brain axis involves interactions among the nervous system, the neuroendocrine system, the gut microbiota, and the host immune system. Increasing published data indicate that psychological stress exacerbates the severity of IBD due to its negative effects on the microbiota-gut-brain axis, including alterations in the stress response of the hypothalamic-pituitary-adrenal (HPA) axis, the balance between the sympathetic nervous system and vagus nerves, the homeostasis of the intestinal flora and metabolites, and normal intestinal immunity and permeability. Although the current evidence is insufficient, psychotropic agents, psychotherapies, and interventions targeting the microbiota-gut-brain axis show the potential to improve symptoms and quality of life in IBD patients. Therefore, further studies that translate recent findings into therapeutic approaches that improve both physical and psychological well-being are needed.
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Affiliation(s)
- Yuhan Chen
- Shantou University Medical College, Shantou, Guangdong 515041, China
- Department of Gastroenterology and Hepatology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, China
| | - Xiaofen Chen
- Shantou University Medical College, Shantou, Guangdong 515041, China
- Department of Gastroenterology and Hepatology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, China
| | - Suqin Lin
- Medical College, Southern Medical University, Guangzhou, Guangdong 510515, China
| | - Shengjun Huang
- Department of Gastroenterology and Hepatology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, China
- Medical College, Southern Medical University, Guangzhou, Guangdong 510515, China
| | - Lijuan Li
- Department of Gastroenterology and Hepatology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, China
- Medical College, Southern Medical University, Guangzhou, Guangdong 510515, China
| | - Mingzhi Hong
- Department of Gastroenterology and Hepatology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, China
- Medical College, Southern Medical University, Guangzhou, Guangdong 510515, China
| | - Jianzhou Li
- Department of Diagnosis and Treatment Center of High Altitude Digestive Disease, The Second People's Hospital of Xining, Xining, Qinghai 810003, China
| | - Lili Ma
- Department of Gastroenterology and Hepatology, Qinghai Provincial People's Hospital, Xining, Qinghai 810007, China
| | - Juan Ma
- Department of Gastroenterology and Hepatology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, China
- Department of Diagnosis and Treatment Center of High Altitude Digestive Disease, The Second People's Hospital of Xining, Xining, Qinghai 810003, China
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Gopinath D, Pandiar D, Li Z, Panda S. Rodent models for oral microbiome research: considerations and challenges- a mini review. FRONTIERS IN ORAL HEALTH 2024; 5:1439091. [PMID: 39421460 PMCID: PMC11484444 DOI: 10.3389/froh.2024.1439091] [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: 05/27/2024] [Accepted: 09/16/2024] [Indexed: 10/19/2024] Open
Abstract
Rodent models have been commonly employed in oral microbiota research to investigate the relationship between bacteria and oral disease. Nevertheless, to apply the knowledge acquired from studies conducted on rodents to a human context, it is crucial to consider the significant spatial and temporal parallels and differences between the oral microbiota of mice and humans. Initially, we outline the comparative physiology and microbiology of the oral cavity of rodents and humans. Additionally, we highlight the strong correlation between the oral microbiome of rodents and genetic makeup, which is influenced by factors including vendor, husbandry practices, and environmental conditions. All of these factors potentially impact the replicability of studies on rodent microbiota and the resulting conclusions. Next, we direct our attention toward the diversity in the microbiome within mice models of disease and highlight the diversity that may potentially affect the characteristics of diseases and, in turn, alter the ability to replicate research findings and apply them to real-world situations. Furthermore, we explore the practicality of oral microbial models for complex oral microbial diseases in future investigations by examining the concept of gnotobiotic and germ-free mouse models. Finally, we stress the importance of investigating suitable techniques for characterizing and managing genetically modified organisms. Future research should consider these aspects to improve oral microbiome research's translational potential.
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Affiliation(s)
- Divya Gopinath
- Basic Medical and Dental Sciences Department, College of Dentistry, Ajman University, Ajman, United Arab Emirates
- Centre of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates
| | - Deepak Pandiar
- Department of Oral Pathology and Microbiology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India
| | - Zhengrui Li
- Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
- National Center for Stomatology, Shanghai, China
- National Clinical Research Center for Oral Diseases, Shanghai, China
- Shanghai Key Laboratory of Stomatology, Shanghai, China
- Shanghai Research Institute of Stomatology, Shanghai, China
- Shanghai Center of Head and Neck Oncology Clinical and Translational Science, Shanghai, China
| | - Swagatika Panda
- Department of Oral Pathology and Microbiology, Institute of Dental Sciences, Siksha 'O' Anusandhan University, Bhubaneswar, India
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Chen HJ, Bischoff A, Galley JD, Peck L, Bailey MT, Gur TL. Discrete role for maternal stress and gut microbes in shaping maternal and offspring immunity. Neurobiol Stress 2022; 21:100480. [PMID: 36532381 PMCID: PMC9755033 DOI: 10.1016/j.ynstr.2022.100480] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Revised: 07/28/2022] [Accepted: 08/18/2022] [Indexed: 01/11/2023] Open
Abstract
Psychosocial stress is prevalent during pregnancy, and is associated with immune dysfunction, both for the mother and the child. The gut microbiome has been implicated as a potential mechanism by which stress during pregnancy can impact both maternal and offspring immune function; however, the complex interplay between the gut microbiome and the immune system is not well-understood. Here, we leverage a model of antimicrobial-mediated gut microbiome reduction, in combination with a well-established model of maternal restraint stress, to investigate the independent effects of and interaction between maternal stress and the gut microbiome in shaping maternal and offspring immunity. First, we confirmed that the antimicrobial treatment reduced maternal gut bacterial load and altered fecal alpha and beta diversity, with a reduction in commensal microbes and an increase in the relative abundance of rare taxa. Prenatal stress also disrupted the gut microbiome, according to measures of both alpha and beta diversity. Furthermore, prenatal stress and antimicrobials independently induced systemic and gastrointestinal immune suppression in the dam with a concomitant increase in circulating corticosterone. While stress increased neutrophils in the maternal circulation, lymphoid cells and monocytes were not impacted by either stress or antimicrobial treatment. Although the fetal immune compartment was largely spared, stress increased circulating neutrophils and CD8 T cells, and antibiotics increased neutrophils and reduced T cells in the adult offspring. Altogether, these data indicate similar, but discrete, roles for maternal stress and gut microbes in influencing maternal and offspring immune function.
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Affiliation(s)
- Helen J. Chen
- Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, Columbus, OH, USA,Department of Psychiatry & Behavioral Health, The Ohio State University Wexner Medical Center, Columbus, OH, USA,Department of Neuroscience, The Ohio State University Wexner Medical Center, Columbus, OH, USA,Medical Scientist Training Program, The Ohio State University, Columbus, OH, USA
| | - Allison Bischoff
- Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Jeffrey D. Galley
- Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, Columbus, OH, USA,Department of Psychiatry & Behavioral Health, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Lauren Peck
- Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, Columbus, OH, USA,The Ohio State University College of Medicine, Columbus, OH, USA
| | - Michael T. Bailey
- Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, Columbus, OH, USA,Center for Microbial Pathogenesis, The Research Institute, Nationwide Children's Hospital, Columbus, OH, USA,Biosciences Division, College of Dentistry, The Ohio State University, Columbus, OH, USA
| | - Tamar L. Gur
- Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, Columbus, OH, USA,Department of Psychiatry & Behavioral Health, The Ohio State University Wexner Medical Center, Columbus, OH, USA,Department of Neuroscience, The Ohio State University Wexner Medical Center, Columbus, OH, USA,Medical Scientist Training Program, The Ohio State University, Columbus, OH, USA,Department of Pediatrics, The Ohio State University Wexner Medical Center, Columbus, OH, USA,Department of Obstetrics & Gynecology, The Ohio State University Wexner Medical Center, Columbus, OH, USA,Corresponding author. 120A Institute for Behavioral Medicine Research Building, 460 Medical Center Drive, Columbus, OH, 43210, USA.
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Vorvul AO, Bobyntsev II, Medvedeva OA, Mukhina AY, Svishcheva MV, Azarova IE, Andreeva LA, Myasoedov NF. ACTH(6-9)-Pro-Gly-Pro ameliorates anxiety-like and depressive-like behaviour and gut mucosal microbiota composition in rats under conditions of chronic restraint stress. Neuropeptides 2022; 93:102247. [PMID: 35487169 DOI: 10.1016/j.npep.2022.102247] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 03/02/2022] [Accepted: 04/18/2022] [Indexed: 12/30/2022]
Abstract
The effects of the peptide ACTH(6-9)-Pro-Gly-Pro at doses of 5; 50; 500 μg/kg on the Wistar rats' behaviour and gut mucosal microbiota composition under conditions of chronic immobilization stress (CRS) were studied. CRS increased anxiety-like and depressive-like behaviour, disturbances in locomotor activity and gut dysbiosis. Administration of ACTH(6-9)-Pro-Gly-Pro showed many phenotypic results. Peptide demonstrated anti-depressant activity at doses of 5 and 500 μg/kg by a decrease in the total immobile time in the FST. ACTH(6-9)-Pro-Gly-Pro administered at a dose of 50 μg/kg resulted in an anxiolytic effect which is shown by an increase in the time in the open arms of EPM (p < 0.05) and a decrease in the time in the closed arms (p < 0.05). Moreover, the peptide led to a decrease in alpha- and beta-diversity of the gut microbiota (p < 0.01). Correlation and linear regression analysis demonstrated central mechanisms of ACTH(6-9)-Pro-Gly-Pro anxiolytic activity and both central and peripheral ones in an anti-depressant effect. In this way, peptide ACTH(6-9)-Pro-Gly-Pro could prevent the development of behavioural disturbances and gut dysbiosis caused by chronic restraint stress.
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Affiliation(s)
- Anton O Vorvul
- Kursk State Medical University, 3 Karl Marx street, Kursk 305041, Russia.
| | - Igor I Bobyntsev
- Kursk State Medical University, 3 Karl Marx street, Kursk 305041, Russia
| | - Olga A Medvedeva
- Kursk State Medical University, 3 Karl Marx street, Kursk 305041, Russia
| | | | - Maria V Svishcheva
- Kursk State Medical University, 3 Karl Marx street, Kursk 305041, Russia
| | - Iuliia E Azarova
- Kursk State Medical University, 3 Karl Marx street, Kursk 305041, Russia
| | - Lyudmila A Andreeva
- Institute of Molecular Genetics, Kurchatov Institute, 2 Akademika Kurchatova square, Moscow 123182, Russia
| | - Nikolay F Myasoedov
- Institute of Molecular Genetics, Kurchatov Institute, 2 Akademika Kurchatova square, Moscow 123182, Russia
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Maltz RM, Marte-Ortiz P, Rajasekera TA, Loman BR, Gur TL, Bailey MT. Stressor-Induced Increases in Circulating, but Not Colonic, Cytokines Are Related to Anxiety-like Behavior and Hippocampal Inflammation in a Murine Colitis Model. Int J Mol Sci 2022; 23:ijms23042000. [PMID: 35216112 PMCID: PMC8877477 DOI: 10.3390/ijms23042000] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 01/31/2022] [Accepted: 02/08/2022] [Indexed: 01/27/2023] Open
Abstract
Stressor exposure increases colonic inflammation. Because inflammation leads to anxiety-like behavior, we tested whether stressor exposure in mice recovering from dextran-sulfate-sodium (DSS)-induced colitis enhances anxiety-like behavior. Mice received 2% DSS for five consecutive days prior to being exposed to a social-disruption (SDR) stressor (or being left undisturbed). After stressor exposure, their behavior was tested and colitis was assessed via histopathology and via inflammatory-cytokine measurement in the serum and colon. Cytokine and chemokine mRNA levels in the colon, mesenteric lymph nodes (MLNs), hippocampus, and amygdala were measured with RT-PCR. SDR increased anxiety-like behaviors, which correlated with serum and hippocampal IL-17A. The stressor also reduced IL-1β, CCL2, and iNOS in the colonic tissue, but increased iNOS, IFNγ, IL-17A, and TNFα in the MLNs. A network analysis indicated that reductions in colonic iNOS were related to elevated MLN iNOS and IFNγ. These inflammatory markers were related to serum and hippocampal IL-17A and associated with anxiety-like behavior. Our data suggest that iNOS may protect against extra-colonic inflammation, and when suppressed during stress it is associated with elevated MLN IFNγ, which may coordinate gut-to-brain inflammation. Our data point to hippocampal IL-17A as a key correlate of anxiety-like behavior.
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Affiliation(s)
- Ross M. Maltz
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Nationwide Children’s Hospital, Columbus, OH 43205, USA
- Department of Pediatrics, The Ohio State Wexner Medical Center, Columbus, OH 43210, USA;
- The Center for Microbial Pathogenesis, The Research Institute, Nationwide Children’s Hospital, Columbus, OH 43205, USA; (P.M.-O.); (B.R.L.)
- Oral and Gastrointestinal Microbiology Research Affinity Group, Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OH 43205, USA
- Correspondence: ; Tel.: +1-614-722-5116; Fax: +1-614-722-2979
| | - Pedro Marte-Ortiz
- The Center for Microbial Pathogenesis, The Research Institute, Nationwide Children’s Hospital, Columbus, OH 43205, USA; (P.M.-O.); (B.R.L.)
| | - Therese A. Rajasekera
- Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; (T.A.R.); (T.L.G.)
- Department of Psychiatry & Behavioral Health, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
| | - Brett R. Loman
- The Center for Microbial Pathogenesis, The Research Institute, Nationwide Children’s Hospital, Columbus, OH 43205, USA; (P.M.-O.); (B.R.L.)
| | - Tamar L. Gur
- Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; (T.A.R.); (T.L.G.)
- Department of Psychiatry & Behavioral Health, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
| | - Michael T. Bailey
- Department of Pediatrics, The Ohio State Wexner Medical Center, Columbus, OH 43210, USA;
- The Center for Microbial Pathogenesis, The Research Institute, Nationwide Children’s Hospital, Columbus, OH 43205, USA; (P.M.-O.); (B.R.L.)
- Oral and Gastrointestinal Microbiology Research Affinity Group, Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OH 43205, USA
- Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; (T.A.R.); (T.L.G.)
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Chen X, Chen W, Ci W, Zheng Y, Han X, Huang J, Zhu J. Effects of Dietary Supplementation with Lactobacillus acidophilus and Bacillus subtilis on Mucosal Immunity and Intestinal Barrier Are Associated with Its Modulation of Gut Metabolites and Microbiota in Late-Phase Laying Hens. Probiotics Antimicrob Proteins 2022:10.1007/s12602-022-09923-7. [PMID: 35138584 DOI: 10.1007/s12602-022-09923-7] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/21/2022] [Indexed: 02/07/2023]
Abstract
We investigated the effects of dietary supplementation with Lactobacillus acidophilus and Bacillus subtilis on the intestinal immune response, intestinal barrier function, cecal microbiota profile, and metabolite profile in late-phase laying hens. Hens were divided into three groups and fed with the basal diet (NC group), basal diet supplementation with 250 mg/kg B. subtilis and L. acidophilus mixture powder (LD group), and basal diet supplementation with 500 mg/kg B. subtilis and L. acidophilus mixture powder (HD group), respectively. The results indicated that the dietary supplementation with L. acidophilus and B. subtilis increased the integrity of the intestinal barrier as evidenced by the significant increase in the number of ileal goblet cells and improve the expression of occludin, claudin-1, and ZO-1 genes in the HD group. Moreover, the levels of IL-6, TNF-α, and IFN-γ were significantly decreased in the LD and HD groups. The levels of immunoglobulin G (IgG) increased in the LD and HD group, and the levels of secretory immunoglobulin A (sIgA) increased with the HD treatment. Furthermore, 16 s rRNA sequencing revealed L. acidophilus in combination with B. subtilis increased the diversity of gut microbiota. The metabolomic analysis revealed beneficial changes in the amino acid metabolism and lipid metabolism (decrease in LysoPC and LysoPE levels). In conclusion, dietary supplementation with L. acidophilus and B. subtilis could improve intestinal barrier function and maintain immune homeostasis. These beneficial effects may be associated with the modulation of the intestinal microbiome and metabolites.
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Affiliation(s)
- Xin Chen
- Centre for Food Nutrition and Functional Food Engineering, School of Food Science and Technology, Jiangnan University, Jiangsu, 214122, China
| | - Weiwen Chen
- Centre for Food Nutrition and Functional Food Engineering, School of Food Science and Technology, Jiangnan University, Jiangsu, 214122, China
| | - Wenjia Ci
- Centre for Food Nutrition and Functional Food Engineering, School of Food Science and Technology, Jiangnan University, Jiangsu, 214122, China
| | - Yingying Zheng
- Centre for Food Nutrition and Functional Food Engineering, School of Food Science and Technology, Jiangnan University, Jiangsu, 214122, China
| | - Xinyan Han
- Key Laboratory of Animal Nutrition and Feed Science in East China, Ministry of Agriculture, College of Animal Science, Zhejiang University, Hangzhou, 310058, China
| | - Jianping Huang
- Food Processing Technology Laboratory, School of Food Science and Technology, Jiangnan University, Jiangsu, 214122, China
| | - Jianjin Zhu
- Centre for Food Nutrition and Functional Food Engineering, School of Food Science and Technology, Jiangnan University, Jiangsu, 214122, China.
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Anisman H, Kusnecov AW. Stress, immunity, and cancer. Cancer 2022. [DOI: 10.1016/b978-0-323-91904-3.00017-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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Specific Changes in the Mammalian Gut Microbiome as a Biomarker for Oxytocin-Induced Behavioral Changes. Microorganisms 2021; 9:microorganisms9091938. [PMID: 34576833 PMCID: PMC8465812 DOI: 10.3390/microorganisms9091938] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2021] [Revised: 08/22/2021] [Accepted: 09/06/2021] [Indexed: 12/12/2022] Open
Abstract
Prolonged exposure to psychiatric pharmacological agents is often associated with marked gastrointestinal phenomena, including changes in food intake, bowel motility, gastric emptying, and transit time. Those changes are reflected in the gut microbiota composition of the patient and can, therefore, be objectively measured. This is in contrast to the standard psychiatric evaluation of patients, which includes symptoms that are subjectively assessed (i.e., mood, anxiety level, perception, thought disorders, etc.). The association between a drug’s effect on the microbiota and psychiatric symptoms may allow for quantifiable surrogate markers of treatment effectiveness. Changes in the levels of specific drug-sensitive bacterial species can, thus, potentially serve as biomarkers for the intake and effectiveness of psychiatric drugs. Here, we show substantial microbiota changes that were associated with oxytocin administration and the decreased anxiety/depression-like behaviors it conferred in a rat model of corticosterone-induced stress. Compared with oxytocin, citalopram produced more minor effects on the rats’ microbiota. Alterations in the gut microbiota may, therefore, reflect the consumption and effectiveness of some psychiatric drugs.
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Citrobacter rodentium infection at the gut-brain axis interface. Curr Opin Microbiol 2021; 63:59-65. [PMID: 34217915 DOI: 10.1016/j.mib.2021.06.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Accepted: 06/16/2021] [Indexed: 01/07/2023]
Abstract
The gut-brain axis plays a critical role in the maintenance of the gastrointestinal tract homeostasis. Several enteric pathogens have developed strategies to sense neurochemical molecules to regulate their virulence in the gut. Additionally, there is growing evidence that gut dysbiosis can strongly affect host brain responses. Here we review different mechanisms that have been proposed to mediate gut-brain axis communication using Citrobacter rodentium, a natural murine enteric pathogen and one of the most widely used small animal models for studying host-microbe interactions. We highlight studies that have identified-specific pathways used by C. rodentium to sense host neurochemicals during colonization as well as behavioral responses and brain pathologies affected by pathogen colonization of the gut.
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Baranyi A, Enko D, von Lewinski D, Rothenhäusler HB, Amouzadeh-Ghadikolai O, Harpf H, Harpf L, Traninger H, Obermayer-Pietsch B, Schweinzer M, Braun CK, Meinitzer A. Assessment of trimethylamine N-oxide (TMAO) as a potential biomarker of severe stress in patients vulnerable to posttraumatic stress disorder (PTSD) after acute myocardial infarction. Eur J Psychotraumatol 2021; 12:1920201. [PMID: 34104352 PMCID: PMC8168738 DOI: 10.1080/20008198.2021.1920201] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Background: Posttraumatic stress disorder (PTSD) is a frequently observed stress-related disorder after acute myocardial infarction (AMI) and it is characterized by numerous symptoms, such as flashbacks, intrusions and anxiety, as well as uncontrollable thoughts and feelings related to the trauma. Biological correlates of severe stress might contribute to identifying PTSD-vulnerable patients at an early stage. Objective: Aims of the study were (1) to determine whether blood levels of trimethylamine N-oxide (TMAO) vary immediately after AMI in patients with/without AMI-induced PTSD symptomatology, (2) to investigate whether TMAO is a potential biomarker that might be useful in the prediction of PTSD and the PTSD symptom subclusters re-experiencing, avoidance and hyperarousal, and (3) to investigate whether TMAO varies immediately after AMI in patients with/without depression 6 months after AMI. Method: A total of 114 AMI patients were assessed with the Hamilton-Depression Scale after admission to the hospital and 6 months later. The Clinician Administered PTSD Scale for DSM-5 was used to explore PTSD-symptoms at the time of AMI and 6 months after AMI. To assess patients' TMAO status, serum samples were collected at hospitalization and 6 months after AMI. Results: Participants with PTSD-symptomatology had significantly higher TMAO levels immediately after AMI than patients without PTSD-symptoms (ANCOVA: TMAO(PTSD x time), F = 4.544, df = 1, p = 0.035). With the inclusion of additional clinical predictors in a hierarchical logistic regression model, TMAO became a significant predictor of PTSD-symptomatology. No significant differences in TMAO levels immediately after AMI were detected between individuals with/without depression 6 months after AMI. Conclusions: An elevated TMAO level immediately after AMI might reflect severe stress in PTSD-vulnerable patients, which might also lead to a short-term increase in gut permeability to trimethylamine, the precursor of TMAO. Thus, an elevated TMAO level might be a biological correlate for severe stress that is associated with vulnerability to PTSD.
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Affiliation(s)
- Andreas Baranyi
- Department of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria
| | - Dietmar Enko
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
| | - Dirk von Lewinski
- Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Hans-Bernd Rothenhäusler
- Department of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria
| | | | - Hanns Harpf
- ZARG Zentrum Für Ambulante Rehabilitation GmbH, Graz, Austria
| | - Leonhard Harpf
- ZARG Zentrum Für Ambulante Rehabilitation GmbH, Graz, Austria
| | - Heimo Traninger
- ZARG Zentrum Für Ambulante Rehabilitation GmbH, Graz, Austria
| | - Barbara Obermayer-Pietsch
- Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Melanie Schweinzer
- Department of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria
| | - Celine K Braun
- Department of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria
| | - Andreas Meinitzer
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
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Farmer N, Gutierrez-Huerta CA, Turner BS, Mitchell VM, Collins BS, Baumer Y, Wallen GR, Powell-Wiley TM. Neighborhood Environment Associates with Trimethylamine-N-Oxide (TMAO) as a Cardiovascular Risk Marker. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:4296. [PMID: 33919545 PMCID: PMC8072883 DOI: 10.3390/ijerph18084296] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 04/15/2021] [Accepted: 04/16/2021] [Indexed: 12/30/2022]
Abstract
BACKGROUND Neighborhoods and the microbiome are linked to cardiovascular disease (CVD), yet investigations to identify microbiome-related factors at neighborhood levels have not been widely investigated. We sought to explore relationships between neighborhood deprivation index (NDI) and the microbial metabolite, trimethylamine-N-oxide. We hypothesized that inflammatory markers and dietary intake would be mediators of the relationship. METHODS African-American adults at risk for CVD living in the Washington, DC area were recruited to participate in a cross-sectional community-based study. US census-based neighborhood deprivation index (NDI) measures (at the census-tract level) were determined. Serum samples were analyzed for CVD risk factors, cytokines, and the microbial metabolite, trimethylamine-N-oxide (TMAO). Self-reported dietary intake based on food groups was collected. RESULTS Study participants (n = 60) were predominantly female (93.3%), with a mean (SD) age of 60.83 (+/-10.52) years. Mean (SD) NDI was -1.54 (2.94), and mean (SD) TMAO level was 4.99 (9.65) µmol/L. Adjusting for CVD risk factors and BMI, NDI was positively associated with TMAO (β = 0.31, p = 0.02). Using mediation analysis, the relationship between NDI and TMAO was significantly mediated by TNF-α (60.15%) and interleukin)-1 β (IL; 49.96%). When controlling for clustering within neighborhoods, the NDI-TMAO association was no longer significant (β = 5.11, p = 0.11). However, the association between NDI and IL-1 β (β = 0.04, p = 0.004) and TNF-α (β = 0.17, p = 0.003) remained. Neither NDI nor TMAO was significantly associated with daily dietary intake. Conclusion and Relevance: Among a small sample of African-American adults at risk for CVD, there was a significant positive relationship with NDI and TMAO mediated by inflammation. These hypothesis-generating results are initial and need to be confirmed in larger studies.
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Affiliation(s)
- Nicole Farmer
- Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA;
| | - Cristhian A. Gutierrez-Huerta
- Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA; (C.A.G.-H.); (B.S.T.); (V.M.M.); (B.S.C.); (Y.B.); (T.M.P.-W.)
| | - Briana S. Turner
- Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA; (C.A.G.-H.); (B.S.T.); (V.M.M.); (B.S.C.); (Y.B.); (T.M.P.-W.)
| | - Valerie M. Mitchell
- Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA; (C.A.G.-H.); (B.S.T.); (V.M.M.); (B.S.C.); (Y.B.); (T.M.P.-W.)
| | - Billy S. Collins
- Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA; (C.A.G.-H.); (B.S.T.); (V.M.M.); (B.S.C.); (Y.B.); (T.M.P.-W.)
| | - Yvonne Baumer
- Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA; (C.A.G.-H.); (B.S.T.); (V.M.M.); (B.S.C.); (Y.B.); (T.M.P.-W.)
| | - Gwenyth R. Wallen
- Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA;
| | - Tiffany M. Powell-Wiley
- Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA; (C.A.G.-H.); (B.S.T.); (V.M.M.); (B.S.C.); (Y.B.); (T.M.P.-W.)
- Intramural Research Program, National Institute on Minority and Health Disparities, Bethesda, MD 20892, USA
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12
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Antonson AM, Evans MV, Galley JD, Chen HJ, Rajasekera TA, Lammers SM, Hale VL, Bailey MT, Gur TL. Unique maternal immune and functional microbial profiles during prenatal stress. Sci Rep 2020; 10:20288. [PMID: 33219314 PMCID: PMC7679384 DOI: 10.1038/s41598-020-77265-x] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Accepted: 10/14/2020] [Indexed: 12/22/2022] Open
Abstract
Maternal stress during pregnancy is widespread and is associated with poor offspring outcomes, including long-term mental health issues. Prenatal stress-induced fetal neuroinflammation is thought to underlie aberrant neurodevelopment and to derive from a disruption in intrauterine immune homeostasis, though the exact origins are incompletely defined. We aimed to identify divergent immune and microbial metagenome profiles of stressed gestating mice that may trigger detrimental inflammatory signaling at the maternal-fetal interface. In response to stress, maternal glucocorticoid circuit activation corresponded with indicators of systemic immunosuppression. At the maternal-fetal interface, density of placental mononuclear leukocytes decreased with stress, yet maternal whole blood leukocyte analysis indicated monocytosis and classical M1 phenotypic shifts. Genome-resolved microbial metagenomic analyses revealed reductions in genes, microbial strains, and metabolic pathways in stressed dams that are primarily associated with pro-inflammatory function. In particular, disrupted Parasutterella excrementihominis appears to be integral to inflammatory and metabolic dysregulation during prenatal stress. Overall, these perturbations in maternal immunological and microbial regulation during pregnancy may displace immune equilibrium at the maternal-fetal interface. Notably, the absence of and reduction in overt maternal inflammation during stress indicates that the signaling patterns driving fetal outcomes in this context are more nuanced and complex than originally anticipated.
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Affiliation(s)
- Adrienne M Antonson
- Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, Columbus, OH, USA
- Department of Psychiatry & Behavioral Health, The Ohio State University Wexner Medical Center, Columbus, OH, USA
- Biosciences Division, College of Dentistry, The Ohio State University, Columbus, OH, USA
| | - Morgan V Evans
- Environmental Health Sciences Division, College of Public Health, The Ohio State University, Columbus, OH, USA
- Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA
| | - Jeffrey D Galley
- Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, Columbus, OH, USA
- Department of Psychiatry & Behavioral Health, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Helen J Chen
- Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, Columbus, OH, USA
- Department of Psychiatry & Behavioral Health, The Ohio State University Wexner Medical Center, Columbus, OH, USA
- Medical Scientist Training Program, The Ohio State University Wexner Medical Center, Columbus, OH, USA
- Department of Neuroscience, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Therese A Rajasekera
- Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, Columbus, OH, USA
- Department of Psychiatry & Behavioral Health, The Ohio State University Wexner Medical Center, Columbus, OH, USA
- Environmental Health Sciences Division, College of Public Health, The Ohio State University, Columbus, OH, USA
| | - Sydney M Lammers
- Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, Columbus, OH, USA
- Barnes Medical Student Research Scholarship Program, College of Medicine, The Ohio State University, Columbus, OH, USA
| | - Vanessa L Hale
- Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA
| | - Michael T Bailey
- Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, Columbus, OH, USA
- Biosciences Division, College of Dentistry, The Ohio State University, Columbus, OH, USA
- Center for Microbial Pathogenesis, The Research Institute, Nationwide Children's Hospital, Columbus, OH, USA
- Department of Pediatrics, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Tamar L Gur
- Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
- Department of Psychiatry & Behavioral Health, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
- Medical Scientist Training Program, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
- Department of Neuroscience, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
- Department of Obstetrics & Gynecology, The Ohio State University Wexner Medical Center, 120A Institute for Behavioral Medicine Research Building, 460 Medical Center Drive, Columbus, OH, 43210, USA.
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13
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Alauzet C, Cunat L, Wack M, Lanfumey L, Legrand-Frossi C, Lozniewski A, Agrinier N, Cailliez-Grimal C, Frippiat JP. Impact of a Model Used to Simulate Chronic Socio-Environmental Stressors Encountered during Spaceflight on Murine Intestinal Microbiota. Int J Mol Sci 2020; 21:ijms21217863. [PMID: 33114008 PMCID: PMC7672645 DOI: 10.3390/ijms21217863] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Revised: 10/14/2020] [Accepted: 10/21/2020] [Indexed: 12/27/2022] Open
Abstract
During deep-space travels, crewmembers face various physical and psychosocial stressors that could alter gut microbiota composition. Since it is well known that intestinal dysbiosis is involved in the onset or exacerbation of several disorders, the aim of this study was to evaluate changes in intestinal microbiota in a murine model used to mimic chronic psychosocial stressors encountered during a long-term space mission. We demonstrate that 3 weeks of exposure to this model (called CUMS for Chronic Unpredictable Mild Stress) induce significant change in intracaecal β-diversity characterized by an important increase of the Firmicutes/Bacteroidetes ratio. These alterations are associated with a decrease of Porphyromonadaceae, particularly of the genus Barnesiella, a major member of gut microbiota in mice and humans where it is described as having protective properties. These results raise the question of the impact of stress-induced decrease of beneficial taxa, support recent data deduced from in-flight experimentations and other ground-based models, and emphasize the critical need for further studies exploring the impact of spaceflight on intestinal microbiota in order to propose strategies to countermeasure spaceflight-associated dysbiosis and its consequences on health.
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Affiliation(s)
- Corentine Alauzet
- Stress Immunity Pathogens unit (SIMPA), EA 7300, Université de Lorraine, F-54000 Nancy, France; (L.C.); (C.L.-F.); (A.L.); (C.C.-G.); (J.-P.F.)
- CHRU-Nancy, Service de Microbiologie, F-54000 Nancy, France
- Correspondence: ; Tel.: +33-383-153-938
| | - Lisiane Cunat
- Stress Immunity Pathogens unit (SIMPA), EA 7300, Université de Lorraine, F-54000 Nancy, France; (L.C.); (C.L.-F.); (A.L.); (C.C.-G.); (J.-P.F.)
| | - Maxime Wack
- Département d’Informatique Médicale, Biostatistiques et Santé Publique, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, 75015 Paris, France;
- Centre de Recherche des Cordeliers, INSERM, UMRS 1138, Université de Paris, 75006 Paris, France
| | - Laurence Lanfumey
- Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, Université de Paris, F-75014 Paris, France;
| | - Christine Legrand-Frossi
- Stress Immunity Pathogens unit (SIMPA), EA 7300, Université de Lorraine, F-54000 Nancy, France; (L.C.); (C.L.-F.); (A.L.); (C.C.-G.); (J.-P.F.)
| | - Alain Lozniewski
- Stress Immunity Pathogens unit (SIMPA), EA 7300, Université de Lorraine, F-54000 Nancy, France; (L.C.); (C.L.-F.); (A.L.); (C.C.-G.); (J.-P.F.)
- CHRU-Nancy, Service de Microbiologie, F-54000 Nancy, France
| | - Nelly Agrinier
- CHRU-Nancy, INSERM, Université de Lorraine, CIC, Epidémiologie Clinique, F-54000 Nancy, France;
| | - Catherine Cailliez-Grimal
- Stress Immunity Pathogens unit (SIMPA), EA 7300, Université de Lorraine, F-54000 Nancy, France; (L.C.); (C.L.-F.); (A.L.); (C.C.-G.); (J.-P.F.)
| | - Jean-Pol Frippiat
- Stress Immunity Pathogens unit (SIMPA), EA 7300, Université de Lorraine, F-54000 Nancy, France; (L.C.); (C.L.-F.); (A.L.); (C.C.-G.); (J.-P.F.)
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14
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Thomann AK, Mak JWY, Zhang JW, Wuestenberg T, Ebert MP, Sung JJY, Bernstein ÇN, Reindl W, Ng SC. Review article: bugs, inflammation and mood-a microbiota-based approach to psychiatric symptoms in inflammatory bowel diseases. Aliment Pharmacol Ther 2020; 52:247-266. [PMID: 32525605 DOI: 10.1111/apt.15787] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2019] [Revised: 01/13/2020] [Accepted: 04/21/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND Psychiatric co-morbidities including depression and anxiety are common in inflammatory bowel diseases (IBD). Emerging evidence suggests that interactions between the gut microbiota and brain may play a role in the pathogenesis of psychiatric symptoms in IBD. AIM To review the literature on microbiota-brain-gut interactions in gut inflammation, psychosocial stress and mental disorders and to discuss the putative mediating role of gut microbiota in the development of psychiatric symptoms or co-morbidities in IBD. METHODS A literature search was conducted on Ovid and Pubmed to select relevant animal and human studies reporting an association between IBD, mental disorders and gut microbiota. RESULTS Gut microbial alterations are frequently reported in subjects with IBD and with mental disorders. Both have been associated with reduced faecal bacterial diversity, decreased taxa within the phylum Firmicutes and increased Gammaproteobacteria. In animal studies, microbial perturbations induce behavioural changes and modulate inflammation in mice. Anxiety- and depression-like behaviours in animals can be transferred via faecal microbiota. In humans, modulation of the gut microbiota with probiotics is associated with behavioural and mood changes. Recent data show correlations in changes of faecal and mucosal microbiota and psychological distress in patients with IBD independent of disease activity. CONCLUSION Both IBD and mental disorders are associated with gut microbial alterations. Preclinical and preliminary human studies have shown a mediating role of the gut microbiota in intestinal inflammation and anxiety, depression and stress. Targeting the gut microbiota may represent a useful therapeutic approach for the treatment of psychiatric co-morbidities in IBD.
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Affiliation(s)
- Anne K Thomann
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Joyce W Y Mak
- Department of Medicine and Therapeutics, Institute of Digestive Disease, LKS Institute of Health Science, The Chinese University of Hong Kong, Hong Kong
| | - Jing Wan Zhang
- Department of Medicine and Therapeutics, Institute of Digestive Disease, LKS Institute of Health Science, The Chinese University of Hong Kong, Hong Kong
| | - Torsten Wuestenberg
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Department of Psychiatry and Psychotherapy, Charite, Berlin, Germany
| | - Matthias P Ebert
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Joseph J Y Sung
- Department of Medicine and Therapeutics, Institute of Digestive Disease, LKS Institute of Health Science, The Chinese University of Hong Kong, Hong Kong
| | | | - Wolfgang Reindl
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Siew C Ng
- Department of Medicine and Therapeutics, Institute of Digestive Disease, LKS Institute of Health Science, The Chinese University of Hong Kong, Hong Kong
- Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong
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15
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Yang J, Wang C, Huang K, Zhang M, Wang J, Pan X. Compound Lactobacillus sp. administration ameliorates stress and body growth through gut microbiota optimization on weaning piglets. Appl Microbiol Biotechnol 2020; 104:6749-6765. [PMID: 32556411 DOI: 10.1007/s00253-020-10727-4] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2019] [Revised: 05/24/2020] [Accepted: 06/07/2020] [Indexed: 02/07/2023]
Abstract
The composition of bacteria in the gastrointestinal tract of piglets is easily affected by environmental changes, particularly during the weaning period. Compound strains of Lactobacillus reuteri and Lactobacillus salivarius were supplemented to piglets during pre- and post-weaning to determine their effects in improving the growth performance and ameliorating the diarrhea rate and stress caused by antioxidation in piglets. A larger number of L. reuteri and L. salivarius colonized the distal segment of the ileum and the total numbers of Lactobacillus spp. and Bifidobacteria were higher in the ileal mucous membrane and cecal lumen with probiotics supplementation. The numbers of antioxidants and immune molecules increased, levels of cortisol and endotoxin reduced, and growth hormone and insulin-like growth factor 1 improved in the plasma following compound bacteria (CL) supplementation. Spearman's and KEGG analysis of the bacterial operational taxonomic unit and antioxidative and immune indices and metabolic genes indicated that the body growth modulation by CL supplementation could be attributed to optimization of the intestinal bacterial composition; functional strains of L. delbrueckii, L. salivarius, L. formicilis, L. reuteri, and L. mucosae were positively correlated with body antioxidation and immunity derived by CL supplementation. Strains of L. agilis and L. pontis were diverse and negatively correlated with body antioxidation and immunity. Collectively, these results suggest that supplementation with CL could reduce stress and improve the growth performance of piglets during weaning by optimizing the intestinal bacterial composition. KEY POINTS: • The colonization of L. reuteri and L. salivarius in ileal mucous membrane optimize bacterial composition of GIT, mainly some functional strains of Lactobacillus, L. delbrueckii, L. salivarius, L. formicilis, L. reuteri, and L. mucosae. • The optimized bacterial composition of piglets in both ileal mucous membrane and cecal content improves body growth hormone level, immunity, and antioxidation, which is helpful to defend the stress. These benefits induce to increased growth performance of animal model piglets during weaning.
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Affiliation(s)
- Jiajun Yang
- Institute of Animal Husbandry and Veterinary Medicine, Anhui Academy of Agriculture Science, Anhui Province Key Laboratory of Livestock and Poultry Product Safety Engineering, No. 40 of NongKe South of Road, Hefei, 230031, Anhui, China
| | - Chonglong Wang
- Institute of Animal Husbandry and Veterinary Medicine, Anhui Academy of Agriculture Science, Anhui Province Key Laboratory of Livestock and Poultry Product Safety Engineering, No. 40 of NongKe South of Road, Hefei, 230031, Anhui, China. .,Key Laboratory of Pig Molecular Quantitative Genetics, Institute of Animal Husbandry and Veterinary Medicine, Anhui Academy of Agricultural Sciences, No. 40 of Nongke South Road, Hefei, 230031, Anhui, China.
| | - Kehe Huang
- Institute of Nutritional and Metabolic Disorders, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China.
| | - Minhong Zhang
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Yuanminyuan West Road, Haidian District, Beijing, 100094, China
| | - Jing Wang
- Institute of Animal Husbandry and Veterinary Medicine, Anhui Academy of Agriculture Science, Anhui Province Key Laboratory of Livestock and Poultry Product Safety Engineering, No. 40 of NongKe South of Road, Hefei, 230031, Anhui, China.,Key Laboratory of Pig Molecular Quantitative Genetics, Institute of Animal Husbandry and Veterinary Medicine, Anhui Academy of Agricultural Sciences, No. 40 of Nongke South Road, Hefei, 230031, Anhui, China
| | - Xiaocheng Pan
- Institute of Animal Husbandry and Veterinary Medicine, Anhui Academy of Agriculture Science, Anhui Province Key Laboratory of Livestock and Poultry Product Safety Engineering, No. 40 of NongKe South of Road, Hefei, 230031, Anhui, China.,Livestock and Poultry Epidemic Diseases Research Center of Anhui Province, Hefei, 230031, Anhui, China
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16
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Sinagra E, Utzeri E, Morreale GC, Fabbri C, Pace F, Anderloni A. Microbiota-gut-brain axis and its affect inflammatory bowel disease: Pathophysiological concepts and insights for clinicians. World J Clin Cases 2020; 8:1013-1025. [PMID: 32258072 PMCID: PMC7103973 DOI: 10.12998/wjcc.v8.i6.1013] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 02/14/2020] [Accepted: 03/05/2020] [Indexed: 02/05/2023] Open
Abstract
Despite the bi-directional interaction between gut microbiota and the brain not being fully understood, there is increasing evidence arising from animal and human studies that show how this intricate relationship may facilitate inflammatory bowel disease (IBD) pathogenesis, with consequent important implications on the possibility to improve the clinical outcomes of the diseases themselves, by acting on the different components of this system, mainly by modifying the microbiota. With the emergence of precision medicine, strategies in which patients with IBD might be categorized other than for standard gut symptom complexes could offer the opportunity to tailor therapies to individual patients. The aim of this narrative review is to elaborate on the concept of the gut-brain-microbiota axis and its clinical significance regarding IBD on the basis of recent scientific literature, and finally to focus on pharmacological therapies that could allow us to favorably modify the function of this complex system.
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Affiliation(s)
- Emanuele Sinagra
- Gastroenterology and Endoscopy Unit, Fondazione Istituto Giuseppe Giglio, Contrada Pietra Pollastra Pisciotto, Cefalù 90015, Italy
- Euro-Mediterranean Institute of Science and Technology, Palermo 90100, Italy
| | - Erika Utzeri
- Nuova Casa di Cura di Decimomannu, Cagliari 09100, Italy
| | | | - Carlo Fabbri
- Gastroenterology and Digestive Endoscopy Unit, Forlì-Cesena, Azienda USL Romagna, Forlì 47121, Italy
| | - Fabio Pace
- Unit of Gastroenterology, Bolognini Hospital, Bergamo 24100, Italy
| | - Andrea Anderloni
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital, Rozzano 20089, Italy
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17
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Abstract
Stress is a nonspecific response of the body to any demand imposed upon it, disrupting the body homoeostasis and manifested with symptoms such as anxiety, depression or even headache. These responses are quite frequent in the present competitive world. The aim of this review is to explore the effect of stress on gut microbiota. First, we summarize evidence of where the microbiota composition has changed as a response to a stressful situation, and thereby the effect of the stress response. Likewise, we review different interventions that can modulate microbiota and could modulate the stress according to the underlying mechanisms whereby the gut-brain axis influences stress. Finally, we review both preclinical and clinical studies that provide evidence of the effect of gut modulation on stress. In conclusion, the influence of stress on gut microbiota and gut microbiota on stress modulation is clear for different stressors, but although the preclinical evidence is so extensive, the clinical evidence is more limited. A better understanding of the mechanism underlying stress modulation through the microbiota may open new avenues for the design of therapeutics that could boost the pursued clinical benefits. These new designs should not only focus on stress but also on stress-related disorders such as anxiety and depression, in both healthy individuals and different populations.
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18
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van de Wouw M, Boehme M, Dinan TG, Cryan JF. Monocyte mobilisation, microbiota & mental illness. Brain Behav Immun 2019; 81:74-91. [PMID: 31330299 DOI: 10.1016/j.bbi.2019.07.019] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2019] [Revised: 07/12/2019] [Accepted: 07/18/2019] [Indexed: 12/13/2022] Open
Abstract
The gastrointestinal microbiome has emerged as a key player in regulating brain and behaviour. This has led to the strategy of targeting the gut microbiota to ameliorate disorders of the central nervous system. Understanding the underlying signalling pathways in which the microbiota impacts these disorders is crucial for the development of future therapeutics for improving CNS functionality. One of the major pathways through which the microbiota influences the brain is the immune system, where there is an increasing appreciation for the role of monocyte trafficking in regulating brain homeostasis. In this review, we will shed light on the role of monocyte trafficking as a relay of microbiota signals in conditions where the central nervous system is in disorder, such as stress, peripheral inflammation, ageing, traumatic brain injury, stroke, multiple sclerosis, Alzheimer's disease and Parkinson's disease. We also cover how the gastrointestinal microbiota is implicated in these mental illnesses. In addition, we aim to discuss how the monocyte system can be modulated by the gut microbiota to mitigate disorders of the central nervous system, which will lead to novel microbiota-targeted strategies.
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Affiliation(s)
| | - Marcus Boehme
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
| | - Timothy G Dinan
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioral Science, University College Cork, Cork, Ireland
| | - John F Cryan
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.
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19
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Mackos AR, Allen JM, Kim E, Ladaika CA, Gharaibeh RZ, Moore C, Parry NMA, Boyaka PN, Bailey MT. Mice Deficient in Epithelial or Myeloid Cell Iκκβ Have Distinct Colonic Microbiomes and Increased Resistance to Citrobacter rodentium Infection. Front Immunol 2019; 10:2062. [PMID: 31552024 PMCID: PMC6746829 DOI: 10.3389/fimmu.2019.02062] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Accepted: 08/15/2019] [Indexed: 12/31/2022] Open
Abstract
The colonic microenvironment, stemming from microbial, immunologic, stromal, and epithelial factors, serves as an important determinant of the host response to enteric pathogenic colonization. Infection with the enteric bacterial pathogen Citrobacter rodentium elicits a strong mucosal Th1-mediated colitis and monocyte-driven inflammation activated via the classical NF-κB pathway. Research has focused on leukocyte-mediated signaling as the main driver for C. rodentium-induced colitis, however we hypothesize that epithelial cell NF-κB also contributes to the exacerbation of infectious colitis. To test this hypothesis, compartmentalized classical NF-κB defective mice, via the deletion of IKKβ in either intestinal epithelial cells (IKKβΔIEC) or myeloid-derived cells (IKKβΔMY), and wild type (WT) mice were challenged with C. rodentium. Both pathogen colonization and colonic histopathology were significantly reduced in IKKβ-deficient mice compared to WT mice. Interestingly, colonic IL-10, RegIIIγ, TNF-α, and iNOS gene expression were increased in IKKβ-deficient mice in the absence of bacterial challenge. This was associated with increased p52, which is involved with activation of NF-κβ through the alternative pathway. IKKβ-deficient mice also had distinct differences in colonic tissue-associated and luminal microbiome that may confer protection against C. rodentium. Taken together, these data demonstrate that classical NF-κB signaling can lead to enhanced enteric pathogen colonization and resulting colonic histopathology.
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Affiliation(s)
- Amy R Mackos
- Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, OH, United States
| | - Jacob M Allen
- Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, OH, United States
| | - Eunsoo Kim
- Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, United States
| | - Chris A Ladaika
- Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, OH, United States
| | - Raad Z Gharaibeh
- Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, NC, United States.,Bioinformatics Services Division, Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Kannapolis, NC, United States
| | - Cathy Moore
- Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, NC, United States
| | - Nicola M A Parry
- Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, United States
| | - Prosper N Boyaka
- Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, United States
| | - Michael T Bailey
- Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, OH, United States.,Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, OH, United States
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The Role of Gut Microbiota in Intestinal Inflammation with Respect to Diet and Extrinsic Stressors. Microorganisms 2019; 7:microorganisms7080271. [PMID: 31430948 PMCID: PMC6722800 DOI: 10.3390/microorganisms7080271] [Citation(s) in RCA: 189] [Impact Index Per Article: 31.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Revised: 08/09/2019] [Accepted: 08/15/2019] [Indexed: 12/12/2022] Open
Abstract
The gut microbiota maintains a symbiotic relationship with the host and regulates several important functions including host metabolism, immunity, and intestinal barrier function. Intestinal inflammation and inflammatory bowel disease (IBD) are commonly associated with dysbiosis of the gut microbiota. Alterations in the gut microbiota and associated changes in metabolites as well as disruptions in the intestinal barrier are evidence of the relationship between the gut microbiota and intestinal inflammation. Recent studies have found that many factors may alter the gut microbiota, with the effects of diet being commonly-studied. Extrinsic stressors, including environmental stressors, antibiotic exposure, sleep disturbance, physical activity, and psychological stress, may also play important roles in altering the composition of the gut microbiota. Herein, we discuss the roles of the gut microbiota in intestinal inflammation in relation to diet and other extrinsic stressors.
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21
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Allen JM, Jaggers RM, Solden LM, Loman BR, Davies RH, Mackos AR, Ladaika CA, Berg BM, Chichlowski M, Bailey MT. Dietary Oligosaccharides Attenuate Stress-Induced Disruptions in Immune Reactivity and Microbial B-Vitamin Metabolism. Front Immunol 2019; 10:1774. [PMID: 31417554 PMCID: PMC6681768 DOI: 10.3389/fimmu.2019.01774] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2018] [Accepted: 07/15/2019] [Indexed: 01/12/2023] Open
Abstract
Background: Exposure to stressful stimuli dysregulates inflammatory processes and alters the gut microbiota. Prebiotics, including long-chain fermentable fibers and milk oligosaccharides, have the potential to limit inflammation through modulation of the gut microbiota. To determine whether prebiotics attenuate stress-induced inflammation and microbiota perturbations, mice were fed either a control diet or a diet supplemented with galactooligosaccharides, polydextrose and sialyllactose (GOS+PDX+SL) or sialyllactose (SL) for 2 weeks prior to and during a 6-day exposure to a social disruption stressor. Spleens were collected for immunoreactivity assays. Colon contents were examined for stressor- and diet- induced changes in the gut microbiome and metabolome through 16S rRNA gene sequencing, shotgun metagenomic sequencing and UPLC-MS/MS. Results: Stress increased circulating IL-6 and enhanced splenocyte immunoreactivity to an ex vivo LPS challenge. Diets containing GOS+PDX+SL or SL alone attenuated these responses. Stress exposure resulted in large changes to the gut metabolome, including robust shifts in amino acids, peptides, nucleotides/nucleosides, tryptophan metabolites, and B vitamins. Multiple B vitamins were inversely associated with IL-6 and were augmented in mice fed either GOS+PDX+SL or SL diets. Stressed mice exhibited distinct microbial communities with lower abundances of Lactobacillus spp. and higher abundances of Bacteroides spp. Diet supplementation with GOS+PDX+SL, but not SL alone, orthogonally altered the microbiome and enhanced the growth of Bifidobacterium spp. Metagenome-assembled genomes (MAGs) from mice fed the GOS+PDX+SL diet unveiled genes in a Bifidobacterium MAG for de novo B vitamin synthesis. B vitamers directly attenuated the stressor-induced exacerbation of cytokine production in LPS-stimulated splenocytes. Conclusions: Overall, these data indicate that colonic metabolites, including B vitamins, are responsive to psychosocial stress. Dietary prebiotics reestablish colonic B vitamins and limit stress-induced inflammation.
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Affiliation(s)
- Jacob M Allen
- Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, OH, United States
| | - Robert M Jaggers
- Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, OH, United States
| | - Lindsey M Solden
- Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, OH, United States
| | - Brett R Loman
- Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, OH, United States
| | - Ronald H Davies
- Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, OH, United States
| | - Amy R Mackos
- Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, OH, United States
| | - Christopher A Ladaika
- Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, OH, United States
| | - Brian M Berg
- Mead Johnson Pediatric Nutrition Institute, Evansville, IN, United States
| | - Maciej Chichlowski
- Mead Johnson Pediatric Nutrition Institute, Evansville, IN, United States
| | - Michael T Bailey
- Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, OH, United States.,Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, United States
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22
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Mills S, Lane JA, Smith GJ, Grimaldi KA, Ross RP, Stanton C. Precision Nutrition and the Microbiome Part II: Potential Opportunities and Pathways to Commercialisation. Nutrients 2019; 11:E1468. [PMID: 31252674 PMCID: PMC6683087 DOI: 10.3390/nu11071468] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Revised: 06/05/2019] [Accepted: 06/05/2019] [Indexed: 12/11/2022] Open
Abstract
Modulation of the human gut microbiota through probiotics, prebiotics and dietary fibre are recognised strategies to improve health and prevent disease. Yet we are only beginning to understand the impact of these interventions on the gut microbiota and the physiological consequences for the human host, thus forging the way towards evidence-based scientific validation. However, in many studies a percentage of participants can be defined as 'non-responders' and scientists are beginning to unravel what differentiates these from 'responders;' and it is now clear that an individual's baseline microbiota can influence an individual's response. Thus, microbiome composition can potentially serve as a biomarker to predict responsiveness to interventions, diets and dietary components enabling greater opportunities for its use towards disease prevention and health promotion. In Part I of this two-part review, we reviewed the current state of the science in terms of the gut microbiota and the role of diet and dietary components in shaping it and subsequent consequences for human health. In Part II, we examine the efficacy of gut-microbiota modulating therapies at different life stages and their potential to aid in the management of undernutrition and overnutrition. Given the significance of an individual's gut microbiota, we investigate the feasibility of microbiome testing and we discuss guidelines for evaluating the scientific validity of evidence for providing personalised microbiome-based dietary advice. Overall, this review highlights the potential value of the microbiome to prevent disease and maintain or promote health and in doing so, paves the pathway towards commercialisation.
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Affiliation(s)
- Susan Mills
- APC Microbiome Ireland, University College Cork, Cork T12 K8AF, Ireland.
| | - Jonathan A Lane
- H&H Group, Technical Centre, Global Research and Technology Centre, Cork P61 C996, Ireland.
| | - Graeme J Smith
- H&H Group, Technical Centre, Global Research and Technology Centre, Cork P61 C996, Ireland.
| | | | - R Paul Ross
- APC Microbiome Ireland, University College Cork, Cork T12 K8AF, Ireland.
| | - Catherine Stanton
- APC Microbiome Ireland, Teagasc Food Research Centre, Fermoy P61 C996, Co Cork, Ireland.
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23
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Maltz RM, Keirsey J, Kim SC, Mackos AR, Gharaibeh RZ, Moore CC, Xu J, Somogyi A, Bailey MT. Social Stress Affects Colonic Inflammation, the Gut Microbiome, and Short-chain Fatty Acid Levels and Receptors. J Pediatr Gastroenterol Nutr 2019; 68:533-540. [PMID: 30540706 PMCID: PMC6428608 DOI: 10.1097/mpg.0000000000002226] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVES Gastrointestinal disorders, such as inflammatory bowel diseases (IBDs) and functional gastrointestinal disorders (FGIDs), involve disrupted homeostatic interactions between the microbiota and the host. Both disorders are worsened during stress, and in laboratory mice, stress exposure has been shown to change the composition of the gut microbiome. Stress-induced changes to the microbiome exacerbate intestinal inflammation and alter intestinal motility in mice. It is, however, not yet known whether microbiota-derived short-chain fatty acids (butyrate, propionate, and acetate) and their receptors contribute to this effect. METHODS Mice were exposed to a social disruption stress, or left undisturbed as a control. After the first stress exposure, mice were orally challenged with Citrobacter rodentium or with vehicle. The levels of short-chain fatty acids (SCFAs) were measured using gas chromatography-mass spectrometry. SCFA receptors were measured via real-time polymerase chain reaction. Microbial community composition was assessed using 16S rRNA gene sequencing. RESULTS Stress exposure reduced colonic SCFA levels. Stress exposure and C rodentium, however, significantly increased SCFA levels and changed the expression of SCFA receptors. The levels of SCFAs did not correlate with the severity of colonic inflammation, but the colonic expression of the SCFA receptor GPR41 was positively associated with inflammatory cytokines and colonic histopathology scores. The relative abundances of several taxa of colonic bacteria were significantly changed by stress exposure, including SCFA producers. CONCLUSIONS Social stress can have a significant effect on infection-induced colonic inflammation, and stress-induced changes in microbial-produced metabolites and their receptors may be involved.
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Affiliation(s)
- Ross M. Maltz
- Pediatric Gastroenterology, Nationwide Children’s Hospital, Columbus, OH, United States
- Center for Microbial Pathogenesis, The Research Institute, Nationwide Children’s Hospital, Columbus, OH, United States
- Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, United States
| | - Jeremy Keirsey
- Campus Chemical Instrumentation Center Mass Spec and Proteomics, The Ohio State University, Columbus, OH, United States
| | - Sandra C. Kim
- Pediatric Gastroenterology, Nationwide Children’s Hospital, Columbus, OH, United States
- Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine
| | - Amy R. Mackos
- College of Nursing, The Ohio State University, Columbus, OH, United States
| | - Raad Z. Gharaibeh
- Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, NC, United States
- Bioinformatics Services Division, Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Kannapolis, NC, United States
| | - Cathy C. Moore
- Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, NC, United States
| | - Jinyu Xu
- Center for Microbial Pathogenesis, The Research Institute, Nationwide Children’s Hospital, Columbus, OH, United States
| | - Arpad Somogyi
- Campus Chemical Instrumentation Center Mass Spec and Proteomics, The Ohio State University, Columbus, OH, United States
| | - Michael T. Bailey
- Center for Microbial Pathogenesis, The Research Institute, Nationwide Children’s Hospital, Columbus, OH, United States
- Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, United States
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24
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Relative abundance of Akkermansia spp. and other bacterial phylotypes correlates with anxiety- and depressive-like behavior following social defeat in mice. Sci Rep 2019; 9:3281. [PMID: 30824791 PMCID: PMC6397238 DOI: 10.1038/s41598-019-40140-5] [Citation(s) in RCA: 88] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2018] [Accepted: 02/11/2019] [Indexed: 12/20/2022] Open
Abstract
As discussion of stress and stress-related disorders rapidly extends beyond the brain, gut microbiota have emerged as a promising contributor to individual differences in the risk of illness, disease course, and treatment response. Here, we employed chronic mild social defeat stress and 16S rRNA gene metagenomic sequencing to investigate the role of microbial composition in mediating anxiety- and depressive-like behavior. In socially defeated animals, we found significant reductions in the overall diversity and relative abundances of numerous bacterial genera, including Akkermansia spp., that positively correlated with behavioral metrics of both anxiety and depression. Functional analyses predicted a reduced frequency of signaling molecule pathways, including G-protein-coupled receptors, in defeated animals. Collectively, our data suggest that shifts in microbial composition may play a role in the pathogenesis of anxiety and depression.
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25
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Wei CL, Wang S, Yen JT, Cheng YF, Liao CL, Hsu CC, Wu CC, Tsai YC. Antidepressant-like activities of live and heat-killed Lactobacillus paracasei PS23 in chronic corticosterone-treated mice and possible mechanisms. Brain Res 2019; 1711:202-213. [PMID: 30684456 DOI: 10.1016/j.brainres.2019.01.025] [Citation(s) in RCA: 84] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2018] [Revised: 01/04/2019] [Accepted: 01/22/2019] [Indexed: 02/07/2023]
Abstract
Emerging evidence indicates that ingestion of specific probiotics, known as "psychobiotics", confer beneficial effects on mental health. This study investigated antidepressant-like effects and possible underlying mechanisms of Lactobacillus paracasei PS23 (PS23), live or heat-killed, in a mouse model of corticosterone-induced depression using fluoxetine as standard drug. PS23 were orally gavaged to mice from day 1 to 41 or fluoxetine from day 17 to 41 and injected with corticosterone from day 17 to 37. After the last corticosterone treatment, anxiety- and depression-like behaviors were tested within 4 days. On day 42, serum and brain tissue were collected 24 min after forced swim stress. Abnormal behavioral changes induced by corticosterone were ameliorated by treatment with live PS23 in open field and sucrose preference tests, with heat-killed PS23 in open field, forced swim and sucrose preference tests, and with fluoxetine in open field and forced swim tests. Furthermore, both live and heat-killed PS23 and fluoxetine reversed corticosterone-reduced protein levels of brain-derived neurotropic factor, mineralocorticoid, and glucocorticoid receptors in the hippocampus. In addition, live PS23 also reverses corticosterone-reduced serotonin levels in hippocampus, prefrontal cortex and striatum; whereas heat-killed PS23 reverses corticosterone-reduced dopamine levels in hippocampus and prefrontal cortex. And fluoxetine normalized reduced corticosterone level in serum. These studies showed that both live and heat-killed PS23 can reverse chronic corticosterone-induced anxiety- and depression-like behaviors and that may provide insights into the mechanism and a potential psychobiotic for depression management.
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Affiliation(s)
- Chia-Li Wei
- Department of Biochemical Science and Technology, National Chiayi University, 300 Syuefu Rd., Chiayi City 60004, Taiwan.
| | - Sabrina Wang
- Institute of Anatomy and Cell Biology, National Yang-Ming University, 155, Sec. 2, Li-Nong St., Taipei 11221, Taiwan
| | - Jui-Ting Yen
- Institute of Biochemistry and Molecular Biology, National Yang-Ming University, 155, Sec. 2, Li-Nong St., Taipei 11221, Taiwan
| | - Yun-Fang Cheng
- Bened Biomedical Co., Ltd., 2F-2, No. 129, Sec. 2, Zhongshan N. Rd., Taipei 10448, Taiwan
| | - Chia-Li Liao
- Institute of Biochemistry and Molecular Biology, National Yang-Ming University, 155, Sec. 2, Li-Nong St., Taipei 11221, Taiwan
| | - Chih-Chieh Hsu
- Bened Biomedical Co., Ltd., 2F-2, No. 129, Sec. 2, Zhongshan N. Rd., Taipei 10448, Taiwan
| | - Chien-Chen Wu
- Bened Biomedical Co., Ltd., 2F-2, No. 129, Sec. 2, Zhongshan N. Rd., Taipei 10448, Taiwan
| | - Ying-Chieh Tsai
- Institute of Biochemistry and Molecular Biology, National Yang-Ming University, 155, Sec. 2, Li-Nong St., Taipei 11221, Taiwan; Microbiome Research Center, National Yang-Ming University, 155, Sec. 2, Li-Nong St., Taipei 11221, Taiwan.
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26
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Karl JP, Hatch AM, Arcidiacono SM, Pearce SC, Pantoja-Feliciano IG, Doherty LA, Soares JW. Effects of Psychological, Environmental and Physical Stressors on the Gut Microbiota. Front Microbiol 2018; 9:2013. [PMID: 30258412 PMCID: PMC6143810 DOI: 10.3389/fmicb.2018.02013] [Citation(s) in RCA: 303] [Impact Index Per Article: 43.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2018] [Accepted: 08/09/2018] [Indexed: 12/13/2022] Open
Abstract
Stress, a ubiquitous part of daily human life, has varied biological effects which are increasingly recognized as including modulation of commensal microorganisms residing in the gastrointestinal tract, the gut microbiota. In turn, the gut microbiota influences the host stress response and associated sequelae, thereby implicating the gut microbiota as an important mediator of host health. This narrative review aims to summarize evidence concerning the impact of psychological, environmental, and physical stressors on gut microbiota composition and function. The stressors reviewed include psychological stress, circadian disruption, sleep deprivation, environmental extremes (high altitude, heat, and cold), environmental pathogens, toxicants, pollutants, and noise, physical activity, and diet (nutrient composition and food restriction). Stressors were selected for their direct relevance to military personnel, a population that is commonly exposed to these stressors, often at extremes, and in combination. However, the selected stressors are also common, alone or in combination, in some civilian populations. Evidence from preclinical studies collectively indicates that the reviewed stressors alter the composition, function and metabolic activity of the gut microbiota, but that effects vary across stressors, and can include effects that may be beneficial or detrimental to host health. Translation of these findings to humans is largely lacking at present. This gap precludes concluding with certainty that transient or cumulative exposures to psychological, environmental, and physical stressors have any consistent, meaningful impact on the human gut microbiota. However, provocative preclinical evidence highlights a need for translational research aiming to elucidate the impact of stressors on the human gut microbiota, and how the gut microbiota can be manipulated, for example by using nutrition, to mitigate adverse stress responses.
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Affiliation(s)
- J. Philip Karl
- Military Nutrition Division, U.S. Army Research Institute of Environmental Medicine, Natick, MA, United States
| | - Adrienne M. Hatch
- Military Nutrition Division, U.S. Army Research Institute of Environmental Medicine, Natick, MA, United States
| | - Steven M. Arcidiacono
- Soldier Performance Optimization, Natick Soldier Research, Development and Engineering Center, Natick, MA, United States
| | - Sarah C. Pearce
- Combat Feeding Directorate, Natick Soldier Research, Development and Engineering Center, Natick, MA, United States
| | - Ida G. Pantoja-Feliciano
- Soldier Performance Optimization, Natick Soldier Research, Development and Engineering Center, Natick, MA, United States
| | - Laurel A. Doherty
- Soldier Performance Optimization, Natick Soldier Research, Development and Engineering Center, Natick, MA, United States
| | - Jason W. Soares
- Soldier Performance Optimization, Natick Soldier Research, Development and Engineering Center, Natick, MA, United States
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27
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van de Wouw M, Boehme M, Lyte JM, Wiley N, Strain C, O'Sullivan O, Clarke G, Stanton C, Dinan TG, Cryan JF. Short-chain fatty acids: microbial metabolites that alleviate stress-induced brain-gut axis alterations. J Physiol 2018; 596:4923-4944. [PMID: 30066368 DOI: 10.1113/jp276431] [Citation(s) in RCA: 486] [Impact Index Per Article: 69.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2018] [Accepted: 06/22/2018] [Indexed: 02/06/2023] Open
Abstract
KEY POINTS Chronic (psychosocial) stress changes gut microbiota composition, as well as inducing behavioural and physiological deficits. The microbial metabolites short-chain fatty acids (SCFAs) have been implicated in gastrointestinal functional, (neuro)immune regulation and host metabolism, but their role in stress-induced behavioural and physiological alterations is poorly understood. Administration of SCFAs to mice undergoing psychosocial stress alleviates enduring alterations in anhedonia and heightened stress-responsiveness, as well as stress-induced increases in intestinal permeability. In contrast, chronic stress-induced alterations in body weight gain, faecal SCFAs and the gene expression of the SCFA receptors FFAR2 and FFAR3 remained unaffected by SCFA supplementation. These results present novel insights into mechanisms underpinning the influence of the gut microbiota on brain homeostasis, behaviour and host metabolism, informing the development of microbiota-targeted therapies for stress-related disorders. ABSTRACT There is a growing recognition of the involvement of the gastrointestinal microbiota in the regulation of physiology and behaviour. Microbiota-derived metabolites play a central role in the communication between microbes and their host, with short-chain fatty acids (SCFAs) being perhaps the most studied. SCFAs are primarily derived from fermentation of dietary fibres and play a pivotal role in host gut, metabolic and immune function. All these factors have previously been demonstrated to be adversely affected by stress. Therefore, we sought to assess whether SCFA supplementation could counteract the enduring effects of chronic psychosocial stress. C57BL/6J male mice received oral supplementation of a mixture of the three principle SCFAs (acetate, propionate and butyrate). One week later, mice underwent 3 weeks of repeated psychosocial stress, followed by a comprehensive behavioural analysis. Finally, plasma corticosterone, faecal SCFAs and caecal microbiota composition were assessed. SCFA treatment alleviated psychosocial stress-induced alterations in reward-seeking behaviour, and increased responsiveness to an acute stressor and in vivo intestinal permeability. In addition, SCFAs exhibited behavioural test-specific antidepressant and anxiolytic effects, which were not present when mice had also undergone psychosocial stress. Stress-induced increases in body weight gain, faecal SCFAs and the colonic gene expression of the SCFA receptors free fatty acid receptors 2 and 3 remained unaffected by SCFA supplementation. Moreover, there were no collateral effects on caecal microbiota composition. Taken together, these data show that SCFA supplementation alleviates selective and enduring alterations induced by repeated psychosocial stress and these data may inform future research into microbiota-targeted therapies for stress-related disorders.
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Affiliation(s)
- Marcel van de Wouw
- Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.,APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Marcus Boehme
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Joshua M Lyte
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Niamh Wiley
- APC Microbiome Ireland, University College Cork, Cork, Ireland.,Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland
| | - Conall Strain
- APC Microbiome Ireland, University College Cork, Cork, Ireland.,Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland
| | - Orla O'Sullivan
- APC Microbiome Ireland, University College Cork, Cork, Ireland.,Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland
| | - Gerard Clarke
- APC Microbiome Ireland, University College Cork, Cork, Ireland.,Department of Psychiatry and Neurobehavioral Science, University College Cork, Cork, Ireland
| | - Catherine Stanton
- APC Microbiome Ireland, University College Cork, Cork, Ireland.,Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland
| | - Timothy G Dinan
- APC Microbiome Ireland, University College Cork, Cork, Ireland.,Department of Psychiatry and Neurobehavioral Science, University College Cork, Cork, Ireland
| | - John F Cryan
- Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.,APC Microbiome Ireland, University College Cork, Cork, Ireland.,Department of Psychiatry and Neurobehavioral Science, University College Cork, Cork, Ireland
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28
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Maltz RM, Keirsey J, Kim SC, Mackos AR, Gharaibeh RZ, Moore CC, Xu J, Bakthavatchalu V, Somogyi A, Bailey MT. Prolonged restraint stressor exposure in outbred CD-1 mice impacts microbiota, colonic inflammation, and short chain fatty acids. PLoS One 2018; 13:e0196961. [PMID: 29742146 PMCID: PMC5942810 DOI: 10.1371/journal.pone.0196961] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2017] [Accepted: 04/24/2018] [Indexed: 12/13/2022] Open
Abstract
Stressor-exposure has been shown to exacerbate inflammation and change the composition of the gastrointestinal microbiota; however stressor-induced effects on microbiota-derived metabolites and their receptors are unknown. Thus, bacterial-produced short chain fatty acids (SCFAs), as well as microbial community composition, were assessed in the colons of mice exposed to stress during infection with Citrobacter rodentium. Mice were exposed to overnight restraint on 7 consecutive nights, or left undisturbed as a control. After the first exposure of restraint, mice were orally challenged with C. rodentium or with vehicle. Microbial community composition was assessed using 16S rRNA gene sequencing and SCFA levels measured using gas chromatography-mass spectrometry (GC-MS). Pathogen levels and colonic inflammation were also assessed 6 days post-infection. Results demonstrated that the microbial community structure and SCFA production were significantly affected by both stressor exposure and C. rodentium-infection. Exposure to prolonged restraint in the absence of infection significantly reduced SCFAs (acetic acid, butyric acid, and propionic acid). Multiple bacterial taxa were affected by stressor exposure, with the relative abundance of Lactobacillus being significantly reduced and directly correlated with propionic acid. Lactobacillus abundances were inversely correlated with colonic inflammation, supporting the contention that Lactobacillus helps to regulate mucosal inflammatory responses. Our data indicates that restraint stressor can have significant effects on pathogen-induced colonic inflammation and suggest that stressor-induced changes in the microbiota, microbial-produced SCFAs and their receptors may be involved.
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Affiliation(s)
- Ross M. Maltz
- Pediatric Gastroenterology, Nationwide Children's Hospital, Columbus, OH, United States of America
- Center for Microbial Pathogenesis, The Research Institute, Nationwide Children’s Hospital, Columbus, OH, United States of America
- Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, United States of America
| | - Jeremy Keirsey
- Campus Chemical Instrumentation Center Mass Spec and Proteomics, The Ohio State University, Columbus, OH, United States of America
| | - Sandra C. Kim
- Pediatric Gastroenterology, Nationwide Children's Hospital, Columbus, OH, United States of America
- Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America
| | - Amy R. Mackos
- Center for Microbial Pathogenesis, The Research Institute, Nationwide Children’s Hospital, Columbus, OH, United States of America
| | - Raad Z. Gharaibeh
- Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, NC, United States of America
- Bioinformatics Services Division, Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Kannapolis, NC, United States of America
| | - Cathy C. Moore
- Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, NC, United States of America
| | - Jinyu Xu
- Center for Microbial Pathogenesis, The Research Institute, Nationwide Children’s Hospital, Columbus, OH, United States of America
| | - Vasudevan Bakthavatchalu
- The Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, United States of America
| | - Arpad Somogyi
- Campus Chemical Instrumentation Center Mass Spec and Proteomics, The Ohio State University, Columbus, OH, United States of America
| | - Michael T. Bailey
- Center for Microbial Pathogenesis, The Research Institute, Nationwide Children’s Hospital, Columbus, OH, United States of America
- Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, United States of America
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29
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Mu Q, Tavella VJ, Luo XM. Role of Lactobacillus reuteri in Human Health and Diseases. Front Microbiol 2018; 9:757. [PMID: 29725324 PMCID: PMC5917019 DOI: 10.3389/fmicb.2018.00757] [Citation(s) in RCA: 438] [Impact Index Per Article: 62.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2017] [Accepted: 04/04/2018] [Indexed: 12/13/2022] Open
Abstract
Lactobacillus reuteri (L. reuteri) is a well-studied probiotic bacterium that can colonize a large number of mammals. In humans, L. reuteri is found in different body sites, including the gastrointestinal tract, urinary tract, skin, and breast milk. The abundance of L. reuteri varies among different individuals. Several beneficial effects of L. reuteri have been noted. First, L. reuteri can produce antimicrobial molecules, such as organic acids, ethanol, and reuterin. Due to its antimicrobial activity, L. reuteri is able to inhibit the colonization of pathogenic microbes and remodel the commensal microbiota composition in the host. Second, L. reuteri can benefit the host immune system. For instance, some L. reuteri strains can reduce the production of pro-inflammatory cytokines while promoting regulatory T cell development and function. Third, bearing the ability to strengthen the intestinal barrier, the colonization of L. reuteri may decrease the microbial translocation from the gut lumen to the tissues. Microbial translocation across the intestinal epithelium has been hypothesized as an initiator of inflammation. Therefore, inflammatory diseases, including those located in the gut as well as in remote tissues, may be ameliorated by increasing the colonization of L. reuteri. Notably, the decrease in the abundance of L. reuteri in humans in the past decades is correlated with an increase in the incidences of inflammatory diseases over the same period of time. Direct supplementation or prebiotic modulation of L. reuteri may be an attractive preventive and/or therapeutic avenue against inflammatory diseases.
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Affiliation(s)
| | | | - Xin M. Luo
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States
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