Natural bioactive compounds-The promising candidates for the treatment of intestinal failure-associated liver disease.

Parenteral nutrition (PN) is a life-saving procedure conducted to maintain a proper nutritional state in patients with severe intestinal failure who cannot be fed orally. A serious complication of PN therapy is liver failure, known as intestinal failure-associated liver disease (IFALD). The pathogenesis of IFALD is multifactorial and includes inhibition of the farnesoid X receptor (FXR) by PN components, bacteria translocation from impaired intestines, and intravenous line-associated bloodstream infection. Currently, the most frequently researched therapeutic option for IFALD is using lipid emulsions based on soy or fish oil and, therefore, free from phytosterols known as FXR antagonists. Nevertheless, the potential side effects of the lack of soybean oil delivery seem to outweigh the benefits, especially in the pediatric population. PN admixture provides all the necessary nutrients; however, it is deprived of exogenous natural bioactive compounds (NBCs) of plant origin, such as polyphenols, characterized by health-promoting properties. Among them, many substances have already been known to demonstrate the hepatoprotective effect in various liver diseases. Therefore, searching for new therapeutic options for IFALD among NBCs seems reasonable and potentially successful. This review summarizes the recent research on polyphenols and their use in treating various liver diseases, especially metabolic dysfunction-associated steatotic liver diseases (MASLD). Furthermore, based on scientific reports, we have described the molecular mechanism of action of selected NBCs that exert hepatoprotective properties. We also summarized the current knowledge on IFALD pathogenesis, described therapeutic options undergoing clinical trials, and presented the future perspective of the potential use of NBCs in PN therapy.

Carrageenan in the Diet: Friend or Foe for Inflammatory Bowel Disease?

While the exact pathogenesis of IBD remains unclear, genetic, environmental and nutritional factors as well as the composition of the gut microbiome play crucial roles. Food additives, which are increasingly consumed in the Western diet, are being investigated for their potential effects on IBD. These additives can affect gut health by altering the composition of the microbiota, immune responses, and intestinal permeability, contributing to autoimmune diseases and inflammation. Despite the growing number of studies on food additives and IBD, the specific effects of carrageenan have not yet been sufficiently researched. This review addresses this gap by critically analyzing recent studies on the effects of carrageenan on the gut microbiota, intestinal permeability, and inflammatory processes. We searched the MEDLINE and SCOPUS databases using the following terms: carrageenan, carrageenan and inflammatory bowel disease, carrageenan and cancer, food additives and microbiome, food additives and intestinal permeability, and food additives and autoimmune diseases. In animal studies, degraded carrageenan has been shown to trigger intestinal ulceration and inflammation, highlighting its potential risk for exacerbating IBD. It can affect the gut microbiota, reduce bacterial diversity, and increase intestinal permeability, contributing to "leaky gut" syndrome. Some studies suggest that carrageenan may inhibit the growth of cancer cells by influencing the progression of the cell cycle, but the anti-cancer effect is still unclear. Carrageenan may also increase glucose intolerance and insulin resistance. Further research is needed to determine whether carrageenan should be excluded from the diet of individuals with IBD.

Management of Adult Patients with Gastrointestinal Symptoms from Food Hypersensitivity-Narrative Review.

The incidence of food hypersensitivity has increased dramatically over the years not only among children but also in adults. Adult patients are usually less suspected of food hypersensitivity symptoms since food allergies are more typical for small children, with a tendency to outgrow the condition. The aim of this article is to increase awareness of hypersensitivity to food symptoms and their diagnosis and treatment possibilities among gastroenterologists and other health care professionals dealing with this type of patient. Symptoms of many gastrointestinal disorders, especially functional, may be driven by different types of mechanisms, and food intolerance or allergy should be considered as a potential cause. This article presents the current understanding of the epidemiology, diagnosis and treatment of immune- and non-immune-mediated food-induced diseases. Diagnosis of food hypersensitivity is based mainly on medical history, different types of sensitivity tests, e.g., hydrogen breath test, specific IgE (sIgE) serum concentration, tissue eosinophil count, skin tests and oral food challenges considered as a "gold standard" for food allergy. Elimination diet and pharmacologic treatment for allergy symptoms are first-line therapies. Eosinophilic gastrointestinal diseases are often caused by non-IgE-mediated food allergies, require endoscopic biopsy samples to confirm diagnosis and proper elimination diet often combined with steroids or proton pump inhibitor agents for treatment. Mast cell activation syndrome (MCAS) derives from pathologic reaction of mast cells with increased tryptase serum level as a marker. Symptoms may occur in the digestive, respiratory, skin, neurologic and cardiovascular system. Treatment is based on histamine type 1, type 2 (H1, H2) receptor antagonists and other mast cell stabilizing agents. Carbohydrate intolerances are the most common type of food hypersensitivity in adult patients, and an elimination diet is effective for reducing symptoms. Food additives hypersensitivity remains difficult to diagnose, but use of a diet low in chemical substances alleviates symptoms and helps to diagnose the triggering factors.

Home parenteral nutrition a life-saving therapy in a primary intestinal lymphangiectasia patient affecting the entire GI tract - 3 year follow-up case report.

INTRODUCTION AND IMPORTANCE: Primary intestinal lymphangiectasia (PIL) is a rare protein-losing gastroenteropathy of unknown etiology, characterized by impaired lymphatic vessels drainage. The pathological changes in PIL result in usually localized or diffuse dilatation of intestinal lacteals, leading to leakage of lymphatic fluid rich of proteins, lymphocytes, and immunoglobulins into the intestinal lumen. PIL may be asymptomatic or mildly symptomatic in moderate forms of the disease. In some patients, though, the outcome may be poor or even life-threatening. This case report demonstrates the severity of protein malnutrition, in some cases, and the extent of GI tract affected, requiring to start PN early and the need for its continuation as home parenteral nutrition (HPN). CASE PRESENTATION: We present a case of 39-year-old male with Factor V Leiden deficiency, who presented initially with symptoms of malnutrition and anasarca. The diagnosis was confirmed by histopathological findings pathognomonic for PIL from biopsies of the stomach, small intestine and colon. CLINICAL DISCUSSION: The patient was started on low fat, high protein parenteral nutrition from the beginning of the treatment and required a long-term HPN for 3 years, because trials of tapering off and discontinuation of PN led to worsening of the biochemical results and recurrence of symptoms. Patient gradually improved and stabilized with persistent nutritional support. CONCLUSIONS: The presented case report shows the magnitude of nutritional support (HPN) needed for severe PIL patients. HPN offers PIL patients with poor outcome and life-threatening complications a chance to improve and lead a normal life.

Role of Probiotics in Modulating Human Gut Microbiota Populations and Activities in Patients with Colorectal Cancer-A Systematic Review of Clinical Trials.

BACKGROUND: Growing attention has been given to the role of nutrition and alterations of microbial diversity of the gut microbiota in colorectal cancer (CRC) pathogenesis. It has been suggested that probiotics and synbiotics modulate enteric microbiota and therefore may be used as an intervention to reduce the risk of CRC. The aim of this study was to evaluate the influence of probiotics/synbiotics administration on gut microbiota in patients with CRC. METHODS: PubMed, Scopus, and Web of Science were searched between December 2020 and January 2021. Randomized controlled trials (RCTs) recruiting adults with CRC, who have taken probiotics/synbiotics for at least 6 days were included. Changes in gut microbiota and selected biochemical and inflammatory parameters (i.e., hsCRP, IL-2, hemoglobin) were retrieved. RESULTS: The search resulted in 198 original research articles and a final 6 were selected as being eligible, including 457 subjects. The median age of patients was 65.4 years old and they were characterized by the median BMI value: 23.8 kg/m2. The literature search revealed that probiotic/synbiotic administration improved enteric microbiota by increasing the abundance of beneficial bacteria such as Lactobacillus, Eubacterium, Peptostreptococcus, Bacillus and Bifidobacterium, and decreased the abundance of potentially harmful bacteria such as Fusobacterium, Porhyromonas, Pseudomonas and Enterococcus. Additionally, probiotic/synbiotic intervention improved release of antimicrobials, intestinal permeability, tight junction function in CRC patients. CONCLUSIONS: The use of probiotics/synbiotics positively modulates enteric microbiota, improves postoperative outcomes, gut barrier function and reduces inflammatory parameters in patients suffering from CRC.

Interventions Preventing Vaginitis, Vaginal Atrophy after Brachytherapy or Radiotherapy Due to Malignant Tumors of the Female Reproductive Organs-A Systematic Review.

BACKGROUND: Radiotherapy, as a method of treatment of cervical and uterine cancers, may induce severe late-onset vaginal side effects. Unfortunately, little evidence on the management of adverse effects has been presented. This study aimed to evaluate the available interventions which reduce symptoms of vaginitis and vaginal atrophy by improving dyspareunia, mucosal inflammation, vaginal pH and vaginal dryness in women who have undergone brachytherapy or radiotherapy due to uterine or cervical malignancies. MATERIALS AND METHODS: A comprehensive literature search was performed following PRISMA guidelines. The systematic search was conducted using electronic databases, namely Scopus, Web of Science and PubMed, between October and November 2020 to identify randomized controlled trials (RCT) and, prospective randomized studies (PRS). RESULTS: The analyzed population consists of 376 patients with uterine or cervical cancer, treated with hyaluronic acid, vitamin A, vitamin E, alpha-tocopherol acetate and dienestrol. Intervention with HA along with vitamin A and vitamin E revealed advantage in endpoints such as reduced dyspareunia, vaginal mucosal inflammation, vaginal dryness, bleeding, fibrosis and cellular atypia. Administration of alpha-tocopherol acetate reduced vaginal mucosal inflammation and improved vaginal acanthosis, whereas dienestrol resulted in reduced dyspareunia, vaginal caliber and bleeding. CONCLUSIONS: Vaginal suppositories were found to be clinically effective at the management of late-onset vulvovaginal side effects after radiotherapy.

Parenteral and Enteral Nutrition: A Bridge to Healing and Biological Therapy in a Patient With Enterocutaneous Fistula and Sepsis Complicated Crohn's Disease.

Inflammatory bowel disease (IBD) patients with severe infections, abscess, or sepsis are ineligible for standard treatment using biological and immunosuppressive drug regimens. We report a case of complicated Crohn's disease with ruptured abdominal abscess, presence of enterocutaneous fistula, and sepsis. We also report and discuss patient management with parenteral nutrition (PN) and enteral nutrition (EN) and treatment outcomes. We report a case of a 31-year-old female with a 10-year history of IBD in clinical remission, who, after previous total proctocolectomy with J-pouch, presented to the clinic with severe abdominal pain of 2 days, unintentional weight loss, fatigue, fever, and abdominal abscess, which ruptured, and her clinical state became complicated by sepsis. PN was initiated using individually prepared admixture according to patient requirements, because of inability to tolerate any oral intake. Following the remittance of ileus symptoms, EN was added using a semielemental formula via a nasojejunal tube. Upon completion of the treatment, the fistula resolved, the wound had healed, and Crohn's Disease Activity Index score showed remission. This qualified the patient for initiation of biological therapy with infliximab. Patients with severe infections, abscesses, or sepsis are ineligible for standard IBD treatment using biological and immunosuppressive drug regimens. Furthermore, usually patients' nutrition condition prevents them from combating infection and initiating proper healing process. This case demonstrates the importance of considering nutrition therapy-PN and EN-in unstable patients who cannot be treated with standard pharmacological therapy. Nutrition therapy offers a bridge that allows patients to stabilize and heal before starting standard pharmacological treatment with immunosuppressive agents or biological therapy.

High Dose Intravenous Fish Oil Reduces Inflammation-A Retrospective Tale from Two Centers.

AIM: Patients on parenteral nutrition (PN) are prone to inflammation. This may aggravate an existing proinflammatory state and become a critical factor in the development of liver dysfunction (LD). Intravenous fish oil may attenuate this inflammatory state, but data on its use in adults are scarce. The aim of this study was to investigate the effects of adding a pure fish oil intravenous lipid emulsion (ILE) into short- and long-term PN in patients either at risk of, or with existing, inflammation. METHODS: A retrospective analysis of 61 patients (32 female, 29 male, mean age 51.5 ± 12.6 years) who received all-in-one PN, including amino acids, glucose, and lipids supplemented with pure fish oil ILE, was performed. Pure fish oil ILE (Omegaven®, Fresenius Kabi, Bad Homburg, Germany) was used along with the standard ILE to reach a fish oil dose of 0.4-0.5 g fish oil/kg/d. Diagnoses were chronic intestinal failure (CIF, n = 20), Crohn's disease (CD, n = 22), and ulcerative colitis (UC, n = 19). The observation period was 12 months for CIF and 21 days for UC and CD. RESULTS: A reduction in inflammation was noticeable in all patients and became statistically significant in CD (hsCRP p < 0.0001, ESR p = 0.0034, procalcitonin p = 0.0014, Il-6 p = 0.001) and UC groups (hsCRP and ESR p < 0.0001, Il-6 p = 0.0001, TNF-α p = 0.0113). In the CIF group, the total bilirubin concentration (p = 0.2157) and aspartate transaminase SGOT (p = 0.1785) did not vary over time. CONCLUSIONS: PN with pure fish oil ILE reduces some inflammatory parameters in IBD and maintains liver function parameters in CIF patients. Fish oil might become a valuable ingredient in both short- and long-term PN in patients at risk of liver dysfunction.

The Effectiveness of Multi-Session FMT Treatment in Active Ulcerative Colitis Patients: A Pilot Study.

The modification of the microbiome through fecal microbiota transplantation (FMT) is becoming a very promising therapeutic option for inflammatory bowel disease (IBD) patients. Our pilot study aimed to assess the effectiveness of multi-session FMT treatment in active ulcerative colitis (UC) patients. Ten patients with UC were treated with multi-session FMT (200 mL) from healthy donors, via colonoscopy/gastroscopy. Patients were evaluated as follows: at baseline, at week 7, and after 6 months, routine blood tests (including C reactive protein (CRP) and calprotectin) were performed. 16S rRNA gene (V3V4) sequencing was used for metagenomic analysis. The severity of UC was classified based on the Truelove-Witts index. The assessment of microbial diversity showed significant differences between recipients and healthy donors. FMT contributed to long-term, significant clinical and biochemical improvement. Metagenomic analysis revealed an increase in the amount of Lactobacillaceaea, Micrococcaceae, Prevotellaceae, and TM7 phylumsp.oral clone EW055 during FMT, whereas Staphylococcaceae and Bacillaceae declined significantly. A positive increase in the proportion of the genera Bifidobacterium, Lactobacillus, Rothia, Streptococcus, and Veillonella and a decrease in Bacillus, Bacteroides, and Staphylococcus were observed based on the correlation between calprotectin and Bacillus and Staphylococcus; ferritin and Lactobacillus, Veillonella, and Bifidobacterium abundance was indicated. A positive change in the abundance of Firmicutes was observed during FMT and after 6 months. The application of multi-session FMT led to the restoration of recipients' microbiota and resulted in the remission of patients with active UC.

The Clinical Importance of 21-Day Combined Parenteral and Enteral Nutrition in Active Inflammatory Bowel Disease Patients.

The aim of the study was to show the clinical magnitude of short-term feeding: enteral nutrition (EN) combined with parenteral nutrition (PN) in active Crohn's disease and ulcerative colitis patients. Among 122 eligible inflammatory bowel disease (IBD) patients, 65 met the inclusion criteria. Combined EN and PN was administered for 21 days, wherein over the first 3-5 days of treatment, trophic enteral nutrition (300 kcal/day) was used with an energy increase of up to 1500 kcal. An EN was administered using a nasogastric tube or, in case of intolerance, using a naso-jejunal tube. For PN, the "All in One" system was used according to individually prepared admixtures (ESPEN Guidelines). In addition to routine blood measurement (i.e., ALAT, ASPAT, GGTP, creatinine, lipid profile), the following parameters were assessed: adiponectin, leptin, (hs)TNF-α, hsIL-6 and hsIL-10, TSH, NT-proBNP, serum vitamin B12 concentration, and tHcy. The results showed a considerable improvement in all clinically significant parameters (p < 0.05), showing the benefits and importance of short-term well-balanced EN combined with PN for nutritional and clinical status in IBD patients with active disease. The daily work at hospitals with active IBD patients demonstrates the potential of continued administration of home-based nutrition by patients.

C-reactive protein as a diagnostic and prognostic factor in inflammatory bowel diseases.

AIM: The study aimed to evaluate high-sensitivity CRP (hsCRP) as a diagnostic and predictive marker in patients with inflammatory bowel disease (IBD). MATERIAL/METHODS: Medical history of 106 patients with IBD revealed hsCRP concentrations at diagnosis and during the follow-up period. RESULTS: The study showed that the majority of investigated patients had elevated hsCRP concentrations at diagnosis, although the mean concentration was much higher in the group of patients with Crohn's disease (CD) than the group with ulcerative colitis (UC) (P<0.001). The overall decrease in mean hsCRP concentration observed during the follow-up period was larger in the group of CD patients. The analysis showed a correlation between hsCRP concentrations at diagnosis and risk of surgery in the group of CD patients (r=0.408, P=0.002), but not in the group of UC patients. In a logistic regression analysis, surgery in CD patients was associated with age (OR: 0.89, 95% CI: 0.8-1.0, P=0.05) and hsCRP concentration (OR: 1.02, 95% CI: 1.0-1.04, P=0.03) at diagnosis. DISCUSSION: HsCRP might be a useful diagnostic marker in differentiating active IBD from other diseases. Particularly important however seems to be the predictive value of hsCRP at diagnosis in prognosing the clinical outcome of the disease in CD patients.

Applicability of endoscopic indices in the determination of disease activity in patients with ulcerative colitis.

OBJECTIVE: The combination of clinical remission and mucosal healing represents a major goal of different treatment strategies for ulcerative colitis (UC). This study aimed to assess which of the endoscopic indices used to evaluate mucosal changes in UC are correlated with clinical indices currently used to determine disease activity, as well as which of the endoscopic indices are correlated with the Geboes Index used for histological evaluation. It also aimed to find correlations between the currently used clinical activity indices and the histological Geboes Index. METHODS: A group of 49 patients with a confirmed diagnosis of UC and a group of 52 individuals without a diagnosis of gastrointestinal disease, who constituted the control group, were investigated. All patients were evaluated by colonoscopy, and the severity of mucosal changes was scored in terms of nine different endoscopic indices commonly used in both pharmacological trials and clinical practice. Evaluation was also carried out using clinical and histological indices. Endoscopic indices used for UC were then correlated with different clinical and histological indices to find the strongest correlations. RESULTS AND CONCLUSION: A high correlation was demonstrated between three of the 11 evaluated clinical indices - Improvement Based on Individual Symptom Scores, Ulcerative Colitis Disease Activity Index, and Schroeder Index - and all nine endoscopic indices - Ulcerative Colitis Endoscopic Index of Severity, Baron Score, Schroeder Index, Feagan Index, Powell-Tuck Index, Rachmilewitz Index, Sutherland Index, Lofberg Index, and Lemman Index. Improvement Based on Individual Symptom Scores was the index with the highest correlation with all the endoscopic indices used for UC. The above indices are recommended for clinical evaluation of UC activity. The Ulcerative Colitis Endoscopic Index of Severity was moderately correlated with a histological index, and it is therefore recommended for routine endoscopic mucosal evaluation in patients with UC.

Circulating Visfatin in Hypothyroidism Is Associated with Free Thyroid Hormones and Antithyroperoxidase Antibodies.

We hypothesized that regulation of visfatin in hypothyroidism might be altered by coexisting chronic autoimmune thyroiditis. This is a prospective case-control study of 118 subjects. The autoimmune study group (AIT) consisted of 39 patients newly diagnosed with hypothyroidism in a course of chronic autoimmune thyroiditis. The nonautoimmune study group (TT) consisted of 40 patients thyroidectomized due to the differentiated thyroid cancer staged pT1. The control group comprised 39 healthy volunteers adjusted for age, sex, and BMI with normal thyroid function and negative thyroid antibodies. Exclusion criteria consisted of other autoimmune diseases, active neoplastic disease, diabetes mellitus, and infection, which were reported to alter visfatin level. Fasting blood samples were taken for visfatin, TSH, free thyroxine (FT4), free triiodothyronine (FT3), antithyroperoxidase antibodies (TPOAb), antithyroglobulin antibodies (TgAb), glucose, and insulin levels. The highest visfatin serum concentration was in AIT group, and healthy controls had visfatin level higher than TT (p = 0.0001). Simple linear regression analysis revealed that visfatin serum concentration was significantly associated with autoimmunity (ß = 0.1014; p = 0.003), FT4 (ß = 0.05412; p = 0.048), FT3 (ß = 0.05242; p = 0.038), and TPOAb (ß = 0.0002; p = 0.0025), and the relationships were further confirmed in the multivariate regression analysis.

Usefulness of selected laboratory markers in ulcerative colitis.

INTRODUCTION: This study aimed to compare the accuracy of selected laboratory markers in assessing disease activity in patients with ulcerative colitis (UC). The analysis included serum IL-2, IL-4, IL-6, IL-10, IL-17, TNF-, IFN-, hsCRP, peripheral regulatory T cells, as well as fecal calprotectin and lactoferrin. PATIENTS AND METHODS: A group of 45 adults with UC was enrolled in the study. Disease activity was assessed using the Mayo endoscopic index, while for clinical activity scoring, the Clinical Activity Index (CAI) was used. Concentrations of markers investigated were estimated by means of flow cytometry and enzyme-linked immunosorbent assays: the results were correlated with both indices. RESULTS: The study demonstrated that both fecal markers, i.e. calprotectin (r = 0.880, P<0.001) and lactoferrin (r = 0.799, P<0.001) correlated closely with the Mayo endoscopic score, and might be used to evaluate the severity of UC in the clinical setting. The correlation of these markers with CAI was also significant, with r = 0.831 for calprotectin (P<0.001) and r = 0.672 for lactoferrin (P<0.05). As for the other markers investigated, only IL-6 (r = 0.598, P<0.001), IL-17A (r = 0.587, P<0.005), and TNF- (r = 0.701, P<0.001) correlated closely with the Mayo endoscopic index. The correlation of the markers with CAI was also significant, though weaker, with r = 0.525 for IL-6 (P<0.001), r = 0.587 for IL-17A (P<0.05), and r = 0.624 for TNF- (P<0.001). DISCUSSION: Despite the fact, that UC is generally considered to be an IL-13-driven, Th2-like type of disease, markers of inflammation such as serum interleukin (IL)-6, IL-17, TNF-, fecal calprotectin and lactoferrin might be useful in assessing disease activity.