Gastrointest. Disord., Volume 4, Issue 4 (December 2022) – 11 articles

Nicotinamide phosphoribosyltransferase (NAMPT) represents a major component in cellular energy metabolism, which is also crucial for cancer cells that have elevated aerobic glycolysis; moreover, targeting the NAD salvage pathway by inhibition of NAMPT was shown effective in a subgroup of gastric cancer cell lines. In order to study the expression levels of NAMPT in adenocarcinoma of the esophagogastric junction and stomach (AEG/S) we performed immunohistochemical analysis in a cohort of 296 tumor samples using tissue-microarrays (TMAs). In the present investigation, we saw a high expression of NAMPT in only a minority of our large AEG/S cohort. Although we did not find a correlation between NAMPT expression and survival, subgroup analysis showed that NAMPT expression was more frequent in older patients (>65 years, p = 0.049) and was associated with a numerical shorter survival that did not reach statistical significance within this age group. In conclusion, we did not find significance for any prognostic effect of NAMPT in our AEG/S cohort; however, the evaluation of other NAD metabolic enzymes is needed as molecular predictors of response to potential NAMPT inhibition in the treatment of patients with AEG/S. Full article

Background: Newer antidiarrheal agents include the mucoprotectants gelatin tannate and xyloglucan. Methods: Rat models of cholera toxin (CT)-induced water secretion were used to evaluate the mucoprotective effects of gelatin tannate, xyloglucan, and related compounds. Results: Oral pretreatment for 4 days with gelatin tannate (250 and 500 mg/kg/day), but not tannic acid or gelatin (both 125 mg/kg/day), blocked CT-induced intestinal water secretion. CT-induced intestinal water secretion was also attenuated by oral xyloglucan 12.5 mg/kg + gelatin 125 mg/kg (6 h pre-CT) and gelatin 250 mg/kg (12 h pre-CT), and by local (intra-jejunal loop) administration of gelatin, gelatin tannate and xyloglucan concomitantly with CT. Conclusions: Gelatin tannate and xyloglucan + gelatin attenuated CT-induced intra-loop water secretion in this experimental model, supporting previous evidence that their mechanisms of mucosal protection are closely related to their chemical structures, which confer film-forming properties via the formation of mucoadhesive films. Full article

Background: Physical activity (PA) in inflammatory bowel disease (IBD) has many potential favourable outcomes including anti-inflammatory effects, improvement in quality of life and improvements in patient body composition. It is recognised that patients with IBD have a significantly decreased exercise tolerance. Aim: 1. To assess physical activity levels, behaviours and barriers to PA in IBD. 2. To assess the likelihood of patients with IBD to engage in a community-based exercise programme. 3. To examine the presence of body image concerns in IBD. Method: Patient surveys were distributed in Beaumont and Connolly Hospitals between October and December 2021. Descriptive statistics, Chi-squared testing and Pearson’s correlations were completed using Minitab. p < 0.05 denoted statistical significance. Results: Data were recorded for a total of 203 patients. Out of all patients, 62% (n = 126) had Crohn’s disease (CD). Over half of the cohort were male (n = 115). Mean weight among females was 75 kg and 83 kg among males. Exercise behaviours: Out of all patients, 71% exercise regularly, on average for 59 min, 3.2 days/week. Walking was the most common form of PA (74%). A post-diagnosis change in exercise behaviour was found in 66% with three-quarters exercising less. The primary barrier to exercise was fatigue (54%). Female gender (p = 0.007) and age < 45 years (p = 0.02) were associated with body image dissatisfaction reported in 62% of patients. Conclusion: These data demonstrate the patient-reported impact of IBD on patient participation in PA. Concerns regarding body image were common and associated with gender and age. A feasibility study of a physician-derived exercise programme in patients with active IBD is underway in Beaumont Hospital to determine the effect on patient response to therapy, inflammation and body composition outcomes (NCT05174754). Full article

While the importance of the intestinal microbiome has been realised for a number of years, the significance of the phrase microbiota–gut–brain axis is only just beginning to be fully appreciated. Our recent work has focused on the microbiome as if it were a single entity, modifying the expression of the genetic inheritance of the individual by the generation of interkingdom signalling molecules, semiochemicals, such as dopamine. In our view, the purpose of the microbiome is to convey information about the microbial environment of the mother so as to calibrate the immune system of the new-born, giving it the ability to distinguish harmful pathogens from the harmless antigens of pollen, for example, or to help distinguish self from non-self. In turn, this requires the partition of nutrition between the adult and its microbiome to ensure that both entities remain viable until the process of reproduction. Accordingly, the failure of a degraded microbiome to interact with the developing gut of the neonate leads to failure of this partition in the adult: to low faecal energy excretion, excessive fat storage, and concomitant problems with the immune system. Similarly, a weakened gut–brain axis distorts interoceptive input to the brain, increasing the risk of psychiatric diseases such as autism. These effects account for David Barker’s 1990 suggestion of “the fetal and infant origins of adult disease”, including schizophrenia, and David Strachan’s 1989 observation of childhood immune system diseases, such as hay fever and asthma. The industrialisation of modern life is increasing the intensity and scale of these physical and psychiatric diseases and it seems likely that subclinical heavy metal poisoning of the microbiome contributes to these problems. Finally, the recent observation of Harald Brüssow, that reported intestinal bacterial composition does not adequately reflect the patterns of disease, would be accounted for if microbial eukaryotes were the key determinant of microbiome effectiveness. In this view, the relative success of “probiotic” bacteria is due to their temporary immune system activation of the gut–brain axis, in turn suggesting a potential mechanism for the placebo effect. Full article

In Japanese hospitals, patients undergoing invasive procedures or surgery are screened for anti-HCV antibodies; however, the majority of possible HCV careers are not referred to hepatologists. In addition to the conventional alert email system, a hepatologist extracted monthly lists of anti-HCV-antibody-positive patients who had been tested two months previously and checked medical records to determine whether the doctors who ordered the tests had properly dealt with the positive results. If the doctors had not yet properly followed up, the hepatologist would send emails to both the doctor and a medical clerk to inform them to conduct an HCV-RNA test and to refer HCV-RNA-positive patients to hepatologists. In total, 130 patients managed in the pre-intervention period and 151 patients managed in the post-intervention period were included in this study. The number of anti-HCV-positive patients whose results were not properly handled showed a significant decrease after the introduction of the double alert system (p = 0.034). Among patients undergoing screening anti-HCV antibody testing, a significant number of patients with probable chronic HCV hepatitis were overlooked by the email alert system and their results were not properly handled. The double alert system was useful for reducing the number of positive anti-HCV antibody patients whose results were not properly handled. Full article

Hepatitis D virus (HDV) globally affects nearly 5% of people with chronic hepatitis B virus (HBV) infection. Bulevirtide (BLV) is an HDV/HBV entry inhibitor recently approved for adult patients with chronic hepatitis delta (CHD). In this real-life case report, we describe the virological efficacy, the safety, and the liver function amelioration of one patient with liver compensated cirrhosis with esophageal varices after one-year combo treatment with BLV (2 mg/day in sub-cutaneous injection) and tenofovir disoproxil fumarate (TDF) (245 mg/day). The patient had HDV RNA levels of 9300 IU/mL, 1100 IU/mL, and undetectable at baseline, after three months, and after six months of treatment, respectively. In addition, the model for end-stage liver disease (MELD) score has declined from 11 at baseline to 8 after twelve months of treatment accompanied by alanine aminotransferase (ALT) normalization. Moreover, the treatment significantly improved the liver stiffness measurement (LSM) since a reduction from 34.3 kPa to 24.5 kPa was observed after twelve months of treatment. Furthermore, the treatment was well tolerated, and no dose reduction was needed. Full article

Neutrophils are short-lived cells that play a crucial role in inflammation. As in other tissues, these polymorphonuclear phagocytes are involved in the intestinal inflammatory response, on the one hand, contributing to the activation and recruitment of other immune cells, but on the other hand, facilitating intestinal mucosa repair by releasing mediators that aid in the resolution of inflammation. Even though these responses are helpful in physiological conditions, excessive recruitment of activated neutrophils in the gut correlates with increased mucosal damage and severe symptoms in patients with inflammatory bowel disease (IBD) and pre-clinical models of colitis. Thus, there is growing interest in controlling their biology to generate novel therapeutic approaches capable of reducing exacerbated intestinal inflammation. However, the beneficial and harmful effects of neutrophils on intestinal inflammation are still controversial. With this review, we summarise and discuss the most updated literature showing how neutrophils (and neutrophil extracellular traps) contribute to developing and resolving intestinal inflammation and their putative use as therapeutic targets. Full article

Crohn’s disease is a chronic inflammatory disease affecting the gastrointestinal tract. Expert guidelines now recommend regular objective assessments as part of a treat-to-target approach. Intestinal ultrasound provides a noninvasive, patient-friendly modality for assessing Crohn’s disease without the risk of radiation exposure and does not require fasting or bowel preparation. Enhancement techniques, including oral and intravenous contrast, can improve disease-activity and complication detection. Due to its acceptability, intestinal ultrasound can be performed frequently, allowing for closer disease-activity monitoring and treatment adjustments. There have been significant advances in the utility of intestinal ultrasound; particularly for assessing disease activity during pregnancy and fibrosis detection utilising elastography. This review provides a comprehensive overview of performing intestinal ultrasound, the diagnostic accuracy, role in disease-activity monitoring, and recent advances in utilising ultrasound for the assessment of luminal Crohn’s disease. Full article

Objective: The aim of this prospective study was to determine the role of the gut-brain hormonal axis and the effect of the enteric peptides, as well as the role of genetically determined sensitivity to the bitter taste, on the development of child food neophobia (CFN). Methods: 114 children were enrolled in the study: 43 in food neophobia group (FNG), 21 In the control group (CG) and 50 in prospective group (PG). All patients were assessed with the child food neophobia scale (CFNS), underwent an oral 6-propylthiouracil (6-PROP) test, buccal swab for bitter-taste genotyping, anthropometric measurements, and were tested for serum levels of leptin, adiponectin, insulin-like growth factor-1(IGF-1), ghrelin, and neuropeptide Y (NPY), and complete blood count (CBC); measurements were taken from a blood sample after 4 h fasting. Results: Subjects from FNG were more often hypersensitive to bitter taste (6-PROP) than CG (p = 0.001). There was no correlation between the result of genetic analysis and CFNS (p = 0.197), nor the body mass index (BMI) at the age of 18–36 months (p = 0.946) found. Correlation between 6-PRO perception and genotype have not been confirmed (p = 0.064). The score of CFNS was positively related to the serum level of NPY (p = 0.03). BMI percentile was negatively related to serum level of NPY (p = 0.03), but positively related to leptin serum level (p = 0.027). Conclusions: Bitter taste sensitivity to 6-PROP plays an important role in the development of the CFN, but correlation between 6-PROP perception and genotype have not been confirmed. Children with food neophobia due to elevated serum NPY level should be constantly monitored in order to control the nutritional status at a later age. Full article

We developed infliximab and a plant-based diet as first-line (IPF) therapies for severe ulcerative colitis (UC). It increased the remission rate and decreased the colectomy rate compared to those of current standards. We encountered a case with severe UC in which the consecutive use of IPF therapy and corticosteroid therapy was required to induce remission. A 21-year-old male worker developed diarrhea, abdominal pain, marked weight loss from 70 to 55 kg, and anorexia. He was diagnosed with severe ulcerative colitis. IPF therapy was initiated. Improvement in symptoms and biomarkers was seen soon after the first infusion of infliximab (300 mg). Further improvement in symptoms was observed after both the second and third infliximab infusions. Loose stool and abdominal pain on defecation were still present, however, and biomarkers were above the reference range. Therefore, oral prednisolone (40 mg/day) was consecutively initiated. This resulted in clinical and endoscopic remission. In conclusion, we present a severe UC case in which the response to IPF therapy was insufficient. Consecutive oral prednisolone successfully induced remission. This new stepwise modality will make IPF therapy the first-choice therapy for severe UC. Full article

No case has been reported in which ulcerative colitis occurred in a patient with type 2 diabetes mellitus and the patient was treated with a plant-based diet. A 56-year-old man with a 3-year history of diabetes noticed bloody stool about 2 months after his worst glycated hemoglobin A1c test. Endoscopy revealed diffuse inflammation in the rectum. He was diagnosed with ulcerative colitis (proctitis, mild severity). He underwent educational hospitalization. A plant-based diet (1400 kcal/day) was provided. The same dosage of metformin was continued, but no medication was prescribed for ulcerative colitis. At the end of hospitalization, fecal occult blood 271 ng/mL became negative. Glycated hemoglobin A1c 6.9% had decreased to 6.6%. Two months after discharge, glycated hemoglobin A1c decreased to normal for the first time in 3.5 years. Ulcerative colitis had been in remission without medication for one and a half years after the educational hospitalization. Thereafter, however, he experienced two flareups. Deterioration in glycated hemoglobin A1c preceded the flareups. We described a scarcely reported case in which ulcerative colitis occurred in a patient with diabetes and the patient was treated with a plant-based diet. The plant-based diet was effective for both diseases. It seemed that the status of diabetes influenced the onset and relapse of ulcerative colitis. Full article