Casein glycomacropeptide is well tolerated in healthy adults and changes neither high-sensitive C-reactive protein, gut microbiota nor faecal butyrate: a restricted randomised trial.

Casein glycomacropeptide (CGMP) is a bioactive milk-derived peptide with potential anti-inflammatory effects. Animal studies suggest that CGMP may work by altering gut microbiota composition and enhancing butyrate production. Its effects on intestinal homoeostasis, microbiota and metabolites in humans are unknown. The aim of the present study was to assess both the intestinal and systemic immunomodulatory effects of orally ingested CGMP. We hypothesised that daily oral CGMP intake would reduce high-sensitive C-reactive protein (hsCRP) in healthy adults. In a single-centre limited but randomised, double-blinded, reference-controlled study, we compared the effects of a 4-week intervention of either 25 g of oral powder-based chocolate-flavoured CGMP or a reference drink. We included twenty-four healthy adults who all completed the study. CGMP had no systemic or intestinal immunomodulatory effects compared with a reference drink, with regard to either hsCRP or faecal calprotectin level, faecal microbiota composition or faecal SCFA content. CGMP ingestion did not affect satiety or body weight, and it caused no severe adverse events. The palatability of CGMP was acceptable, and adherence was high. CGMP did not induce or change gastrointestinal symptoms. In conclusion, we found no immunomodulatory effects of CGMP in healthy adults. In a minor group of healthy adults, oral ingestion of 25 g of CGMP during 4 weeks was safe, well tolerated, had acceptable palatability and was without any effects on body weight.

Current, experimental, and future treatments in inflammatory bowel disease: a clinical review.

Inflammatory bowel diseases (IBDs) may result from dysregulated mucosal immune responses directed toward the resident intestinal microbiota. This review describes the hallmark immunobiology of Crohn's disease and ulcerative colitis as well as therapeutic targets and mechanisms of action for current, experimental, and future treatments in IBD. Conventional therapies include 5-aminosalicylic acid, glucocorticosteroids, thiopurines, and methotrexate. Since 1997, monoclonal antibodies have gained widespread use. These consist of antibodies directed against pro-inflammatory cytokines such as tumor necrosis factor α, interleukin (IL)-12, and IL-23, or anti-homing antibodies directed against α4ß7 integrin. Emerging oral therapies include modulators of intracellular signal transduction such as Janus kinase inhibitors. Vitamin D may help to regulate innate and adaptive immune responses. Modulation of the intestinal microbiota, using live microorganisms (probiotics), substrates for the colonic microbiota (prebiotics), or fecal microbiota transplantation (FMT), is in development. Dietary supplements are in widespread use, but providing evidence for their benefit is challenging. Stem cell treatment and nervous stimulation are promising future treatments.

A Proposal for a Study on Treatment Selection and Lifestyle Recommendations in Chronic Inflammatory Diseases: A Danish Multidisciplinary Collaboration on Prognostic Factors and Personalised Medicine.

Chronic inflammatory diseases (CIDs), including Crohn's disease and ulcerative colitis (inflammatory bowel diseases, IBD), rheumatoid arthritis, psoriasis, psoriatic arthritis, spondyloarthritides, hidradenitis suppurativa, and immune-mediated uveitis, are treated with biologics targeting the pro-inflammatory molecule tumour necrosis factor-α (TNF) (i.e., TNF inhibitors). Approximately one-third of the patients do not respond to the treatment. Genetics and lifestyle may affect the treatment results. The aims of this multidisciplinary collaboration are to identify (1) molecular signatures of prognostic value to help tailor treatment decisions to an individual likely to initiate TNF inhibitor therapy, followed by (2) lifestyle factors that support achievement of optimised treatment outcome. This report describes the establishment of a cohort that aims to obtain this information. Clinical data including lifestyle and treatment response and biological specimens (blood, faeces, urine, and, in IBD patients, intestinal biopsies) are sampled prior to and while on TNF inhibitor therapy. Both hypothesis-driven and data-driven analyses will be performed according to pre-specified protocols including pathway analyses resulting from candidate gene expression analyses and global approaches (e.g., metabolomics, metagenomics, proteomics). The final purpose is to improve the lives of patients suffering from CIDs, by providing tools facilitating treatment selection and dietary recommendations likely to improve the clinical outcome.

Casein glycomacropeptide for active distal ulcerative colitis: a randomized pilot study.

BACKGROUND: In ulcerative colitis (UC), dietary supplements may have anti-inflammatory properties and improve disease course. We investigated the effects of casein glycomacropeptide (CGMP), a fraction of bovine whey protein, in active UC. MATERIALS AND METHODS: In a randomized open-label intervention study, 24 patients with active UC involving 10-40 cm of the distal colon were randomized in a 2 : 1 ratio into two groups. The first group was administered their usual treatment plus a daily supplement of CGMP 30 g, and the second group was administered a dose escalation to 4800 mg oral mesalamine daily (standard treatment) for 4 weeks. Clinical, endoscopic, mucosal and circulating disease activity markers were monitored. Acceptance of and adherence to CGMP up to 8 weeks were documented. RESULTS: After 4 weeks of treatment, 10 of 16 (63%) patients who received CGMP had an unchanged or decreased Simple Clinical Colitis Activity Index (SCCAI), which was similar to the four of eight (50%) (P = 0·67) patients on the standard treatment. The number of patients in which SCCAI decreased by three or more did not differ between the two groups: nine of 16 (56%) in the CGMP group vs. four of eight (50%) in the standard treatment group (P = 0·77). Changes in disease extent and severity were similar between the two groups. CGMP was well tolerated and accepted by the patients. CONCLUSIONS: The addition of CGMP as a nutritional therapy to standard treatment was safe and accepted by patients with active distal UC. The disease-modifying effect of CGMP was similar to that of the mesalamine dose escalation.

Patient-reported outcomes after acute nonvariceal upper gastrointestinal hemorrhage.

OBJECTIVE: Nonvariceal acute upper gastrointestinal bleeding (AUGIB) is often associated with significant blood loss and anemia. Both the bleeding episode itself and the subsequent anemia are likely to significantly impact a patient's health-related quality of life (HRQoL). Treating the anemia is essential to increase the hemoglobin levels. The HRQoL impact has not been investigated. This longitudinal study aimed to determine the relationship between anemia, HRQoL, and fatigue in patients after nonvariceal AUGIB. MATERIALS AND METHODS: A total of 97 patients (51 males and 46 females; mean age 70 years) were followed in a longitudinal study with a 6-month follow-up. All patients had AUGIB and were anemic at inclusion. Anemia, HRQoL (EQ-5D-3L), and fatigue (using the Multidimensional Fatigue Inventory) were assessed at baseline, and at 1, 3, and 6 months. The patients were initially included in an iron supplementation study. RESULTS: The patients' HRQoL increased and their fatigue levels decreased from baseline to month 3 and month 6. Approximately half of the patients had full health at month 3; similar results were observed in the general population. Three and six months after the bleeding episodes, neither the HRQoL nor fatigue was affected by the anemia. CONCLUSION: This study did not uncover relationships between anemia and HRQoL or anemia and fatigue after nonvariceal AUGIB.

Oral vitamin D3 supplementation reduces monocyte-derived dendritic cell maturation and cytokine production in Crohn's disease patients.

BACKGROUND: Low serum vitamin D levels may provoke or aggravate Crohn's disease (CrD). Vitamin D3 is a well-known immune modulator that affects immune functions in vitro and may prevent CrD flares. Dendritic cells (DC) are key mediators of vitamin D3 effects. In this study, we describe changes in monocyte-derived DC (mo-DC) maturation marker expression and cytokine production following 26 weeks of oral vitamin D3 supplementation in CrD patients. METHODS: Ten CrD patients who had increased serum 25-hydroxy vitamin D levels after oral vitamin D3 and calcium treatment and ten seasonally matched placebo-treated patients were selected for this study. Mo-DC were generated before and after the 26 weeks and induced to mature upon lipopolysaccharide (LPS) stimulation. Maturation marker expression and cytokine production were analysed. Mo-DC function was analysed in a mixed leucocyte reaction (MLR). RESULTS: Compared with baseline values, LPS-matured mo-DC exhibited reduced expression of CD80 and reduced production of the cytokines IL-10, IL-1ß, and IL-6 following 26 weeks of oral vitamin D3 supplementation. Mo-DC performance in an allogeneic MLR was unchanged after vitamin D3 supplementation. Treatment with the placebo did not affect maturation markers, cytokine production, or the MLR. CONCLUSIONS: Vitamin D3 treatment in CrD patients led to hypo-responsive LPS-stimulated mo-DC. This finding indicates that vitamin D3 levels have an impact on the monocytic precursors of mo-DC in vivo and may explain the positive effects of vitamin D3 supplementation on CrD patients. Alternatively, CrD patients with high serum vitamin D3 levels may represent a subgroup with low disease activity.

Lack of follow-up of anaemia after discharge from an upper gastrointestinal bleeding centre.

INTRODUCTION: Acute upper gastrointestinal bleeding is common and anaemia at discharge also occurs frequently. Follow-up studies of patients after discharge are limited. Furthermore, guidelines for follow-up and treatment of post-discharge anaemia have not been published. MATERIAL AND METHODS: We performed a local, retrospective evaluation of patients admitted for acute upper gastrointestinal bleeding. RESULTS: The retrospective evaluation found that more than 80% of the patients admitted for acute upper gastrointestinal bleeding were discharged with apparent anaemia, and oral iron supplementation was recommended for 16% of the discharged anaemic patients. Our study revealed no standardised follow-up protocols for anaemic patients. CONCLUSION: The follow-up practice for patients with anaemia was inconsistent. Based on our research, well-designed studies are needed to determine the most effective post-discharge treatment for patients who are still anaemic at discharge after endoscopic treatment of acute non-variceal upper gastrointestinal bleeding. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

The effect of a single oral megadose of vitamin D provided as either ergocalciferol (D2) or cholecalciferol (D3) in alcoholic liver cirrhosis.

OBJECTIVE: The goal of this study was to examine the effects of a single oral dose of 300,000 international units of either ergocalciferol (D2) or cholecalciferol (D3) on the plasma levels of 25-hydroxyvitamin D in patients with alcoholic liver cirrhosis. METHODS: Inclusion criteria for this study were diagnosis of alcoholic liver cirrhosis and plasma levels of 25-hydroxyvitamin D less than 25 nmol/l. At baseline, patients were divided into Child-Pugh groups A, B, or C and were given one oral dose of 300,000 international units of ergocalciferol (D2 group, N=23) or cholecalciferol (D3 group, N=13). Plasma concentrations of 25(OH) vitamin D and vitamin D-binding protein were measured on days 0, 7, 30, and 90. RESULTS: On days 7 and 30, patients from the D3 group had higher vitamin D levels than patients from the D2 group (P<0.05). On day 7, vitamin D levels were found to correlate with Child-Pugh scores from patients in the D3 group. For patients in the D2 group, there was a positive correlation between vitamin D and vitamin D-binding protein as indicated by the area under the concentration versus time curves (Spearmen's ρ=0.64 P<0.001). CONCLUSION: In patients with alcoholic liver cirrhosis, a single oral megadose of cholecalciferol was more effective than ergocalciferol in the treatment of vitamin D deficiency. Severe liver disease and low levels of vitamin D-binding protein were predictors for poor treatment outcomes.