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Akerele CA, Koralnik LR, Lafont E, Gilman C, Walsh-Messinger J, Malaspina D. Nutrition and brain health: Implications of Mediterranean diet elements for psychiatric disorders. Schizophr Res 2025; 281:30-44. [PMID: 40315757 DOI: 10.1016/j.schres.2025.04.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2024] [Revised: 04/03/2025] [Accepted: 04/23/2025] [Indexed: 05/04/2025]
Abstract
The Mediterranean diet is an anti-inflammatory diet now recognized for prevention and intervention against cardiometabolic disorders, although emerging literature also shows its benefits for mental health. This paper surveys literature pertinent to the Mediterranean diet with respect to schizophrenia, bipolar and unipolar depression and cognition. The National Library of Medicine database of literature was searched for publications relating to our topic through June 2024. Our results highlight the Mediterranean diet's potential role in mediating inflammation, potentially through the gut-brain axis, and its neuroprotective role against cognitive decline. Moreover, individual components of the Mediterranean diet are potentially therapeutic as well as protective, particularly fruits, vegetables, fatty fish, and whole grains. These dietary components reduce systemic inflammation, modulate gut microbiota and influence critical pathways such as moderating oxidative stress. Overall, this survey of recent literature highlights the potential of the Mediterranean diet to promote mental health and reduce the risk or severity of psychiatric and neurodegenerative disorders. The analysis underscores broader implications for the Mediterranean diet in advancing mental health outcomes and emphasizes the need for further studies and increased public education to encourage healthier eating habits and dietary interventions.
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Affiliation(s)
| | | | - Ezequiel Lafont
- Icahn School of Medicine at Mount Sinai, Department of Psychiatry, New York, NY 10029, USA
| | - Caitlin Gilman
- Albert Einstein College of Medicine, Bronx, NY 10461, USA
| | | | - Dolores Malaspina
- Icahn School of Medicine at Mount Sinai, Department of Psychiatry, New York, NY 10029, USA.
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2
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Hung LY, Margolis KG. Autism spectrum disorders and the gastrointestinal tract: insights into mechanisms and clinical relevance. Nat Rev Gastroenterol Hepatol 2024; 21:142-163. [PMID: 38114585 DOI: 10.1038/s41575-023-00857-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/11/2023] [Indexed: 12/21/2023]
Abstract
Autism spectrum disorders (ASDs) are recognized as central neurodevelopmental disorders diagnosed by impairments in social interactions, communication and repetitive behaviours. The recognition of ASD as a central nervous system (CNS)-mediated neurobehavioural disorder has led most of the research in ASD to be focused on the CNS. However, gastrointestinal function is also likely to be affected owing to the neural mechanistic nature of ASD and the nervous system in the gastrointestinal tract (enteric nervous system). Thus, it is unsurprising that gastrointestinal disorders, particularly constipation, diarrhoea and abdominal pain, are highly comorbid in individuals with ASD. Gastrointestinal problems have also been repeatedly associated with increased severity of the core symptoms diagnostic of ASD and other centrally mediated comorbid conditions, including psychiatric issues, irritability, rigid-compulsive behaviours and aggression. Despite the high prevalence of gastrointestinal dysfunction in ASD and its associated behavioural comorbidities, the specific links between these two conditions have not been clearly delineated, and current data linking ASD to gastrointestinal dysfunction have not been extensively reviewed. This Review outlines the established and emerging clinical and preclinical evidence that emphasizes the gut as a novel mechanistic and potential therapeutic target for individuals with ASD.
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Affiliation(s)
- Lin Y Hung
- Department of Molecular Pathobiology, College of Dentistry, New York University, New York, NY, USA
| | - Kara Gross Margolis
- Department of Molecular Pathobiology, College of Dentistry, New York University, New York, NY, USA.
- Department of Cell Biology, NYU Grossman School of Medicine and Langone Medical Center, New York, NY, USA.
- Department of Pediatrics, NYU Grossman School of Medicine and Langone Medical Center, New York, NY, USA.
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3
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Reaney L, Collins A. Complex visceral hyperalgesia in an adolescent with Pitt-Hopkins syndrome. BMJ Case Rep 2024; 17:e258257. [PMID: 38373809 PMCID: PMC10882374 DOI: 10.1136/bcr-2023-258257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2024] Open
Abstract
An early-adolescent boy with a background of Pitt-Hopkins syndrome was transferred to a tertiary paediatric hospital with symptoms of a functional large bowel obstruction. He required extensive surgical intervention including a transverse colectomy, drainage of an abdominal abscess, laparotomy and adhesionolysis, and insertion of a gastrostomy and jejunostomy. He had significant ongoing issues with visceral hyperalgesia that was refractory to a wide range of pharmacological treatments and required admission to the intensive care unit on multiple occasions, and consultations with international experts in Pitt-Hopkins syndrome and pain specialists. An individualised pain plan was created and adjusted over time, with eventual good effect, and he was transferred back to his regional hospital and subsequently discharged home.
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Affiliation(s)
- Laura Reaney
- General Paediatrics, Children's Health Ireland at Crumlin, Dublin 12, Ireland
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4
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Xiong RG, Li J, Cheng J, Zhou DD, Wu SX, Huang SY, Saimaiti A, Yang ZJ, Gan RY, Li HB. The Role of Gut Microbiota in Anxiety, Depression, and Other Mental Disorders as Well as the Protective Effects of Dietary Components. Nutrients 2023; 15:3258. [PMID: 37513676 PMCID: PMC10384867 DOI: 10.3390/nu15143258] [Citation(s) in RCA: 59] [Impact Index Per Article: 29.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 07/20/2023] [Accepted: 07/21/2023] [Indexed: 07/30/2023] Open
Abstract
The number of individuals experiencing mental disorders (e.g., anxiety and depression) has significantly risen in recent years. Therefore, it is essential to seek prevention and treatment strategies for mental disorders. Several gut microbiota, especially Firmicutes and Bacteroidetes, are demonstrated to affect mental health through microbiota-gut-brain axis, and the gut microbiota dysbiosis can be related to mental disorders, such as anxiety, depression, and other mental disorders. On the other hand, dietary components, including probiotics (e.g., Lactobacillus and Bifidobacterium), prebiotics (e.g., dietary fiber and alpha-lactalbumin), synbiotics, postbiotics (e.g., short-chain fatty acids), dairy products, spices (e.g., Zanthoxylum bungeanum, curcumin, and capsaicin), fruits, vegetables, medicinal herbs, and so on, could exert protective effects against mental disorders by enhancing beneficial gut microbiota while suppressing harmful ones. In this paper, the mental disorder-associated gut microbiota are summarized. In addition, the protective effects of dietary components on mental health through targeting the gut microbiota are discussed. This paper can be helpful to develop some dietary natural products into pharmaceuticals and functional foods to prevent and treat mental disorders.
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Affiliation(s)
- Ruo-Gu Xiong
- School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; (R.-G.X.); (J.C.); (D.-D.Z.); (S.-X.W.); (S.-Y.H.); (A.S.); (Z.-J.Y.)
| | - Jiahui Li
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China;
| | - Jin Cheng
- School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; (R.-G.X.); (J.C.); (D.-D.Z.); (S.-X.W.); (S.-Y.H.); (A.S.); (Z.-J.Y.)
| | - Dan-Dan Zhou
- School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; (R.-G.X.); (J.C.); (D.-D.Z.); (S.-X.W.); (S.-Y.H.); (A.S.); (Z.-J.Y.)
| | - Si-Xia Wu
- School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; (R.-G.X.); (J.C.); (D.-D.Z.); (S.-X.W.); (S.-Y.H.); (A.S.); (Z.-J.Y.)
| | - Si-Yu Huang
- School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; (R.-G.X.); (J.C.); (D.-D.Z.); (S.-X.W.); (S.-Y.H.); (A.S.); (Z.-J.Y.)
| | - Adila Saimaiti
- School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; (R.-G.X.); (J.C.); (D.-D.Z.); (S.-X.W.); (S.-Y.H.); (A.S.); (Z.-J.Y.)
| | - Zhi-Jun Yang
- School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; (R.-G.X.); (J.C.); (D.-D.Z.); (S.-X.W.); (S.-Y.H.); (A.S.); (Z.-J.Y.)
| | - Ren-You Gan
- Singapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, Singapore 138669, Singapore
| | - Hua-Bin Li
- School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; (R.-G.X.); (J.C.); (D.-D.Z.); (S.-X.W.); (S.-Y.H.); (A.S.); (Z.-J.Y.)
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5
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Frame NW, Allas MJ, Pequegnat B, Vinogradov E, Liao VCH, Al-Abdul-Wahid S, Arroyo L, Allen-Vercoe E, Lowary TL, Monteiro MA. Structure and synthesis of a vaccine and diagnostic target for Enterocloster bolteae, an autism-associated gut pathogen – Part II. Carbohydr Res 2023; 526:108805. [PMID: 37023666 DOI: 10.1016/j.carres.2023.108805] [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: 08/13/2022] [Revised: 03/25/2023] [Accepted: 03/29/2023] [Indexed: 04/03/2023]
Abstract
Enterocloster bolteae (formerly known as Clostridium bolteae) is a gastro-intestinal pathogenic bacterium often detected in the fecal microbiome of children in the autism spectrum. E. bolteae excretes metabolites that are thought to act as neurotoxins. This study is an update of our first E. bolteae investigation that discovered an immunogenic polysaccharide. Through a combination of chemical derivatizations/degradations, spectrometry and spectroscopy techniques, a polysaccharide composed of disaccharide repeating blocks comprised of 3-linked β-d-ribofuranose and 4-linked α-l-rhamnopyranose, [→3)-β-D-Ribf-(1 → 4)-α-L-Rhap-(1→]n, was identified. To confirm the structure, and to provide material for subsequent investigations, the chemical synthesis of a corresponding linker-equipped tetrasaccharide, β-D-Ribf-(1 → 4)-α-L-Rhap-(1 → 3)-β-D-Ribf-(1 → 4)-α-L-Rhap-(1→O(CH2)8N3, is also described. Research tools based on this immunogenic glycan structure can form the foundation for serotype classification, diagnostic/vaccine targets and clinical studies into the hypothesized role of E. bolteae in the onset/augmentation of autism related conditions in children.
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Affiliation(s)
- Nolan W Frame
- Department of Chemistry, University of Guelph, Guelph, ON, N1G 2W1, Canada
| | - Mikel Jason Allas
- Department of Chemistry, University of Alberta, Edmonton, AB, T6G 2G2, Canada; Institute of Biological Chemistry, Academia Sinica, Nangang, Taipei, 11529, Taiwan
| | - Brittany Pequegnat
- Department of Chemistry, University of Guelph, Guelph, ON, N1G 2W1, Canada
| | | | - Victor C-H Liao
- Institute of Biological Chemistry, Academia Sinica, Nangang, Taipei, 11529, Taiwan
| | | | - Luis Arroyo
- Department of Clinical Studies, University of Guelph, N1G 2W1, Guelph, ON, Canada
| | - Emma Allen-Vercoe
- Department of Microbiology, University of Guelph, N1G 2W1, Guelph, ON, Canada
| | - Todd L Lowary
- Institute of Biological Chemistry, Academia Sinica, Nangang, Taipei, 11529, Taiwan; Institute of Biochemical Sciences, National Taiwan University, Taipei, 106, Taiwan.
| | - Mario A Monteiro
- Department of Chemistry, University of Guelph, Guelph, ON, N1G 2W1, Canada.
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6
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Nanda H, Frye RE. Synchrony 2022: Catalyzing Research and Treatments to Benefit Individuals with Neurodevelopmental Disorders including Autism Spectrum Disorders. J Pers Med 2023; 13:jpm13030490. [PMID: 36983672 PMCID: PMC10053654 DOI: 10.3390/jpm13030490] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Accepted: 03/07/2023] [Indexed: 03/12/2023] Open
Abstract
A unique translational medicine conference for research into treatments that can benefit individuals with neurodevelopmental disorders (NDD), including autism spectrum disorder (ASD), has been developed and hosted by The BRAIN Foundation (Pleasanton, CA, USA) since 2019 [...]
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Affiliation(s)
- Heer Nanda
- University of California, Berkeley, CA 94720, USA
| | - Richard E. Frye
- Autism Discovery and Treatment Foundation, Phoenix, AZ 85050, USA
- Rossignol Medical Center, Phoenix, AZ 85050, USA
- Southwest Autism Research and Resource Center, Phoenix, AZ 85006, USA
- Correspondence:
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7
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Zheng L. New insights into the interplay between intestinal flora and bile acids in inflammatory bowel disease. World J Clin Cases 2022; 10:10823-10839. [PMID: 36338232 PMCID: PMC9631134 DOI: 10.12998/wjcc.v10.i30.10823] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 06/08/2022] [Accepted: 09/16/2022] [Indexed: 02/05/2023] Open
Abstract
Intestinal flora plays a key role in nutrient absorption, metabolism and immune defense, and is considered to be the cornerstone of maintaining the health of human hosts. Bile acids synthesized in the liver can not only promote the absorption of fat-soluble substances in the intestine, but also directly or indirectly affect the structure and function of intestinal flora. Under the action of intestinal flora, bile acids can be converted into secondary bile acids, which can be reabsorbed back to the liver through the enterohepatic circulation. The complex dialogue mechanism between intestinal flora and bile acids is involved in the development of intestinal inflammation such as inflammatory bowel disease (IBD). In this review, the effects of intestinal flora, bile acids and their interactions on IBD and the progress of treatment were reviewed.
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Affiliation(s)
- Lie Zheng
- Department of Gastroenterology, Shaanxi Hospital of Traditional Chinese Medicine, Xi’an 710003, Shaanxi Province, China
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8
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West KA, Yin X, Rutherford EM, Wee B, Choi J, Chrisman BS, Dunlap KL, Hannibal RL, Hartono W, Lin M, Raack E, Sabino K, Wu Y, Wall DP, David MM, Dabbagh K, DeSantis TZ, Iwai S. Multi-angle meta-analysis of the gut microbiome in Autism Spectrum Disorder: a step toward understanding patient subgroups. Sci Rep 2022; 12:17034. [PMID: 36220843 PMCID: PMC9554176 DOI: 10.1038/s41598-022-21327-9] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 09/26/2022] [Indexed: 12/29/2022] Open
Abstract
Observational studies have shown that the composition of the human gut microbiome in children diagnosed with Autism Spectrum Disorder (ASD) differs significantly from that of their neurotypical (NT) counterparts. Thus far, reported ASD-specific microbiome signatures have been inconsistent. To uncover reproducible signatures, we compiled 10 publicly available raw amplicon and metagenomic sequencing datasets alongside new data generated from an internal cohort (the largest ASD cohort to date), unified them with standardized pre-processing methods, and conducted a comprehensive meta-analysis of all taxa and variables detected across multiple studies. By screening metadata to test associations between the microbiome and 52 variables in multiple patient subsets and across multiple datasets, we determined that differentially abundant taxa in ASD versus NT children were dependent upon age, sex, and bowel function, thus marking these variables as potential confounders in case-control ASD studies. Several taxa, including the strains Bacteroides stercoris t__190463 and Clostridium M bolteae t__180407, and the species Granulicatella elegans and Massilioclostridium coli, exhibited differential abundance in ASD compared to NT children only after subjects with bowel dysfunction were removed. Adjusting for age, sex and bowel function resulted in adding or removing significantly differentially abundant taxa in ASD-diagnosed individuals, emphasizing the importance of collecting and controlling for these metadata. We have performed the largest (n = 690) and most comprehensive systematic analysis of ASD gut microbiome data to date. Our study demonstrated the importance of accounting for confounding variables when designing statistical comparative analyses of ASD- and NT-associated gut bacterial profiles. Mitigating these confounders identified robust microbial signatures across cohorts, signifying the importance of accounting for these factors in comparative analyses of ASD and NT-associated gut profiles. Such studies will advance the understanding of different patient groups to deliver appropriate therapeutics by identifying microbiome traits germane to the specific ASD phenotype.
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Affiliation(s)
| | | | | | | | | | | | - Kaiti L Dunlap
- Departments of Pediatrics (Systems Medicine), Stanford University, Stanford, CA, USA
| | | | | | | | | | | | - Yonggan Wu
- Second Genome Inc., Brisbane, CA, USA
- Labii Inc., South San Francisco, CA, USA
| | - Dennis P Wall
- Departments of Pediatrics (Systems Medicine), Stanford University, Stanford, CA, USA
- Department of Biomedical Data Science, Stanford University, Stanford, CA, USA
- Department of Psychiatry and Behavioral Sciences (By Courtesy), Stanford University, Stanford, CA, USA
| | - Maude M David
- Department of Microbiology, Oregon State University, Corvallis, OR, USA
- Department of Pharmaceutical Sciences, Oregon State University, Corvallis, OR, USA
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9
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Altered Blood Brain Barrier Permeability and Oxidative Stress in Cntnap2 Knockout Rat Model. J Clin Med 2022; 11:jcm11102725. [PMID: 35628852 PMCID: PMC9146766 DOI: 10.3390/jcm11102725] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Revised: 05/02/2022] [Accepted: 05/03/2022] [Indexed: 02/04/2023] Open
Abstract
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by three core symptoms, specifically impaired social behavior, stereotypic/repetitive behaviors, and sensory/communication deficits. Although the exact pathophysiology of ASD is still unknown, host genetics, oxidative stress, and compromised blood brain barrier (BBB) have been implicated in predisposition to ASD. With regards to genetics, mutations in the genes such as CNTNAP2 have been associated with increased susceptibility of developing ASD. Although some studies observed conflicting results suggesting no association of CNTNAP2 with ASD, other investigations correlated this gene with autism. In addition, CNTNAP2 mediated signaling is generally considered to play a role in neurological disorders due to its critical role in neurodevelopment, neurotransmission, and synaptic plasticity. In this investigation, we studied BBB integrity and oxidative stress in Cntnap2−/− rats. We observed that the BBB permeability was significantly increased in Cntnap2−/− rats compared to littermate wild-type (WT) animals as determined by FITC-dextran and Evans blue assay. High levels of thiobarbituric acid reactive substances and lower amounts of reduced glutathione were observed in brain homogenates of Cntnap2−/− rats, suggesting oxidative stress. Brain sections from Cntnap2−/− rats showed intense inducible nitric oxide synthase immunostaining, which was undetectable in WT animals. Quantification of nitric oxide in brain homogenates revealed significantly high levels in Cntnap2−/− rats compared to the control group. As increased permeability of the BBB and oxidative stress have been observed in ASD individuals, our results suggest that Cntnap2−/− rats have a high construct and face validity and can be explored to develop effective therapeutic modalities.
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