scholarly journals The gut microbiome from patients with schizophrenia modulates the glutamate-glutamine-GABA cycle and schizophrenia-relevant behaviors in mice

2019 ◽  
Vol 5 (2) ◽  
pp. eaau8317 ◽  
Author(s):  
Peng Zheng ◽  
Benhua Zeng ◽  
Meiling Liu ◽  
Jianjun Chen ◽  
Junxi Pan ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Brain Function ◽  
Molecular Mechanisms ◽  
Diversity Index ◽  
Area Under The Curve ◽  
Healthy Controls ◽  
Microbial Composition ◽  
Germ Free ◽  
Α Diversity ◽  
Neurologic Function

Schizophrenia (SCZ) is a devastating mental disorder with poorly defined underlying molecular mechanisms. The gut microbiome can modulate brain function and behaviors through the microbiota-gut-brain axis. Here, we found that unmedicated and medicated patients with SCZ had a decreased microbiome α-diversity index and marked disturbances of gut microbial composition versus healthy controls (HCs). Several unique bacterial taxa (e.g., Veillonellaceae and Lachnospiraceae) were associated with SCZ severity. A specific microbial panel (Aerococcaceae, Bifidobacteriaceae, Brucellaceae, Pasteurellaceae, and Rikenellaceae) enabled discriminating patients with SCZ from HCs with 0.769 area under the curve. Compared to HCs, germ-free mice receiving SCZ microbiome fecal transplants had lower glutamate and higher glutamine and GABA in the hippocampus and displayed SCZ-relevant behaviors similar to other mouse models of SCZ involving glutamatergic hypofunction. Together, our findings suggest that the SCZ microbiome itself can alter neurochemistry and neurologic function in ways that may be relevant to SCZ pathology.

scholarly journals Gut Microbial Dysbiosis in Individuals with Sjögren’s Syndrome

2020 ◽  
Author(s):  
Roberto Mendez ◽  
Arjun Watane ◽  
Monika Farhangi ◽  
Kara M. Cavuoto ◽  
Tom Leith ◽  
...  
Keyword(s):  
Dry Eye ◽  
Gut Microbiome ◽  
Diversity Index ◽  
Healthy Controls ◽  
Microbial Composition ◽  
Operational Taxonomic Units ◽  
Microbial Dysbiosis ◽  
16S Pyrosequencing ◽  
Symptoms And Signs ◽  
Shannon’S Diversity Index

Abstract Background: Autoimmune diseases have been associated with changes in the gut microbiome. In this study, the gut microbiome was evaluated in individuals with dry eye and bacterial compositions were correlated to dry eye (DE) measures. We prospectively included 13 individuals with who met full criteria for Sjögren’s (SDE) and 8 individuals with features of Sjögren’s but who did not meet full criteria (NDE) for a total of 21 cases as compared to 21 healthy controls. Stool was analyzed by 16S pyrosequencing, and associations between bacterial classes and DE symptoms and signs were examined. Results: Results showed that Firmicutes was the dominant phylum in the gut, comprising 40-60% of all phyla. On a phyla level, subjects with DE (SDE and NDE) had depletion of Firmicutes (1.1-fold) and an expansion of Proteobacteria (3.0-fold), Actinobacteria (1.7-fold), and Bacteroidetes (1.3-fold) compared to controls. Shannon’s diversity index showed no differences between groups with respect to the numbers of different operational taxonomic units (OTUs) encountered (diversity) and the instances these unique OTUs were sampled (evenness). On the other hand, Faith’s phylogenetic diversity showed increased diversity in cases vs controls, which reached significance when comparing SDE and controls (13.57 ± 0.89 and 10.96 ± 0.76, p=0.02). Using Principle Co-ordinate Analysis, qualitative differences in microbial composition were noted with differential clustering of cases and controls. Dimensionality reduction and clustering of complex microbial data further showed differences between the three groups, with regard to microbial composition, association and clustering. Finally, differences in certain classes of bacteria were associated with DE symptoms and signs. Conclusions: In conclusion, individuals with DE had gut microbiome alterations as compared to healthy controls. Certain classes of bacteria were associated with DE measures. These findings set the foundation for gut microbiome modulation as a potential therapeutic approach for DE.

scholarly journals Gut microbial dysbiosis in individuals with Sjögren’s disease

2019 ◽  
Author(s):  
Roberto Mendez ◽  
Arjun Watane ◽  
Monika Farhangi ◽  
Kara M. Cavuoto ◽  
Tom Leith ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Diversity Index ◽  
Case Series ◽  
Healthy Controls ◽  
Microbial Composition ◽  
Operational Taxonomic Units ◽  
Microbial Dysbiosis ◽  
Prospective Case Series ◽  
16S Pyrosequencing ◽  
Symptoms And Signs

AbstractPurposeTo evaluate the gut microbiome in individuals with Sjögrens and correlate bacterial profiles to dry eye (DE) measures.MethodsProspective case series of individuals with confirmed (n=13) and unconfirmed (n=8) Sjögrens (n=21; total cases) as compared to healthy controls (n=10). Stool was analyzed by 16S pyrosequencing and associations between bacterial classes and DE symptoms and signs were examined.ResultsFirmicutes was the dominant phylum in the gut, comprising 40-60% of all phyla. On a phyla level, subjects with Sjögrens (confirmed and unconfirmed) had depletion of Firmicutes (1.1- fold) and an expansion of Proteobacteria (3.0-fold), Actinobacteria (1.7-fold), and Bacteroidetes (1.3-fold) compared to controls. Shannon’s diversity index showed no differences between groups with respect to the numbers of different operational taxonomic units (OTUs) encountered (diversity) and the instances these unique OTUs were sampled (evenness). On the other hand, Faith’s phylogenetic diversity showed increased diversity in cases vs controls, which reached significance when comparing confirmed Sjögrens and controls (13.57 ± 0.89 and 10.96 ± 0.76, p=0.02). Using Principle Co-ordinate Analysis, qualitative differences in microbial composition were noted with differential clustering of cases and controls. Dimensionality reduction and clustering of complex microbial data further showed differences between the three groups, with regard to microbial composition, association and clustering. Finally, differences in certain classes of bacteria correlated with DE symptoms and signs.ConclusionsIndividuals with Sjögrens have gut microbiome alterations as compared to healthy controls. Certain classes of bacteria were associated with DE measures.

scholarly journals Gut Microbial Dysbiosis in Individuals with Sjögren’s Syndrome

2020 ◽  
Author(s):  
Roberto Mendez ◽  
Arjun Watane ◽  
Monika Farhangi ◽  
Kara M. Cavuoto ◽  
Tom Leith ◽  
...  
Keyword(s):  
Dry Eye ◽  
Gut Microbiome ◽  
Diversity Index ◽  
Healthy Controls ◽  
Microbial Composition ◽  
Operational Taxonomic Units ◽  
Microbial Dysbiosis ◽  
16S Pyrosequencing ◽  
Symptoms And Signs ◽  
Shannon’S Diversity Index

Abstract Background: Autoimmune diseases have been associated with changes in the gut microbiome. In this study, the gut microbiome was evaluated in individuals with dry eye and bacterial compositions were correlated to dry eye (DE) measures. We prospectively included 13 individuals with who met full criteria for Sjögren’s (SDE) and 8 individuals with features of Sjögren’s but who did not meet full criteria (NDE) for a total of 21 cases as compared to 21 healthy controls. Stool was analyzed by 16S pyrosequencing, and associations between bacterial classes and DE symptoms and signs were examined. Results: Results showed that Firmicutes was the dominant phylum in the gut, comprising 40-60% of all phyla. On a phyla level, subjects with DE (SDE and NDE) had depletion of Firmicutes (1.1-fold) and an expansion of Proteobacteria (3.0-fold), Actinobacteria (1.7-fold), and Bacteroidetes (1.3-fold) compared to controls. Shannon’s diversity index showed no differences between groups with respect to the numbers of different operational taxonomic units (OTUs) encountered (diversity) and the instances these unique OTUs were sampled (evenness). On the other hand, Faith’s phylogenetic diversity showed increased diversity in cases vs controls, which reached significance when comparing SDE and controls (13.57 ± 0.89 and 10.96 ± 0.76, p=0.02). Using Principle Co-ordinate Analysis, qualitative differences in microbial composition were noted with differential clustering of cases and controls. Dimensionality reduction and clustering of complex microbial data further showed differences between the three groups, with regard to microbial composition, association and clustering. Finally, differences in certain classes of bacteria were associated with DE symptoms and signs. Conclusions: In conclusion, individuals with DE had gut microbiome alterations as compared to healthy controls. Certain classes of bacteria were associated with DE measures.

scholarly journals Gut microbiome as a response marker for pancreatic enzyme replacement therapy in a porcine model of exocrine pancreas insufficiency

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Sabrina Ritz ◽  
Daniela Hahn ◽  
Haleluya T. Wami ◽  
Karin Tegelkamp ◽  
Ulrich Dobrindt ◽  
...  
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Gut Microbiome ◽  
Pancreatic Enzyme ◽  
Microbial Composition ◽  
Enzyme Replacement ◽  
Β Diversity ◽  
Healthy State ◽  
Α Diversity ◽  
Pancreatic Enzyme Replacement Therapy

Abstract Background Exocrine pancreatic insufficiency (EPI) is characterized by the loss of active pancreatic enzymes and a resulting severely reduced food digestion. EPI therapy requires orally applied pancreatic enzyme replacement. The gut microbiome is a known mediator of intestinal diseases and may influence the outcome of EPI and the effects of a pancreatic enzyme replacement therapy (PERT). Here, we analyzed the effects of EPI and PERT on the gut microbiome in the model of pancreatic duct ligated minipigs. Results The microbial community composition in pig feces was analyzed by next generation sequencing of 16S rRNA amplicons. The data were evaluated for α- and β-diversity changes and changes at the different Operational Taxonomic Unit (OTU) levels by Shannon–Wiener and inverse Simpson index calculation as well as by Principal Coordinates Analysis based on Bray–Curtis dissimilarity. Microbial α-diversity was reduced after EPI induction and reverted to nearly healthy state after PERT. Analysis of microbial composition and β-diversity showed distinctive clusters of the three study groups and a change towards a composition comparable to healthy animals upon PERT. The relative abundance of possible pathobionts like Escherichia/Shigella, Acinetobacter or Stenotrophomonas was reduced by PERT. Conclusion These data demonstrate that EPI-induced dysbiosis could be reverted by PERT to a nearly healthy state. Elevated α-diversity and the reduction of bacterial overgrowth after PERT promises benefits for EPI patients. Non-invasive microbiome studies may be useful for EPI therapy monitoring and as marker for response to PERT.

scholarly journals Faecal microbiota transplantation from metabolically compromised human donors accelerates osteoarthritis in mice

2020 ◽  
Vol 79 (5) ◽  
pp. 646-656 ◽  
Author(s):  
ZeYu Huang ◽  
Jing Chen ◽  
BoLei Li ◽  
Benhua Zeng ◽  
Ching-Heng Chou ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Gut Microbiome ◽  
Joint Damage ◽  
The Other ◽  
Gut Permeability ◽  
Microbial Composition ◽  
Germ Free ◽  
Knee Oa ◽  
Inflammatory Protein ◽  
Faecal Samples

ObjectivesEmerging evidence suggests that the microbiome plays an important role in the pathogenesis of osteoarthritis (OA). We aimed to test the two-hit model of OA pathogenesis and potentiation in which one ‘hit’ is provided by an adverse gut microbiome that activates innate immunity; the other ‘hit’ is underlying joint damage.MethodsMedical history, faecal and blood samples were collected from human healthy controls (OA-METS-, n=4), knee OA without metabolic syndrome (OA+METS-, n=7) and knee OA with metabolic syndrome (OA+METS+, n=9). Each group of human faecal samples, whose microbial composition was identified by 16S rRNA sequencing, was pooled and transplanted into germ-free mice 2 weeks prior to meniscal/ligamentous injury (MLI) (n≥6 per group). Eight weeks after MLI, mice were evaluated for histological OA severity and synovitis, systemic inflammation and gut permeability.ResultsHistological OA severity following MLI was minimal in germ-free mice. Compared with the other groups, transplantation with the OA+METS+ microbiome was associated with higher mean systemic concentrations of inflammatory biomarkers (interleukin-1β, interleukin-6 and macrophage inflammatory protein-1α), higher gut permeability and worse OA severity. A greater abundance of Fusobacterium and Faecalibaterium and lesser abundance of Ruminococcaceae in transplanted mice were consistently correlated with OA severity and systemic biomarkers concentrations.ConclusionThe study clearly establishes a direct gut microbiome-OA connection that sets the stage for a new means of exploring OA pathogenesis and potentially new OA therapeutics. Alterations of Fusobacterium, Faecalibaterium and Ruminococcaceae suggest a role of these particular microbes in exacerbating OA.

Alterations of gut microbiome in autoimmune hepatitis

Gut ◽  
2019 ◽  
Vol 69 (3) ◽  
pp. 569-577 ◽  
Author(s):  
Yiran Wei ◽  
Yanmei Li ◽  
Li Yan ◽  
Chunyan Sun ◽  
Qi Miao ◽  
...  
Keyword(s):  
Autoimmune Hepatitis ◽  
Gut Microbiome ◽  
Alpha Diversity ◽  
Disease Status ◽  
16S Rrna Gene Sequencing ◽  
Rrna Gene ◽  
Healthy Controls ◽  
Microbial Composition ◽  
Cross Sectional ◽  
Treatment Naïve

ObjectiveThe significance of the liver-microbiome axis has been increasingly recognised as a major modulator of autoimmunity. The aim of this study was to take advantage of a large well-defined corticosteroids treatment-naïve group of patients with autoimmune hepatitis (AIH) to rigorously characterise gut dysbiosis compared with healthy controls.DesignWe performed a cross-sectional study of individuals with AIH (n=91) and matched healthy controls (n=98) by 16S rRNA gene sequencing. An independent cohort of 28 patients and 34 controls was analysed to validate the results. All the patients were collected before corticosteroids therapy.ResultsThe gut microbiome of steroid treatment-naïve AIH was characterised with lower alpha-diversity (Shannon and observed operational taxonomic units, both p<0.01) and distinct overall microbial composition compared with healthy controls (p=0.002). Depletion of obligate anaerobes and expansion of potential pathobionts including Veillonella were associated with disease status. Of note, Veillonella dispar, the most strongly disease-associated taxa (p=8.85E–8), positively correlated with serum level of aspartate aminotransferase and liver inflammation. Furthermore, the combination of four patients with AIH-associated genera distinguished AIH from controls with an area under curves of approximately 0.8 in both exploration and validation cohorts. In addition, multiple predicted functional modules were altered in the AIH gut microbiome, including lipopolysaccharide biosynthesis as well as metabolism of amino acids that can be processed by bacteria to produce immunomodulatory metabolites.ConclusionOur study establishes compositional and functional alterations of gut microbiome in AIH and suggests the potential for using gut microbiota as non-invasive biomarkers to assess disease activity.

scholarly journals Characterizing the Skin and Gut Microbiome of Alopecia Areata Patients

2020 ◽  
Vol 4 (1) ◽  
pp. 23-30
Author(s):  
Margit Juhasz ◽  
Siwei Chen ◽  
Arash Khosrovi-Eghbal ◽  
Chloe Ekelem ◽  
Yessica Landaverde ◽  
...  
Keyword(s):  
Alopecia Areata ◽  
Gut Microbiome ◽  
Healthy Controls ◽  
Healthy Individuals ◽  
Microbial Composition ◽  
Future Directions ◽  
Fecal Microbiome ◽  
Autoimmune Attack ◽  
Significant Difference ◽  
Control Study

Background: Alopecia areata (AA) is caused by autoimmune attack of the hair follicle. The exact pathogenesis is unknown, but hypotheses include innate immunity imbalance, environmental exposures, genetic predisposition, and possibly the microbiome. The objective of this study was to characterize the skin and gut microbiome of AA patients, and compare microbial composition to healthy individuals. Methods: This was a pilot, case-control study. Scalp and fecal microbiome samples were collected from 25 AA patients, and 25 age, gender, and race-matched healthy controls in Southern California with no significant difference in demographic characteristics. After library preparation and identification of bacterial and fungal taxonomy, multivariant analysis was performed to compare AA and healthy microbiomes. Results: The AA scalp microbiome was significant for decreased Clostridia and Malasseziomycetes, and the gut microbiome was significant for decreased Bacteroidia and increased Bacilli (p<0.05) compared to healthy controls. Conclusions: The composition of the AA bacterial and fungal, scalp and gut microbiome is significantly different than healthy individuals. Future directions include using this data to characterize microbial changes associated with AA patient diet, relating to disease severity, and predicting disease progression, prognosis and/or therapeutic response.

scholarly journals Impairment of Intestinal Barrier Function Induced by Early Weaning via Autophagy and Apoptosis Associated With Gut Microbiome and Metabolites

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenjie Tang ◽  
Jingliang Liu ◽  
Yanfei Ma ◽  
Yusen Wei ◽  
Jianxin Liu ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Barrier Function ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Clustering Coefficient ◽  
Autophagic Flux ◽  
Early Weaning ◽  
Microbial Composition ◽  
Apoptosis Pathway

Early weaning piglet is frequently accompanied by severe enteric inflammatory responses and microbiota dysbiosis. The links between the gut microbiome and the etiology of gut inflammation are not fully understood. The study is aimed to investigate the potential molecular mechanisms mediating inflammatory reactivity following early weaning, and to find whether these changes are correlated with gut microbiota and metabolite signatures by comparison between suckling piglets (SPs) and weaning piglets (WPs). Histopathology analysis showed a severe inflammatory response and the disruption of epithelial barrier function. Early weaning resulted in reduced autophagy indicated as the suppression of autophagic flux, whereas induced the TLR4/P38MAPK/IL-1β-mediated apoptotic pathway, as well as activation of the IL-1β precursor. The alpha-diversity and microbial composition were changed in WPs, such as the decreased abundances of Bifidobacterium, Bacteroides, Bacillus, Lactobacillus, and Ruminococcus. Microbial co-concurrence analysis revealed that early weaning significantly decreased network complexity, including network size, degree, average clustering coefficient and number of keystone species, as compared with the SP group. Differentially abundant metabolites were mainly associated with amino acid and purine metabolism. Strong correlations were detected between discrepant microbial taxa and multiple inflammatory parameters. In conclusion, we found that dysregulations of autophagy and apoptosis pathway were involved in colon inflammation during weaned period, which may result from gut microbiota dysbiosis. This study may provide possible intervention modalities for preventing or treating post-weaning infections through maintaining gut microbial ecosystem integrity.

scholarly journals Elucidating the Gut Microbiome of Colorectal Cancer: 40 Fecal Bacteria as Non-invasive Biomarkers

2020 ◽  
Author(s):  
Biao Yuan ◽  
SiPing Ma ◽  
Qingkai Meng ◽  
Tao Du ◽  
Yueyan Zhu ◽  
...  
Keyword(s):  
Microbial Community ◽  
Early Diagnosis ◽  
Sensitivity And Specificity ◽  
Gut Microbiome ◽  
Microbial Community Analysis ◽  
Support Vector ◽  
Healthy Controls ◽  
Microbial Composition ◽  
Non Invasive ◽  
Specificity And Sensitivity

Abstract Background: Colorectal adenocarcinoma (CRC) ranks one of the 5 most lethal malignant tumors both in China and worldwide. Emerging evidences have revealed the importance of gut microbiome on CRC, thus microbial community could be termed as a potential screen for early diagnosis. Importantly, compared with the whole microbial community analysis, few numbers of bacteria genus as non-invasive biomarkers with high sensitivity and specificity causing less cost would benefit more in clinical. Methods: Here we analyzed the gut microbiome from 226 CRC patients and 156 healthy people by 16s rRNA sequencing. We analyzed the microbiome diversity between CRC patients and healthy controls. We used ExtraTrees classifier to screening the biomarkers and took SVM (Support Vector Machine) model to test the specificity and sensitivity of our biomarkers. Results: Compared with the healthy gut, the microbial composition are divergent in CRC, especially the increase of some bacteria related to CRC and the decrease of some healthy bacteria. 40 bacteria genus exhibiting high weight for the healthy and CRC microbiome classification were screened as biomarkers for CRC. In addition, the combination of 40 biomarkers and FOBT showed an outstanding sensitivity and specificity for discrimination CRC patients from healthy controls. Conclusion: The method could be used as a non-invasive method for CRC early diagnosis.

scholarly journals The Association Between Breast Density and Gut Microbiota Composition at 2 Years Post-Menarche: A Cross-Sectional Study of Adolescents in Santiago, Chile

2021 ◽  
Vol 11 ◽  
Author(s):  
Lara S. Yoon ◽  
Jonathan P. Jacobs ◽  
Jessica Hoehner ◽  
Ana Pereira ◽  
Juan Cristóbal Gana ◽  
...  
Keyword(s):  
Breast Density ◽  
Gut Microbiome ◽  
Beta Diversity ◽  
Diversity Index ◽  
Alpha Diversity ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Linear Modeling ◽  
Microbial Composition ◽  
Cross Sectional

The gut microbiome has been linked to breast cancer via immune, inflammatory, and hormonal mechanisms. We examined the relation between adolescent breast density and gut microbial composition and function in a cohort of Chilean girls. This cross-sectional study included 218 female participants in the Growth and Obesity Cohort Study who were 2 years post-menarche. We measured absolute breast fibroglandular volume (aFGV) and derived percent FGV (%FGV) using dual energy X-ray absorptiometry. All participants provided a fecal sample. The gut microbiome was characterized using 16S ribosomal RNA sequencing of the V3-V4 hypervariable region. We examined alpha diversity and beta diversity across terciles of %FGV and aFGV. We used MaAsLin2 for multivariable general linear modeling to assess differential taxa and predicted metabolic pathway abundance (MetaCyc) between %FGV and aFGV terciles. All models were adjusted for potential confounding variables and corrected for multiple comparisons. The mean %FGV and aFGV was 49.5% and 217.0 cm3, respectively, among study participants. Similar median alpha diversity levels were found across %FGV and aFGV terciles when measured by the Shannon diversity index (%FGV T1: 4.0, T2: 3.9, T3: 4.1; aFGV T1: 4.0, T2: 4.0, T3: 4.1). %FGV was associated with differences in beta diversity (R2 =0.012, p=0.02). No genera were differentially abundant when comparing %FGV nor aFGV terciles after adjusting for potential confounders (q &gt; 0.56 for all genera). We found no associations between predicted MetaCyc pathway abundance and %FGV and aFGV. Overall, breast density measured at 2 years post-menarche was not associated with composition and predicted function of the gut microbiome among adolescent Chilean girls.

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