Neurogastroenterology and Motility最新文献

Background: Postoperative ileus (POI) is a condition marked by a temporary suppression of gastrointestinal motility following abdominal surgery. The mechanism of POI encompasses various factors and is characterized by two phases: the early neurogenic phase involving both adrenergic and non-adrenergic neural pathways; the later immune-mediated phase is characterized by a sterile inflammatory response that lasts several days. Activation of muscularis macrophages triggers a sterile inflammatory process that results in dysfunction of the enteric nervous system (ENS) and a reversible inhibition of gastrointestinal motility.

Purpose: In this minireview, recent insights in the pathophysiological mechanisms underlying POI and potential new therapeutic strategies are described.

Background: Accumulating evidence has suggested that neuropeptides such as orexin, ghrelin, or oxytocin act centrally in the brain to regulate intestinal barrier function through the vagus nerve. It has been reported that the vagal cholinergic anti-inflammatory pathway was blocked by splenectomy. In the present study, we therefore examined the effect of splenectomy on neuropeptides-induced improvement of increased intestinal permeability.

Methods: Colonic permeability was determined in vivo by quantifying the absorbed Evans blue in colonic tissue for 15 min spectrophotometrically in rats.

Results: Splenectomy increased colonic permeability. The increased permeability by splenectomy was significantly blocked by vagal activation induced by carbachol or 2-deoxy-d-glucose which was prevented by atropine, suggesting vagal activation could prevent colonic hyperpermeability in splenectomized rats. In the splenectomized rats, intracisternal injection of orexin, ghrelin, oxytocin, or butyrate failed to inhibit increased colonic permeability while intracisternal glucagon-like peptide-1 (GLP-1) analogue, liraglutide, potently blocked the increased colonic permeability in a dose-dependent manner. The liraglutide-induced improvement of increased colonic permeability was blocked by atropine in splenectomized rats. Intracisternal injection of GLP-1 receptor antagonist attenuated 2-deoxy-d-glucose-induced improvement of colonic hyperpermeability in splenectomized rats.

Conclusion: The present results suggested that the spleen is important in the improvement of intestinal barrier function by brain orexin, ghrelin or oxytocin, and butyrate. On the other hand, GLP-1 acts centrally in the brain to improve colonic hyperpermeability in a spleen-independent manner. All these results suggest that dual mechanisms (spleen dependent or independent) may exist for the brain-gut regulation in intestinal barrier function.

Background: Functional defecation disorders (FDD) are a common etiology of refractory chronic constipation (CC). FDD diagnosis (dyssynergic defecation [DD] and inadequate defecatory propulsion [IDP]), requires diagnostic tests including anorectal manometry (ARM) and balloon expulsion test (BET). Biofeedback (BF) is the treatment of choice for DD. The aims of our study were to evaluate: the outcome of BF in a group of constipated patients with defecatory disorders of any etiology; the efficacy of two simple diagnostic tools in predicting BF outcome in the short-term.

Methods: One hundred and thirty-one refractory CC patients failing the BET underwent BF therapy. Before BF, all patients underwent the following: ARM. Straining questionnaire. The answers were: "belly muscles"; "anal muscles"; "both"; "Don't know/No answer." Digital rectal examination augmented by abdominal palpation on straining (augmented-DRE). The BF therapist was blinded to ARM, straining questionnaire, and augmented-DRE results.

Key results: Eighty-one patients responded to BF. Gender, age, and IBS-C showed no significant impact on BF response. Both DD and IDP responded equally to BF, while the rate of response in patients with isolated structural pelvic floor abnormalities was lower (p < 0.001). The answer "anal muscles" to straining questionnaire showed a strong association with BF response (p < 0.001). A lack in abdominal contraction and in anal relaxation on augmented-DRE were strongly associated with BF response (p < 0.01). Absence of manual maneuvers to facilitate defecation was associated with BF response (p < 0.001).

Conclusions & inferences: BF is the therapy of choice for refractory constipation due to FDD of any etiology, inducing both clinical and anorectal physiology improvement in the short term. Comorbid IBS-C did not affect outcome while symptomatic isolated pelvic floor abnormalities appeared refractory to behavior treatment. The straining questionnaire and augmented-DRE outcomes showed a strong correlation with BF response and can be implemented in clinical practice to improve the management of constipated patients by prompting early referral to BF.

Enteric glia are a heterogeneous population of peripheral glia within the enteric nervous system and play pivotal roles in gut homeostasis, tissue integrity, coordination of motility, and intestinal immune responses. Under physiological conditions, they communicate with enteric neurons to control intestinal motility. In contrast, enteric glia undergo reactive changes in response to inflammatory signals during enteric neuroinflammation and participate in immune control. In this state, these glia are called reactive enteric glia, which promote cytokine and chemokine secretion and perpetuate immune cell recruitment, thereby affecting disease progression. Interestingly, reactive glia exhibit a huge plasticity and adapt to or shape the immune environment towards a resolving phenotype during inflammation and neuropathies. Recent studies revealed a bidirectional communication between enteric glia and resident and infiltrating immune cells under healthy conditions and in the context of inflammation-based intestinal disorders and neuropathies. While recent reviews give a superb general overview of enteric glial reactivity, we herein discuss the latest evidence on enteric glial reactivity in two prominent inflammatory conditions: acute postoperative inflammation, resulting in postoperative ileus, and chronic inflammation in inflammatory bowel diseases. We define their plasticity during inflammation and the interplay between reactive enteric glia and intestinal macrophages. Finally, we sketch important questions that should be addressed to clarify further the impact of enteric glial reactivity on intestinal inflammation.

Background: Oropharyngeal dysphagia is prevalent among neurological patients, often necessitating enteral tube feeding with a nasogastric tube (NGT) or percutaneous endoscopic gastrostomy (PEG). These patients are at significant risk of developing aspiration pneumonia. This study aimed to assess the impact of oropharyngeal dysphagia on pneumonia risk requiring hospitalization in neurological patients on long-term enteral tube feeding.

Methods: This retrospective observational study was conducted between 2015 and 2022. It included neurological patients who underwent upper gastrointestinal endoscopy combined with a Modified Flexible Endoscopic Evaluation of Swallowing (mFEES) for suspect dysphagia, characterized by difficulty or discomfort in swallowing. Participants were either orally fed or had been on long-term enteral tube feeding via NGT or PEG. A 2-year follow-up was conducted to monitor pneumonia cases requiring hospitalization. Multivariate analyses were conducted to identify risk factors for pneumonia requiring hospitalization.

Key results: A total of 226 orally fed and 152 enteral tube-fed patients were enrolled. Multivariate analyses showed a significantly increased risk of pneumonia in patients with a history of pneumonia and those receiving enteral tube feeding. Subgroup analysis indicated a significantly lower risk of pneumonia among enteral tube-fed patients with oropharyngeal dysphagia who PEG-fed patients compared to NGT-fed patients (adjusted HR: 0.21, 95% CI: 0.10-0.44, p < 0.001). The cumulative incidence of pneumonia requiring hospitalization was significantly lower in the PEG group than in the NGT group (p < 0.001).

Conclusion: mFEES could be a screening tool for oropharyngeal dysphagia. PEG is preferred over NGT for long-term enteral feeding, as it significantly reduces the risk of pneumonia requiring hospitalization, especially in patients with oropharyngeal dysphagia.

Background: Cyclic vomiting syndrome (CVS), a disorder of gut-brain interaction, presents with recurrent episodes of severe nausea and vomiting. It is often associated with missed or delayed diagnoses and substantial healthcare utilization. Despite historical recognition dating back to the 19th century, epidemiological insights remain limited, with research predominantly originating from specific regions, such as the US. CVS prevalence and incidence rates vary widely and are hindered by inconsistent methodologies and disease recognition.

Purpose: This review aims to provide a comprehensive overview of CVS prevalence and incidence rates. It reviews the currently available data and identifies gaps in knowledge. Understanding the global epidemiology of CVS, increasing awareness of the disease, and fostering global collaboration are crucial. Other pertinent issues include disparities in outcomes, particularly among African Americans and Hispanics in the United States, underscoring the need to understand the social determinants of health that drive disease outcomes. This understanding can inform targeted interventions to address these barriers and achieve equitable healthcare both in the United States and globally.

Background: Chronic constipation is a gastrointestinal functional disorder which affects patient quality of life. Therefore, many studies were oriented to search herbal laxative agents. In this study, we investigated the phytochemical composition of beetroot juice (BJ) and its laxative potential in an experimental model of constipation and colonic dysmotility induced by loperamide (LOP) in Wistar rats.

Methods: Animals were concurrently pretreated with LOP (3 mg/kg, b.w., i.p.) and BJ (5 and 10 mL/kg, b.w., p.o.), or yohimbine (2 mg/kg, b.w., i.p.), during 1 week. The laxative activity was determined based on the weight, frequency, and water content of the feces matter. The gastric-emptying test and intestinal transit were determined. Colon histology was examined, and oxidative status was evaluated using biochemical-colorimetric methods.

Key results: The in vivo study revealed that LOP induced a significant inhibition of gastrointestinal motility, negative consequences on defecation parameters, oxidative stress, and colonic mucosa lesions. Conversely, administration of BJ reestablished these parameters and restored colonic oxidative balance. Importantly, BJ treatment protected against LOP-induced inflammatory markers (pro-inflammatory cytokines and WBC) and the increase in intracellular mediators such as hydrogen peroxide, free iron, and calcium levels.

Conclusions & inferences: This study demonstrated that the bioactive compounds in BJ provided an anti-constipation effect by modulating intestinal motility and regulating oxidative stress and inflammation induced by LOP intoxication.

Introduction: The herbal preparation STW 5 ameliorates functional dyspepsia partly by relaxing smooth muscle of the proximal stomach, thus improving gastric accommodation. We explored the unknown pathways responsible for this effect by testing targets known to modulate gastric smooth muscle relaxation.

Methods: STW 5-induced relaxation of smooth muscle strips from guinea pig gastric corpus before and after pharmacological interventions were recorded with force transducers in an organ bath. ORAI1 mRNA expression was tested in the proximal stomach.

Key results: Blockade of Ca²⁺-activated K⁺ and Cl^- channels, voltage-gated L- or T-type Ca2+ channels, TRPA1-, TRPV1-, adenosine or 5-HT₄ receptors, antagonizing ryanodine receptors, inhibiting cyclooxygenase or sarcoplasmic reticulum calcium ATPase did not affect STW 5-evoked relaxation. Likewise, protein-kinase A or G were not involved. However, the relaxation evoked by STW 5 was significantly reduced by phorbol-12-myristat-13-acetat, an activator of protein-kinase C, by 2- aminoethyldiphenylborinate, an inhibitor of the IP3 receptor-mediated Ca²⁺ release from the sarcoplasmic reticulum or by SKF-96365, a nonselective store-operated calcium entry (SOCE) blocker. Furthermore, the mixed TRPC3/SOCE inhibitor Pyr3, but not the selective TRPC3 blocker Pyr10, reduced the effect of STW 5. Finally, BTP2, a potent blocker of ORAI-coupled SOCE, almost abolished STW 5-evoked relaxation. Expression of ORAI1 could be demonstrated in the corpus/fundus.

Conclusions & inferences: STW 5 inhibited SOCE, most likely ORAI channels, which are modulated by IP3- and PKC-dependent mechanisms. Our findings impact on the design of drugs to induce muscle relaxation and help identify phytochemicals with similar modes of actions to treat gastrointestinal disturbances.

Background: In placebo-controlled clinical trials, reboxetine, a selective noradrenaline reuptake inhibitor, increases urethral pressure and relieves stress urinary incontinence symptoms in women. Considering the close connection in neural regulation of the external urethral and anal sphincters, we hypothesized that reboxetine may also enhance anal sphincter pressure. Conversely, it is believed that selective serotonin reuptake inhibitors may contribute to fecal incontinence by reducing anal sphincter pressure. In this study, we investigated the effect of reboxetine and citalopram on anal opening pressure in healthy female volunteers.

Methods: In a double-blind, three-way crossover trial, 24 female participants received single doses of 40 mg citalopram, 8 mg reboxetine, and matching placebos, with a minimum of 8-day washout between sessions. Using anal acoustic reflectometry, we measured anal opening pressure during both resting and squeezing conditions at the estimated time of peak plasma concentration for both study drugs.

Key results: Compared with placebo, reboxetine increased anal opening pressure with 23.4 cmH₂O (95% confidence interval [CI] 16.5-30.2, p < 0.001) during rest and with 22.5 cmH₂O (95% CI 15.2-29.8, p < 0.001) during squeeze. Citalopram did not change anal opening pressure statistically significantly compared to placebo.

Conclusions & inferences: An 8-mg dose of reboxetine increased anal opening pressure substantially in healthy women, suggesting potential benefits for fecal incontinence symptoms. In contrast, a 40-mg dose of citalopram showed a marginal and statistically insignificant effect on anal opening pressure, indicating that selective serotonin reuptake inhibitors do not contribute to fecal incontinence by reducing anal sphincter tone.