Interdisciplinary insights into the link between gut microbiome and gastric carcinogenesis-what is currently known?

Currently, gastric cancer is one of the leading death-related cancer globally. The etiopathogenesis of gastric cancer is multifactorial and includes among others dysbiotic alterations of gastric microbiota. Molecular techniques revealed that stomach is not a sterile organ and it is resides with ecosystem of microbes. Due to the fact that the role of Helicobacter pylori infection in development of gastric cancer is established and well-studied, this paper is mainly focused on the role of other bacterial as well as viral and fungal gut microbiota imbalance in gastric carcinogenesis. Notably, not only the composition of gastric microbiota may play an important role in development of gastric cancer, but also its activity. Microbial metabolites, such as short-chain fatty acids, polyamines, N-nitroso compounds, and lactate, may significantly affect gastric carcinogenesis. Therefore, this paper discussed aforementioned aspects with the interdisciplinary insights (regarding also immunological point of view) into the association between gut microbiome and gastric carcinogenesis based on up-to-date studies.

Molecular Mechanisms Leading from Periodontal Disease to Cancer.

Periodontitis is prevalent in half of the adult population and raises critical health concerns as it has been recently associated with an increased risk of cancer. While information about the topic remains somewhat scarce, a deeper understanding of the underlying mechanistic pathways promoting neoplasia in periodontitis patients is of fundamental importance. This manuscript presents the literature as well as a panel of tables and figures on the molecular mechanisms of Porphyromonas gingivalis and Fusobacterium nucleatum, two main oral pathogens in periodontitis pathology, involved in instigating tumorigenesis. We also present evidence for potential links between the RANKL-RANK signaling axis as well as circulating cytokines/leukocytes and carcinogenesis. Due to the nonconclusive data associating periodontitis and cancer reported in the case and cohort studies, we examine clinical trials relevant to the topic and summarize their outcome.

The use of Lactobacillus plantarum 299v (DSM 9843) in cancer patients receiving home enteral nutrition - study protocol for a randomized, double-blind, and placebo-controlled trial.

BACKGROUND: Nutritional treatment is one of the most important components of multidisciplinary anti-cancer therapy. Home enteral nutrition is considered as a safe procedure, however, it may be associated with the risk of side effects, such as nausea, vomiting, abdominal pain, and diarrhoea. It is uncertain whether diarrhoea is the result of the enteral formula administration or gut dysbiosis. One of the methods which may be used to alter the composition of gut microbiota is the administration of a probiotic strain. Lactobacillus plantarum 299v ingestion was found to diminish the adverse events of irritable bowel syndrome and Clostridium difficile infection - entities that share the symptoms with enteral nutrition side effects. Therefore, the primary aim of this study is to determine the effect of Lactobacillus plantarum 299v on prevention of weight loss of cancer patients receiving home enteral nutrition. The secondary aims are to evaluate the role of this probiotic strain in the improvement of nutritional status, enteral nutrition tolerance, and patients' quality of life. METHODS: Forty patients with cancer receiving home enteral nutrition will be enrolled in this clinical trial and randomized to receive one capsule of Lactobacillus plantarum 299v (Sanprobi IBS®) twice a day or placebo for 12 weeks in a double-blind manner. Laboratory tests (the level of albumin, total protein, transferrin, and total lymphocyte count), anthropometric parameters (body mass, the content of fat mass, muscle mass, and total body water), Nutritional Risk Screening (NRS 2002), enteral nutrition tolerance as well as quality of life will be measured. Measurements will be obtained at the baseline and after 4 and 12 weeks of treatment. DISCUSSION: The adverse events observed during administration of enteral nutrition have an negative impact on enteral formula tolerance and as a consequence patients' quality of life. The previous studies have demonstrated that probiotics may reduce the gastrointestinal symptoms related to enteral nutrition. Thus, administration of Lactobacillus plantarum 299v may be effective in improvement of nutritional status, enteral nutrition tolerance, and quality of life of cancer patients receiving home enteral nutrition. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03940768 .

Saccharomyces boulardii CNCM I-745: A Non-bacterial Microorganism Used as Probiotic Agent in Supporting Treatment of Selected Diseases.

The yeast Saccharomyces boulardii CNCM I-745 is a unique, non-bacterial microorganism classified as a probiotic agent. In this review article, at first, we briefly summarized the mechanisms responsible for its probiotic properties, e.g. adhesion to and elimination of enteropathogenic microorganisms and their toxins; extracellular cleavage of pathogens' virulent factors; trophic and anti-inflammatory effects on the intestinal mucosa. The efficacy of S. boulardii administration was tested in variety of human diseases. We discussed the results of S. boulardii CNCM I-745 use in the treatment or prevention of Helicobacter pylori infections, diarrhoea (Clostridium difficile infections, antibiotic-associated diarrhoea, and traveller's diarrhoea), inflammatory bowel diseases, irritable bowel syndrome, candidiasis, dyslipidemia, and small intestine bacterial overgrowth in patients with multiple sclerosis. In case of limited number of studies regarding this strain, we also presented studies demonstrating properties and efficacy of other strains of S. boulardii. Administration of S. boulardii CNCMI I-745 during antibiotic therapy has certain advantage over bacterial probiotics, because-due to its fungal natural properties-it is intrinsically resistant to the antibiotics and cannot promote the spread of antimicrobial resistance. Even though cases of fungemia following S. boulardii CNCM I-745 administration were reported, it should be treated as a widely available and safe probiotic strain.

Immunonutritional support as an important part of multidisciplinary anti-cancer therapy.

Immunonutrition is one of the most important parts of nutritional treatment in patients with cancer. There are studies which confirm positive effects of using immunonutrition (arginine, glutamine, omega-3 fatty acids, nucleotides, pre- and probiotics) among others on the reduction of the pro-inflammatory cytokines concentrations, shortening of the hospital stay and improvement of the nutritional status. Arginine takes part not only in wound healing process, but also it improves body's immunity and reduces the incidence of infections. Glutamine reduces the incidence of acute grade 2 and 3 esophagitis and improves quality of life of gastric cancer patients. Omega 3-fatty acids have the ability to inhibit the activity of NF-κB. They also reduce the symptoms of graft-versus-host disease in patients undergoing hematopoietic cell transplantation. Nucleotides support the regeneration of intestinal villi. Probiotics play many roles, mainly inhibit the process of carcinogenesis, reduce the incidence of diarrhea and modify intestinal microbiome. However, there are studies indicating the lack of advantages of using immunonutrition compared to standard nutrition. Currently, there is no clear evidence for the use of formulae enriched with immunonutrients versus standard oral nutritional supplements exclusively in the preoperative period. This review summarizes the current knowledge about the role of immunonutrition in supporting treatment of cancer diseases.

The role of Lactobacillus plantarum 299v in supporting treatment of selected diseases.

Alterations in composition of human gut microbiome can lead to its dysbiosis. It is associated with gastrointestinal side effects during anti-cancer treatment, antibiotics administration, or infectious agents. There are studies confirming positive effect of consuming Lactobacillus plantarum 299v on intestinal microflora. This review summarizes the current knowledge about the role of L. plantarum 299v in supporting treatment of selected diseases, such as cancer, irritable bowel syndrome (IBS), and Clostridium difficile infection. The immunomodulating properties of L. plantarum 299v include an increase in the level of anti-inflammatory cytokines, which reduce the risk of cancer and improve the efficacy of regimens. The intake of L. plantarum 299v provides benefits for IBS patients, mainly due to normalization of stool and relief of abdominal pain, which significantly improves the quality of life of IBS patients. In addition, the intake of L. plantarum 299v prevents C. difficile-associated diarrhea among patients receiving antibiotic treatment. Due to the limited possibilities of treating these diseases and numerous complications of cancer treatment, there is a need for new therapeutic strategies. The administration of L. plantarum 299v seems to be useful in these cases.

Gastrointestinal cancers: the role of microbiota in carcinogenesis and the role of probiotics and microbiota in anti-cancer therapy efficacy.

The gut epithelium is a habitat of a variety of microorganisms, including bacteria, fungi, viruses and Archaea. With the advent of sophisticated molecular techniques and bioinformatics tools, more information on the composition and thus function of gut microbiota was revealed. The gut microbiota as an integral part of the intestinal barrier has been shown to be involved in shaping the mucosal innate and adaptive immune response and to provide protection against pathogens. Consequently, a set of biochemical signals exchanged within microbes and communication between the microbiota and the host have opened a new way of thinking about cancer biology. Probiotics are living organisms which administered in adequate amounts may bring health benefits and have the potential to be an integral part of the prevention/treatment strategies in clinical approaches. Here we provide a comprehensive review of data linking gut microbiota to cancer pathogenesis and its clinical course. We focus on gastrointestinal cancers, such as gastric, colorectal, pancreatic and liver cancer.

Anti-cancer management of head and neck cancers and oral microbiome-what can we clinically obtain?

Head and neck squamous cell carcinoma (HNSCC) exhibits significant genetic heterogeneity and primarily concerns the oral cavity and oropharynx. These cancers occur more frequently in men with a 5-year survival rate below 50%. Major risk factors include human papilloma virus (HPV) (notably type 16), Epstein-Barr virus, tobacco, alcohol, and poor oral hygiene with approximately 4.5% of global cancers linked to HPV. Notably, differences in the microbiome between healthy individuals and patients with head and neck cancers (HNCs) have been identified. Recent studies highlight the significance of certain oral microbes in risk assessment and the potential of the microbiome as a biomarker for HNCs. Additionally, role of the microbiome in metastasis has been acknowledged. Treatment for HNCs includes local methods, such as surgery and radiotherapy, and systemic approaches, such as immunotherapy. Numerous side effects accompany these treatments. Emerging research suggests the beneficial role of preoperative immunonutrition and probiotics in patient outcomes, emphasizing the influence of the microbiome on treatment efficacy. This review explores the reciprocal effects of HNC treatment and the gut microbiome using radiotherapy, brachytherapy, surgery, immunotherapy, and chemotherapy.

Untargeted metabolomics in gastric and colorectal cancer patients - preliminary results.

Introduction: Recent years, microbiota-associated aspects have been analysed in multiple disorders regarding cancers. Existing evidence pints that gut microorganisms might take part in tumour origin and therapy efficacy. Nevertheless, to date, data on faecal metabolomics in cancer patients is still strongly limited. Therefore, we aimed to analyse gut untargeted metabolome in gastrointestinal cancer patients (i.e., gastric and colorectal cancer). Patients and methods: There were 12 patients with either gastric (n=4) or colorectal cancer (n=8) enrolled and 8 analysed (n=4 each). Stool samples were collected prior to anti-cancer treatments. Untargeted metabolomics analyses were conducted by means of mass spectrometry. Results: A plethora of metabolites in cancer patients we analysed were noted, with higher homogenity in case of gastric cancer patients. We found that the level of Deoxyguanosine,m/z 266.091,[M-H]-, Uridine,m/z 245.075,[M+H]+, Deoxyguanosine,m/z 268.104,[M]+, 3-Indoleacetic acid,m/z 176.07,[M+H]+, Indoxyl,m/z 132.031,[M-H]-, L-Phenylalanine,m/z 164.073,[M-H]-, L-Methionine,m/z 150.058,[M+NH4]+, was significantly higher in colorectal cancer patients and Ethyl hydrogen malonate,m/z 133.031,[M+H]+ in gastric cancer. Conclusion: The overall insights into untargeted metabolomics showed that most often higher levels of analysed metabolites were detected in colorectal cancer patients compared to gastric cancer patients. The link between gut metabolome and both local and distal metastasis might exist, however it requires confirmation in further multi-centre studies regarding larger sample size.

Gut Microbiome-How Does Two-Month Consumption of Fiber-Enriched Rolls Change Microbiome in Patients Suffering from MASLD?

BACKGROUND: The occurrence of metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global problem which commonly affects patients with co-existing diseases/conditions, such as type 2 diabetes and dyslipidemia. The effective treatment of MASLD is still limited; however, diet plays a significant role in its management. There are multiple beneficial properties of dietary fiber, including its ability to modify the gut microbiome. Therefore, the aim of this study was to determine the effect of the consumption of fiber-enriched rolls on the gut microbiome and microbial metabolites in patients suffering from MASLD. METHODS: The participants were recruited according to the inclusion criteria and were required to consume fiber-enriched rolls containing either 6 g or 12 g of fiber. There were three assessment timepoints, when the anthropometric and laboratory parameters were measured, and 16s on nanopore sequencing of the fecal microbiome was conducted. RESULTS: Firmicutes and Bacteroidetes were the most abundant phyla in the patients living with MASLD. It was demonstrated that the amount of short-chain fatty acids (SCFAs) changed after the consumption of fiber-enriched rolls; however, this was strongly associated with both the timepoint and the type of SCFAs-acetate and butyrate. Additionally, the high-fiber diet was related to the increase in phyla diversity (p = 0.006571). CONCLUSIONS: Overall, the introduction of an appropriate amount of fiber to the diet seems to be promising for patients suffering from MASLD due to its ability to create an improvement in gut microbiome-related aspects.

Nutritional Support for Liver Diseases.

The liver is a key organ that is responsible for the metabolism of proteins, fats, and carbohydrates and the absorption and storage of micronutrients. Unfortunately, the prevalence of chronic liver diseases at various stages of advancement in the world population is significant. Due to the physiological function of the liver, its dysfunction can lead to malnutrition and sarcopenia, and the patient's nutritional status is an important prognostic factor. This review discusses key issues related to the diet therapy of patients with chronic liver diseases, as well as those qualified for liver transplantation and in the postoperative period.

Postbiotics in oncology: science or science fiction?

The gut microbiome has been increasingly understood to play a critical role in carcinogenesis and cancer disease progression. The most recent research advancements have shown that different tools of microbiota manipulation contribute to gut microbiome-immune-oncology axis modulation, offering exciting opportunities for targeted interventions aimed at improving the efficacy of established anti-cancer therapy. Postbiotics are a new entry among the biotics showing beneficial effects on human health while not requiring living cells to obtain the health effect and therefore not subjected to food safety rules for live microorganisms. Postbiotics are recently defined as the "preparation of inanimate microorganisms and/or their components that confers a health benefit on the host" and have gradually become the focus of the scientific community. Since the beginning of research on this topic, numerous studies about postbiotics have been proven to strengthen the gut barrier, reduce inflammation, and promote antimicrobial activity. However, research on the potential application of cancer therapy is still at the early stages of its efforts to uncover all the secrets surrounding postbiotics. This review aims to increase our understanding of the anti-cancer effect of postbiotics throughout a "bibliographic journey" on the biological activity of their components, including exopolysaccharides, cell wall fragments, tryptophan metabolites, enzymes, bacterial lysates, extracellular vesicles, and short-chain fatty acids, highlighting their perspective as a new supportive therapeutic method of treatment and identifying the literature gaps where further research is needed.

Insights into oral microbiome and colorectal cancer - on the way of searching new perspectives.

Microbiome is a keystone polymicrobial community that coexist with human body in a beneficial relationship. These microorganisms enable the human body to maintain homeostasis and take part in mechanisms of defense against infection and in the absorption of nutrients. Even though microbiome is involved in physiologic processes that are beneficial to host health, it may also cause serious detrimental issues. Additionally, it has been proven that bacteria can migrate to other human body compartments and colonize them even although significant structural differences with the area of origin exist. Such migrations have been clearly observed when the causes of genesis and progression of colorectal cancer (CRC) have been investigated. It has been demonstrated that the oral microbiome is capable of penetrating into the large intestine and cause impairments leading to dysbiosis and stimulation of cancerogenic processes. The main actors of such events seem to be oral pathogenic bacteria belonging to the red and orange complex (regarding classification of bacteria in the context of periodontal diseases), such as Porphyromonas gingivalis and Fusobacterium nucleatum respectively, which are characterized by significant amount of cancerogenic virulence factors. Further examination of oral microbiome and its impact on CRC may be crucial on early detection of this disease and would allow its use as a precise non-invasive biomarker.

Nutritional Status and the Outcomes of Endoscopic Stenting in Benign and Malignant Diseases of Esophagus.

BACKGROUND: Endoscopic stenting (ES) is a widely known method for palliative dysphagia treatment in esophageal strictures. Esophageal cancer is often associated with advanced malnutrition, which may increase the risk of complications of the procedure. The aim of this study was to evaluate complication rates and the impact of nutritional status on the outcomes of ES. PATIENTS AND METHODS: A single-center retrospective study was conducted at Copernicus Hospital in Gdansk, Poland. Adult patients who underwent endoscopic stenting between February 2014 and December 2018 were included. The influence of patient characteristics (age, sex, indications for esophageal stenting, and location of stenosis) and nutritional status (BMI, NRS 2002, GLIM, and dysphagia score) on complication rates and survival were analyzed. RESULTS: Eighty-one patients (69% men) were enrolled in the study. In 69%, the indication for ES was malignancy (mainly esophageal cancer). The median dysphagia score significantly decreased from 2.8 to 0.6 after the procedure (p < 0.001). Complications were observed in 27% (n = 22) of the patients. Early complications were bleeding (2.5%), stent unexpansion (2.5%), and stent migration during the procedure (3.7%). There were no early fatal complications of the procedure. Late complications included: stent migration (6.2%), tissue overgrowth (6.2%), food impaction (2.2%), fistula formation (3.7%), bleeding (3.7%), and stent malposition (1.2%). A total of 76% of the participants scored ≥ 3 points in nutritional screening (NRS2002) and 70% were diagnosed with severe malnutrition (GLIM -stage 2). A stent diameter of < 2.2 cm compared with ≥ 2.2 was associated with a higher rate of migrations (15.5% vs. 2.5%). The median survival time in the malignant group was 90 days. Histopathological diagnosis and patients' nutritional status (BMI, NRS 2002, GLIM, and dysphagia score) had no significant effect on complication rates and survival after esophageal stent insertion. CONCLUSIONS: Endoscopic stenting is a relatively safe procedure for the palliative treatment of esophageal strictures. Severe malnutrition, although common, does not affect the outcomes of the procedure.

Pharmacomicrobiomics of cell-cycle specific anti-cancer drugs - is it a new perspective for personalized treatment of cancer patients?

Intestinal bacteria are equipped with an enzyme apparatus that is involved in the active biotransformation of xenobiotics, including drugs. Pharmacomicrobiomics, a new area of pharmacology, analyses interactions between bacteria and xenobiotics. However, there is another side to the coin. Pharmacotherapeutic agents can significantly modify the microbiota, which consequently affects their efficacy. In this review, we comprehensively gathered scientific evidence on the interplay between anticancer therapies and gut microbes. We also underlined how such interactions might impact the host response to a given therapy. We discuss the possibility of modulating the gut microbiota to increase the effectiveness/decrease the incidence of adverse events during tumor therapy. The anticipation of the future brings new evidence that gut microbiota is a target of interest to increase the efficacy of therapy.

Current Trends in Volume and Surgical Outcomes in Gastric Cancer.

Gastric cancer is ranked as the fifth most frequently diagnosed type of cancer. Complete resection with adequate lymphadenectomy represents the goal of treatment with curative intent. Quality assurance is a crucial factor in the evaluation of oncological surgical care, and centralization of healthcare in referral hospitals has been proposed in several countries. However, an international agreement about the setting of "high-volume hospitals" as well as "minimum volume standards" has not yet been clearly established. Despite the clear postoperative mortality benefits that have been described for gastric cancer surgery conducted by high-volume surgeons in high-volume hospitals, many authors have highlighted the limitations of a non-composite variable to define the ideal postoperative period. The textbook outcome represents a multidimensional measure assessing the quality of care for cancer patients. Transparent and easily available hospital data will increase patients' awareness, providing suitable elements for a more informed hospital choice.

Sodium butyrate in both prevention and supportive treatment of colorectal cancer.

Accumulating evidence suggests that selected microbiota-derived metabolites play a significant role in both tumor prevention and supportive treatment of cancer. Short-chain fatty acids (SCFAs), i.e., mainly acetate, proprionate, and butyrate, are one of them. Nowadays, it is known that butyrate is a key microbial metabolite. Therefore, in the current review, we focused on butyrate and sodium butyrate (NaB) in the context of colorectal cancer. Notably, butyrate is characterized by a wide range of beneficial properties/activities. Among others, it influences the function of the immune system, maintains intestinal barrier integrity, positively affects the efficiency of anti-cancer treatment, and may reduce the risk of mucositis induced by chemotherapy. Taking into consideration these facts, we analyzed NaB (which is a salt of butyric acid) and its impact on gut microbiota as well as anti-tumor activity by describing molecular mechanisms. Overall, NaB is available as, for instance, food with special medical purposes (depending on the country's regulation), and its administration seems to be a promising option for colorectal cancer patients.

Next-generation probiotics - do they open new therapeutic strategies for cancer patients?

Gut microbiota and its association with cancer development/treatment has been intensively studied during the past several years. Currently, there is a growing interest toward next-generation probiotics (NGPs) as therapeutic agents that alter gut microbiota and impact on cancer development. In the present review we focus on three emerging NGPs, namely Faecalibacterium prausnitzii, Akkermansia muciniphila, and Bacteroides fragilis as their presence in the digestive tract can have an impact on cancer incidence. These NGPs enhance gastrointestinal immunity, maintain intestinal barrier integrity, produce beneficial metabolites, act against pathogens, improve immunotherapy efficacy, and reduce complications associated with chemotherapy and radiotherapy. Notably, the use of NGPs in cancer patients does not have a long history and, although their safety remains relatively undefined, recently published data has shown that they are non-toxigenic. Notwithstanding, A. muciniphila may promote colitis whereas enterotoxigenic B. fragilis stimulates chronic inflammation and participates in colorectal carcinogenesis. Nevertheless, the majority of B. fragilis strains provide a beneficial effect to the host, are non-toxigenic and considered as the best current NGP candidate. Overall, emerging studies indicate a beneficial role of these NGPs in the prevention of carcinogenesis and open new promising therapeutic options for cancer patients.

Esophageal cancer and bacterial part of gut microbiota - A multidisciplinary point of view.

There is an urgent need to search for new screening methods that allow early detection of esophageal cancer and thus achieve better clinical outcomes. Nowadays, it is known that the esophagus is not a sterile part of the gastrointestinal tract. It is colonized with various microorganisms therefore a "healthy" esophageal microbiome exists. The dysbiotic changes of esophageal microbiome can lead to the development of esophageal diseases including esophageal cancer. There is a strong consensus in the literature that the intestinal microbiome may be involved in esophageal carcinogenesis. Recently, emphasis has also been placed on the relationship between the oral microbiome and the occurrence of esophageal cancer. According to recent studies, some of the bacteria present in the oral cavity, such as Tannerella forsythia, Streptococcus anginosus, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Fusobacterium nucleatum may contribute to the development of this cancer. Moreover, the oral microbiome of patients with esophageal cancer differs significantly from that of healthy individuals. This opens new insights into the search for a microbiome-associated marker for early identification of patients at high risk for developing this cancer.

Unhealthy Food Choices among Healthcare Shift Workers: A Cross-Sectional Study.

Shift healthcare workers are a group particularly exposed to an increased risk of poor eating habits and are affected by many diseases. The aim of the study was to evaluate the dietary patterns (DPs), including the Polish-adapted Mediterranean Diet (Polish-aMED®) score, and dietary fat intake in association with the shift work of healthcare workers. This cross-sectional study involved 445 healthcare workers from the West Pomeranian in Poland. Dietary data were collected using an FFQ-6®. A posteriori DPs were derived with a Principal Component Analysis (PCA). The Polish-aMED® score and the individual's percentage of energy from dietary fat (Pfat) were calculated. Healthcare shift work compared to the daily work was associated with approximately 2-times higher odds of adherence to the 'Meat/fats/alcohol/fish' DP in the upper tertile (OR: 2.38; 95% Cl: 1.27−4.47; p < 0.01) and higher Pfat >35% of total energy intake (OR: 1.73; 95% Cl: 1.06−2.83; p < 0.05). Healthcare shift work compared to the daily work was associated with approximately 50% lower odds of adherence to the 'Pro-healthy' DP in the middle tertile (OR: 0.48; 95% Cl: 0.26−0.89; p < 0.05) and a higher level of the Polish-aMED® score (OR: 0.57; 95% Cl: 0.33−0.98; p < 0.05), as well as lower odds of the constants of mealtime (OR: 0.54; 95% Cl: 0.33−0.89; p < 0.05). The obtained findings highlight the unhealthy food choices among shift healthcare workers. Thus, to avoid the negative health consequences, there is a need for nutritional education for healthcare workers, especially those working shifts.