Comparison of the Human Gut Microbiota between Normal Control Subjects and Patients with Colonic Polyps and Colorectal Cancer

Abstract Background: The human gut microbiota has been related to numerous colonic diseases. To identify colorectal cancer (CRC)-associated microbiota, the gut microbiomes of patients with colonic polyps and CRC compared to normal controls were analyzed.Methods: Between July and December 2020, forty-four stool samples were obtained from participants older than 50 years who were scheduled for elective colonoscopies at the Surgery Clinic, Songklanagarind Hospital. The samples were divided into 3 groups (17 normal control, 17 colonic polyps, and 10 CRC) and were collected for analysis with a 16s metagenomic sequencing library preparation with MiSeq Reporter software (MSR) following the protocol of the 16s metagenomics workflow. The microbiome data were analyzed with Kruskal–Wallis test with the Dunn-Bonferroni post hoc method.Results: The relative proportions of beneficial butyrate-producers Kineothrix alysoides, Eubacterium rectale, and Roseburia inulinsivorans were significantly higher in healthy control and colonic polyp groups compared with the CRC group at the top three lowest p-values. The recommended CRC biomarker Clostridium symbiosum was shown in a significantly higher proportion in the CRC group than in the normal control group. The prevalences and relative proportion of the novel CRC-associated species Acutalibacter muris and the familiar CRC-associated species Christensenella massiliensis and lntestinimonas butyriciproducens were significantly higher in the CRC group than in the normal control and colonic polyp groups at the top three lowest p-values.Conclusions: A correlation between specific bacteria and clinical outcomes was found in this pilot study. The microbiome data revealed possible microbial biomarkers associated with CRC. Studies with larger numbers of stool samples are required to substantiate our findings.

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Postoperative Complications Are Associated with Long-Term Changes in the Gut Microbiota Following Colorectal Cancer Surgery

Life ◽

10.3390/life11030246 ◽

2021 ◽

Vol 11 (3) ◽

pp. 246

Author(s):

Felix C.F. Schmitt ◽

Martin Schneider ◽

William Mathejczyk ◽

Markus A. Weigand ◽

Jane C. Figueiredo ◽

...

Keyword(s):

Colorectal Cancer ◽

Postoperative Complications ◽

Gut Microbiota ◽

Gut Microbiome ◽

Tumor Resection ◽

Microbial Composition ◽

Colorectal Cancer Surgery ◽

Long Term Changes ◽

Stool Samples

Changes in the gut microbiome have already been associated with postoperative complications in major abdominal surgery. However, it is still unclear whether these changes are transient or a long-lasting effect. Therefore, the aim of this prospective clinical pilot study was to examine long-term changes in the gut microbiota and to correlate these changes with the clinical course of the patient. Methods: In total, stool samples of 62 newly diagnosed colorectal cancer patients undergoing primary tumor resection were analyzed by 16S-rDNA next-generation sequencing. Stool samples were collected preoperatively in order to determine the gut microbiome at baseline as well as at 6, 12, and 24 months thereafter to observe longitudinal changes. Postoperatively, the study patients were separated into two groups—patients who suffered from postoperative complications (n = 30) and those without complication (n = 32). Patients with postoperative complications showed a significantly stronger reduction in the alpha diversity starting 6 months after operation, which does not resolve, even after 24 months. The structure of the microbiome was also significantly altered from baseline at six-month follow-up in patients with complications (p = 0.006). This was associated with a long-lasting decrease of a large number of species in the gut microbiota indicating an impact in the commensal microbiota and a long-lasting increase of Fusobacterium ulcerans. The microbial composition of the gut microbiome shows significant changes in patients with postoperative complications up to 24 months after surgery.

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Microbiota-Associated Metabolites and Related Immunoregulation in Colorectal Cancer

Cancers ◽

10.3390/cancers13164054 ◽

2021 ◽

Vol 13 (16) ◽

pp. 4054

Author(s):

Yan Chen ◽

Ying-Xuan Chen

Keyword(s):

Colorectal Cancer ◽

Fatty Acids ◽

Gut Microbiota ◽

Immune Responses ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Indole Derivatives ◽

Human Gut ◽

Growing Body ◽

Specific Influence

A growing body of research has found close links between the human gut microbiota and colorectal cancer (CRC), associated with the direct actions of specific bacteria and the activities of microbiota-derived metabolites, which are implicated in complex immune responses, thus influencing carcinogenesis. Diet has a significant impact on the structure of the microbiota and also undergoes microbial metabolism. Some metabolites, such as short-chain fatty acids (SCFAs) and indole derivatives, act as protectors against cancer by regulating immune responses, while others may promote cancer. However, the specific influence of these metabolites on the host is conditional. We reviewed the recent insights on the relationships among diet, microbiota-derived metabolites, and CRC, focusing on their intricate immunomodulatory responses, which might influence the progression of colorectal cancer.

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Altered Fecal Small RNA Profiles in Colorectal Cancer Reflect Gut Microbiome Composition in Stool Samples

mSystems ◽

10.1128/msystems.00289-19 ◽

2019 ◽

Vol 4 (5) ◽

Cited By ~ 9

Author(s):

Sonia Tarallo ◽

Giulio Ferrero ◽

Gaetano Gallo ◽

Antonio Francavilla ◽

Giuseppe Clerico ◽

...

Keyword(s):

Colorectal Cancer ◽

Gut Microbiota ◽

Small Rna ◽

Gut Microbiome ◽

Small Rnas ◽

Area Under The Curve ◽

Small Rna Sequencing ◽

Predictive Tool ◽

Cross Sectional ◽

Stool Samples

ABSTRACT Dysbiotic configurations of the human gut microbiota have been linked to colorectal cancer (CRC). Human small noncoding RNAs are also implicated in CRC, and recent findings suggest that their release in the gut lumen contributes to shape the gut microbiota. Bacterial small RNAs (bsRNAs) may also play a role in carcinogenesis, but their role has been less extensively explored. Here, we performed small RNA and shotgun sequencing on 80 stool specimens from patients with CRC or with adenomas and from healthy subjects collected in a cross-sectional study to evaluate their combined use as a predictive tool for disease detection. We observed considerable overlap and a correlation between metagenomic and bsRNA quantitative taxonomic profiles obtained from the two approaches. We identified a combined predictive signature composed of 32 features from human and microbial small RNAs and DNA-based microbiome able to accurately classify CRC samples separately from healthy and adenoma samples (area under the curve [AUC] = 0.87). In the present study, we report evidence that host-microbiome dysbiosis in CRC can also be observed by examination of altered small RNA stool profiles. Integrated analyses of the microbiome and small RNAs in the human stool may provide insights for designing more-accurate tools for diagnostic purposes. IMPORTANCE The characteristics of microbial small RNA transcription are largely unknown, while it is of primary importance for a better identification of molecules with functional activities in the gut niche under both healthy and disease conditions. By performing combined analyses of metagenomic and small RNA sequencing (sRNA-Seq) data, we characterized both the human and microbial small RNA contents of stool samples from healthy individuals and from patients with colorectal carcinoma or adenoma. With the integrative analyses of metagenomic and sRNA-Seq data, we identified a human and microbial small RNA signature which can be used to improve diagnosis of the disease. Our analysis of human and gut microbiome small RNA expression is relevant to generation of the first hypotheses about the potential molecular interactions occurring in the gut of CRC patients, and it can be the basis for further mechanistic studies and clinical tests.

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Study Insights into Gastrointestinal Cancer through the Gut Microbiota

BioMed Research International ◽

10.1155/2019/8721503 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 5

Author(s):

Fanli Kong ◽

Yi Cai

Keyword(s):

Colorectal Cancer ◽

Inflammatory Bowel Disease ◽

Gut Microbiota ◽

Bowel Disease ◽

Gastrointestinal Diseases ◽

Human Gut ◽

Future Studies ◽

Common Cancer ◽

Inflammatory Bowel ◽

Gi Cancers

The gut microbiome in human is recognized as a “microbial organ” for its roles and contributions in regulating the human homeostasis and metabolism. Gastrointestinal (GI) cancers, especially colorectal cancer (CRC), rank as the most common cancer-related deaths worldwide. Evidences have suggested that the disorder of gut microbiota, also named as “dysbiosis,” is related to the development of a variety of diseases such as inflammatory bowel disease (IBD) and the CRC. However, detailed mechanisms between disease and gut microbiota remain largely unknown. This review introduced the correlation between gastrointestinal diseases and the microbiota in human gut from the recent studies, as well as the roles of microbiota in manipulating the CRC and IBDs development, in order to facilitate future studies and to develop novel methods for the precaution, diagnosis, or even cure of gastrointestinal diseases. Additionally, we also elucidated the possibility of probiotics in treatment against CRC.

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Understanding Microbiome Data: A Primer for Clinicians

Digestive Diseases ◽

10.1159/000437034 ◽

2015 ◽

Vol 33 (Suppl. 1) ◽

pp. 11-16 ◽

Cited By ~ 13

Author(s):

Philippe Seksik ◽

Cécilia Landman

Keyword(s):

Gut Microbiota ◽

Bacterial Colonization ◽

Data Sets ◽

Human Gut ◽

Microbial Composition ◽

Host Determinants ◽

Host Interaction ◽

Bacterial Genes ◽

Micro Organisms ◽

Microbiome Data

The human gut contains 1014 bacteria and many other micro-organisms such as Archaea, viruses and fungi. This gut microbiota has co-evolved with host determinants through symbiotic and co-dependent relationships. Bacteria, which represent 10 times the number of human cells, form the most depicted part of this black box owing to new tools. Re-evaluating the gut microbiota showed how this entity participates in gut physiology and beyond this in human health. Studying and handling this real ‘hidden organ' remains a challenge for clinicians. In this review, we aimed to bring information about gut microbiota, its structure, its roles and the way to capture and measure it. After bacterial colonization in infant, intestinal microbial composition is unique for each individual although more than 95% can be assigned to 4 major phyla. Besides its biodiversity, the major characteristics of gut microbiota are stability over time and resilience after perturbation. In pathological situations, dysbiosis (i.e. imbalance in gut microbiota composition) is observed with a loss in overall diversity. Dysbiosis associated with inflammatory bowel disease was specified with the reduction in biodiversity, the decreased representation of different taxa in the Firmicutes phylum and an increase in Gammaproteobacteria. Beyond depicting gut microbial composition, metagenomics allows the description of the combined genomes of the microorganisms present in the gut, giving access to their potential functions. In fact, each individual overall microbial metagenome outnumbers the size of human genome by a factor of 150. Besides a functional core in which there is redundancy for mandatory functions assuring the robustness of the ecosystem, human gut contains an important diversity and high number of non-redundant bacterial genes. Clinical data, treatment and all the factors able to influence microbiome should enter integrated big data sets to put in light pathways of interplay within the supra organism composed of gut microbiome and host. A better understanding of dynamics within human gut microbiota and microbes-host interaction will allow new insight into gut pathophysiology especially regarding resilience mechanisms and dysbiosis onset and maintenance. This will lead to description of biomarkers of diseases, development of new probiotics/prebiotics and new therapies.

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Macrophage depletion using clodronate liposomes decreases tumorigenesis and alters gut microbiota in the AOM/DSS mouse model of colon cancer

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00229.2017 ◽

2018 ◽

Vol 314 (1) ◽

pp. G22-G31 ◽

Cited By ~ 36

Author(s):

Jackie E. Bader ◽

Reilly T. Enos ◽

Kandy T. Velázquez ◽

Meredith S. Carson ◽

Mitzi Nagarkatti ◽

...

Keyword(s):

Colorectal Cancer ◽

Transcription Factors ◽

Gut Microbiota ◽

Therapeutic Strategies ◽

Colon Tissue ◽

Macrophage Depletion ◽

Data Support ◽

Tumor Number ◽

Clodronate Liposomes ◽

Stool Samples

We examined the role of macrophages in inflammation associated with colorectal cancer (CRC). Given the emerging evidence on immune-microbiota interactions in CRC, we also sought to examine the interaction between macrophages and gut microbiota. To induce CRC, male C57BL/6 mice ( n = 32) received a single injection of azoxymethane (AOM), followed by three cycles of dextran sodium sulfate (DSS)-supplemented water in weeks 1, 4, and 7. Prior to the final DSS cycle ( week 7) and twice weekly until euthanasia, mice ( n = 16/group) received either 200 μl ip of clodronate-filled liposomes (CLD) or phosphate-buffered saline (PBS) encapsulated liposomes to deplete macrophages. Colon tissue was analyzed for polyp burden, macrophage markers, transcription factors, and inflammatory mediators. Stool samples were collected, and DNA was isolated and subsequently sequenced for 16S rRNA. Clodronate liposomes decreased tumor number by ∼36% and specifically large (≥1 mm) tumors by ∼36% ( P < 0.05). This was consistent with a decrease in gene expression of EMR1 in the colon tissue and polyp tissue as well as expression of select markers associated with M1 (IL-6) and M2 macrophages (IL-13, IL-10, TGFβ, CCL17) in the colon tissue ( P < 0.05). Similarly, there was a decrease in STAT3 and p38 MAPK and ERK signaling in colon tissue. Clodronate liposomes increased the relative abundance of the Firmicutes phylum ( P < 0.05) and specifically Lactobacillaceae and Clostridiaceae families, which have been associated with reduced CRC risk. Overall, these data support the development of therapeutic strategies to target macrophages in CRC and provide support for further evaluation of immune-microbiota interactions in CRC. NEW & NOTEWORTHY We found that macrophage depletion during late-stage tumorigenesis is effective at reducing tumor growth. This was associated with a decrease in macrophage markers and chemokines in the colon tissue and a decrease in transcription factors that are linked to colorectal cancer. The macrophage-depleted group was found to have an increased abundance of Firmicutes, a phylum with documented anti-tumorigenic effects. Overall, these data support the development of therapeutic strategies to target macrophages in colorectal cancer.

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Variational Approach Based Image Pre- Processing Techniques for Virtual Colonoscopy

Clinical Technologies ◽

10.4018/978-1-60960-561-2.ch419 ◽

2011 ◽

pp. 1340-1359

Author(s):

Dongqing Chen ◽

Aly A. Farag ◽

Robert L. Falk ◽

Gerald W. Dryden

Keyword(s):

Colorectal Cancer ◽

Variational Approach ◽

Virtual Colonoscopy ◽

Colonic Polyps ◽

Colonic Polyp ◽

Polyp Detection ◽

Segmentation Accuracy ◽

Processing Techniques ◽

Colonic Polyp Detection ◽

Colon Segmentation

Colorectal cancer includes cancer of the colon, rectum, anus and appendix. Since it is largely preventable, it is extremely important to detect and treat the colorectal cancer in the earliest stage. Virtual colonoscopy is an emerging screening technique for colon cancer. One component of virtual colonoscopy, image preprocessing, is important for colonic polyp detection/diagnosis, feature extraction and classification. This chapter aims at an accurate and fast colon segmentation algorithm and a general variational-approach based framework for image pre-processing techniques, which include 3D colon isosurface generation and 3D centerline extraction for navigation. The proposed framework has been validated on 20 real CT Colonography (CTC) datasets. The average segmentation accuracy has achieved 96.06%, and it just takes about 5 minutes for a single CT scan of 512*512*440. All the 12 colonic polyps with sizes of 6 mm and above in the 20 clinical CTC datasets are found by this work.

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Role of the oral and gut microbiota as a biomarker in locoregionally advanced oropharyngeal squamous cell carcinoma (ROMA LA-OPSCC).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.6045 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 6045-6045 ◽

Cited By ~ 3

Author(s):

Marc Oliva Bernal ◽

Pierre H.H. Schneeberger ◽

Rachel Taylor ◽

Victor Rey ◽

Aaron Richard Hansen ◽

...

Keyword(s):

Gut Microbiota ◽

Relative Abundance ◽

Smoking Status ◽

Single Agent ◽

Stage I ◽

Stage Iii ◽

P Value ◽

Stool Samples ◽

Tumor Metastases ◽

Associated Species

6045 Background: The ROMA LA-OPSCC ( NCT03759730) study prospectively evaluated the oral and gut microbiota in a single-centre cohort of LA-OPSCC patients (pts) receiving chemoradiotherapy (CRT). Methods: LA-OPSCC pts treated with definitive CRT (IMRT plus single-agent cisplatin) were eligible. Oral swabs over the tumor site and stool samples were collected at baseline and end of CRT (EOT). Taxonomic profiles were generated by 16S rRNA sequencing. ANOSIM/Kruskal-Wallis tests were used to identify differences between baseline and EOT samples. Results: A total of 96 samples were collected from 24 evaluable pts (100% compliance). Baseline characteristics: median age = 61 (range, 50-71); smoking status current/former/never = 5/11/8; HPV+/- = 23/1; stage I/II/III/IVA = 7/7/9/1; use of antibiotics = 12 pts. In oral swabs, decreased Shannon diversity ( p< 0.01) and changes in abundance (adjusted p value: q< 0.05) of multiple taxa including Prevotella, Veillonella, and Streptococcuswere observed at EOT vs baseline. Stool diversity did not differ between baseline and EOT ( p= 0.42), but abundance of Ruminoccocus and Roseburia decreased ( q< 0.05). CRT-associated changes remained significant when controlled for stage, smoking, antibiotics, cisplatin dose and mucositis grade ( p< 0.01). In HPV+ pts, stage I-II baseline oral swabs had higher relative abundance of Clostridium IV ( p= 0.02) and Escherichia ( p= 0.04) than stage III, which had higher Fusobacterium ( p =0.03) and Gemella ( p< 0.01). Relative abundance of Actinobacteria (p < 0.01), Proteobacteria (p < 0.01) and Firmicutes (p = 0.03) was higher in stool from stage III pts . Akkermansia muciniphila was present in 57% of the stage I-II stool samples, and 11% in stage III ( p= 0.04). Conclusions: CRT in LA-OPSCC is associated with increases in potentially pathogenic genera in the oropharynx. HPV+ stage III disease was associated with higher Fusobacterium in the oropharynx, which has been implicated in tumor metastases, and with decreased prevalence of the immunotherapy-response-associated species Akkermansia in stool. These preliminary observations suggest an opportunity for the evaluation of IO based therapies or manipulation of the gut microbiota in this patient population. Clinical trial information: NCT03759730.

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