Unravelling the role of intratumoral bacteria in digestive system cancers: current insights and future perspectives.

Recently, research on the human microbiome, especially concerning the bacteria within the digestive system, has substantially advanced. This exploration has unveiled a complex interplay between microbiota and health, particularly in the context of disease. Evidence suggests that the gut microbiome plays vital roles in digestion, immunity and the synthesis of vitamins and neurotransmitters, highlighting its significance in maintaining overall health. Conversely, disruptions in these microbial communities, termed dysbiosis, have been linked to the pathogenesis of various diseases, including digestive system cancers. These bacteria can influence cancer progression through mechanisms such as DNA damage, modulation of the tumour microenvironment, and effects on the host's immune response. Changes in the composition and function within the tumours can also impact inflammation, immune response and cancer therapy effectiveness. These findings offer promising avenues for the clinical application of intratumoral bacteria for digestive system cancer treatment, including the potential use of microbial markers for early cancer detection, prognostication and the development of microbiome-targeted therapies to enhance treatment outcomes. This review aims to provide a comprehensive overview of the pivotal roles played by gut microbiome bacteria in the development of digestive system cancers. Additionally, we delve into the specific contributions of intratumoral bacteria to digestive system cancer development, elucidating potential mechanisms and clinical implications. Ultimately, this review underscores the intricate interplay between intratumoral bacteria and digestive system cancers, underscoring the pivotal role of microbiome research in transforming diagnostic, prognostic and therapeutic paradigms for digestive system cancers.

Digestive disorders and Intestinal microbiota.

In the last decade, a barge body of scientific literature has suggested that specific alterations of the gut microbiota may be associated with ther development and clinical course of several gastrointestinal diseases, including irritable bowel syndrome, inflammatory bowel disease, celiac disease, gastrointestinal cancer and Clostridium difficile infection. These alterations are often referred to as "dysbiosis", a generic term designing reduction of gut microbiota biodiversity and alterations in its composition. Here, we provide a synthetic overview of the key concepts on the relationship between intestinal microbiota and gastrointestinal diseases, focusing on the translation of these concepts into clinical practice.

The oral cavity microbiota: between health, oral disease, and cancers of the aerodigestive tract.

Many studies show that the human microbiome plays a critical role in the chronic pathologies of obesity, inflammatory bowel diseases, and diabetes. More recently, the interaction between cancer and the microbiome has been highlighted. Most studies have focused on the gut microbiota because it represents the most extensive bacterial community, and the body of evidence correlating it with gut syndromes is increasing. However, in the strict sense, the gastrointestinal (GI) tract begins in the oral cavity, and special attention should be paid to the specific flora of this cavity. This study reviewed the current knowledge about the various microbial ecosystems of the upper part of the GI tract and discussed their potential link to carcinogenesis. The overall composition of the microbial communities, as well as the presence or absence of "key species", in relation to carcinogenesis is addressed. Alterations in the oral microbiota can potentially be used to predict the risk of cancer. Molecular advances and the further monitoring of the microbiota will increase our understanding of the role of the microbiota in carcinogenesis and open new perspectives for future therapeutic and prophylactic modalities.

[Microbiota and Cancer: a "pas de deux"?] / Gastrointestinale Mikrobiota und Tumorerkrankungen ­ ein "pas de deux"?

Malignant diseases pose an enormous challenge to today's health care system. Advanced pathophysiological understanding of gastrointestinal microbiota and a viable, causal relation to the development of malignant tumors is increasingly becoming the focus of medical research. The following article presents key pathomechanisms of reciprocal interaction between microbiota and malignancy and illustrates the associated role of diet.

[Helicobacter pylori -- 2014]. / Helicobacter pylori -- 2014.

The author reviews the main achievements in Helicobacter pylori research in the past 2 years. Of the more than 1000 microRNAs described thus far, sets of over- and underexpressed samples were identified that are associated with either gastric cancer or precancerous lesions, and some of them could be either markers or therapeutic targets in the near future. Meta-analyses involved 95 new publications: the association between infection and oesophageal, colorectal, pancreatic and liver carcinomas is supported by the increased odds ratios, but the results do not reach the strength seen in gastric carcinoma. Epstein-Barr virus is an emerging pathogen: 10% of gastric cancers are virus-associated; the prevalence of the virus in normal mucosa, chronic gastritis and peptic ulcer are currently being studied. Current Helicobacter pylori eradication regimens frequently achieve suboptimal results: a few optimisation methods are presented, although not all are supported by the meta-analyses. In 2013, the European Helicobacter Study Group proposed the development of a pan-European registry; data from 5792 patients registered so far indicated that many therapeutic regimens resulted in a low eradication rate. In 2013, the Healthy Stomach Initiative was started with the aim of supporting and disseminating research performed in the field of healthy and diseased stomachs.

Impact of bacterial infections on aging and cancer: impairment of DNA repair and mitochondrial function of host cells.

The commensal floras that inhabit the gastrointestinal tract play critical roles in immune responses, energy metabolism, and even cancer prevention. Pathogenic and out of place commensal bacteria, can however have detrimental effects on the host, by introducing genomic instability and mitochondrial dysfunction, which are hallmarks of both aging and cancer. Helicobacter pylori and Enterococcus faecalis are bacteria of the gastrointestinal tract that have been demonstrated to affect these two hallmarks. These, and other bacteria, have been shown to decrease the transcription and translation of essential DNA repair subunits of major DNA repair pathways and increase production of reactive oxygen species (ROS). Defects in DNA repair cause mutations and genomic instability and are found in several cancers as well as in progeroid syndromes. This review describes our contemporary view on how bacterial infections impact DNA repair and damage, and the consequence on the mitochondrial and nuclear genomes. We argue that in the gastrointestinal tract, these mechanisms can contribute to tumorigenesis as well as cellular aging of the digestive system.

Looking in the Porphyromonas gingivalis cabinet of curiosities: the microbium, the host and cancer association.

The past decades of biomedical research have yielded massive evidence for the contribution of the microbiome in the development of a variety of chronic human diseases. There is emerging evidence that Porphyromonas gingivalis, a well-adapted opportunistic pathogen of the oral mucosa and prominent constituent of oral biofilms, best known for its involvement in periodontitis, may be an important mediator in the development of a number of multifactorial and seemingly unrelated chronic diseases, such as rheumatoid arthritis and orodigestive cancers. Orodigestive cancers represent a large proportion of the total malignancies worldwide, and include cancers of the oral cavity, gastrointestinal tract and pancreas. For prevention and/or enhanced prognosis of these diseases, a good understanding of the pathophysiological mechanisms and the interaction between P. gingivalis and host is much needed. With this review, we introduce the currently accumulated knowledge on P. gingivalis's plausible association with cancer as a risk modifier, and present the putative cancer-promoting cellular and molecular mechanisms that this organism may influence in the oral mucosa.

Efficacy of micafungin in empirical therapy of deep mycosis in surgically ill patients.

Micafungin (MCFG), an echinocandin antifungal agent, exhibits antifungal activity against Candida albicans and non-albicans Candida. The fungicidal activity of MCFG against clinical isolates of Candida species was investigated, and the clinical efficacy of MCFG in therapy of deep mycosis in surgery was studied using the AKOTT algorithm. The minimum inhibitory concentration and minimum fungicidal concentration values of fluconazole were ≤0.06-4 and >64 µg/ml, respectively, for each strain, whereas these values of MCFG were 0.008-0.5 and 0.016-1 µg/ml, suggesting that MCFG provided superior fungicidal ability against Candida albicans and non-albicans Candida. The subjects were separated into two groups: group A consisted of 20 subjects with both persisting fever refractory to broad-spectrum antibiotics and positive reaction to ß-D-glucan test, and group B consisted of 20 subjects with either of those conditions. The overall response was evaluated as "effective" in 17 patients (85%) and 20 patients (100%) in groups A and B, respectively. In total, response was evaluated as "effective" in 37 patients (92.5%) and "ineffective" in 3 patients (7.5%). These findings suggest that MCFG administration should be used as empirical therapy for deep mycosis in surgically ill patients as it was shown to be an effective antifungal drug lacking serious adverse effects.

PCR in Helicobacter spp. diagnostic in extragastric malignancies of digestive system.

Recognition of Helicobacter pylori as an important factor in genesis of gastric adenocarcinoma lead to a large number of studies concerning potential role of Helicobacter spp. in the development of extragastric digestive malignancies. The serological studies indicated possible localizations in the digestive system being from interest in enlightening Helicobacter spp. carcinogenic potential. The PCR obtruded itself as a gold standard in proving existence of actual correlation. In this review, the authors have examined studies conducted in the last 10 years examining Helicobacter spp. correlation with extragastric digestive carcinogenesis. Studies have been observed in four groups referring to hepatic carcinoma, bile duct cancer, pancreatic cancer, and colon cancer. The results of these researches have shown that there is a strong correlation between Helicobacter spp. colonization and primary liver tumors as well as bile duct tumors, whereas conclusions made by authors examining pancreatic cancer are contradictory and demands further investigation. No correlation between Helicobacter spp. and colon cancer have been proven. The PCR subtype most widely used in studies included in this review was nested PCR, whereas genes targeted most frequently for amplification are 16S rDNA of Helicobacter spp. and UreA gene or cagA gene of H. pylori. During the last 10 years PCR has proven itself as a sovereign method for Helicobacter spp. diagnostic in extragastric organs in the digestive system. Knowledge and experiences obtained in this domain could be encouraging for researchers in analogous fields of interest.

Microorganismos y cáncer: evidencias científicas y nuevas hipótesis / Microorganisms and cancer: Scientific evidence and new hypotheses

La implicación de los microorganismos en el cáncer humano se conoce desde hace más de un siglo y diferentes tipos de parásitos, bacterias y virus se han relacionado con procesos oncogénicos. Dentro de las bacterias, la primera reconocida como carcinogénica fue Helicobacter pylori, que causa cáncer gástrico y podría estar relacionada con cánceres extragástricos en el hombre. Helicobacter hepaticus se ha relacionado con cánceres hepáticos utilizando modelos animales. Otras bacterias, como Chlamydia psitacii, Borrelia burgdorferi y Streptococcus bovis, se han relacionado con cánceres oculares, de piel y colorrectal, respectivamente. Además, una bacteria comensal del intestino humano, Bacteroides fragilis, se ha vinculado muy recientemente con el cáncer colorrectal utilizando modelos animales (AU)

Microorganism involvement in cancer has been known for over a century, and different types of parasites, bacteria and viruses have been associated with oncogenic processes. Among the bacteria, the first recognised was Helicobacter pylori which causes gastric cancer and might be related to extra-gastric cancer in humans. Helicobacter hepaticus has been associated with liver cancers using animal models. Other bacteria such as, Chlamydia psitacii, Borrelia burgdorferi and Streptococcus bovis have been associated with ocular, skin and colorectal cancers, respectively. Also, a commensal bacterium in the human intestine, Bacteroides fragilis, has been linked, very recently, with colorectal cancer using animal models (AU)

[Microorganisms and cancer: scientific evidence and new hypotheses]. / Microorganismos y cáncer: evidencias científicas y nuevas hipótesis.

Microorganism involvement in cancer has been known for over a century, and different types of parasites, bacteria and viruses have been associated with oncogenic processes. Among the bacteria, the first recognised was Helicobacter pylori which causes gastric cancer and might be related to extra-gastric cancer in humans. Helicobacter hepaticus has been associated with liver cancers using animal models. Other bacteria, such as Chlamydia psitacii, Borrelia burgdorferi and Streptococcus bovis, have been associated with ocular, skin and colorectal cancers, respectively. Also, a commensal bacterium in the human intestine, Bacteroides fragilis, has been linked, very recently, with colorectal cancer using animal models.

Acetaldehyde, microbes, and cancer of the digestive tract.

Excessive alcohol consumption and heavy smoking are the main risk factors of upper digestive tract cancer in industrialized countries. The association between heavy drinking and cancer appears to he particularly prominent in Asian individuals who have an inherited deficient ability to detoxify the first metabolite of ethanol oxidation, acetaldehyde. Alcohol itself is not carcinogenic. However, according to cell culture and animal experiments acetaldehyde is highly toxic, mutagenic, and carcinogenic. In addition to somatic cells, microbes representing normal human gut flora are also able to produce acetaldehyde from ethanol. After the ingestion of alcoholic beverages, this results in high local acetaldehyde concentrations in the saliva, gastric juice, and the contents of the large intestine. In addition, microbes may produce acetaldehyde endogenously without alcohol administration. This review summarizes the epidemiological, genetic, and biochemical evidence supporting the role of locally produced acetaldehyde in the pathogenesis of digestive tract cancer. Special emphasis is given to those factors that regulate local acetaldehyde concentration in the contents of the gastrointestinal tract. The new evidence presented in this review may open a microbiological approach to the pathogenesis of digestive tract cancer and may have an influence on future preventive strategies.

EBV DNA in nodal and extranodal non-Hodgkin's lymphomas: impact of cell lineage, morphology, and site of origin.

The Epstein-Barr virus (EBV) is a transforming herpes virus which is found in high frequencies in lymphoproliferative disorders arising in immunocompromised patients. To address the question of viral involvement in lymphomas of immunocompetent patients, we investigated 299 nodal and extranodal non-Hodgkin's, non-Burkitt's lymphomas of B- and T-cell lineage for the presence of EBV DNA. Epstein-Barr nucleic acid sequences were detected in 23 of 226 (10%) cases of B-cell lymphomas, in 24/72 (33%) T-cell lymphomas and one non-B, non-T lymphoma. Our data imply a possible role for the EBV in lymphoma development or propagation, an influence of viral factors on morphology and an impact of the anatomic site in which lymphoma development occurs.

The Harvey ras 1 gene is activated in papillomavirus-associated carcinomas of the upper alimentary canal in cattle.

The possible activation of ras sequences in papillomavirus-associated carcinomas of the upper alimentary canal of cattle was investigated by restriction enzyme and hybridization analysis, and by DNA-mediated transformation of NIH3T3 cells. In three cancers, a squamous cell carcinoma of the palate, a squamous cell carcinoma of the rumen, and a transitional cell carcinoma of the urinary bladder, repetitive DNA sequences present in the Ha-ras 1 locus showed anomalous restriction patterns, indicating rearrangements and, in the case of the palate cancer, amplification. Genomic DNA from several cancers was capable of inducing focus formation in the NIH3T3 transformation test. DNA from primary, secondary and tertiary transformants was analysed by hybridization to bovine ras probes and by nucleotide sequencing of polymerase chain reaction products. Bovine Ha-ras 1 sequences were found in all transformants, but no nucleotide differences were detected in exon 1 or exon 2 between normal, cancer and transformed cells. It is concluded that the Ha-ras 1 gene is activated in alimentary canal carcinomas, although the activating mutation has not yet been mapped. The possible relationship between papillomavirus infection and activation of the ras gene is considered.

Papillomavirus infection in cattle: viral and chemical cofactors in naturally occurring and experimentally induced tumours.

Six different types of bovine papillomavirus (BPV-1 to BPV-6) have been identified and classified into two subgroups: subgroup A, which induce fibropapillomas, and subgroup B, which induce true epithelial papillomas. BPV-4, a member of subgroup B, is the aetiological agent of papillomas of the upper alimentary canal, which can become a focus for transformation to squamous-cell carcinomas in animals feeding on bracken fern. Strong circumstantial evidence suggests that the progression to malignancy is due to the interplay between BPV-4 and carcinogen(s) present in the fern. The carcinomas of the upper alimentary canal are often accompanied by adenomas and adenocarcinomas of the lower bowels, and by carcinomas and hemangiosarcomas of the urinary bladder. Bracken-grazing animals are also heavily immunosuppressed. Florid papillomatosis of the upper alimentary canal and cancers of the urinary bladder have been experimentally reproduced in animals either kept on a diet of bracken or immunosuppressed with azathioprine. Several bladder cancers contained multiple episomal copies of BPV-2 DNA, suggesting that this virus, or its genome, can be present in a latent form, and that it can be implicated in malignant transformation. Further indication of latent infection is provided by the onset of skin warts in papillomatosis-free animals. These warts developed at sites of damaged skin and harboured either BPV-1 or BPV-2. BPV-4 DNA has not been found in the naturally occurring cancers of the upper alimentary canal and of the lower bowels, except in one tongue carcinoma and one transforming papilloma, indicating that the viral genome is not required for the maintenance of the malignant state in the alimentary canal.

The presence of bovine papillomavirus type 4 DNA is not required for the progression to, or the maintenance of, the malignant state in cancers of the alimentary canal in cattle.

In the Western Highlands of Scotland there is a very high incidence of alimentary cancers in cattle. The carcinomas of the upper alimentary canal are found in association with virus-induced benign papillomas, and transformation of papillomas to carcinomas has been observed. Strong circumstantial evidence suggests that the progression to malignancy is due to the interplay between the virus, bovine papillomavirus type 4 (BPV-4), and carcinogen(s) present in bracken fern, which infests the marginal upland grazing grounds. The carcinomas are often accompanied by adenomas and adenocarcinomas of the lower bowels. To elucidate the role of the virus in the transformation process, we have analysed several malignancies of the alimentary canal, and have detected the viral genome in only one case of transforming papilloma of the oesophagus and one case of carcinoma of the tongue. We conclude that, although required for the induction of papillomas, the presence of the BPV-4 DNA is not necessary for the progression to, or the maintenance of, the transformed state.