Gut microbiome in Schizophrenia: Altered functional pathways related to immune modulation and atherosclerotic risk

•SZ is associated with altered gut microbial composition and functional potential.•Models based on the gut microbiome differentiated SZ from NCs with high accuracy.•Lachnospiraceae was associated with SZ.•TMAO reductase and Kdo2-lipid A biosynthesis functional pathways were altered in SZ.•Pathways w...

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Published inBrain, behavior, and immunity Vol. 91; pp. 245 - 256
Main Authors Nguyen, Tanya T., Kosciolek, Tomasz, Daly, Rebecca E., Vázquez-Baeza, Yoshiki, Swafford, Austin, Knight, Rob, Jeste, Dilip V.
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier Inc 01.01.2021
Subjects
Accelerated aging
Bacteria
Clostridiales
Functional pathways
Gastrointestinal Microbiome
Gut-brain axis
Humans
Inflammation
Microbes
Microbiota
Psychosis
RNA, Ribosomal, 16S - genetics
Schizophrenia
Serious mental illness
Psychosis
Functional pathways
Accelerated aging
Gut-brain axis
Serious mental illness
Bacteria
Inflammation
Microbes
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Abstract •SZ is associated with altered gut microbial composition and functional potential.•Models based on the gut microbiome differentiated SZ from NCs with high accuracy.•Lachnospiraceae was associated with SZ.•TMAO reductase and Kdo2-lipid A biosynthesis functional pathways were altered in SZ.•Pathways were associated with inflammatory cytokines and risk for coronary heart disease in SZ. Emerging evidence has linked the gut microbiome changes to schizophrenia. However, there has been limited research into the functional pathways by which the gut microbiota contributes to the phenotype of persons with chronic schizophrenia. We characterized the composition and functional potential of the gut microbiota in 48 individuals with chronic schizophrenia and 48 matched (sequencing plate, age, sex, BMI, and antibiotic use) non-psychiatric comparison subjects (NCs) using 16S rRNA sequencing. Patients with schizophrenia demonstrated significant beta-diversity differences in microbial composition and predicted genetic functional potential compared to NCs. Alpha-diversity of taxa and functional pathways were not different between groups. Random forests analyses revealed that the microbiome predicts differentiation of patients with schizophrenia from NCs using taxa (75% accuracy) and functional profiles (67% accuracy for KEGG orthologs, 70% for MetaCyc pathways). We utilized a new compositionally-aware method incorporating reference frames to identify differentially abundant microbes and pathways, which revealed that Lachnospiraceae is associated with schizophrenia. Functional pathways related to trimethylamine-N-oxide reductase and Kdo2-lipid A biosynthesis were altered in schizophrenia. These metabolic pathways were associated with inflammatory cytokines and risk for coronary heart disease in schizophrenia. Findings suggest potential mechanisms by which the microbiota may impact the pathophysiology of the disease through modulation of functional pathways related to immune signaling/response and lipid and glucose regulation to be further investigated in future studies.
AbstractList Emerging evidence has linked the gut microbiome changes to schizophrenia. However, there has been limited research into the functional pathways by which the gut microbiota contributes to the phenotype of persons with chronic schizophrenia. We characterized the composition and functional potential of the gut microbiota in 48 individuals with chronic schizophrenia and 48 matched (sequencing plate, age, sex, BMI, and antibiotic use) non-psychiatric comparison subjects (NCs) using 16S rRNA sequencing. Patients with schizophrenia demonstrated significant beta-diversity differences in microbial composition and predicted genetic functional potential compared to NCs. Alpha-diversity of taxa and functional pathways were not different between groups. Random forests analyses revealed that the microbiome predicts differentiation of patients with schizophrenia from NCs using taxa (75% accuracy) and functional profiles (67% accuracy for KEGG orthologs, 70% for MetaCyc pathways). We utilized a new compositionally-aware method incorporating reference frames to identify differentially abundant microbes and pathways, which revealed that Lachnospiraceae is associated with schizophrenia. Functional pathways related to trimethylamine-N-oxide reductase and Kdo2-lipid A biosynthesis were altered in schizophrenia. These metabolic pathways were associated with inflammatory cytokines and risk for coronary heart disease in schizophrenia. Findings suggest potential mechanisms by which the microbiota may impact the pathophysiology of the disease through modulation of functional pathways related to immune signaling/response and lipid and glucose regulation to be further investigated in future studies.Emerging evidence has linked the gut microbiome changes to schizophrenia. However, there has been limited research into the functional pathways by which the gut microbiota contributes to the phenotype of persons with chronic schizophrenia. We characterized the composition and functional potential of the gut microbiota in 48 individuals with chronic schizophrenia and 48 matched (sequencing plate, age, sex, BMI, and antibiotic use) non-psychiatric comparison subjects (NCs) using 16S rRNA sequencing. Patients with schizophrenia demonstrated significant beta-diversity differences in microbial composition and predicted genetic functional potential compared to NCs. Alpha-diversity of taxa and functional pathways were not different between groups. Random forests analyses revealed that the microbiome predicts differentiation of patients with schizophrenia from NCs using taxa (75% accuracy) and functional profiles (67% accuracy for KEGG orthologs, 70% for MetaCyc pathways). We utilized a new compositionally-aware method incorporating reference frames to identify differentially abundant microbes and pathways, which revealed that Lachnospiraceae is associated with schizophrenia. Functional pathways related to trimethylamine-N-oxide reductase and Kdo2-lipid A biosynthesis were altered in schizophrenia. These metabolic pathways were associated with inflammatory cytokines and risk for coronary heart disease in schizophrenia. Findings suggest potential mechanisms by which the microbiota may impact the pathophysiology of the disease through modulation of functional pathways related to immune signaling/response and lipid and glucose regulation to be further investigated in future studies.
Emerging evidence has linked the gut microbiome changes to schizophrenia. However, there has been limited research into the functional pathways by which the gut microbiota contributes to the phenotype of persons with chronic schizophrenia. We characterized the composition and functional potential of the gut microbiota in 48 individuals with chronic schizophrenia and 48 matched (sequencing plate, age, sex, BMI, and antibiotic use) non-psychiatric comparison subjects (NCs) using 16S rRNA sequencing. Patients with schizophrenia demonstrated significant beta-diversity differences in microbial composition and predicted genetic functional potential compared to NCs. Alpha-diversity of taxa and functional pathways were not different between groups. Random forests analyses revealed that the microbiome predicts differentiation of patients with schizophrenia from NCs using taxa (75% accuracy) and functional profiles (67% accuracy for KEGG orthologs, 70% for MetaCyc pathways). We utilized a new compositionally-aware method incorporating reference frames to identify differentially abundant microbes and pathways, which revealed that Lachnospiraceae is associated with schizophrenia. Functional pathways related to trimethylamine-N-oxide reductase and Kdo -lipid A biosynthesis were altered in schizophrenia. These metabolic pathways were associated with inflammatory cytokines and risk for coronary heart disease in schizophrenia. Findings suggest potential mechanisms by which the microbiota may impact the pathophysiology of the disease through modulation of functional pathways related to immune signaling/response and lipid and glucose regulation to be further investigated in future studies.
•SZ is associated with altered gut microbial composition and functional potential.•Models based on the gut microbiome differentiated SZ from NCs with high accuracy.•Lachnospiraceae was associated with SZ.•TMAO reductase and Kdo2-lipid A biosynthesis functional pathways were altered in SZ.•Pathways were associated with inflammatory cytokines and risk for coronary heart disease in SZ. Emerging evidence has linked the gut microbiome changes to schizophrenia. However, there has been limited research into the functional pathways by which the gut microbiota contributes to the phenotype of persons with chronic schizophrenia. We characterized the composition and functional potential of the gut microbiota in 48 individuals with chronic schizophrenia and 48 matched (sequencing plate, age, sex, BMI, and antibiotic use) non-psychiatric comparison subjects (NCs) using 16S rRNA sequencing. Patients with schizophrenia demonstrated significant beta-diversity differences in microbial composition and predicted genetic functional potential compared to NCs. Alpha-diversity of taxa and functional pathways were not different between groups. Random forests analyses revealed that the microbiome predicts differentiation of patients with schizophrenia from NCs using taxa (75% accuracy) and functional profiles (67% accuracy for KEGG orthologs, 70% for MetaCyc pathways). We utilized a new compositionally-aware method incorporating reference frames to identify differentially abundant microbes and pathways, which revealed that Lachnospiraceae is associated with schizophrenia. Functional pathways related to trimethylamine-N-oxide reductase and Kdo2-lipid A biosynthesis were altered in schizophrenia. These metabolic pathways were associated with inflammatory cytokines and risk for coronary heart disease in schizophrenia. Findings suggest potential mechanisms by which the microbiota may impact the pathophysiology of the disease through modulation of functional pathways related to immune signaling/response and lipid and glucose regulation to be further investigated in future studies.
Emerging evidence has linked the gut microbiome changes to schizophrenia. However, there has been limited research into the functional pathways by which the gut microbiota contributes to the phenotype of persons with chronic schizophrenia. We characterized the composition and functional potential of the gut microbiota in 48 individuals with chronic schizophrenia and 48 matched (sequencing plate, age, sex, BMI, and antibiotic use) non-psychiatric comparison subjects (NCs) using 16S rRNA sequencing. Patients with schizophrenia demonstrated significant beta-diversity differences in microbial composition and predicted genetic functional potential compared to NCs. Alpha-diversity of taxa and functional pathways were not different between groups. Random forests analyses revealed that the microbiome predicts differentiation of patients with schizophrenia from NCs using taxa (75% accuracy) and functional profiles (67% accuracy for KEGG orthologs, 70% for MetaCyc pathways). We utilized a new compositionally-aware method incorporating reference frames to identify differentially abundant microbes and pathways, which revealed that Lachnospiraceae is associated with schizophrenia. Functional pathways related to trimethylamine-N-oxide reductase and Kdo 2 -lipid A biosynthesis were altered in schizophrenia. These metabolic pathways were associated with inflammatory cytokines and risk for coronary heart disease in schizophrenia. Findings suggest potential mechanisms by which the microbiota may impact the pathophysiology of the disease through modulation of functional pathways related to immune signaling/response and lipid and glucose regulation to be further investigated in future studies.
Author Daly, Rebecca E.
Jeste, Dilip V.
Vázquez-Baeza, Yoshiki
Swafford, Austin
Knight, Rob
Kosciolek, Tomasz
Nguyen, Tanya T.
AuthorAffiliation 4 Małopolska Centre of Biotechnology, Jagiellonian University, Kraków, Poland
8 Department of Neurosciences, University of California San Diego, California
3 Department of Pediatrics, University of California San Diego California
1 Department of Psychiatry, University of California San Diego, California
2 Sam and Rose Stein Institute for Research on Aging, University of California San Diego, California
7 Department of Computer Science and Engineering, University of California San Diego, California
5 Center for Microbiome Innovation, University of California San Diego California
6 Department of Computer Science and Engineering, University of California San Diego, California
AuthorAffiliation_xml – name: 8 Department of Neurosciences, University of California San Diego, California
– name: 5 Center for Microbiome Innovation, University of California San Diego California
– name: 6 Department of Computer Science and Engineering, University of California San Diego, California
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– name: 4 Małopolska Centre of Biotechnology, Jagiellonian University, Kraków, Poland
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  organization: Department of Psychiatry, University of California, San Diego, CA, United States
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Gut-brain axis
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Snippet •SZ is associated with altered gut microbial composition and functional potential.•Models based on the gut microbiome differentiated SZ from NCs with high...
Emerging evidence has linked the gut microbiome changes to schizophrenia. However, there has been limited research into the functional pathways by which the...
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SubjectTerms Accelerated aging
Bacteria
Clostridiales
Functional pathways
Gastrointestinal Microbiome
Gut-brain axis
Humans
Inflammation
Microbes
Microbiota
Psychosis
RNA, Ribosomal, 16S - genetics
Schizophrenia
Serious mental illness
Title Gut microbiome in Schizophrenia: Altered functional pathways related to immune modulation and atherosclerotic risk
URI https://www.clinicalkey.com/#!/content/1-s2.0-S0889159120316822
https://dx.doi.org/10.1016/j.bbi.2020.10.003
https://www.ncbi.nlm.nih.gov/pubmed/33098964
https://www.proquest.com/docview/2454140241
https://pubmed.ncbi.nlm.nih.gov/PMC8023565
Volume 91
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