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Recent advancements in the exploitation of the gut microbiome in the diagnosis and treatment of colorectal cancer.

ABSTRACT: Over the last few decades it has been established that the complex interaction between the host and the multitude of organisms that compose the intestinal microbiota plays an important role in human metabolic health and disease. Whilst there is no defined consensus on the composition of a healthy microbiome due to confounding factors such as ethnicity, geographical locations, age and sex, there are undoubtably populations of microbes that are consistently dysregulated in gut diseases including colorectal cancer (CRC). In this review, we discuss the most recent advances in the application of the gut microbiota, not just bacteria, and derived microbial compounds in the diagnosis of CRC and the potential to exploit microbes as novel agents in the management and treatment of CRC. We highlight examples of the microbiota, and their derivatives, that have the potential to become standalone diagnostic tools or be used in combination with current screening techniques to improve sensitivity and specificity for earlier CRC diagnoses and provide a perspective on their potential as biotherapeutics with translatability to clinical trials.

SUBMITTER: Stott KJ

PROVIDER: S-EPMC8314433 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Recent advancements in the exploitation of the gut microbiome in the diagnosis and treatment of colorectal cancer.

Stott Katie J KJ Phillips Bethan B Parry Lee L May Stephanie S

Bioscience reports 20210701 7

Over the last few decades it has been established that the complex interaction between the host and the multitude of organisms that compose the intestinal microbiota plays an important role in human metabolic health and disease. Whilst there is no defined consensus on the composition of a healthy microbiome due to confounding factors such as ethnicity, geographical locations, age and sex, there are undoubtably populations of microbes that are consistently dysregulated in gut diseases including c ...[more]

PMID: 34236075

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Project description:Accumulating evidence indicates that the gut microbiome and metabolites are associated with colorectal cancer (CRC). However, the influence of surgery for CRC treatment on the gut microbiome and metabolites and how it relates to CRC risk in postoperative CRC patients remain partially understood. Here, we collected 170 fecal samples from 85 CRC patients pre- and approximately 1 year postsurgery and performed shotgun metagenomic sequencing and capillary electrophoresis-time of flight mass spectrometry-based metabolomics analyses to characterize alterations between pre- and postsurgery. We determined that the relative abundance of 114 species was altered postsurgery (P < 0.005). CRC-associated species, such as Fusobacterium nucleatum, were decreased postsurgery. On the other hand, Clostridium scindens, carcinogenesis-associated deoxycholate (DCA)-producing species, and its biotransformed genes (bai operon) were increased postsurgery. The concentration of 60 fecal metabolites was also altered postsurgery (P < 0.005). Two bile acids, cholate and DCA, were increased postsurgery. We developed methods to estimate postoperative CRC risk based on the gut microbiome and metabolomic compositions using a random forest machine-learning algorithm that classifies large adenoma or early-stage CRC and healthy controls from publicly available data sets. We applied methods to preoperative samples and then compared the estimated CRC risk between the two groups according to the presence of large adenoma or tumors 5 years postsurgery (P < 0.05). Overall, our results show that the gut microbiome and metabolites dynamically change from pre- to postsurgery. In postoperative CRC patients, potential CRC risk derived from gut microbiome and metabolites still remains, which indicates the importance of follow-up assessments. IMPORTANCE The gut microbiome and metabolites are associated with CRC progression and carcinogenesis. Postoperative CRC patients are reported to be at an increased CRC risk; however, how gut microbiome and metabolites are related to CRC risk in postoperative patients remains only partially understood. In this study, we investigated the influence of surgical CRC treatment on the gut microbiome and metabolites. We found that the CRC-associated species Fusobacterium nucleatum was decreased postsurgery, whereas carcinogenesis-associated DCA and its producing species and genes were increased postsurgery. We developed methods to estimate postoperative CRC risk based on the gut microbiome and metabolomic compositions. We applied methods to compare the estimated CRC risk between two groups according to the presence of large adenoma or tumors after 5 years postsurgery. To our knowledge, this study is the first report on differences between pre- and postsurgery using metagenomics and metabolomics data analysis. Our methods might be used for CRC risk assessment in postoperative patients.

Project description:ObjectiveLeukemia is the most common pediatric malignancy and a major cause of morbidity and mortality in children. Among all subtypes, a lack of consensus exists regarding the diagnosis and treatment of acute myeloid leukemia (AML). Patient survival rates have remained modest for the past three decades in AML. Recently, targeted therapy has emerged as a promising treatment.Data sourcesWe searched the PubMed database for recently published research papers on diagnostic development, target therapy, and other novel therapies of AML. Clinical trial information was obtained from ClinicalTrials.gov. For the major purpose of this review that is to outline the latest therapeutic development of AML, we only listed the ongoing clinical trials for reference. However, the published results of complete clinical trials were also mentioned.Study selectionThis article reviewed the latest developments related to the diagnosis and treatment of AML. In the first portion, we provided some novel insights on the molecular basis of AML, as well as provided an update on the classification of AML. In the second portion, we summarized the results of research on potential molecular therapeutic agents including monoclonal antibodies, tyrosine kinase/Fms-like tyrosine kinase 3 (FLT3) inhibitors, epigenetic/demethylating agents, and cellular therapeutic agents. We will also highlight ongoing research and clinical trials in pediatric AML.ResultsWe described clonal evolution and how it changes our view on leukemogenesis, treatment responses, and disease relapse. Pediatric-specific genomic mapping was discussed with a novel diagnostic method highlighted. In the later portion of this review, we summarized the researches on potential molecular therapeutic agents including monoclonal antibodies, tyrosine kinase/FLT3 inhibitors, epigenetic/demethylating agents, and cellular therapeutic agents.ConclusionGene sequencing techniques should set the basis for next-generation diagnostic methods of AML, and target therapy should be the focus of future clinical research in the exploration of therapeutic possibilities.

Dataset Information

Recent advancements in the exploitation of the gut microbiome in the diagnosis and treatment of colorectal cancer.

Publications

Recent advancements in the exploitation of the gut microbiome in the diagnosis and treatment of colorectal cancer.

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