Colorectal Cancer (CRC) & Gut microbiota

Colorectal cancer ranks as a major cause of cancer and cancer-related fatalities globally. It has a multifactorial etiology, which probably involves carcinogenic bacteria.
Drewes et al. 2022 Cancer Discov 12: 1873-85

Several studies have suggested that the gut microbiota can secrete metabolites [short-chain fatty acids (SCFAs), vitamins, polyphenols and polyamines] that modulate the susceptibility of the colon and rectum by altering inflammation and DNA damage.
Abdulla et al. 2021 Int. J. of Oncology 58:

Gut microbiota is involved in the metabolic transformations of dietary components into oncometabolites and tumor-suppressive metabolites that affect CRC development
Chattopadhyay et al. 2021 Applied Biochemistry and Biotechnology 193:1780-1799

Escherichia coli, Enterococcus faecalis, Fusobacterium nucleatum, and Streptococcus gallolyticus showed higher abundance in Colorectal Cancer (CRC) patients
Chattopadhyay et al. 2021 Applied Biochemistry and Biotechnology 193:1780-1799

Bifidobacterium, Clostridium, Faecalibacterium, and Roseburia showed reduced abundance in Colorectal Cancer (CRC) patients
Chattopadhyay et al. 2021 Applied Biochemistry and Biotechnology 193:1780-1799

Aberrant composition of the microbiota, together with alteration in the diet-derived microbial metabolites content (such as butyrate and polyamines) and environmental compounds has been related to Colorectal Cancer (CRC)
Hanus et al. 2021

Fusobacterium, Parvimonas, and Staphylococcus were increased in colorectal cancer (CRC) while the Lachnospiraceae family were reduced.
Bisht et al. 2021 Int. J. Mol. Sci. 22: 5763

Bacteria can affect colorectal cancer both directly and indirectly. They may secrete metabolites, invade tissues, or modulate the host's immune response, all of which can contribute to cancer progression. Several bacteria are notably associated with colorectal cancer. These include:

• Fusobacterium


• Peptostreptococcus


• Porphyromonas


• Prevotella


• Parvimonas


• Bacteroides


• Gemella

Ternes et al. 2020 Trends Microbiol 28: 401-423

A limited number of bacteria , including enterotoxigenic Bacteroides fragilis (ETBF), colibactin-producing Escherichia coli (pks+Ec), and oral Fusobacteria strains, have been implicated in colorectal cancer in cross-sectional clinical cohorts and drive tumorigenesis in animal models
Sears et al. 2014 Cell Host Microbe 15: 317-28
Cheng et al. 2020e Front Immunol 11: 615056
Janney et al. 2020

Colon tumors can be induced in susceptible mouse models by gavage with fecal or colonic mucosal slurry from colorectal cancer patients and even some healthy individuals
Baxter et al. 2014 Microbiome 2: 20
Wong et al. 2017a Gastroenterology 153: 1621-33.;
Tomkovich et al. 2019 J Clin Invest 129: 1699-712

Organs with a high tumor incidence interact closely with microbiota and their products. Especially in Colorectal Cancer (CRC), the microbiota has been associated with tumorigenesis, due to its distinct composition and organization in CRC patients. Various microbes (and microbial communities) are found more frequently in the stool and mucosa of individuals with Colorectal Cancer (CRC) than healthy controls, including in the primary tumors themselves, and even in distant metastases.
Allen & Sears 2019 Genome Med. 11: 11

Gut microbes exert distinct impacts on DNA damage, DNA methylation, chromatin structure and non-coding RNA expression in colonocytes.
Allen & Sears 2019 Genome Med. 11: 11

There are 7 clinical trials with patients investigating the relationship between Colorectal Cancer (CRC) and gut microbiota
Shuwen et al. 2019

A detailed study of the gut microbiome's abilities found that certain processes, like making glucose and breaking down substances, are linked to colorectal cancer (CRC). People with CRC had a more diverse gut microbiome compared to those without the disease (P < 0.01). This was partly because there were more types of bacteria usually found in the mouth.
Thomas et al. 2019a Nat Med 25: 667-78

More granular findings include the association of Bacteroides, Coprococcus, Corynebacterium, Enterococcus, and Neisseria enrichment with a higher likelihood of CRC development, although the causative mechanisms remain unclear
Ai et al. 2019 Front. Microbiol. 10: 826
Pu et al. 2019a J Gastroenterol Hepatol 35: 433-437

The role of the gut microbiota in the genesis of colorectal cancer remains an exciting though unresolved question. Gut microbiota might be important for the initiation and progression of colorectal cancer via chronic inflammation although most proposed mechanisms remain hypothetical and deserve further study.
Massaut et al. 2019 Curr Opin Oncol 31: 362

Many studies have identified the associated genera of bacteria that increase or decrease the risk of Colorectal Cancer (CRC)
Han et al. 2018b Cancer Management and Research 10: 199-206

Colorectal cancer patients often exhibit a distinct microbiota composition compared to that of a healthy population
Feng et al. 2015a Nat Commun 6: 6528
Nakatsu et al. 2015
Tilg et al. 2018 Cancer Cell 33: 954–64

Gut bacteria can promote Colorectal Cancer (CRC) by affecting DNA integrity, regulating the immune response, inducing inflammatory reactions, promoting cell proliferation, changing stem cell dynamics and so on.
Sun 2011 Cancers 3(1): 285–297
Gagniere et al. 2017
Andrews et al. 2018 Front. Immunol. 9: 946

The colonic microbiota is altered in patients with colorectal cancer (CRC).
Hibberd et al. 2017 BMJ Open Gastro 4: e000145

Human Colorectal Cancer (CRC) are enriched for mucus-invasive microbial biofilms (BF) that interact directly with the colonic epithelium and are associated with carcinogenic changes, including elevations in antigen KI-67 / Ki-67, phospho-STAT3 (pSTAT3), and the polyamine N1, N12 -Diacetylspermine
Dejea et al. 2014 Proc Natl Acad Sci U S A 111: 18321-6
Johnson et al. 2015b Cell Metab 21: 891-7
Drewes et al. 2017 NPJ Biofilms Microbiomes 3: 34.

An abundance of Fusobacterium nucleatum, Bacteroides fragilis, Escherichia coli, Enterococcus faecalis, Helicobacter hepaticus, Peptostreptococcus anaerobius, Helicobacter pylori, Streptococcus bovis, and Porphyromonas gingivalis has been related to CRC cancer development
Gagnière et al. 2016 World J Gastroenterol 22(2): 501-518

Latest advances in meta-omic microbial data and metabolome analysis have provided essential insights into the role of gut microbes and their metabolism. Increasing evidence suggests that the gut microbiota contributes to the development of colorectal cancer, not only through the pro-carcinogenic activities of specific pathogens but also through the influence of bacterial metabolites.
Ohtani 2015 Semin Immunopathol 37(1): 65-72

The gut microbiome composition varies between individuals diagnosed with colorectal cancer (CRC) and those who are healthy, as reported by several studies.
Marchesi et al. 2011 PloS one 6(5): e20447
Sobhani et al. 2011 PloS one 6(1): e16393
Weir et al. 2013 PloS one 8(8): e70803
Zackular et al. 2013 mBio. 4(6): e00692-00613

The gut microbiota might influence the development or prevention of CRC by affecting the inflammatory process, as it is in close contact with the host colonic mucosa or mucous membrane.
Jobin 2013 Cancer discovery 3(4): 384-387

We propose that barrier deterioration induced by colorectal-cancer-initiating genetic lesions results in adenoma invasion by Microbial products that trigger tumor-elicited inflammation, which in turn drives tumor growth.
Grivennikov et al. 2012 Nature 491(7423): 254-258

The "Driver-passenger" model suggests that certain bacteria, known as "bacterial drivers," start the formation of colonic tumors by causing gene damage, which then encourages the colonization of passenger bacteria within the Tumor Microenvironment (TME).
Sears & Pardoll 2011 J Infect Dis 203: 306-311
Tjalsma et al. 2012 Nat Rev Microbiol 10(8): 575-582

Some “keystone pathogens” that emerge during dysbiosis and are likely to be part of carcinogenesis include Bacteroides, Enterococcus, Fusobacterium, Streptococcus, Escherichia coli, and Clostridium
Boleij & Tjalsma 2012 Biol Rev Camb Philos Soc 87: 701-730
Tjalsma et al. 2012 Nat Rev Microbiol 10(8): 575-582

Bacteria are key in Colorectal Cancer (CRC). They can start, develop, and progress the cancer. Tjalsma et al. established a colon cancer model where bacteria played the role of “drivers” and “passengers”. Some bacteria drive cells to become cancerous. Others thrive in the cancer environment. They may outgrow the drivers. They might or might not aid in cancer progression
Tjalsma et al. 2012 Nat Rev Microbiol 10(8): 575-582

Role of metabolites

Gut microbiota is involved in the metabolic transformations of dietary components into oncometabolites and tumor-suppressive metabolites that in turn affect CRC development.
Chattopadhyay et al. 2021 Applied Biochemistry and Biotechnology 193:1780-1799

tumor tissue analysis

Choi and co-authors' work shows the presence of bacteria in CRC tissue samples from Korean patients compared to non-tumor tissue. The increased occurrence of Fusobacterium nucleatum and Bacteroides fragilis in tumor tissue was noticeable.
Choi et al. 2021a Journal of Translational Medicine 19: 485

Mechanisms

We identified multiple potential interactions, for example, 5-aminovalerate interacting with Adlercreutzia; Cholesteryl esters interacting with bacterial genera Staphylococcus, Blautia, and Roseburia.
Bisht et al. 2021 Int. J. Mol. Sci. 22: 5763

In addition, using single public cell and bulk RNA sequencing, we identified 17 overlapping genes involved in epithelial cell pathways, with particular significance of the oxidative phosphorylation pathway and the acat1 gene that indirectly regulates the esterification of cholesterol.
Bisht et al. 2021 Int. J. Mol. Sci. 22: 5763

Polyamines, which are thought to contribute to carcinogenesis, show a higher abundance in Colorectal Cancer (CRC) patients than healthy individuals. Conversely, Polyunsaturated Fatty Acids (PUFAs) and monounsaturated fatty acids, short-chain fatty acids, and Hydrocinnamic acid are decreased in multiple CRC cohorts
Yang et al. 2019a Theranostics 9: 4101-4114

Intestinal microorganisms have a direct effect on the initiation and progression of Sporadic colorectal cancer (CRC)
Tjalsma et al. 2012 Nat Rev Microbiol 10(8): 575-582

for diagnosis

It was confirmed that there was a link between Fusobacterium nucleatum and Peptostreptococcus stomatis and Colorectal Cancer (CRC). Furthermore, an association was found with several other species, such as Parvimonas micra and Solobacterium. Additionally, the co-occurrence of Parvimonas micra and Fusobacterium nucleatum suggests that there may be cooperation between those two species in colonization and the progression of CRC
Kaźmierczak-Siedlecka et al. 2022 Gut Microbes 11(6): 1518-1530

Twenty microbial gene markers were identified in a Chinese population that differentiated between the microbiome of CRC patients and healthy controls, and four of those markers were also present in the Danish cohort.
Kaźmierczak-Siedlecka et al. 2022 Gut Microbes 11(6): 1518-1530

These four genes distinguished colorectal cancer metagenomes from controls with areas under the receiver-operating curve (AUC) of 0.72 and 0.77 in French and Austrian cohorts.
Kaźmierczak-Siedlecka et al. 2022 Gut Microbes 11(6): 1518-1530

Researchers have focused extensively on colorectal cancer (CRC) in the diagnostic microbiome field. Two metagenomic analyses of datasets from different regions identified microbial signatures that consistently correlate with CRC, enhancing the diagnostic accuracy of the fecal occult blood test.
Thomas et al. 2019a Nat Med 25: 667-78
Wirbel et al. 2019 Nat Med 25: 679-689

The identification of CRC-associated pathogens is crucial for establishing gut microbiota as a potential screening tool for Colorectal Cancer (CRC)
Cao et al. 2014 Fam Cancer 13(4): 563-571
Bruneau et al. 2018 Bull Cancer 105(1): 70-80

The fecal microbiome can be used as a tool toward developing targeted non-invasive biomarkers for colorectal cancer, as shown by Yu et al., who investigated ethnically different cohorts (Danish, French, Austrian, and Chinese). It is possible that if an abundance of those bacteria is present in CRC samples as early as in stage II of CRC, these might be useful as non-invasive early diagnostic biomarkers for colorectal cancer when assayed from fecal samples
Yu et al. 2017 Gut 66(1): 70-78

Experimental Data

Chemically induced injury and proliferation induced by Azoxymethane (AOM) and sodium dextran sulfate (DSS) were enhanced in germ-free mice lacking protective commensals.
Sheflin et al. 2014 Curr Oncol Rep. 16(10): 406

Furthermore, tumor development in germ-free miceresulted in significantly more and larger tumors than in specific pathogen-free mice.
Zhan et al. 2013 Cancer Research 73(24): 7199-7210

see also:
Actinomycetes / Actinomycetales
Cancer microbiome / Tumor microbiome & Colorectal cancer (CRC)
Cancer / Tumors & Deoxycholic acid (DCA)
Cancer / Tumors & Gut microbiota
Cancer / Tumors & Infection diseases / Infections / Bacterial infection
Carcinogenesis / Oncogenesis / Tumorigenesis & Gut microbiota
Colitis-Associated Colorectal Cancer (CAC) & Gut microbiota
Colorectal Cancer (CRC) & Dysbiosis
Colorectal tumorigenesis & Gut microbiota
Coprococcus
Corynebacterium
Diseases / Disorders & Gut microbiota
Gut microbiota & Immunity
Oncomicrobes