A Predictive Model Based on the Gut Microbiota Improves the Diagnostic Effect in Patients With Cholangiocarcinoma

Cholangiocarcinoma (CCA) is a malignant hepatic tumor with a poor prognosis, which needs early diagnosis urgently. The gut microbiota has been shown to play a crucial role in the progression of liver cancer. Here, we explored a gut microbiota model covering genera Burkholderia-Caballeronia-Paraburkholderia, Faecalibacterium, and Ruminococcus_1 (B-F-R) for CCA early diagnosis. A case-control study was conducted to enroll 53 CCA patients, 47 cholelithiasis patients, and 40 healthy controls. The feces samples and clinical information of participants were collected in the same period. The gut microbiota and its diversity of individuals were accessed with 16S rDNA sequencing, and the gut microbiota profile was evaluated according to microbiota diversity. Finally, four enriched genera in the CCA group (genera Bacteroides, Muribaculaceae_unclassified, Muribaculum, and Alistipes) and eight enriched genera in the cholelithiasis group (genera Bifidobacterium, Streptococcus, Agathobacter, Ruminococcus_gnavus_group, Faecalibacterium, Subdoligranulum, Collinsella, Escherichia-Shigella) constitute an overall different microbial community composition (P = 0.001). The B-F-R genera model with better diagnostic value than carbohydrate antigen 19-9 (CA19-9) was identified by random forest and Statistical Analysis of Metagenomic Profiles (STAMP) to distinguish CCA patients from healthy controls [area under the curve (AUC) = 0.973, 95% CI = 0.932–1.0]. Moreover, the correlative analysis found that genera Burkholderia-Caballeronia-Paraburkholderia were positively correlated with body mass index (BMI). The significantly different microbiomes between cholelithiasis and CCA were found via principal coordinates analysis (PCoA) and linear discriminant analysis effect size (LEfSe), and Venn diagram and LEfSe were utilized to identify four genera by comparing microbial compositions among patients with malignant obstructive jaundice (MOJ-Y) or not (MOJ-N). In brief, our findings suggest that gut microbiota vary from benign and malignant hepatobiliary diseases to healthy people and provide evidence supporting gut microbiota to be a non-invasive biomarker for the early diagnosis of CCA.

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Changes in the gut microbiota after hepatitis C virus eradication

Scientific Reports ◽

10.1038/s41598-021-03009-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Takashi Honda ◽

Masatoshi Ishigami ◽

Kenta Yamamoto ◽

Tomoaki Takeyama ◽

Takanori Ito ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Gut Microbiota ◽

Rrna Gene ◽

Principal Coordinates Analysis ◽

Virus Eradication ◽

Fecal Samples ◽

Linear Discriminant ◽

Sequencing Platform ◽

Principal Coordinates

AbstractThe gut microbiota interacts with infectious diseases and affects host immunity. Liver disease is also reportedly associated with changes in the gut microbiota. To elucidate the changes in the gut microbiota before and after hepatitis C virus (HCV) eradication through direct-acting antiviral (DAA) treatment in patients with chronic hepatitis C (CHC), we investigated 42 samples from 14 patients who received DAA therapy for HCV. Fecal samples were obtained before treatment (Pre), when treatment ended (EOT), and 24 weeks after treatment ended (Post24). The target V3–4 region of the 16S rRNA gene from fecal samples was amplified using the Illumina Miseq sequencing platform. The diversity of the gut microbiota did not significantly differ between Pre, EOT, and Post24. Principal coordinates analysis showed that for each patient, the values at Pre, EOT, and Post24 were concentrated within a small area. The linear discriminant analysis of effect size showed that the relative abundances of Faecalibacterium and Bacillus increased at EOT, further increased at Post24, and were significantly increased at Post24 compared to Pre. These suggest that changes in the gut microbiota should be considered as among the various effects observed on living organisms after HCV eradication.

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Lupus Gut Microbiota Transplants Cause Autoimmunity and Inflammation

10.1101/2021.08.15.456375 ◽

2021 ◽

Author(s):

Yiyangzi Ma ◽

Ruru Guo ◽

Yiduo Sun ◽

Xin Li ◽

Lun He ◽

...

Keyword(s):

Gut Microbiota ◽

Lupus Erythematosus ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Healthy Controls ◽

Germ Free ◽

Autoimmune Antibodies ◽

Expression Of Genes ◽

Rdna Sequencing

Background: The etiology of systemic lupus erythematosus (SLE) is multifactorial. Recently, growing evidence suggests that the microbiota plays a role in SLE, yet whether gut microbiota participates in the development of SLE remains largely unknown. To investigate this issue, we carried out 16s rDNA sequencing analyses in a cohort of 18 female un-treated active SLE patients and 7 female healthy controls, and performed fecal microbiota transplantation from patients and healthy controls to germ-free mice. Results: Compared to the healthy controls, we found no significant different microbial diversity but some significantly different species in SLE patients including Turicibacter genus and other 5 species. Fecal transfer from SLE patients to germ free (GF) C57BL/6 mice caused GF mice to develop a series of lupus-like phenotyptic features, which including an increased serum autoimmune antibodies, and imbalanced cytokines, altered distribution of immune cells in mucosal and peripheral immune response, and upregulated expression of genes related to SLE in recipient mice that received SLE fecal microbiota transplantation (FMT). Moreover, the metabolism of histidine was significantly altered in GF mice treated with SLE patient feces, as compared to those which received healthy fecal transplants. Conclusions: Overall, our results describe a causal role of aberrant gut microbiota in contributing to the pathogenesis of SLE. The interplay of gut microbial and histidine metabolism may be one of the mechanisms intertwined with autoimmune activation in SLE.

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Abstract P162: Butyrate, a Microbial Metabolite, Attenuates Angiotensin II-induced Hypertension and Gut Dysbiosis

Hypertension ◽

10.1161/hyp.68.suppl_1.p162 ◽

2016 ◽

Vol 68 (suppl_1) ◽

Author(s):

Seungbum Kim ◽

Gilberto O Lobaton ◽

Mohan K Raizada

Keyword(s):

Angiotensin Ii ◽

Sodium Butyrate ◽

Ang Ii ◽

Principal Coordinates Analysis ◽

Gut Dysbiosis ◽

Microbial Dysbiosis ◽

Inflammatory Status ◽

Principal Coordinates ◽

Rdna Sequencing ◽

Butyrate Treatment

Objectives: We have previously established that hypertension (HTN) is associated with gut dysbiosis in rat models and patients with high blood pressure. Gut dysbiosis was associated with an increase in Firmicutes/Bacteriodetes ratio and a decrease in butyrate-producing microbial populations. This led us to hypothesize that infusion of butyrate would overcome gut microbial dysbiosis induced butyrate deficiency and reverse angiotensin II (Ang II)-induced HTN. Design and Method: Four groups of C57BL6 mice were infused with either saline, Ang II (1000ng/kg/min), Ang II + sodium butyrate (1mg/kg), or sodium butyrate alone for 4 weeks. Fecal samples were analyzed by 16S bacterial rDNA sequencing for gut microbiome identification. Intestinal leukocytes were analyzed using FACS. Results: Ang II induced increase in MAP was significantly attenuated in mice co-administrated with butyrate (Control, 102.1±5.7 mmHg; Ang II, 148.3±8.1 mmHg; Ang II+Butyrate, 120.5±11.2 mmHg). Microbiota analysis demonstrated a significant increase of gut dysbiosis in Ang II-HTN that was normalized by butyrate treatment (F/B ratio: Control, 2.6; Ang II, 5.4; Ang II+Butyrate, 2.0). Principal Coordinates Analysis indicated each group in the input phylogenetic tree had significantly different microbial communities. LEfSe analysis showed that there were decreases of beneficial bacteria such as Lactobacillus and Bifidobacterium , and increases of Corynebacterium and Staphylococcus at the genus level of Ang II-HTN mice. Furthermore, inflammatory status of the gut as evidenced by the level of mucosal T cells in lamina propria from these groups showed that there was an increase of CCR2 + Th17 cells in Ang II-HTN mice, but not in butyrate co-treated mice (Control, 15.7%; Ang II, 28.4%; Ang II+Butyrate, 15%). Conclusions: These observations show that gut dysbiosis and the decrease of butyrate producing bacteria are associated with Ang II-HTN. Thus, supplementing butyrate in Ang II treated mice attenuated HTN and reversed gut dysbiosis, as well as normalizing the intestinal Th17. These data suggest butyrate producing bacteria could be considered as a novel probiotic therapy for hypertension.

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Comparative analysis of the tonsillar microbiota in IgA nephropathy and other glomerular diseases

Scientific Reports ◽

10.1038/s41598-020-73035-x ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Ji In Park ◽

Tae-Yoon Kim ◽

Bumjo Oh ◽

Hyunjeong Cho ◽

Ji Eun Kim ◽

...

Keyword(s):

Immunoglobulin A ◽

Upper Airway ◽

Illumina Miseq ◽

Rrna Gene ◽

Healthy Controls ◽

Principal Coordinates Analysis ◽

Glomerular Diseases ◽

Principal Coordinates ◽

Airway Infections ◽

Repeated Events

Abstract Immunoglobulin A nephropathy (IgAN) involves repeated events of gross haematuria with concurrent upper airway infections. The mucosal immune system, especially the tonsil, is considered the initial site of inflammation, although the role of the tonsillar microbiota has not been established in IgAN. In this study, we compared the tonsillar microbiota of patients with IgAN (n = 21) and other glomerular diseases (n = 36) as well as, healthy controls (n = 23) from three medical centres in Korea. The microbiota was analysed from tonsil swabs using the Illumina MiSeq system based on 16S rRNA gene. Tonsillar bacterial diversity was higher in IgAN than in other glomerular diseases, although it did not differ from that of healthy controls. Principal coordinates analysis revealed differences between the tonsillar microbiota of IgAN and both healthy and disease controls. The proportions of Rahnella, Ruminococcus_g2, and Clostridium_g21 were significantly higher in patients with IgAN than in healthy controls (corrected p < 0.05). The relative abundances of several taxa were correlated with the estimated glomerular filtration rate, blood urea nitrogen, haemoglobin, and serum albumin levels. Based on our findings, tonsillar microbiota may be associated with clinical features and possible immunologic pathogenesis of IgAN.

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Effects of Xylo-Oligosaccharide on the Gut Microbiota of Patients With Ulcerative Colitis in Clinical Remission

Frontiers in Nutrition ◽

10.3389/fnut.2021.778542 ◽

2021 ◽

Vol 8 ◽

Author(s):

Zongwei Li ◽

Zhengpeng Li ◽

Liying Zhu ◽

Ning Dai ◽

Gang Sun ◽

...

Keyword(s):

Ulcerative Colitis ◽

Gut Microbiota ◽

Healthy Volunteers ◽

Clinical Remission ◽

Principal Component ◽

Fecal Samples ◽

Linear Discriminant ◽

Wilcoxon Rank Sum Test ◽

Rdna Sequencing

Gut microbiota dysbiosis is closely associated with ulcerative colitis (UC). Prebiotic therapy is a potential approach for UC management especially remission maintaining. Xylo-oligosaccharide (XOS) is an efficient prebiotic with proven health benefits and few side effects. However, the effects of XOS on the gut microbiota of patients with UC have not been investigated previously. The aim of this study was to evaluate the prebiotic effects of XOS on the fecal microbiota of patients with UC in clinical remission using an in vitro fermentation model. Five patients with UC in clinical remission and five healthy volunteers were enrolled in this study. Fresh fecal samples of UC patients were diluted and inoculated in yeast extract, casitone and fatty acid (YCFA) medium alone or with XOS. After fermentation for 48 h, samples were collected for 16S rDNA sequencing to investigate the gut microbiota composition. Differences in the gut microbiota between healthy volunteers and UC patients in clinical remission were detected using original fecal samples. Subsequently, the differences between the YCFA medium alone or with XOS samples were analyzed to illustrate the effects of XOS on the gut microbiota of UC patients. In both principal coordinate analysis (PCoA) and principal component analysis (PCA), the fecal samples of UC patients differed from those of healthy volunteers. Linear discriminant analysis effect size (LEfSe) analysis revealed that the relative abundances of g_Roseburia and g_Lachnospiraceae_ND3007_group were higher in healthy volunteers than in UC patients, while o_Lactobacillales abundance showed the opposite trend (P < 0.05). Wilcoxon rank-sum test bar plot showed that the abundances of g_Eubacterium_halli_group and g_Lachnospiraceae_ND3007_group were higher in the healthy volunteers than in the UC patients (P < 0.05). In addition, in UC patients, the Wilcoxon rank-sum test showed that XOS fermentation promoted the growth of bacterial groups including g_Roseburia, g_Bifidobacterium, and g_Lactobacillus, which is beneficial for recovery of intestinal diseases. These results suggest that XOS can relieve dysbiosis in the feces of UC patients in clinical remission and thus represent a potential prebiotic material for maintaining remission.

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Comparison of human gut microbial profiles of matched faecal and biopsy samples from healthy individuals using culture dependent and independent methods

Access Microbiology ◽

10.1099/acmi.ac2020.po0261 ◽

2020 ◽

Vol 2 (7A) ◽

Author(s):

Indrani Mukhopadhya ◽

Jenny Martin ◽

Sophie Shaw ◽

Irini Lazou Ahrén ◽

Niklas Larsson ◽

...

Keyword(s):

Gut Microbiota ◽

Healthy Volunteers ◽

Distance Matrix ◽

Gastrointestinal Diseases ◽

Rrna Gene ◽

Sequence Variant ◽

Principal Coordinates Analysis ◽

Principal Coordinates ◽

Faecal Samples ◽

The Family

Faecal samples have often been used to characterise the gut microbiota in health and disease. There is significant debate whether faecal bacterial communities accurately reflect the mucosa associated bacterial populations, which are considered critical in the aetiopathogenesis of several gastrointestinal diseases. We simultaneously assessed faecal and mucosal microbiota from healthy volunteers to unravel the degree of concordance between the two profiles. Paired fresh rectal biopsies and faecal samples were obtained from ten healthy volunteers and processed under stringent anaerobic conditions. Composition and diversity of the microbiota were studied using next generation sequencing targeting the 16S ribosomal nucleic acid (rRNA) gene and culturomics. Bacterial richness and diversity were comparable between mucosal and faecal samples with no significant statistical differences. The relative abundance of Oxalobacteraceae, Propionibacteriaceae, Campylobacteraceae and Corynebacteriaceae were significantly increased (Corncob analysis; FDR=0.00027, 0.000046, 0.011 and 0.025 respectively) in biopsy compared to faecal samples at the family level. Conversely, there was increased abundance from the family Ruminococcaceae and Clostridiaceae (Corncob analysis; FDR=0.025 and 0.025 respectively) in faecal samples. Principal Coordinates Analysis of a Bray Curtis distance matrix generated from sequence variant tables did not show distinct clustering of biopsy and faecal samples (PERMANOVA; p=0.991). A total of 528 bacteria were isolated from a subset of 6 volunteer samples (biopsy and faeces) out of which there were 97 unique and 39 novel species identified. Our study showed good concordance between faecal and gut mucosal microbial profile, corroborating that faecal samples can act as a convenient surrogate to study gut microbiota.

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Elderly patients of mild cognitive impairment exhibit altered profiles of the gut microbiota

10.21203/rs.3.rs-74865/v1 ◽

2020 ◽

Author(s):

Qiong Pan ◽

Ya-Qian Li ◽

Ke Guo ◽

Min Xue ◽

Yu Gan ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Gut Microbiota ◽

Bacterial Species ◽

Natural Aging ◽

Microbial Composition ◽

Principal Coordinates Analysis ◽

Transitional State ◽

Staphylococcus Intermedius ◽

Principal Coordinates

Abstract Background As the transitional state between normal aging and Alzheimer’s disease (AD), mild cognitive impairment (MCI) is characterized by cognitive decline greater than natural aging. While the association between AD and gut microbiota has been reported in a number of studies, there is still very limited microbial research about MCI. Methods Here we enrolled 48 participants, including 22 MCI cases and 26 normal controls. Fecal samples were collected for 16S rRNA quantitative arrays and bioinformatics analysis. Results Both Principal Coordinates Analysis (PCoA) and Non-metric Multidimensional scaling (NMDS) demonstrated that the microbial composition of MCI individuals deviated from the cluster of healthy controls. Multiple bacterial species were significantly increased (e.g., Staphylococcus intermedius) or decreased (e.g., Bacteroides salyersiae) in the samples from MCI group. Conclusion Therefore, the composition of gut microbiota differed between control subjects and MCI cases. Our study is the first to identify a series of MCI signature species in the gut microbiota, thus providing a new direction for future development of early diagnosis and probiotics regimen.

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Gut microbial characteristics of adult patients with allergy rhinitis

Microbial Cell Factories ◽

10.1186/s12934-020-01430-0 ◽

2020 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Libing Zhu ◽

Feng Xu ◽

Wenrong Wan ◽

Bin Yu ◽

Lin Tang ◽

...

Keyword(s):

Gut Microbiota ◽

Bacterial Diversity ◽

Bacterial Invasion ◽

Rrna Gene ◽

Life Questionnaire ◽

Healthy Individuals ◽

Alpha Linolenic Acid ◽

Principal Coordinates Analysis ◽

Principal Coordinates ◽

Significant Difference

Abstract Background Although recent studies have indicated that intestinal microbiota dweller are involved in the pathogenesis of allergy rhinitis (AR), the influence of gut microbiota on AR adult has not been fully elucidated yet. Hence, we carried out this study to uncover the distinctive bacterial taxa that differentiate allergy rhinitis patients from healthy individuals. Feces samples from thirty three AR patients and thirty one healthy individuals were analyzed by 16S rRNA gene sequencing. Results Results showed that the bacterial diversity in AR group was significantly higher than that of the non-AR group. Bacterial communities between AR and non-AR group were significantly differentiated as revealed by Principal coordinates analysis (PCoA) and the variation within non-AR were higher than that of the counterpart. Firmicutes, Fusobacteria, Actinobacteria, Cyanobacteria and Chloroflexi were the significantly differed phyla taxa and the top significantly distinguished bacterial genus included Prevotella_9, Phascolarctobacterium, Roseburia, Megamonas, Alistipes, Lachnoclostridium and Fusobacterium. The higher network complexity in AR group were dominated by taxa belonging to Firmicutes. The predicted function, alpha linolenic acid metabolism and bacterial invasion of epithelial cells pathway were higher in non-AR group while gonadotropin-releasing hormone (GnRH) signaling pathway, Fc γ-R mediated phagocytosis and endocytosis were higher in AR patients. Although the bacterial diversity between moderate and severe AR patients showed no significant difference, the significant correlation between featured genus and total nasal symptom score or rhinoconjunctivitis quality of life questionnaire, such as Butyricicoccus and Eisenbergiella, revealed the potential to intervene the AR status by means of gut microbiota. Conclusions In conclusion, patients with allergy rhinitis had distinguished gut microbiota characteritics in comparison with healthy controls. The results suggest that gut microbiota might play crucial roles in influencing the course and different symptoms of AR. Trial registration ChiCTR, ChiCTR1900028613. Registered 29 December 2019, https://www.chictr.org.cn/showproj.aspx?proj=47650.

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Variations in the Compositions of Soil Bacterial and Fungal Communities Due to Microhabitat Effects Induced by Simulated Nitrogen Deposition of a Bamboo Forest in Wetland

Forests ◽

10.3390/f10121098 ◽

2019 ◽

Vol 10 (12) ◽

pp. 1098 ◽

Cited By ~ 1

Author(s):

Weicheng Li ◽

Haiyan Sheng ◽

Desy Ekawati ◽

Yueping Jiang ◽

Huimin Yang

Keyword(s):

Nitrogen Deposition ◽

Soil Ph ◽

Solid Phase ◽

Wetland Management ◽

Alpha Diversity ◽

Principal Coordinates Analysis ◽

Linear Discriminant ◽

Fungal Abundance ◽

Principal Coordinates ◽

Bacteria And Fungi

Although numerous studies have been published on nitrogen (N) deposition, little is known about its impact on microbial communities in wetland forests. Here, we used simulated nitrogen deposition (SND) to analyze the importance of differences in soil microhabitats in promoting the diversity of soil bacteria and fungi. We compared various levels of SND (control (CK), low N (N30), medium N (N60), and high N (N90)) and found that these were associated with changes in soil microhabitats. Additionally, SND affected soil pH, clay and sand content of the soil, and specific surface area (SSA). Bacteria and fungi responded differently to increased SND levels. The alpha diversity of bacteria decreased with an increased SND level, while fungal abundance, diversity, and community evenness reached their maximum values at the N60 threshold. Principal coordinates analysis (PCoA), nonparametric multivariate analysis of variance (PERMANOVA), and linear discriminant analysis (LDA) coupled with effect size measurements (LefSe) also confirmed that the bacterial composition was different at N90 compared to other levels of SND while that of fungi was different at N60. A higher discriminant level (LDA score ≥4) may be a valuable index of selecting indicator microbial clades sensitive to SND for wetland management. Further, an increased pH was associated with a greater abundance of bacteria and fungi. In addition, the volume contents of clay and SSA were negatively correlated with bacteria but fungi are associated with soil specific gravity (SSG). Overall, in a neutral soil pH environment, pH fluctuation is the main influencing factor in terms of bacterial and fungal abundance and diversity. The diversity of fungi is more dependent on the type and relative content of solid phase components in soil than that of bacteria, implying the presence of species-specific niches for bacteria and fungi. These results demonstrate that changes in SND can induce short-term microbial and microhabitat changes.

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