Can Nutraceuticals Support the Treatment of MASLD/MASH, and thus Affect the Process of Liver Fibrosis?

Currently, metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are considered to be the main causes of fibrosis. In turn, fibrosis may lead to the development of hepatocellular carcinoma or advanced cirrhosis, i.e., potentially life-threatening conditions. It is likely that therapy aimed at reducing the risk of developing hepatic steatosis and inflammation could be helpful in minimizing the threat/probability of organ fibrosis. In recent years, increasing attention has been paid to the influence of nutraceuticals in the prevention and treatment of liver diseases. Therefore, the aim of this review was to describe the precise role of selected ingredients such as vitamin C, beta-carotene, omega-3 fatty acids, and curcumin. It is likely that the use of these ingredients in the treatment of patients with MASLD/MASH, along with behavioral and pharmacological therapy, may have a beneficial effect on combating inflammation, reducing oxidative stress, and thereby preventing liver damage.

Epidemiological Study of Pathogens in Spontaneous Bacterial Peritonitis in 2017-2024-A Preliminary Report of the University Hospital in South-Eastern Poland.

Spontaneous Bacterial Peritonitis (SBP) is a serious complication and a common cause of death in patients with liver cirrhosis. Between January 2017 and March 2024, a retrospective study was conducted involving 302 patients (>18 years old) with ascites treated at a tertiary referral center in south-eastern Poland. Microbiological analysis of the ascitic fluids was performed in all patients. The presence of microorganisms was found in samples from 17 patients, and 21 pathogens were isolated, including 15 Gram-positive bacteria and 6 Gram-negative bacteria. Staphylococcus epidermidis, MRCNS (methicillin-resistant coagulase-negative staphylococci, resistant to all beta-lactam antibiotics: penicillins, penicillins with beta-lactamase inhibitor, cephalosporins and carbapenems) was the main pathogen detected (19.05%, 4/21), followed by Enterococcus faecalis (9.52%, 2/21), Enterococcus faecium (9.52%, 2/21), Staphylococcus haemolyticus, MRCNS (4.76%, 1/21), Streptococcus mitis (9.52%, 2/21), Streptococcus parasanguinis (9.52%, 2/21), Micrococcus luteus (4.76%, 1/21) and Bacillus spp. (4.76%, 1/21). The following Gram-negative bacteria were also found in the specimens examined: Escherichia coli, ESBL (extended-spectrum ß-lactamase producing E. coli) (4.76%, 1/21), Escherichia coli (4.76%, 1/21), Pseudomonas aeruginosa (4.76%, 1/21), Klebsiella oxytoca (9.52%, 2/21) and Sphingomonas paucimobilis (4.76%, 1/21). Gram-positive bacteria caused nosocomial infections in nine patients with SBP, Gram-negative bacteria caused nosocomial infections in two patients. In six patients with SBP, community-acquired infections caused by Gram-negative bacteria were found in three cases, Gram-positive bacteria in two cases, and in one case, community-acquired infection was caused by mixed Gram-positive and Gram-negative. Bacteria isolated from patients with hospital-acquired SBP showed higher drug resistance than those found in patients with non-hospital SBP. Bacterial infections in cirrhotic patients with complications may be responsible for their deteriorating health. Prompt intervention is critical to reducing mortality.

The Complex Relationship between Mechanisms Underlying Inflammatory Bowel Disease, Its Treatment, and the Risk of Lymphomas: A Comprehensive Review.

Patients with inflammatory bowel disease may be at higher risk of developing lymphomas and other cancers of the gastrointestinal tract. In addition, there may be a link between the use of thiopurines or anti-tumor necrosis factor drugs (anti-TNF) and these pathologies. The treatment of patients with Crohn's disease who have previously been diagnosed with lymphoma is a challenge for gastroenterologists. In this report, we examine important clinical issues related to the treatment of patients with inflammatory bowel disease with active lymphoma, as well as of patients with hematological cancer history. In this discussion, we take into account most of the available treatments for inflammatory bowel disease, as well as the impact of chronic inflammation and viral infections. In addition, we try to find common ground for the development of lymphoproliferative disorders and autoimmune diseases. Patients with inflammatory bowel disease may be at higher risk of developing lymphomas and other cancers of the gastrointestinal tract. Chronic inflammatory processes and viral infections play an important role in carcinogenesis. In addition, there may be a link between the use of thiopurines or anti-TNF drugs and these pathologies. A significant risk of the development of lymphoma in people undergoing each therapy should be considered, and it should be estimated how much greater this risk will be in patients with a history of lymphoproliferative disorders. The following review is an attempt to answer which therapy would be the most appropriate for patients with Crohn's disease and a history of lymphoma treatment. A lack of clear guidelines creates great challenges for doctors.

Nutritional Support: The Use of Antioxidants in Inflammatory Bowel Disease.

The problem of treating inflammatory bowel disease continues to be a topic of great interest for researchers. Despite the complexity surrounding their treatment and strategies to prolong periods of remission, there is a promising exploration of various compounds that have potential in combating inflammation and alleviating symptoms. Selenium, calcium, magnesium, zinc, and iron are among these compounds, offering a glimpse of hope in the treatment of IBD. These essential minerals not only hold the promise of reducing inflammation in these diseases, but also show the potential to enhance immune function and possibly influence the balance of intestinal microflora. By potentially modulating the gut microbiota, they may help support overall immune health. Furthermore, these compounds could play a crucial role in mitigating inflammation and minimising complications in patients with IBD. Furthermore, the protective effect of these compounds against mucosal damage in IBD and the protective effect of calcium itself against osteoporosis in this group of patients are notable.

Transplant of microbiota from Crohn's disease patients to germ-free mice results in colitis.

Although the role of the intestinal microbiota in the pathogenesis of inflammatory bowel disease (IBD) is beyond debate, attempts to verify the causative role of IBD-associated dysbiosis have been limited to reports of promoting the disease in genetically susceptible mice or in chemically induced colitis. We aimed to further test the host response to fecal microbiome transplantation (FMT) from Crohn's disease patients on mucosal homeostasis in ex-germ-free (xGF) mice. We characterized and transferred fecal microbiota from healthy patients and patients with defined Crohn's ileocolitis (CD_L3) to germ-free mice and analyzed the resulting microbial and mucosal homeostasis by 16S profiling, shotgun metagenomics, histology, immunofluorescence (IF) and RNAseq analysis. We observed a markedly reduced engraftment of CD_L3 microbiome compared to healthy control microbiota. FMT from CD_L3 patients did not lead to ileitis but resulted in colitis with features consistent with CD: a discontinued pattern of colitis, more proximal colonic localization, enlarged isolated lymphoid follicles and/or tertiary lymphoid organ neogenesis, and a transcriptomic pattern consistent with epithelial reprograming and promotion of the Paneth cell-like signature in the proximal colon and immune dysregulation characteristic of CD. The observed inflammatory response was associated with persistently increased abundance of Ruminococcus gnavus, Erysipelatoclostridium ramosum, Faecalimonas umbilicate, Blautia hominis, Clostridium butyricum, and C. paraputrificum and unexpected growth of toxigenic C. difficile, which was below the detection level in the community used for inoculation. Our study provides the first evidence that the transfer of a dysbiotic community from CD patients can lead to spontaneous inflammatory changes in the colon of xGF mice and identifies a signature microbial community capable of promoting colonization of pathogenic and conditionally pathogenic bacteria.

Modulation of the Gut Microbiota by Nutrition and Its Relationship to Epigenetics.

The intestinal microbiota is a community of microorganisms inhabiting the human intestines, potentially influencing both physiological and pathophysiological processes in the human body. Existing evidence suggests that nutrients can influence the modulation of the gut microbiota. However, there is still limited evidence regarding the effects of vitamin and mineral supplementation on the human gut microbiota through epigenetic modification. It is plausible that maintaining an adequate dietary intake of vitamin D, iron, fibre, zinc and magnesium may have a beneficial effect on alleviating inflammation in the body, reducing oxidative stress, and improving the condition of the intestinal microbiota through various epigenetic mechanisms. Moreover, epigenetics involves alterations in the phenotype of a cell without changing its fundamental DNA sequence. It appears that the modulation of the microbiota by various nutrients may lead to epigenetic regulation. The correlations between microbiota and epigenetics are potentially interdependent. Therefore, the primary objective of this review is to identify the complex relationships between diet, gut microbiota, and epigenetic regulation. These interactions could play a crucial role in systemic health.

Real-world effectiveness and safety of vedolizumab induction therapy for ulcerative colitis: A prospective nationwide Polish observational study.

BACKGROUND: Vedolizumab is recommended as a first-line biological treatment, along with other biological drugs, in ulcerative colitis (UC) patients in whom conventional therapy failed and as a second-line biological treatment following a failure of a tumor necrosis factor alpha (TNF-α) antagonist. OBJECTIVES: We aimed to assess the real-world effectiveness and safety of vedolizumab induction therapy in UC patients treated in the scope of the National Drug Program (NDP) in Poland. MATERIAL AND METHODS: The endpoints were the proportions of patients who reached clinical response, clinical remission and mucosal healing at week 14. Partial Mayo scores, Mayo subscores and C-reactive protein (CRP) levels were also evaluated. RESULTS: Our study population consisted of 100 patients (55 biologic-naïve and 45 biologic-exposed). The median total Mayo score at baseline was 10 (interquartile range (IQR): 9-11), and 52 patients (52%) had extensive colitis. The clinical response at week 14 was achieved in 83 (83%) and clinical remission in 24 (24%) cases. Mucosal healing was observed in 56 (62%) patients at week 14. In patients with prior failure of biologic treatment (n = 25), 17 (68%) responded to vedolizumab treatment. A decrease in the median CRP level (from 3.7 mg/L to 2.6 mg/L) and the median total Mayo score (from 10 to 4) was observed. No new safety concerns were recorded and no patients discontinued the treatment due to adverse events (AEs). CONCLUSIONS: Vedolizumab was effective and safe as induction therapy for UC in a Polish real-world population including patients with severely active UC and a low number of patients with prior biological treatment failures.

An Analysis of the Content of Metalloproteinases in the Intestinal Wall of Patients with Crohn's Disease.

One of the inflammatory bowel diseases is Crohn's disease. Although this term has been used in the medical community since 1932, a significant increase in the number of publications occurs at the end of the 20th century and the beginning of the 21st century. Crohn's disease is a disease that cannot be fully cured. In many cases, it is chronic, i.e., recurrent. All preventive and therapeutic measures taken by doctors are aimed at inhibiting the development of the disease and minimizing the occurrence of any potential "side effects" resulting from the developing disease. One of the diagnostic methods is the qualitative and quantitative determination of metalloproteinases in inflammatory tissues and in the blood. The aim of the study was the quantitative and qualitative determination of metalloproteinases in inflammatory bowel tissues in patients diagnosed with Crohn's disease. The in vitro study was performed on surgical tissues from patients diagnosed with Crohn's disease. The results show that in inflammatory tissues the concentration of metalloproteinases -3, -7, -8, -9 was higher compared to tissues taken from the resection margin without signs of inflammation, defined as healthy. The experiment confirmed that the biochemical test, which is the determination of metalloproteinases in tissues, is a useful diagnostic tool to differentiate inflammatory from non-inflammatory tissues.

Crohn's Disease: Basic Characteristics of the Disease, Diagnostic Methods, the Role of Biomarkers, and Analysis of Metalloproteinases: A Review.

Crohn's disease is a chronic inflammatory bowel disease that affects the ileum and/or large intestine. At the same time, it can also affect any other part of the human body, i.e., from the mouth to the anus. In Crohn's disease, the physiology and functioning of the epithelial barrier are inhibited due to the correlation of various factors, such as the environment, genetic susceptibility or intestinal microbiota. The symptoms are very troublesome and cause a significant reduction in quality of life, sometimes occurring with paralyzing permanent damage to the digestive tract, requiring enteral or parenteral nutrition throughout life. In order to make a proper and accurate diagnosis, an appropriately selected diagnostic path in a given clinical entity is necessary. Standard diagnostic methods are: laboratory examination, histopathological examination, endoscopic examination, X-ray, computed tomography, ultrasound examination and magnetic resonance imaging. Medical biology and the analysis of metalloproteinases have also proved helpful in diagnosing changes occurring as a result of Crohn's disease. Here we provide a thorough review of the latest reports on Crohn's disease and its genetic conditions, symptoms, morphology, diagnosis (including the analysis of Crohn's disease biomarkers, i.e., metalloproteinases) and treatment.

Real-Life Efficacy of Tofacitinib in Various Situations in Ulcerative Colitis: A Retrospective Worldwide Multicenter Collaborative Study.

BACKGROUND AND AIMS: Tofacitinib (TFB) appears to be effective in the treatment of ulcerative colitis (UC); however, available real-world studies are limited by cohort size. TFB could be an option in the treatment of acute severe ulcerative colitis (ASUC). We aimed to investigate efficacy and safety of TFB in moderate-to-severe colitis and ASUC. METHODS: This retrospective, international cohort study enrolling UC patients with ≥6-week follow-up period was conducted from February 1 to July 31, 2022. Indications were categorized as ASUC and chronic activity (CA). Baseline demographic and clinical data were obtained. Steroid-free remission (SFR), colectomy, and safety data were analyzed. RESULTS: A total of 391 UC patients (median age 38 [interquartile range, 28-47] years; follow-up period 26 [interquartile range, 14-52] weeks) were included. A total of 27.1% received TFB in ASUC. SFR rates were 23.7% (ASUC: 26.0%, CA: 22.8%) at week 12 and 41.1% (ASUC: 34.2%, CA: 43.5%) at week 52. The baseline partial Mayo score (odds ratio [OR], 0.850; P = .006) was negatively associated with week 12 SFR, while biologic-naïve patients (OR, 2.078; P = .04) more likely achieved week 52 SFR. The colectomy rate at week 52 was higher in ASUC group (17.6% vs 5.7%; P < .001) and decreased with age (OR, 0.94; P = .013). A total of 67 adverse events were reported, and 17.9% resulted in cessation of TFB. One case of thromboembolic event was reported. CONCLUSIONS: TFB is effective in both studied indications. TFB treatment resulted in high rates of SFR in the short and long terms. Higher baseline disease activity and previous biological therapies decreased efficacy. No new adverse event signals were found.

The Role of Genetic and Epigenetic Regulation in Intestinal Fibrosis in Inflammatory Bowel Disease: A Descending Process or a Programmed Consequence?

Inflammatory bowel diseases (IBDs) are a group of chronic diseases characterized by recurring periods of exacerbation and remission. Fibrosis of the intestine is one of the most common complications of IBD. Based on current analyses, it is evident that genetic factors and mechanisms, as well as epigenetic factors, play a role in the induction and progression of intestinal fibrosis in IBD. Key genetic factors and mechanisms that appear to be significant include NOD2, TGF-ß, TLRs, Il23R, and ATG16L1. Deoxyribonucleic acid (DNA) methylation, histone modification, and ribonucleic acid (RNA) interference are the primary epigenetic mechanisms. Genetic and epigenetic mechanisms, which seem to be important in the pathophysiology and progression of IBD, may potentially be used in targeted therapy in the future. Therefore, the aim of this study was to gather and discuss selected mechanisms and genetic factors, as well as epigenetic factors.

Effect of Nigella sativa on Selected Gastrointestinal Diseases.

Nigella sativa L. (family Ranunculaceae), also known as black cumin, has been used in cuisine around the world for many years. Due to its health-promoting properties, it can be used not only in the food industry but also in medicine. The main bioactive compound contained in the black cumin extract is thymoquinone (TQ), which has a special therapeutic role. The results of research in recent years confirmed its hypoglycemic, hypolipemic, and hepatoprotective effects, among others. In addition, the results of laboratory tests also indicate its immunomodulatory and anticancer effects, although there is still a lack of data on the mechanisms of how they are involved in the fight against cancer. Including this plant material in one's diet can be both an element of prophylaxis and therapy supporting the treatment process, including pharmacological treatment. However, attention should be paid to its potential interactions with drugs used in the treatment of chronic diseases.

Antioxidants as Protection against Reactive Oxidative Stress in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) belongs to a group of chronic diseases characterised by periods of exacerbation and remission. Despite many studies and observations, its aetiopathogenesis is still not fully understood. The interactions of genetic, immunological, microbiological, and environmental factors can induce disease development and progression, but there is still a lack of information on these mechanisms. One of the components that can increase the risk of occurrence of IBD, as well as disease progression, is oxidative stress. Oxidative stress occurs when there is an imbalance between reactive oxygen species (ROS) and antioxidants. The endogenous and exogenous components that make up the body's antioxidant defence can significantly affect IBD prophylaxis and reduce the risk of exacerbation by neutralising and removing ROS, as well as influencing the inflammatory state.

What Do NAFLD, Liver Fibrosis, and Inflammatory Bowel Disease Have in Common? Review of the Current Literature.

Liver disease is one of the most common extraintestinal manifestations of inflammatory bowel disease (IBD). Often the course of liver disease is associated with an exacerbation of the underlying disease (Crohn's Disease/Ulcerative Colitis). Nonalcoholic steatohepatitis encompasses a wide spectrum of liver damage. The most common form is nonalcoholic fatty liver disease (NAFLD) (75-80%), and the less common but more dangerous form is nonalcoholic steatohepatitis (NASH). NAFLD is now the most common cause of chronic liver disease in developed countries and the leading indication for liver transplantation in the United States. Genetic, demographic, clinical, and environmental factors can play a role in the pathogenesis of NAFLD. The increasing prevalence of NAFLD is associated with a widespread obesity epidemic, metabolic complications, including hypertension, type 2 diabetes, and dyslipidaemia. Some of the most common manifestations of IBD are liver, biliary tract, and gallbladder diseases. The liver fibrosis process has a complex pathophysiology and is often dependent on exogenous factors such as the treatment used and endogenous factors such as the gut microbiome. However, the factors that link IBD and liver fibrosis are not yet clear. The main purpose of the review is to try to find links between IBD and selected liver diseases and to identify knowledge gaps that will inform further research.

Real-world outcomes of 54-week vedolizumab therapy and response durability after treatment discontinuation in ulcerative colitis: results from a multicenter prospective POLONEZ study.

Background: Vedolizumab is a gut-selective anti-lymphocyte trafficking agent used to treat ulcerative colitis (UC) and Crohn's disease. Objectives: We aimed to evaluate the effectiveness, safety, and durability of the therapeutic effect of vedolizumab after treatment discontinuation in a real-world cohort of patients with UC treated in Poland. Design: This was a multicenter, prospective study involving patients with moderate to severely active UC from 12 centers in Poland who qualified for reimbursed treatment with vedolizumab between February and November 2019. Methods: The primary endpoints were clinical response (⩾2-point improvement from baseline on partial Mayo score) and clinical remission (partial Mayo score 0-1), including steroid-free remission, at week 54. Other outcomes included response durability at 26 weeks after treatment discontinuation, identification of predictors of response and remission, and safety assessment. Results: In all, 100 patients with UC were enrolled (55 biologic naïve and 45 biologic exposed). At baseline, 68% of patients were on corticosteroids and 45% on immunomodulators. Clinical response was observed in 62% of patients, clinical remission in 50%, and steroid-free remission in 42.6% at week 54. Within 26 weeks after treatment discontinuation, 37% of patients who maintained response by week 54 relapsed. The decreased number of liquid stools and rectal bleeding and endoscopic response at week 14 were predictive factors for response at week 54. Time from diagnosis ranging 2-5 years, decreased stool frequency, and non-concomitant use of corticosteroids at baseline and at week 14 were predictive factors for remission at week 54. Partial Mayo score < 3 with no subscale score > 1 at week 54 was a predictive factor for durable response after treatment discontinuation. The rate of serious adverse events related to treatment was 3.63 per 100 patient-years. Conclusion: Vedolizumab is effective and safe in UC treatment in Polish patients. However, the relapse rate after the treatment cessation was high. Registration: ENCePP (EUPAS34119).

What Does Sarcopenia Have to Do with Nonalcoholic Fatty Liver Disease?

Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease. As the second stage of developing steatosis, nonalcoholic hepatitis (NASH) carries the risk of fibrosis, cirrhosis, and hepatocellular carcinoma. Sarcopenia is defined as a condition characterized by a decrease in muscle mass and functional decline. Both NAFLD and sarcopenia are global problems. The pathophysiological mechanisms that link the two entities of the disease are insulin resistance, inflammation, nutritional deficiencies, impairment of myostatin and adiponectin, or physical inactivity. Furthermore, disorders of the gut-liver axis appear to induce the process of developing NAFLD and sarcopenia. The correlations between NAFLD and sarcopenia appear to be bidirectional, so the main objective of the review was to determine the cause-and-effect relationship between the two diseases.

Genetic and Epigenetic Etiology of Inflammatory Bowel Disease: An Update.

Inflammatory bowel disease (IBD) is a chronic disease with periods of exacerbation and remission of the disease. The etiology of IBD is not fully understood. Many studies point to the presence of genetic, immunological, environmental, and microbiological factors and the interactions between them in the occurrence of IBD. The review looks at genetic factors in the context of both IBD predisposition and pharmacogenetics.

The impact of selected food additives on the gastrointestinal tract in the example of nonspecific inflammatory bowel diseases.

Various types of food additives are widely used in the food industry. Due to their properties extending the usefulness for consuming food products, they give them different colours, consistency, or taste. The products are marked 'E' and the code is assigned to the subscription used. Many of the supplements affect human health negatively. Emulsifiers or stabilizers can lead to epithelial loads and the development of inflammation. Sucrose and other sweeteners may change the composition of the intestinal microflora and thus lead to intestinal blockage. Some additives classified as preservatives are available and may predispose to intestinal dysbiosis. Available substances belonging to food dyes may predispose to genotoxic and cytotoxic effects and cause inflammation in the intestines. Substances added to food can also cause disorders of intestinal homeostasis.

Glucocorticosteroids and the Risk of NAFLD in Inflammatory Bowel Disease.

Each year, the incidence of nonalcoholic fatty liver (NAFLD) disease increases. NAFLD is a chronic disease. One of the most common causes of NAFLD is an inadequate lifestyle, which is characterized by a lack or low physical activity and eating highly processed foods rich in saturated fat and salt and containing low amount of fiber. Moreover, disturbances in intestinal microbiome and the use of certain drugs may predispose to NAFLD. NAFLD is an increasingly described disease in patients with inflammatory bowel disease (IBD). Recent data also indicate a frequent coexistence of metabolic syndrome in this group of patients. Certain groups of drugs also increase the risk of developing inflammation, liver fibrosis, and cirrhosis. Particularly important in the development of NAFLD are steroids, which are used in the treatment of many diseases, for example, IBD. NAFLD is one of the most frequent parenteral manifestations of the disease in IBD patients. However, there is still insufficient information on what dose and exposure time of selected types of steroids may lead to the development of NAFLD. It is necessary to conduct further research in this direction. Therefore, patients with IBD should be constantly monitored for risk factors for the development of NAFLD.