Summary The aging process is associated with gradual and progressive loss of muscle mass along with lowered strength and physical endurance. This condition, sarcopenia, has been widely observed with ...aging in sedentary adults. Regular aerobic and resistance exercise programs have been shown to counteract most aspects of sarcopenia. In addition, good nutrition, especially adequate protein and energy intake, can help limit and treat age-related declines in muscle mass, strength, and functional abilities. Protein nutrition in combination with exercise is considered optimal for maintaining muscle function. With the goal of providing recommendations for health care professionals to help older adults sustain muscle strength and function into older age, the European Society for Clinical Nutrition and Metabolism (ESPEN) hosted a Workshop on Protein Requirements in the Elderly, held in Dubrovnik on November 24 and 25, 2013. Based on the evidence presented and discussed, the following recommendations are made (a) for healthy older people, the diet should provide at least 1.0–1.2 g protein/kg body weight/day, (b) for older people who are malnourished or at risk of malnutrition because they have acute or chronic illness, the diet should provide 1.2–1.5 g protein/kg body weight/day, with even higher intake for individuals with severe illness or injury, and (c) daily physical activity or exercise (resistance training, aerobic exercise) should be undertaken by all older people, for as long as possible.
The information on microbiota composition in the human gastrointestinal tract predominantly originates from the analyses of human faeces by application of next generation sequencing (NGS). However, ...the detected composition of the faecal bacterial community can be affected by various factors including experimental design and procedures. This study evaluated the performance of different protocols for collection and storage of faecal samples (native and OMNIgene.GUT system) and bacterial DNA extraction (MP Biomedicals, QIAGEN and MO BIO kits), using two NGS platforms for 16S rRNA gene sequencing (Ilumina MiSeq and Ion Torrent PGM). OMNIgene.GUT proved as a reliable and convenient system for collection and storage of faecal samples although favouring Sutterella genus. MP provided superior DNA yield and quality, MO BIO depleted Gram positive organisms while using QIAGEN with OMNIgene.GUT resulted in greatest variability compared to other two kits. MiSeq and IT platforms in their supplier recommended setups provided comparable reproducibility of donor faecal microbiota. The differences included higher diversity observed with MiSeq and increased capacity of MiSeq to detect Akkermansia muciniphila, Odoribacteraceae, Erysipelotrichaceae and Ruminococcaceae (primarily Faecalibacterium prausnitzii). The results of our study could assist the investigators using NGS technologies to make informed decisions on appropriate tools for their experimental pipelines.
The Lémann Index is a tool measuring cumulative structural bowel damage in Crohn’s disease (CD). We reported on its validation and updating.
This was an international, multicenter, prospective, ...cross-sectional observational study. At each center, 10 inclusions, stratified by CD duration and location, were planned. For each patient, the digestive tract was divided into 4 organs, upper tract, small bowel, colon/rectum, anus, and subsequently into segments, explored systematically by magnetic resonance imaging and by endoscopies in relation to disease location. For each segment, investigators retrieved information on previous surgical procedures, identified predefined strictures and penetrating lesions of maximal severity (grades 1–3) at each organ investigational method (gastroenterologist and radiologist for magnetic resonance imaging), provided segmental damage evaluation ranging from 0.0 to 10.0 (complete resection). Organ resection-free cumulative damage evaluation was then calculated from the sum of segmental damages. Then investigators provided a 0–10 global damage evaluation from the 4-organ standardized cumulative damage evaluations. Simple linear regressions of investigator damage evaluations on their corresponding Lémann Index were studied, as well as calibration plots. Finally, updated Lémann Index was derived through multiple linear mixed models applied to combined development and validation samples.
In 15 centers, 134 patients were included. Correlation coefficients between investigator damage evaluations and Lémann Indexes were >0.80. When analyzing data in 272 patients from both samples and 27 centers, the unbiased correlation estimates were 0.89, 0,97, 0,94, 0.81, and 0.91 for the 4 organs and globally, and stable when applied to one sample or the other.
The updated Lémann Index is a well-established index to assess cumulative bowel damage in CD that can be used in epidemiological studies and disease modification trials.
Abstract
Background and Aims
Endoscopy and the use of faecal calprotectin faecal CP are among the least-favoured methods for assessing disease activity by inflammatory bowel disease IBD patients; the ...handling/processing of faecal samples is also impractical. Therefore, we sought to develop a novel neo-epitope serum calprotectin enzyme-linked immunosorbent assay ELISA, CPa9-HNE, with the aim of quantifying neutrophil activity and neutrophil extracellular trap NET-osis and proposing a non-invasive method for monitoring disease activity in IBD patients.
Methods
In vitro cleavage was performed by mixing calprotectin S100A9/S100A8 with human neutrophil elastase HNE, and a novel HNE-derived calprotectin neo-epitope CPa9-HNE was identified by mass spectrometry for ELISA development. The CPa9-HNE ELISA was quantified in supernatants from ex vivo activated neutrophils and serum samples from patients with ulcerative colitis UC, n = 43, Crohn’s disease CD, n = 93, and healthy subjects HS, n = 23. For comparison, faecal CP and MRP8/14 biomarkers were also measured.
Results
CPa9-HNE was specific for activated neutrophils ex vivo. Serum CPa9-HNE levels were 4-fold higher in CD p <0.0001 and UC p <0.0001 patients than in HS. CPa9-HNE correlated well with the Simple Endoscopic Score SES-CD score r = 0.61, p <0.0001, MES r = 0.46, p = 0.0141, and the full Mayo score r = 0.52, p = 0.0013. CPa9-HNE was able to differentiate between CD and UC patients in endoscopic remission and moderate/severe disease activity (CD: area under the curve AUC = 0.82 p = 0.0003, UC: AUC = 0.87 p = 0.0004). The performance of CPa9-HNE was equipotent or slightly better than that of faecal CP.
Conclusions
Serum CPa9-HNE levels were highly associated with CD and UC patients. CPa9-HNE correlated with the SES-CD score and the full Mayo score, indicating a strong association with disease activity.
Background
We aimed to determine if there was a higher incidence of small intestinal bacterial overgrowth (SIBO) in non‐alcoholic fatty liver disease (NAFLD) than in patients without NAFLD. Moreover, ...we assessed whether patients with significant fibrosis (SF) had a higher incidence of SIBO compared with patients with non‐significant or no liver fibrosis.
Methods
NAFLD was diagnosed in 117 patients by using Fibroscan with a controlled attenuation parameter (CAP) as well as liver biopsy (LB). SIBO was defined by esophagogastroduodenoscopy with an aspiration of the descending duodenum.
Results
Patients with non‐alcoholic steatohepatitis (NASH) and those with SF on LB had a significantly higher incidence of SIBO than patients without NASH and those without SF, respectively (P < .05). According to histological characteristics, there was a higher proportion of patients in the SIBO group with higher steatosis and fibrosis grade, lobular and portal inflammation, and ballooning grade (P < .001). In multivariate analysis, significant predictors associated with SF and NASH were type 2 diabetes mellitus (T2DM) and SIBO. Moreover, in multivariate analysis, significant predictors that were independently associated with SIBO were T2DM, fibrosis stage and ballooning grade (OR 8.80 (2.07‐37.37), 2.50 (1.16‐5.37) and 27.6 (6.41‐119), respectively). The most commonly isolated were gram‐negative bacteria, predominantly Escherichia coli and Klebsiella pneumoniae.
Conclusion
In this relatively large population of patients, we used a gold standard for both SIBO (quantitative culture of duodenum's descending part aspirate) and NAFLD (LB), and we demonstrated that NASH patients and those with SF had a higher incidence of SIBO. Moreover, significant predictors independently associated with SIBO were T2DM, fibrosis stage and ballooning grade. Although TE is a well‐investigated method for steatosis and fibrosis detection, in our study, independent predictors of SIBO were histological characteristics of NAFLD, while elastographic parameters did not reach statistical significance.
Summary Background & aims Disease-related malnutrition has deleterious consequences on patients' outcome and healthcare costs. The demonstration of improved outcome by appropriate nutritional ...management is on occasion difficult. The European Society of Clinical Nutrition and Metabolism (ESPEN) appointed the Nutrition Education Study Group (ESPEN-NESG) to increase recognition of nutritional knowledge and support in health services. Methods To obtain the best available evidence on the potential effects of malnutrition on morbidity, mortality and hospital stay; cost of malnutrition; effect of nutritional treatment on outcome parameters and pharmaco-economics of nutritional therapy, a systematic review of the literature was performed following Cochrane methodology, to answer the following key questions: Q1) Is malnutrition an independent predictive factor for readmission within 30 days from hospital discharge? Q2) Does nutritional therapy reduce the risk of readmission within 30 days from hospital discharge? Q3) Is nutritional therapy cost-effective/does it reduce costs in hospitalized patients? and Q4) Is nutritional therapy cost effective/does it reduce costs in outpatients? Results For Q1 six of 15 identified observational studies indicated that malnutrition was predictive of re-admissions, whereas the remainder did not. For Q2 nine randomized controlled trials and two meta-analyses gave non-conclusive results whether re-admissions could be reduced by nutritional therapy. Economic benefit and cost-effectiveness of nutritional therapy was consistently reported in 16 identified studies for hospitalized patients (Q3), whereas the heterogeneous and limited corresponding data on out-patients (Q4) indicated cost-benefits in some selected sub-groups. Conclusions This result of this review supports the use of nutritional therapy to reduce healthcare costs, most evident from large, homogeneous studies. In general, reports are too heterogeneous and overall of limited quality for conclusions on impact of malnutrition and its treatment on readmissions.
Neutrophils play a significant role in sustaining chronic inflammation in Inflammatory Bowel Disease. The intestinal basement membrane acts as a barrier for immunological homeostasis, where the α3 ...and α4 chains of type IV collagen are expressed on the mucosal surface. We wanted to develop a biomarker reflecting early tissue injury, providing an opportunity for intervention. Two competitive enzyme-linked immunosorbent assays (ELISAs) quantifying human neutrophil elastase (HNE) degraded neo-epitopes of COL4A3 and COL4A4 were developed and investigated in two observational cohorts (n = 161, n = 100). A biomarker of MMP-mediated degradation of COL4A1 (C4M) was used for comparison. In Cohort 1, patients with mild endoscopic ulcerative colitis showed elevated levels of C4A3-HNE compared to those with severe disease. C4M had a strong positive correlation with disease activity. C4A3-HNE/C4M provided superior discrimination between mild and severe endoscopic disease and negatively correlated to disease activity. In Cohort 2, C4A4-HNE and C4A4-HNE/C4M showed similar trends. C4A3-HNE and C4A4-HNE possibly reflect early intestinal tissue injury. Combining the markers with a biomarker of another α-chain of the same collagen provides information on two distinct stages of mucosal damage. These biomarkers may be used to monitor disease flare-up in patients in remission, reducing the need for frequent endoscopic procedures.
The healthy intestine represents a remarkable interface where sterile host tissues come in contact with gut microbiota, in a balanced state of homeostasis. The imbalance of gut homeostasis is ...associated with the onset of many severe pathological conditions, such as inflammatory bowel disease (IBD), a chronic gastrointestinal disorder increasing in incidence and severely influencing affected individuals. Despite the recent development of next generation sequencing and bioinformatics, the current scientific knowledge of specific triggers and diagnostic markers to improve interventional approaches in IBD is still scarce. In this review we present and discuss currently available and emerging therapeutic options in modulating composition and metabolic activity of gut microbiota in patients affected by IBD. Therapeutic approaches at the microbiota level, such as dietary interventions alone or with probiotics, prebiotics and synbiotics, administration of antibiotics, performing fecal microbiota transplantation (FMT) and the use of nematodes, all represent a promising opportunities towards establishing and maintaining of well-being as well as improving underlying IBD symptoms.
The knowledge on how gut microbes contribute to the inflammatory bowel disease (IBD) at the onset of disease is still scarce. We compared gut microbiota in newly diagnosed, treatment-naïve adult IBD ...(Crohn's disease (CD) and ulcerative colitis (UC)) to irritable bowel syndrome (IBS) patients and healthy group. Mucosal and fecal microbiota of 49 patients (13 UC, 10 CD, and 26 IBS) before treatment initiation, and fecal microbiota of 12 healthy subjects was characterized by 16S rRNA gene sequencing. Mucosa was sampled at six positions, from terminal ileum to rectum. We demonstrate that mucosal microbiota is spatially homogeneous, cannot be differentiated based on the local inflammation status and yet provides bacterial footprints superior to fecal in discriminating disease phenotypes. IBD groups showed decreased bacterial diversity in mucosa at all taxonomic levels compared to IBS. In CD and UC, Dialister was significantly increased, and expansion of Haemophilus and Propionibacterium characterized UC. Compared to healthy individuals, fecal microbiota of IBD and IBS patients had increased abundance of Proteobacteria, Enterobacteriaceae, in particular. Shift toward reduction of Adlercreutzia and butyrate-producing taxa was found in feces of IBD patients. Microbiota alterations detected in newly diagnosed treatment-naïve adult patients indicate that the microbiota changes are set and detectable at the disease onset and likely have a discerning role in IBD pathophysiology. Our results justify further investigation of the taxa discriminating between disease groups, such as H. parainfluenzae, R. gnavus, Turicibacteriaceae, Dialister, and Adlercreutzia as potential biomarkers of the disease.
The link between metabolic syndrome (MetS) and sarcopenia has not been extensively studied, but it is evident that they share several common features. Crucial mechanisms involved in ...sarcopenia-nonalcoholic fatty liver disease (NAFLD) interplay are based on effects of insulin resistance, chronic inflammation, oxidative stress, and crosstalk between organs by secretion of cytokines (hepatokines, adipokines, and myokines). Currently, published studies confirm the association of sarcopenia with the degree of NAFLD defined by liver histology. However, prospective studies that will give us information regarding the causal effect of NAFLD and sarcopenia are still needed. Furthermore, there is a need for a patient-friendly, noninvasive, low-cost method for detection of loss of skeletal muscle mass, strength, and physical performance in the context of NAFLD. Moreover, potential treatment strategies such as physical exercise and nutritional supplementation, that are usually a part of management of sarcopenia, should also be investigated in NAFLD patients, especially given the fact that for now, we do not have a good treatment option for NAFLD. Therefore, future investigations should combine studies on NAFLD and sarcopenia in terms of physical activity and nutritional interventions such as vitamin D supplementation. This review aims to report recent evidence concerning the links between sarcopenia and NAFLD and methods to assess sarcopenia.
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