Bowel function and inflammation: Is motility the other side of the coin?

Digestion and intestinal absorption allow the body to sustain itself and are the emblematic functions of the bowel. On the flip side, functions also arise from its role as an interface with the environment. Indeed, the gut houses microorganisms, collectively known as the gut microbiota, which interact with the host, and is the site of complex immune activities. Its role in human pathology is complex and scientific evidence is progressively elucidating the functions of the gut, especially regarding the pathogenesis of chronic intestinal diseases and inflammatory conditions affecting various organs and systems. This editorial aims to highlight and relate the factors involved in the pathogenesis of intestinal and systemic inflammation.

Pathophysiology of ascites: The importance of the intestine. A surgical contribution to the understanding of a medical problem.

The understanding of the mechanisms for the development of ascites has evolved over the years, involving the liver, peritoneum, heart, and kidneys as key responsible for its formation. In this article, we review the pathophysiology of ascites formation, introducing the role of the intestine as a major responsible for ascites production through "a game changer" case.

Bowel Stiffness Assessed by Shear-Wave Ultrasound Elastography Predicts Disease Behavior Progression in Patients With Crohn's Disease.

INTRODUCTION: There is a lack of reliable predictors of disease behavior progression in patients with Crohn's disease (CD). Real-time shear-wave elastography (SWE) is a novel method for evaluating tissue stiffness. However, its value for assessing CD has not yet been investigated. We aimed to explore the value of SWE and other ultrasound parameters at diagnosis in predicting CD behavior progression. METHODS: We retrospectively collected data from patients with CD with the nonstenotic nonpenetrating disease (B1 phenotype based on the Montreal classification). All patients underwent intestinal ultrasound at baseline and were followed up. The end point was defined as disease behavior progression to stricturing (B2) or penetrating (B3) disease. Cox regression analysis was performed for the association between baseline characteristics and subsequent end points. In addition, a multivariate nomogram was established to predict the risk of disease behavior progression quantitatively. RESULTS: A total of 130 patients with CD with B1 phenotype were enrolled. Twenty-seven patients (20.8%) developed B2 or B3 disease, with a median follow-up of 33 months. Multivariate analysis identified that SWE was the only independent predictor of disease behavior progression (hazard ratio 1.08, 95% confidence interval 1.03-1.12, P = 0.001). A reverse of the HR appeared at the cutoff 12.75 kPa. The nomogram incorporating SWE and other clinical characteristics showed a good prediction performance (area under the curve = 0.792). DISCUSSION: Intestinal stiffness assessed using SWE is an independent predictor of disease behavior progression in patients with CD. Patients with CD with SWE >12.75 kPa at diagnosis are prone to progress toward stricturing or penetrating diseases.

Improving Bowel Function Recovery and Quality of Life in Han Chinese Patients with Spinal Cord Injuries: A Quantitative Assessment-Based Nursing Intervention Study.

BACKGROUND Neurological bowel dysfunction (NBD) due to spinal cord injuries (SCIs) is common and significantly impacts patients' quality of life. This study evaluated the efficacy of quantitative assessment-based nursing interventions on bowel function recovery, quality of life, and caregivers' satisfaction with SCI patients with NBD. MATERIAL AND METHODS The study included 418 SCI patients with NBD. Patients were categorized into 3 cohorts: quantitative assessment-based nursing intervention (QN, n=114), conventional nursing intervention (CN, n=125), or no nursing intervention (DN, n=189). The 3 cohorts were followed over a 6-month period. RESULTS At 6 months post-intervention, patients in the QN and CN cohorts showed significant reductions in symptoms of fecal incontinence, constipation, and abdominal distension compared to the DN cohort. Additionally, defecation time decreased significantly in the QN and CN cohorts compared to both initial measures and the DN cohort. Notably, patients in the QN cohort demonstrated substantial improvement in overall quality of life scores compared to baseline, CN, and DN cohorts. The QN cohort also reported marked improvement in caregivers' satisfaction, surpassing that of caregivers in the CN and DN cohorts. CONCLUSIONS Six months of quantitative assessment-based nursing interventions significantly improved bowel function, quality of life, and caregiver satisfaction in SCI patients with NBD. This intervention appears beneficial for managing NBD in SCI patients and improving their quality of life and caregiver satisfaction.

Pictograms to assess bloating and distension symptoms in the general population in Mexico: Results of The Rome Foundation Global Epidemiology Study.

BACKGROUND: There is no term for bloating in Spanish and distension is a very technical word. "Inflammation"/"swelling" are the most frequently used expressions for bloating/distension in Mexico, and pictograms are more effective than verbal descriptors (VDs) for bloating/distension in general GI and Rome III-IBS patients. However, their effectiveness in the general population and in subjects with Rome IV-DGBI is unknown. We analyzed the use of pictograms for assessing bloating/distension in the general population in Mexico. METHODS: The Rome Foundation Global Epidemiology Study (RFGES) in Mexico (n = 2001) included questions about the presence of VDs "inflammation"/"swelling" and abdominal distension, their comprehension, and pictograms (normal, bloating, distension, both). We compared the pictograms with the Rome IV question about the frequency of experiencing bloating/distension, and with the VDs. KEY RESULTS: "Inflammation"/"swelling" was reported by 51.5% and distension by 23.8% of the entire study population; while 1.2% and 25.3% did not comprehend "Inflammation"/"swelling" or distension, respectively. Subjects without (31.8%) or not comprehending "inflammation"/"swelling"/distension (68.4%) reported bloating/distension by pictograms. Bloating and/or distension by the pictograms were much more frequent in those with DGBI: 38.3% (95%CI: 31.7-44.9) vs. without: 14.5% (12.0-17.0); and in subjects with distension by VDs: 29.4% (25.4-33.3) vs. without: 17.2% (14.9-19.5). Among subjects with bowel disorders, those with IBS reported bloating/distension by pictograms the most (93.8%) and those with functional diarrhea the least (71.4%). CONCLUSIONS & INFERENCES: Pictograms are more effective than VDs for assessing the presence of bloating/distension in Spanish Mexico. Therefore, they should be used to study these symptoms in epidemiological research.

Serum Levels of IFABP2 and Differences in Lactobacillus and Porphyromonas gingivalis Abundance on Gut Microbiota Are Associated with Poor Therapeutic Response in Rheumatoid Arthritis: A Pilot Study.

Intestinal dysbiosis is related to the physiopathology and clinical manifestation of rheumatoid arthritis (RA) and the response to pharmacologic treatment. The objectives of this study were (1) to analyze the effect of conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) on the abundance of gut microbiota's bacteria; (2) to evaluate the relationship between the differences in microbial abundance with the serum levels of intestinal fatty-acid binding protein 2 (IFABP2), cytokines, and the response phenotype to csDMARDs therapy in RA. A cross-sectional study was conducted on 23 women diagnosed with RA. The abundance of bacteria in gut microbiota was determined with qPCR. The ELISA technique determined serum levels of IFABP2, TNF-α, IL-10, and IL-17A. We found that the accumulated dose of methotrexate or prednisone is negatively associated with the abundance of Lactobacillus but positively associated with the abundance of Bacteroides fragilis. The Lactobacillus/Porphyromonas gingivalis ratio was associated with the Disease Activity Score-28 for RA with Erythrocyte Sedimentation Rate (DAS28-ESR) (r = 0.778, p = 0.030) and with the levels of IL-17A (r = 0.785, p = 0.027) in the group treated with csDMARD. Moreover, a relation between the serum levels of IFABP2 and TNF-α (r = 0.593, p = 0.035) was observed in the group treated with csDMARD. The serum levels of IFABP2 were higher in patients with secondary non-response to csDMARDs therapy. In conclusion, our results suggest that the ratios of gut microbiota's bacteria and intestinal permeability seems to establish the preamble for therapeutic secondary non-response in RA.

Serum claudin-5, claudin-11, occludin, vinculin, paxillin, and beta-catenin levels in preschool children with autism spectrum disorder.

AIM: Increased intestinal and blood-brain barriers (BBB) permeability has been suggested to have a role in autism spectrum disorder (ASD). Claudin-5, claudin-11, occludin, ß-catenin, vinculin, and paxillin are crucial components of these barriers. This study assessed concentrations of these molecules in preschool children with ASD. METHODS: A total of 80 children with ASD and 40 controls aged 18-60 months were enrolled in this study. Serum levels of biochemical variables were determined using commercial enzyme-linked immunosorbent assay kits. RESULTS: Serum claudin-11, occludin, and ß-catenin levels were significantly higher in the ASD group than in the control group. However, no significant difference for serum claudin-5, vinculin, and paxillin levels was detected between the groups. CONCLUSION: These findings suggest that claudin-11, occludin, and ß-catenin may be involved in the pathogenesis of ASD. These proteins may affect the brain by causing dysregulation in intestinal or blood-brain barrier permeability or with other unknown mechanisms.

Impairments of intestinal arginine and NO metabolisms trigger aging-associated intestinal barrier dysfunction and 'inflammaging'.

Aging is considered a state of low grade inflammation, occurring in the absence of any overt infection often referred to as 'inflammaging'. Maintaining intestinal homeostasis may be a target to extend a healthier status in older adults. Here, we report that even in healthy older men low grade bacterial endotoxemia is prevalent. In addition, employing multiple mouse models, we also show that while intestinal microbiota composition changes significantly during aging, fecal microbiota transplantation to old mice does not protect against aging-associated intestinal barrier dysfunction in small intestine. Rather, intestinal NO homeostasis and arginine metabolism mediated through arginase and NO synthesis is altered in small intestine of aging mice. Treatment with the arginase inhibitor norNOHA prevented aging-associated intestinal barrier dysfunction, low grade endotoxemia and delayed the onset of senescence in peripheral tissue e.g., liver. Intestinal arginine and NO metabolisms could be a target in the prevention of aging-associated intestinal barrier dysfunction and subsequently decline and 'inflammaging'.

A multistrain probiotic improves handgrip strength and functional capacity in patients with COPD: A randomized controlled trial.

PURPOSE: The age-related muscle loss, termed sarcopenia and functional dependency, are common findings in patients with chronic obstructive pulmonary disease (COPD). However, an effective bedside treatment remains elusive. OBJECTIVE: To assess the effects of probiotics on sarcopenia and physical capacity in COPD patients. METHODS: Randomized, double-blind, computer-controlled, multicenter trial in two tertiary-care hospitals for 16 weeks. A central computer system randomly allocated male, 63-73 years old COPD patients into placebo (n=53) and probiotic (n=51) groups. The intervention was Vivomix 112 billion*, one capsule a day for 16 weeks. The main outcomes measured were sarcopenia phenotype, short physical performance battery (SPPB), plasma markers of intestinal permeability (zonulin and claudin-3) and neuromuscular junction degradation (CAF22), body composition, and handgrip strength (HGS) before and following the probiotics treatment. FINDINGS: 4 patients discontinued intervention due to poor compliance and 100 patients, including placebo (n=53) and probiotic (n=47) groups were analyzed. Probiotics reduced plasma zonulin, claudin-3, and CAF22, along with an improvement in HGS, gait speed, and SPPB scores (all p<0.05). Probiotic treatment also reduced the plasma c-reactive proteins and 8-isoprostane levels, the markers of systemic inflammation and oxidative stress (p<0.05). Correlation analysis revealed varying degrees of association of plasma biomarkers with sarcopenia indexes. Despite a statistical trend, we did not find a reduction in sarcopenia prevalence in the probiotic group. CONCLUSION: Taken together, the multistrain probiotic improves muscle strength and functional performance in COPD patients by reducing intestinal permeability and stabilizing neuromuscular junction. TRIAL REGISTRATION: GMC clinical trial unit, GMC-CREC-00263.

The Role of AGE-RAGE Signalling as a Modulator of Gut Permeability in Diabetes.

There is increasing evidence for the role of intestinal permeability as a contributing factor in the pathogenesis of diabetes; however, the molecular mechanisms are poorly understood. Advanced glycation endproducts, of both exogenous and endogenous origin, have been shown to play a role in diabetes pathophysiology, in part by their ligation to the receptor for advanced glycation endproducts (RAGE), leading to a proinflammatory signalling cascade. RAGE signalling has been demonstrated to play a role in the development of intestinal inflammation and permeability in Crohn's disease and ulcerative colitis. In this review, we explore the role of AGE-RAGE signalling and intestinal permeability and explore whether activation of RAGE on the intestinal epithelium may be a downstream event contributing to the pathogenesis of diabetes complications.

Strategies for circadian rhythm disturbances and related psychiatric disorders: a new cue based on plant polysaccharides and intestinal microbiota.

Circadian rhythm is essential to human physiological homeostasis and health. The oscillation of host circadian rhythm affects the composition and function of intestinal microbiota, meanwhile, the normal operation of host circadian rhythm depends on the diurnal changes of intestinal microbiota. The imbalance of intestinal micro-ecology or the disorder of host circadian rhythm may lead to psychiatric disorders, while the intervention of plant polysaccharides is a possible way to alleviate circadian rhythm disturbance and the related psychiatric diseases. This review discusses the interaction between host circadian rhythm and intestinal microbiota and their effects on psychiatric disorders, and proposes a possible strategy of plant polysaccharides to alleviate circadian rhythm disorders and related psychiatric disorders by regulating intestinal micro-ecology.

The Intestinal Barrier and Its Dysfunction in Patients with Metabolic Diseases and Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) represents an increasing cause of liver disease worldwide, mirroring the epidemics of obesity and metabolic syndrome. As there are still no licensed medications for treating the disease, there is an ongoing effort to elucidate the pathophysiology and to discover new treatment pathways. An increasing body of evidence has demonstrated a crosstalk between the gut and the liver, which plays a crucial role in the development and progression of liver disease. Among other intestinal factors, gut permeability represents an interesting factor at the interface of the gut-liver axis. In this narrative review, we summarise the evidence from human studies showing the association between increased gut permeability and NAFLD, as well as with type-2 diabetes and obesity. We also discuss the manipulation of the gut permeability as a potential therapeutical target in patients with NAFLD.

High-altitude exposures and intestinal barrier dysfunction.

Gastrointestinal complaints are often reported during ascents to high altitude (>2,500 m), though their etiology is not known. One potential explanation is injury to the intestinal barrier which has been implicated in the pathophysiology of several diseases. High-altitude exposures can reduce splanchnic perfusion and blood oxygen levels causing hypoxic and oxidative stress. These stressors might injure the intestinal barrier leading to consequences such as bacterial translocation and local/systemic inflammatory responses. The purpose of this mini-review is to 1) discuss the impact of high-altitude exposures on intestinal barrier dysfunction and 2) present medications and dietary supplements which may have relevant impacts on the intestinal barrier during high-altitude exposures. There is a small but growing body of evidence which shows that acute exposures to high altitudes can damage the intestinal barrier. Initial data also suggest that prolonged hypoxic exposures can compromise the intestinal barrier through alterations in immunological function, microbiota, or mucosal layers. Exertion may worsen high-altitude-related intestinal injury via additional reductions in splanchnic circulation and greater hypoxemia. Collectively these responses can result in increased intestinal permeability and bacterial translocation causing local and systemic inflammation. More research is needed to determine the impact of various medications and dietary supplements on the intestinal barrier during high-altitude exposures.

Efficacy and Safety of Anti-Tumor Necrosis Factor-Alpha Agents for Patients with Intestinal Behcet's Disease: A Systematic Review and Meta-Analysis.

PURPOSE: Intestinal Behcet's disease (BD) is a systemic autoimmune disease for which treatment options are limited. As a prospective therapeutic strategy for intestinal BD, anti-tumor necrosis factor-alpha (anti-TNF-α) agents have received increasing attention. In this study, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of anti-TNF-α agents for patients with intestinal BD. MATERIALS AND METHODS: We searched PubMed, Embase, and Cochrane Library databases up to July 1, 2021 and articles that met the eligibility criteria were further assessed. Pooled rates were synthesized by a randomized effects model using Stata software. RESULTS: Eleven clinical trials covering 671 patients with intestinal BD were included. According to compositive data, the pooled rate for remission was 39% [95% confidence interval (CI) 26-52] in patients receiving anti-TNF-α agents. Intestinal symptoms were cured in 70% (95% CI 53-84) of the patients, and the rate for endoscopic healing was 65% (95% CI 52-78). Corticosteroid discontinuation was achieved in 43% (95% CI 28-58) of the patients, and the dose reduction of corticosteroid was 20.43 mg (95% CI 13.4-27.46). There were 239 adverse events and 80 serious adverse events during follow-up. CONCLUSION: Our study indicated that anti-TNF-α agents may serve as an effective treatment with acceptable safety for patients with intestinal BD. However, more robust evidence from randomized controlled trials is urgently needed to assess the long-term efficacy and safety of anti-TNF-α agents for those patients.

Optimal timing of definitive surgery for Hirschsprung's disease to achieve better long-term bowel function.

PURPOSE: Few studies have focused on the operative age for Hirschsprung's disease (HD). We evaluated the optimal timing of surgery in HD patients based on their long-term bowel function. METHODS: HD was diagnosed in 65 pediatric patients in our institute between 1992 and 2018. Twenty-five patients underwent the Soave-Denda procedure (SD) and 40 underwent transanal endorectal pull-through (TA). We divided these patients into two groups: those who underwent surgery at < 6 months of age (younger group) and those who underwent surgery at 6-12 months of age (older group). We assessed bowel function at 5, 7, and 9 years of age. RESULTS: The bowel function of the patients who underwent the SD did not differ significantly between the groups. Similarly, the total bowel-function scores of the patients who underwent TA did not differ between the groups at any age. However, the soiling score at 7 years of age in the older group of patients who underwent TA was significantly lower than that in the younger group (p = 0.02). CONCLUSIONS: Our data suggest that to achieve optimal bowel function, TA should be performed at < 6 months of age.

Exploring the pathogenesis of type 2 diabetes mellitus intestinal damp-heat syndrome and the therapeutic effect of Gegen Qinlian Decoction from the perspective of exosomal miRNA.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetes is a common, complex, chronic metabolic disease. A randomized, double-blind, placebo-parallel controlled clinical study has shown that Gegen Qinlian Decoction (GQD) can reduce glycosylated hemoglobin in type 2 diabetes mellitus (T2DM) intestinal damp-heat syndrome patients in a dose-dependent manner. AIM: To explore the pathogenesis of T2DM intestinal damp-heat syndrome and the therapeutic effect of GQD from the perspective of exosomal microRNA (miRNA). METHODS: Eligible patients were selected and treated with GQD for 3 months to evaluate their clinical efficacy. Effective cases were matched with healthy volunteers, and saliva samples were collected. Exosomal miRNA was extracted from saliva and analyzed by chip sequencing. Subsequently, the function of the differential gene and the signal transduction pathway were analyzed using bioinformatics technology. Finally, three target miRNAs were randomly selected from the T2DM group/healthy group, and two target miRNAs in the T2DM before treatment/after treatment group were randomly selected for qPCR verification. Finally, we conducted a correlation analysis of the miRNAs and clinical indicators. The registration number for this research is ChiCTR-IOR-15006626. RESULTS: (1) The expression of exosomal miRNA chips showed that there were 14 differentially expressed miRNAs in the T2DM group/healthy group, and 26 differentially expressed miRNAs in the T2DM before treatment/after treatment group. (2) Enrichment results showed that in the T2DM group/healthy group, it was primarily related to cell development, body metabolism, TGF-ß, and ErbB signaling pathways. In the T2DM before treatment/after treatment group, it was mainly related to cellular metabolic regulation processes, and insulin, Wnt, and AMPK signaling pathways. (3) The qPCR verification showed that the expressions of hsa-miR-9-5p, hsa-miR-150-5p, and hsa-miR-216b-5p in the T2DM group was higher (P<0.05). Following GQD treatment, hsa-miR-342-3p and hsa-miR-221-3p were significantly downregulated (P<0.05). (4) hsa-miR-9-5p was positively correlated with BMI (P<0.05), and hsa-miR-150-5p was positively correlated with total cholesterol and triglycerides (P<0.05). The GQD efficacy-related gene hsa-miR-342-3p was positively correlated with the patient's initial blood glucose level (P<0.05), and hsa-miR-221-3p was positively correlated with total cholesterol and triglycerides (P<0.05). CONCLUSION: The exosomal miRNA expression profile and signaling pathways related to T2DM intestinal damp-heat syndrome and the efficacy of GQD were established, which provides an alternative strategy for precision traditional Chinese medicine treatment.

Clinical efficacy of non-invasive ventilation combined with Chinese medicine for intestinal regulation in Chinese children with respiratory disorders.

Chinese medicine for intestinal regulation is an emerging method for pediatric respiratory disorders, which has better clinical value when combined with NIV (Non-invasive ventilation). This study aims to observe the clinical efficacy of NIV plus Chinese medicine for intestinal regulation in Chinese children with respiratory disorders. Thirty-nine patients admitted to Huaihua First People's Hospital, between March 2016 and July 2018 were enrolled, including 14 children with chronic hypercapnic respiratory failure, 19 with non-surgical OSAS, 5 with OB and 1 with central hypoventilation syndrome. After NIV, the blood gas carbon dioxide retention and labored breathing were improved, respiratory rate and heart rate were decreased and the feeding condition of some children improved. After NIV treatment, clinical symptoms of children with OSAS were significantly ameliorated. In polysomnography monitoring, the AHI, OAI and SpO2 were significantly enhanced following NIV. In addition, patients with OB and central hypoventilation had different degrees of improvement of their symptoms. NIV plus Chinese medicine for intestinal regulation alleviate the clinical symptoms and enhances the quality of life of children with chronic hypercapnic respiratory failure. Some children could be transferred out of the intensive care unit and into home mechanical ventilation.