Exacerbation of symptoms, nocturnal acid reflux, and impaired autonomic function are associated with sleep disturbance in gastroesophageal reflux disease patients.

Background and aim: Gastroesophageal reflux disease (GERD) patients often report sleep disturbance (SD); however, the relationship between GERD and SD is unknown. This study investigated whether SD affects symptoms, acid reflux, and autonomic function in GERD patients. Methods: A total of 257 subjects (126 patients with SD and 99 patients without SD) participated in this survey from January 2020 to August 2022. Participants were required to complete questionnaires including the GERD impact scale (GIS), Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HAMD). Esophageal mucosal injury, acid exposure, peristaltic function, and autonomic function were assessed by upper endoscopy, high-resolution esophageal manometry (HRAM), 24-h multichannel intraluminal impedance with pH (24 h-MII-pH), and electrocardiography (ECG). Results: Gastroesophageal reflux disease patients with SD experienced a higher frequency of prolonged reflux (p < 0.001), longest reflux event (p < 0.001), acid exposure time (p < 0.001) during the recumbent period, and a higher incidence of erosive esophagitis (EE) (59.5 vs. 45.5%, p = 0.036) than those without SD. Pearson's correlation analysis showed that SD was positively correlated with GIS (r = 0.725, p < 0.001), HAMA (r = 0.680, p < 0.001), and HAMD (r = 0.323, p < 0.001) scores, and negatively correlated with parasympathetic or vagal nerve activity (r = -0.770, p < 0.001). Conclusion: Gastroesophageal reflux disease patients with SD experience more severe reflux symptoms and nocturnal acid reflux, which may be related to autonomic dysfunction.

Post-reflux swallow-induced peristaltic wave index and mean nocturnal baseline impedance predict proton pump inhibitor response in patients with reflux hypersensitivity.

BACKGROUND AND AIM: Post-reflux swallow-induced peristaltic wave (PSPW) index and mean nocturnal baseline impedance (MNBI) have been shown to influence proton pump inhibitor (PPI) response in GERD patients. However, currently, little data concerning these variables in patients with reflux hypersensitivity (RH) are available. In this study, we aimed to evaluate, in RH patients, the prevalence of PPI responders and nonresponders and investigate the predictive value of impedance-pH variables, including PSPW and MNBI, on responses to PPI. METHODS: A total of 108 RH patients who met ROME IV criteria were prospectively recruited from June 2018 to December 2022. The prevalence of PPI responders/nonresponders was calculated, and impedance-pH variables were compared between the response and nonresponse groups. Multiple logistic regression was used to investigate predictors for PPI response. RESULTS: Among 108 patients with RH, 60 patients (55.56%) were the PPI responders, and 48 (44.44%) were the nonresponders. Compared with the nonresponders, the PPI responders had a lower PSPW index (47.05 ± 4.43 vs 51.33 ± 3.50, P = 0.004) and a decreased value of MNBI (1866.68 ± 390.62 vs 2181.14 ± 338.42, P = 0.017). Multivariate logistic regression revealed that only the pathologic PSPW index (OR: 2.064) and MNBI (OR: 1.800) significantly influenced PPI response. CONCLUSIONS: Nearly half of RH patients were PPI nonresponders. Impedance-pH monitoring was more valuable than pH-only monitoring in associating PPI response to reflux in RH patients owing to the appraisal of the PSPW index and MNBI.

Colorectal motility patterns and psychiatric traits in functional constipation and constipation-predominant irritable bowel syndrome: A study from China.

BACKGROUND: Functional constipation (FC) and constipation-predominant irritable bowel syndrome (IBS-C) represent a spectrum of constipation disorders. However, the majority of previous clinical investigations have focused on Western populations, with limited data originating from China. AIM: To determine and compare the colorectal motility and psychiatric features of FC and IBS-C in an Eastern Chinese population. METHODS: Consecutive chronic constipation patients referred to our motility clinic from December 2019 to February 2023 were enrolled. FC and IBS-C diagnoses were established using ROME IV criteria, and patients underwent high-resolution anorectal manometry (ARM) and a colonic transmit test using the Sitz marker study. Constipation-related symptoms were obtained through questionnaires. Anxiety and depression were assessed by the Hamilton anxiety rating scale and the Hamilton Depression Rating Scale-21. The clinical characteristics and colorectal motility patterns of FC and IBS-C patients were compared. RESULTS: No significant differences in sex, age or abdominal discomfort symptoms were observed between IBS-C and FC patients (all P > 0.05). The proportion of IBS-C patients with delayed colonic transit was higher than that of patients with FC (36.63% vs 15.91%, P < 0.05), while rectosigmoid accumulation of radiopaque markers was more common in the FC group than in the IBS-C group (50% vs 26.73%, P < 0.05). Diverse proportions of these dyssynergic patterns were noted within both the FC and IBS-C groups by ARM. IBS-C patients were found to have a higher prevalence of depression than FC patients (66.30% vs 42.42%, P < 0.05). The scores for feelings of guilt, suicide, psychomotor agitation, diurnal variation, obsessive/compulsive disorder, hopelessness, self-abasedment and gastrointestinal symptoms were significantly higher in IBS-C patients than that in FC patients (P < 0.05). For IBS-C (χ2 = 5.438, P < 0.05) but not FC, patients with normal colon transit time were significantly more likely to have anxiety than those with slow colon transit time. For IBS-C patients but not FC patients, the threshold of first constant sensation, desire to defecate and sustained urgency were all weakly correlated with the degree of anxiety (r = 0.414, r = 0.404, and r = 0.418, respectively, P < 0.05). The proportion of patients with a low threshold of desire to defecate among IBS-C patients with depression was lower than that in those without depression (69.6% vs 41.9%, χ2 = 4.054, P < 0.05). CONCLUSION: Our findings highlight both overlapping and distinctive patterns of colon transit, dyssynergic patterns, anorectal sensation, psychological distress, and associations of psychiatric and colorectal motility characteristics in FC and IBS-C patients in an Eastern Chinese population, providing valuable insights into the pathophysiological underpinnings of these disorders.

Gut Microbiome and Metabonomic Profile Predict Early Remission to Anti-Integrin Therapy in Patients with Moderate to Severe Ulcerative Colitis.

Patients with ulcerative colitis (UC) have low response rates to anti-integrin medications, necessitating the identification of noninvasive biomarkers for predicting remission to anti-integrin therapy. In this study, patients with moderate to severe UC commencing anti-integrin therapy (n = 29), inactive to mild UC patients (n = 13), and healthy controls (n = 11) were selected. Besides clinical evaluation, fecal samples were collected at baseline and week 14 from moderate to severe UC patients. The clinical remission was defined based on the Mayo score. Fecal samples were assessed with 16S rRNA gene sequencing, liquid chromatography-tandem mass spectrometry, and gas chromatography-mass spectrometry (GC-MS). We identified that Verrucomicrobiota was significantly more abundant in the remission group (P < 0.001) than that of nonremission group at phylum level for patients commencing vedolizumab. GC-MS analysis revealed that the concentrations of butyric acid (P = 0.024) and isobutyric acid (P = 0.042) were significantly higher in the remission group compared to the nonremission group at baseline. Finally, the combination of Verrucomicrobiota, butyric acid, and isobutyric acid improved the diagnosis of early remission to anti-integrin therapy (area under the concentration-time curve = 0.961). We identified significantly higher phylum level diversity of Verrucomicrobiota in remission than the nonremission groups at baseline. Notably, the combination of gut microbiome and metabonomic profiles improved the diagnosis of early remission to anti-integrin therapy. IMPORTANCE It is reported that patients with ulcerative colitis (UC) have low response rates to anti-integrin medications in the latest VARSITY study. Therefore, our primary goals were to discover differences in the gut microbiome and metabonomics patterns between early remission and nonremission patients and to explore the diagnostic value in predicting clinical remission to anti-integrin therapy accurately. In this study, we found that Verrucomicrobiota was significantly more abundant in the remission group (P < 0.001) than that of nonremission group at phylum level for patients commencing vedolizumab. Gas chromatography-mass spectrometry analysis revealed that the concentrations of butyric acid (P = 0.024) and isobutyric acid (P = 0.042) were significantly higher in the remission group compared with the nonremission group at baseline. Notably, the combination of Verrucomicrobiota, butyric acid, and isobutyric acid improved the diagnosis of early remission to anti-integrin therapy (area under the concentration-time curve = 0.961).

Slow, deep breathing intervention improved symptoms and altered rectal sensitivity in patients with constipation-predominant irritable bowel syndrome.

Background and aim: Limited treatment options have been shown to alter the natural course of irritable bowel syndrome (IBS). Slow, deep breathing (SDB) is a common pain self-management intervention. This pilot study aimed to explore the impact of SDB on measures of autonomic and anorectal functions as well as patient-reported symptoms in constipation-predominant IBS (IBS-C). Methods: Eighty-five IBS-C patients were enrolled in this study and randomly assigned to the experimental group (Group A, n = 42) and the control group (Group B, n = 43). SDB was conducted at six breathing cycles per minute with an inhalation for 4 s and exhalation for 6 s at a ratio of 2:3 and repeated for 30 min during the intervention. All subjects underwent high-resolution anorectal manometry (HRAM) and completed the standardized IBS symptom severity system (IBS-SSS) questionnaire. Meanwhile, changes in stool consistency, weekly frequency of complete spontaneous bowel movements (CSBMs), and weekly frequency of spontaneous bowel movements (SBMs) were recorded. All IBS-C patients received electrocardiogram (ECG) recordings for heart rate variability (HRV) analysis at baseline, weeks 3, 6. Results: At baseline, no differences were found between Groups A and B. The IBS-SSS score and its five sub-scores of Group B patients were significantly higher at week 6 than those of Group A patients (all p < 0.001). Furthermore, compared with Group B patients, Group A patients had a significantly higher threshold volume for the first sensation (p < 0.001), desire to defecate (p = 0.017), and maximum tolerable volume (p = 0.018) at week 6 of the SDB treatment. We also noted significant improvements in stool consistency (p = 0.002), weekly SBM frequencies (p < 0.001), and weekly CSBM frequencies (p = 0.018) of Group A patients at week 6 when compared with Group B patients. Finally, the corrected high frequency (HF) of Group A patients was significantly higher than the HF of Group B patients at week 3 (p < 0.001) and at week 6 (p < 0.001). Likewise, patients in Group A had a significantly higher root mean square of the successive differences (RMSSD) than that of patients in Group B at week 3 (p < 0.001) and at week 6 (p < 0.001). Conclusion: We found that a 6-week SDB intervention improved symptoms and altered rectal sensation in IBS-C patients. Moreover, SDB enhanced vagal activity. These findings suggest that the effect of SDB on IBS-C may be due to mechanisms involving autonomic responses.

Sleep Deficiency Is Associated With Exacerbation of Symptoms and Impairment of Anorectal and Autonomic Functions in Patients With Functional Constipation.

Objective: Sleep deficiency (SD) is commonly seen in patients with functional constipation (FC). Our aim was to determine whether the presence of SD would influence symptoms, anorectal motility, sensation, and autonomic function in FC patients. Materials and Methods: A total of 85 FC patients with SD and 193 FC patients without SD underwent high-resolution anorectal manometry. SD was assessed by using the Pittsburgh Sleep Quality Index (PSQI) score. Participants were required to fill in the entire questionnaires, including Patients' Constipation-symptoms, State-Trait Anxiety Inventory, and Hamilton Depression Scale. Autonomic dysfunction was studied by recording the heart rate variability. Multiple logistic regression was performed to explore the potential risk factors for anorectal function. Results: Functional constipation patients with SD had a higher total score of constipation symptom (P < 0.001), in comparison with those without SD. FC patients with SD demonstrated significantly lower threshold volume for first sensation (P < 0.001) and urge (P < 0.001), as compared to those without SD. The PSQI score positively correlated with constipation symptom total score (P < 0.001), and negatively correlated with threshold volume for first sensation (P < 0.001) and urge (P < 0.001). FC patients with SD had a reduced vagal activity (P = 0.016) and a higher sympathetic activity as compared to those without SD (P = 0.003). Multivariate logistic regression revealed that SD, anxiety and depression were independent risk factors for anorectal function, with SD exhibiting the highest degree of association with first sensation (OR: 4.235). Conclusion: Sleep deficiency is associated with worse constipation related symptoms, altered anorectal function and perception, and impaired autonomic function in FC patients.