Disorders of Gut-brain Interaction on the US-Mexico Border: A Survey Using Rome IV Criteria.

BACKGROUND: Disorders of gut-brain interaction (DGBI) cause a substantial health burden. Herein we studied the prevalence and characteristics of DGBI and symptoms of bloating/distension in El Paso, Texas on the US-Mexico border, providing a unique opportunity to study the effects of acculturation. METHODS: Subjects from community centers completed the Rome IV questionnaire for DGBI, short acculturation scale for Hispanics questionnaire, and bloating/distention Pictograms. Data were presented as prevalence (95% CI) and compared using χ 2 . RESULTS: Of 216 participants, 197 (127 Hispanics, 90 with English acculturation) were included and 177 completed the Pictograms. Fifty-one [25.9% (20 to 32.6)] subjects fulfilled the criteria for at least one DGBI. Globus and functional dyspepsia were the most common upper DGBI, each in [3.0% (1.1 to 6.5)]. Unspecified functional bowel disorders [8.6% (5.1 to 13.5)], followed by functional abdominal bloating/distention [8.1% (4.7 to 12.9], and irritable bowel syndrome [6.1% (3.2 to 10.4] were the most common functional bowel disorder. Ninety-one (51.4%) reported bloating and/or distension with Pictograms; more frequently in those with DGBI (80.9% vs 40.8%, P < 0.001). Bloating and/or distension were reported by Pictograms in 30% of those not reporting it in the Rome IV Questionnaire. There were no differences based on acculturation or in Hispanics versus non-Hispanics. CONCLUSIONS: On the US-Mexico border, we found a lower prevalence of DGBI than in the US or Mexico. Functional abdominal bloating/distention was more prevalent on the US-Mexico border than in either country. Bloating/distension was more commonly reported with Pictograms than with verbal descriptors. There were no differences between Hispanics and non-Hispanics, suggesting shared environmental/acquired including dietary factors as the underlying mechanisms.

Gastric Electrical Stimulation for Treatment of Refractory Gastroparesis: the Current Approach to Management.

PURPOSE OF REVIEW: Gastroparesis is one of the more challenging entities in the landscape of gastroenterology, posing difficulties for both patients and physicians with regard to effective management and therapies. In this article, we reviewed various gastroparesis treatment options, with an emphasis on gastric electrical stimulation (GES). RECENT FINDINGS: GES has demonstrated a significant reduction of cardinal symptoms in refractory gastroparetic patients, particularly nausea and vomiting, across multiple studies. However, GES has not been shown to conclusively decrease gastric emptying time in these patients. Such finding has led the investigators to analyze the impact of combining GES with pyloroplasty. While this treatment pathway is nascent, its results thus far reveal an amplified improvement of gastroparesis symptomatology in addition to significant reduction of gastric transit, compared to GES by itself. Limited treatment choices are available for refractory gastroparesis. Combining GES with pyloroplasty holds promise but requires further assessment in large-scale trials to fully evaluate the risks and benefits.

Coronavirus: Pure Infectious Disease or Genetic Predisposition.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes novel coronavirus disease (COVID-19), is the seventh pathogenic coronavirus recently discovered in December 2019 in Wuhan, China. To date, our knowledge about its effect on the human host remains limited. It is well known that host genetic factors account for the individual differences in the susceptibility to infectious diseases. The genetic susceptibility factors to COVID-19 and its severity are associated with several unanswered questions. However, the experience gained from an earlier strain of coronavirus, SARS-CoV-1, which shows 78% genetic similarity to SARS-CoV-2 and uses the same receptor to bind to host cells, could provide some clues. It, therefore, seems possible to assemble new evidence in order to solve a potential genetic predisposition puzzle for COVID-19. In this chapter, the puzzle pieces, including virus entry receptors, immune response, and inflammation-related genes, as well as the probable genetic predisposition models to COVID-19, are discussed.

Central Nervous System Mechanisms of Nausea in Gastroparesis: An fMRI-Based Case-Control Study.

BACKGROUND/AIMS: Nausea is a major complaint of gastroparesis (GP), and the pathophysiology of this condition is poorly understood. Therefore, this study utilized fMRI to investigate the possible central nervous system (CNS) mechanisms of nausea in 10 GP patients versus 8 healthy controls (HCs). METHODS: Nausea severity was assessed on a 0-10 scale and presented as mean ± SD. Nausea was increased from baseline utilizing up to 30 min of visual stimulation (VS). Functional network connectivity was measured with fMRI at baseline and after 30 min of VS. fMRI data were preprocessed using statistical parametric mapping software. Thirty-four independent components were identified as meaningful resting-state networks (RSNs) by group independent component analysis. The Functional Network Connectivity (FNC) among 5 RSNs considered important in CNS nausea mechanisms was calculated as the Pearson's pairwise correlation. RESULTS: Baseline nausea score in GP patients was 2.7 ± 2.0 and increased to 7.0 ± 1.5 after stimulation (P < 0.01). In HCs nausea scores did not increase from baseline after stimulus (0.3 ± 0.5). When comparing GP patients to HCs after VS, a significant reduction (P < 0.001) in bilateral insula network connectivity compared to the right insula network was detected. No significant differences in connectivity were noted among the other RSNs. Additionally, the average gray matter volume was non-significantly reduced in the insula in GP patients compared to HC. CONCLUSIONS: The insula connectivity network is impaired in nauseated GP patients. This phenomenon could explain the susceptibility of GP patients to nausea or may have resulted from a state of chronic nausea.

The role of oral simethicone on the adenoma detection rate and other quality indicators of screening colonoscopy: a randomized, controlled, observer-blinded clinical trial.

BACKGROUND AND AIMS: Combining simethicone (SIM) with a colon preparation agent has been shown to improve mucosal visibility during screening colonoscopy, but its effect on the adenoma detection rate (ADR) remains unclear. SIM is commonly used through the endoscope to eliminate bubbles during endoscopy. However, this practice recently has been associated with endoscope-transmitted infections. Our aims were to determine the role of SIM added to a polyethylene glycol preparation on the ADR, procedure times, colon preparation, and intraprocedural use of SIM. METHODS: This was a randomized, controlled, observer-blinded, clinical trial of patients undergoing screening colonoscopy. Patients with a high risk of colorectal cancer were excluded. Patients were randomly assigned to 2 different preparations: polyethylene glycol plus SIM or polyethylene glycol. Two endoscopists blinded to patient preparation regimens scored its quality by using the Boston Bowel Preparation scale (BBPS) and the bubble scale. Interobserver agreement was calculated. The polyp detection rate, ADR, intraprocedural use of SIM, cecal intubation time, and withdrawal time were recorded. For study purposes, cecal intubation time and withdrawal time were combined to determine the effective procedure time. RESULTS: No significant difference between the polyethylene glycol plus SIM and polyethylene glycol arms was seen regarding the ADR (33.3% vs 38.8%; P = .881) and effective procedure time (759.3 ± 253.1 seconds vs 800.2 ± 459.6 seconds; P = .373), respectively. Intraprocedural use of SIM as well as the bubble scale score were significantly lower in the polyethylene glycol plus SIM arm (1.6% vs 48.9%; P ≤ .05) and (0.1 vs 2.1; P ≤ .05), respectively. Conversely, no difference was found in the BBPS scores. The interobserver agreement for both scores was strong (bubble scale score kappa = .537; P < .05; BBPS score kappa = .184; P <.05). CONCLUSION: Adding SIM to a polyethylene glycol preparation did not improve the ADR or effective procedure time. Nevertheless, it resulted in lower bubble scale scores, and more importantly, in less intraprocedural use of SIM. This simple and inexpensive intervention may have the potential to reduce the risk of endoscope-transmitted infections. (Clinical trial registration number: NCT03119168.).

COLORECTAL CANCER IN HISPANICS LIVING NEAR THE U.S.-MEXICO BORDER.

BACKGROUND: The incidence of colorectal cancer (CRC) in the US has declined. The decreasing trend is observed in non-Hispanic Whites, Blacks, and Hispanics. However, close analysis of the trends demonstrates that the decline among Hispanics is less than other races/ethnicities. We investigate the burden of CRC in Hispanics living near the U.S.-Mexico border, a subpopulation of Hispanics composed primarily of individuals of Mexican origin. OBJECTIVES: The objective of this study was to investigate and compare incidence rates of CRC in non-Hispanic Whites and Hispanics living in counties along the U.S.-Mexico border. METHODS: Data from the National Institutes of Health National Cancer Institute and State Cancer Profiles were analyzed to obtain CRC incidence rates (per 100,000 population) for persons ≥ 50 years of age residing in counties along the U.S.-Mexico border by race (non-Hispanic White and Hispanic) and gender from 2011 to 2015. RESULTS: Incidence rates of CRC in Hispanic men ≥ 50 years of age, living in counties along the U.S.-Mexico border, were higher than the national average for Hispanic men of similar age. In contrast, the incidence of CRC declined or remained stable in non-Hispanic Whites and women. CONCLUSIONS: Our study unveils a significant disparity in CRC incidence among Hispanics living near the U.S.-Mexico border, disproportionally affecting men ≥ 50 years of age. Socioeconomic and cultural/lifestyle factors are likely contributing to these disparities.

Irritable Bowel Syndrome on the US Mexico Border: A Survey in an Indigent Population Using Rome III Criteria.

GOALS: To investigate the prevalence of irritable bowel syndrome (IBS), and its association with health perception and health care-seeking behavior in this Mexican American population. BACKGROUND: The prevalence of IBS ranges from 3% to 20.4% in the United States and 4.4% to 16% in Mexico, based on Rome III and II criteria. However, its epidemiological profile in the US Mexico border is unknown. STUDY: We conducted a survey in a randomly selected indigent population (N=521) recruited into a colon cancer screening program (ACCION). The prevalence of IBS was estimated and a multivariable logistic regression was carried out to determine the associated risk factors. Results are summarized using odds ratio and 95% confidence interval (CI). RESULTS: A total of 464 (89%) completed the survey (mean age, 56.7 y; female, 74.8%). Country of birth was Mexico in 90.5% and the United States in 8.2% and acculturation was more Spanish (94.8%) than English (5.2%). Overall, 5.6% (95% CI, 3.7-8.1) fulfilled criteria for IBS with a predominance among women (6.9%) versus men (1.7%) (P=0.03). On the basis of multivariable analysis, lower number of bowel movements/week (odds ratio, 0.89; 95% CI, 0.80-1.00), having a primary care physician: 4.09 (1.51-11.12), using herbal treatments: 2.76 (1.08-7.06) and a previous IBS diagnosis: 23.11 (3.44-155.45), were significantly associated with the presence of IBS. CONCLUSIONS: The prevalence of IBS on the US Mexico border is comparable with data obtained from studies in both countries. Consulting a primary care physician as an associated factor may reveal the high rate of health-care seeking in IBS patients, while herbal treatments may reflect a cultural influence.

Hispanic Americans and Non-Hispanic White Americans Have a Similar Inflammatory Bowel Disease Phenotype: A Systematic Review with Meta-Analysis.

BACKGROUND: Inflammatory bowel disease (IBD) is a devastating immune-mediated disease on the rise in Hispanics living in the USA. Prior observational studies comparing IBD characteristics between Hispanics and non-Hispanic whites (NHW) have yielded mixed results. AIMS: We performed a meta-analysis of observational studies examining IBD phenotype in Hispanics compared to NHW. METHODS: We conducted a systematic search of US-based studies comparing IBD subtype (Ulcerative Colitis: UC or Crohn's disease: CD) and phenotype (disease location and behavior) between Hispanics and NHW. We evaluated differences in age at IBD diagnosis, the presence of family history and smoking history. A random effects model was chosen "a priori." Categorical and continuous variables were analyzed using odds ratio (OR) or standard mean difference (SMD), respectively. RESULTS: Seven studies were included with 687 Hispanics and 1586 NHW. UC was more common in Hispanics compared to NHW (OR 2.07, CI 1.13-3.79, p = 0.02). Location of disease was similar between Hispanics and NHW except for the presence of upper gastrointestinal CD, which was less common in Hispanics (OR 0.58, CI 0.32-1.06, p = 0.07). Hispanics were less likely to smoke (OR 0.48, CI 0.26-0.89, p = 0.02) or have a family history of IBD (OR 0.35, CI 0.22-0.55, p < 0.001). CD behavior classified by Montreal classification and age at IBD diagnosis were similar between Hispanics and NHW. CONCLUSION: UC was more common among US Hispanics compared to NHW. Age at IBD diagnosis is similar for both Hispanics and NHW. For CD, disease behavior is similar, but Hispanics show a trend for less upper gastrointestinal involvement. A family history of IBD and smoking history were less common in Hispanics.

Interleukin-6 in irritable bowel syndrome: A systematic review and meta-analysis of IL-6 (-G174C) and circulating IL-6 levels.

BACKGROUND: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder which presents with abdominal pain and alterations of the bowel habits. The pathophysiology of IBS is not well-recognized. Low grade inflammation has been suggested as one of the underlying mechanisms of IBS. Variations in the circulating pro-inflammatory interleukin-6 (IL-6) levels and IL-6 gene polymorphisms have been demonstrated in IBS. However, the results of published studies are not consistent, probably due to their small sample sizes. To address this inconsistency, we conducted the current systematic review and meta-analysis on serum/plasma IL-6 levels and IL-6 (-G174C; rs1800795) gene polymorphism in IBS. METHODS: PubMed was searched in July 2016. Case-control studies on serum/plasma IL-6 levels and IL-6 (-G174C) gene polymorphisms in IBS versus control were retrieved. The quality of studies was evaluated based on the modified Newcastle-Ottawa Scale (NOS) with 0 indicating the lowest and 9 as the highest score. Results were pooled using: (a) the standardized mean difference (SMD) for IL-6 levels which was considered statistically significant when the 0 value was not within the 95% confidence interval (CI), or (b) odds ratio (OR; 95% CI) through converting and pooling the IL-6 (-G174C) genotypes and alleles data into individual 2×2 tables. Heterogeneity was assessed based on I2 values; where I2≤50% and I2>50% designated using fixed and random effect models, respectively. RESULTS: Circulating IL-6 levels are higher in IBS patients compared to controls (SMD: 2.40 [95%CI: 0.53-4.28]; p=0.01). Categorizing data based on IBS subtypes, showed that IL-6 level is significantly higher in diarrhea predominant IBS (IBS-D) compared to control (SMD: 2.62 [95%CI: 0.29-4.95]; p=0.03), while it is comparable in constipation predominant IBS (IBS-C) and alternating IBS (IBS-A) patients with healthy controls. The meta-analysis of IL-6 (-G174C) polymorphism in IBS and based on IBS subtypes showed no difference in the distribution of genotypes or alleles compared to control. CONCLUSION: The higher IL-6 levels in IBS and more specifically in IBS-D suggests a pro-inflammatory phenotype in these patients, while this phenomenon is not supported by the polymorphism of IL-6 (-G174C). Increased IL-6 in IBS might be an acquired phenomenon or mediated by other genotypes. Any potential association between gene polymorphisms and IL-6 levels in IBS should be tested by assessing both IL-6 levels and IL-6 (-G174C) simultaneously in the same IBS subjects compared to their healthy controls. Categorizing patients based on their circulating IL-6 levels may introduce a new opportunity for personalized anti-inflammatory therapies of IBS.

Pathological Findings of the Antral and Pyloric Smooth Muscle in Patients with Gastroparesis-Like Syndrome Compared to Gastroparesis: Similarities and Differences.

BACKGROUND: Gastroparesis (GP)-like syndrome presents with the symptoms of GP but without delayed gastric emptying (GE). Whether GP-like syndrome is part of a spectrum of GP is not clear. This study aimed to compare the histopathological features of antral and pyloric smooth muscle tissue in GP and GP-like syndrome. METHODS: Full-thickness antral and/or pyloric biopsies were obtained from 37 GP and 18 GP-like syndrome patients who underwent abdominal surgery to place a gastric electrical stimulator or jejunal feeding tube and/or pyloroplasty. The tissues were stained with H&E, C-Kit, and trichrome. Based on previous control data, an interstitial cells of Cajal (ICC) count of <10 per high power field in the antrum and/or pylorus was considered depletion. Baseline total symptom score (TSS) was recorded. RESULTS: Twenty-four GP and 7 GP-like patients had pyloric biopsies. Pyloric ICC loss was observed in 20/24 (83.3%) GP and 2/7 (28.6%) GP-like patients (p < 0.01). Fibrosis was detected in the pyloric tissue of 20/24 (83.3%) GP and 2/7 (28.6%) GP-like patients who had pyloric trichrome staining (p < 0.01). Seventeen out of 24 (70.8%) GP patients with pyloric biopsies had concomitant pyloric ICC loss and fibrosis, while only one GP-like patient had ICC loss and simultaneous pyloric fibrosis. GP patients had a greater TSS compared to GP-like patients. In GP patients, those with pyloric ICC loss had a greater TSS compared to those with normal ICC. GP patients with pyloric fibrosis had a higher TSS compared to those without pyloric fibrosis. CONCLUSIONS: Compared to GP-like patients, the pyloric histopathological findings of ICC loss and fibrosis are common in GP and predict a greater symptom score. These pathological findings might be considered as markers of "pyloric dysfunction" and explain delayed GE in GP.

Plasma endocannabinoids and cannabimimetic fatty acid derivatives are altered in cyclic vomiting syndrome: The effects of sham feeding.

Cyclic vomiting syndrome (CVS) is an underdiagnosed disorder of the gut-brain interaction. Our understanding of the pathophysiology of CVS is evolving. Here, we tested the hypotheses that: (1) the levels of endocannabinoids and related lipids are altered in CVS, and (2) cephalic-vagal stimulation drive changes in endolipid levels. Ten adult patients with CVS and eight healthy controls were included. Indirect measurements of parasympathetic (RFa) functions were performed with spectral analysis of heart rate variability and respiratory activity. Plasma levels of endocannabinoids and related lipids were measured at baseline and during a sham feeding. Values are reported as mean ± standard error of the mean and compared using t-test or ANOVA. CVS patients had a lower parasympathetic tone and response to the Valsalva maneuver and deep breathing than the controls. The baseline 2-Arachidonoylglycerol (2-AG) had a significantly higher concentration in CVS (5.9e-008 ± 3.7e-008 mol/L) than control (3.7e-008 ± 1.3e-008 mol/; p < 0.05). Sham feeding did not change the concentration of 2-AG. 2-oleoylglycerol (2-OG) was significantly higher in CVS than control and did not change with sham feeding. Levels of N-acylethanolamines, including anandamide (AEA), were not different in CVS vs control. After sham feeding, AEA showed a trend toward increasing (p = 0.08) in CVS, but not in control. With sham feeding, palmitoyl ethanolamine significantly increased in both CVS and control groups; oleoyl ethanolamine in CVS only, and stearoyl ethanolamine in the control group. Levels of endocannabinoids and related lipids are altered in CVS patients. Sham feeding affects endogenous signaling lipids in a disease and time-dependent manner.

Cytokines and irritable bowel syndrome: where do we stand?

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder, which presents with one or more gastrointestinal symptoms without any structural or organic abnormality. The etiology and pathophysiological mechanisms of IBS remain uncertain. Residual or reactivated inflammation at the molecular level is considered the underlying mechanism of post-infectious IBS. On the other hand, genetic variations in the immunological components of the body, including cytokine gene polymorphisms, are proposed as a potential mechanism of IBS even in patients without previous gastrointestinal infection. Several studies have suggested imbalanced cytokine signaling as an etiology for IBS. In this review, recent findings on cytokine profiles and cytokine gene polymorphisms in patients with IBS are described and the role of cytokines in animal models of IBS is discussed.

Inhibiting Fatty Acid Amide Hydrolase Ameliorates Enteropathy in Diabetic Mice: A Cannabinoid 1 Receptor Mediated Mechanism.

Gastrointestinal (GI) dysmotility in diabetics exhibits fecal incontinence or constipation which affects patients' quality of life. In this study, we aimed to understand the pattern of GI transit in type 1 diabetic (T1D) mice and whether inhibiting endocannabinoid degradation would exhibit therapeutic effect. Whole gut-transit time and fecal-pellet output were measured at 16 week post-diabetes. T1D mice treated with fatty acid amide hydrolase (FAAH) inhibitor URB597 showed reduced fecal output as well as improved gut transit time. Cannabinoid 1 receptor antagonist, AM251 blocked the effects of URB597, which may demonstrate that FAAH inhibitor is a potential remedial strategy for GI dysmotility.

Gastrointestinal symptoms and the severity of COVID-19: Disorders of gut-brain interaction are an outcome.

BACKGROUND: Many of the studies on COVID-19 severity and its associated symptoms focus on hospitalized patients. The aim of this study was to investigate the relationship between acute GI symptoms and COVID-19 severity in a clustering-based approach and to determine the risks and epidemiological features of post-COVID-19 Disorders of Gut-Brain Interaction (DGBI) by including both hospitalized and ambulatory patients. METHODS: The study utilized a two-phase Internet-based survey on: (1) COVID-19 patients' demographics, comorbidities, symptoms, complications, and hospitalizations and (2) post-COVID-19 DGBI diagnosed according to Rome IV criteria in association with anxiety (GAD-7) and depression (PHQ-9). Statistical analyses included univariate and multivariate tests. RESULTS: Five distinct clusters of symptomatic subjects were identified based on the presence of GI symptoms, loss of smell, and chest pain, among 1114 participants who tested positive for SARS-CoV-2. GI symptoms were found to be independent risk factors for severe COVID-19; however, they did not always coincide with other severity-related factors such as age >65 years, diabetes mellitus, and Vitamin D deficiency. Of the 164 subjects with a positive test who participated in Phase-2, 108 (66%) fulfilled the criteria for at least one DGBI. The majority (n = 81; 75%) were new-onset DGBI post-COVID-19. Overall, 86% of subjects with one or more post-COVID-19 DGBI had at least one GI symptom during the acute phase of COVID-19, while 14% did not. Depression (65%), but not anxiety (48%), was significantly more common in those with post-COVID-19 DGBI. CONCLUSION: GI symptoms are associated with a severe COVID-19 among survivors. Long-haulers may develop post-COVID-19 DGBI. Psychiatric disorders are common in post-COVID-19 DGBI.

Plasma endocannabinoids and cannabimimetic fatty acid derivatives are altered in gastroparesis: A sex- and subtype-dependent observation.

BACKGROUND: Gastroparesis (GP) is a motility disorder of the stomach presenting with upper gastrointestinal symptoms in the setting of delayed gastric emptying. Endocannabinoids are involved in the regulation of GI function including motility. However, their role in the pathophysiology of GP has not been sufficiently investigated. Our goal was to compare the circulating levels of endocannabinoids and cannabimimetic fatty acid derivatives in GP versus control subjects. METHODS: The study compared plasma concentrations of endocannabinoids and their lipoamine and 2-acyl glycerol congeners, measured by high-pressure liquid chromatography/tandem mass spectrometry (HPLC-MS-MS), in adult patients with diabetic gastroparesis (DM-GP; n = 24; n = 16 female), idiopathic gastroparesis (ID-GP; n = 19; n = 11 female), diabetic patients without GP (DM; n = 19; n = 10 female), and healthy controls (HC; n = 18; n = 10 female). Data, presented as mean ± SEM, were analyzed with ANOVA (Sidak post hoc). KEY RESULTS: Endocannabinoids anandamide (AEA: 0.5 ± 0.1 nMol/L) and 2-arachidonoyl glycerol (2-AG: 2.6 ± 0.7 nMol/L) were significantly lower in female DM-GP patients vs. DM females (AEA: 2.5 ± 0.7 nMol/L and 2-AG: 9.4 ± 3.3 nMol/L). Other monoacylglycerols including 2-palmitoyl glycerol and 2-oleoyl glycerol were also lower in female DM-GP patients compared to DM females. No changes were observed in men. CONCLUSIONS & INFERENCES: Endocannabinoids and other fatty acid derivatives with cannabimimetic properties are reduced in female DM-GP patients. Since GP, particularly with diabetic etiology, is more prevalent among women and since cannabinoids are antiemetic, this decrease in levels may contribute to symptom development in these subjects. Targeting the endocannabinoid system may be a future therapeutic option in DM-GP patients.