Gut Microbiome Analysis As A Non-Invasive Tool for the Early Diagnosis of Cholangiocarcinoma

Abstract BACKGROUNDThe liver-microbiome axis is implicated in the pathogenesis of hepatobiliary cancer, and the role of the gut microbiota in cholangiocarcinoma (CCA) remains unclear.METHODWe conducted a case-control study on the intestinal flora of 33 CCA patients and 47 cholelithiasis individuals. We performed 16S rRNA gene sequencing to identify disease-related gut microbiota and assess the potential of the intestinal microbiome as a non-invasive biomarker for CCA.RESULTWe found that gut microbiome of CCA patients had a significantly higher alpha diversity (Shannon and Observed species indices, p = 0.006 and p = 0.02, respectively) and an overall different microbial community composition (p = 0.032). The genus Muribaculaceae_unclassified was most strongly associated with CCA (p < 0.001). We put forward a disease predictive model including twelve intestinal microbiome genera distinguished CCA patients from CF patients with an area under curve (AUC) of approximately 0.93 (95%CI, 0.85–0.987). The forecasting performance of this model was better than CA19-9. Moreover, genera Ezakiella and Garciella were only observed among intrahepatic cholangiocarcinoma patients. Further, we assessed predicted functional modules alternations CCA patients and uncovered a microbiota pattern specific to CCA.CONCLUSIONOur findings provide evidence of the intestinal microbiome as a non-invasive biomarker for CCA.

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Changes in Microbial Community Composition Related to Sex and Colon Cancer by Nrf2 Knockout

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.636808 ◽

2021 ◽

Vol 11 ◽

Author(s):

Chin-Hee Song ◽

Nayoung Kim ◽

Ryoung Hee Nam ◽

Soo In Choi ◽

Jeong Eun Yu ◽

...

Keyword(s):

Gut Microbiome ◽

Microbial Community Composition ◽

Alpha Diversity ◽

16S Rrna Gene Sequencing ◽

Rrna Gene ◽

Related Factor ◽

Invasive Adenocarcinoma ◽

Linear Discriminant ◽

Microbiome Composition ◽

Male Control

The frequency of azoxymethane/dextran sulfate sodium (AOM/DSS)-induced carcinogenesis in male mice is higher than that in female mice. Previous studies have reported that 17β-estradiol inhibits tumorigenesis in males by modulating nuclear factor-erythroid 2-related factor 2 (Nrf2). This study aimed to investigate the changes in mouse gut microbiome composition based on sex, AOM/DSS-induced colorectal cancer (CRC), and Nrf2 genotype. The gut microbiome composition was determined by 16S rRNA gene sequencing fecal samples obtained at week 16 post-AOM administration. In terms of sex differences, our results showed that the wild-type (WT) male control mice had higher alpha diversity (i.e. Chao1, Shannon, and Simpson) than the WT female control mice. The linear discriminant analysis effect size (LEfSe) results revealed that the abundances of Akkermansia muciniphila and Lactobacillus murinus were higher in WT male control mice than in WT female controls. In terms of colon tumorigenesis, the alpha diversity of the male CRC group was lower than that of the male controls in both WT and Nrf2 KO, but did not show such changes in females. Furthermore, the abundance of A. muciniphila was higher in male CRC groups than in male controls in both WT and Nrf2 KO. The abundance of Bacteroides vulgatus was higher in WT CRC groups than in WT controls in both males and females. However, the abundance of L. murinus was lower in WT female CRC and Nrf2 KO male CRC groups than in its controls. The abundance of A. muciniphila was not altered by Nrf2 KO. In contrast, the abundances of L. murinus and B. vulgatus were changed differently by Nrf2 KO depending on sex and CRC. Interestingly, L. murinus showed negative correlation with tumor numbers in the whole colon. In addition, B. vulgatus showed positive correlation with inflammatory markers (i.e. myeloperoxidase and IL-1β levels), tumor numbers, and high-grade adenoma, especially, developed mucosal and submucosal invasive adenocarcinoma at the distal part of the colon. In conclusion, Nrf2 differentially alters the gut microbiota composition depending on sex and CRC induction.

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Evaluation of the gut microbiome in association with biological signatures of inflammation in murine polytrauma and shock

Scientific Reports ◽

10.1038/s41598-021-85897-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sandra A. Appiah ◽

Christine L. Foxx ◽

Dominik Langgartner ◽

Annette Palmer ◽

Cristian A. Zambrano ◽

...

Keyword(s):

Gut Microbiota ◽

Community Composition ◽

Gut Microbiome ◽

Beta Diversity ◽

Microbial Community Composition ◽

Alpha Diversity ◽

Global Changes ◽

Rrna Gene ◽

Alpha And Beta Diversity ◽

Increased Risk

AbstractSevere injuries are frequently accompanied by hemorrhagic shock and harbor an increased risk for complications. Local or systemic inflammation after trauma/hemorrhage may lead to a leaky intestinal epithelial barrier and subsequent translocation of gut microbiota, potentially worsening outcomes. To evaluate the extent with which trauma affects the gut microbiota composition, we performed a post hoc analysis of a murine model of polytrauma and hemorrhage. Four hours after injury, organs and plasma samples were collected, and the diversity and composition of the cecal microbiome were evaluated using 16S rRNA gene sequencing. Although cecal microbial alpha diversity and microbial community composition were not found to be different between experimental groups, norepinephrine support in shock animals resulted in increased alpha diversity, as indicated by higher numbers of distinct microbial features. We observed that the concentrations of proinflammatory mediators in plasma and intestinal tissue were associated with measures of microbial alpha and beta diversity and the presence of specific microbial drivers of inflammation, suggesting that the composition of the gut microbiome at the time of trauma, or shortly after trauma exposure, may play an important role in determining physiological outcomes. In conclusion, we found associations between measures of gut microbial alpha and beta diversity and the severity of systemic and local gut inflammation. Furthermore, our data suggest that four hours following injury is too early for development of global changes in the alpha diversity or community composition of the intestinal microbiome. Future investigations with increased temporal-spatial resolution are needed in order to fully elucidate the effects of trauma and shock on the gut microbiome, biological signatures of inflammation, and proximal and distal outcomes.

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Effects of Psychotropics on the Microbiome in Patients With Depression and Anxiety: Considerations in a Naturalistic Clinical Setting

The International Journal of Neuropsychopharmacology ◽

10.1093/ijnp/pyaa070 ◽

2020 ◽

Author(s):

Yoshihiro Tomizawa ◽

Shunya Kurokawa ◽

Daiki Ishii ◽

Katsuma Miyaho ◽

Chiharu Ishii ◽

...

Keyword(s):

Gut Microbiota ◽

Microbial Diversity ◽

Depressive Disorders ◽

Alpha Diversity ◽

16S Rrna Gene Sequencing ◽

Shannon Index ◽

Rrna Gene ◽

Depression And Anxiety ◽

The Impact ◽

Whole Tree

Abstract Background The antibacterial effects of psychotropics may be part of their pharmacological effects when treating depression. However, limited studies have focused on gut microbiota in relation to prescribed medication. Method We longitudinally investigated the relationship between patients’ prescribed medications and intestinal bacterial diversity in a naturalistic treatment course for patients with major depressive disorders and anxiety disorders. Patients were recruited and their stool was collected at 3 time points during their usual psychiatric treatments. Gut microbiota were analyzed using 16S rRNA gene sequencing. We examined the impact of psychotropics (i.e., antidepressants, anxiolytics, antipsychotics) on their gut microbial diversity and functions. Results We collected 246 stool samples from 40 patients. Despite no differences in microbial diversity between medication groups at the baseline, over the course of treatment, phylogenic diversity whole-tree diversity decreased in patients on antipsychotics compared with patients without (P = .027), and beta diversity followed this trend. Based on a fixed-effect model, antipsychotics predicted microbial diversity; the higher doses correlated with less diversity based on the Shannon index and phylogenic diversity whole tree (estimate = −0.00254, SE = 0.000595, P < .0001; estimate = −0.02644, SE = 0.00833, P = .002, respectively). Conclusion Antipsychotics may play a role in decreasing the alpha diversity of the gut microbiome among patients with depression and anxiety, and our results indicate a relationship with medication dosage. Future studies are warranted and should consider patients’ types and doses of antipsychotics in order to further elucidate the mechanisms of gut-brain interactions in psychiatric disorders.

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Alterations of gut microbiota in gestational diabetes patients during the second trimester of pregnancy in the Shanghai Han population

Journal of Translational Medicine ◽

10.1186/s12967-021-03040-9 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Yao Su ◽

Hong-Kun Wang ◽

Xu-Pei Gan ◽

Li Chen ◽

Yan-Nan Cao ◽

...

Keyword(s):

Gestational Diabetes ◽

Gut Microbiota ◽

Gut Microbiome ◽

Sugar Metabolism ◽

16S Rrna Gene Sequencing ◽

Amino Sugar ◽

Fecal Microbiota ◽

Rrna Gene ◽

Second Trimester ◽

Metabolic Hormone

Abstract Background The causes of gestational diabetes mellitus (GDM) are still unclear. Recent studies have found that the imbalance of the gut microbiome could lead to disorders of human metabolism and immune system, resulting in GDM. This study aims to reveal the different gut compositions between GDM and normoglycemic pregnant women and find the relationship between gut microbiota and GDM. Methods Fecal microbiota profiles from women with GDM (n = 21) and normoglycemic women (n = 32) were assessed by 16S rRNA gene sequencing. Fasting metabolic hormone concentrations were measured using multiplex ELISA. Results Metabolic hormone levels, microbiome profiles, and inferred functional characteristics differed between women with GDM and healthy women. Additionally, four phyla and seven genera levels have different correlations with plasma glucose and insulin levels. Corynebacteriales (order), Nocardiaceae (family), Desulfovibrionaceae (family), Rhodococcus (genus), and Bacteroidetes (phylum) may be the taxonomic biomarkers of GDM. Microbial gene functions related to amino sugar and nucleotide sugar metabolism were found to be enriched in patients with GDM. Conclusion Our study indicated that dysbiosis of the gut microbiome exists in patients with GDM in the second trimester of pregnancy, and gut microbiota might be a potential diagnostic biomarker for the diagnosis, prevention, and treatment of GDM.

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Integrative analysis of the gut microbiome and metabolome in a rat model with stress induced irritable bowel syndrome

Scientific Reports ◽

10.1038/s41598-021-97083-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yue Hu ◽

Fang Chen ◽

Haiyong Ye ◽

Bin Lu

Keyword(s):

Irritable Bowel Syndrome ◽

Gut Microbiota ◽

Rat Model ◽

Gut Microbiome ◽

16S Rrna Gene Sequencing ◽

Metabolic Phenotype ◽

Control Group ◽

Rrna Gene ◽

Microbial Dysbiosis ◽

Irritable Bowel

AbstractStress is one of the major causes of irritable bowel syndrome (IBS), which is well-known for perturbing the microbiome and exacerbating IBS-associated symptoms. However, changes in the gut microbiome and metabolome in response to colorectal distention (CRD), combined with restraint stress (RS) administration, remains unclear. In this study, CRD and RS stress were used to construct an IBS rat model. The 16S rRNA gene sequencing was used to characterize the microbiota in ileocecal contents. UHPLC-QTOF-MS/MS assay was used to characterize the metabolome of gut microbiota. As a result, significant gut microbial dysbiosis was observed in stress-induced IBS rats, with the obvious enrichment of three and depletion of 11 bacterial taxa in IBS rats, when compared with those in the control group (q < 0.05). Meanwhile, distinct changes in the fecal metabolic phenotype of stress-induced IBS rats were also found, including five increased and 19 decreased metabolites. Furthermore, phenylalanine, tyrosine and tryptophan biosynthesis were the main metabolic pathways induced by IBS stress. Moreover, the altered gut microbiota had a strong correlation with the changes in metabolism of stress-induced IBS rats. Prevotella bacteria are correlated with the metabolism of 1-Naphthol and Arg.Thr. In conclusion, the gut microbiome, metabolome and their interaction were altered. This may be critical for the development of stress-induced IBS.

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Changes in the Intestinal Microbiome during a Multispecies Probiotic Intervention in Compensated Cirrhosis

Nutrients ◽

10.3390/nu12061874 ◽

2020 ◽

Vol 12 (6) ◽

pp. 1874 ◽

Cited By ~ 1

Author(s):

Angela Horvath ◽

Marija Durdevic ◽

Bettina Leber ◽

Katharina di Vora ◽

Florian Rainer ◽

...

Keyword(s):

Gut Microbiome ◽

Controlled Trial ◽

16S Rrna Gene Sequencing ◽

Intestinal Microbiome ◽

Rrna Gene ◽

Microbiome Composition ◽

Beneficial Effects ◽

Compensated Cirrhosis ◽

Gut Barrier Function ◽

Probiotic Treatment

Probiotics have been used in trials to therapeutically modulate the gut microbiome and have shown beneficial effects in cirrhosis. However, their effect on the microbiome of cirrhosis patients is not fully understood yet. Here, we tested the effects of a multispecies probiotic on microbiome composition in compensated cirrhosis. The gut microbiome composition of 58 patients with compensated cirrhosis from a randomized controlled trial who received a daily dose of multispecies probiotics or placebo for six months was analysed by 16S rRNA gene sequencing. Microbiome composition of patients who received probiotics was enriched with probiotic strains and the abundance of Faecalibacterium prausnitzii, Syntrophococcus sucromutans, Bacteroides vulgatus, Alistipes shahii and a Prevotella species was increased in the probiotic group compared to the placebo group. Patients who had microbiome changes in response to probiotic treatment also showed a significant increase in neopterin and a significant decrease in faecal zonulin levels after intervention, which was not observed in placebo-treated patients or patients with unchanged microbiome compositions. In conclusion, multispecies probiotics may enrich the microbiome of compensated cirrhotic patients with probiotic bacteria during a six-month intervention and beneficially change the residential microbiome and gut barrier function.

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Inbreeding Alters the Gut Microbiota of the Banna Minipig

Animals ◽

10.3390/ani10112125 ◽

2020 ◽

Vol 10 (11) ◽

pp. 2125

Author(s):

Limin Wei ◽

Bo Zeng ◽

Siyuan Zhang ◽

Feng Li ◽

Fanli Kong ◽

...

Keyword(s):

Gut Microbiota ◽

Gene Sequencing ◽

Alpha Diversity ◽

16S Rrna Gene Sequencing ◽

Rrna Gene ◽

Rrna Gene Sequencing ◽

Isoleucine Metabolism ◽

Dominant Bacteria ◽

The Impact ◽

Predicted Function

The gut microbiota coevolve with the host and can be stably transmitted to the offspring. Host genetics plays a crucial role in the composition and abundance of gut microbiota. Inbreeding can cause a decrease of the host’s genetic diversity and the heterozygosity. In this study, we used 16S rRNA gene sequencing to compare the differences of gut microbiota between the Diannan small-ear pig and Banna minipig inbred, aiming to understand the impact of inbreeding on the gut microbiota. Three dominant bacteria (Stenotrophlomonas, Streptococcus, and Lactobacillus) were steadily enriched in both the Diannan small-ear pig and Banna minipig inbred. After inbreeding, the gut microbiota alpha diversity and some potential probiotics (Bifidobacterium, Tricibacter, Ruminocaccae, Christensenellaceae, etc.) were significantly decreased, while the pathogenic Klebsiella bacteria was significantly increased. In addition, the predicted metagenomic analysis (PICRUSt2) indicated that several amino acid metabolisms (‘‘Valine, leucine, and isoleucine metabolism’’, ‘‘Phenylalanine, tyrosine, and tryptophan biosynthesis’’, ‘‘Histidine metabolism’’) were also markedly decreased after the inbreeding. Altogether our data reveal that host inbreeding altered the composition and the predicted function of the gut microbiome, which provides some data for the gut microbiota during inbreeding.

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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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Microbe-Metabolite Associations Linked to the Rebounding Murine Gut Microbiome Postcolonization with Vancomycin-Resistant Enterococcus faecium

mSystems ◽

10.1128/msystems.00452-20 ◽

2020 ◽

Vol 5 (4) ◽

Author(s):

Andre Mu ◽

Glen P. Carter ◽

Lucy Li ◽

Nicole S. Isles ◽

Alison F. Vrbanac ◽

...

Keyword(s):

Gut Microbiome ◽

Enterococcus Faecium ◽

Molecular Mechanisms ◽

Microbial Community Composition ◽

16S Rrna Gene Sequencing ◽

Rrna Gene ◽

Content Type ◽

Functional Roles ◽

Specific Pathogen ◽

Vancomycin Resistant

ABSTRACT Vancomycin-resistant Enterococcus faecium (VREfm) is an emerging antibiotic-resistant pathogen. Strain-level investigations are beginning to reveal the molecular mechanisms used by VREfm to colonize regions of the human bowel. However, the role of commensal bacteria during VREfm colonization, in particular following antibiotic treatment, remains largely unknown. We employed amplicon 16S rRNA gene sequencing and metabolomics in a murine model system to try and investigate functional roles of the gut microbiome during VREfm colonization. First-order taxonomic shifts between Bacteroidetes and Tenericutes within the gut microbial community composition were detected both in response to pretreatment using ceftriaxone and to subsequent VREfm challenge. Using neural networking approaches to find cooccurrence profiles of bacteria and metabolites, we detected key metabolome features associated with butyric acid during and after VREfm colonization. These metabolite features were associated with Bacteroides, indicative of a transition toward a preantibiotic naive microbiome. This study shows the impacts of antibiotics on the gut ecosystem and the progression of the microbiome in response to colonization with VREfm. Our results offer insights toward identifying potential nonantibiotic alternatives to eliminate VREfm through metabolic reengineering to preferentially select for Bacteroides. IMPORTANCE This study demonstrates the importance and power of linking bacterial composition profiling with metabolomics to find the interactions between commensal gut bacteria and a specific pathogen. Knowledge from this research will inform gut microbiome engineering strategies, with the aim of translating observations from animal models to human-relevant therapeutic applications.

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Dietary Correlates of Oral and Gut Microbiota in the Water Monitor Lizard, Varanus salvator (Laurenti, 1768)

Frontiers in Microbiology ◽

10.3389/fmicb.2021.771527 ◽

2022 ◽

Vol 12 ◽

Author(s):

Yu Du ◽

Jun-Qiong Chen ◽

Qian Liu ◽

Jian-Chao Fu ◽

Chi-Xian Lin ◽

...

Keyword(s):

Gut Microbiota ◽

Water Environment ◽

Alpha Diversity ◽

16S Rrna Gene Sequencing ◽

Rrna Gene ◽

Oral Microbiota ◽

Monitor Lizard ◽

Varanus Salvator ◽

In The Wild ◽

Monitor Lizards

Numerous studies have demonstrated that food shapes the structure and composition of the host’s oral and gut microbiota. The disorder of oral and gut microbiota may trigger various host diseases. Here, we collected oral and gut samples from wild water monitor lizards (Varanus salvator) and their captive conspecifics fed with bullfrogs, eggs, and depilated chicken, aiming to examine dietary correlates of oral and gut microbiota. We used the 16S rRNA gene sequencing technology to analyze the composition of the microbiota. Proteobacteria and Bacteroidota were the dominant phyla in the oral microbiota, and so were in the gut microbiota. The alpha diversity of microbiota was significantly higher in the gut than in the oral cavity, and the alpha diversity of oral microbiota was higher in captive lizards than in wild conspecifics. Comparing the relative abundance of oral and gut bacteria and their gene functions, differences among different animal groups presumably resulted from human contact in artificial breeding environments and complex food processing. Differences in gene function might be related to the absolute number and/or the taxonomic abundance of oral and gut microorganisms in the wild and the water environment. This study provides not only basic information about the oral and gut microbiota of captive and wild water monitor lizards, but also an inference that feeding on frogs and aquatic products and reducing human exposure help water monitor lizards maintain a microbiota similar to that in the wild environment.

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