Correction: Atuahene et al. A Supplement with Bromelain, Lentinula edodes, and Quercetin: Antioxidant Capacity and Effects on Morphofunctional and Fecal Parameters (Calprotectin, Cortisol, and Intestinal Fermentation Products) in Kennel Dogs. Vet. Sci. 2023, 10, 486.

There was an error in the original publication [...].

A Supplement with Bromelain, Lentinula edodes, and Quercetin: Antioxidant Capacity and Effects on Morphofunctional and Fecal Parameters (Calprotectin, Cortisol, and Intestinal Fermentation Products) in Kennel Dogs.

Oxidative stress causes several pathological conditions in humans and animals, including gastrointestinal disorders. The aim of this study was to analyze the antioxidant capacity of three natural powdered raw materials containing quercetin, bromelain, and Lentinula edodes and develop a new feed supplement for dogs using a combination of them. The total phenolic content (TPC), antioxidant activity, DPPH (2,2-diphenyl-1-picrylhydrazyl), and ABTS (2,2'-Azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt) of the extracts, either individually or in combination, were evaluated colorimetrically. The effects of this supplement on healthy adult dogs' nutritional, inflammatory, and stress status were evaluated. American Staffordshire Terrier adult female dogs (n = 30) were randomly assigned to a control (n = 15) or a treated (n = 15) group. The supplement was added as powder to the food of the treated dogs once daily for 28 days. There was no significant difference in the body weight and body condition scores between the initial and final phases of the experiment. At the end of our study, a significant decrease in fecal calprotectin, cortisol, indole/skatole, and N-methylhistamine and a significant increase in short-chain fatty acids were observed as compared to the control group. In conclusion, this natural feed supplement can be used to improve gastrointestinal health and psycho-physical conditions in dogs.

Prevalence, Pathogenesis and Management of Anemia in Inflammatory Bowel Disease: An IG-IBD Multicenter, Prospective, and Observational Study.

BACKGROUND: Anemia is a common extraintestinal manifestation of inflammatory bowel disease (IBD), with a 6% to 74% prevalence and a negative impact on patient survival and quality of life, although the prevalence is apparently declining due to improved disease treatment. We aimed to investigate the prevalence, pathogenesis, and clinical correlates of anemia in Italian patients with IBD. METHODS: A multicenter, prospective, observational study, involving 28 Italian gastroenterology centers, was conducted to investigate the epidemiology and consequences of IBD-associated anemia. Clinical and laboratory data of anemic patients were obtained at study enrolment. RESULTS: Anemia was diagnosed in 737 of 5416 adult IBD outpatients (prevalence 13.6%); females were more commonly affected than males (odds ratio, 1.5; 95% confidence interval [CI], 1.2-1.7) and had more severe anemia. In the majority of cases, anemia was due to iron deficiency (62.5% of cases; 95% CI, 58.3%-66.6%), either isolated or in association with inflammation and/or vitamin deficiencies; anemia of inflammation accounted for only 8.3% of cases. More severe anemia was associated with increasing fatigue and worse quality of life. Only 68.9% of anemic patients with iron deficiency (95% CI, 63.4%-73.8%) and 34.6% of those with vitamin deficiencies (95% CI, 26.2%-44.2%) were properly treated with supplementation therapy. CONCLUSIONS: In Italy, the prevalence of IBD-associated anemia is lower than previously reported. Anemia of IBD is most commonly due to iron deficiency and contributes to fatigue and poor quality of life, but remains untreated in a large proportion of patients with iron and/or vitamin deficiencies. This study is registered at clinicaltrials.gov as NCT02872376.

The prevalence of inflammatory bowel disease­associated anemia is 13.6%. The prevalence is higher among females younger than 50. Anemia is usually due to iron deficiency and adversely affects fatigue and quality of life. Many patients with iron or vitamin deficiency (31% and 65%, respectively) remain untreated.

Possible Impact of Vitamin D Status and Supplementation on SARS-CoV-2 Infection Risk and COVID-19 Symptoms in a Cohort of Patients with Inflammatory Bowel Disease.

The coronavirus disease (COVID-19) pandemic represents a global health challenge, particularly considering concomitant diseases. Patients with inflammatory bowel diseases (IBD) can be considered a population at risk. On the other hand, the risk of developing IBD and COVID-19 have both been described as modulated by vitamin D (VD) levels. In this work, a cohort of 106 adult patients affected by IBD was prospectively enrolled, during the second wave of the pandemic in Italy. In these patients, VD plasma levels, demographic, and clinical characteristics were tested for a correlation/an association with the risk of infection with SARS-CoV-2 in the study period (anti-spike IgG positivity) and the severity of COVID-19 symptoms. By multivariate logistic regression analysis, VD supplementation (Odds Ratio; OR 0.116, p = 0.002), therapy with monoclonal antibodies (OR 0.227, p = 0.007), and the use of mesalazine (OR 2.968, p = 0.046) were found to be independent predictors of SARS-CoV-2 positivity. Moreover, hypertension was associated with severe disease (p = 0.019), while a VD level higher than 30 ng/mL (p = 0.031, OR 0.078) was associated with asymptomatic infection. No interplay between IBD activity and COVID-19 risk of infection or symptoms was observed. These results confirm the importance of VD levels in defining the risk of COVID-19 and give encouraging data about the safety of maintaining immunomodulatory treatments for IBD during the COVID-19 pandemic.

Vitamin D-Related Genetics as Predictive Biomarker of Clinical Remission in Adalimumab-Treated Patients Affected by Crohn's Disease: A Pilot Study.

Adalimumab (ADA) is a human anti-tumor necrosis factor (TNF-α) monoclonal antibody used in inflammatory bowel diseases, such as Crohn's disease (CD). Vitamin-D (VD) is important for biological functions, such as the modulation of expression of genes encoding enzymes and transporters involved in drug metabolism and transport. ADA trough levels were associated with VD concentrations in patients with IBD, but no data are present in the literature concerning VD pathway-related gene single-nucleotide polymorphisms (SNPs) in affecting clinical outcomes. For this reason, the aim of this study was to evaluate the ability of VD-related genetics to predict clinical remission at 3 and 12 months in patients affected by CD treated with ADA. Patients affected by CD were included in this study. SNPs in CYP27B1, CYP24A1, GC, and VDR genes were analyzed through real-time PCR. A total of 63 patients were enrolled. Calprotectin, hemoglobin, and C-reactive protein levels were influenced by SNPs in VDR, CYP27B1, and GC genes. After 3 months of therapy, clinical remission was predicted by smoke, systemic steroids, and VDR BsmI, whereas at 12 months by GC 1296AA/AC and VD supplementation. This study reports the association between VD pathway-related genetics and ADA treatment. Further studies are needed to confirm these promising data.

Efficacy of a Preparation Based on Calcium Butyrate, Bifidobacterium bifidum, Bifidobacterium lactis, and Fructooligosaccharides in the Prevention of Relapse in Ulcerative Colitis: A Prospective Observational Study.

Several compounds based on short chain fatty acids and/or probiotics/prebiotics have shown promising results in the therapy of ulcerative colitis (UC), possibly due to its key role in restoring gut homeostasis as well as intestinal barrier integrity. Here, we investigated the efficacy of a patented preparation based on calcium butyrate, Bifidobacterium bifidum, Bifidobacterium lactis, and fructooligosaccharides (FEEDColon®, Princeps, Cuneo, Italy) in maintaining remission and improving subjective symptoms and inflammatory indices in patients with UC receiving 5-ASA therapy. A total of 42 patients were prospectively recruited and randomized in 21 patients receiving combination therapy with mesalamine (5-ASA) plus FEEDColon® and 21 patients treated with standard 5-ASA therapy. Patients were assessed at baseline, at 6-month, and 12-month follow-up (FU). Therapeutic success (defined as Mayo partial score ≤ 2 and faecal calprotectin (FC) < 250 µg/g at 12-month FU) was reached by 32 (76%) patients: 20 (95%) among those treated with 5-ASA + FeedColon®, and 12 (57%) among those treated with 5-ASA only (p = 0.009). Consistently, patients treated with combination therapy improved subjective symptoms (quality of life, abdominal pain, and stool consistency) and reduced FC values, while those treated with 5-ASA alone, improved neither subjective symptoms nor FC during the FU. In conclusion, FEEDColon® supplementation appears to be a valid add-on therapy for the maintenance of remission in patients with UC. Further multicentre, placebo-controlled, double-blind clinical trials are needed to validate our results on larger cohorts of patients with UC.

The Usefulness of Microencapsulated Sodium Butyrate Add-On Therapy in Maintaining Remission in Patients with Ulcerative Colitis: A Prospective Observational Study.

Butyrate is a short-chain fatty acid that plays a key role in maintaining gut homeostasis as well as the integrity of the intestinal barrier. In the present study, we investigated the effect of oral microencapsulated sodium butyrate (BLM) administration in maintaining remission and improving residual symptoms and inflammatory markers in a population of patients with ulcerative colitis (UC). Forty-two patients with UC in clinical remission were enrolled in the study. Three patients were lost to follow up; 39 patients (18 treated with BLM add-on therapy and 21 with standard mesalamine only) that reached 12 months of follow up were included in the final analysis. Therapeutic success (defined as Mayo partial score ≤ 2 and faecal calprotectin (FC) < 250 µg/g at 12 months of follow up) was achieved in 25 patients (64.1%); 15/18 (83.3%) in BLM group and 10/21 (47.6%) in control group (p = 0.022). Consistently, 13/18 patients (72.2%) receiving BLM improved residual symptoms compared to 5/21 patients (23.8%) in control group (p = 0.003). FC values significantly diminished from the baseline to the end of follow up in patients that received BLM, while FC values remained almost stable in the control group. In conclusion, oral BLM supplementation appears to be a valid add-on therapy in order to maintain remission in patients with UC. Further randomized, placebo-controlled, double-blind clinical trials are needed to validate our results on a larger population or cohort of patients.

Dual biological therapy with anti-TNF, vedolizumab or ustekinumab in inflammatory bowel disease: a systematic review with pool analysis.

Background: Inflammatory bowel diseases patients eligible for biological therapy represent a group with considerable disease burden and biologics only achieve 40% clinical remission rates in responders after 1 year of therapy. Aims: To collect all the published data about patients treated with dual biological therapy with an Anti-TNF, vedolizumab or ustekinumab, for a period of at least 3 months and to pool the data about the effectiveness and safety. Methods: A MEDLINE, and Web of Science search of all studies published in English until 1 January 2019 was conducted. Results: We included 7 studies with a total of 18 patients. Fifteen patients were treated with a combination of an anti-TNF and vedolizumab, 3 patients were treated with vedolizumab and ustekinumab. Fifty-six percent of patients were affected by Crohn's disease and 50% of patients were treated with an immunosuppressant drug or steroid too. A clinical improvement was obtained in 100% of patients, and an endoscopic improvement in 93% of patients. No serious adverse events were reported. Conclusions: The use of dual biological therapy is an attractive therapeutic option and may be an opportunity to better tailor and personalize the therapies for patients. Further studies, as randomized control trials, to provide comparative efficacy and safety endpoints of combination therapies, and to clarify potential advantages of combined biological therapies, are needed.

Oral iron supplementation with Feralgine® in inflammatory bowel disease: a retrospective observational study.

BACKGROUND: Inflammatory bowel disease (IBD) is a relapsing chronic disease of the gastrointestinal (GI) tract. Among IBD patients, anemia is more frequent than in general population. Recent studies demonstrated a good iron absorption using Feralgine®, a compound of ferrous bysglicinate chelate and alginic acid, oral supplementation with both good compliance rate and efficacy in treating iron deficiency anemia especially due to its high oral bioavailability. In this study we evaluated hemoglobin (Hb) improvement after Feralgine® supplementation in patients with IBD and anemia. METHODS: This is a retrospective observational study. All data were derived from the patients' registry of the Inflammatory Bowel Disease Center, San Giovanni Antica Sede-Molinette Hospital, Turin, Italy. All IBD patients suffering from anemia and treated with Feralgine® (Tecnofer Plus), 1 capsule daily, were selected. RESULTS: Mean Hb value increased from 11 g/dL (95% confidence interval [CI]: 10.72-11.47) to 12.2 g/dL (95% CI: 11.6-12.52, P=0.0001), after three months of Feralgine® supplementation. While 90% of the patients did not report adverse events, 10% experienced dyspepsia and worsening of diarrhea. Only 6% of patients suspended oral iron supplementation due to GI intolerance (adherence rate 94%). CONCLUSIONS: Oral supplementation with Feralgine® induced a significant improvement in Hb levels, suggesting that in IBD patients with mild or moderate anemia, oral iron supplementation could be considered the first line therapy. We suggest further studies on larger cohorts to assess iron, ferritin and transferrin saturation improvement after this treatment.