Microbiota-Gastric Cancer Interactions and the Potential Influence of Nutritional Therapies.

Gastric cancer (GC) is one of the most common causes of cancer deaths, and GC treatments represent a large area of research. Although initially regarded as a sterile organ and unsuitable for microbial communities, the discovery of Helicobacter pylori made us realize that some microbes can colonize the stomach. In recent years, growing interest in gastric bacteria has expanded to the gut microbiota and, more recently, to the oral microbiota. Indeed, the oral-gastric-gut microbiota axis may play a crucial role in maintaining homeostasis, while changes in microbiota composition in GC patients can influence clinical outcomes. On the one hand, the microbiota and its metabolites may significantly influence the progression of GC, while anti-GC treatments such as gastrectomy and chemotherapy may significantly impact the oral-gastric-gut microbiota axis of GC patients. In this context, the role of nutritional therapies, including diet, prebiotics, and probiotics, in treating GC should not be underestimated. Wit this review, we aim to highlight the main role of the gastric, oral, and gut microbiota in GC onset and progression, representing potential future biomarkers for early GC detection and a target for efficient nutritional therapies during the course of GC.

Leptin-mediated meta-inflammation may provide survival benefit in patients receiving maintenance immunotherapy for extensive-stage small cell lung cancer (ES-SCLC).

BACKGROUND: Only few ES-SCLC patients experience long-term survival benefit by maintenance IT. Adipokines-induced metabolic meta-inflammation has been related to enhanced responsiveness to IT in obese patients; however, their prognostic role in SCLC is currently controversial. METHODS: Pre-treatment CT scan was used for determining distribution of abdominal adiposity, and blood samples were collected at fasting for measuring glycemia, insulin, ghrelin, leptin and adipokines (TNF-α, IFN-γ, IL-6 and MCP-1). Patients with known history of DM type II or metabolic syndrome with HOMA index > 2.5 were considered insulin resistant (IR). RESULTS: In ES-SCLC pts receiving maintenance IT, increased leptin concentration and higher leptin/visceral adipose tissue (VAT) ratio were significantly associated with prolonged PFS. By applying a hierarchical clustering algorithm, we identified a cluster of patients characterized by higher leptin values and lower pro-inflammatory cytokines (TNF-α, IFN-γ and IL-6) who experienced longer PFS (13.2 vs 8.05 months; HR: 0.42 [0.18-0.93] p = 0.02) and OS (18.04 vs 12.09 mo; HR: 0.53 [0.25-1.29] p = 0.07). CONCLUSIONS: Adipokines can play a crucial role to determining effectiveness of anti-cancer immunotherapy. The role of metabolic immune dysfunctions needs further pre-clinical validation and is currently investigated in the larger prospective cohort.

Metabolic Disorders and Psoriasis: Exploring the Role of Nutritional Interventions.

(1) Background: Psoriasis is a chronic autoimmune disease with a close relationship with metabolic diseases such as obesity, diabetes, and dyslipidemia. The aim of this review was to identify the relationship between psoriasis, metabolic diseases, and dietetic therapies. According to recent findings, there is a strong association between psoriasis and obesity as well as vitamin D and micronutrient deficiencies. (2) Methods: This review was conducted via PubMed, aiming to search for studies involving psoriasis linked with metabolic disorders or with nutritional treatments. (3) Results: Our review shows that a healthy lifestyle can positively influence the course of the disease. The maintaining of a proper body weight together with physical activity and good nutritional choices are associated with an improvement in psoriasis severity. A Mediterranean diet rich in fiber, vitamins, and polyphenols may indeed be a strategy for controlling psoriasis symptoms. The effectiveness of this diet lies not only in its anti-inflammatory power, but also in its ability to favorably influence the intestinal microbiota and counteract dysbiosis, which is a risk factor for many autoimmune diseases. (4) Conclusions: In synergy with standard therapy, the adoption of an appropriate diet can be recommended to improve the clinical expression of psoriasis and reduce the incidence of comorbidities.

Short-Chain Fatty-Acid-Producing Bacteria: Key Components of the Human Gut Microbiota.

Short-chain fatty acids (SCFAs) play a key role in health and disease, as they regulate gut homeostasis and their deficiency is involved in the pathogenesis of several disorders, including inflammatory bowel diseases, colorectal cancer, and cardiometabolic disorders. SCFAs are metabolites of specific bacterial taxa of the human gut microbiota, and their production is influenced by specific foods or food supplements, mainly prebiotics, by the direct fostering of these taxa. This Review provides an overview of SCFAs' roles and functions, and of SCFA-producing bacteria, from their microbiological characteristics and taxonomy to the biochemical process that lead to the release of SCFAs. Moreover, we will describe the potential therapeutic approaches to boost the levels of SCFAs in the human gut and treat different related diseases.

Polypharmacy and malnutrition in older people: A narrative review.

Polypharmacy is the simultaneous use of multiple medicines, usually more than five. Polypharmacy is highly prevalent among older individuals and is associated with several adverse health outcomes, including frailty. The role of polypharmacy in nutritional status seems to be crucial: although a clear association between polypharmacy and malnutrition has been widely reported in older people, the magnitude of the effect of increased number of drugs in combination with their type on the risk for malnutrition remains to be largely explored. Therefore, this review aims to discuss the association between polypharmacy and malnutrition in older people and to provide suggestions for its management. Polypharmacy is prevalent among malnourished frail patients, and the relative contribution of comorbidities and polypharmacy to malnutrition is difficult to be determined. Several mechanisms by which commonly used medications have the potential to affect nutritional status have been identified and described. Deprescribing (i.e., a systematic process of identification and discontinuation of drugs or a reduction of drug regimens) could be an essential step for minimizing the effects of polypharmacy on malnutrition. In this regard, the literature suggests that in older patients taking several medications, the best method to solve this problem is the comprehensive geriatric assessment, based on a holistic approach, including drug review, to find potential unnecessary and inappropriate medications. Nutritional and deprescribing interventions must be tailored to patient needs and to the local context to overcome barriers when applied in different settings.

Dynamics of liver stiffness predicts complications in patients with HCV related cirrhosis treated with direct-acting antivirals.

BACKGROUND: Direct acting antivirals(DAAs) are effective in reducing inflammatory ant fibrotic markers in patients with chronic hepatitis C virus(HCV) infection and to prevent liver-related complications. Two-dimensional shear wave elastography(2D-SWE) is an effective technique for the assessment of liver fibrosis. AIM: To evaluate changes in liver stiffness(LS) in HCV cirrhotic patients undergoing DAA therapy and to identify non-invasive parameters that predict the occurrence of liver-related events. METHODS: We enrolled 229 patients who received DAAs between January 2015 and October 2018. Ultrasound parameters and laboratory data were assessed before treatment and 24(T1) and 48(T2) weeks after end of treatment. Patients were followed up every 6 months to evaluate the development of HCC and other liver related complications. Multiple Cox regression analysis was used to determine parameters associated with the development of complications. RESULTS: Model for End-stage Liver Disease(MELD) score(HR 1.16; CI 95% 1.01-1.33; p = 0.026) and a change in LS at T2(1-year Delta LS) < 20%(HR 2.98; CI 95% 1.01-8.1; p = 0.03) were independently associated with HCC risk. One-year Delta-LS <20% was independently associated with the development of ascites(HR 5.08; CI 95% 1.03 - 25.14; p = 0.04). CONCLUSIONS: Dynamic changes of 2D-SWE-measured LS after DAA therapy may be a useful tool to identify patients who are at higher risk of liver related complications.

The role of diet in shaping human gut microbiota.

Gut microbiota plays a fundamental role within human health, and exerts key functions within the human body. Diet is one of the most powerful modulators of gut microbiota functions and composition. This complex interplay involves also the immune system and the intestinal barrier, highlighting the central role of diet in the pathogenesis and treatment of multiple diseases. In this review article we will paint the landscape of the effects of specific dietary nutrients, and of the detrimental or beneficial outcomes of different dietary patterns, on the composition of human gut microbiota. Moreover, we will discuss the potential application of diet as a therapeutic modulator of gut microbiota, including cutting-edge ways of exploitation, including the use of dietary components as adjuvants to promote microbial engraftment after fecal microbiota transplantation, or personalized nutritional approaches, targeted to the patient microbiome.

Special Issue "Gastrointestinal Microbiota and Gut Barrier Impact Human Health and Disease": Editorial.

The increasing incidence of non-communicable diseases is a worldwide public health issue, and the role of gut microbiota is becoming evident [...].

COntrolling NUTritional Status (CONUT) as Predictive Score of Hospital Length of Stay (LOS) and Mortality: A Prospective Cohort Study in an Internal Medicine and Gastroenterology Unit in Italy.

BACKGROUND: Hospital malnutrition affects nearly 30% of patients in medical wards and correlates with worse outcomes. An early assessment is necessary to stratify the risk of short-term outcomes and mortality. The predictive role of COntrolling NUTritional status (CONUT) score in this context has not yet been elucidated in Western countries. We aimed to test CONUT at admission as a predictive score of hospital outcomes, in an Internal Medicine and Gastroenterology Department of an Italian Tertiary Care University hospital. METHODS: We prospectively enrolled patients admitted to our center, stratifying them into the four CONUT classes (normal = 0-1; mild = 2-4; moderate = 5-8; severe = 9-12 points) according to serum albumin (g/dL), total lymphocyte count (/mm3), and total cholesterol (mg/dL); the primary outcome measure was length of stay (LOS) and the secondary one was in-hospital mortality. RESULTS: Out of a total of 203 patients enrolled, 44 (21.7%) patients had a normal status (0-1), 66 (32.5%) had a mild impairment (2-4), 68 (33.5%) had a moderate impairment (5-8), and 25 (12.3%) a severe impairment (9-12). The mean LOS was 8.24 ± 5.75 days; nine patients died. A moderate-severe CONUT correlated with a higher LOS at the univariate [HR 1.86 (95% CI 13.9-3.47); p < 0.0001] and multivariate analysis [HR 1.52 (95% CI 1.10-2.09); p = 0.01]. The CONUT score was also a predictor of mortality, with an AUC of 0.831 (95% CI 0.680-0.982) and with an optimal cut-off at 8.5 points. Nutritional supplementation within 48 h from admission correlated with lower mortality [OR 0.12 (95% CI 0.02-0.56) p = 0.006]. CONCLUSIONS: CONUT is a reliable and simple predictor of LOS and in-hospital mortality in medical wards.

Sorghum (Sorghum vulgare): an ancient grain, a novel choice for a healthy gluten-free diet.

Celiac disease (CD) is an autoimmune disease related to gluten consumption. To date, the only effective therapy that can reverse symptoms and prevent complications is the gluten-free diet (GFD), which is challenging to maintain and has potential health risks. Identifying foods that can help diversify the GFD and that best match the nutritional needs of people with CD may improve the health and quality of life of celiac patients. This review, conducted through a non-systematic search of the available literature, aims to gather the most recent research on nutritional issues in CD and GFD. Moreover, it highlights how sorghum characteristics could provide health benefits to CD patients that counteract the nutritional problems due to CD and the nutritional consequences of GFD acceptance. Sorghum contains a wide variety of bioactive compounds, such as flavones and tannins, that have shown anti-inflammatory activity in preclinical studies. They can also regulate blood sugar levels and lower cholesterol to reduce the effects of common chronic diseases such as metabolic and cardiovascular diseases. Because it is gluten-free, its use in making foods for celiac patients is increasing, especially in the United States. In conclusion, sorghum is a fascinating grain with nutritional properties and health benefits for supplementing GFD. However, only one study confirms the short-term safety of sorghum inclusion in the GFD, and further long-term studies with a large sample are needed.

Nutritional Interventions during Chemotherapy for Pancreatic Cancer: A Systematic Review of Prospective Studies.

BACKGROUND: Pancreatic cancer incidence is growing, but the prognosis for survival is still poor. Patients with pancreatic cancer often suffer from malnutrition and sarcopenia, two clinical conditions that negatively impact oncological clinical outcomes. The aim of this systematic review was to analyze the impact of different nutritional interventions on clinical outcomes in patients with pancreatic cancer during chemotherapy. METHODS: A systematic review of MedLine, EMBASE, and Web of Science was carried out in December 2022, identifying 5704 articles. Titles and abstracts of all records were screened for eligibility based on inclusion criteria, and nine articles were included. RESULTS: All nine articles included were prospective studies, but a meta-analysis could not be performed due to heterogenicity in nutritional intervention. This Systematic Review shows an improvement in Quality of Life, nutritional status, body composition, oral intake, and Karnofsky Performance Status, following nutritional interventions. CONCLUSIONS: This Systematic Review in pancreatic cancer patients during chemotherapies does not allow one to draw firm conclusions. However, nutritional support in pancreatic cancer patients is advisable to ameliorate oncological care. Further well-designed prospective studies are needed to identify nutritional support's real impact and to establish a reliable way to improve nutritional status of pancreatic cancer patients during chemotherapy.

The Role of Immunonutrition in Patients.

Immunonutrition (IN) is defined as "the use of specific nutritional substrates, called «immunonutrients¼ having the ability of modulating specific mechanisms involved in several immune and inflammatory pathways" [...].

Hospital Services to Improve Nutritional Intake and Reduce Food Waste: A Systematic Review.

BACKGROUND AND AIMS: Patients' nutritional intake is a crucial issue in modern hospitals, where the high prevalence of disease-related malnutrition may worsen clinical outcomes. On the other hand, food waste raises concerns in terms of sustainability and environmental burden. We conducted a systematic review to ascertain which hospital services could overcome both issues. METHODS: A systematic literature search following PRISMA guidelines was conducted across MEDLINE, Web of Science, and Scopus for randomised controlled trials (RCTs) and observational studies comparing the effect of hospital strategies on energy intake, protein intake, and plate/food waste. The quality of included studies was assessed using the Newcastle-Ottawa Scale for cohort studies and the Cochrane Risk of Bias tool from the Cochrane Handbook for Systematic Reviews of Interventions for RCTs. RESULTS: Nineteen studies were included, assessing as many hospital strategies such as food service systems-including catering and room service-(n = 9), protected mealtimes and volunteer feeding assistance (n = 4), food presentation strategies (n = 3), nutritional counseling and education (n = 2), plant-based proteins meal (n = 1). Given the heterogeneity of the included studies, the results were narratively analysed. CONCLUSIONS: Although the results should be confirmed by prospective and large sample-size studies, the personalisation of the meal and efficient room service may improve nutritional intake while decreasing food waste. Clinical nutritionist staff-especially dietitians-may increase food intake reducing food waste through active monitoring of the patients' nutritional needs.

Insulin-sensitizing effect and antioxidant action of alpha lipoic acid in oligomenorrheic women with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a low-grade inflammatory disease characterized by anovulation and hyperandrogenism, associated with insulin-resistance. The aim of our study was to investigate the effects of a treatment with alpha-lipoic acid on clinical, endocrine, and metabolic features of women affected by PCOS. METHODS: In this pilot cohort study, 60 women (30 hyperinsulinemic and 30 normoinsulinemic patients; age 15-34 years) were enrolled and clinical, hormonal, and metabolic parameters were evaluated before and after a six-months treatment with alpha-lipoic acid 800 mg/daily. Investigations were performed during the early follicular phase of the menstrual cycles (spontaneous or progestin-induced cycles): after fasting overnight for 10-12 h, blood samples were collected for hormonal and metabolic assays and oral glucose tolerance test and pelvic ultrasound were performed. Total Antioxidant Capacity was expressed as LAG time. RESULTS: The treatment was able to increase the number of menstrual cycles during the 6 months considered in all patients and to reduce BMI in the normoinsulinemic population. In hyperinsulinemic patients we observed a statistically significant reduction in AUC-I as well as an increase of total antioxidant capacity. CONCLUSIONS: The relevant results in restoring menstrual cyclicity in both groups, in addition to the antioxidant effect, confirm that hyperinsulinemia influences only the metabolic response to the treatment, without predict the ovarian function. Even if alpha-lipoic acid mechanisms of action is not clear and further studies are needed to confirm these results, it could be considered a valid therapeutic alternative to traditional drugs, without side effects as reported.

Noninvasive Evaluation of Clinically Significant Portal Hypertension in Patients with Liver Cirrhosis: The Role of Contrast-Enhanced Ultrasound Perfusion Imaging and Elastography.

BACKGROUND: Hepatic venous pressure gradient (HVPG) is the gold standard for assessing the degree of portal hypertension (PH), but it is not suitable for routine clinical use. The recently developed ultrasonography techniques, dynamic contrast-enhanced ultrasound (D-CEUS) and liver stiffness (LS), have expanded the possibilities for noninvasive evaluation. AIMS: To investigate the usefulness of D-CEUS and elastographic parameters in assessing the presence and degree of PH. METHODS: This is a prospective monocentric study. Patients with liver cirrhosis referred for HVPG measurements underwent hepatic Doppler ultrasound, LS measurement, and D-CEUS with a second-generation contrast agent. Pearson's correlation and a receiver operating characteristic (ROC) curve analysis were performed to assess the role of noninvasive findings in predicting clinically significant PH (CSPH) and severe PH (SPH). RESULTS: 46 consecutive patients (31 men; mean age±SD: 57±11 years) were enrolled. A significant positive correlation was noted between LS and HVPG (r = 0.809, p<0.0001) with an area under the ROC curve of 0.923. A cut-off value of 24.2 kPa best predicted CSPH with a positive predictive value of 85%. Among the D-CEUS features, the area under the ROC curves of liver parenchyma peak intensity (PI-LP) was greater than the other indices both for CSPH and SPH (1.000 and 0.981, respectively). A PI-LP under 23.3 arbitrary units indicated the presence of CSPH with a sensitivity and a specificity of 100%. CONCLUSION: A multimodal ultrasound approach based on D-CEUS and LS might become a reliable predictor of CSPH and SPH and a useful alternative to HVPG.

Predictive and prognostic effect of computed tomography-derived body composition analysis during neoadjuvant chemotherapy for operable and locally advanced breast cancer.

OBJECTIVES: Excess adiposity is associated with several factors involved in carcinogenesis and breast cancer progression. Evidence supporting the role of body composition in breast cancer treatment is promising, but still scanty and mainly focused on adjuvant treatment. The aim of this study was to evaluate the changes in body composition during neoadjuvant chemotherapy and its association with pathologic complete response and survival outcome in patients treated for operable/locally advanced breast cancer. METHODS: A retrospective review of patients with breast cancer treated with neoadjuvant chemotherapy was performed in the Oncology Section of the Department of Medicine, University of Verona between 2014 and 2019. Body composition was evaluated from clinically acquired computed tomography scans at diagnosis and after neoadjuvant chemotherapy. Descriptive statistic was adopted. The associations of body composition measures with pathologic complete response and disease-free survival were analyzed. Kaplan-Meier curves were compared with log-rank analysis. RESULTS: Data from 93 patients were collected. After neoadjuvant chemotherapy, the adipose compound changed significantly across all body mass index categories. Body composition parameters had no significant effect on pathologic complete response. Survival analysis showed that a high gain of visceral adipose tissue during neoadjuvant chemotherapy was associated with shorter disease-free survival (hazard ratio, 10.2; P = 0.026). In particular, disease-free survival was significantly worse in patients who gained ≥10% of visceral adipose tissue compared with patients who gained <10% of visceral adipose tissue (5-y disease-free survival 71.4 versus 96.3, P = 0.009, respectively). CONCLUSIONS: Our results indicated that neoadjuvant chemotherapy significantly affects body composition, which seems to have an effect on survival outcome of breast cancer, highlighting the relevance of the body composition assessment when estimating treatment outcomes.

The Role of Gut Microbiota and Leaky Gut in the Pathogenesis of Food Allergy.

Food allergy (FA) is a growing public health concern, with an increasing prevalence in Western countries. Increasing evidence suggests that the balance of human gut microbiota and the integrity of our intestinal barrier may play roles in the development of FA. Environmental factors, including industrialization and consumption of highly processed food, can contribute to altering the gut microbiota and the intestinal barrier, increasing the susceptibility to allergic sensitization. Compositional and functional alterations to the gut microbiome have also been associated with FA. In addition, increased permeability of the gut barrier allows the translocation of allergenic molecules, triggering Th2 immune responses. Preclinical and clinical studies have highlighted the potential of probiotics, prebiotics, and postbiotics in the prevention and treatment of FA through enhancing gut barrier function and promoting the restoration of healthy gut microbiota. Finally, fecal microbiota transplantation (FMT) is now being explored as a promising therapeutic strategy to prevent FA in both experimental and clinical studies. In this review article, we aim to explore the complex interplay between intestinal permeability and gut microbiota in the development of FA, as well as depict potential therapeutic strategies.

Impact of Diet on Gut Microbiota Composition and Microbiota-Associated Functions in Heart Failure: A Systematic Review of In Vivo Animal Studies.

Heart failure (HF) represents a cardiovascular disease with high mortality and morbidity. The latest evidence shows that changes in the composition of the gut microbiota might play a pivotal role in the prevention and management of HF. This systematic review aims at assessing the potential associations between the diet, gut microbiota, and derived metabolites with the outcomes of HF. A systematic literature search was performed up to July 2022 on the PubMed, Web of Science, and Scopus databases. The PRISMA guidelines were followed when possible. The risk of bias was assessed with the SYRCLE and ARRIVE tools. A total of nine pre-clinical studies on animal models, with considerable heterogeneity in dietary interventions, were included. High-fiber/prebiotic diets (n = 4) and a diet rich in polyphenols (n = 1) modified the gut microbiota composition and increased microbial metabolites' activities, linked with an improvement in HF outcomes, such as a reduction in systolic blood pressure, cardiac hypertrophy, and left ventricular thickness. A high-fat diet (n = 2) or a diet rich in choline (n = 2) induced an increase in TMAO and indole derivative production associated with a decrease in cardiac function, systemic endotoxemia, and inflammation and an increase in cardiac fibrosis and cardiac remodeling. Although results are retrieved from animal studies, this systematic review shows the key role of the diet-especially a high-fiber and prebiotic diet-on gut microbial metabolites in improving HF outcomes. Further studies on human cohorts are needed to identify personalized therapeutic dietary interventions to improve cardiometabolic health.

Food Emulsifiers and Metabolic Syndrome: The Role of the Gut Microbiota.

The use of emulsifiers in processed foods and the rapid epidemic development of metabolic syndrome in Western countries over the past 20 years have generated growing interest. Evidence for the role of emulsifiers in metabolic syndrome through gut microbiota has not been clearly established, thus making it challenging for clinical nutritionists and dietitians to make evidence-based associations between the nature and the quantity of emulsifiers and metabolic disorders. This narrative review summarizes the highest quality clinical evidence currently available about the impact of food emulsifiers on gut microbiota composition and functions and the potential development of metabolic syndrome. The state-of-the-art of the different common emulsifiers is performed, highlighting where they are present in daily foods and their roles. Recent findings of in vitro, in vivo, and human studies assessing the effect of different emulsifiers on gut microbiota have been recently published. There is some progress in understanding how some food emulsifiers could contribute to developing metabolic diseases through gut microbiota alterations while others could have prebiotic effects. However, there are still many unanswered questions regarding daily consumption amounts and the synergic effects between emulsifiers' intake and responses by the microbial signatures of each individual.

Body composition and immunonutritional status in patients treated with pressurized intraperitoneal aerosol chemotherapy (PIPAC) for gastrointestinal peritoneal metastases: a prospective single-center analysis.

Objectives: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel drug administration method with promising efficacy for the treatment of peritoneal metastases (PM). This study aimed to evaluate the prognostic value of an immunonutritional assessment on the feasibility, safety, and survival in this setting. Methods: Data of PM patients undergoing PIPAC between September 2018 and May 2020 were prospectively recorded. A CT scan-derived body composition assessment was performed for each patient. Results: Fifty-one patients were enrolled, of which 30 (58%) underwent multiple PIPAC cycles, with a pathological response rate of 55%. Prognostic nutritional index (PNI) and neutrophil-to-lymphocytes predicted completion of more than one PIPAC cycle, with a cut off of 36.5 and 4.8 respectively. Muscle attenuation and body fat tissues were associated with pathological response. At multivariate Cox regression analysis, only the presence of a low PNI (HR 2.41, 95% CI 1.08-5.46) was significantly associated with a worse OS. Conclusions: A pretreatment immunonutritional assessment may provide valuable information for PIPAC patients' selection and survival, while body composition parameters are able to predict pathological response. Further larger studies are needed to validate the role of these biomarkers in tailoring the treatment and monitoring PM patients undergoing PIPAC.