Neurogastroenterology and Motility最新文献

Background: The functional relationship of striated esophagus (St.Eso) motor function with pharyngeal deglutitive biomechanical events has not been systematically studied. The aim of this study was to determine the spatio-temporal characteristics of St.Eso function and its correlation with pharyngeal biomechanics and bolus transport.

Methods: We studied 50 healthy volunteer subjects (age range: 21-82 years, 31 female) by digital videofluoroscopy. All subjects were studied in a seated, upright position. Thirteen of these 50 volunteers also underwent high-resolution manometry (HRM) concurrent with fluoroscopy. We used laryngeal excursion as a surrogate for St.Eso excursion.

Key results: Median duration of St.Eso excursion was 2.35 [1.93,2.85, 5th and 95th percentile] seconds. Mean maximum extent of St.Eso excursion was 2.84 ± 0.72 cm. We identified four distinct periods in deglutitive St.Eso motor function: P1. Anterosuperior ascent without bolus or peristaltic activity, P2. Non-peristaltic bolus receiving at the apogee of St.Eso excursion concurrent with UES opening and pharyngeal peristalsis P3. Peristaltic bolus transport as St.Eso descends and P4. Continued peristalsis in resting position.

Conclusions and inferences: 1. St.Eso motor function spans both pharyngeal and esophageal phases of swallowing for receiving and transporting the bolus, 2. Pressure signatures in HRM recordings currently attributed to St.Eso deglutitive motor activity does not represent the entirety of St.Eso peristalsis, only the part that occurs in its resting position. St.Eso peristalsis that occurs during its descent is recorded by pressure sensors initially in the pharynx. This finding needs to be considered when interpreting HRM recordings of the pharynx and proximal esophagus.

Background: An impaired intestinal barrier with the activation of corticotropin-releasing factor (CRF), Toll-like receptor 4 (TLR4), and proinflammatory cytokine signaling, resulting in visceral hypersensitivity, is a crucial aspect of irritable bowel syndrome (IBS). The gut exhibits abundant expression of neurotensin; however, its role in the pathophysiology of IBS remains uncertain. This study aimed to clarify the effects of PD149163, a specific agonist for neurotensin receptor 1 (NTR1), on visceral sensation and gut barrier in rat IBS models.

Methods: The visceral pain threshold in response to colonic balloon distention was electrophysiologically determined by monitoring abdominal muscle contractions, while colonic permeability was measured by quantifying absorbed Evans blue in colonic tissue in vivo in adult male Sprague-Dawley rats. We employed the rat IBS models, i.e., lipopolysaccharide (LPS)- and CRF-induced visceral hypersensitivity and colonic hyperpermeability, and explored the effects of PD149163.

Key results: Intraperitoneal PD149163 (160, 240, 320 μg kg^-1) prevented LPS (1 mg kg^-1, subcutaneously)-induced visceral hypersensitivity and colonic hyperpermeability dose-dependently. It also prevented the gastrointestinal changes induced by CRF (50 μg kg^-1, intraperitoneally). Peripheral atropine, bicuculline (a GABA_A receptor antagonist), sulpiride (a dopamine D₂ receptor antagonist), astressin₂-B (a CRF receptor subtype 2 [CRF₂] antagonist), and intracisternal SB-334867 (an orexin 1 receptor antagonist) reversed these effects of PD149163 in the LPS model.

Conclusions and inferences: PD149163 demonstrated an improvement in visceral hypersensitivity and colonic hyperpermeability in rat IBS models through the dopamine D₂, GABA_A, orexin, CRF₂, and cholinergic pathways. Activation of NTR1 may modulate these gastrointestinal changes, helping to alleviate IBS symptoms.

Background and aims: The group of disorders known as Disorders of Gut Brain Interaction (DGBI) were originally labeled functional GI disorders and were thought to be disorders of the gastrointestinal tract that had several psychological conditions as comorbidities. Despite mounting evidence that psychological morbidity plays an innate role in the etiology and maintenance of DGBI, none of the Rome IV criteria include any measure of psychological symptoms. This study tested the hypothesis that individuals would cluster differently if GI symptoms alone were considered versus GI symptoms combined with measures of psychological symptoms.

Methods: Data were obtained from the Rome Foundation Global Epidemiology Study measuring Rome IV GI symptoms, psychological measures and demographic characteristics. Latent profile models were used to cluster individuals based on (i) GI symptoms only (GI only) and then (ii) GI and psychological measures (GI + Psych).

Key results: Individuals clustering into the same group of individuals whether formed via GI only or GI + Psych, ranged from 96% for a 2-class solution (the most simplistic) to 76% with 6 classes (the parsimonious system) and 59% with twenty-two classes (mimicking Rome IV). The generalisability of this finding between six geographic regions was confirmed with agreement varying between 95%-97% for 2 clusters and 71-79% for 6 classes and 51%-63% for 22 classes. These findings were also consistent between DGBI (range 94% with 2 classes to 50% with 22 classes) and non-DGBI (range 97% with 2 clusters to 65% with 22 classes) groups.

Conclusions & inferences: Our data suggest that considering psychological as well as gastrointestinal symptoms would lead to a different clustering of individuals in more complex, and accurate, classification systems. For this reason, future work on DGBI classification should consider inclusion of psychological traits.

Objective: Intestinal ischemia-reperfusion injury (IIRI) is common in a variety of critical diseases and acute stress, and acupuncture is a promising treatment for IIRI. The aim of this study is to explore the mechanism of electroacupuncture (EA) at Zusanli (ST36) in improving IIRI from the perspective of the cholinergic anti-inflammatory pathway (CAP) and miRNA 124.

Methods: Seven groups of mice were performed: Control group, I/R group (IIRI model), EA group (I/R + EA), miRNA mimic group (I/R + EA + miRNA 124 mimic), miRNA inhibitor group (I/R + EA + miRNA 124 inhibitor), PNU group (I/R + EA + α7nAChR agonist), and MLA group (I/R + EA+ α7nAChR antagonist). The expression of intestinal macrophages, α7nAChR, miRNA 124, and related molecules, including p-STAT3 and IL-6, as well as histological damage (Chiu's score) and mucosal permeability (serum FD4 concentration), were detected.

Results: The serum FD4 concentrations in the EA and PNU groups were significantly lower compared to the I/R group (p < 0.05). The expression of intestinal α7nAChR and miRNA 124 in the EA, miRNA mimic, and PNU groups was higher than that in the I/R group (p < 0.05), while levels of p-STAT3 and IL-6 were reduced (p < 0.05). Conversely, in the miRNA inhibitor and MLA groups, miRNA 124 levels were significantly lower than in the EA group (p < 0.05), and IL-6 levels were increased (p < 0.05).

Conclusion: EA at Zusanli may induce miRNA124 through the cholinergic pathway on intestinal macrophages, which may be a key neuro-immune target of EA in the treatment of IIRI.

Background: The movement of intestinal smooth muscle is regulated by the external autonomic nervous system (ANS) and its internal enteric nervous system (ENS). Previous studies have shown that acupuncture has a bidirectional regulating effect on intestinal motility through the sympathetic and vagal ANSs. ENS can independently regulate the sensory, secretory, and motor functions of the intestine. The interstitial cells of Cajal (ICC), the pacemaker cells in ENS, play a key role in maintaining gastrointestinal motility. However, studies on the role and mechanism of ICC in the regulation of intestinal function by acupuncture are still unclear.

Methods: To investigate the effect of ICC on the regulation of intestinal motility by manual acupuncture (MA), we recorded the pressure of warm water-filled manometric balloons in duodenum, jejunum, and distal colon in ICC deficiency WsWs^-/- rats and wild-type littermates WsRC^+/+ rats, and performed MA at ST25 (Tianshu), ST37 (Shangjuxu), LI11 (Quchi), and BL25 (Danchangshu) acupoints. Furthermore, the excretion of phenol red in feces before and after MA at ST37 or ST25 was assessed.

Key result: In WsRC^+/+ rats, MA at ST37, LI11, and BL25 promoted duodenal, jejunal, and distal colon motility, whereas MA at ST25 significantly inhibited duodenal and jejunal motility and promoted distal colon motility. ICC deficiency in WsWs^-/- rats led to a reduction in the promoting effect of LI11 on duodenal motility, a decrease in the promoting effect of ST37 on jejunal motility, and a significant reduction in the promoting effect of BL25 on distal colonic motility in those rats. Additionally, ICC absence significantly attenuated the inhibitory effect of ST25 on duodenal motility. MA at ST37 or ST25 did not change the content of phenol red in the feces in WsRC^+/+ and WsWs^-/- rats.

Conclusion and inferences: Our results suggest that the absence of ICC impairs the bidirectional regulatory effect of MA on intestinal function. It reveals the important role of ICC in the treatment of intestinal dysfunction diseases by acupuncture and provides a new theoretical basis for the treatment of such diseases by MA.

Background: Irritable bowel syndrome (IBS) and functional dyspepsia (FD) are common disorders of gut-brain interaction (DGBI). The Rome IV criteria are the gold standard for research when diagnosing DGBI. However, bothersomeness, or the degree to which symptoms are distressing or disruptive to a person's daily life, is a potential treatment-seeking motivator that is not assessed by the Rome criteria. The Rome Foundation developed and published diagnostic criteria for clinical practice that include bothersomeness. We aimed to evaluate these constructs via patient focus groups to determine what prompts healthcare-seeking as a means to assess its value in the Rome clinical criteria.

Methods: Adults meeting Rome IV criteria for IBS, FD, or both participated in focus groups in Australia and the United States. Semi-structured interview transcripts were analyzed using Template Thematic Analysis, with three a priori and other a posteriori themes refined iteratively through team discussion and consensus.

Key results: Participants confirmed the frequency and duration of symptoms was not sufficient to reflect illness experience. Four major themes emerged: (1) Bothersomeness should be included in assessments of IBS and FD; (2) Patients find many DGBI symptoms bothersome; (3) Bothersomeness traverses multiple domains of quality of life; (4) Patients may hesitate to seek medical advice due to past negative experiences.

Conclusions and inferences: These findings support the value of the Rome Clinical Criteria. They emphasize the importance of expanding assessments of patients with DGBI to include how bothersome they perceive symptoms to be, how much symptoms interfere with their daily life, and what may moderate their decisions to seek treatment.

Background: Capsaicin-containing red pepper sauce suspension augments esophageal contraction amplitude on conventional manometry. This study used high-resolution manometry (HRM) to investigate if capsaicin infusion modulates segmental esophageal smooth muscle peristalsis in healthy adults.

Methods: Sixteen healthy volunteers (mean age 37 years, 14 male) underwent HRM for the evaluation of primary peristalsis and secondary peristalsis using slow and rapid air distensions. Both primary and secondary peristalsis were assessed following infusions of capsaicin-containing red pepper sauce and saline.

Key results: Capsaicin infusion significantly increased heartburn symptoms compared to saline infusion (p < 0.001), and significantly decreased threshold volumes of secondary peristalsis during rapid air distensions (p = 0.02). The frequency of secondary peristalsis during rapid air distensions was significantly increased by capsaicin infusion (p = 0.03). Neither capsaicin infusion (p = 0.06) nor saline infusion (p = 0.27) altered threshold volume during slow air distensions. Capsaicin infusion significantly increased distal contractile integral (DCI) of primary peristalsis (p = 0.04), particularly in the proximal smooth muscle segment (p = 0.048). It enhanced secondary peristalsis during rapid air distensions (p = 0.003) but not during slow air distension (p = 0.23). Saline infusion significantly increased DCI of secondary peristalsis during rapid air distension (p = 0.01).

Conclusions and inferences: Augmentation of distension-induced secondary peristalsis can be modulated by activation of capsaicin-sensitive afferents similar to mechanosensitive afferents. Capsaicin-induced augmentation of primary peristalsis isolates to the cholinergic-mediated proximal smooth muscle segment, which warrants study in ineffective esophageal motility to determine therapeutic potential.

Background: GI-specific psychological factors are important contributors to patients' symptom experience and quality of life across all disorders of gut-brain interaction (DGBI). Clinicians' ability to recognize the role of these psychological factors is essential for formulating a biopsychosocial case conceptualization and informing treatment decisions.

Purpose: This article will familiarize gastroenterology providers with conceptualizing the role of GI-specific psychological factors in DGBI and provides stepwise, practical guidance for how to assess these during clinical encounters in a time-efficient manner.

Background: Understanding the relationship between distal contractile integral (DCI) and mean nocturnal baseline impedance (MNBI) could shed light on new diagnostic and treatment strategies, specifically concerning nocturnal reflux. This study aimed to assess this relationship to enhance our comprehension of the interplay between esophageal contractility and mucosal permeability.

Methods: We identified adult patients who had high resolution esophageal manometry and pH-impedance tests performed within a 30-day period between December 2018 and March 2022. A random forest model was used to identify significant predictors of MNBI, assisting with variable selection for a following regression analysis. Subsequently, both univariable and multivariable regression models were utilized to measure the association between predictors and MNBI.

Key results: Our study included 188 patients, primarily referred for testing due to reflux. The most common motility diagnoses were normal (62%) followed by possible esophagogastric junction outflow obstruction (22%). The mean DCI was 2020 mmHg∙s∙cm and MNBI was 3.05 kΩ. The random forest model identified 12 significant predictors for MNBI, key variables being acid exposure time (AET), total proximal reflux events, intraabdominal lower esophageal sphincter length, hiatal hernia presence, and DCI. Subsequent multivariable regression analyses demonstrated log AET (β = -0.69, p = <0.001), total proximal reflux events (β = -0.16, p = 0.008), hiatal hernia presence (β = -0.82, p = 0.014), log DCI (β = 1.26, p < 0.001), and age (β = -0.13, p = 0.036) as being significantly associated with MNBI.

Conclusions and inferences: DCI is a key manometric predictor of MNBI emphasizing the role of manometry in detecting reflux risk and the need for its consideration in reflux management.

Background and aims: The endocannabinoid (eCB) system includes ligands (anandamide and 2-arachidonoyl glycerol, 2-AG), receptors and catabolizing enzymes (fatty acid amide hydrolase, FAAH and monoacylglycerol lipase) expressed in both the brain and gut. We investigated whether the FAAH inhibitor, URB597, influenced visceral pain to colorectal distension (CRD) in an acute stress-related model of visceral hypersensitivity induced by the selective corticotropin-releasing factor receptor subtype 1 (CRF₁) agonist, cortagine.

Methods: Male Sprague-Dawley rats were injected subcutaneously (SC) with URB597 (3 mg/kg) or vehicle and 2 h later, intraperitoneally with cortagine (10 μg/kg) or vehicle. The visceromotor responses (VMR) were assessed to a first CRD (baseline) before injections, and to a second CRD 15 min after the last treatment. Brain, jejunum, and proximal colon were collected from treated and naïve rats for levels quantification of three fatty acid amides (FAAs) [anandamide (arachidonyl-ethanolamide, AEA), oleoyl-ethanolamide (OEA) and palmitoyl-ethanolamide (PEA)], and 2-AG. In separate animals, defecation/diarrhea were monitored after URB597 and cortagine.

Key results: URB597 inhibited cortagine-induced increased VMR at 40 mmHg (89.0 ± 14.8% vs. 132.5 ± 15.6% for vehicle SC, p < 0.05) and 60 mmHg (107.5 ± 16.1% vs. 176.9 ± 24.4% for vehicle SC, p < 0.001) while not influencing basal VMR. In URB597 plus cortagine group, FAAs levels increased in the brain and intestinal tissue while 2-AG did not change. URB597 did not modify cortagine-induced defecation/diarrhea versus vehicle.

Conclusions and inferences: URB597 shows efficacy to elevate brain and intestinal FAAs and to counteract the colonic hypersensitivity induced by peripheral activation of CRF₁ signaling supporting a potential strategy of FAAH inhibitors to alleviate stress-related visceral hypersensitivity.