Human Milk Oligosaccharides Influence Intestinal Epithelial Cell Maturation In Vitro.

OBJECTIVES: Human milk oligosaccharides (HMOs) are reported to promote epithelial cell differentiation in vitro. The aim of the present study was to assess induction of epithelial cell differentiation by individual and combined administration of 3 HMOs. METHODS: An in vitro epithelial model of the crypt-villus axis consisting of preconfluent HT-29, preconfluent Caco-2Bbe, and postconfluent Caco-2Bbe cells was used. Cultures were randomized to 17 treatments for 72 hours of incubation: low- and high-dose HMOs (3'sialyllactose [3'SL] at 0.2 and 1.0 g/L, 6'siallylactose [6'SL] at 0.4 and 1.0 g/L, and 2'fucosyllactose at 0.2 and 2.0 g/L), HMO combinations at both low and high doses, and controls (culture medium, 4 g/L pooled HMO, and lipopolysaccharide). RESULTS: High doses of individual HMOs (P < 0.05), combined HMOs (P < 0.05), and pooled HMO decreased (P < 0.001) proliferation in preconfluent HT-29 cultures. Pooled means of individual low and high treatments with 3'SL and 6'SL, combinations of 2 or 3 high-dose HMOs, and total HMO significantly reduced (P < 0.05) proliferation in preconfluent Caco-2Bbe cells. HMOs increased differentiation in preconfluent HT-29 and Caco-2Bbe cells. 3'SL and 6'SL increased alkaline phosphatase activity but did not affect disaccharidase activity in postconfluent Caco-2Bbe cells. Apoptosis and necrosis were both decreased (P < 0.001) in postconfluent Caco-2Bbe cells treated with pooled HMO. CONCLUSIONS: HMO treatments inhibited proliferation with some associated enhancement of epithelial differentiation. Effects of HMOs were additive but no specific combinations of HMOs were especially potent. These results suggest that commercially viable individual HMOs and specific combinations may promote intestinal epithelial cell maturation.

Nondigestible Fructans Alter Gastrointestinal Barrier Function, Gene Expression, Histomorphology, and the Microbiota Profiles of Diet-Induced Obese C57BL/6J Mice.

BACKGROUND: Obesity is associated with compromised intestinal barrier function and shifts in gastrointestinal microbiota that may contribute to inflammation. Fiber provides benefits, but impacts of fiber type are not understood. OBJECTIVE: We aimed to determine the impact of cellulose compared with fructans on the fecal microbiota and gastrointestinal physiology in obese mice. METHODS: Eighteen-wk-old male diet-induced obese C57BL/6J mice (n = 6/group; 40.5 g) were fed high-fat diets (45% kcal fat) containing 5% cellulose (control), 10% cellulose, 10% short-chain fructooligosaccharides (scFOS), or 10% inulin for 4 wk. Cecal and colon tissues were collected to assess barrier function, histomorphology, and gene expression. Fecal DNA extracts were subjected to 16S ribosomal RNA amplicon-based Illumina MiSeq sequencing to assess microbiota. RESULTS: Body weight gain was greater (P < 0.05) in scFOS-fed than in 10% cellulose-fed mice. Both groups of fructan-fed mice had greater (P < 0.05) cecal crypt depth (scFOS: 141 µm; inulin: 145 µm) than both groups of cellulose-fed mice (5% and 10%: 109 µm). Inulin-fed mice had greater (P < 0.05) cecal transmural resistance (101 Ω × cm(2)) than 5% cellulose-fed controls (45 Ω × cm(2)). Inulin-fed mice had lower (P < 0.05) colonic mRNA abundance of Ocln (0.41) and Mct1 (0.35) than those fed 10% cellulose (Ocln: 1.28; Mct1: 0.90). Fructan and cellulose groups had different UniFrac distances of fecal microbiota (P < 0.05) and α diversity, which demonstrated lower (P < 0.01) species richness in fructan-fed mice. Mice fed scFOS had greater (P < 0.05) Actinobacteria (15.9%) and Verrucomicrobia (Akkermansia) (17.0%) than 5% controls (Actinobacteria: 0.07%; Akkermansia: 0.08%). Relative abundance of Akkermansia was positively correlated (r = 0.56, P < 0.01) with cecal crypt depth. CONCLUSIONS: Fructans markedly shifted gut microbiota and improved intestinal physiology in obese mice, but the mechanisms by which they affect gut integrity and inflammation in the obese are still unknown.

A Novel Neonatal Feeding Intolerance and Necrotizing Enterocolitis Risk-Scoring Tool Is Easy to Use and Valued by Nursing Staff.

BACKGROUND: Preterm infants are at increased risk of developing feeding intolerance and necrotizing enterocolitis. Comprehensive, targeted nursing assessments can evaluate the risk for and identify early signs of these conditions in an effort to prevent their destructive sequela. PURPOSE: While the long-term goal is to develop a validated risk-scoring tool for the prediction of feeding intolerance and necrotizing enterocolitis, the objective of the preliminary phase presented here is to assess the ease of use and nurses' attitudes toward a novel feeding intolerance and necrotizing enterocolitis risk-scoring tool. METHODS: A novel risk-scoring nursing tool was implemented in a University of Illinois-affiliated 48-bed level III neonatal intensive care unit. Data were collected from the electronic medical record of all preterm infants with parental consent during the initial 6-month study period. Scoring accuracy (accuracy of selection of risk factors based on electronic medical record data), ease of use, and nurses' attitudes toward the tool were assessed at the study site and by evaluators at a national neonatal nursing conference. RESULTS: Fourteen nurses scored 166 tools on the 63 enrolled infants. Sixteen tools (9.6%) contained errors. Mean study site tool ease of use was 8.1 (SD: 2.2) on a 10-point scale. Ninety percent of conference evaluators agreed/strongly agreed that the tool addressed important knowledge gaps. IMPLICATIONS FOR PRACTICE: The tool is easy to use and valued by nurses. Following validation, widespread implementation is expected to be a clinically feasible means to improve infant clinical outcomes for minimal time and financial cost. IMPLICATIONS FOR RESEARCH: Tool validation and refinement based on nursing feedback will improve its broad applicability and predictive utility.

Human milk oligosaccharides influence maturation of human intestinal Caco-2Bbe and HT-29 cell lines.

Stimulation of gastrointestinal tract maturation is 1 of the many benefits of human milk. Human milk oligosaccharides (HMOs) are abundant in human milk and are reported to promote enterocyte differentiation in vitro. The objective of this study was to assess the impact of 3 predominant HMOs on multiple aspects of enterocyte maturation in vitro. Ranging from crypt-like to differentiated enterocytes, we used the well-characterized intestinal cell lines HT-29 and Caco-2Bbe to model early and late stages of differentiation, respectively. With this model of the crypt-villus axis made up of preconfluent HT-29, preconfluent Caco-2Bbe, and postconfluent Caco-2Bbe cultures, we characterized the impact of lacto-N-neotetraose (LNnT), 2'-fucosyllactose (2'FL), and 6'-sialyllactose on epithelial cell kinetics and function. All 3 HMOs dose-dependently inhibited cell proliferation in undifferentiated HT-29 and Caco-2Bbe cultures (P < 0.05). In contrast to previous reports, only treatment with 2'FL at concentrations similar to human milk increased alkaline phosphatase activity by 31% (P = 0.044) in HT-29 cultures and increased sucrase activity by 54% (P = 0.005) in well-differentiated Caco-2Bbe cultures. LNnT at concentrations similar to that reported for human milk increased transepithelial resistance by 21% (P = 0.002) in well-differentiated Caco-2Bbe cells. In summary, all 3 HMOs reduced cell proliferation in an epithelial cell model of the crypt-villus axis. However, effects on differentiation, digestive function, and epithelial barrier function differed between the HMOs tested. These results suggest differential roles for specific HMOs in maturation of the gastrointestinal tract.

Teduglutide enhances structural adaptation of the small intestinal mucosa in patients with short bowel syndrome.

BACKGROUND: Intestinotrophic therapies, such as glucagon-like peptide-2 (GLP-2) analogs, may enhance intestinal adaptation and reduce dependence on parenteral nutrition (PN) in patients with intestinal failure associated with short bowel syndrome (SBS-IF). However, because GLP-2 enhances cellular growth, there is concern that GLP-2 analogs may also encourage growth of malignant cells. AIMS: To histologically examine the effects of teduglutide, a recombinant human GLP-2 analog, on the mucosa of the small and large intestine for indications of dysplastic transformation. METHODS: In a multicenter, prospective, randomized, placebo-controlled study, 83 PN-dependent patients with SBS-IF were monitored for several weeks to ensure optimal and stable PN. Patients were then randomized to receive 24 weeks of placebo (n=16), teduglutide (0.5 mg/kg/d; n=35), or teduglutide (0.10 mg/kg/d; n=32). RESULTS: Biopsies were obtained from 77 patients to yield 390 individual histologic interpretations. After 6 months of treatment, no features of dysplasia were found in any biopsy from the large or small intestine of patients receiving placebo or either dose of teduglutide. New secondary diagnoses, such as eosinophilic colitis or Crohn's disease, were found at a low frequency overall: teduglutide (0.05 mg/kg/d; range, 3.1% to 6.3%); teduglutide (0.10 mg/kg/d, 3.3%); placebo (range, 6.7% to 13.3%). CONCLUSIONS: Although this histologic substudy of biopsy samples was not powered to detect differences in occurrence of dysplasia between teduglutide-treated patients and those randomized to placebo, it demonstrated that no dysplasia or other pathologic processes were evident within the intestinal mucosa in the placebo group or the 2 teduglutide groups after 6 months of treatment.

Critical role of nutrition in improving quality of care: an interdisciplinary call to action to address adult hospital malnutrition.

The current era of health care delivery, with its focus on providing high-quality, affordable care, presents many challenges to hospital-based health professionals. The prevention and treatment of hospital malnutrition offers a tremendous opportunity to optimize the overall quality of patient care, improve clinical outcomes, and reduce costs. Unfortunately, malnutrition continues to go unrecognized and untreated in many hospitalized patients. This article represents a call to action from the interdisciplinary Alliance to Advance Patient Nutrition to highlight the critical role of nutrition intervention in clinical care and suggest practical ways for prompt diagosis and treatment of malnourished patients and those at risk for malnutrition. We underscore the importance of an interdisciplinary approach to addressing malnutrition both in the hospital and in the acute post-hospital phase. It is well recognized that malnutrition is associated with adverse clinical outcomes. Although data vary across studies, available evidence shows early nutrition intervention can reduce complication rates, length of hospital stay, re-admission rates, mortality, and cost of care. The key is to identify patients systematically who are malnourished or at risk and to promptly intervene. We present a novel care model to drive improvement, emphasizing the following six principles: (1) create an institutional culture where all stakeholders value nutrition; (2) redefine clinicians' roles to include nutrition care; (3) recognize and diagnose all malnourished patients and those at risk; (4) rapidly implement comprehensive nutrition interventions and continued monitoring; (5) communicate nutrition care plans; and (6) develop a comprehensive discharge nutrition care and education plan.

Anatomical and physiological considerations in short bowel syndrome: Emphasis on intestinal adaptation and the role of enterohormones.

Short bowel syndrome (SBS)-associated intestinal failure (IF) is a complex, life-threatening condition that requires complex care of multiple factors impacting the patient's long-term prognosis. Various etiologies result in SBS-IF, with three primary anatomical subtypes occurring following intestinal resection. Depending on the extent and segment(s) of the intestine resected, malabsorption can be nutrient specific or sweeping; however, such issues and the associated prognosis for the patient can be predicted with analysis of the residual intestine, along with baseline nutrient and fluid deficits and extent of malabsorption. The provision of parenteral nutrition/intravenous (PN-IV) fluids and antisymptomatic agents is fundamental; however, optimal management should focus on intestinal rehabilitation, wherein intestinal adaptation is prioritized and PN-IV fluids are weaned over time. Key strategies to maximize intestinal adaptation include hyperphagic consumption of an individualized SBS diet and the appropriate use of trophic agents, such as a glucagon-like peptide 2 analog.

Impact of a specialized oral nutritional supplement on quality of life in older adults following hospitalization: Post-hoc analysis of the NOURISH trial.

BACKGROUND & AIMS: Both during and after hospitalization, nutritional care with daily intake of oral nutritional supplements (ONS) improves health outcomes and decreases risk of mortality in malnourished older adults. In a post-hoc analysis of data from hospitalized older adults with malnutrition risk, we sought to determine whether consuming a specialized ONS (S-ONS) containing high protein and beta-hydroxy-beta-methylbutyrate (HMB) can also improve Quality of Life (QoL). METHODS: We analyzed data from the NOURISH trial-a randomized, placebo-controlled, multi-center, double-blind study conducted in patients with congestive heart failure, acute myocardial infarction, pneumonia, or chronic obstructive pulmonary disease. Patients received standard care + S-ONS or placebo beverage (target 2 servings/day) during hospitalization and for 90 days post-discharge. SF-36 and EQ-5D QoL outcomes were assessed at 0-, 30-, 60-, and 90-days post-discharge. To account for the missing QoL observations (27.7%) due to patient dropout, we used multiple imputation. Data represent differences between least squares mean (LSM) values with 95% Confidence Intervals for groups receiving S-ONS or placebo treatments. RESULTS: The study population consisted of 622 patients of mean age ±standard deviation: 77.9 ± 8.4 years and of whom 52.1% were females. Patients consuming placebo had lower (worse) QoL domain scores than did those consuming S-ONS. Specifically for the SF-36 health domain scores, group differences (placebo vs S-ONS) in LSM were significant for the mental component summary at day 90 (-4.23 [-7.75, -0.71]; p = 0.019), the domains of mental health at days 60 (-3.76 [-7.40, -0.12]; p = 0.043) and 90 (-4.88 [-8.41, -1.34]; p = 0.007), vitality at day 90 (-3.33 [-6.65, -0.01]; p = 0.049) and social functioning at day 90 (-4.02 [-7.48,-0.55]; p = 0.023). Compared to placebo, differences in LSM values for the SF-36 general health domain were significant with improvement in the S-ONS group at hospital discharge and beyond: day 0 (-2.72 [-5.33, -0.11]; p = 0.041), day 30 (-3.08 [-6.09, -0.08]; p = 0.044), day 60 (-3.95 [-7.13, -0.76]; p = 0.015), and day 90 (-4.56 [-7.74, -1.38]; p = 0.005). CONCLUSIONS: In hospitalized older adults with cardiopulmonary diseases and evidence of poor nutritional status, daily intake of S-ONS compared to placebo improved post-discharge QoL scores for mental health/cognition, vitality, social functioning, and general health. These QoL benefits complement survival benefits found in the original NOURISH trial analysis. CLINICAL TRIAL REGISTRATION: NCT01626742.

Management of short-bowel syndrome: A survey of unmet educational needs among healthcare providers.

BACKGROUND: Management of short-bowel syndrome with intestinal failure (SBS-IF) is complex and requires a multidisciplinary approach. Because of the rarity of SBS-IF, healthcare professionals (HCPs) often lack clinical experience with the disease and may benefit from education regarding SBS-IF and its management. This study identified unmet educational needs related to the management of patients with SBS-IF. METHODS: This was a prospective, web-based survey (December 2019-January 2020) in which a series of clinical questions were posed to US HCPs after presenting three standardized SBS-IF cases to assess current practice patterns. HCPs were then asked a series of questions to identify potential knowledge gaps and unmet educational needs relating to SBS-IF management. RESULTS: Overall, 558 HCPs completed the survey, with 12%-38% having a formal SBS-IF multidisciplinary team currently available to make treatment decisions within their institution. Clinicians involved in care included gastroenterologists (93%), registered dietitians (79%), gastroenterology nurse practitioners and physician assistants (37%), registered nurses (43%), social workers (45%), and psychologists/psychiatrists (27%). There was underuse of published guidelines and limited understanding of the course of intestinal adaptation. Responses to the clinical scenarios highlighted disparities in SBS-IF care delivery, including diagnosis, management goals, medications prescribed, and nutrition practices. CONCLUSIONS: Future SBS-IF educational interventions for HCPs should aim to improve awareness and understanding of the disease, facilitate timely diagnosis, and standardize management practices to ensure patients receive optimal interdisciplinary care as widely as possible.

Utilization and validation of the Global Leadership Initiative on Malnutrition (GLIM): A scoping review.

BACKGROUND & AIMS: The diagnosis of malnutrition remains a significant challenge despite various published diagnostic criteria. In 2018, the Global Leadership Initiative on Malnutrition (GLIM) published a set of evidence-based criteria as a framework for malnutrition diagnosis in adults. A scoping review was conducted to understand how the GLIM criteria have been used in published literature and compare the reported validation methods to published validation guidance. METHODS: Dialog and Dimensions databases were searched by publication date (January 1, 2019, through January 29, 2021). Data were extracted and mapped to the research objectives. RESULTS: Seventy-nine studies were reviewed; 32% were in patients at least 65 years of age; 67% occurred in hospitals. The majority were cohort studies (61%). Fifty-seven percent employed all 5 GLIM criteria. Regarding phenotypic criteria, 92% used low BMI, and 45% applied anthropometry as a marker for muscle mass, of which 54% used calf circumference. Regarding etiologic criteria, 72% used reduced food intake/assimilation, and 85% applied inflammation/disease burden. Validation of GLIM criteria was described in 77% of publications. CONCLUSIONS: The GLIM criteria have been studied extensively since their publication. Low BMI was the phenotypic criterion used most often, whereas both reduced food intake/assimilation and inflammation/disease burden were frequently employed as the etiologic criteria. However, how the criteria were combined and how validation was conducted were not clear in most studies. Adequately powered, methodologically sound validation studies using the complete GLIM criteria are needed in various patient populations and disease settings to assess validity for the diagnosis of malnutrition.

Apical Na+-D-glucose cotransporter 1 (SGLT1) activity and protein abundance are expressed along the jejunal crypt-villus axis in the neonatal pig.

Gut apical Na(+)-glucose cotransporter 1 (SGLT1) activity is high at the birth and during suckling, thus contributing substantially to neonatal glucose homeostasis. We hypothesize that neonates possess high SGLT1 maximal activity by expressing apical SGLT1 protein along the intestinal crypt-villus axis via unique control mechanisms. Kinetics of SGLT1 activity in apical membrane vesicles, prepared from epithelial cells sequentially isolated along the jejunal crypt-villus axis from neonatal piglets by the distended intestinal sac method, were measured. High levels of maximal SGLT1 uptake activity were shown to exist along the jejunal crypt-villus axis in the piglets. Real-time RT-PCR analyses showed that SGLT1 mRNA abundance was lower (P < 0.05) by 30-35% in crypt cells than in villus cells. There were no significant differences in SGLT1 protein abundances on the jejunal apical membrane among upper villus, middle villus, and crypt cells, consistent with the immunohistochemical staining pattern. Higher abundances (P < 0.05) of total eukaryotic initiation factor 4E (eIF4E) protein and eIE4E-binding protein 1 γ-isoform in contrast to a lower (P < 0.05) abundance of phosphorylated (Pi) eukaryotic elongation factor 2 (eEF2) protein and the eEF2-Pi to total eEF2 abundance ratio suggest higher global protein translational efficiency in the crypt cells than in the upper villus cells. In conclusion, neonates have high intestinal apical SGLT1 uptake activity by abundantly expressing SGLT1 protein in the epithelia and on the apical membrane along the entire crypt-villus axis in association with enhanced protein translational control mechanisms in the crypt cells.

Learn Intestinal Failure Tele-ECHO Project: An innovative online telementoring and case-based learning clinic.

Intestinal failure (IF) is a rare chronic disease requiring intravenous (IV) fluids or parenteral nutrition (PN) dependency for optimal patient health and sustenance. The complex care is best managed by specialized multidisciplinary teams. Patients who have limited access to intestinal rehabilitation centers often receive IV/PN care from clinicians lacking specialty expertise. An innovative videoconferencing project was launched in May 2019 to provide online telementoring and case-based learning in IF. The Extension for Community Healthcare Outcomes (ECHO) model was adopted to provide education and virtual support via the Learn Intestinal Failure Tele-ECHO (LIFT-ECHO) project. Online clinics include patient case presentations, moderated discussion, best-practice recommendations, and didactic continuing education lectures on IF- and PN-related topics. Participation is interprofessional and international. Via knowledge dissemination and specialty mentorship, LIFT-ECHO is expected to improve healthcare for patients with IF and transform care delivery by overcoming the limitations in access to expertise.

Reduced mortality risk in malnourished hospitalized older adult patients with COPD treated with a specialized oral nutritional supplement: Sub-group analysis of the NOURISH study.

BACKGROUND: Hospitalized, malnourished older adults with chronic obstructive pulmonary disease (COPD) have an elevated risk of readmission and mortality. OBJECTIVE: Post-hoc, sub-group analysis from the NOURISH study cohort examined the effect of a high-protein oral nutritional supplement (ONS) containing HMB (HP-HMB) in malnourished, hospitalized older adults with COPD and to identify predictors of outcomes. METHODS: The NOURISH study (n = 652) was a multicenter, randomized, placebo-controlled, double-blind trial. The COPD subgroup (n = 214) included hospitalized, malnourished (based on Subjective Global Assessment), older adults (≥65 y), with admission diagnosis of COPD who received either standard-of-care plus HP-HMB (n = 109) or standard-of-care and a placebo supplement (n = 105) prescribed 2 servings/day from within 3 days of hospital admission (baseline) and up to 90 days after discharge. The primary study outcome was a composite endpoint of incidence of death or non-elective readmission up to 90-day post-discharge, while secondary endpoints included changes in hand-grip strength, body weight, and nutritional biomarkers over time. Categorical outcomes were analyzed using Cochran-Mantel-Haenszel tests, longitudinal data by repeated measures analysis of covariance; and changes from baseline by analysis of covariance. p-values ≤ 0.05 were considered statistically significant. Multivariate logistic regression was used to model predictors of the primary outcome and components. RESULTS: In patients with COPD, 30, 60, and 90-day hospital readmission rate did not differ, but in contrast, 30, 60, and 90-day mortality risk was approximately 71% lower with HP-HMB supplementation relative to placebo (1.83%, 2.75%, 2.75% vs. 6.67%, 9.52% and 10.48%, p = 0.0395, 0.0193, 0.0113, resp.). In patients with COPD, compared to placebo, intake of HP-HMB resulted in a significant increase in handgrip strength (+1.56 kg vs. -0.34 kg, p = 0.0413) from discharge to day 30; increased body weight from baseline to hospital discharge (0.66 kg vs. -0.01 kg, p < 0.05) and, improvements in blood nutritional biomarker concentrations. The multivariate logistic regression predictors of the death, readmission or composite endpoints in these COPD patients showed that participants who were severely malnourished (p = 0.0191) and had a Glasgow prognostic score (GPS) Score of 1 or 2 had statistically significant odds of readmission or death (p = 0.0227). CONCLUSIONS: Among malnourished, hospitalized patients with COPD, supplementation with HP-HMB was associated with a markedly decreased mortality risk, and improved handgrip strength, body weight, and nutritional biomarkers within a 90-day period after hospital discharge. This post-hoc, subgroup analysis highlights the importance of early identification of nutritional risk and administration of high-protein ONS in older, malnourished patients with COPD after hospital admission and continuing after hospital discharge.

Micronutrients in parenteral nutrition: too little or too much? The past, present, and recommendations for the future.

This research workshop in 2009 grew out of a concern in the United States, Europe, and other countries with advanced medicine that it was time to revisit the parenteral requirements for a number of micronutrients. Critical questions sought to be answered included the following: Were there micronutrients not routinely added that should be part of a parenteral nutrition (PN) formula? Were other micronutrients present but in inappropriate amounts? How are various micronutrient requirements altered in the critically or chronically ill?

Sickness behavior induced by endotoxin can be mitigated by the dietary soluble fiber, pectin, through up-regulation of IL-4 and Th2 polarization.

Peripheral activation of the immune system by infectious agents triggers the brain-cytokine system causing sickness behaviors which profoundly impact well-being. Dietary fiber is a beneficial foodstuff that, from a gastrointestinal tract perspective, exists in both insoluble and soluble forms. We show that a diet rich in soluble fiber protects mice from endotoxin-induced sickness behavior by polarizing mice Th2 when compared to a diet containing only insoluble fiber. Mice fed soluble fiber became less sick and recovered faster from endotoxin-induced sickness behaviors than mice fed insoluble fiber. In response to intraperitoneal endotoxin, mice fed soluble fiber had up-regulated IL-1RA and reduced IL-1beta and TNF-alpha in the brain as compared to mice fed insoluble fiber. Importantly, mice fed soluble fiber had a basal increase in IL-4 in the ileum and spleen which was absent in MyD88 knockout mice. Con-A stimulated splenocytes from mice fed soluble fiber showed increased IL-4 and IL-5 and decreased IL-2, IL-12 and IFN-gamma when compared to mice fed insoluble fiber. Likewise, endotoxin-stimulated macrophages from mice fed soluble fiber demonstrated decreased IL-1beta, TNF-alpha, IFN-gamma, IL-12 and nitrate and increased IL-1RA, arginase 1 and Ym1 when compared to mice fed insoluble fiber. Finally, the behavioral protection afforded by feeding mice soluble fiber was reduced in IL-4 knockout mice, as was the impact of soluble fiber on Con-A stimulated splenocytes and endotoxin activated macrophages. These data show that a diet rich in soluble fiber protects against endotoxin-induced sickness behavior by polarizing mice Th2 and promoting alternative activation of macrophages.

Fermentable Fibers Enhance Aspects of Innate and Adaptive Immunity in Piglets infected with Salmonella Typhimurium.

OBJECTIVE: To test the hypothesis that fermentable fiber prevents Salmonella typhimurium infection-associated symptoms by enhancing innate and adaptive immune system in neonatal pigs. METHODS: Two-d-old piglets (n=120) were randomized to receive either a nutritionally complete sow milk replacer formula (CON), or supplemented with methylcellulose (MCEL-non-fermentable), soy polysaccharides (SPS-moderately fermentable), or fructooligosaccharides (FOS-highly fermentable). On d7, piglets received an oral gavage of S. typhimurium-798, and continued receiving the same diets up to 48h post-infection. Ileal mucosal samples were obtained for further analyses. RESULTS: A reduction in chloride secretion was observed in FOS when compared to other diets (p<0.0003). The number of ileal sulfo-acidomucins was higher (p<0.05) in FOS before infection compared with other diets. NFkB was inhibited in FOS following infection (p<0.05), when compared with CON. IL-1ß expression was increased at 4h post-infection (p<0.05) in CON; however, this response was attenuated in the fiber groups. IL-6 expression was higher (p<0.05) in CON post- infection, higher in SPS at 24h (p<0.05), but unchanged in MCEL and FOS when compared to pre-infection values. FOS had a higher expression of neutrophil-chemoattractant IL-8 before infection (p<0.05) compared to other groups. CONCLUSION: The reduction in chloride secretion, proinflammatory cytokines expression and NFkB activation, and increased number of sulfo-acidomucins, and IL-8 expression in the fiber groups, indicates that the degree of fermentability impacts the innate and adaptive immune system, and could be the mechanisms by which dietary fibers reduce S. typhimurium infection-associated-symptoms in neonatal pigs and apply these results to infants.

GLIM Criteria for the Diagnosis of Malnutrition: A Consensus Report From the Global Clinical Nutrition Community.

BACKGROUND: This initiative aims to build a global consensus around core diagnostic criteria for malnutrition in adults in clinical settings. METHODS: The Global Leadership Initiative on Malnutrition (GLIM) was convened by several of the major global clinical nutrition societies. Empirical consensus was reached through a series of face-to-face meetings, telephone conferences, and e-mail communications. RESULTS: A 2-step approach for the malnutrition diagnosis was selected, that is, first screening to identify at risk status by the use of any validated screening tool, and second, assessment for diagnosis and grading the severity of malnutrition. The malnutrition criteria for consideration were retrieved from existing approaches for screening and assessment. Potential criteria were subjected to a ballot among GLIM participants that selected 3 phenotypic criteria (non-volitional weight loss, low body mass index, and reduced muscle mass) and 2 etiologic criteria (reduced food intake or assimilation, and inflammation or disease burden). To diagnose malnutrition at least 1 phenotypic criterion and 1 etiologic criterion should be present. Phenotypic metrics for grading severity are proposed. It is recommended that the etiologic criteria be used to guide intervention and anticipated outcomes. The recommended approach supports classification of malnutrition into four etiology-related diagnosis categories. CONCLUSIONS: A consensus scheme for diagnosing malnutrition in adults in clinical settings on a global scale is proposed. Next steps are to secure endorsements from leading nutrition professional societies, to identify overlaps with syndromes like cachexia and sarcopenia, and to promote dissemination, validation studies, and feedback. The construct should be re-considered every 3-5 years.

Induction of mucosal tolerance in Peyer's patch-deficient, ligated small bowel loops.

To explore the requirement for M cells and the Peyer's patch (PP) in induction of oral tolerance and address the potential in vivo role of intestinal epithelial cells as nonprofessional APCs, we have attempted to induce tolerance in mice with ligated small bowel loops without M cells and Peyer's patches. A 2-centimeter section of vascularized small bowel was spliced away from the gut without disruption of the mesenteric attachments. We introduced OVA directly into the lumen of the loop prior to footpad immunization. By excising segments of bowel that contain PPs in some mice and segments without patches in others, we could study the necessity of the M cell and the underlying patch versus epithelial cells in induction of mucosal tolerance. We show that OVA-specific T cell proliferation and serum antibody responses are reduced in mice that have previously been given OVA both in PP-containing loops and in loops without patches. Furthermore, both high- and low-dose tolerance could be induced in the absence of PPs. Low-dose tolerance is associated with bystander suppression and requires IL-10, which indicates active suppression and the induction of regulatory cells. These data suggest that there is a critical role for components of the mucosal immune system other than PPs in antigen sampling and induction of oral tolerance.

Inflammation and intestinal function: where does it start and what does it mean?

Various key elements of intestinal function, such as digestion, absorption, and barrier function, are impaired during inflammation. Although intestinal damage associated with inflammation originating within the intestine is well-known, inflammation in distant organs can impair intestinal function, despite normal histological appearance of the impacted intestinal mucosa. Widespread clinical dogma indicating that intestinal dysfunction drives inflammation should be reconsidered based on data indicating that, in many situations, inflammation precedes intestinal damage and appears to be the injurious factor. Finally, various nutrients have been shown to protect and/or repair the intestinal mucosa from the effects of inflammation; therefore, strategies for optimizing the nutrients provided during inflammatory states should be considered.

Implications of low muscle mass across the continuum of care: a narrative review.

Abnormalities in body composition can occur at any body weight. Low muscle mass is a predictor of poor morbidity and mortality and occurs in several populations. This narrative review provides an overview of the importance of low muscle mass on health outcomes for patients in inpatient, outpatient and long-term care clinical settings. A one-year glimpse at publications that showcases the rapidly growing research of body composition in clinical settings is included. Low muscle mass is associated with outcomes such as higher surgical and post-operative complications, longer length of hospital stay, lower physical function, poorer quality of life and shorter survival. As such, the potential clinical benefits of preventing and reversing this condition are likely to impact patient outcomes and resource utilization/health care costs. Clinically viable tools to measure body composition are needed for routine screening and intervention. Future research studies should elucidate the effectiveness of multimodal interventions to counteract low muscle mass for optimal patient outcomes across the healthcare continuum. Key messages Low muscle mass is associated with several negative outcomes across the healthcare continuum. Techniques to identify and counteract low muscle mass in clinical settings are needed.