Tissue homeostasis, density, architecture and function can normally be maintained by a balance between cell growth and programmed cell death signals, together with other cellular control mechanisms(1).
Microorganisms have been proven to be involved in the etiopathogenesis of some neoplasms(2). Among the multitude of hypothetical mechanisms, some bacteria interfere with carcinogenesis processes either by activating signaling pathways and transcription factors, or by producing toxins and other metabolic products which have the ability to influence the body’s cells. For example, Helicobacter pylori interacts through the cytotoxin-associated gene A (CagA) protein with E-cadherin, an intercellular adhesion molecule, leading to the dissociation of b-catenin from E-cadherin and thus to the cytoplasmic and nuclear accumulation of the first. b-catenin couples with T cell factor/lymphoid enhancer factor (TCF/LEF), forming complexes which activate gene expression(3). Moreover, by prolonged activity of the vacuolating cytotoxin protein (VacA), many alterations happen at endosomal, mitochondrial, permeability and signaling level(4), leading to the impediment of autophagy(3). Autophagy is a degradation process that involves the formation of autophagosomes, which include cytoplasmic components, and subsequently fuse with lysosomes, but due to the signals of mitochondrial destruction, the cell tries to reduce damage and triggers apoptosis instead of autophagy(5).
Oncoviruses also present many mechanisms by which they can be involved in carcinogenesis through two main paths: directly by genes insertion or indirectly by sustained inflammation(3). Viruses such as human papillomavirus, hepatitis B and C viruses, human T-cell lymphotropic viruses, Epstein-Barr virus and Kaposi’s sarcoma-associated herpesvirus encode oncoproteins and can activate tumor-inducing pathways in animal models(3). For some types of cancers, parasitic etiologies have been suggested: Schistosoma haematobium, Schistosoma japonicum and Schistosoma mansoni through inflammation and oxidative stress; Opistorchis viverrini, Opistorchis felineus and Clonorchis sineses through inflammation, oxidative stress and cell proliferation(6). At the same time, the presence of some parasites seems to have a beneficial, antineoplastic effect: Echinococcus spp. or Fasciola hepatica can produce some molecules that have an inhibitory effect on ovarian cancer cell lines(7).
The microbiota represents all the microorganisms that are physiologically located in and on the surface of the human body, while the microbiome comprises their genetic material(8).
In recent years, the growing interest for the microbiota and its implications in various pathologies has been observed through the multitude of studies, publications, but also scientific meetings on this topic. The role of the microbiota has been highlighted in numerous molecular mechanisms of human body development, autoimmune diseases, hypersensitivity pathologies, and in many others, including neoplastic disorders(9). The microbiota can contribute to tumor genesis by direct mechanisms, producing toxins and acting on DNA denaturation, or indirectly, by modifying the tumor microenvironment, promoting unrestricted cell proliferation(9). In both of these mechanisms, it should be taken into account the numerous effects of the microbiota on the immune system(9).
A. Microorganisms with procarcinogenic effect
The involvement of microbiota in the carcinogenesis of colon and rectum has been explained through several ways, such as altering cell proliferation, influencing the immune system or metabolizing food factors. Some studies claim that up to 16% of colorectal cancers are caused by alterations of the normal microbiota(10).
1. Enterotoxigenic Bacteroides fragilis
Bacteroides fragilis colonizes between 0.5% and 2% of the entire intestinal tract. So far, two strains have been identified: one toxigenic and the other one non-toxigenic(11). The latter strain has beneficial effects in protective mechanisms against cancer(11), while the first one, enterotoxigenic B. fragilis (ETBF), has the ability to produce a toxin, fragilisyn. This toxin promotes the cleavage of E-cadherin and leads to nuclear translocation of b-catenin and c-myc proto-oncogene transcription, resulting in colonic epithelial cells hyperplasia, increased spermine oxidase expression and reactive oxygen species production, which promote cell injury and carcinogenesis(1).
Another toxin-mediated mechanism is achieved with the implication of the immune system: the accumulation of regulatory T lymphocytes in the intestinal lamina propria, the suppression of mucosal immune response by T helper-1 lymphocytes, the increased interleukin-17 (IL-17) secretion, ultimately leading to tumor genesis. In addition, STAT3 and nuclear factor kappa B (NF-kB) pathways activated by immune response cells might also be involved(11). The toxin, on the one hand, and the abundance of IL-17 by overexpression of chemokines CXCL1, CXCL2 and CXCL5, on the other hand, can also promote differentiation and recruitment of myeloid-derived suppressor cells (MDSC)(11). Increased MDSC can lead to increase in nitric oxide (NO) and arginase 1 levels, thus being responsible for inhibiting T lymphocytes and avoiding the antitumor immune response(11).
Bacteroides fragilis is considered an “alpha-bug” in colon cancer. The “alpha-bug hypothesis” focuses more on the role of a single microorganism that has a proven role in carcinogenesis, like the classic examples of cervical cancer and HPV or gastric cancer and Helicobacter pylori. According to the alpha-bug hypothesis, ETBF remodels the colonic microbiota and cooperates with environmental factors and host genetics to induce colon cancer(1).
2. Fusobacterium nucleatum
Fusobacterium nucleatum is an opportunistic anaerobic commensal of the oral cavity, which may be involved in the production of periodontal disease, but it can also cause diseases in other areas of the body, such as intrauterine infections with major pregnancy complications(12). Recently, F. nucleatum has been identified in colon biopsies of malignant lesions or in the stool of patients with colon cancer(11). One of the virulence factors expressed on its surface is FadA, which exists in two forms: the intact form (pre-FadA), anchored in the membrane, and the secreted mature FadA (mFadA). Only the pairing of the two forms represents an active complex (the pre-FadA-mFadA complex), which has the ability to attach to the endothelial cells through E-cadherin and activate signaling pathways through b-catenin(12). This process leads to increased expression of transcription factors, oncogenes, inflammatory genes and stimulates the development of cancer cells(12). Fusobacterium varum may also act through the same mechanism(10).
Several mechanisms have been proposed regarding the involvement of F. nucleatum in the etiopathogenesis of cancer, including the possibility of playing a role in colorectal cancer progression by producing Fap2, which inhibits cellular immune activity(10). This protein appears to be involved in the adhesion of tumor cells, which overexpress Gal-GalNAc molecules(11). This process is followed by the interaction between F. nucleatum and Toll-like receptor 4 (TLR4), phosphorylation of b-catenin by serine/threonine-protein kinase PAK-1 and activation of the Wnt/b-catenin signaling pathway, therefore promoting cell proliferation(11). In the absence of Wnt, b-catenin is constantly degraded by the multiprotein Axin complex (“destruction complex”), composed of the tumor suppressors Axin and adenomatous polyposis coli, the Ser/Thr kinases GSK-3 and CK1, protein phosphatase 2A and the E3-ubiquitin ligase b-TrCP(13). CK1 and GSK-3 phosphorylate the N-terminal region of b-catenin, so that it is recognized by b-TrCP and degraded, therefore not reaching the nucleus. As a consequence, the DNA genes TCF/LEF are repressed(13). When a Wnt ligand binds to the transmembrane domain of Frizzled proteins (family of G protein-coupled receptor proteins) and its coreceptors, low-density lipoprotein receptor related protein 5 or 6 (LRP5-6), they form a complex together with the recruitment of the Dishevelled protein, which results in the phosphorylation and activation of LRP6. Further, the Axin complex is recruited, which no longer phosphorylates b-catenin and leads to its accumulation, reaching the nucleus, where it forms complexes with TCF/LEF and activates the expression of Wnt genes(13).
Moreover, in the infection with F. nucleatum, there has been observed a decrease in TOX family proteins (thymocyte selection associated high-mobility group box), which are involved in cell multiplication, apoptosis, DNA repair and metastatic processes(11).
In addition to this, studies on F. nucleatum infection in colon cancer patients have associated the bacterial presence and invasion with the CpG island methylation phenotype (CIMP), microsatellite instability, as well as mutations of the BRAF and KRAS genes(11). Another possible involved mechanism is inflammation, with high levels of TNF-a and IL-10 being observed in people with concurrent colonic adenomas and F. nucleatum infection(11). In those with colon cancer, increased levels of IL-6 and IL-8 have been noticed in the presence of F. nucleatum, both being proinflammatory cytokines regulated by the transcription factor NF-kB(11). Increased CCL20 chemokine (C-C motif ligand 20), also known as liver activation regulated chemokine (LARC) or macrophage inflammatory protein-3 (MIP3A), associated with cancer progression and increased MIR135B (MicroRNA 135b) expression were also observed(11). The presence of this bacterium has been associated with poor survival in patients with colon cancer and also with resistance to chemotherapy(11).
3. Escherichia coli
Escherichia coli is a widespread Gram-negative bacterium, also part of the human gut microbiota. It is divided into 5 phylogenetic groups, but the most commonly involved in human pathologies is the one belonging to B2 group(11). The mechanism by which this leads to the development of colon cancer is not exactly known, but there are two main pathways currently under investigation: one indirectly by inflammation and the other one directly through molecular mechanisms(11). For example, both adherent invasive E. coli (AIEC) and enteropathogenic E. coli (EPEC) can produce the effector protein EspF(11) and a cyclomodulin called colibactin (polyketide-peptide genotoxin), which is synthetized by the pks genomic island of pks+ E. coli. Colibactin induces apoptosis of immune cells and chromosomal instability with DNA damage in the epithelial cells, leading to their senescence (secretory phenotype of senescent cells)(11). Although the cells are no longer dividing, they may secrete growth factors which allow tumor development(11).
AIEC can bind to the cellular adhesion receptor associated to carcinoembryonic antigen, which is overexpressed in patients with Crohn’s disease or colon cancer(11). As a result of binding, pks+ E. coli can lead to DNA damage by acting as an alkylating agent(11), aneuploidy and cell division defects(11).
By stimulating the macrophage-inhibitory cytokine-1 (MIC-1), EPEC results in increased cell survival and dissemination through RhoA GTPase protein (Ras homolog family member A, also known as transforming protein RhoA)(11). Through the autophosphorylation of the EGFR receptor in EPEC-infected cells, survival pathways depending on phosphoinositide 3-kinase/Akt and also the proinflammatory MAP pathway (mitogen-activated protein kinase)(11) are activated.
EspF may decrease the level of repair proteins MLH1 and MLH2(11) and it may also contribute to metastasis process by acting on the intercellular tight junction proteins occludin and claudin-1(11).
Other proteins produced by E. coli and studied for their implications in carcinogenesis are cytolethal distending toxin, which blocks the cell cycle and induces malignant cell transformation, cycle inhibiting factor, which can induce DNA elongation and stimulate its synthesis, even when cells do not divide, and cytotoxic necrotizing factor 1, which induces gene transcription and cell proliferation(11).
4. Salmonella spp.
Salmonella enterica comprises several serotypes, such as Salmonella typhi, Salmonella paratyphi, Salmonella enteritidis and Salmonella typhimurium(11). In recent years, cancers of the colon, gall bladder and other cancers of the gastrointestinal tract have been correlated with infections caused by S. enterica(11).
The mechanism of cancer transformation can also be direct and indirect, as in the case of other pathogens described(11). S. enterica can modulate the immune response and promote carcinogenesis by affecting DNA and increasing cell proliferation, but also through chronic inflammation and cell migration(11). There are two identified toxins responsible for these mechanisms: typhoid toxin (a cyclomodulin similar to the one produced by E. coli) and AvrA protein(11). Typhoid toxin can increase cell survival and promote intestinal dysbiosis(11). AvrA has been identified in the stool samples from colon cancer patients and several possible mechanisms of action have been suggested, including the inhibition of NF-kB signaling pathway, inhibition of IL-12, INF-g, TNF-a secretion, IL-6 transcription and stimulation of IL-10 transcription(11). This protein could also be involved in the activation of the b-catenin pathway and JAK/STAT signaling pathway, with implications in the cell apoptosis, proliferation and differentiation, as well as in inflammation processes(11). By its activity of acetyl transferase, AvrA can affect p53 activity, decreasing apoptosis(11).
It has been observed that the higher incidence of gallbladder cancer in some geographical areas corresponds to the increased incidence of Salmonella spp. infection(11). S. typhi and S. paratyphi serotypes have been detected in most of biopsies, but the mechanism has not yet been elucidated. It is assumed that chronic inflammation, together with mutations of TP53 and activation of MAPK and AKT signaling pathways may be responsible for Salmonella-induced carcinogenesis(11).
5. Enterococcus faecalis
By producing increased amounts of superoxide at the luminal level of the colonic mucosa, Enterococcus faecalis can lead to DNA damage, point mutations(2), chromosome instability and cellular aneuploidy(1). These alterations can stimulate COX-2, which generates pro-proliferative and inflammatory signaling through prostaglandin E2 (PGE2)(10). In vitro studies have proven that E. faecalis activates the Wnt/b-catenin pathway and pluripotent transcription factors associated with cell dedifferentiation, raising the hypothesis of its role in inducing colorectal cancer(14). However, some studies even suggest a possible protective role of E. faecalis, by lowering the expression of the fasting-induced apoptose factor, which is associated with the development of some cancers(14).
6. Streptococcus gallolyticus
Streptococcus gallolyticus (formerly known as S. bovis) is a Gram-positive bacterium commonly identified in people with colorectal cancer; between 25% and 80% of the patients with S. gallolyticus infection are also diagnosed with colorectal neoplasm(15). Although frequently reported, the mechanism of action is not yet fully elucidated, but carcinogenic effect is most likely produced by inflammatory effects(10). In vitro studies have shown that mucosal exposure to this bacterium leads to increased IL-1(16), but also IL-8, the latter being involved in carcinogenesis processes by increasing oxidative stress, promoting angiogenesis, tumor proliferation and overexpression of COX-2(15).
Another recent theory mentions the ability of S. gallolyticus to trigger malignancy even when it does not produce a chronic infection/inflammation (“the driver-passenger hypothesis”), with the condition that preneoplastic lesions are present at the moment of the bacterial exposure(16). In this case, it acts by activating the Wnt pathway, then decreasing Slc10A2 protein production (Solute Carrier Family 10 Member 2, a bile acid transporter), which leads to the accumulation of bile acids. Moreover, bacteriocine production is activated, allowing S. gallolyticus to destroy commensal bacteria such as enterococci, causing microbiota imbalance, which can lead to carcinogenesis initiation(16).
7. Clostridium septicum
Due to its ability to produce alpha-toxin that binds to GPI (glycosylphosphatidylinositol) receptors on the cell surface, including folate receptors, Clostridium septicum has been associated in some studies with carcinogenesis(10).
B. Microorganisms with possible protective effect
Some studies have pointed out that certain bacteria may play a protective role in neoplastic processes through numerous mechanisms, including the production of short-chain fatty acids(1). They are produced in the intestine by microbial fermentation of the dietary fibres, representing the primary energy source for the colon epithelial cells, as opposed to the cancer cells, which are based on carbon source metabolism, especially on glucose(1).
Eubacterium rectale and Faecalibacterium prausnitzii may be involved in the butyrate production, having an anti-inflammatory role by inducing IL-10 expression(10). Furthermore, the intracellular increased level of butyrate concentration may act as an inhibitor of histone deacetylation, which stimulates apoptosis and inhibits cell proliferation(1).
Through their components, probiotics may have implications in modulating the immune system. For example, the lipopolysaccharide from the bacterial membrane of Gram-negative bacteria may activate the TLR4 surface receptor, which stimulates the T-cell-mediated immune response against cancer cells(17). Bifidobacterium, Bacteroides thetaiotamicron and non-toxigenic B. fragilis promote dendritic cell function and therefore the antitumor properties of CD8+ cytotoxic T cells(1). Lactobacillus casei BL23 has immunomodulatory effects by lowering IL-22 and also antiproliferative influence by increasing caspase-7 and caspase-9(10). In addition to this, it produces ferrichrome, a tumour-suppressive molecule, by which it can trigger apoptosis in tumor cells(10). Clostridium nexile may contribute to the anticancer effects of Pseudomonas aeruginosa(10). Monophosphoryl lipid A, a modified synthetic form of lipid A, derivatived from Salmonella enterica (Salmonella minnesota), has been used as an adjuvant in anticancer vaccines(17).
The composition of gut microbiota
One of the studies that compared the composition of the microbiota of healthy people with the one of those with different types of cancers identified the following five most frequent phyla: Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria and Verrucomicrobia(18).
The abundance of Firmicutes was high in all groups, but this bacterium was predominant in healthy individuals, those with hyperplastic polips and low-risk or high-risk adenomas, compared with adenocarcinoma group, where it was found in a lower proportion(18). Bacteroidetes was lower in healthy people and in those with low-risk lesions, but more abundent in people with adenocarcinoma(18). Actinobacteria and Verrucomicrobia were very low in the adenocarcinoma group, but much more frequent in the others(18).
Firmicutes, Bacteroidetes, Actinobacteria and Proteobacteria predominated in healthy people. A decrease in Firmicutes and Actinobacteria, together with increased Proteobacteria, has been observed in patients with adenocarcinoma(18). In patients with preneoplastic and neoplastic lesions, the ratio of Firmicutes/Bacteroidetes was low(18).
Studies investigating the oral microbiome, performed on people with preneoplastic or neoplastic lesions, showed a decrease of the Firmicutes and Actinobacteria phyla(19).
In tests using saliva specimens, a decrease of the microbial diversity and abundance has been observed, together with the increase of Lactobacillus representation and total loss of various bacterial genera such as Haemophilus spp., Neisseria spp., Gemellaceae spp. or Aggregatibacter spp.(19).
The mechanism of action of the microbiome in the etiopathogenesis of esophageal cancer is not confirmed, but there are several hypotheses available and it seems that inflammation may be the basis of carcinogenesis(20).
Usually, people without esophageal diseases have a type I microbiota at this level, which is composed predominantly of Gram-positive bacteria. In cancer patients, there has been observed a replacement of the normal bacterial populations with the Gram-negative ones (type II microbiota)(20).
The lipopolysaccharide produced by bacteria in the type II microbiota can act directly on the lower esophageal sphincter and delay stomach emptying through COX1/2 pathways, leading to increased gastric pressure and possible manifestation of gastroesophageal reflux(20).
TLR can recognize some microbial molecules and leads to the activation of important transcriptional pathways, such as TLR4 present in the esophagus, which was shown to have an increased expression in diseases such as Barrett’s esophagus or esophageal neoplasm(20).
The interaction of the microbial molecules with TLR4 activates the NF-kB pathway involved in inflammation-associated carcinogenesis(20). It is also possible to activate the Wnt/b-catenin signaling pathway, which can affect tight intercellular junctions and decrease mucus production(20).
In addition to these mechanisms, there are also toxins produced by some bacteria, which can affect DNA and therefore promote carcinogenesis(20).
Dysbiosis and increased intestinal wall permeability may amplify the risk of liver cancer by several mechanisms, including by release of deoxycholic acid caused by the modified microbiota or by liver exposure to other molecules (gut-derived microbiota associated molecular patterns), such as lipopolysaccharide from the Gram-negative bacteria. These bacteria may play a role in inflammation, fibrosis, proliferation and activation of anti-apoptotic signaling pathways(21).
One of the mechanisms may be through the interaction of lipopolysaccharide with TLR, which results in the inhibition of hepatocyte apoptosis by the NF-kB pathway(21). The activation of this pathway in Kupffer cells leads to proliferation of TNF- and IL-6-dependent hepatocytes(21).
The identification of Haemophilus spp., Porphyromonas spp., Leptotrichia spp. and Fusobacterium spp. in the oral cavity has been associated with an increased risk of pancreatic cancer(22). Porphyromonas gingivalis found also in the oral cavity is considered to be a risk factor for pancreatic neoplasm, being involved in carcinogenesis, most likely through the secretion of an enzyme (peptidyl-arginine deiminase), which can lead to p53 and K-ras mutations(22).
Other proposed mechanisms are based on the effect of bacteria from the oral cavity on the immune response, including IL-1b, IFN-ɣ or TNF(22). Moreover, bacterial DNA of microorganisms present in the oral cavity has been identified in the pancreatic cysts formed by mucus produced in a form of pancreatic cancer (intraductal papillary mucinous neoplasm)(22). P. gingivalis and H. pylori have been identified in pancreatic cancer biopsy samples(22).
Another suggested mechanism for the correlation of microbiota and pancreatic carcinogenesis is the interaction of lipopolysaccharide with TLR4, inhibition of mTOR (mammalian target of rapamycin) and phosphorylation of ERK1/2 (extracellular regulated protein kinases)(22). This interaction may also lead to the activation of the NF-kB signaling pathway, with the formation of the c-fos/Jun and p50/p65 complexes, but also the activation of the AP-1 (activator protein 1) or STAT3 pathways(22).
In a study that included men with suspected prostate neoplasm, the investigators performed urine culture tests prior to prostate needle biopsies and observed an association between the presence of cancer cells at this level and the identification of a group of bacteria most commonly involved in urogenital infections: Streptococcus anginosus, Anaerococcus lactolyticus, Anaerococcus obesiensis, Actinobaculum schaalii, Varibaculum cambriense and Propionimicrobium lymphophilum(23). Other studies have highlighted an increase in Bacteroides and Streptococcus spp. at the rectal level(23).
The mechanism is not yet fully elucidated, but appears to be due to inflammation and the production of reactive oxygen species that can affect DNA, leading to genetic instability(23). The direct ability of bacteria to produce cancerous lesions has not been described, but in the presence of other factors, such as physical injury through corpora amylacea or urinary reflux, bacteria may invade the organ and find favourable environment for multiplication, with the well-known inflammatory consequences(23).
Cutibacterium acnes seems to be involved also in prostate cancer, not only in acne, being identified in prostate biopsy samples. However, the one isolated from the prostate proved to have different characteristics than the cutaneous one(24). These strains are able to invade host cells and induce COX-2 signaling pathway, after being injected in the prostate of laboratory mice, leading to tumor formation at this level, as it was shown in a murine study(24).
The breast microbiota can be dominated by Proteobacteria and Firmicutes(25). Regarding the difference between healthy individuals and breast cancer patients, in the first group the predominance of Enterobacteriacae, Bacillus spp. and Staphylococcus spp. has been observed, while in the second group Lactobacillus spp., Thermoanaerobacterium thermosaccharolyticum, Candidatus Aquilluna sp. IMCC13023, Anoxybacillus, Leuconostoc, Lactococcus, Geobacillus, Methylobacterium and Turicella otidis were more frequent(25).
The possible mechanisms include DNA damage, but also the production of enzymes. One example is Bacillus cereus, which can produce various enzymes that metabolize progesterone and testosterone(25). At the same time, there have been identified some microorganisms which, by their ability to modify the structure of certain hormones, can reduce the risk of breast cancer(25).
One of the bacteria involved in the development of lung cancer is Mycobacterium tuberculosis, most likely through TNF, resulting inflammation and consecutive fibrosis, which lead to extracellular matrix synthesis(26).
In addition, an abundance of some bacteria, such as Enterobacter spp., Escherichia coli and Haemophilus influenzae, has been observed in people with lung cancer(26). Their mechanism of action may be represented by reactive oxygen species, but also by the production of toxins such as cytolethal distending toxin, cytotoxic necrotizing factor 1, and the toxin produced by Bacteroides fragilis, which can all alter the DNA(26). Some studies also suggest other mechanisms, such as the presence of FadA produced by Fusobacterium nucleatum(26).
The FadA virulence factor present on the surface of F. nucleatum could represent a diagnostic element for colorectal cancer(12). Quantitative polymerase chain reaction for FadA detection could be a screening solution to identify people at risk for developing adenomas or adenocarcinomas(12).
IgA and IgG antibodies produced against F. nucleatum have been detected in increased amounts in the serum of colorectal cancer patients, which can represent another diagnostic method(11).
Some studies have pointed out the association between salivary detection of P. gingivalis RNA and pancreatic cancer, which could be a simple way of rapidly detecting individuals at risk(22).
Other research on cervical and vaginal cancer has highlighted the importance of examining flora at this level, as a high diversity in the cervicovaginal microbiota could represent an alarming signal and a possible diagnostic marker(27).
Colorectal cancer has frequently been identified in patients with sepsis or infectious endocarditis produced by S. gallolyticus(15). Although the mechanism is not yet elucidated and it cannot be stated with certainty whether the bacterium is involved in the carcinogenesis process or it is only associated after the malignancy has developed, most meta-analyses performed up to date on this subject recommend that patients with infectious endocarditis or sepsis produced by S. gallolyticus should be screened for the presence of colorectal neoplasm by colonoscopy(15).
In the last decades, research on the microbiome and its role in numerous medical fields has been explosive, with results proving more and more its involvement in various mechanisms of metabolic disorders, autoimmune pathologies, cancers and others.
In some neoplasms, certain microorganisms have been identified more frequently, being associated with increased cancer risk or inadequate response to treatment. Unfortunately, although there has been a multitude of studies characterizing the microbiota composition in people with different neoplasms, most of them were only descriptive from an epidemiological point of view, highlighting the predominance of some genera or lower identification of others. The role of microbiota in the mechanisms of carcinogenesis remains to be clearly demonstrated, and certain associations and hypothesis have been launched. There have often been conflicting results on some genera, some studies reporting their beneficial/protective role, while others underlining negative or procarcinogenic effects.
More studies are needed to conclude on the role of the microbiome in the development of cancers, as the results could be essential in the oncology field, for identifying groups at risk, facilitating the diagnosis process, or even estimating the response to treatment.
Conflict of interests: The authors declare no conflict of interests.