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.

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.

Datterino Trial: A Double Blind, Randomized, Controlled, Crossover, Clinical Trial on the Use of Hydroponic Cultivated Tomato Sauce in Systemic Nickel Allergy Syndrome.

A low-nickel (Ni) diet, a key treatment for Systemic Nickel Allergy Syndrome (SNAS), is difficult in the long term and strongly impacts quality of life (QoL). Hydroponic agriculture could be an alternative to allow the reintroduction of tomato, an essential food in the global diet. In a first interventional, randomized, double-blind, single-center crossover study, we compared the possible effects of eating tomato puree deriving from hydroponic agriculture versus tomato puree from conventional cultivation, collecting data on subjective control of SNAS symptoms, adherence to treatment, and impact on QoL. Thirty subjects were randomly assigned to one of the following treatment groups: (1) a 12-week low-Ni diet plus 100% Italian Datterino tomato puree deriving from hydroponic technology; (2) a 12-week low-Ni diet plus 100% Italian Datterino tomato puree deriving from conventional cultivation. Then, after a 2-week washout period on the low-Ni diet, each patient crossed over to the other treatment. Patients reported lower symptom scores after eating Datterino tomato puree deriving from hydroponic technology; specifically, bloating (p = 0.0111, p = 0.0060), flatulence (p = 0.0090), abdominal cramps (p = 0.0207), constipation (p = 0.0395), and diarrhea (p = 0.0105). Overall, the adherence rate was high for both treatment arms. At baseline, QoL was poor, but significant improvement was observed after two treatments. In our study, precision medicine and precision agriculture merge in a holistic approach to the challenges of food allergies.

Lipid-Enriched Parenteral Nutrition and Bloodstream Infections in Hospitalized Patients: Is It a Real Concern?

Today, few clinicians are still convinced that lipids are sepsis risk factors in patients receiving parenteral nutrition. This dogma is principally based on old literature. This review deals with the most recent literature search that provided up-to-date data over the past ten years. Systematic research was performed on Pubmed, MEDLINE, and Web of Science. The recent evidence does not justify the exclusion of lipid emulsions in patients receiving parenteral nutrition for fear of bloodstream infection risk. Moreover, lipids represent a substantial proportion of the energy source providing essential fatty acids, potentially improving clinical outcomes in patients often malnourished. Understanding the actual risk factors of sepsis during parenteral nutrition is necessary to optimize patient nutritional status and care and avoid essential fatty acid deficiency. There is an urgent need to make updated nutrition training available at all levels of medical education.

The prognostic value of skeletal muscle index on clinical and survival outcomes after cytoreduction and HIPEC for peritoneal metastases from colorectal cancer: A systematic review and meta-analysis.

BACKGROUND: Cytoreductive surgery (CRS) and hypertermic intraperitoneal chemotherapy (HIPEC) represent the most effective strategy to manage peritoneal metastases (PM). This systematic review and meta-analysis aimed to assess the impact of body composition on clinical outcomes in patients with PM. METHODS: A systematic literature search was performed using Medline, Web of Science and EMBASE databases from inception to the 20st August 2020. Data were independently extracted by 3 authors. Newcastle-Ottawa Scale was used to assess quality and risk of bias of studies. Pooled analyses were performed using Mantel-Haenszel method to estimate overall effect size with mean differences or odd ratios (ORs) and 95% confidence interval (CI). The primary outcome was postoperative complication (POC) rate, while secondary outcomes were severe POC and postoperative mortality. RESULTS: A total of 4 studies were included in the systematic review and meta-analysis, including 582 patients. A significant association between low skeletal muscle mass and POC was found (OR 1.45, 95% CI 1.04 to 2.03; p = 0.03), while no differences were found in terms operative time, estimated blood loss, length of hospital stay, and postoperative mortality (p > 0.05). CONCLUSIONS: Low skeletal muscle mass at diagnosis is a valid prognostic factor for POC development in colorectal and PM patients undergoing CRS. Prospective and larger studies are needed to better investigate the role of CT scan derived body composition and to understand how to implement this tool in clinical practice.

Neoadjuvant treatment: A window of opportunity for nutritional prehabilitation in patients with pancreatic ductal adenocarcinoma.

Patients affected by pancreatic ductal adenocarcinoma (PDAC) frequently present with advanced disease at the time of diagnosis, limiting an upfront surgical approach. Neoadjuvant treatment (NAT) has become the standard of care to downstage non-metastatic locally advanced PDAC. However, this treatment increases the risk of a nutritional status decline, which in turn, may impact therapeutic tolerance, postoperative outcomes, or even prevent the possibility of surgery. Literature on prehabilitation programs on surgical PDAC patients show a reduction of postoperative complications, length of hospital stay, and readmission rate, while data on prehabilitation in NAT patients are scarce and randomized controlled trials are still missing. Particularly, appropriate nutritional management represents an important therapeutic strategy to promote tissue healing and to enhance patient recovery after surgical trauma. In this regard, NAT may represent a new interesting window of opportunity to implement a nutritional prehabilitation program, aiming to increase the PDAC patient's capacity to complete the planned therapy and potentially improve clinical and survival outcomes. Given these perspectives, this review attempts to provide an in-depth view of the nutritional derangements during NAT and nutritional prehabilitation program as well as their impact on PDAC patient outcomes.

Nutritional Interventions Targeting Gut Microbiota during Cancer Therapies.

The gut microbiome is increasingly being recognized for its influence on intestinal and extra-intestinal disorders such as cancer. Today, diet is the most studied environmental modulator of gut microbiota, capable of altering or improving it in terms of richness and diversity. Recent evidence from several preclinical and clinical trials suggested that gut microbiota composition could modulate cancer therapies (toxicities, treatment responses) and vice versa. This review highlights the latest research on the bidirectional associations between gut microbiota and cancer. We also dissect the role of gut microbiota during cancer therapies in terms of toxicity and treatment response and, in turn, how cancer therapies could impact gut microbiota composition and functions. In this context, we summarize the state-of-the-art research regarding the role of various nutritional interventions-prebiotics, dietary strategies, and dietary restrictions-as cutting-edge possibilities to modulate gut microbiota during cancer therapies.

Prognostic value of skeletal muscle mass during tyrosine kinase inhibitor (TKI) therapy in cancer patients: a systematic review and meta-analysis.

Low muscle mass has been associated with worse clinical outcomes in various cancers. This work investigated whether, during tyrosine kinases inhibitors (TKIs) therapy, low muscle mass was associated with treatment toxicity and survival outcomes. A systematic literature search was performed in Pubmed, Web of Science, and Scopus databases from inception to June 2020, based on fixed inclusion and exclusion criteria. Effect sizes were estimated with hazard ratios (HR) and odds ratios (OR) with 95% confidence interval (CI) and heterogeneity was assessed by measuring inconsistency (I2) based on the Chi squared test. A total of 24 retrospective studies were identified, enrolling patients treated with sorafenib (n = 12), sunitinib (n = 6), lenvatinib (n = 3), regorafenib (n = 2), gefitinib (n = 1), imatinib (n = 1), and pazopanib (n = 1). Thirteen studies were deemed eligible for pooled analyses. Meta-analyses found a significant effect of low muscle mass on dose-limiting toxicity (DLT) (OR 2.40, 95% CI 1.26-4.58, p = 0.008, I2 = 51%) in patients treated with TKI therapy. A subgroup analysis by treatment showed an association between DLT and low muscle during sorafenib or sunitinib, although not significant. A significant association between low skeletal muscle index and poorer overall survival was observed in HCC patients treated with sorafenib (HR 1.45, 95% CI 1.07-1.96, p = 0.02). For other TKIs, although some results showed an association between low muscle mass and worse outcomes, the number of studies for each TKI therapy was too small to reach conclusions. Skeletal muscle mass could influence the prognosis of some TKI-treated patients. This effect is demonstrated in sorafenib-treated HCC patients but remains almost unexplored in other cancer patients undergoing TKI therapy. Further prospective studies with large sample size and sufficient follow-up are needed to clarify the role of muscle mass in the metabolism of TKI-based cancer treatment, and its association with toxicity and survival.

Food Additives, Gut Microbiota, and Irritable Bowel Syndrome: A Hidden Track.

The interactions between diet, gut microbiota, and irritable bowel syndrome (IBS) have many complex mechanisms that are not fully understood. Food additives are one component of the modern human diet that deserves attention from science and government policies. This review aims at identifying the current knowledge about the impact of food additives on gut microbiota and their potential role in the development of IBS. To date, few data on the effect of food additives on gut microbiota in IBS patients are available. However, exposure to food additives could induce the dysbiosis and dysregulation of gut homeostasis with an alteration of the gut barrier and activation of the immune response. These microbial changes could exacerbate the gut symptoms associated with IBS, such as visceral pain, low-grade inflammation, and changes in bowel habits. Some additives (polyols) are excluded in the low fermentable oligo-, di- and monosaccharide, and polyol (FODMAP), diets for IBS patients. Even if most studies have been performed in animals, and human studies are required, many artificial sweeteners, emulsifiers, and food colorants could represent a potential hidden driver of IBS, through gut microbiota alterations. Consequently, food additives should be preventively avoided in the diet as well as dietary supplements for patients with IBS.

Skeletal Muscle Loss during Multikinase Inhibitors Therapy: Molecular Pathways, Clinical Implications, and Nutritional Challenges.

In cancer patients, loss of muscle mass is significantly associated with low tolerability of chemotherapy and poor survival. Despite the great strides in the treatment of cancer, targeted therapies such as tyrosine kinase inhibitors (TKIs) could exacerbate muscle wasting. Over recent years, the impact of skeletal muscle loss during TKI therapy on clinical outcomes has been in the spotlight. In this review, we focus on the different molecular pathways of TKIs potentially involved in muscle wasting. Then, we report the results of the studies assessing the effects of different TKI therapies-such as sorafenib, regorafenib, sunitinib, and lenvatinib-on muscle mass, and highlight their potential clinical implications. Finally, we discuss an integrative nutritional approach to be adopted during TKI treatment. The assessment of muscle mass from computerized tomography imaging could be helpful in predicting toxicity and prognosis in patients treated with TKI such as sorafenib. Early recognition of low muscle mass and effective personalized nutritional support could prevent or attenuate muscle mass wasting. However, the role of nutrition is still overlooked, and future clinical trials are needed to find the optimal nutritional support to countermeasure muscle mass depletion during TKI therapy.

The impact of personalized nutritional support on postoperative outcome within the enhanced recovery after surgery (ERAS) program for liver resections: results from the NutriCatt protocol.

BACKGROUND: Malnutrition in liver surgery is correlated with higher postoperative complications and longer length of hospital stay (LOHS), the same items that ERAS programs try to optimize. However, to date, standardized dietary protocols have not been defined within ERAS programs. Aim of this study was to evaluate the impact on LOHS and postoperative complications, of a personalized nutritional protocol (NutriCatt) with diet and oral branched-chain amino acid (BCAA) supplementation, adopted within the ERAS program. METHODS: 1960 consecutive liver resections were performed from January 2000 to September 2018. EXCLUSION CRITERIA: perihilar cholangiocarcinoma, simultaneous colorectal and liver resections. Four groups for analysis: resections before 2009 (1st period); from 2009 to 2016 (2nd period, including laparoscopic resections); between 2016 and September 2017 (ERAS); after September 2017 (ERAS + NutriCatt). RESULTS: LOHS declined (p < 0.0001), from a median of 10 days (1st period) to 8, 7 and 6 in 2nd period, ERAS and ERAS + NutriCatt groups, respectively. At multivariable analysis for risk of LOHS > 8 days, the 2nd period, ERAS and ERAS + NutriCatt groups showed a protective effect. These results were confirmed for both minor and major resections. LOHS was significantly lower in ERAS + Nutricatt group than in ERAS group, without increasing risk of postoperative complications, although the rate of laparoscopic resections was similar in these two groups and complexity of liver resections was significantly higher in the last period. CONCLUSIONS: Adoption of a personalized nutritional protocol with BCAA supplementation within the ERAS program for liver resections was a safe and effective approach that may impact on reducing the LOHS.

The Role of Diet, Micronutrients and the Gut Microbiota in Age-Related Macular Degeneration: New Perspectives from the Gut⁻Retina Axis.

Age-related macular degeneration (AMD) is a complex multifactorial disease and the primary cause of legal and irreversible blindness among individuals aged ≥65 years in developed countries. Globally, it affects 30⁻50 million individuals, with an estimated increase of approximately 200 million by 2020 and approximately 300 million by 2040. Currently, the neovascular form may be able to be treated with the use of anti-VEGF drugs, while no effective treatments are available for the dry form. Many studies, such as the randomized controlled trials (RCTs) Age-Related Eye Disease Study (AREDS) and AREDS 2, have shown a potential role of micronutrient supplementation in lowering the risk of progression of the early stages of AMD. Recently, low-grade inflammation, sustained by dysbiosis and a leaky gut, has been shown to contribute to the development of AMD. Given the ascertained influence of the gut microbiota in systemic low-grade inflammation and its potential modulation by macro- and micro-nutrients, a potential role of diet in AMD has been proposed. This review discusses the role of the gut microbiota in the development of AMD. Using PubMed, Web of Science and Scopus, we searched for recent scientific evidence discussing the impact of dietary habits (high-fat and high-glucose or -fructose diets), micronutrients (vitamins C, E, and D, zinc, beta-carotene, lutein and zeaxanthin) and omega-3 fatty acids on the modulation of the gut microbiota and their relationship with AMD risk and progression.

Dietary Conjugated Linoleic Acid-Enriched Cheeses Influence the Levels of Circulating n-3 Highly Unsaturated Fatty Acids in Humans.

n-3 highly unsaturated fatty acids (n-3 HUFA) directly and indirectly regulate lipid metabolism, energy balance and the inflammatory response. We investigated changes to the n-3 HUFA score of healthy adults, induced by different types and amounts of conjugated linoleic acid (CLA)-enriched (ENCH) cheeses consumed for different periods of time, compared to dietary fish oil (FO) pills (500 mg, each containing 100 mg of eicosapentaenoic and docosahexaenoic acids­EPA+DHA) or α-linolenic acid (ALA)-rich linseed oil (4 g, containing 2 g of ALA). A significant increase in the n-3 HUFA score was observed, in a dose-dependent manner, after administration of the FO supplement. In terms of the impact on the n-3 HUFA score, the intake of ENCH cheese (90 g/day) for two or four weeks was equivalent to the administration of one or two FO pills, respectively. Conversely, the linseed oil intake did not significantly impact the n-3 HUFA score. Feeding ENCH cheeses from different sources (bovine, ovine and caprine) for two months improved the n-3 HUFA score by increasing plasma DHA, and the effect was proportional to the CLA content in the cheese. We suggest that the improved n-3 HUFA score resulting from ENCH cheese intake may be attributed to increased peroxisome proliferator-activated receptor alpha (PPAR-α) activity. This study demonstrates that natural ENCH cheese is an alternative nutritional source of n-3 HUFA in humans.

Application of the Co-culture Membrane System Pointed to a Protective Role of Catestatin on Hippocampal Plus Hypothalamic Neurons Exposed to Oxygen and Glucose Deprivation.

Depletion of oxygen and glucose even for brief periods is sufficient to cause cerebral ischemia, which is a predominant worldwide cause of motor deficits with the reduction of life quality and subsequently death. Hence, more insights regarding protective measures against ischemic events are becoming a major research goal. Among the many neuronal factors, N-methyl-D-aspartate receptors (NMDAR), orexinergic neuroreceptors (ORXR), and sympatho-inhibitory neuropeptide catestatin (CST) are widely involved with ischemic episodes. In this study, it was possible to induce in vitro ischemic conditions of the hamster (Mesocricetus auratus) hippocampal and hypothalamic neuronal cultures, grown on a newly compartmentalized membrane system, via oxygen and glucose deprivation (OGD). These cultures displayed notably differentiated NMDARergic and ORXergic receptor expression activities along with evident brain-derived neurotrophic factor (BDNF) plus orexin A (ORX-A) secretion, especially under co-cultured conditions. Interestingly, addition of CST in OGD-insulted hippocampal cells accounted for upregulated GluN1 and ORX1R transcripts that in the case of the latter neuroreceptor was very strongly (p < 0.001) increased when co-cultured with hypothalamic cells. Similarly, hypothalamic neurons supplied very evident upregulations of GluN1, ORX1R, and above all of GluN2A transcripts along with increased BDNF and ORX-A secretion in the presence of hippocampal cells. Overall, the preferential CST effects on BDNF plus ORX-A production together with altered NMDAR and ORXR levels, especially in co-cultured hypothalamic cells pointed to ORX-containing neurons as major protective constituents against ischemic damages thus opening new scenarios on the cross-talking roles of CST during ischemic disorders.

Metabolism of c9,t11-conjugated linoleic acid (CLA) in humans.

The c9,t11 isomer of conjugated linoleic acid (CLA) is the most abundant CLA form present in the human diet, and is particularly prevalent in milk and dairy products, and is known to exert several health benefits in experimental animal models. A possible mechanism of action of c9,t11CLA relies on its metabolism via desaturases and elongases and partial beta oxidation in peroxisomes. In this study, we aimed to establish plasma incorporation of c9,t11CLA and its downstream metabolites in healthy volunteers after daily dietary intakes of 0.8g, 1.6g or 3.2g of c9,t11CLA in capsule form for two months. Following supplementation, the plasma concentrations of c9,t11CLA and its metabolites conjugated dienes (CD) 18:3 and the beta oxidation product CD 16:2 were incorporated in a linear fashion, while on the other hand CD 20:3 reached a plateau following intakes of 1.6g/d of dietary intake, and was not further increased following higher CLA intakes. We may conclude that supplementation of c9,t11 CLA levels result in linear responses of CLA and its main metabolites in plasma. In addition, only the highest concentration of CLA intake tested (3.2g/d) yielded plasma concentrations of CLA and metabolites close to the range found sufficient to exert nutritional effects in experimental animal models.

Endothelial function in post-menopausal women: effect of folic acid supplementation.

BACKGROUND: Higher than normal homocysteine levels are associated with an increased incidence of adverse cardiovascular events in post-menopausal women, perhaps via hyperhomocysteinaemia-induced vascular endothelial damage. Because folic acid supplementation reduces homocysteine levels, we attempted to evaluate whether folic acid supplementation may affect endothelial function in post-menopausal women. METHODS: Brachial artery flow-mediated dilatation (endothelium-dependent) and nitroglycerin-induced dilatation (endothelium-independent) before and after a methionine load were analysed in 15 healthy post-menopausal women. Plasma levels of folate, homocysteine, glucose, insulin and lipids were measured, as was blood pressure. All studies were repeated after 1 month supplementation with 7.5 mg/day of folic acid. RESULTS: After folate, endothelial function rose 37% over pre-folic acid supplementation value (P < 0.001), and flow-mediated dilation before folic acid was reduced by 62% subsequent to methionine loading (P < 0.0001); this reduction was still present after folic acid, but was only 19% (P < 0.001). Nitroglycerin-induced dilatation did not change in response to methionine loading before or after folic acid supplementation. Among the other cardiovascular risk factors studied, only high-density lipoprotein (HDL)-cholesterol and low-density lipoprotein (LDL)-cholesterol showed significant changes after folic acid supplementation, with a 6% increase (P < 0.03) and a 9% decrease (P < 0.03) respectively. CONCLUSIONS: Although preliminary, these results indicate that folic acid supplementation may improve endothelial function and lipid profile in post-menopausal women, thus contributing to reduce their cardiovascular risk.