Pseudo-obstruction Research Articles

Gastrointestinal dysmotility in rodent models of Parkinson's disease.

Multiple studies describe prodromal, nonmotor dysfunctions that affect the quality of life of patients who subsequently develop Parkinson's disease (PD). These prodromal dysfunctions comprise a wide array of autonomic issues, including severe gastrointestinal (GI) motility disorders such as dysphagia, delayed gastric emptying, and chronic constipation. Indeed, strong evidence from studies in humans and animal models suggests that the GI tract and its neural, mainly vagal, connection to the central nervous system (CNS) could have a major role in the etiology of PD. In fact, misfolded α-synuclein aggregates that form Lewy bodies and neurites, i.e., the histological hallmarks of PD, are detected in the enteric nervous system (ENS) before clinical diagnosis of PD. The aim of the present review is to provide novel insights into the pathogenesis of GI dysmotility in PD, focusing our attention on functional, neurochemical, and molecular alterations in animal models.

Gastrointestinal Complications of Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS) Syndrome Managed By Parenteral Nutrition.

Gastrointestinal complications of MELAS such as chronic intestinal pseudo-obstruction, pancreatitis and gastroparesis can lead to undernutrition.Superior mesenteric artery syndrome is a rare condition but should be considered in cases with significant weight loss and resistance to symptomatic treatment.Optimal caloric intake and energy support can improve the condition of patients with MELAS.

Metabolic and other morbid complications in congenital generalized lipodystrophy type 4.

Morbidity and mortality rates in patients with autosomal recessive, congenital generalized lipodystrophy type 4 (CGL4), an ultra-rare disorder, remain unclear. We report on 30 females and 16 males from 10 countries with biallelic null variants in CAVIN1 gene (mean age, 12 years; range, 2 months to 41 years). Hypertriglyceridemia was seen in 79% (34/43), hepatic steatosis in 82% (27/33) but diabetes mellitus in only 21% (8/44). Myopathy with elevated serum creatine kinase levels (346-3325 IU/L) affected all of them (38/38). 39% had scoliosis (10/26) and 57% had atlantoaxial instability (8/14). Cardiac arrhythmias were detected in 57% (20/35) and 46% had ventricular tachycardia (16/35). Congenital pyloric stenosis was diagnosed in 39% (18/46), 9 had esophageal dysmotility and 19 had intestinal dysmotility. Four patients suffered from intestinal perforations. Seven patients died at mean age of 17 years (range: 2 months to 39 years). The cause of death in four patients was cardiac arrhythmia and sudden death, while others died of prematurity, gastrointestinal perforation, and infected foot ulcers leading to sepsis. Our study highlights high prevalence of myopathy, metabolic abnormalities, cardiac, and gastrointestinal problems in patients with CGL4. CGL4 patients are at high risk of early death mainly caused by cardiac arrhythmias.

Airway pepsinogen A4 identifies lung transplant recipients with microaspiration and predicts chronic lung allograft dysfunction

BackgroundAspiration is a known risk-factor for adverse outcomes post-lung transplantation. Airway bile acids are the gold-standard biomarker of aspiration – however they are released into the duodenum and likely reflect concurrent gastrointestinal dysmotility. Previous studies investigating total airway pepsin have found conflicting results on its relationship with adverse outcomes post-lung transplantation. These studies measured total pepsin and pepsinogen in the airways. Certain pepsinogens are constitutively expressed in the lungs while others, like pepsinogen A4 (PGA4), are not. We sought to evaluate the utility of measuring airway PGA4 as a biomarker of aspiration and predictor of adverse outcomes in lung transplant recipients (LTRs) early post-transplant. MethodsExpression of PGA4 was compared to other pepsinogens in lung tissue. Total pepsin and PGA4 were measured in large airway bronchial washings and compared to pre-existing markers of aspiration. Two independent cohorts of LTRs were used to assess the relationship between airway PGA4 and chronic lung allograft dysfunction (CLAD). Changes to airway PGA4 after anti-reflux surgery was assessed in a third cohort of LTRs. ResultsPGA4 was expressed in healthy human stomach but not lung. Airway PGA4, but not total pepsin, was associated with aspiration. Airway PGA4 was associated with an increased risk of CLAD in two independent cohorts of LTRs. Anti-reflux surgery was associated with reduced airway PGA4. ConclusionsAirway PGA4 is a marker of aspiration that predicts CLAD in LTRs. Measuring PGA4 at surveillance bronchoscopies can help triage high-risk LTRs for anti-reflux surgery.

Faster Gastrointestinal Transit, Reduced Small Intestinal Smooth Muscle Tone and Dysmotility in the Nlgn3R451C Mouse Model of Autism.

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 (Nlgn3R451C 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 Nlgn3R451C 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 Nlgn3R451C 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 Nlgn3R451C 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 Nlgn3R451C mouse colons, short contractions were inhibited to a greater extent (57.2% by the GABAA 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, Nlgn3R451C p = 0.002), but not the ileum, in both wild-type and Nlgn3R451C 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.

Efficacy and safety of rifaximin in patients with chronic intestinal pseudo-obstruction: a randomized, double-blind, placebo-controlled, phase II-a exploratory trial.

Chronic intestinal pseudo-obstruction (CIPO) is a rare intractable disease with limited treatment options. Small intestinal bacterial overgrowth (SIBO) often co-occurs with several diseases, including CIPO. While rifaximin (RFX) is effective in treating SIBO, its efficacy for CIPO remains unclear. Here, we aimed to investigate the efficacy and safety of RFX in adult patients with CIPO. Twelve patients were randomly assigned to receive RFX (400 mg three times daily, n=8) or a placebo (PBO, n=4) for 4 weeks. The global symptom score for abdominal bloating (GSS-bloating) and an original whole gastrointestinal symptoms score (O-WGSS) were collected, and a glucose hydrogen breath test (GHBT) and abdominal computed tomography (CT) were performed. No significant differences were observed in the primary endpoint. GSS-bloating improved by 75% and 25% in the PBO and RFX groups, respectively, and O-WGSS improved by 25% in both groups. No significant differences were observed in secondary and other endpoints, including the SIBO eradication rate in the GHBT and small intestinal volume on CT. In a post hoc analysis of SIBO-positive patients with CIPO (4/4 and 4/8 in the PBO and RFX groups), SIBO was eradicated in 25% and 75% of the patients (PBO and RFX groups, respectively) at the end of treatment, indicating a high eradication rate in the RFX group. Furthermore, the small intestinal gas volume decreased in the RFX group, and no severe adverse events occurred. Although no significant improvements were observed in subjective indicators, RFX may be beneficial in alleviating SIBO and reducing the small intestinal gas volume in SIBO-positive patients with CIPO.

GI Manifestation in Scleroderma

The gastrointestinal (GI) system frequently experiences complications in systemic sclerosis. Pathological changes in the GI system can be revealed from the early onset of the disease, such as esophageal hypomotility, to the late stage of the disease, where severe complications like intestinal pseudo-obstruction may occur. Systemic sclerosis can cause pathological changes throughout the entire gastrointestinal tract. Common symptoms include dysphagia, choking, heartburn, hoarseness, abdominal distension, diarrhea, constipation, and fecal incontinence. Oropharyngeal involvement in systemic sclerosis presents as weakened pharyngeal muscles, leading to oropharyngeal dysphagia, choking, food leakage, and aspiration, attributed to the dysfunction between the pharyngeal muscles and the upper esophageal sphincter due to muscle weakness. However, weak pharyngeal muscles may also be a clinical feature of the systemic sclerosis-polymyositis overlap syndrome. Esophageal involvement is frequently observed, with conditions such as esophageal hypomotility and lower esophageal sphincter incompetence, leading to early symptoms of dysphagia, gastroesophageal reflux, and potential complications such as esophagitis, esophageal stricture, Barrett’s esophagus, and aspiration pneumonia. Furthermore, gastric involvement includes gastric antral vascular ectasia, commonly known as “watermelon stomach,” which leads to gastrointestinal bleeding and chronic anemia. Intestinal manifestations comprise malabsorption, intestinal pseudo-obstruction, and bacterial overgrowth. Additionally, wide-mouthed diverticulosis and fecal incontinence are frequently found. Liver involvement includes primary biliary cirrhosis, most prevalent in limited cutaneous systemic sclerosis or certain overlap syndromes rather than diffuse cutaneous systemic sclerosis. The severity of these changes varies among patients, ranging from asymptomatic to severe conditions, which may result in malnutrition. Severe and chronic GI involvement significantly impacts daily life, making normal eating difficult, diminishing the quality of life, and potentially causing depression. Managing patients with systemic sclerosis who have GI involvement requires a multidisciplinary approach, involving collaboration among rheumatologists, gastroenterologists, nutritionists, surgeons, and possibly psychiatrists. This teamwork is essential to achieve successful patient care outcomes.

Chronic Atrial and Intestinal Dysrhythmia: A Rare Syndrome Presenting as Intestinal Pseudoobstruction

Chronic atrial and intestinal dysrhythmia (CAID) syndrome is a rare disorder affecting the heart and digestive systems. It results in bradycardia and arrhythmia due to sinoatrial node involvement. Concurrently, intestinal pseudoobstruction arises from anomalies in the Cajal cells, recognized as the pacemakers of the intestine. Patients may experience dizziness, drowsiness, syncope, and palpitations attributed to the arrhythmia, while abdominal pain, distension, vomiting, and constipation can occur due to intestinal pseudoobstruction. This report discusses the treatment management for two patients diagnosed with CAID syndrome.

Time is Gut. Approaching Intestinal Leiomyositis: Case Presentation and Literature Review.

T-lymphocytic intestinal leiomyositis is a rare cause of "pediatric intestinal pseudo-obstructions." Diagnosis may be difficult and requires full-thickness bowel biopsies during laparotomy or laparoscopy with possible enterostomy. Currently, immunosuppressive therapy is the only available treatment. A delay in diagnosis and therapy may negatively affect the prognosis because of ongoing fibrotic alterations; therefore, early diagnosis and consequent treatment are crucial. This review summarizes the available information on the nosology, diagnostic steps, and treatment modalities. Here, we report the youngest case of enteric leiomyositis reported in the last two decades and analyze its management by reviewing previous cases.

Acute Colonic Pseudo-Obstruction (ACPO): An Expanding Colon with Unusual Risk Factors

Acute Colonic Pseudo-Obstruction (ACPO): An Expanding Colon with Unusual Risk Factors

TOGA Therapeutic Oxygen for Gastrointestinal Atony

Background and aimsIleus, mechanical bowel obstruction and acute colonic pseudo-obstruction [ACPO] are characterized by distension of the intestines with accumulated bowel gas. Current treatments are not completely satisfactory. MethodsBy manipulating the partial pressures of oxygen and nitrogen in the trapped air with a novel 6-hour treatment with 100% oxygen via non-rebreather mask [NRB], the bowel can be successfully decompressed, facilitating resolution of the underlying condition. ResultsA positive clinical response was seen in 7/8 [87.5%] patients after TOGA [therapeutic oxygen for gastrointestinal atony]. Maximal lumen diameter decreased by an average of 1.14 ± 0.87 cm [16%]. ConclusionsIn this first clinical report of TOGA, the provision of 100% oxygen via NRB is a useful therapy. It decreased the diameter of the intestinal lumen and enhanced resolution of ileus, ACPO, and bowel obstruction. This is a low-morbidity, low-cost treatment of gastrointestinal luminal distension. ClinicalTrials.gov Identifier NCT03386136.st

Colitis-Induced Small Intestinal Hypomotility Is Dependent on Enteroendocrine Cell Loss in Mice

The abdominal discomfort experienced by patients with colitis may be attributable in part to the presence of small intestinal dysmotility, yet mechanisms linking colonic inflammation with small-bowel motility remain largely unexplored. We hypothesize that colitis results in small intestinal hypomotility owing to a loss of enteroendocrine cells (EECs) within the small intestine that can be rescued using serotonergic-modulating agents. Male C57BL/6J mice, as well as mice that overexpress (EECOVER) or lack (EECDEL) NeuroD1+ enteroendocrine cells, were exposed to dextran sulfate sodium (DSS) colitis (2.5% or 5% for 7 days) and small intestinal motility was assessed by 70-kilodalton fluorescein isothiocyanate-dextran fluorescence transit. EEC number and differentiation were evaluated by immunohistochemistry, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining, and quantitative reverse-transcriptase polymerase chain reaction. Mice were treated with the 5-hydroxytryptamine receptor 4 agonist prucalopride (5 mg/kg orally, daily) to restore serotonin signaling. DSS-induced colitis was associated with a significant small-bowel hypomotility that developed in the absence of significant inflammation in the small intestine and was associated with a significant reduction in EEC density. EEC loss occurred in conjunction with alterations in the expression of key serotonin synthesis and transporter genes, including Tph1, Ddc, and Slc6a4. Importantly, mice overexpressing EECs revealed improved small intestinal motility, whereas mice lacking EECs had worse intestinal motility when exposed to DSS. Finally, treatment of DSS-exposed mice with the 5-hydroxytryptamine receptor 4 agonist prucalopride restored small intestinal motility and attenuated colitis. Experimental DSS colitis induces significant small-bowel dysmotility in mice owing to enteroendocrine loss that can be reversed by genetic modulation of EEC or administering serotonin analogs, suggesting novel therapeutic approaches for patients with symptomatic colitis.

Histopatološki nalaz u enteričkim nervnim pleksusima kod dece sa poremećajima intestinalnog motiliteta - iskustvo jednog centra

Introduction/Aim: The aim of the study was to determine the frequency of various histopathological findings in biopsies of children with intestinal hypomotility and the incidence and characteristics of Hirschsprung disease (HD). Methods: Biopsies of colon and rectum taken due to intestinal hypomotility and chronic constipation at the Department of Pediatric Surgery of the University Children's Hospital in Belgrade over the 10-year period (from 2009 to 2018) were reviewed using pathology reports from the archive of the Institute of pathology, Faculty of Medicine, University of Belgrade. Results: A total of 287 patients with intestinal motility disorder were identified, with 554 biopsy samples. Of the total number of patients, 56% (161/287) were without any morphological changes in enteric nervous system (ENS). The most common histopathological findings were HD (69/287; 24%) and immaturity of ganglion cells (29/287; 10%). Isolated hypoganglionosis of ENS was found in 5 (2%) cases. Heterotopia of ganglion cells was the only finding in 8 (3%) cases. Rare causes of intestinal dysmotility were: eosinophilic proctitis/colitis (EPC) (4/287), neuronal intestinal dysplasia B (2/287), unclassified disganglionoses (3/287). Rectosigmoid variant of HD was the most frequent HD variant (80.3%). Acetylcholinesterase method and immunohistochemical staining were used in 19.5% cases. Conclusions: HD and immaturity of ganglion cells were the most common pathological findings in ENS of constipated children. It is important to differentiate EPC from other lesions of enteric plexuses due to different natural history and therapy.

Mind shift I: Fructus Aurantii - Rhizoma Chuanxiong synergistically anchors stress-induced depression-like behaviours and gastrointestinal dysmotility cluster by regulating psycho-immune-neuroendocrine network

BackgroundResearchers have not studied the integrity, orderly correlation, and dynamic openness of complex organisms and explored the laws of systems from a global perspective. In the context of reductionism, antidepressant development formerly focused on advanced technology and molecular details, clear targets and mechanisms, but the clinical results were often unsatisfactory. PurposeMDD represents an aggregate of different and highly diverse disease subtypes. The co-occurrence of stress-induced nonrandom multimorbidity is widespread, whereas only a fraction of the potential clusters are well known, such as the MDD-FGID cluster. Mapping these clusters, and determining which are nonrandom, is vital for discovering new mechanisms, developing treatments, and reconfiguring services to better meet patient needs. Study designAcute stress 15-minute forced swimming (AFS) or CUMS protocols can induce the nonrandom MDD-FGID cluster. Multiple biological processes of rats with depression-like behaviours and gastrointestinal dysmobility will be captured under conditions of stress, and the Fructus Aurantii-Rhizoma Chuanxiong (ZQCX) decoction will be utilized to dock the MDD-FGID cluster. Methods/resultsHere, Rhizoma Chuanxiong, one of the seven components of Chaihu-shugan-San, elicited the best antidepressant effect on CUMS rats, followed by Fructus Aurantii. ZQCX reversed AFS-induced depression-like behaviours and gastrointestinal dysmobility by regulating the glutamatergic system, AMPAR/BDNF/mTOR/synapsin I pathway, ghrelin signalling and gastrointestinal nitric oxide synthase. Based on the bioethnopharmacological analysis strategy, the determined meranzin hydrate (MH) and senkyunolide I (SI) by UPLC-PDA, simultaneously absorbed by the jejunum and hippocampus of rats, have been considered major absorbed bioactive compounds acting on behalf of ZQCX. Cotreatment with MH and SI at an equivalent dose in ZQCX synergistically replicated over 50.33 % efficacy of the parent formula in terms of antidepressant and prokinetic actions by modulating neuroinflammation and ghrelin signalling. ConclusionBrain-centric mind shifts require the integration of multiple central and peripheral systems and the elucidation of the underlying neurobiological mechanisms that ultimately contribute to novel therapeutic options. Ghrelin signalling and the immune system may partially underlie multimorbidity vulnerability, and ZQCX anchors stress-induced MDD-FGID clusters by docking them. Combining the results of micro details with the laws of the macro world may be more effective in finding treatments for MDD.

Lymphocytic myenteric ganglionitis associated with equine herpesvirus infection: A cause of chronic intestinal pseudo‐obstruction and recurrent colic in an adult horse

SummaryThis report describes a rare case of chronic intestinal pseudo‐obstruction (CIPO) in a 12‐year‐old Quarter Horse gelding, caused by lymphocytic myenteric ganglionitis (MG) associated with equine herpesvirus 1 (EHV‐1) and equine herpesvirus 5 (EHV‐5) infection. The horse presented with recurrent colic and weight loss over 1.5 years. Repetitive transrectal examinations consistently revealed small colon impaction and enlargement. During postmortem examination alternating segments of enlarged and reduced luminal diameter were observed throughout the entire intestinal tract. MG with lymphocytic infiltrates and neuronal degeneration of the large intestine were found on histopathological analysis. Additionally, polymerase chain reaction (PCR) analysis confirmed the presence of EHV‐1 and EHV‐5 DNA in affected intestinal tissues. Further research is needed to understand the pathophysiology of MG and its association with herpesviruses. Early recognition and diagnosis of MG‐associated CIPO may improve treatment approaches and outcomes for future cases.

A rare cause of anejaculation: mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) syndrome: case report.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) syndrome is an extremely rare multisystem disorder with autosomal recessive inheritance and impairs mitochondrial DNA replication, which causes myopathy and neurodegeneration. The classical symptoms of this syndrome are progressive gastrointestinal dysmotility and peripheral neuropathy. We are presenting a patient who had MNGIE syndrome and presented with anejaculation for the first time in the literature. A 27-year-old male patient applied to the urology clinic with anejaculation. It was learned that the patient had lifelong anejaculation and had no problems with libido, erection, or orgasm from his sexual history. In the evaluation of the etiology of anejaculation, the patient did not have any known causes of anejaculation. From the patient's medical history, it was learned that he was diagnosed with MNGIE syndrome when he presented to another hospital with gastrointestinal symptoms 5 years ago. Neurodegenerative diseases are the potential cause of anejaculation due to sensorimotor neuropathy and paresthesia. The patient was given genetic counseling and was informed about assisted reproductive techniques and that his partner should be screened for MNGIE syndrome. In conclusion, when evaluating neurodegenerative diseases, it is of great importance to question the patients' sexual problems, which are important for their quality of life, and to provide appropriate counseling.

Age-associated changes in lineage composition of the enteric nervous system regulate gut health and disease.

The enteric nervous system (ENS), a collection of neural cells contained in the wall of the gut, is of fundamental importance to gastrointestinal and systemic health. According to the prevailing paradigm, the ENS arises from progenitor cells migrating from the neural crest and remains largely unchanged thereafter. Here, we show that the lineage composition of maturing ENS changes with time, with a decline in the canonical lineage of neural-crest derived neurons and their replacement by a newly identified lineage of mesoderm-derived neurons. Single cell transcriptomics and immunochemical approaches establish a distinct expression profile of mesoderm-derived neurons. The dynamic balance between the proportions of neurons from these two different lineages in the post-natal gut is dependent on the availability of their respective trophic signals, GDNF-RET and HGF-MET. With increasing age, the mesoderm-derived neurons become the dominant form of neurons in the ENS, a change associated with significant functional effects on intestinal motility which can be reversed by GDNF supplementation. Transcriptomic analyses of human gut tissues show reduced GDNF-RET signaling in patients with intestinal dysmotility which is associated with reduction in neural crest-derived neuronal markers and concomitant increase in transcriptional patterns specific to mesoderm-derived neurons. Normal intestinal function in the adult gastrointestinal tract therefore appears to require an optimal balance between these two distinct lineages within the ENS.

Age-associated changes in lineage composition of the enteric nervous system regulate gut health and disease

The enteric nervous system (ENS), a collection of neural cells contained in the wall of the gut, is of fundamental importance to gastrointestinal and systemic health. According to the prevailing paradigm, the ENS arises from progenitor cells migrating from the neural crest and remains largely unchanged thereafter. Here, we show that the lineage composition of maturing ENS changes with time, with a decline in the canonical lineage of neural-crest derived neurons and their replacement by a newly identified lineage of mesoderm-derived neurons. Single cell transcriptomics and immunochemical approaches establish a distinct expression profile of mesoderm-derived neurons. The dynamic balance between the proportions of neurons from these two different lineages in the post-natal gut is dependent on the availability of their respective trophic signals, GDNF-RET and HGF-MET. With increasing age, the mesoderm-derived neurons become the dominant form of neurons in the ENS, a change associated with significant functional effects on intestinal motility which can be reversed by GDNF supplementation. Transcriptomic analyses of human gut tissues show reduced GDNF-RET signaling in patients with intestinal dysmotility which is associated with reduction in neural crest-derived neuronal markers and concomitant increase in transcriptional patterns specific to mesoderm-derived neurons. Normal intestinal function in the adult gastrointestinal tract therefore appears to require an optimal balance between these two distinct lineages within the ENS.

Vasoactive Intestinal Polypeptide Plays a Key Role in the Microbial-Neuroimmune Control of Intestinal Motility

Background and AimsAlthough chronic diarrhea and constipation are common, the treatment is symptomatic as their pathophysiology is poorly understood. Accumulating evidence suggests that the microbiota modulates gut function but the underlying mechanisms are unknown. We therefore investigated the pathways by which microbiota modulates gastrointestinal motility in different sections of the alimentary tract. MethodsGastric emptying, intestinal transit, muscle contractility, acetylcholine release, gene expression and vasoactive intestinal polypeptide (VIP) immunoreactivity were assessed in wild-type and Myd88-/-Trif-/- mice in germ-free, gnotobiotic and SPF conditions. Effects of transient colonization and antimicrobials, as well as immune cell blockade were investigated. VIP levels were assessed in human full thickness biopsies by Western blot. ResultsGerm-free mice had similar gastric emptying but slower intestinal transit compared with SPF mice, or mice monocolonized with Lactobacillus rhamnosus or Escherichia coli, the latter having stronger effects. While muscle contractility was unaffected, its neural control was modulated by microbiota by upregulating jejunal VIP, which co-localized with and controlled cholinergic nerve function. This process was responsive to changes in the microbial composition and load, and mediated through TLR signaling, with enteric glia cells playing a key role. Jejunal VIP was lower in patients with chronic intestinal pseudo-obstruction compared with control subjects. ConclusionMicrobial control of gastrointestinal motility is both region- and bacteria-specific, it reacts to environmental changes, and is mediated by innate immunity-neural system interactions. Small intestinal VIP, by regulating cholinergic nerves, plays a key role in this process, thus providing a new therapeutic target for patients with motility disorders.

Surgical Treatment of Gastroparesis.

Gastroparesis and intestinal dysmotility are life-altering diagnoses with no cure. Lifestyle changes, pharmacological, and surgical interventions are combined in a multidisciplinary fashion to improve the quality of life in this patient population. Starting with lifestyle changes, adjustments are made to the types and amounts of food consumed, medical conditions are optimized, and the use of narcotic pain medications as well as smoking is discontinued. For many, these changes are not enough, and antiemetics and promotility agents are used to control symptoms. Finally, when these measures fail, patients turn to surgery, which can include surgical alterations to the stomach, implantation of a gastric stimulator, placement of drainage tubes, and possibly even the complete removal of different organs, including the stomach or gallbladder. In our clinic, patients not only see a surgeon but also a gastroenterologist, dietitian, and psychologist. We strongly believe in a multidisciplinary approach to this condition. The goal is to provide patients with hope and help them live fuller and happier lives. The study primarily addresses technical considerations and the surgical approach for patients diagnosed with gastroparesis. It outlines the entire process, starting from preparations before the surgery, encompassing the preoperative work-up, and detailing the steps involved in the surgical procedure. One of the key diagnostic challenges faced in treating gastroparesis patients is determining the underlying cause of the condition, as this information is critical for selecting the appropriate surgical intervention. Once the patient's condition has been categorized based on the cause, the medical team engages in a discussion with the patient regarding potential treatment options, which may include endoscopic procedures, minimally invasive techniques, or open surgery.