Gut Microbial Dysbiosis in Individuals with Sjögren’s Syndrome

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.

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Gut Microbial Dysbiosis in Individuals with Sjögren’s Syndrome

10.21203/rs.2.21989/v2 ◽

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

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Gut microbial dysbiosis in individuals with Sjögren’s disease

10.1101/645739 ◽

2019 ◽

Cited By ~ 1

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.

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

Science Advances ◽

10.1126/sciadv.aau8317 ◽

2019 ◽

Vol 5 (2) ◽

pp. eaau8317 ◽

Cited By ~ 98

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.

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Gut Microbial Dysbiosis and Plasma Metabolic Profile in Individuals With Vitiligo

Frontiers in Microbiology ◽

10.3389/fmicb.2020.592248 ◽

2020 ◽

Vol 11 ◽

Author(s):

Qingrong Ni ◽

Zhubiao Ye ◽

Yinghan Wang ◽

Jianru Chen ◽

Weigang Zhang ◽

...

Keyword(s):

Gut Microbiome ◽

Prediction Models ◽

Healthy Controls ◽

Microbial Composition ◽

Microbial Dysbiosis ◽

Β Diversity ◽

Metabolomic Profiling ◽

Joint Prediction ◽

Learning Analysis ◽

Control Study

Autoimmune diseases are increasingly linked to aberrant gut microbiome and relevant metabolites. However, the association between vitiligo and the gut microbiome remains to be elucidated. Thus, we conducted a case-control study through 16S rRNA sequencing and serum untargeted-metabolomic profiling based on 30 vitiligo patients and 30 matched healthy controls. In vitiligo patients, the microbial composition was distinct from that of healthy controls according to the analysis on α- and β-diversity (P < 0.05), with a characteristic decreased Bacteroidetes: Firmicutes ratio. Meanwhile, the levels of 23 serum metabolites (including taurochenodeoxycholate and L-NG-monomethyl-arginine) in the vitiligo patients were different from those in the healthy individuals and showed significant correlations with some microbial markers. We found that Corynebacterium 1, Ruminococcus 2, Jeotgalibaca and Psychrobacter were correlated significantly with disease duration and serum IL-1β level in vitiligo patients. And Psychrobacter was identified as the most predictive features for vitiligo by machine learning analysis (“importance” = 0.0236). Finally, combining multi-omics data and joint prediction models with accuracies up to 0.929 were established with dominant contribution of Corynebacterium 1 and Psychrobacter. Our findings replenished the previously unknown relationship between gut dysbiosis and vitiligo circulating metabolome and enrolled the gut-skin axis into the understanding of vitiligo pathogenesis.

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Alterations of gut microbiome in autoimmune hepatitis

Gut ◽

10.1136/gutjnl-2018-317836 ◽

2019 ◽

Vol 69 (3) ◽

pp. 569-577 ◽

Cited By ~ 27

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.

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Characterizing the Skin and Gut Microbiome of Alopecia Areata Patients

SKIN The Journal of Cutaneous Medicine ◽

10.25251/skin.4.1.4 ◽

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.

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A260 THE LACK OF CHROMOGRANIN-A MODIFIES THE GUT MICROBIOTA COMPOSITION AND REGULATES EXPERIMENTAL COLONIC INFLAMMATION

Journal of the Canadian Association of Gastroenterology ◽

10.1093/jcag/gwz047.259 ◽

2020 ◽

Vol 3 (Supplement_1) ◽

pp. 137-138

Author(s):

N Eissa ◽

A Diarra ◽

H Hussein ◽

C N Bernstein ◽

J Ghia

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Chromogranin A ◽

Bacterial Community Composition ◽

Alpha Diversity ◽

Lactobacillus Species ◽

Wild Type ◽

Microbial Composition ◽

Colonic Inflammation ◽

Microbial Dysbiosis

Abstract Background Ulcerative colitis (UC)is characterized by distinct changes in the gut microbiome and elevated chromogranin-A (CHGA) level, which seem to be a relevant pathogenetic mechanism.CHGA, a prohormone produced by enterochromaffin (EC) cells and cleaved into several bioactive peptides, regulates experimental colonic inflammation. In the rodent, intra-rectal infusion of catestatin, a Chga-derived peptide, alters the distal colonic microbial composition. However, the interplay between CHGA, as a pro-hormone, and the gut microbiome remains elusive. Aims in homoeostatic and pathophysiologic conditions, we investigated the functional consequences of the lack of Chgaon the distal colonic microbiota. Methods Acute colitis (5 % dextran sulfate sodium [DSS], 5 days) was induced in Chga-C57BL/6-deficient (Chga-/-) and wild-type (Chga+/+)mice. Feces and mucosa-associated microbiota (MAM) samples were collected and the V4 region of 16s rRNA was subjected to Miseq Illumina sequencing. Alpha diversity was calculated using Shannon’s diversity index. OTU abundances were summarized using the Bray-Curtis index and non-metric multidimensional scaling (NMDS) analysis to visualize microbiome similarities and a permutational analysis of variance (PERMANOVA) to test the significance of groups were performed respectively. Results In non-colitic homoeostatic condition, the absence of Chga (Chga-/) significantly increased the bacterial richness and modified the bacterial community composition at the genera level between the groups, represented by increased abundance of Lactobacillus species and reduced abundance of Helicobacter& Oscillospira species compared to Chga+/+mice in fecal and colonic MAM. Moreover, the absence of Chga (Chga-/-) resulted in a significant change in the alpha-diversity of fecal and colonic MAM compared to Chga+/+mice. DSS induced-colitis resulted in a significant microbial dysbiosis in Chga+/+mice, however, deletion of Chgaprotected against DSS-induced colitis and reduced the microbial dysbiosis, reduced the family of Rikenellaceaeand maintained the abundance of Bacteroides species, compared to wild-type (Chga+/+). Conclusions The lack of CHGA regulates the biodiversity and the composition of the colonic gut microbiota suggesting a cross-talk between the EC cell and the microbiome. Therefore, targeting CHGA could provide a novel therapeutic strategy by regulating the gut microbiome in physiological and pathophysiological conditions. Funding Agencies CIHR

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

10.21203/rs.3.rs-113328/v1 ◽

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.

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

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.794610 ◽

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 > 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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Glioma and temozolomide induced alterations in gut microbiome

Scientific Reports ◽

10.1038/s41598-020-77919-w ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Anthony Patrizz ◽

Antonio Dono ◽

Soheil Zorofchian ◽

Gabriella Hines ◽

Takeshi Takayasu ◽

...

Keyword(s):

Mouse Model ◽

Gut Microbiome ◽

Healthy Controls ◽

Fecal Samples ◽

Fecal Microbiome ◽

Therapeutic Modalities ◽

Microbial Dysbiosis ◽

Rrna Sequencing ◽

Before And After ◽

Immune Oncology

AbstractThe gut microbiome is fundamental in neurogenesis processes. Alterations in microbial constituents promote inflammation and immunosuppression. Recently, in immune-oncology, specific microbial taxa have been described to enhance the effects of therapeutic modalities. However, the effects of microbial dysbiosis on glioma are still unknown. The aim of this study was to explore the effects of glioma development and Temozolomide (TMZ) on fecal microbiome in mice and humans. C57BL/6 mice were implanted with GL261/Sham and given TMZ/Saline. Fecal samples were collected longitudinally and analyzed by 16S rRNA sequencing. Fecal samples were collected from healthy controls as well as glioma patients at diagnosis, before and after chemoradiation. Compared to healthy controls, mice and glioma patients demonstrated significant differences in beta diversity, Firmicutes/Bacteroides (F/B) ratio, and increase of Verrucomicrobia phylum and Akkermansia genus. These changes were not observed following TMZ in mice. TMZ treatment in the non-tumor bearing mouse-model diminished the F/B ratio, increase Muribaculaceae family and decrease Ruminococcaceae family. Nevertheless, there were no changes in Verrucomicrobia/Akkermansia. Glioma development leads to gut dysbiosis in a mouse-model, which was not observed in the setting of TMZ. These findings seem translational to humans and warrant further study.

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