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.

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.

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.

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.

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.

Association between Fecal Microbiota, SCFA, Gut Integrity Markers and Depressive Symptoms in Patients Treated in the Past with Bariatric Surgery-The Cross-Sectional Study.

(1) Background: Depressive symptoms often appear after surgical treatment. (2) Methods: We involved 41 adults who underwent bariatric surgery a minimum of 6 months before the study and had the Beck scale ≥12. We analysed patients' mental state, gut barrier markers, faecal short chain fatty acids, and microbiota. (3) Results: Gut microbiota composition differed significantly among patients undergoing two different types of surgery (F = 1.64, p = 0.00002). Additionally, we discovered an association between short chain fatty acids and the Beck scale (F = 1.22, p = 0.058). The rearrangement of bacterial metabolites may be due to the patients' use of increased dietary protein, with insufficient intake of products containing vegetable fiber (Diet Quality Index (DQI-I )adequacy 22.55 (±3.46) points). (4) Conclusions: Bariatric surgery affects the gut microbiota, which may play an important role in the development of depressive and gastrointestinal symptoms in patients after bariatric surgery. Low fiber consumption and increased levels of faecal isobutyric acid may lead to intestinal inflammation. There is a need for further research on this topic including a larger sample size.

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.

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.

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.

Autoimmunity and Cancer-Two Sides of the Same Coin.

Autoimmune disease results from the immune response against self-antigens, while cancer develops when the immune system does not respond to malignant cells. Thus, for years, autoimmunity and cancer have been considered as two separate fields of research that do not have a lot in common. However, the discovery of immune checkpoints and the development of anti-cancer drugs targeting PD-1 (programmed cell death receptor 1) and CTLA-4 (cytotoxic T lymphocyte antigen 4) pathways proved that studying autoimmune diseases can be extremely helpful in the development of novel anti-cancer drugs. Therefore, autoimmunity and cancer seem to be just two sides of the same coin. In the current review, we broadly discuss how various regulatory cell populations, effector molecules, genetic predisposition, and environmental factors contribute to the loss of self-tolerance in autoimmunity or tolerance induction to cancer. With the current paper, we also aim to convince the readers that the pathways involved in cancer and autoimmune disease development consist of similar molecular players working in opposite directions. Therefore, a deep understanding of the two sides of immune tolerance is crucial for the proper designing of novel and selective immunotherapies.

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.

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.

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.

Pancreatic Cancer and Gut Microbiome-Related Aspects: A Comprehensive Review and Dietary Recommendations.

Gut microbiota plays a significant role in the human body providing many beneficial effects on the host. However, its dysbiotic alterations may affect the tumorigenic pathway and then trigger the development of pancreatic cancer. This dysbiosis can also modulate the aggressiveness of the tumor, influencing the microenvironment. Because pancreatic cancer is still one of the most lethal cancers worldwide with surgery as the only method that influences prognosis and has curative potential, there is a need to search for other strategies which will enhance the efficiency of standard therapy and improve patients' quality of life. The administration of prebiotics, probiotics, next-generation probiotics (Faecalibacterium prausnitzii, Akkermansia muciniphila), synbiotics, postbiotics, and fecal microbiota transplantation through multiple mechanisms affects the composition of the gut microbiota and may restore its balance. Despite limited data, some studies indicate that the aforementioned methods may allow to achieve better effect of pancreatic cancer treatment and improve therapeutic strategies for pancreatic cancer patients.

Reply to Cantarelli et al. Chronic Recurrent Multifocal Osteomyelitis Associated with Crohn Disease: A Potential Role of Exclusion Diet? Comment on "Starz et al. The Modification of the Gut Microbiota via Selected Specific Diets in Patients with Crohn's Disease. Nutrients 2021, 13, 2125".

We congratulate Erika Cantarelli and colleagues for the presented case report in the comment entitled "Chronic Recurrent Multifocal Osteomyelitis associated to Crohn Disease (CD): a potential role of exclusion diet [...].

Patient Nutrition and Probiotic Therapy in COVID-19: What Do We Know in 2021?

BACKGROUND: The main nutritional consequences of COVID-19 include reduced food intake, hypercatabolism, and rapid muscle wasting. Some studies showed that malnutrition is a significant problem among patients hospitalized due to COVID-19 infection, and the outcome of patients with SARS-CoV-2 is strongly associated with their nutritional status. The purpose of this study was to collect useful information about the possible elements of nutritional and probiotic therapy in patients infected with the SARS-CoV-2 virus. METHODS: A narrative review of the literature, including studies published up to 13 September 2021. RESULTS: Probiotics may support patients by inhibiting the ACE2 receptor, i.e., the passage of the virus into the cell, and may also be effective in suppressing the immune response caused by the proinflammatory cytokine cascade. In patients' diet, it is crucial to ensure an adequate intake of micronutrients, such as omega-3 fatty acids (at 2-4 g/d), selenium (300-450 µg/d) and zinc (30-50 mg/d), and vitamins A (900-700 µg/d), E (135 mg/d), D (20,000-50,000 IU), C (1-2 g/d), B6, and B12. Moreover, the daily calorie intake should amount to ≥1500-2000 with 75-100 g of protein. CONCLUSION: In conclusion, the treatment of gut dysbiosis involving an adequate intake of prebiotic dietary fiber and probiotics could turn out to be an immensely helpful instrument for immunomodulation, both in COVID-19 patients and prophylactically in individuals with no history of infection.

Gut Microbiome Modulation and Faecal Microbiota Transplantation Following Allogenic Hematopoietic Stem Cell Transplantation.

Nowadays, allogenic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy that is mainly recommended for hematologic malignancies. However, complications (such as graft-versus-host disease, mucositis, disease relapse, and infections) associated with the HSCT procedure contribute to the development of gut microbiota imbalance, gut-barrier disruption, and increased intestinal permeability. In the present narrative review, the crosstalk between gut microbiota products and intestinal homeostasis is discussed. Notably, gut-microbiota-related aspects have an impact on patients' clinical outcomes and overall survival. In accordance with the most recent published data, gut microbiota is crucial for the treatment effectiveness of many diseases, not only gastrointestinal cancers but also hematologic malignancies. Therefore, it is necessary to indicate a therapeutic method allowing to modulate gut microbiota in HSCT recipients. Currently, fecal microbiota transplantation (FMT) is the most innovative method used to alter/restore gut microbiota composition, as well as modulate its activity. Despite the fact that some previous data have shown promising results, the knowledge regarding FMT in HSCT is still strongly limited, except for the treatment of Clostridium difficile infection. Additionally, administration of prebiotics, probiotics, synbiotics, and postbiotics can also modify gut microbiota; however, this strategy should be considered carefully due to the high risk of fungemia/septicemia (especially in case of fungal probiotics).

Gut Microbiota Modulation in the Context of Immune-Related Aspects of Lactobacillus spp. and Bifidobacterium spp. in Gastrointestinal Cancers.

Accumulating evidence has revealed the critical roles of commensal microbes in cancer progression and recently several investigators have evaluated the therapeutic effectiveness of targeting the microbiota. This gut microbiota-related approach is especially attractive in the treatment of gastrointestinal cancers. Probiotics supplementation is a microbiota-targeted strategy that appears to improve treatment efficacy; Lactobacillus spp. and Bifidobacterium spp. are among the most commonly used probiotic agents. These bacteria seem to exert immunomodulatory effects, impacting on the immune system both locally and systemically. The gut microbiota are able to affect the efficiency of immunotherapy, mainly acting as inhibitors at immune checkpoints. The effects of immunotherapy may be modulated using traditional probiotic strains and/or next generation probiotics, such as Akkermansia municiphila. It is possible that probiotics might enhance the efficiency of immunotherapy based on PD-1/PD-L1 and CTLA-4 but more data are needed to confirm this speculation. Indeed, although there is experimental evidence for the efficacy of several strains, the health-promoting effects of numerous probiotics have not been demonstrated in human patients and furthermore the potential risks of these products, particularly in oncologic patients, are rarely mentioned.