Prognostic implications of the arginine metabolism in patients at nutritional risk: A secondary analysis of the randomized EFFORT trial.

BACKGROUND: Arginine, a conditionally essential amino acid, is key component in metabolic pathways including immune regulation and protein synthesis. Depletion of arginine contributes to worse outcomes in severely ill and surgical patient populations. We assessed prognostic implications of arginine levels and its metabolites and ratios in polymorbid medical inpatients at nutritional risk regarding clinical outcomes and treatment response. METHODS: Within this secondary analysis of the randomized controlled Effect of early nutritional support on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT), we investigated the association of arginine, its metabolites and ratios (i.e., ADMA and SDMA, ratios of arginine/ADMA, arginine/ornithine, and global arginine bioavailability ratio) measured on hospital admission with short-term and long-term mortality by means of regression analysis. RESULTS: Among the 231 patients with available measurements, low arginine levels ≤90.05 µmol/l (n = 86; 37 %) were associated with higher all-cause mortality at 30 days (primary endpoint, adjusted HR 3.27, 95 % CI 1.86 to 5.75, p < 0.001) and at 5 years (adjusted HR 1.50, 95 % CI 1.07 to 2.12, p = 0.020). Arginine metabolites and ratios were also associated with adverse outcome, but had lower prognostic value. There was, however, no evidence that treatment response was influenced by admission arginine levels. CONCLUSION: This secondary analysis focusing on medical inpatients at nutritional risk confirms a strong association of low plasma arginine levels and worse clinical courses. The potential effects of arginine-enriched nutritional supplements should be investigated in this population of patients. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov as NCT02517476 (registered 7 August 2015).

Potential Modulation of Inflammation and Physical Function by Combined Probiotics, Omega-3 Supplementation and Vitamin D Supplementation in Overweight/Obese Patients with Chronic Low-Grade Inflammation: A Randomized, Placebo-Controlled Trial.

Obesity is characterized by low-grade inflammation and increased gut permeability. Here, we aim to evaluate the effect of a nutritional supplement on these parameters in subjects with overweight and obesity. A double-blinded, randomized clinical trial was conducted in 76 adults with overweight or obesity (BMI 28 to 40) and low-grade inflammation (high-sensitivity C-reactive protein (hs-CRP) between 2 and 10 mg/L). The intervention consisted of a daily intake of a multi-strain probiotic of Lactobacillus and Bifidobacterium, 640 mg of omega-3 fatty acids (n-3 FAs), and 200 IU of vitamin D (n = 37) or placebo (n = 39), administered for 8 weeks. hs-CRP levels did not change post-intervention, other than an unexpected slight increase observed in the treatment group. Interleukin (IL)-6 levels decreased in the treatment group (p = 0.018). The plasma fatty acid (FA) levels of the arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio and n-6/n-3 ratio (p < 0.001) decreased, and physical function and mobility improved in the treatment group (p = 0.006). The results suggest that hs-CRP may not be the most useful inflammatory marker, but probiotics, n-3 FAs, and vitamin D, as non-pharmaceutical supplements, may exert modest effects on inflammation, plasma FA levels, and physical function in patients with overweight and obesity and associated low-grade inflammation.

ESPEN guideline on Clinical Nutrition in inflammatory bowel disease.

The present guideline is an update and extension of the ESPEN scientific guideline on Clinical Nutrition in Inflammatory Bowel Disease published first in 2017. The guideline has been rearranged according to the ESPEN practical guideline on Clinical Nutrition in Inflammatory Bowel Disease published in 2020. All recommendations have been checked and, if needed, revised based on new literature, before they underwent the ESPEN consensus procedure. Moreover, a new chapter on microbiota modulation as a new option in IBD treatment has been added. The number of recommendations has been increased to 71 recommendations in the guideline update. The guideline is aimed at professionals working in clinical practice, either in hospitals or in outpatient medicine, and treating patients with IBD. General aspects of care in patients with IBD, and specific aspects during active disease and in remission are addressed. All recommendations are equipped with evidence grades, consensus rates, short commentaries and links to cited literature.

Potentially Beneficial Effects on Healthy Aging by Supplementation of the EPA-Rich Microalgae Phaeodactylum tricornutum or Its Supernatant-A Randomized Controlled Pilot Trial in Elderly Individuals.

Dietary supplements that promote healthy aging are mostly warranted in an aging society. Because of age-related risks, anti-inflammatory and anti-oxidative agents such as microalgae are potential candidates for intervention. In a randomized controlled trial, we tested Phaeodactylum tricornutum (PT), a microalgae rich in eicosapentaenoic acid (EPA), carotenoids, vitamins, and ß-glucans, cultured in bioreactors. In this pilot trial, 19 healthy elderly received supplements for two weeks based on either the whole PT (A), the ß-1,3-glucan-rich PT supernatant (SupB), the combination thereof (A+SupB), or a Comparator product (Comp). The primary outcome variable plasma interleukin-6 was reduced after treatment with A+SupB compared to the Comp group (p = 0.04). The mobility parameters 5 s sit-to-stand test (p = 0.04 in the A group) and by trend gait speed (p = 0.08 in the A+SupB diet) were improved compared to Comp. No treatment effects were observed for fatty acids, compared to Comp but omega-6 to -3 fatty acid ratio (p = 0.006) and arachidonic acid/EPA ratio (p = 0.006) were reduced within group A+SupB. Further, the SupB study product reduced faecal zonulin (p = 0.03) compared to the Comp. The data revealed an anti-inflammatory and potentially anti-oxidative effect of particular PT preparations, suggesting that they might be suitable for effects in healthy elderly.

Potential Modulation of Inflammation by Probiotic and Omega-3 Supplementation in Elderly with Chronic Low-Grade Inflammation-A Randomized, Placebo-Controlled Trial.

Probiotic and omega-3 supplements have been shown to reduce inflammation, and dual supplementation may have synergistic health effects. We investigated if the novel combination of a multi-strain probiotic (containing B. lactis Bi-07, L. paracasei Lpc-37, L. acidophilus NCFM, and B. lactis Bl-04) alongside omega-3 supplements reduces low-grade inflammation as measured by high-sensitivity C-reactive protein (hs-CRP) in elderly participants in a proof-of-concept, randomized, placebo-controlled, parallel study (NCT04126330). In this case, 76 community-dwelling elderly participants (median: 71.0 years; IQR: 68.0-73.8) underwent an intervention with the dual supplement (n = 37) or placebo (n = 39) for eight weeks. In addition to hs-CRP, cytokine levels and intestinal permeability were also assessed at baseline and after the eight-week intervention. No significant difference was seen for hs-CRP between the dual supplement group and placebo. However, interestingly, supplementation did result in significant increases in the level of the anti-inflammatory marker IL-10. In addition, dual supplementation increased levels of valeric acid, further suggesting the potential of the supplements in reducing inflammation and conferring health benefits. Together, the results suggest that probiotic and omega-3 dual supplementation exerts modest effects on inflammation and may have potential use as a non-pharmacological treatment for low-grade inflammation in the elderly.

Changes in serum omega fatty acids on a Mediterranean diet intervention in patients with gingivitis: An exploratory study.

BACKGROUND: Omega-6 and omega-3 polyunsaturated fatty acids (PUFAs) are precursors of pro- and anti-inflammatory lipid mediators. Serum PUFA levels could influence the severity of inflammatory oral diseases, such as gingivitis. OBJECTIVE: The study analyzed serum PUFA levels in a six-week randomized controlled trial in individuals on the Mediterranean diet (MedD), associations with the intake of specific foods, and possible correlations with oral inflammatory parameters. METHODS: Data from 37 study participants on either a MedD (MedDG; n = 18) or a "Western diet" in the control group (CG, n = 19) were analyzed. Dental examinations and serum analyses were performed at two time points, T1 (baseline) and T2 (week 6). Serum PUFA status, adherence to the MedD, and data from a Food Frequency Questionnaire were analyzed. RESULTS: Within the MedDG omega-6 fatty acid levels decreased significantly. In the overall sample, the proportional decrease in sites with bleeding on probing correlated weakly to moderately with the decrease in total omega-6 fatty acid level (Spearman's ρ = 0.274) and the decrease in gingival index correlated moderately with the decrease in linoleic acid level (Spearman's ρ = 0.351). Meat and fast-food consumption correlated positively with levels of various omega-6 fatty acids, whereas nut, fish, and dairy product consumption correlated positively with omega-3 levels. CONCLUSION: Adherence to a MedD was associated with a decrease in serum omega-6 levels, which positively affected the omega-6/omega-3 ratio. The MedD associated reduction in serum omega-6 levels may be a mechanism that favorably affects gingival inflammatory parameters.

Elucidating the role of the gut microbiota in the physiological effects of dietary fiber.

BACKGROUND: Dietary fiber is an integral part of a healthy diet, but questions remain about the mechanisms that underlie effects and the causal contributions of the gut microbiota. Here, we performed a 6-week exploratory trial in adults with excess weight (BMI: 25-35 kg/m2) to compare the effects of a high-dose (females: 25 g/day; males: 35 g/day) supplement of fermentable corn bran arabinoxylan (AX; n = 15) with that of microbiota-non-accessible microcrystalline cellulose (MCC; n = 16). Obesity-related surrogate endpoints and biomarkers of host-microbiome interactions implicated in the pathophysiology of obesity (trimethylamine N-oxide, gut hormones, cytokines, and measures of intestinal barrier integrity) were assessed. We then determined whether clinical outcomes could be predicted by fecal microbiota features or mechanistic biomarkers. RESULTS: AX enhanced satiety after a meal and decreased homeostatic model assessment of insulin resistance (HOMA-IR), while MCC reduced tumor necrosis factor-α and fecal calprotectin. Machine learning models determined that effects on satiety could be predicted by fecal bacterial taxa that utilized AX, as identified by bioorthogonal non-canonical amino acid tagging. Reductions in HOMA-IR and calprotectin were associated with shifts in fecal bile acids, but correlations were negative, suggesting that the benefits of fiber may not be mediated by their effects on bile acid pools. Biomarkers of host-microbiome interactions often linked to bacterial metabolites derived from fiber fermentation (short-chain fatty acids) were not affected by AX supplementation when compared to non-accessible MCC. CONCLUSION: This study demonstrates the efficacy of purified dietary fibers when used as supplements and suggests that satietogenic effects of AX may be linked to bacterial taxa that ferment the fiber or utilize breakdown products. Other effects are likely microbiome independent. The findings provide a basis for fiber-type specific therapeutic applications and their personalization. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02322112 , registered on July 3, 2015. Video Abstract.

Chitin-glucan supplementation improved postprandial metabolism and altered gut microbiota in subjects at cardiometabolic risk in a randomized trial.

Chitin-glucan (CG), an insoluble dietary fiber, has been shown to improve cardiometabolic disorders associated with obesity in mice. Its effects in healthy subjects has recently been studied, revealing its interaction with the gut microbiota. In this double-blind, randomized, cross-over, twice 3-week exploratory study, we investigated the impacts of CG on the cardiometabolic profile and gut microbiota composition and functions in 15 subjects at cardiometabolic risk. They consumed as a supplement 4.5 g of CG daily or maltodextrin as control. Before and after interventions, fasting and postprandial metabolic parameters and exhaled gases (hydrogen [H2] and methane [CH4]) were evaluated. Gut microbiota composition (16S rRNA gene sequencing analysis), fecal concentrations of bile acids, long- and short-chain fatty acids (LCFA, SCFA), zonulin, calprotectin and lipopolysaccharide binding protein (LBP) were analyzed. Compared to control, CG supplementation increased exhaled H2 following an enriched-fiber breakfast ingestion and decreased postprandial glycemia and triglyceridemia response to a standardized test meal challenge served at lunch. Of note, the decrease in postprandial glycemia was only observed in subjects with higher exhaled H2, assessed upon lactulose breath test performed at inclusion. CG decreased a family belonging to Actinobacteria phylum and increased 3 bacterial taxa: Erysipelotrichaceae UCG.003, Ruminococcaceae UCG.005 and Eubacterium ventriosum group. Fecal metabolites, inflammatory and intestinal permeability markers did not differ between groups. In conclusion, we showed that CG supplementation modified the gut microbiota composition and improved postprandial glycemic response, an early determinant of cardiometabolic risk. Our results also suggest breath H2 production as a non-invasive parameter of interest for predicting the effectiveness of dietary fiber intervention.

ESPEN micronutrient guideline.

BACKGROUND: Trace elements and vitamins, named together micronutrients (MNs), are essential for human metabolism. Recent research has shown the importance of MNs in common pathologies, with significant deficiencies impacting the outcome. OBJECTIVE: This guideline aims to provide information for daily clinical nutrition practice regarding assessment of MN status, monitoring, and prescription. It proposes a consensus terminology, since many words are used imprecisely, resulting in confusion. This is particularly true for the words "deficiency", "repletion", "complement", and "supplement". METHODS: The expert group attempted to apply the 2015 standard operating procedures (SOP) for ESPEN which focuses on disease. However, this approach could not be applied due to the multiple diseases requiring clinical nutrition resulting in one text for each MN, rather than for diseases. An extensive search of the literature was conducted in the databases Medline, PubMed, Cochrane, Google Scholar, and CINAHL. The search focused on physiological data, historical evidence (published before PubMed release in 1996), and observational and/or randomized trials. For each MN, the main functions, optimal analytical methods, impact of inflammation, potential toxicity, and provision during enteral or parenteral nutrition were addressed. The SOP wording was applied for strength of recommendations. RESULTS: There was a limited number of interventional trials, preventing meta-analysis and leading to a low level of evidence. The recommendations underwent a consensus process, which resulted in a percentage of agreement (%): strong consensus required of >90% of votes. Altogether the guideline proposes sets of recommendations for 26 MNs, resulting in 170 single recommendations. Critical MNs were identified with deficiencies being present in numerous acute and chronic diseases. Monitoring and management strategies are proposed. CONCLUSION: This guideline should enable addressing suboptimal and deficient status of a bundle of MNs in at-risk diseases. In particular, it offers practical advice on MN provision and monitoring during nutritional support.

ESPEN guideline on hospital nutrition.

In hospitals through Europe and worldwide, the practices regarding hospital diets are very heterogeneous. Hospital diets are rarely prescribed by physicians, and sometimes the choices of diets are based on arbitrary reasons. Often prescriptions are made independently from the evaluation of nutritional status, and without taking into account the nutritional status. Therapeutic diets (low salt, gluten-free, texture and consistency modified, …) are associated with decreased energy delivery (i.e. underfeeding) and increased risk of malnutrition. The European Society for Clinical Nutrition and Metabolism (ESPEN) proposes here evidence-based recommendations regarding the organization of food catering, the prescriptions and indications of diets, as well as monitoring of food intake at hospital, rehabilitation center, and nursing home, all of these by taking into account the patient perspectives. We propose a systematic approach to adapt the hospital food to the nutritional status and potential food allergy or intolerances. Particular conditions such as patients with dysphagia, older patients, gastrointestinal diseases, abdominal surgery, diabetes, and obesity, are discussed to guide the practitioner toward the best evidence based therapy. The terminology of the different useful diets is defined. The general objectives are to increase the awareness of physicians, dietitians, nurses, kitchen managers, and stakeholders towards the pivotal role of hospital food in hospital care, to contribute to patient safety within nutritional care, to improve coverage of nutritional needs by hospital food, and reduce the risk of malnutrition and its related complications.

ESPEN practical guideline: Clinical nutrition in chronic intestinal failure.

BACKGROUND: This practical guideline is based on the ESPEN Guidelines on Chronic Intestinal Failure in Adults. METHODOLOGY: ESPEN guidelines have been shortened and transformed into flow charts for easier use in clinical practice. The practical guideline is dedicated to all professionals including physicians, dieticians, nutritionists, and nurses working with patients with chronic intestinal failure. RESULTS: This practical guideline consists of 112 recommendations with short commentaries for the management and treatment of benign chronic intestinal failure, including home parenteral nutrition and its complications, intestinal rehabilitation, and intestinal transplantation. CONCLUSION: This practical guideline gives guidance to health care providers involved in the management of patients with chronic intestinal failure.

ESPEN practical guideline: Clinical nutrition in surgery.

Early oral feeding is the preferred mode of nutrition for surgical patients. Avoidance of any nutritional therapy bears the risk of underfeeding during the postoperative course after major surgery. Considering that malnutrition and underfeeding are risk factors for postoperative complications, early enteral feeding is especially relevant for any surgical patient at nutritional risk, especially for those undergoing upper gastrointestinal surgery. The focus of this guideline is to cover both nutritional aspects of the Enhanced Recovery After Surgery (ERAS) concept and the special nutritional needs of patients undergoing major surgery, e.g. for cancer, and of those developing severe complications despite best perioperative care. From a metabolic and nutritional point of view, the key aspects of perioperative care include the integration of nutrition into the overall management of the patient, avoidance of long periods of preoperative fasting, re-establishment of oral feeding as early as possible after surgery, the start of nutritional therapy immediately if a nutritional risk becomes apparent, metabolic control e.g. of blood glucose, reduction of factors which exacerbate stress-related catabolism or impaired gastrointestinal function, minimized time on paralytic agents for ventilator management in the postoperative period, and early mobilization to facilitate protein synthesis and muscle function.

Prebiotic Inulin and Sodium Butyrate Attenuate Obesity-Induced Intestinal Barrier Dysfunction by Induction of Antimicrobial Peptides.

Defects in the mucosal barrier have been associated with metabolic diseases such as obesity and non-alcoholic fatty liver disease (NAFLD). Mice fed a Western-style diet (WSD) develop obesity and are characterized by a diet-induced intestinal barrier dysfunction, bacterial endotoxin translocation and subsequent liver steatosis. To examine whether inulin or sodium butyrate could improve gut barrier dysfunction, C57BL/6 mice were fed a control diet or a WSD ± fructose supplemented with either 10% inulin or 5% sodium butyrate for 12 weeks respectively. Inulin and sodium butyrate attenuated hepatosteatitis in the WSD-induced obesity mouse model by reducing weight gain, liver weight, plasma and hepatic triglyceride level. Furthermore, supplementation with inulin or sodium butyrate induced expression of Paneth cell α-defensins and matrix metalloproteinase-7 (MMP7), which was impaired by the WSD and particularly the fructose-added WSD. Effects on antimicrobial peptide function in the ileum were accompanied by induction of ß-defensin-1 and tight junction genes in the colon resulting in improved intestinal permeability and endotoxemia. Organoid culture of small intestinal crypts revealed that the short chain fatty acids (SCFA) butyrate, propionate and acetate, fermentation products of inulin, induce Paneth cell α-defensin expression in vitro, and that histone deacetylation and STAT3 might play a role in butyrate-mediated induction of α-defensins. In summary, inulin and sodium butyrate attenuate diet-induced barrier dysfunction and induce expression of Paneth cell antimicrobials. The administration of prebiotic fiber or sodium butyrate could be an interesting therapeutic approach to improve diet-induced obesity.

Effect of an intensified individual nutrition therapy on serum metabolites in critically ill patients - A targeted metabolomics analysis of the ONCA study.

PURPOSE: The effect of medical nutrition on serum metabolomics has been poorly explored. The aim of the study was to investigate the relation between energy supply and metabolic profiles in critically ill patients. MATERIALS AND METHODS: Twenty mechanically ventilated patients on enteral nutrition (EN) or enteral/parenteral nutrition (EN/PN) were randomized into two groups. One group received an individual energy supply based on indirect calorimetry (IC group, n = 9), the other group received a standard energy supply based on a formula, the standard care group (SC group, n = 11). Targeted metabolomics was performed in early-, late- and post-acute metabolic phase. RESULTS: Individual versus standard care energy supply resulted in a metabolite class separation between the IC and the SC group (P < 0.001). In the SC group concentrations of four glucogenic amino acids and three biogenic amines increased between the early- and late-acute metabolic phase (P < 0.05). The metabolomics pattern differed between the routes of nutrition administration (P < 0.01). CONCLUSIONS: The amount of energy supply by EN or PN, besides other factors, seems to modulate serum metabolites. Nutrition therapy based on individualized energy supply is associated with a reduction of metabolites reflecting catabolism. Therefore, metabolomics could be a new tool to determine metabolic phases in critically ill patients.

Fructose-Induced Intestinal Microbiota Shift Following Two Types of Short-Term High-Fructose Dietary Phases.

High consumption of fructose and high-fructose corn syrup is related to the development of obesity-associated metabolic diseases, which have become the most relevant diet-induced diseases. However, the influences of a high-fructose diet on gut microbiota are still largely unknown. We therefore examined the effect of short-term high-fructose consumption on the human intestinal microbiota. Twelve healthy adult women were enrolled in a pilot intervention study. All study participants consecutively followed four different diets, first a low fructose diet (< 10 g/day fructose), then a fruit-rich diet (100 g/day fructose) followed by a low fructose diet (10 g/day fructose) and at last a high-fructose syrup (HFS) supplemented diet (100 g/day fructose). Fecal microbiota was analyzed by 16S rRNA sequencing. A high-fructose fruit diet significantly shifted the human gut microbiota by increasing the abundance of the phylum Firmicutes, in which beneficial butyrate producing bacteria such as Faecalibacterium, Anareostipes and Erysipelatoclostridium were elevated, and decreasing the abundance of the phylum Bacteroidetes including the genus Parabacteroides. An HFS diet induced substantial differences in microbiota composition compared to the fruit-rich diet leading to a lower Firmicutes and a higher Bacteroidetes abundance as well as reduced abundance of the genus Ruminococcus. Compared to a low-fructose diet we observed a decrease of Faecalibacterium and Erysipelatoclostridium after the HFS diet. Abundance of Bacteroidetes positively correlated with plasma cholesterol and LDL level, whereas abundance of Firmicutes was negatively correlated. Different formulations of high-fructose diets induce distinct alterations in gut microbiota composition. High-fructose intake by HFS causes a reduction of beneficial butyrate producing bacteria and a gut microbiota profile that may affect unfavorably host lipid metabolism whereas high consumption of fructose from fruit seems to modulate the composition of the gut microbiota in a beneficial way supporting digestive health and counteracting harmful effects of excessive fructose.

Metabolite profiling reveals the interaction of chitin-glucan with the gut microbiota.

Dietary fibers are considered beneficial nutrients for health. Current data suggest that their interaction with the gut microbiota largely contributes to their physiological effects. In this context, chitin-glucan (CG) improves metabolic disorders associated with obesity in mice, but its effect on gut microbiota has never been evaluated in humans. This study explores the effect of a 3-week intervention with CG supplementation in healthy individuals on gut microbiota composition and bacterial metabolites. CG was given to healthy volunteers (n = 15) for three weeks as a supplement (4.5 g/day). Food diary, visual analog and Bristol stool form scales and a "quality of life" survey were analyzed. Among gut microbiota-derived metabolites, bile acids (BA), long- and short-chain fatty acids (LCFA, SCFA) profiling were assessed in stool samples. The gut microbiota (primary outcome) was analyzed by Illumina sequencing. A 3-week supplementation with CG is well tolerated in healthy humans. CG induces specific changes in the gut microbiota composition, with Eubacterium, Dorea and Roseburia genera showing the strongest regulation. In addition, CG increased bacterial metabolites in feces including butyric, iso-valeric, caproic and vaccenic acids. No major changes were observed for the fecal BA profile following CG intervention. In summary, our work reveals new potential bacterial genera and gut microbiota-derived metabolites characterizing the interaction between an insoluble dietary fiber -CG- and the gut microbiota.

ESPEN expert statements and practical guidance for nutritional management of individuals with SARS-CoV-2 infection.

The COVID-19 pandemics is posing unprecedented challenges and threats to patients and healthcare systems worldwide. Acute respiratory complications that require intensive care unit (ICU) management are a major cause of morbidity and mortality in COVID-19 patients. Patients with worst outcomes and higher mortality are reported to include immunocompromised subjects, namely older adults and polymorbid individuals and malnourished people in general. ICU stay, polymorbidity and older age are all commonly associated with high risk for malnutrition, representing per se a relevant risk factor for higher morbidity and mortality in chronic and acute disease. Also importantly, prolonged ICU stays are reported to be required for COVID-19 patients stabilization, and longer ICU stay may per se directly worsen or cause malnutrition, with severe loss of skeletal muscle mass and function which may lead to disability, poor quality of life and additional morbidity. Prevention, diagnosis and treatment of malnutrition should therefore be routinely included in the management of COVID-19 patients. In the current document, the European Society for Clinical Nutrition and Metabolism (ESPEN) aims at providing concise guidance for nutritional management of COVID-19 patients by proposing 10 practical recommendations. The practical guidance is focused to those in the ICU setting or in the presence of older age and polymorbidity, which are independently associated with malnutrition and its negative impact on patient survival.

Fatty acid profiles in erythrocyte membranes following the Mediterranean diet - data from a multicenter lifestyle intervention study in women with hereditary breast cancer (LIBRE).

BACKGROUND & AIMS: Evidence-based concepts to prevent breast cancer in women with BRCA1/2 mutations are limited. Adherence to a Mediterranean diet (MedD) has been associated with a lower risk for breast cancer, possibly due to a favorable fatty acid (FA) intake. Here, we studied in an at-risk population the effect of a lifestyle intervention that included the MedD on FA composition in red blood cell membranes (RBCM). METHODS: Data derived from the German multicenter trial LIBRE, from which 68 women were randomized into an intervention group (IG) trained for MedD and increased physical activity for 12 months, and a usual care control group (CG). Adherence to the diet was assessed after 3 and 12 months using the validated Mediterranean Diet Adherence Screener (MEDAS) and a food frequency questionnaire. RBCM FA were analyzed by gas chromatography with mass spectrometry. RESULTS: The MEDAS was increased in both groups after 3 months (IG: P < 0.001; CG: P = 0.004), and remained increased only in the IG after 12 months (P < 0.001). The food frequency questionnaire revealed an increased intake of omega-3 (n-3) FA at month 3 and month 12 in the IG (both P < 0.01), but not in the CG, in which intake of energy, protein and saturated FA decreased. In both groups n-6 FA in the RBCM decreased (P < 0.001), while n-9 FA increased (P < 0.001) and n-3 FA were unchanged. Women with higher consumption of fish had higher amounts of n-3 fatty acids in the RBCM. The MEDAS was inversely correlated with n-6 fatty acids. CONCLUSIONS: The RBCM FA composition was associated with dietetic parameters related to the MedD. Adherence to the MedD resulted in an altered, likely favorable FA composition. Our data suggest selected FA as biomarkers to monitor compliance to a dietetic intervention such as the MedD. CLINICAL TRIAL REGISTRY: The trial is registered at ClinicalTrials.gov (reference: NCT02087592).

Clinical Nutrition in Critical Care Medicine - Guideline of the German Society for Nutritional Medicine (DGEM).

PURPOSE: Enteral and parenteral nutrition of adult critically ill patients varies in terms of the route of nutrient delivery, the amount and composition of macro- and micronutrients, and the choice of specific, immune-modulating substrates. Variations of clinical nutrition may affect clinical outcomes. The present guideline provides clinicians with updated consensus-based recommendations for clinical nutrition in adult critically ill patients who suffer from at least one acute organ dysfunction requiring specific drug therapy and/or a mechanical support device (e.g., mechanical ventilation) to maintain organ function. METHODS: The former guidelines of the German Society for Nutritional Medicine (DGEM) were updated according to the current instructions of the Association of the Scientific Medical Societies in Germany (AWMF) valid for a S2k-guideline. According to the S2k-guideline classification, no systematic review of the available evidence was required to make recommendations, which, therefore, do not state evidence- or recommendation grades. Nevertheless, we considered and commented the evidence from randomized-controlled trials, meta-analyses and observational studies with adequate sample size and high methodological quality (until May 2018) as well as from currently valid guidelines of other societies. The liability of each recommendation was described linguistically. Each recommendation was finally validated and consented through a Delphi process. RESULTS: In the introduction the guideline describes a) the pathophysiological consequences of critical illness possibly affecting metabolism and nutrition of critically ill patients, b) potential definitions for different disease phases during the course of illness, and c) methodological shortcomings of clinical trials on nutrition. Then, we make 69 consented recommendations for essential, practice-relevant elements of clinical nutrition in critically ill patients. Among others, recommendations include the assessment of nutrition status, the indication for clinical nutrition, the timing and route of nutrient delivery, and the amount and composition of substrates (macro- and micronutrients); furthermore, we discuss distinctive aspects of nutrition therapy in obese critically ill patients and those treated with extracorporeal support devices. CONCLUSION: The current guideline provides clinicians with up-to-date recommendations for enteral and parenteral nutrition of adult critically ill patients who suffer from at least one acute organ dysfunction requiring specific drug therapy and/or a mechanical support device (e.g., mechanical ventilation) to maintain organ function. The period of validity of the guideline is approximately fixed at five years (2018-2023).

Deletion of the Casp8 gene in mice results in ileocolitis, gut barrier dysfunction, and malassimilation, which can be partially attenuated by inulin or sodium butyrate.

Genetically modified mice have been successfully used as models for inflammatory bowel diseases; however, dietary effects were poorly examined. Here, we studied the impact of particular nutrients and supplements on gut functions related to the knockout of the epithelial caspase-8 gene. Caspase-8 knockout (Casp8∆IEC) and control (Casp8fl) mice were fed for 4 wk a control diet (CD) enriched with 10% inulin (CD-Inu) or 5% sodium butyrate (CD-But) while having free access to plain water or water supplemented with 30% fructose (+F). Body weight changes, intestinal inflammation, and selected markers for barrier function and of liver steatosis were assessed. Casp8∆IEC mice developed ileocolitis accompanied by changes in intestinal barrier morphology and reduced expression of barrier-related genes such as mucin-2 (Muc2) and defensins in the ileum and Muc2 in the colon. Casp8∆IEC mice fed a CD also showed impaired body weight gain compared with Casp8fl mice, which was even more pronounced in mice receiving water supplemented with fructose. Furthermore, we observed a marked liver steatosis and inflammation in some but not all Casp8∆IEC mice under a CD, which was on average similar to that observed in control mice under a fructose-rich diet. Hepatic lipid accumulation, as well as markers of ileal barrier function, but not intestinal pathohistology or body weight loss, were attenuated by diets enriched with inulin or butyrate, especially in the absence of fructose supplementation. Our data show that ileocolitis, barrier dysfunction, and malassimilation in Caspase-8 knockout mice can be partially attenuated by oral inulin or butyrate supplementation.NEW & NOTEWORTHY Genetic mouse models for ileocolitis are important to understand inflammatory bowel disease in humans. We examined dietetic factors that might aggravate or attenuate ileocolitis and related pathologies in such a model. Deletion of the caspase-8 gene results not only in ileocolitis but also in gut barrier dysfunction, liver steatosis, and malassimilation, which can be partially attenuated by oral inulin or sodium butyrate. Our data indicate that diet modifications can contribute to disease variability and therapy.