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Primary bile acids (BAs), synthesized from cholesterol in the liver, after their secretion with bile into the intestinal lumen, are transformed by gut microbiota to secondary BAs. As natural detergents, BAs play a key role in the digestion and absorption of lipids and liposoluble vitamins. However, they have also been recognized as important signaling molecules involved in numerous metabolic processes. The close bidirectional interactions between BAs and gut microbiota occur since BAs influence microbiota composition, whereas microbiota determines BA metabolism. In particular, it is well established that BAs modulate Clostridioides difficile life cycle in vivo. C. difficile is a cause of common nosocomial infections that have become a growing concern. The aim of this review is to summarize the current knowledge regarding the impact of BAs on the pathogenesis, prevention, and treatment of C. difficile infection.

Background: Fibroblast growth factor 21 (FGF21) is a stress-inducible hormone that regulates nutrient and metabolic homeostasis. Inflammatory state is one of the stimulators of FGF21 secretion. The aim of the study was to assess correlations between serum FGF21 level and inflammatory markers as well as nutritional status indicators in patients with inflammatory bowel disease (IBD). Methods: Fasting serum FGF21 level was measured using ELISA test in 105 IBD patients and 17 healthy controls. There were 31 subjects with active ulcerative colitis (UC), 16 with inactive UC, 36 with active Crohn's disease (CD), and 22 with inactive CD. Clinical and endoscopic activity of IBD was evaluated based on validated scales and indices. Fecal calprotectin, serum CRP, and selected parameters of nutritional status were tested in all patients. Results: Serum FGF21 level was characterized by fluctuations depending on the IBD activity. FGF21 level was significantly higher in both active UC and CD compared to inactive phases of the diseases and to the controls. A correlation between FGF21 and fecal calprotectin levels was also found in UC and CD. Additionally, in CD, FGF21 level positively correlated with CRP level. In both UC and CD, a negative correlation was noted between FGF21 level and nutritional status parameters including cholesterol, protein, albumin levels, and BMI. Conclusion: The intensity of intestinal inflammation is related to FGF21 level, which correlates negatively with nutritional status indicators in IBD. The disturbances in FGF21 secretion may contribute to the multifactorial pathogenesis of malnutrition and weight loss in IBD patients. [ABSTRACT FROM AUTHOR]

Somatostatin interacts with five G-protein-coupled receptor (sst1-5). Octreotide, a stable sst2≫3≥5 agonist, exerts a visceral anti-hyperalgesic effect in experimental and clinical studies. Little is known on the receptor subtypes involved. We investigated the influence of the stable sst1-5 agonist, ODT8-SST and selective receptor subtype peptide agonists (3 or 10μg/mouse) injected intraperitoneally (ip) on visceral hypersensitivity in mice induced by repeated noxious colorectal distensions (four sets of three CRD, each at 55mmHg) or corticotropin-releasing factor receptor 1 agonist, cortagine given between two sets of graded CRD (15, 30, 45, and 60mmHg, three times each pressure). The mean visceromotor response (VMR) was assessed using a non-invasive manometry method and values were expressed as percentage of the VMR to the 1st set of CRD baseline or to the 60mmHg CRD, respectively. ODT8-SST (10μg) and the sst2 agonist, S-346-011 (3 and 10μg) prevented mechanically induced visceral hypersensitivity in the three sets of CRD, the sst1 agonist (10μg) blocked only the 2nd set and showed a trend at 3μg while the sst4 agonist had no effect. The selective sst2 antagonist, S-406-028 blocked the sst2 agonist but not the sst1 agonist effect. The sst1 agonist (3 and 10μg) prevented cortagine-induced hypersensitivity to CRD at each pressure while the sst2 agonist at 10μg reduced it. These data indicate that in addition to sst2, the sst1 agonist may provide a novel promising target to alleviate visceral hypersensitivity induced by mechanoreceptor sensitization and more prominently, stress-related visceral nociceptive sensitization.

Compelling evidence indicates sex and gender differences in epidemiology, symptomatology, pathophysiology, and treatment outcome in irritable bowel syndrome (IBS). Based on the female predominance as well as the correlation between IBS symptoms and hormonal status, several models have been proposed to examine the role of sex hormones in gastrointestinal (GI) function including differences in GI symptoms expression in distinct phases of the menstrual cycle, in pre- and post-menopausal women, during pregnancy, hormonal treatment or after oophorectomy. Sex hormones may influence peripheral and central regulatory mechanisms of the brain-gut axis involved in the pathophysiology of IBS contributing to the alterations in visceral sensitivity, motility, intestinal barrier function, and immune activation of intestinal mucosa. Sex differences in stress response of the hypothalamic-pituitary-adrenal axis and autonomic nervous system, neuroimmune interactions triggered by stress, as well as estrogen interactions with serotonin and corticotropin-releasing factor signaling systems are being increasingly recognized. A concept of "microgenderome" related to the potential role of sex hormone modulation of the gut microbiota is also emerging. Significant differences between IBS female and male patients regarding symptomatology and comorbidity with other chronic pain syndromes and psychiatric disorders, together with differences in efficacy of serotonergic medications in IBS patients confirm the necessity for more sex-tailored therapeutic approach in this disorder.

Stressors of different psychological, physical or immune origin play a critical role in the pathophysiology of irritable bowel syndrome participating in symptoms onset, clinical presentation as well as treatment outcome. Experimental stress models applying a variety of acute and chronic exteroceptive or interoceptive stressors have been developed to target different periods throughout the lifespan of animals to assess the vulnerability, the trigger and perpetuating factors determining stress influence on visceral sensitivity and interactions within the brain-gut axis. Recent evidence points towards adequate construct and face validity of experimental models developed with respect to animals' age, sex, strain differences and specific methodological aspects such as non-invasive monitoring of visceromotor response to colorectal distension as being essential in successful identification and evaluation of novel therapeutic targets aimed at reducing stress-related alterations in visceral sensitivity. Underlying mechanisms of stress-induced modulation of visceral pain involve a combination of peripheral, spinal and supraspinal sensitization based on the nature of the stressors and dysregulation of descending pathways that modulate nociceptive transmission or stress-related analgesic response.

Background: The aim of the study was to assess sex‐ and gender‐related differences in the epidemiology and impact of disorders of gut–brain interaction (DGBI) in Poland. Methods: Data used for the current analysis were derived from the Polish population sample of 2057 subjects (1030 F, 1027 M) collected via the Internet survey that included the Rome IV diagnostic questionnaire and 80 supplementary questions. Key Results: The overall prevalence of DGBI in Poland was 46.0% (51.7% in women and 40.3% in men, p < 0.001). Comparing women versus men, esophageal disorders were observed in 6.3% vs. 6.0%, respectively (p > 0.05), gastroduodenal disorders in 14.0% vs. 7.8% (p < 0.001), bowel disorders in 44.3% vs. 33.9% (p < 0.001), and anorectal disorders in 9.9% vs. 7.7% (p > 0.05). The six most common DGBI included functional constipation 14.2%, functional dyspepsia 8.3%, proctalgia fugax 6.6%, functional bloating 4.8%, functional diarrhea 4.5%, and irritable bowel syndrome (IBS) 4.4%. All these disorders, except for functional diarrhea, were more common in women. The DGBI overlap was significantly higher in women than in men (16.7% vs. 11.2%, p < 0.001). A higher number of overlapping DGBI correlated positively with IBS severity, higher level of somatization, anxiety and depression, poorer quality of life (QoL), and increased healthcare utilization. Conclusions and Inferences: This is the first comprehensive report on significant sex/gender‐related differences in the prevalence and burden of DGBI in Poland. The revealed differences between women and men with DGBI in the clinical profile, psychosocial variables, and healthcare utilization may have important diagnostic and therapeutic implications. [ABSTRACT FROM AUTHOR]

Background: Gastroparesis is a condition characterized by epigastric symptoms and delayed gastric emptying (GE) rate in the absence of any mechanical obstruction. The condition is challenging in clinical practice by the lack of guidance concerning diagnosis and management of gastroparesis. Methods: A Delphi consensus was undertaken by 40 experts from 19 European countries who conducted a literature summary and voting process on 89 statements. Quality of evidence was evaluated using grading of recommendations assessment, development, and evaluation criteria. Consensus (defined as ≥80% agreement) was reached for 25 statements. Results: The European consensus defined gastroparesis as the presence of symptoms associated with delayed GE in the absence of mechanical obstruction. Nausea and vomiting were identified as cardinal symptoms, with often coexisting postprandial distress syndrome symptoms of dyspepsia. The true epidemiology of gastroparesis is not known in detail, but diabetes, gastric surgery, certain neurological and connective tissue diseases, and the use of certain drugs recognized as risk factors. While the panel agreed that severely impaired gastric motor function is present in these patients, there was no consensus on underlying pathophysiology. The panel agreed that an upper endoscopy and a GE test are required for diagnosis. Only dietary therapy, dopamine‐2 antagonists and 5‐HT4 receptor agonists were considered appropriate therapies, in addition to nutritional support in case of severe weight loss. No consensus was reached on the use of proton pump inhibitors, other classes of antiemetics or prokinetics, neuromodulators, complimentary, psychological, or more invasive therapies. Finally, there was consensus that gastroparesis adversely impacts on quality of life and healthcare costs and that the long‐term prognosis of gastroparesis depends on the cause. Conclusions and Inferences: A multinational group of European experts summarized the current state of consensus on definition, symptom characteristics, pathophysiology, diagnosis, and management of gastroparesis. Key Summary: Current knowledge The epidemiology of gastroparesis is not well known.Diagnosis and treatment of gastroparesis is challenging due to uncertainties in definition and optimal therapeutic approach. What is new here A Delphi panel consisting of 40 experts from 19 European countries established the level of consensus on 89 statements regarding gastroparesis.The statements reaching consensus serve to guide clinicians in recognizing, diagnosing and treating gastroparesis in clinical practice.The statements without consensus identify areas in need of future research. [ABSTRACT FROM AUTHOR]