Search Results (34)

As the major polysaccharide in brown algae, fucoidan possesses broad biological abilities and has been reported to improve gastrointestinal health. Functional dyspepsia, a common non-organic disease, is a complex of symptoms mainly characterized by pathogenesis, such as visceral hypersensitivity, gastric dysmotility, and inflammation. To date, the effects of fucoidan in regulating functional dyspepsia with visceral sensitivity remains unclear. In the current study, iodoacetamide was employed to establish a mouse model of visceral hypersensitivity. Meanwhile, fucoidan was orally administrated for fourteen days. Indicators were conducted to evaluate the potential of fucoidan as the ingredient of complementary and alternative medicine for functional dyspepsia, such as levels of serum hormones, expression of receptors, and gut microbial profile. The results show that oral administration of fucoidan led to significant reductions in the secretion of 5-hydroxytryptamine, cortisol, and corticosterone. Additionally, it decreased the expression of 5-hydroxytryptamine_-3 receptors, with regulation of 5-hydroxytryptamine metabolism and improvement of gut microbial imbalance. The above results suggest fucoidan could ameliorate visceral hypersensitivity by modulating 5-HT metabolism and microbiota. The current findings indicate that fucoidan has potential as a biological component in the adjuvant treatment of functional dyspepsia and for its expanded utilization in the food and medical fields. Full article

Although effects of stress-induced anxiety on the gastrointestinal tract and enteric nervous system (ENS) are well studied, how ENS dysfunction impacts behaviour is not well understood. We investigated whether ENS modulation alters anxiety-related behaviour in rats. We used loperamide, a potent μ-opioid receptor agonist that does not cross the blood–brain barrier, to manipulate ENS function and assess changes in behaviour, gut and brain gene expression, and microbiota profile. Sprague Dawley (male/female) rats were acutely dosed with loperamide (subcutaneous) or control solution, and their behavioural phenotype was examined using open field and elevated plus maze tests. Gene expression in the proximal colon, prefrontal cortex, hippocampus, and amygdala was assessed by RNA-seq and caecal microbiota composition determined by shotgun metagenome sequencing. In female rats, loperamide treatment decreased distance moved and frequency of supported rearing, indicating decreased exploratory behaviour and increased anxiety, which was associated with altered hippocampal gene expression. Loperamide altered proximal colon gene expression and microbiome composition in both male and female rats. Our results demonstrate the importance of the ENS for communication between gut and brain for normo-anxious states in female rats and implicate corticotropin-releasing hormone and gamma-aminobutyric acid gene signalling pathways in the hippocampus. This study also sheds light on sexually dimorphic communication between the gut and the brain. Microbiome and colonic gene expression changes likely reflect localised effects of loperamide related to gut dysmotility. These results suggest possible ENS pharmacological targets to alter gut to brain signalling for modulating mood. Full article

Globally, irritable bowel syndrome (IBS) is present in approximately 10% of the population. While this condition does not pose a risk of complications, it has a substantial impact on the patient’s quality of life. Moreover, this disease has a significant financial impact on healthcare systems. This includes the direct costs associated with the diagnosis and treatment of these patients, as well as the indirect costs that arise from work absenteeism and reduced productivity. In light of these data, recent research has focused on elucidating the pathophysiological basis of this condition in order to improve the quality of life for affected individuals. Despite extensive research to date, we still do not fully understand the precise mechanisms underlying IBS. Numerous studies have demonstrated the involvement of the gut–brain axis, visceral hypersensitivity, gastrointestinal dysmotility, gut microbiota dysbiosis, food allergies and intolerances, low-grade mucosal inflammation, genetic factors, and psychosocial factors. The acquisition of new data is crucial for the advancement of optimal therapeutic approaches aimed at enhancing the general health of these patients while simultaneously reducing the financial burden associated with this ailment. Full article

Diabetes mellitus is one of the most common comorbidities of patients undergoing surgery. Colorectal surgery is frequently associated with postoperative complications, and diabetic patients represent a population that presents a high risk of developing such complications. Understanding the interrelationships between neoplastic disease and diabetes, as well as the pathophysiological mechanisms underlying postoperative complications, are essential for effective therapeutic management. Genetic predispositions, alterations in the gut microbiota, inflammatory response, ischemic, thrombotic and infectious processes contribute significantly to the development of severe surgical complications, such as anastomotic fistulas. Postoperative ileus, characterized by gastrointestinal dysmotility, is common in diabetic patients due to neuropathic dysfunction and altered intestinal metabolism. In addition, diabetic patients are at increased risk of intestinal ischemia, requiring specific perioperative care. The strategies to avoid these complications assume an adequate surgical technique, a personalized anesthesia management, and last but not least, the best possible glycemic control. This article highlights the importance of a better understanding of the interaction between diabetes and postoperative complications, in order to obtain good results with an important impact on the patient's health and well-being. This article highlights the importance of a better understanding of the interplay between diabetes and postoperative complications informs targeted interventions aimed at reducing morbidity and improving patient well-being. Full article

Individuals with autism often experience gastrointestinal issues but the cause is unknown. Many gene mutations that modify neuronal synapse function are associated with autism and therefore may impact the enteric nervous system that regulates gastrointestinal function. A missense mutation in the Nlgn3 gene encoding the cell adhesion protein Neuroligin-3 was identified in two brothers with autism who both experienced severe gastrointestinal dysfunction. Mice expressing this mutation (Nlgn3^R451C mice) are a well-studied preclinical model of autism and show autism-relevant characteristics, including impaired social interaction and communication, as well as repetitive behaviour. We previously showed colonic dysmotility in response to GABAergic inhibition and increased myenteric neuronal numbers in the small intestine in Nlgn3^R451C mice bred on a mixed genetic background. Here, we show that gut dysfunction is a persistent phenotype of the Nlgn3 R451C mutation in mice backcrossed onto a C57BL/6 background. We report that Nlgn3^R451C mice show a 30.9% faster gastrointestinal transit (p = 0.0004) in vivo and have 6% longer small intestines (p = 0.04) compared to wild-types due to a reduction in smooth muscle tone. In Nlgn3^R451C mice, we observed a decrease in resting jejunal diameter (proximal jejunum: 10.6% decrease, p = 0.02; mid: 9.8%, p = 0.04; distal: 11.5%, p = 0.009) and neurally regulated dysmotility as well as shorter durations of contractile complexes (mid: 25.6% reduction in duration, p = 0.009; distal: 30.5%, p = 0.004) in the ileum. In Nlgn3^R451C mouse colons, short contractions were inhibited to a greater extent (57.2% by the GABA_A antagonist, gabazine, compared to 40.6% in wild-type mice (p = 0.007). The inhibition of nitric oxide synthesis decreased the frequency of contractile complexes in the jejunum (WT p = 0.0006, Nlgn3^R451C p = 0.002), but not the ileum, in both wild-type and Nlgn3^R451C mice. These findings demonstrate that changes in enteric nervous system function contribute to gastrointestinal dysmotility in mice expressing the autism-associated R451C missense mutation in the Neuroligin-3 protein. Full article

Chronic gastroduodenal symptoms are prevalent worldwide, and there is a need for new diagnostic and treatment approaches. Several overlapping processes may contribute to these symptoms, including gastric dysmotility, hypersensitivity, gut–brain axis disorders, gastric outflow resistance, and duodenal inflammation. Gastric Alimetry^® (Alimetry, New Zealand) is a non-invasive test for evaluating gastric function that combines body surface gastric mapping (high-resolution electrophysiology) with validated symptom profiling. Together, these complementary data streams enable important new clinical insights into gastric disorders and their symptom correlations, with emerging therapeutic implications. A comprehensive database has been established, currently comprising > 2000 Gastric Alimetry tests, including both controls and patients with various gastroduodenal disorders. From studies employing this database, this paper presents a systematic methodology for Gastric Alimetry test interpretation, together with an extensive supporting literature review. Reporting is grouped into four sections: Test Quality, Spectral Analysis, Symptoms, and Conclusions. This review compiles, assesses, and evaluates each of these aspects of test assessment, with discussion of relevant evidence, example cases, limitations, and areas for future work. The resultant interpretation methodology is recommended for use in clinical practice and research to assist clinicians in their use of Gastric Alimetry as a diagnostic aid and is expected to continue to evolve with further development. Full article

Background: Microorganisms provide various benefits to their human hosts, including assisting with digestion, synthesizing certain vitamins, developing the gastrointestinal and immune systems, regulating metabolism, and protecting against some pathogens. However, microbial imbalances can cause tissue damage and contribute to inflammatory disorders and cancers. Microbial dysbiosis refers to an imbalance or disruption in the normal composition and function of the microbial communities that inhabit various body parts, including the gut, oral cavity, skin, and reproductive tract. Emerging research suggests that microbial dysbiosis plays a significant role in cancer development and progression. This issue is particularly relevant in achalasia, in which food stasis, changes in endoluminal pH, and poor esophageal clearance might contribute to esophageal microbial dysbiosis. This study aimed to evaluate the association between dysbiosis and esophageal cancer development, focused on esophageal dysmotility disorders. Methods: This study is a critical review, gathering the current evidence for the association between dysbiosis and the development of esophageal cancer. Results: Studies have shown that microbiota play a role in cancer development, although the mechanisms for how they do so are not yet fully understood. One possible explanation is that microbiota alterations can lead to chronic inflammation, promoting cancer cell growth. Additionally, some bacteria produce toxins that can damage DNA and cause genomic instability, and certain bacterial products can promote tumor growth. Conclusion: Despite the close relationship between dysbiosis and cancer development in esophageal dysmotility disorders, further investigations are still needed to elucidate the precise mechanisms by which dysbiosis contributes to cancer development and to identify potential therapeutic interventions targeting the microbiota to prevent or treat cancer. Full article

The side effects of antibiotic treatment directly correlate with intestinal dysbiosis. However, a balanced gut microbiota supports the integrity of the enteric nervous system (ENS), which controls gastrointestinal neuromuscular functions. In this study, we investigated the long-term effects of antibiotic-induced microbial dysbiosis on the ENS and the impact of the spontaneous re-establishment of the gut microbiota on gastrointestinal functions. C57BL/6J mice were treated daily for two weeks with antibiotics. After 0–6 weeks of antibiotics wash-out, we determined (a) gut microbiota composition, (b) gastrointestinal motility, (c) integrity of the ENS, (d) neurochemical code, and (e) inflammation. Two weeks of antibiotic treatment significantly altered gut microbial composition; the genera Clostridium, Lachnoclostridium, and Akkermansia did not regain their relative abundance following six weeks of antibiotic discontinuation. Mice treated with antibiotics experienced delayed gastrointestinal transit and altered expression of neuronal markers. The anomalies of the ENS persisted for up to 4 weeks after the antibiotic interruption; the expression of neuronal HuC/D, glial-derived neurotrophic factor (Gdnf), and nerve growth factor (Ngf) mRNA transcripts did not recover. In this study, we strengthened the idea that antibiotic-induced gastrointestinal dysmotility directly correlates with gut dysbiosis as well as structural and functional damage to the ENS. Full article

Intestinal epithelial barrier (IEB) impairment and enteric inflammation are involved in the onset of obesity and gut-related dysmotility. Dietary supplementation with natural plant extracts represents a useful strategy for the management of body weight gain and systemic inflammation associated with obesity. Here, we evaluate the efficacy of a food supplement containing the dry extract of Curcumin, Emblica and Cassia in counteracting enteric inflammation and motor abnormalities in a mouse model of obesity, induced by a high-fat diet (HFD). Male C57BL/6 mice, fed with standard diet (SD) or HFD, were treated with a natural mixture (Curcumin, Emblica and Cassia). After 8 weeks, body weight, BMI, liver and spleen weight, along with metabolic parameters and colonic motor activity were evaluated. Additionally, plasma LBP, fecal calprotectin, colonic levels of MPO and IL-1β, as well as the expression of occludin, TLR-4, MYD88 and NF-κB were investigated. Plant-based food supplement administration (1) counteracted the increase in body weight, BMI and metabolic parameters, along with a reduction in spleen and liver weight; (2) showed strengthening effects on the IEB integrity; and (3) reduced enteric inflammation and oxidative stress, as well as ameliorated the colonic contractile dysfunctions. Natural mixture administration reduced intestinal inflammation and counteracted the intestinal motor dysfunction associated with obesity. Full article

Gastric motility abnormalities are common in patients with disorders of gut-brain interaction, such as functional dyspepsia and gastroparesis. Accurate assessment of the gastric motility in these common disorders can help understand the underlying pathophysiology and guide effective treatment. A variety of clinically applicable diagnostic methods have been developed to objectively evaluate the presence of gastric dysmotility, including tests of gastric accommodation, antroduodenal motility, gastric emptying, and gastric myoelectrical activity. The aim of this mini review is to summarize the advances in clinically available diagnostic methods for evaluation of gastric motility and describe the advantages and disadvantages of each test. Full article

Severe gut motility disorders are characterized by the ineffective propulsion of intestinal contents. As a result, the patients develop disabling/distressful symptoms, such as nausea and vomiting along with altered bowel habits up to radiologically demonstrable intestinal sub-obstructive episodes. Chronic intestinal pseudo-obstruction (CIPO) is a typical clinical phenotype of severe gut dysmotility. This syndrome occurs due to changes altering the morpho-functional integrity of the intrinsic (enteric) innervation and extrinsic nerve supply (hence neuropathy), the interstitial cells of Cajal (ICC) (mesenchymopathy), and smooth muscle cells (myopathy). In the last years, several genes have been identified in different subsets of CIPO patients. The focus of this review is to cover the most recent update on enteric dysmotility related to CIPO, highlighting (a) forms with predominant underlying neuropathy, (b) forms with predominant myopathy, and (c) mitochondrial disorders with a clear gut dysfunction as part of their clinical phenotype. We will provide a thorough description of the genes that have been proven through recent evidence to cause neuro-(ICC)-myopathies leading to abnormal gut contractility patterns in CIPO. The discovery of susceptibility genes for this severe condition may pave the way for developing target therapies for enteric neuro-(ICC)-myopathies underlying CIPO and other forms of gut dysmotility. Full article

Irritable Bowel Syndrome is a gastrointestinal disorder that affects the large intestine, which encompasses several symptoms including, but not limited to, abdominal pain, bloating and dysmotility. In particular, IBS associated with constipation (IBS-C) is characterized by hard and dry stools and inadequate evacuation and difficulty in defecation. Although several drugs ameliorate intestinal modifications and constipation-associated features, management of IBS is still a challenge. Natural compounds including Xyloglucan and pea protein (XP) and Chia seed powder (CS) are widely known to possess beneficial effects in counteracting several gastrointestinal disorders. Here, we aimed to assess the combined effects of XP and CS to treat constipation-related alterations in an IBS-C rat model. IBS-C was induced by gastric instillation of 2 mL of cold water (0–4 °C) for 14 days and Xiloglucan, Pea protein and Chia seeds (XP + CS) treatment was orally administered for 7 days. On day 22, colon tissues were collected for histological analysis. Our results showed that XP + CS administration attenuated constipation-related parameters by increasing body weight and food and water intake. Upon XP + CS treatment, from day 14 to 22, stool moisture content was restored to physiological level. Colonic tissues from IBS-C rats depicted a disruption of the organ architecture accompanied by edema. Loss of colonic structure was reflected by the marked reduction of tight junction protein expression, Occludin and zona occludens-1 (ZO-1). Administration of XP + CS treatment in IBS-C rats significantly ameliorated the colonic histological parameters and exerted a positive effect on barrier integrity by restoring the expression of Occludin and zona occludens-1 (ZO-1). Our findings demonstrated that the efficacy of XP and CS in managing constipation in rats is due to the ability of these compounds to form a protective barrier fortifying intestinal integrity and gut functionality. Full article

Background: Human milk does not meet the nutritional needs to support optimal growth of very preterm infants during the first weeks of life. Nutrient fortifiers are therefore added to human milk, though these products are suspected to increase gut dysmotility. The objective was to evaluate whether fortification with bovine colostrum (BC) improves bowel habits compared to a conventional fortifier (CF) in very preterm infants. Methods: In an unblinded, randomized study, 242 preterm infants (26–31 weeks of gestation) were randomized to receive BC (BC, Biofiber Damino, Gesten, Denmark) or CF (FM85 PreNAN, Nestlé, Vevey, Switzerland) as a fortifier. Stools (Amsterdam Stool Scale), bowel gas restlessness, stomach appearance score, volume, and frequency of gastric residuals were recorded before each meal until 35 weeks post-menstrual age. Results: As intake of fortifiers increased, stools became harder in both groups (p < 0.01) though less in BC infants (p < 0.05). The incidence of bowel gas restlessness increased with laxative treatments and days of fortification in both groups (p < 0.01), but laxatives were prescribed later in BC infants (p < 0.01). With advancing age, stomach appearance scores improved, but more so in BC infants (p < 0.01). Conclusions: Although there are limitations, a minimally processed, bioactive milk product such as BC induced similar or slightly improved bowel habits in preterm infants. Full article

Diabetes mellitus (DM) is a chronic progressive metabolic disorder associated with several gastrointestinal complications, affecting up to 75% of patients. Knowing that Angiotensin II (AngII) also regulates intestinal contraction, we decided to evaluate changes in ileum and colon histomorphometry and AngII reactivity in a rat model of DM. Streptozotocin (STZ, 55 mg/kg) was administered to induce DM to 24 adult male Wistar rats. Diabetic rats displayed all the characteristic signs of type 1 DM (T1DM) and fecal excretion increased about 4-fold over 14 days, while the excretion of controls remained unaltered. Compared to controls, diabetic ileum and colon presented an increase in both macroscopic (length, perimeter and weight) and microscopic (muscular wall thickness) parameters. Functionally, AngII-induced smooth muscle contraction was lower in diabetic rats, except in the distal colon. These differences in the contractile response to AngII may result from an imbalance between AngII type 1 (antagonized by candesartan, 10 nM) and type 2 receptors activation (antagonized by PD123319, 100 nM). Taken together, these results indicate that an early and refined STZ-induced T1DM rat model already shows structural remodelling of the gut wall and decreased contractile response to AngII, findings that may help to explain diabetic dysmotility. Full article

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. Full article