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Frontiers in Cellular and Infection... 2023Immunoglobulin G4 (IgG4) is a member of the human immunoglobulin G (IgG) subclass, a protein involved in immunity to pathogens and the body's resistance system....
INTRODUCTION
Immunoglobulin G4 (IgG4) is a member of the human immunoglobulin G (IgG) subclass, a protein involved in immunity to pathogens and the body's resistance system. IgG4-related diseases (IgG4-RD) are intractable diseases in which IgG4 levels in the blood are elevated, causing inflammation in organs such as the liver, pancreas, and salivary glands. IgG4-RD are known to be more prevalent in males than in females, but the etiology remains to be elucidated. This study was conducted to investigate the relationship between gut microbiota (GM) and serum IgG4 levels in the general population.
METHODS
In this study, the relationship between IgG4 levels and GM evaluated in male and female groups of the general population using causal inference. The study included 191 men and 207 women aged 40 years or older from Shika-machi, Ishikawa. GM DNA was analyzed for the 16S rRNA gene sequence using next-generation sequencing. Participants were bifurcated into high and low IgG4 groups, depending on median serum IgG4 levels.
RESULTS
ANCOVA, Tukey's HSD, linear discriminant analysis effect size, least absolute shrinkage and selection operator logistic regression model, and correlation analysis revealed that , , , and group were associated with IgG4 levels in women, while , group, , 1, and were associated with IgG4 levels in men. Linear non-Gaussian acyclic model indicated three genera, , group, and , and showed a presumed causal association with IgG4 levels in women.
DISCUSSION
This differential impact of the GM on IgG4 levels based on sex is a novel and intriguing finding.
Topics: Humans; Male; Female; Gastrointestinal Microbiome; Immunoglobulin G4-Related Disease; RNA, Ribosomal, 16S; Salivary Glands; Immunoglobulin G
PubMed: 37908763
DOI: 10.3389/fcimb.2023.1272398 -
Parkinsonism & Related Disorders Jan 2022Gut microbiome alterations have been reported in Parkinson's disease (PD), but with heterogenous findings, likely due to differences in study methodology and population.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Gut microbiome alterations have been reported in Parkinson's disease (PD), but with heterogenous findings, likely due to differences in study methodology and population. We investigated the main microbiome alterations in PD, their correlations with disease severity, and the impact of study and geographical differences.
METHODS
After systematic screening, raw 16S rRNA gene sequences were obtained from ten case-control studies totaling 1703 subjects (969 PD, 734 non-PD controls; seven predominantly Caucasian and three predominantly non-Caucasian cohorts). Quality-filtered gene sequences were analyzed using a phylogenetic placement approach, which precludes the need for the sequences to be sourced from similar regions in the 16S rRNA gene, thus allowing a direct comparison between studies. Differences in microbiome composition and correlations with clinical variables were analyzed using multivariate statistics.
RESULTS
Study and geography accounted for the largest variations in gut microbiome composition. Microbiome composition was more similar for subjects from the same study than those from different studies with the same disease status. Microbiome composition significantly differed between Caucasian and non-Caucasian populations. After accounting for study differences, microbiome composition was significantly different in PD vs. controls (albeit with a marginal effect size), with several distinctive features including increased abundances of Megasphaera and Akkermansia, and reduced Roseburia. Several bacterial genera correlated with PD motor severity, motor response complications and cognitive function.
CONCLUSION
Consistent microbial features in PD merit further investigation. The large variations in microbiome findings of PD patients underscore the need for greater harmonization of future research, and personalized approaches in designing microbial-directed therapeutics.
Topics: Case-Control Studies; Gastrointestinal Microbiome; Humans; Parkinson Disease; Phylogeny; RNA, Ribosomal, 16S
PubMed: 34844021
DOI: 10.1016/j.parkreldis.2021.11.017 -
Cellular and Molecular Biology... Feb 2022This work was developed to explore the relationship between intestinal microflora composition and immune function changes in children with asthma and to provide...
This work was developed to explore the relationship between intestinal microflora composition and immune function changes in children with asthma and to provide theoretical references for clinical diagnosis and treatment. Forty-eight children with asthma who received standardized treatment in the outpatient department of pediatric respiratory asthma in Children's Hospital were selected as the research objects, which were rolled into 24 cases of S0 group (complete control) and 24 cases of S1 group (incomplete control group). In addition, ten healthy children with general data matching the research objects were selected as a blank control (D0 group). The intestinal microbial composition and immune function indexes of each group were detected. The results showed that there were differences in the intestinal microbes of the three groups of children with Bifidobacterium, Megasphaera, Oscillibacter, Bilophila, and f_Ruminococcaceae. Among them, the proportions of Bifidobacterium, Megasphaera, and f_Ruminococcaceae in the intestinal microbes of the children in the S1 group were notably less than those in the S0 and D0 groups. The proportion of these three bacterial genera in the S0 group was also considerably smaller than that in the D0 group (P<0.05). In addition, the CD3+ levels of children in the S1 group were notably lower than those in the S0 and D0 groups, while the CD4+ and CD4+/CD3+ were higher than the S0 and D0 groups (P<0.05). The differences between CD3+, CD4+, and CD4+/CD3+ in the S0 and D0 groups were not considerable (P<0.05). The proportions of Bifidobacterium, Megasphaera, f_Ruminococcaceae, and Parasutterella in children with intestinal microbes were significantly positively correlated with CD3+ levels (P<0.05), and significantly negatively correlated with CD4+ and CD4+/CD3+ levels (P<0.05). In short, children with different levels of asthma control had a certain degree of flora disorder and decreased immune function in the intestinal flora. The decrease in the relative abundance of Bifidobacterium, f_Ruminococcaceae of Firmicutes, and Parasutterella of Riken Bacteria, and the increase in the relative abundance of Oscillatoria meant the decline of the immune function of the children.
Topics: Asthma; Bacteria; Child; Gastrointestinal Microbiome; Humans; Intestines
PubMed: 35869726
DOI: 10.14715/cmb/2022.68.2.11 -
Journal of Translational Medicine Aug 2023For many years, the role of the microbiome in tumor progression, particularly the tumor microbiome, was largely overlooked. The connection between the tumor microbiome...
Weighted gene coexpression network analysis and machine learning reveal oncogenome associated microbiome plays an important role in tumor immunity and prognosis in pan-cancer.
BACKGROUND
For many years, the role of the microbiome in tumor progression, particularly the tumor microbiome, was largely overlooked. The connection between the tumor microbiome and the tumor genome still requires further investigation.
METHODS
The TCGA microbiome and genome data were obtained from Haziza et al.'s article and UCSC Xena database, respectively. Separate WGCNA networks were constructed for the tumor microbiome and genomic data after filtering the datasets. Correlation analysis between the microbial and mRNA modules was conducted to identify oncogenome associated microbiome module (OAM) modules, with three microbial modules selected for each tumor type. Reactome analysis was used to enrich biological processes. Machine learning techniques were implemented to explore the tumor type-specific enrichment and prognostic value of OAM, as well as the ability of the tumor microbiome to differentiate TP53 mutations.
RESULTS
We constructed a total of 182 tumor microbiome and 570 mRNA WGCNA modules. Our results show that there is a correlation between tumor microbiome and tumor genome. Gene enrichment analysis results suggest that the genes in the mRNA module with the highest correlation with the tumor microbiome group are mainly enriched in infection, transcriptional regulation by TP53 and antigen presentation. The correlation analysis of OAM with CD8+ T cells or TAM1 cells suggests the existence of many microbiota that may be involved in tumor immune suppression or promotion, such as Williamsia in breast cancer, Biostraticola in stomach cancer, Megasphaera in cervical cancer and Lottiidibacillus in ovarian cancer. In addition, the results show that the microbiome-genome prognostic model has good predictive value for short-term prognosis. The analysis of tumor TP53 mutations shows that tumor microbiota has a certain ability to distinguish TP53 mutations, with an AUROC value of 0.755. The tumor microbiota with high importance scores are Corallococcus, Bacillus and Saezia. Finally, we identified a potential anti-cancer microbiota, Tissierella, which has been shown to be associated with improved prognosis in tumors including breast cancer, lung adenocarcinoma and gastric cancer.
CONCLUSION
There is an association between the tumor microbiome and the tumor genome, and the existence of this association is not accidental and could change the landscape of tumor research.
Topics: Female; Humans; Prognosis; Gene Regulatory Networks; Breast Neoplasms; Ovarian Neoplasms; RNA, Messenger
PubMed: 37573394
DOI: 10.1186/s12967-023-04411-0 -
Frontiers in Cellular and Infection... 2023Cerebral small vessel disease (CSVD) is a cluster of microvascular disorders with unclear pathological mechanisms. The microbiota-gut-brain axis is an essential...
BACKGROUND
Cerebral small vessel disease (CSVD) is a cluster of microvascular disorders with unclear pathological mechanisms. The microbiota-gut-brain axis is an essential regulatory mechanism between gut microbes and their host. Therefore, the compositional and functional gut microbiota alterations lead to cerebrovascular disease pathogenesis. The current study aims to determine the alteration and clinical value of the gut microbiota in CSVD patients.
METHODS
Sixty-four CSVD patients and 18 matched healthy controls (HCs) were included in our study. All the participants underwent neuropsychological tests, and the multi-modal magnetic resonance imaging depicted the changes in brain structure and function. Plasma samples were collected, and the fecal samples were analyzed with 16S rRNA gene sequencing.
RESULTS
Based on the alpha diversity analysis, the CSVD group had significantly decreased Shannon and enhanced Simpson compared to the HC group. At the genus level, there was a significant increase in the relative abundances of Parasutterella, Anaeroglobus, Megasphaera, Akkermansia, Collinsella, and Veillonella in the CSVD group. Moreover, these genera with significant differences in CSVD patients revealed significant correlations with cognitive assessments, plasma levels of the blood-brain barrier-/inflammation-related indexes, and structural/functional magnetic resonance imaging changes. Functional prediction demonstrated that lipoic acid metabolism was significantly higher in CSVD patients than HCs. Additionally, a composite biomarker depending on six gut microbiota at the genus level displayed an area under the curve of 0.834 to distinguish CSVD patients from HCs using the least absolute shrinkage and selection operator (LASSO) algorithm.
CONCLUSION
The evident changes in gut microbiota composition in CSVD patients were correlated with clinical features and pathological changes of CSVD. Combining these gut microbiota using the LASSO algorithm helped identify CSVD accurately.
Topics: Humans; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Brain; Magnetic Resonance Imaging; Cerebral Small Vessel Diseases
PubMed: 37496806
DOI: 10.3389/fcimb.2023.1231541 -
PloS One 2022Premenstrual symptoms can negatively impact the quality of life of women through a range of mood, behavioral, and physical symptoms. The association between the...
PURPOSE
Premenstrual symptoms can negatively impact the quality of life of women through a range of mood, behavioral, and physical symptoms. The association between the microbiota and brain function has been extensively studied. Here, we examined the characteristics of the microbiota in women with premenstrual disorders (PMDs) and the association between premenstrual symptoms and the microbiota.
MATERIALS AND METHODS
In this single center cross-sectional pilot study, we recruited 27 women reporting premenstrual symptoms and 29 women with no serious premenstrual symptoms. Among them, we further selected 21 women experiencing premenstrual symptoms resulting in interference to their social life (PMDs group) and 22 women with no serious premenstrual symptoms and thereby no interference to their social life (control group). The severity of symptoms was evaluated by a premenstrual symptoms questionnaire (PSQ). Inflammatory markers were analyzed in blood samples, including C reactive protein, soluble CD14, and lipopolysaccharide binding protein. Sequencing of 16S ribosomal ribonucleic acid genes was performed on stool samples.
RESULTS
Inflammatory markers in blood samples did not differ significantly between the PMDs and control groups. A difference in beta, but not alpha diversity, was detected for the gut microbiotas of the PMDs and control groups. The relative abundance of the Bacteroidetes phylum was lower in the PMDs group. At the genus level, the prevalence was decreased for Butyricicoccus, Extibacter, Megasphaera, and Parabacteroides and increased for Anaerotaenia in the PMDs group, but after false discovery rate correction, these differences were no longer significant. Linear discriminant effect size analysis revealed a decrease in Extibacter, Butyricicoccus, Megasphaera, and Parabacteroides and an increase in Anaerotaenia in the PMDs group. The PSQ total score correlated with Anaerotaenia, Extibacter, and Parabacteroides. Multiple regression analysis showed that Parabacteroides and Megasphaera negatively predicted the PSQ total score.
CONCLUSION
The properties of the gut microbiota are associated with premenstrual symptoms.
Topics: Bacteroidetes; Clostridiaceae; Clostridiales; Cross-Sectional Studies; Female; Gastrointestinal Microbiome; Humans; Pilot Projects; Premenstrual Syndrome; Quality of Life
PubMed: 35622782
DOI: 10.1371/journal.pone.0268466 -
ILAR Journal Dec 2020The microbiota is heavily involved in both health and disease pathogenesis, but defining a normal, healthy microbiota in the common marmoset has been challenging. The... (Review)
Review
The microbiota is heavily involved in both health and disease pathogenesis, but defining a normal, healthy microbiota in the common marmoset has been challenging. The aim of this review was to systematically review recent literature involving the gastrointestinal microbiome of common marmosets in health and disease. Twelve sources were included in this review. The gut microbiome composition was reviewed across institutions worldwide, and taxonomic shifts between healthy individuals were described. Unlike the human gut microbiome, which is dominated by Firmicutes and Bacteroidetes, the marmoset gut microbiome shows great plasticity across institutions, with 5 different phyla described as dominant in different healthy cohorts. Genera shared across institutions include Anaerobiospirillum, Bacteroides, Bifidobacterium, Collinsella, Fusobacterium, Megamonas, Megasphaera, Phascolarctobacterium, and Prevotella. Shifts in the abundance of Prevotella or Bifidobacterium or invasion by pathogens like Clostridium perfringens may be associated with disease. Changes in microbial composition have been described in healthy and diseased marmosets, but factors influencing the severe changes in microbial composition have not been established. Multi-institutional, prospective, and longitudinal studies that utilize multiple testing methodologies are required to determine sources of variability in the reporting of marmoset microbiomes. Furthermore, methods of microbial manipulation, whether by diet, enrichment, fecal microbiome transplantation, etc, need to be established to modulate and maintain robust and resilient microbiome communities in marmoset colonies and reduce the incidence of idiopathic gastrointestinal disease.
Topics: Animals; Bacteria; Callithrix; Feces; Gastrointestinal Microbiome; Prospective Studies
PubMed: 33620078
DOI: 10.1093/ilar/ilaa025 -
Molecular Neurobiology Nov 2023Depression is one of the complications in patients with polycystic ovary syndrome (PCOS) that leads to considerable mental health. Accumulating evidence suggests that...
Depression is one of the complications in patients with polycystic ovary syndrome (PCOS) that leads to considerable mental health. Accumulating evidence suggests that human gut microbiomes are associated with the progression of PCOS and depression. However, whether microbiota influences depression development in PCOS patients is still uncharacterized. In this study, we employed metagenomic sequencing and transcriptome sequencing (RNA-seq) to profile the composition of the fecal microbiota and gene expression of peripheral blood mononuclear cells in depressed women with PCOS (PCOS-DP, n = 27) in comparison to mentally healthy women with PCOS (PCOS, n = 18) and compared with healthy control (HC, n = 27) and patients with major depressive disorder (MDD, n = 29). Gut microbiota assessment revealed distinct patterns in the relative abundance in the PCOS-DP compared to HC, MDD, and PCOS groups. Several gut microbes exhibited uniquely and significantly higher abundance in the PCOS-DP compared to PCOS patients, inducing EC Ruminococcus torques, Coprococcus comes, Megasphaera elsdenii, Acidaminococcus intestini, and Barnesiella viscericola. Bacteroides eggerthii was a potential gut microbial biomarker for the PCOS-DP. RNA-seq profiling identified that 35 and 37 genes were significantly elevated and downregulated in the PCOS-DP, respectively. The enhanced differential expressed genes (DEGs) in the PCOS-DP were enriched in pathways involved in signal transduction and endocrine and metabolic diseases, whereas several lipid metabolism pathways were downregulated. Intriguingly, genes correlated with the gut microbiota were found to be significantly enriched in pathways of neurodegenerative diseases and the immune system, suggesting that changes in the microbiota may have a systemic impact on the expression of neurodegenerative diseases and immune genes. Gut microbe-related DEGs of CREB3L3 and CCDC173 were possible molecular biomarkers and therapeutic targets of women with PCOS-DP. Our multi-omics data indicate shifts in the gut microbiome and host gene regulation in PCOS patients with depression, which is of possible etiological and diagnostic importance.
PubMed: 37995075
DOI: 10.1007/s12035-023-03744-7 -
Frontiers in Neuroscience 2022To characterize the intestinal flora of patients with epilepsy and its correlation with epilepsy.
OBJECTIVE
To characterize the intestinal flora of patients with epilepsy and its correlation with epilepsy.
METHODS
Patients with ages > 18 years were consecutively enrolled from the outpatient department, Affiliated Hospital of Guizhou Medical University from January 2018 to December 2019. A total of 71 subjects were recruited, including epilepsy patients ( = 41) as an observation group and patient family members ( = 30) as a control group. Fresh stool specimens of all the subjects were collected. The 16S ribosomal RNA sequencing was analyzed to determine changes in intestinal flora composition and its correlation with epilepsy. Subgroup analysis was then conducted. All patients with epilepsy were divided into an urban group ( = 21) and a rural group ( = 20) according to the region, and bioinformatics analyses were repeated between subgroups.
RESULTS
LEfSe analysis showed that , , , and had relatively increased abundance in the epilepsy group at the genus level. Correlation analysis suggested that sp. ( = 0.584, < 0.01), ( = 0.560, < 0.01), ( = 0.541, < 0.01), and ( = 0.506, < 0.01) were significantly positively correlated with the occurrence of epilepsy ( ≥ 0.5, < 0.05). PICRUSt function prediction analysis showed that there were significant differences in 16 pathways between the groups at level 3. Comparing the rural group with the urban group, increased at the phylum level and , , , and increased at the species level in the rural group.
CONCLUSION
There were significant differences in the composition and functional pathways of gut flora between epilepsy patients and patient family members. The may become a potential biomarker for the diagnosis of epilepsy.
PubMed: 35250450
DOI: 10.3389/fnins.2022.803538 -
Research (Washington, D.C.) 2023Newborn ruminants are considered functionally monogastric animals. The poor understanding of cellular differences between newborn and mature ruminants prevents the...
Newborn ruminants are considered functionally monogastric animals. The poor understanding of cellular differences between newborn and mature ruminants prevents the improvement of health and performance of domestic ruminants. Here, we performed the single-cell RNA sequencing on the rumen, reticulum, omasum, abomasum, duodenum, jejunum, ileum, cecum, colon, rectum, liver, salivary gland, and mammary gland from newborn and adult cattle. A comprehensive single-cell transcriptomic atlas covering 235,941 high-quality single cells and 78 cell types was deciphered. A Cattle Cell Landscape database (http://cattlecelllandscape.zju.edu.cn) was established to elaborately display the data and facilitate effective annotation of cattle cell types and subtypes for the broad research community. By measuring stemness states of epithelial cells in each tissue type, we revealed that the epithelial cells from newborn forestomach (rumen, reticulum, and omasum) were more transcriptionally indistinct and stochastic compared with the adult stage, which was in contrast to those of abomasum and intestinal tissues. The rapid forestomach development during the early life of calves was driven by epithelial progenitor-like cells with high DNA repair activities and methylation. Moreover, in the forestomach tissues of newborn calves, the genus was involved in regulating the transcriptional plasticity of the epithelial progenitor-like cells by DNA methylation regulation. A novel cell type, the cell, was found to be newborn-specific. It apparently plays a crucial role in stemness maintenance of its own and cholangiocytes in the hepatic microenvironment. Our results reveal that the age- and microbiota-dependent cell stemness plasticity drives the postnatal functional maturity of ruminants.
PubMed: 37040481
DOI: 10.34133/research.0025