The protective effects of resveratrol on ulcerative colitis via changing the profile of Nrf2 and IL-1ß protein.

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) with increasing incidence and prevalence in developed countries. The presence of inflammatory cytokines is considered the main detrimental factor in severe types of IBD. The Nrf2 transcription factor plays an important role in reducing the expression of inflammatory agents such as interleukin (IL)-1ß and increasing reparative factors such as IL-11. Resveratrol, a plant-derived phenolic compound, reduces the damage in chronic experimentally induced colitis. Twenty patients with UC and also 20 healthy controls were recruited in this study. The proteins expression of Nrf2 and IL-1ß was assessed in colonic biopsies by Western blotting. Caco-2 cells were challenged with TNF-α (in vitro simulation of UC), in the presence or not of 190 nM (24 h) and 75 nM (48 h) Resveratrol. Then, Nrf2 and IL-1ß in gene and protein expression were measured by real time-PCR and Western blotting in different treatments. Finally, IL-11 proteins expression was measured in culture supernatant by ELISA. A significant increase of IL-1ß protein was detected in inflamed colonic tissues from UC patients compared with the control individuals. In Caco-2 cells challenged with TNF-α, protein expression of IL-1ß and p-Nrf2 showed an increase, while gene expression of Nrf2 did not show a significant difference. After treatment with Resveratrol, both IL-1ß mRNA and protein levels were reduced, while IL-11 protein levels showed any increase. The p-Nrf2 is a dominant form which is prevalent in inflamed tissues from UC patients. Resveratrol can reverse the inflammatory effects of TNF-α by reducing IL-1ß and increasing IL-11 production.

COVID-19 and Inflammatory Bowel Disease: Patient Knowledge and Perceptions in a Single Center Survey.

Background and objectives: Spreading of SARS-CoV-2 infection from China to countries with a higher prevalence of inflammatory bowel disease (IBD) has generated concern among gastroenterologists and patients. The aim of this survey is to evaluate knowledge about clinical importance of COVID-19, disease management, prevention measures, and anxiety level during pandemic among patients with IBD. Material and methods: From 15th March to 15th April 2020, a questionnaire survey was administered to 200 patients with IBD by email or phone application. The questionnaire consisted of five sections: (1) anthropometric, demographic and clinical characteristics, (2) knowledge about clinical importance of COVID-19, (3) IBD management, (4) prevention measures, (5) anxiety level during pandemic. Results: One hundred forty two questionnaires were completed. Ninety-seven patients (68.3%) were males with a mean age of 46 years (SD 13; range 17-76). Fifty-four individuals (38%) were affected by Crohn disease and 88 (62%) by Ulcerative Colitis. Most patients reported high knowledge about clinical importance of COVID-19 (80%), IBD management (72%), and prevention measures (97%). Sixty-two percent of them showed moderate-high level of anxiety. High education level was independently associated with high knowledge about clinical importance of COVID-19 (odds ratio [OR] 5, 95% confidence interval [CI] 1.49-16.6, p = 0.009) and older age (OR 1, 95%, CI 1.01-1.1, p = 0.01), while the receipt of e-format educational material with low knowledge about clinical importance of COVID-19 (OR 3, 95%, CI 1.08-9.3, p = 0.03). Displaying an active disease appeared to be independently associated with low knowledge of IBD management (OR 5.8, 95% CI 1.4-22.8, p = 0.01) and no variables other than an older age was independently associated with higher level of anxiety (OR 1.04, 95% CI 1.009-1.09, p = 0.01). Conclusions: High educational level and aging promote knowledge about clinical importance of COVID-19, while e-format educational material does not. Taken together with findings that an active disease status compromises knowledge of IBD management and the high level of anxiety related to increasing age, these data suggest the need of further supporting patient-oriented strategies in IBD during Covid-19 pandemic.

Decreased circulating interleukin-33 concentration in Helicobacter pylori-infected patients with peptic ulcer: Evaluation of its association with a cytokine gene polymorphism, gender of patients and bacterial virulence factor CagA.

IL-33 has powerful immunoregulatory activities such as reinforcement of Th2 cell responses. The aim was to assess the circulating IL-33 levels and IL-33 rs1929992 polymorphism in H. pylori-infected peptic ulcer (PU) patients and asymptomatic (AS) subjects. Blood samples were obtained from 100 PU patients, 100 AS subjects and 100 uninfected individuals. Circulating IL-33 levels were detected by ELISA. After DNA extraction, the IL-33 rs1929992 polymorphism was determined using PCR-RFLP method. Serum IL-33 quantities were significantly lower in PU patients compared with AS and uninfected groups. IL-33 levels were higher in AS subjects compared with uninfected group. In PU, AS and uninfected groups, IL-33 levels were significantly higher in women than men. In PU and AS groups, the CagA+H. pylori-infected subjects exhibit higher IL-33 levels compared with carriers of CagA-H. pylori strains. In PU patients, the frequency of genotype GG and allele G at IL-33 rs1929992 was significantly higher compared with all healthy subjects (AS + uninfected groups). The presence of genotypes GG and AG, and allele G in rs1929992 conferred greater risk for PU. In whole H. pylori-infected population (PU + AS groups), IL-33 levels in individuals with genotype AA or allele A at rs1929992 were higher than subjects with GG genotype or allele G. The reduced IL-33 production could contribute to the PU development during H. pylori infection. The IL-33 levels may be affected by individual gender, rs1929992 polymorphism, and the CagA status of bacteria. The rs1929992-related GG genotype and G allele may be associated with PU development.

Vitamin D down-regulates the expression of some Th17 cell-related cytokines, key inflammatory chemokines, and chemokine receptors in experimental autoimmune encephalomyelitis.

Objectives: A spectrum of immunomodulatory properties was attributed to vitamin D (VD). Here, the VD effects on expression of some Th17 cell- related cytokines, chemokines and chemokine receptors were investigated in experimental autoimmune encephalomyelitis (EAE). Methods: One group of C57BL/6 mice, considered as healthy group, was treated with phosphate buffered saline (PBS). EAE was induced in other three groups and treated from day +3 to +30 with PBS, olive oil (VD vehicle) or 200 ng of VD. At day 31, the expression of interleukin-17 (IL-17), IL-23, chemokine (C-C motif) ligand 20 (CCL20), CCL22, CC chemokine receptor 4 (CCR4) and CCR6 in spinal cord and serum IL-17 and IL-23 levels were measured by real-time PCR and ELISA, respectively. Results: The expression of IL-17, IL-23 P19, IL-23 P40, CCL20, CCL22 and CCR4 in spinal cord and serum IL-17 and IL-23 levels in PBS-administrated EAE mice were significantly increased compared with healthy group. In EAE mice treated with VD, the expression of aforementioned parameters was significantly reduced in comparison with PBS-administrated EAE mice. Conclusion: VD down-regulates the expression of some inflammatory cytokines, chemokines and chemokine receptors in EAE mice. The possible therapeutic potential of VD in multiple sclerosis can be considered in future investigation.

Olive Tree Biophenols in Inflammatory Bowel Disease: When Bitter is Better.

The current therapeutic scenario for inflammatory bowel diseases (IBD) involves aminosalicylates, corticosteroids, and immunomodulators, but concerns regarding their safety profiles and high costs heavily impact their widespread use. In recent years, the beneficial effects thatbiophenols-from fruit and vegetables-have on human health have been investigated. The antioxidant and anti-inflammatory properties of phenolic fraction, from olive leaves and fruits, have been suggested, and a potential application in gut inflammation has been supported by in vitro and IBD-animal models studies. In the present review, we first introduced the potential therapeutic role of olive tree biophenolsin chronic inflammatory disease. Then, we aimed to describe their most interesting application for gut inflammation, as the results of basic science studies and animal experimental models. Finally, the potential role of olive tree biophenols in the setting of human IBD is discussed.

Self-Prescribed Dietary Restrictions are Common in Inflammatory Bowel Disease Patients and Are Associated with Low Bone Mineralization.

Background and objectives: Despite the serious concerns of patients about the role of food in triggering or ameliorating their intestinal disease, there are few studies dealing with patients' beliefs and practices regarding diet in inflammatory bowel disease (IBD). The aim of this study was to investigate how the disease affected the dietary habits of patients with IBD, and to assess if patients' food restrictions were responsible for low bone mineralization. Materials and Methods: For this study, 90 consecutive patients referred for IBD were interviewed regarding their dietary habits. Demographic features and clinical characteristics potentially associated with the dietary habits were collected. A validated and self-administered survey questionnaire dealing with dietary habits and patients' beliefs and perceptions regarding food was analyzed. Multivariate logistic regression analysis was performed in order to identify risk factors for dietary restrictions among participants and to evaluate the relationship between dietary restrictions and low bone mineral density (BMD). Results: Among the 63 (70%) patients who claimed a self-prescribed dietary restriction, 84% avoided dairy products. Significant risk factors (adjusted odds ratio (OR), 95% confidence interval (CI)) for the dietary restrictions were a younger age (p = 0.02), a higher level of education (p = 0.007), and a higher visceral sensitivity index (p = 0.009). Most (80%) of the patients displayed an inadequate calcium intake, and an abnormal result at dual-energy X-ray absorptiometry (DXA) scan accounting for low BMD was reported in 46 (51%) of them. Dietary restrictions (p = 0.03), and in particular avoiding dairy products(p = 0.001), were significant risk factors for a low BMD, along with female gender (p = 0.001), smoking(p = 0.04), and steroid abuse (p = 0.03). Almost all (86%) patients changed their diet after IBD diagnosis, as 8% believed that foods could have been a trigger for IBD and 37% that a proper diet was more important than drugs in controlling disease. Although 61% of the patients claimed to have received nutritional advice, 78% of the participants showed interest in receiving more. Conclusions: Dietary habits of IBD patients should be investigated by healthcare professionals as part of the routine visit. Clinicians are invited to provide nutritional recommendations to these patients in order to avoid unnecessary self-prescribed dietary restrictions.

Use of Complementary and Alternative Medicine by Patients with Irritable Bowel Syndrome According to the Roma IV Criteria: A Single-Center Italian Survey.

Aim: This study was conducted to evaluate the impact of complementary and alternative medicine (CAM) in patients with irritable bowel syndrome (IBS) as assessed by the Rome IV criteria. Methods: Consecutive patients referring for IBS were re-evaluated according to the Rome IV criteria. Demographic features and characteristics potentially associated with the use of CAM were collected. A validated, self-administered, survey questionnaire dealing with CAM and patients' level of knowledge, motivation, perception, and information seeking-behavior toward the use of CAM was analyzed. Multivariate logistic regression analysis was performed in order to identify predictors of CAM use among participants. Results: Among 156 patients claiming IBS, 137 (88%) met the Rome IV criteria, and 62 of them (45%) were CAM users. Biologically based therapy was the most chosen CAM (78%). Significant risk factors (adjusted odds ratio, 95% confidence interval) for the use of CAM were female gender (7.22, 2.31⁻22.51), a higher BMI (1.16, 1.02⁻1.33), and a good knowledge of CAM (4.46, 1.73⁻11.45), while having children was a protective factor (0.25, 0.07⁻0.95). Only 19% of patients used CAM due to medical advice and over half (51%) thought it was a "more natural" approach. Although a minority of patients (16%) had full satisfaction from CAM, 81% of users would repeat the CAM experience for their IBS symptoms. Conclusions: The widespread use of CAM in IBS, the patients' belief in its safety, and their willingness to re-use it suggest that knowledge of health-care providers and patient education should be improved.

T cell subsets play an important role in the determination of the clinical outcome of Helicobacter pylori infection.

Helicobacter pylori (H. pylori) is one of the most prevalent human pathogen and a persistent infection with this bacterium causes common pathologies, such as gastritis or peptic ulcers, and also less common but more serious pathologies, such as gastric cancer or gastric mucosa-associated lymphoid tissue (MALT) lymphoma. The clinical outcome of gastrointestinal infection sustained by H. pylori is determined by the reciprocal interactions between virulence factors of the bacterium and host factors, including immune response genes. Although H. pylori induces a strong immune response, the bacterium is not eliminated. The eradication failure could be attributed to the bacterial capability to regulate helper T (Th) cell-related responses. H. pylori specific CD4+ T cells play a fundamental role in regulating host immunity and immunopathologic events. It has been documented that Th1, Th2, Th9, Th17, Th22 and T regulatory (Treg) cells, separately or in coordination with each other, can affect the outcome of the infection sustained by of H. pylori. Some studies indicated that both Th1 and Th17 cells may be protective or pathogenic, whereas Treg and Th2 cells perform anti-inflammatory impacts during H. pylori infection. This review gathers recent information regarding the association of the CD4+ T cells-mediated immunological responses and the clinical consequence of H. pylori infection.

Diminished circulating concentration of interleukin-35 in Helicobacter pylori-infected patients with peptic ulcer: Its association with FOXP3 gene polymorphism, bacterial virulence factor CagA, and gender of patients.

BACKGROUND: IL-35 modulates immune and inflammatory responses during infections. Here, we investigated IL-35 levels and a single nucleotide polymorphism, rs3761548, in FOXP3 gene in Helicobacter pylori-infected patients with peptic ulcer (PU), to clarify possible associations. MATERIALS AND METHODS: This study includes 100 H. pylori-infected PU patients, 100 H. pylori-infected asymptomatic subjects (AS), and 100 noninfected healthy subjects (NHSs). Serum IL-35 levels and the genotyping were determined using ELISA and RFLP-PCR methods, respectively. RESULTS: In PU patients, the IL-35 levels were lower than AS and NHS groups (P < .001). The IL-35 levels in CagA+ H. pylori-infected participants from PU and AS groups were lower than individuals infected with CagA- strains (P < .02 and P < .04, respectively). Women had higher IL-35 levels than men among PU, AS, and NHS groups (P < .0001). In PU patients, AA genotype and A allele at rs3761548 were more frequent than total healthy subjects (AS + NHS groups) and associated with an increased PU risk (AA genotype: OR = 5.51, P < .0001; A allele: OR = 3.857, P < .002). In PU and AS groups, IL-35 levels were lower in subjects displaying AA genotype or A allele than subjects displaying CC genotype or C allele, respectively (P < .0001 and P < .03 for PU patients; P < .001 and P < .02 for AS group, respectively). CONCLUSIONS: Decreased IL-35 levels could be involved in PU development in H. pylori-infected individuals. IL-35 levels are affected by CagA status of H. pylori, participants gender, and genetic variations at rs3761548. The AA genotype and A allele at rs3761548 could represent a risk factor for PU development.

Enhanced expression of indoleamine 2,3-dioxygenase in Helicobacter pylori-infected human gastric mucosa modulates Th1/Th2 pathway and interleukin 17 production.

BACKGROUND: Indoleamine 2,3 dioxygenase (IDO) interferes with immune responses. Host immune response against Helicobacter pylori is involved in the persistence of the infection and its related diseases. AIM: To investigate the role of IDO in the regulation of Th1/Th2 and Th17 pathways in H. pylori infection. METHODS: Gastric biopsy samples were taken from 42 patients who underwent endoscopy and evaluated for the expression of IDO by Western blotting. Gastritis was assessed by the Sydney system score. In a subgroup of patients, biopsies were treated with the IDO inhibitor 1-methyl-L-tryptophan and the expression of interferon-γ (IFN-γ) mRNA and that of T-bet, interleukin-17 (IL-17), and IL-4 determined by real-time PCR and Western blotting, respectively. RESULTS: IDO expression was found to be enhanced (p = .001) in gastric biopsies from H. pylori-infected (n = 18) compared with uninfected (n = 24) patients. Levels of IDO expression were inversely related to the gastritis score (r = -.684, p = .002) in H. pylori-infected gastric mucosa, but not in uninfected mucosa. In gastric biopsy cultures, IDO inhibition increased the expression of IFN-γ mRNA (p = .014), T-bet (p = .045), and IL-17 (p = .02) while decreasing that of IL-4 (p = .048). CONCLUSIONS: In H. pylori-infected human gastric mucosa, an enhanced expression of IDO is capable of modulating Th1/Th2 and Th17 pathways. This mechanism lowers gastric inflammation, possibly contributing to the persistence of H. pylori. Targeting the IDO pathway may be a new strategy for modulating H. pylori-induced mucosal immune response.

High exposure, spontaneous clearance, and low incidence of active Helicobacter pylori infection: the Sorbo San Basile study.

BACKGROUND: A decreased incidence of Helicobacter pylori infection has been prospected to occur nowadays. AIM: To evaluate the exposure to H. pylori, prevalence and incidence of active infection, and related risk factors in the general population. METHODS: In a small town of Southern Italy (932 inhabitants), 595 (3-97 years) and 157 (12-82 years) subjects among those with no evidence of active H. pylori infection participated at baseline and 10 years later, respectively. A questionnaire was administered. Active H. pylori infection was assessed by (13) C-urea breath test (UBT). Serum VacA and CagA antibodies were determined. RESULTS: Of 518 subjects who were evaluated by both UBT and serology, 310 (59.8%) were UBT positive, 479 (92.4%) VacA positive, and 369 (71.2%) CagA positive. Subjects UBT negative and serology positive were 169 (32%), ranging 1 (14.2%) to 29 (82.8%) from last to first decades of life. Age, female gender, and people per room were independent risk factors for subjects UBT positive compared to those UBT negative and serology positive. Ten years later, subjects who became UBT positive were four of 157 (0.25% per year) while those who became seropositive for VacA and/or CagA were 17 of 26 (6.5% per year). CONCLUSIONS: H. pylori infection is highly dynamic with wide range of spontaneous clearance. It is easily cleared in the first decades of life, more recent years, less crowded homes, and males. It disappears and recurs more often than it was previously thought, implying that the current decline in its prevalence is due to real clearance instead of a fall in infection rate.

Comparison of Performances of Adalimumab Biosimilars SB5, ABP501, GP2017, and MSB11022 in Treating Patients with Inflammatory Bowel Diseases: A Real-Life, Multicenter, Observational Study.

BACKGROUND: Adalimumab (ADA) biosimilars have entered the therapeutic armamentarium of inflammatory bowel disease (IBD), allowing for the treatment of a greater number of patients for their reduced cost than the originator. However, comparative data on the efficacy and safety of the various ADA biosimilars remains scarce.We compare the efficacy and safety of ADA biosimilars SB5, ABP501, GP2017, and MSB11022 in treating IBD outpatients in a real-life Italian setting. METHODS: A retrospective analysis was performed on consecutive IBD outpatients with complete clinical, laboratory, and endoscopic data. Clinical activity was measured using the Mayo score in ulcerative colitis (UC) and the Harvey-Bradshaw Index in Crohn's disease (CD). The primary endpoints were the following: (1) induction of remission in patients new to biologics and patients new to ADA but previously exposed to other anti-tumor necrosis factor agents or other biologics; (2) maintenance of remission in patients switched from the ADA originator to an ADA biosimilar; and (3) safety of various biosimilars. RESULTS: A total of 533 patients were enrolled according to the inclusion criteria: 162 patients with UC and 371 patients with CD. Clinical remission was obtained in 79.6% of patients new to biologics and 59.2% of patients new to ADA but not to other biologics; clinical remission was maintained in 81.0% of patients switched from the originator, and adverse events were recorded in 6.7% of patients. There was no significant difference between the 4 ADA biosimilars for each predetermined endpoint. CONCLUSIONS: Adalimumab biosimilars are effective and safe in IBD treatment, both in new patients and in patients switched from the ADA originator. No difference in efficacy and safety was found between ADA biosimilars.

We treated 533 IBD patients with adalimumab (ADA) biosimilars SB5, APB501, GP2017, and MSB11022. No differences between these 4 ADA biosimilars were found for reaching remission in naive patients, maintaining remission for nonmedical switching, clinical response, steroid-free remission, surgery rate, mucosal healing, or safety.

Safety profile of intravenous iron in inflammatory bowel disease: an up-to-date overview.

Up to 30-70% of patients may experience mild and moderate side effects during iron therapy and this is often associated with a poor adherence to therapy. Anemia is frequent in patients with active inflammatory bowel disease (IBD), due to both iron deficiency and chronic inflammation, therefore iron supplementation is frequently needed. Considering that gastrointestinal disorders are the most common side effects with oral iron, in IBD patients intravenous administration must be preferred. Although intravenous iron supplementation remains the most effective therapy of IBD-associated iron deficiency anemia, the perception of risk related to intravenous administration by clinicians could limit this successful strategy. In this narrative review we provided an up to date on the safety of the different iron formulations for intravenous administration, by reporting the most recent studies in IBD patients.

Comparison of performances of infliximab biosimilars CT-P13 versus SB2 in the treatment of inflammatory bowel diseases: a real-life multicenter, observational study in Italy.

BACKGROUND: To compare the performances of Infliximab (IFX) biosimilar CT-P13 and SB2 in the treatment of Inflammatory Bowel Diseases (IBD) outpatients in Italy. RESEARCH DESIGN AND METHODS: Three hundred and eighty IBD outpatients were retrospectively evaluated. The primary endpoint was to compare the two IFX biosimilars in terms of reaching and maintenance of remission at any timepoint. RESULTS: 197 patients with Ulcerative Colitis (UC) and 183 patients with Crohn's Disease (CD) treated with CT-P13 or SB2 and having a median (IQR) follow-up of 12 (6-36) months were compared: 230 (60.5%) were naïve to anti-TNFα, 20 (5.26%) were switched from IFX originator or from IFX CT-P13 to IFX SB2. Clinical remission was achieved in 133 (67.5%) UC patients and in 164 (89.6%) CD patients (p < 0.000), with no differences between CT-P13 and SB2 in the rate of remission in UC (p = 0.667) and CD (p = 0.286). Clinical response, steroid-free remission, rate of surgery, mucosal healing (MH) in UC, switching from IFX originator or from other biosimilar, and safety were similar. Higher MH rate was obtained in CD patients treated with CT-P13 (p = 0.004). CONCLUSION: This first comparative study found that both IFX biosimilars CT-P13 and SB2 are effective and safe in managing IBD outpatients.

Replacement of Adalimumab Originator to Adalimumab Biosimilar for a Non-Medical Reason in Patients with Inflammatory Bowel Disease: A Real-life Comparison of Adalimumab Biosimilars Currently Available in Italy.

BACKGROUND AND AIMS: Adalimumab (ADA) biosimilars have been included into the therapeutic armamentarium of inflammatory bowel disease (IBD); however, comparative data on the efficacy and safety of the different ADA biosimilars after replacing the ADA originator for a non-medical reason remains scarce. We aimed to compare in a real-life setting the efficacy and safety of four ADA biosimilars SB5, APB501, GP2017, and MSB11022 in IBD patients after replacing the originator for a non-medical reason. METHODS: A multicenter retrospective study was performed on consecutive IBD patients, analyzing clinical, laboratory, and endoscopic data. The primary endpoints of the study were maintenance of clinical remission and safety of the different biosimilars. RESULTS: 153 patients were enrolled, 26 with UC and 127 with CD. Clinical remission was maintained in 124 out of 153 (81%) patients after a median (IQR) follow-up of 12 (6-24) months, without any significant difference between the four ADA biosimilars. ADA biosimilars dosage was optimized in five patients (3.3%). Loss of remission was significantly higher in UC patients (10/26 patients, 38.5%) than in CD patients (19/127 patients, 14.9%, p<0.025). Adverse events occurred in 12 (7.9%) patients; the large majority were mild. CONCLUSIONS: No difference in efficacy and safety was found between ADA biosimilars when used to replace the ADA originator for a non-medical reason. However, in UC patients the replacement of ADA originator for this reason should be carefully assessed.

Crohn disease: Identification, diagnosis, and clinical management.

ABSTRACT: Crohn disease is an inflammatory bowel disorder affecting children and adults. With its increasing prevalence, healthcare providers need adequate resources to assist with diagnosis and management. This article discusses early diagnosis, disease severity and classification, familial predisposition and genomics, and clinical management in the primary care setting.

Dietary Polyphenols and Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD), which is emerging as a major public health issue worldwide, is characterized by a wide spectrum of liver disorders, ranging from simple fat accumulation in hepatocytes, also known as steatosis, to non-alcoholic steatohepatitis (NASH) and cirrhosis. At present, the pharmacological treatment of NAFLD is still debated and dietary strategies for the prevention and the treatment of this condition are strongly considered. Polyphenols are a group of plant-derived compounds whose anti-inflammatory and antioxidant properties are associated with a low prevalence of metabolic diseases, including obesity, hypertension, and insulin resistance. Since inflammation and oxidative stress are the main risk factors involved in the pathogenesis of NAFLD, recent studies suggest that the consumption of polyphenol-rich diets is involved in the prevention and treatment of NAFLD. However, few clinical trials are available on human subjects with NAFLD. Here, we reviewed the emerging existing evidence on the potential use of polyphenols to treat NAFLD. After introducing the physiopathology of NAFLD, we focused on the most investigated phenolic compounds in the setting of NAFLD and described their potential benefits, starting from basic science studies to animal models and human trials.

Gut microbiota and non-alcoholic fatty liver disease.

The gastrointestinal tract of the adult human represents the habitat of the ecological community of commensal, symbiotic and pathogenic microorganisms, defined as the gut microbiota, which has more than 100 trillion microorganisms representing one of the most complex ecosystems. Colonization of the gastrointestinal tract by microorganisms begins at the time of birth. Contrary to what was previously hypothesized, a large number of fundamental functions for the host are attributed to the gut microbiota to date. Therefore, the gut microbiota does not represent a passive set of microbes hosted inside the human organism but plays a crucial role in the balance of the organism itself. An alteration of the microbiota is a phenomenon known as dysbiosis. The latter can be implicated in the development of complex liver diseases like non-alcoholic fatty liver disease. The aim of this review was to describe the most interesting data linking the development of non-alcoholic fatty liver disease with the gut microbiota and, therefore, to underline the importance of the microbiota itself, as a potential therapeutic target in the treatment of non-alcoholic fatty liver disease.

Nutrigenomics and Nutrigenetics in Metabolic- (Dysfunction) Associated Fatty Liver Disease: Novel Insights and Future Perspectives.

Metabolic- (dysfunction) associated fatty liver disease (MAFLD) represents the predominant hepatopathy and one of the most important systemic, metabolic-related disorders all over the world associated with severe medical and socio-economic repercussions due to its growing prevalence, clinical course (steatohepatitis and/or hepatocellular-carcinoma), and related extra-hepatic comorbidities. To date, no specific medications for the treatment of this condition exist, and the most valid recommendation for patients remains lifestyle change. MAFLD has been associated with metabolic syndrome; its development and progression are widely influenced by the interplay between genetic, environmental, and nutritional factors. Nutrigenetics and nutrigenomics findings suggest nutrition's capability, by acting on the individual genetic background and modifying the specific epigenetic expression as well, to influence patients' clinical outcome. Besides, immunity response is emerging as pivotal in this multifactorial scenario, suggesting the interaction between diet, genetics, and immunity as another tangled network that needs to be explored. The present review describes the genetic background contribution to MAFLD onset and worsening, its possibility to be influenced by nutritional habits, and the interplay between nutrients and immunity as one of the most promising research fields of the future in this context.

From Pre- and Probiotics to Post-Biotics: A Narrative Review.

BACKGROUND AND AIMS: gut microbiota (GM) is a complex ecosystem containing bacteria, viruses, fungi, and yeasts. It has several functions in the human body ranging from immunomodulation to metabolic. GM derangement is called dysbiosis and is involved in several host diseases. Pre-, probiotics, and symbiotics (PRE-PRO-SYMB) have been extensively developed and studied for GM re-modulation. Herein, we review the literature data regarding the new concept of postbiotics, starting from PRE-PRO-SYMB. METHODS: we conducted a search on the main medical databases for original articles, reviews, meta-analyses, randomized clinical trials, and case series using the following keywords and acronyms and their associations: gut microbiota, prebiotics, probiotics, symbiotic, and postbiotics. RESULTS: postbiotics account for PRO components and metabolic products able to beneficially affect host health and GM. The deeper the knowledge about them, the greater their possible uses: the prevention and treatment of atopic, respiratory tract, and inflammatory bowel diseases. CONCLUSIONS: better knowledge about postbiotics can be useful for the prevention and treatment of several human body diseases, alone or as an add-on to PRE-PRO-SYMB.