Neurogastroenterology and Motility最新文献

Background: Wearable technology is increasingly used in clinical practice and research to monitor functional gastrointestinal symptoms and mental health.

Aims: This article explores the potential of wearable sensors to enhance the understanding of the autonomic nervous system (ANS), particularly its role in linking psychological and gastrointestinal function. The ANS, facilitates brain-gut communication and is responsive to psychosocial conditions. It is implicated in disorders related to psychological stress and gut-brain interaction. Wearable technology enables tracking of the ANS in daily life, offering complementary and alternative methods from traditional lab-based measures. This review places focus on autonomic metrics such as respiratory sinus arrhythmia, vagal efficiency, and electrodermal activity as well as self-reports of autonomic symptoms.

Discussion: Potential applications include use of wearable sensors for tracking autonomic activity in disorder of gut-brain interaction such as cyclic vomiting syndrome, in which ANS dysregulation may be triggered by psychosocial factors. Considerations for data interpretation and contextualization are addressed, acknowledging challenges such as situational confounders of ANS activity and accuracy of wearable devices.

Background: Increasing age increases the incidence of chronic constipation and fecal impaction. The contribution of the natural aging process to this phenotype is unclear. This study explored the effects of age on key motility patterns in the murine colon and determined the contribution that altered neurokinin 2 (NK₂) -mediated signaling made to the aging phenotype.

Methods: Mucosal reflexes, colonic migrating motor complexes (CMMCs) and colonic motility assays were explored in isolated ex vivo colons from 3, 12-14, 18- and 24-months old mice and the NK₂-mediated response determined. Electrical field stimulation (EFS) or exogenous drug application were used to explore the role of the mucosa in colonic segments.

Key results: Aging reduced the force of contraction of the distal colon mucosal reflex, the frequency and force of contraction of CMMCs and the NK₂-mediated component of both motility patterns. Ondansetron, a 5-HT₃ receptor antagonist, blocked a component of both motility patterns in full thickness but not in mucosa-free segments of the distal colon. 5, hydroxytryptamine (5-HT) and EFS-evoked NK₂-dependent contractions were reduced with increasing age. Smooth muscle sensitivity to 5-HT or neurokinin A (NKA) was not altered with age. In isolated colon motility assays application of NKA decreased transit time in 24-months colon and the NK₂ antagonist GR159897 increased transit times in both 3- and 24-months old colons.

Conclusions and inferences: Aging impairs key motility patterns in the murine colon. These changes involve a decrease in mucosally-evoked NK₂-mediated signaling. Targeting NK₂-mediated signaling may provide a novel approach to treating age-related motility disorders in the lower bowel.

Background: Rikkunshito (RKT), a traditional Japanese medicine, can relieve epigastric discomfort and anorexia in patients with functional dyspepsia. RKT enhances the orexigenic hormone, ghrelin. Ghrelin regulates food motivation by stimulating the appetite control center in the hypothalamus and the brain mesolimbic dopaminergic pathway (MDPW). However, the effect of RKT on MDPW remains unclear. Here, we aimed to investigate the central neural mechanisms underlying the orexigenic effects of RKT, focusing on the MDPW.

Methods: We examined the effects of RKT on food intake and neuronal c-Fos expression in restraint stress- and cholecystokinin octapeptide-induced anorexia in male rats.

Key results: RKT treatment significantly restored stress- and cholecystokinin octapeptide-induced decreased food intake. RKT increased c-Fos expression in the ventral tegmental area (VTA), especially in tyrosine hydroxylase-immunoreactive neurons, and nucleus accumbens (NAc). The effects of RKT were suppressed by the ghrelin receptor antagonist [D-Lys³]-GHRP-6. RKT increased the number of c-Fos/orexin-double-positive neurons in the lateral hypothalamus (LH), which project to the VTA. The orexin receptor antagonist, SB334867, suppressed RKT-induced increase in food intake and c-Fos expression in the LH, VTA, and NAc. RKT increased c-Fos expression in the arcuate nucleus and nucleus of the solitary tract of the medulla, which was inhibited by [D-Lys³]-GHRP-6.

Conclusions & inferences: RKT may restore appetite in subjects with anorexia through ghrelin- and orexin-dependent activation of neurons regulating the brain appetite control network, including the hypothalamus and MDPW.

Background: Gastric fluid plays a key role in food digestion and drug dissolution, therefore, the amount of gastric fluid present in a fasted state may influence subsequent digestion and drug delivery. We aimed to describe intra- and interindividual variation in fasted gastric content volume (FGCV) and to determine the association with age, sex, and body size characteristics.

Methods: Data from 24 MRI studies measuring FGCV in healthy, mostly young individuals after an overnight fast were pooled. The analysis included 366 participants who had up to 6 repeated measurements, with a total of 870 measurements. Linear mixed model analysis was performed to calculate intra- and interindividual variability and to assess the effects of age, sex, weight, height, weight*height as a proxy for body size, and body mass index (BMI).

Results: FGCV ranged from 0 to 156 mL, with a mean (± SD) value of 33 ± 25 mL. The overall coefficient of variation within the study population was 75.6%, interindividual SD was 15 mL, and the intraindividual SD was 19 mL. Age, weight, height, weight*height, and BMI had no effect on FGCV. Women had lower volumes compared to men (MD: -6 mL), when corrected for the aforementioned factors.

Conclusion: FGCV is highly variable, with higher intraindividual compared to interindividual variability, indicating that FGCV is subject to day-to-day and within-day variation and is not a stable personal characteristic. This highlights the importance of considering FGCV when studying digestion and drug dissolution. Exact implications remain to be studied.

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.

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: 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.

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.