Role of Gut Microbiome in Colorectal Cancer

ABSTRACT Recently, dysbiosis in the human gut microbiome and shifts in the relative abundances of several bacterial species have been recognized as important factors in colorectal cancer (CRC). However, these studies have been carried out mainly in developed countries where CRC has a high incidence, and it is unclear whether the host-microbiome relationships deduced from these studies can be generalized to the global population. To test if the documented associations between the microbiome and CRC are conserved in a distinct context, we performed metagenomic and metabolomic association studies on fecal samples from 30 CRC patients and 30 healthy controls from two different locations in India, followed by a comparison of CRC data available from other populations. We confirmed the association of Bacteroides and other bacterial taxa with CRC that have been previously reported in other studies. However, the association of CRC with Flavonifractor plautii in Indian patients emerged as a novel finding. The plausible role of F. plautii appears to be linked with the degradation of beneficial anticarcinogenic flavonoids, which was also found to be significantly correlated with the enzymes and modules involved in flavonoid degradation within Indian CRC samples. Thus, we hypothesize that the degradation of beneficial flavonoids might be playing a role in cancer progression within this Indian cohort. We also identified 20 potential microbial taxonomic markers and 33 potential microbial gene markers that discriminate the Indian CRC from healthy microbiomes with high accuracy based on machine learning approaches. IMPORTANCE This study provides novel insights on the CRC-associated microbiome of a unique cohort in India, reveals the potential role of a new bacterium in CRC, and identifies cohort-specific biomarkers, which can potentially be used in noninvasive diagnosis of CRC. The study gains additional significance, as India is among the countries with a very low incidence of CRC, and the diet and lifestyle in India have been associated with a distinct gut microbiome in healthy Indians compared to other global populations. Thus, in this study, we hypothesize a unique relationship between CRC and the gut microbiome in an Indian population.

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The Role of the Gut Microbiome in Colorectal Cancer

Clinics in Colon and Rectal Surgery ◽

10.1055/s-0037-1602239 ◽

2018 ◽

Vol 31 (03) ◽

pp. 192-198 ◽

Cited By ~ 14

Author(s):

Grace Chen

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Microbial Community ◽

Gut Microbiota ◽

Gut Microbiome ◽

Intestinal Health ◽

Genotoxic Effects ◽

Bacterial Populations ◽

Health And Disease

AbstractThere is increasing evidence that the gut microbiome, which consists of trillions of microbes representing over 1,000 species of bacteria with over 3 million genes, significantly impacts intestinal health and disease. The gut microbiota not only is capable of promoting intestinal homeostasis and antitumor responses but can also contribute to chronic dysregulated inflammation as well as have genotoxic effects that lead to carcinogenesis. Whether the gut microbiota maintains health or promotes colon cancer may ultimately depend on the composition of the gut microbiome and the balance within the microbial community of protective and detrimental bacterial populations. Disturbances in the normal balanced state of a healthful microbiome, known as dysbiosis, have been observed in patients with colorectal cancer (CRC); however, whether these alterations precede and cause CRC remains to be determined. Nonetheless, studies in mice strongly suggest that the gut microbiota can modulate susceptibility to CRC, and therefore may serve as both biomarkers and therapeutic targets.

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The Role of Gut Microbiome and Chronic Inflammation in Young-onset Colorectal Cancer

Case Medical Research ◽

10.31525/ct1-nct04011969 ◽

2019 ◽

Author(s):

Keyword(s):

Colorectal Cancer ◽

Chronic Inflammation ◽

Gut Microbiome ◽

Young Onset

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Potential Role of the Gut Microbiome In Colorectal Cancer Progression

Frontiers in Immunology ◽

10.3389/fimmu.2021.807648 ◽

2022 ◽

Vol 12 ◽

Author(s):

Jaeho Kim ◽

Heung Kyu Lee

Keyword(s):

Colorectal Cancer ◽

Gut Microbiota ◽

Cancer Treatment ◽

Cancer Progression ◽

Gut Microbiome ◽

Intestinal Inflammation ◽

Treatment Modalities ◽

Host Immune System ◽

Anti Cancer

An increasing number of studies have revealed that the progression of colorectal cancer (CRC) is related to gut microbiome composition. Under normal conditions, the gut microbiome acts as a barrier to other pathogens or infections in the intestine and modulates inflammation by affecting the host immune system. These gut microbiota are not only related to the intestinal inflammation associated with tumorigenesis but also modulation of the anti-cancer immune response. Thus, they are associated with tumor progression and anti-cancer treatment efficacy. Studies have shown that the gut microbiota can be used as biomarkers to predict the effect of immunotherapy and improve the efficacy of immunotherapy in treating CRC through modulation. In this review, we discuss the role of the gut microbiome as revealed by recent studies of the growth and progression of CRC along with its synergistic effect with anti-cancer treatment modalities.

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Fecal microbiome as determinant of the effect of diet on colorectal cancer risk: comparison of meat-based versus pesco-vegetarian diets (the MeaTIc study)

Trials ◽

10.1186/s13063-019-3801-x ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 2

Author(s):

Francesco Sofi ◽

Monica Dinu ◽

Giuditta Pagliai ◽

Fabrice Pierre ◽

Francoise Gueraud ◽

...

Keyword(s):

Colorectal Cancer ◽

Gut Microbiome ◽

Epidemiological Data ◽

Convincing Evidence ◽

Alpha Tocopherol ◽

Secondary Outcome ◽

Processed Meat ◽

Food Groups ◽

Fecal Microbiome

Abstract Background Convincing evidence suggests that the risk of colorectal cancer (CRC) is increased by the typical Western diet characterized by high consumption of red and processed meat. In addition, some epidemiological studies suggest a reduction in the risk of CRC associated with fish consumption. The role of the gut microbiome in this diet-associated risk is not well understood. Methods/design This is a randomized parallel open clinical trial comprising a total of 150 clinically healthy subjects randomly assigned to three groups: a meat-based diet of which 4 portions per week are red meat (1 portion = 150 g), 3 portions per week are processed meat (1 portion = 50 g), and 1 portion per week is poultry (1 portion = 150 g), for a total amount of 900 g per week of meat and derivatives; a meat-based diet supplemented with alpha-tocopherol; and a pesco-vegetarian diet excluding fresh and processed meat and poultry, but which includes 3 portions per week of fish for a total amount of 450 g per week. Each intervention will last 3 months. The three diets will be isocaloric and of three different sizes according to specific energy requirements. Anthropometric measurements, body composition, and blood and fecal samples will be obtained from each participant at the beginning and end of each intervention phase. The measure of the primary outcome will be the change from baseline in DNA damage induced by fecal water using the comet assay in a cellular model. Secondary outcome measures will be changes in the profile of fecal microbiomes, global fecal and urinary peroxidation markers, and neoplastic biomarkers. Discussion Although epidemiological data support the promoting role of meat and the possible protective role of fish in colon carcinogenesis, no study has directly compared dietary profiles characterized by the presence of these two food groups and the role of the gut microbiome in these diet-associated CRC risks. This study will test the effect of these dietary profiles on validated CRC risk biomarkers. Trial registration ClinicalTrials.gov, NCT03416777. Registered on 3 May 2018.

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Gut Microbiome: A Promising Biomarker for Immunotherapy in Colorectal Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms20174155 ◽

2019 ◽

Vol 20 (17) ◽

pp. 4155 ◽

Cited By ~ 10

Author(s):

Sally Temraz ◽

Farah Nassar ◽

Rihab Nasr ◽

Maya Charafeddine ◽

Deborah Mukherji ◽

...

Keyword(s):

Colorectal Cancer ◽

Gut Microbiome ◽

Hematopoietic Cell Transplantation ◽

Cytotoxic T Lymphocyte ◽

Predictive Biomarkers ◽

Bacterial Invasion ◽

Host Immune System ◽

T Cell Stimulation

Research has been driven towards finding therapy predictive biomarkers for colorectal cancer (CRC) with a special interest in studying the gut microbiome. Gut microbiome acts not only as a barrier to prevent bacterial invasion and infection, but it also affects the efficacy of hematopoietic-cell transplantation, chemotherapy, and immunotherapy. Recently, immunotherapy, which potentiates the host immune system, has revolutionized cancer therapy in general and CRC treatment specifically by increasing the quality of life and the survival of a subset of patients with this disease. In immunotherapy, the gut microbiome plays an important role in cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) blockade, programmed cell death protein 1 (PD-L1) mediation, and T cell stimulation. As such, this review will cover the role of gut microbiome in CRC, summarize approved immunotherapy treatments for CRC, and focus on the potential use of gut microbiome as a biomarker for immunotherapy.

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Diversity and Distribution of Sulfur Metabolism 1 in the Human Gut Microbiome and its Association with Colorectal Cancer

10.21203/rs.3.rs-809984/v1 ◽

2021 ◽

Author(s):

Patricia G. Wolf ◽

Elise S. Cowley ◽

Adam Breister ◽

Sarah Matatov ◽

Luke Lucio ◽

...

Keyword(s):

Colorectal Cancer ◽

Sulfate Reduction ◽

Gut Microbiome ◽

Sulfur Metabolism ◽

Human Gut ◽

Human Gut Microbiome ◽

Metabolic Genes ◽

Comprehensive Knowledge ◽

Potential Trigger

Abstract Background: Microbial sulfidogenesis produces genotoxic hydrogen sulfide (H2S) in the human gut using inorganic (sulfate) and organic (taurine/cysteine/methionine) substrates, however the majority of studies have focused on sulfate reduction using dissimilatory sulfite reductases (Dsr). Recent evidence implicates microbial sulfidogenesis as a potential trigger of colorectal cancer (CRC), highlighting the need for comprehensive knowledge of sulfur metabolism within the human gut.Results: Here we show that microbial sulfur metabolism is more abundant and diverse than previously studied and is statistically associated with CRC. Using ~17,000 bacterial genomes from publicly available stool metagenomes, we studied the diversity of sulfur metabolic genes in 667 participants across different health statuses: healthy, adenoma, and carcinoma. Sulfidogenic genes were harbored by 142 bacterial genera and both organic and inorganic sulfidogenic genes were associated with carcinoma. Significantly, anaerobic sulfite reductases were twice as abundant as dsr, demonstrating that this enzyme is likely a more important contributor to sulfate reduction in the human gut. We identified twelve potential pathways for reductive taurine metabolism and discovered novel genera harboring these pathways. Finally, prevalence of metabolic genes for organic sulfur indicate that these understudied substrates may be the most abundant source of microbially derived H2S.Conclusions: Our findings significantly expand knowledge of microbial sulfur metabolism in the human gut. We show that microbial sulfur metabolism in the human gut is more prevalent than previously known, irrespective of health status (i.e., in both healthy and diseased states). Our results significantly increase the diversity of pathways and bacteria that are associated with microbial sulfur metabolism in the human gut. Overall, our results have implications for understanding the role of the human gut microbiome and its potential contributions to the pathogenesis of CRC.

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