Gastroparesis Research Articles

Atypical Causes of Gastroparesis: Prevalence, Gastric Emptying, and Clinical Features.

Gastroparesis is commonly attributed to idiopathic or diabetic causes. We aimed to describe atypical causes of gastroparesis and examine the clinical features and severity of delayed gastric emptying compared with idiopathic and diabetic causes. Between 2018 and 2021, gastroparesis patients being evaluated at our tertiary care center completed a 4-hour gastric emptying scintigraphy and questionnaires assessing for gastrointestinal disorders, including patient assessment of upper gastrointestinal symptoms. Patients were divided into groups relating to gastroparesis cause: diabetic, postsurgical (PSGp), connective tissue (CTGp), neurological and idiopathic. Two hundred fifty-six patients with delayed emptying on gastric emptying scintigraphy completed the questionnaires. Gastroparesis causes included 149 (58.2%) idiopathic, 60 (23.4%) diabetic, 29 (11.3%) postsurgical, 13 (5.1%) connective tissue, and 5 (2.0%) neurological. In each group, most patients were female and White. Gastric retention at 4 hours was significantly greater in patients with diabetic (39.3±25.7% P<0.001), postsurgical (41.3±24.0% P=0.002), and connective tissue gastroparesis (37.8±20.0% P=0.049) compared with patients with idiopathic gastroparesis (25.5±17.6%). In PSGp, diabetic and idiopathic causes, the main symptoms were early satiety and postprandial fullness, whereas in CTGp, bloating and abdominal distension were the predominant symptoms. Vomiting severity was significantly greater in patients with diabetes compared with idiopathic gastroparesis (2.9±1.9 vs. 2.1±1.8 P=0.006). Atypical causes contributed to gastroparesis in 47 of 256 (18.4%) patients with delayed gastric emptying. Gastric emptying was significantly more delayed in PSGp and CTGp patients. PSGp patients mainly experienced stomach fullness and early satiety, whereas CTGp patients had predominantly bloating and distension.

S621 Superiority of Nasal Spray Compared to Orally Administered Metoclopramide in Reducing Healthcare Costs in Treating Diabetic Gastroparesis Patients

S621 Superiority of Nasal Spray Compared to Orally Administered Metoclopramide in Reducing Healthcare Costs in Treating Diabetic Gastroparesis Patients

Adeno-associated virus-9 reverses delayed gastric emptying of solids in diabetic mice.

Gastroparesis is defined by delayed gastric emptying (GE) without obstruction. Studies suggest targeting heme oxygenase-1 (HO1) may ameliorate diabetic gastroparesis. Upregulation of HO1 expression via interleukin-10 (IL-10) in the gastric muscularis propria is associated with reversal of delayed GE in diabetic NOD mice. IL-10 activates the M2 cytoprotective phenotype of macrophages and induces expression of HO1 protein. Here, we assess delivery of HO1 by recombinant adeno-associated viruses (AAVs) in diabetic mice with delayed GE. C57BL6 diabetic delayed GE mice were injected with 1 × 1012 vg scAAV9-cre, scAAV9-GFP, or scAAV9-HO1 particles. Changes to GE were assessed weekly utilizing our [13 C]-octanoic acid breath test. Stomach tissue was collected to assess the effect of scAAV9 treatment on Kit, NOS1, and HO1 expression. Delayed GE returned to normal within 2 weeks of treatment in 7/12 mice receiving scAAV9-cre and in 4/5 mice that received the scAAV9-GFP, whereas mice that received scAAV9-HO1 did not respond in the same manner and had GE that took significantly longer to return to normal (6/7 mice at 4-6 weeks). Kit, NOS1, and HO1 protein expression in scAAV9-GFP-treated mice with normal GE were not significantly different compared with diabetic mice with delayed GE. Injection of scAAV9 into diabetic C57BL6 mice produced a biological response that resulted in acceleration of GE independently of the cargo delivered by the AAV9 vector. Further research is needed to determine whether use of AAV mediated gene transduction in the gastric muscularis propria is beneficial and warranted.

A pilot genome-wide association study meta-analysis of gastroparesis.

Gastroparesis (GP) is characterized by delayed gastric emptying in the absence of mechanical obstruction. Genetic predisposition may play a role; however, investigation at the genome-wide level has not been performed. We carried out a genome-wide association study (GWAS) meta-analysis on (i) 478 GP patients from the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium (GpCRC) compared to 9931 population-based controls from the University of Michigan Health and Retirement Study; and (ii) 402 GP cases compared to 48,340 non-gastroparesis controls from the Michigan Genomics Initiative. Associations for 5,811,784 high-quality SNPs were tested on a total of 880 GP patients and 58,271 controls, using logistic mixed models adjusted for age, sex, and principal components. Gene mapping was obtained based on genomic position and expression quantitative trait loci, and a gene-set network enrichment analysis was performed. Genetic associations with clinical data were tested in GpCRC patients. Protein expression of selected candidate genes was determined in full thickness gastric biopsies from GpCRC patients and controls. While no SNP associations were detected at strict significance (p≤5×10-8 ), nine independent genomic loci were associated at suggestive significance (p≤1×10-5 ), with the strongest signal (rs9273363, odds ratio=1.4, p=1×10-7 ) mapped to the human leukocyte antigen region. Computational annotation of suggestive risk loci identified 14 protein-coding candidate genes. Gene-set network enrichment analysis revealed pathways potentially involved in immune and motor dysregulation (pFDR ≤ 0.05). The GP risk allele rs6984536A (Peroxidasin-Like; PXDNL) was associated with increased abdominal pain severity scores (Beta=0.13, p=0.03). Gastric muscularis expression of PXDNL also positively correlated with abdominal pain in GP patients (r=0.8, p=0.02). Dickkopf WNT Signaling Pathway Inhibitor 1 showed decreased expression in diabetic GP patients (p=0.005 vs. controls). We report preliminary GWAS findings for GP, which highlight candidate genes and pathways related to immune and sensory-motor dysregulation. Larger studies are needed to validate and expand these findings in independent datasets.

Diabetic Gastroparesis and its Emerging Therapeutic Options: A Narrative Review of the Literature.

Diabetic gastroparesis (DG) is one of the many complications of diabetes mellitus (DM). Even though this condition surfaces years after uncontrolled disease, it affects the quality of life in several ways and causes significant morbidity. Common symptoms experienced by the patients include postprandial nausea, vomiting, abdominal fullness, and pain. Strict glycemic control is essential to evade the effects of DG. The purpose of this review article is to briefly study the pathophysiology, clinical features, diagnostic modalities, and the effects of DG on different aspects of life. Furthermore, it also focuses on the emerging treatment modalities for DG. Tradipitant and relamorelin are two such treatment options that are gaining noteworthy recognition and are discussed in detail in this review article. As observed through various clinical trials, these drugs help alleviate symptoms like nausea, vomiting, abdominal pain, and bloating in patients suffering from DG, thereby targeting the most common and bothersome symptoms of the disease. This leads to an improvement in the quality of life, making it a reliable treatment option for this disease. But while pharmacological intervention is vital, psychological support and lifestyle changes are equally important and are the reason why a multidisciplinary approach is required for the treatment of DG.

Ultrasonography findings in diabetes and diabetes gastroparesis: A meta-analysis

Background: The gold standard for diagnosis of diabetes gastroparesis (DG) is with gastric emptying scintigraphy (GES) examination. However, GES is not available in every healthcare center worldwide and the examination cost is rather expensive, unlike ultrasonography (USG) examination. This study aims to evaluate gastric changes monitored with USG in diabetes mellitus (DM) and DG. Methods: We performed searches from Google Scholar, PubMed, Science Direct, Proquest, and Scopus in April 30 – May 6, 2022. Random-effect approach on outcomes, standardized mean-difference (SMD) and 95%-confidence interval (CI) was assessed. Results: Compared to healthy control; (1) Antral cross-sectional area (CSA) in DM is bigger in fasting (SMD=1.25cm2; 95%CI, 0.79 to 1.71, I2=81%, P&lt;0.05) and postprandial (SMD=3.70 cm2; 95%CI, 1.45 to 5.34, I2=85%, P&lt;0.05). (2) Gastric emptying time (GET) is longer with DG (SMD=75.44min; 95%CI, 31.61 to 119.27, I2=97%) and in DM (SMD=35.54min; 95% CI, 11.49 to 59.60, I2=94%). (3) Gastric half-emptying time (GE50) were found to be longer in DM (SMD=20.73 min; 95%CI, 14.69 to 26.77, I2=60%, P&lt;0.05) and DG (SMD=7.46min; 95%CI, 5.06 to 9.86, I2=68.2%, P&lt;0.05). (4) Smaller gastric emptying rate (GER) in DG (SMD=-31.95%; 95%CI, -42.22% to -21.69%, I2=84%, P&lt;0.05) and DM (SMD=-16.14%; 95%CI, -30.88% to -1.39%, I2=78%, P&lt;0.05). (5) Less antral contraction in DG (SMD=-1.47; 95%CI, -2.61 to -0.33, I2=82%, P&lt;0.05). Conclusions: Patients with DM and DG have wider antral CSA, longer GET and GE50, reduced GER and reducing antral contraction. USG is useful for assessing gastric emptying in DM and DG. PROSPERO registration: CRD42022328695 (10/05/2022)

Hypoxia-Inducible Factor 1α Stabilization Restores Epigenetic Control of Nitric Oxide Synthase 1 Expression and Reverses Gastroparesis in Female Diabetic Mice

Although depletion of neuronal nitric oxide synthase (NOS1)-expressing neurons contributes to gastroparesis, stimulating nitrergic signaling is not an effective therapy. We investigated whether hypoxia-inducible factor 1α (HIF1A), which is activated by high O2 consumption in central neurons, is a Nos1 transcription factor in enteric neurons and whether stabilizing HIF1A reverses gastroparesis. Mice with streptozotocin-induced diabetes, human and mouse tissues, NOS1+ mouse neuroblastoma cells, and isolated nitrergic neurons were studied. Gastric emptying of solids and volumes were determined by breath test and single-photon emission computed tomography, respectively. Gene expression was analyzed by RNA-sequencing, microarrays, immunoblotting, and immunofluorescence. Epigenetic assays included chromatin immunoprecipitation sequencing (13 targets), chromosome conformation capture sequencing, and reporter assays. Mechanistic studies used Cre-mediated recombination, RNA interference, and clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9)-mediated epigenome editing. HIF1A signaling from physiological intracellular hypoxia was active in mouse and human NOS1+ myenteric neurons but reduced in diabetes. Deleting Hif1a in Nos1-expressing neurons reduced NOS1 protein by 50% to 92% and delayed gastric emptying of solids in female but not male mice. Stabilizing HIF1A with roxadustat (FG-4592), which is approved for human use, restored NOS1 and reversed gastroparesis in female diabetic mice. In nitrergic neurons, HIF1A up-regulated Nos1 transcription by binding and activating proximal and distal cis-regulatory elements, including newly discovered super-enhancers, facilitating RNA polymerase loading and pause-release, and by recruiting cohesin to loop anchors to alter chromosome topology. Pharmacologic HIF1A stabilization is a novel, translatable approach to restoring nitrergic signaling and treating diabetic gastroparesis. The newly recognized effects of HIF1A on chromosome topology may provide insights into physioxia- and ischemia-related organ function.

Low-intensity pulsed ultrasound at ST36 improves the gastric motility by TNF-α/IKKβ/NF-κB signaling pathway in diabetic rats.

Low-intensity pulsed ultrasound (LIPUS) can effectively regulate the central and peripheral nervous system. However, whether LIPUS could act on acupuncture points to modulate the activity of peripheral nervous has rarely been studied. Our study aimed to investigate whether LIPUS at ST36 could improve gastric emptying in diabetic gastroparesis rats. Sprague-Dawley male rats were divided into three groups: control group (CON), diabetic gastroparesis group (DM), and diabetic gastroparesis LIPUS treated group (LIPUS). The body weight and blood glucose were recorded every week. Glucose tolerance, gastric emptying rate, and gastric motility were measured before and after treatment. Gastric motility was assessed by ultrasonic examination and Muscle strip experiment. The expression level of c-Kit was assessed by immunohistochemistry staining. Levels of TNF-α, p-NF-κB p-65, NF-κB p-65, and p-IKKβ, IKKβ were measured by western blot. We reported LIPUS at an intensity of 0.88W/cm2 exhibited significant differences in functional recovery of gastric delayed emptying in diabetic rats. Through ultrasound gastric motility functional testing and analysis of gastric antral smooth muscle strips indirectly and directly proved the effectiveness of LIPUS for the recovery of gastric delayed emptying. Pathological analysis and western blot indicated that the mechanism by which LIPUS applied to ST36 improved gastric motility may be partially attributed to the inhibition of the TNF-α/IKKβ/NF-κB signaling pathway, thereby rescuing the damaged interstitial cells of Cajal network. LIPUS at ST36 improved the gastric motility and rescued the damaged networks of interstitial cells of Cajal. LIPUS may have a promising therapeutic potential for diabetic gastroparesis.

Imaging in Gastroparesis: Exploring Innovative Diagnostic Approaches, Symptoms, and Treatment.

Gastroparesis (GP) is a chronic disease characterized by upper gastrointestinal symptoms, primarily nausea and vomiting, and delayed gastric emptying (GE), in the absence of mechanical GI obstruction. The underlying pathophysiology of GP remains unclear, but factors contributing to the condition include vagal nerve dysfunction, impaired gastric fundic accommodation, antral hypomotility, gastric dysrhythmias, and pyloric dysfunction. Currently, gastric emptying scintigraphy (GES) is considered the gold standard for GP diagnosis. However, the overall delay in GE weakly correlates with GP symptoms and their severity. Recent research efforts have focused on developing treatments that address the presumed underlying pathophysiological mechanisms of GP, such as pyloric hypertonicity, with Gastric Peroral Endoscopic Myotomy (G-POEM) one of these procedures. New promising diagnostic tools for gastroparesis include wireless motility capsule (WMC), the 13 carbon-GE breath test, high-resolution electrogastrography, and the Endoluminal Functional Lumen Imaging Probe (EndoFLIP). Some of these tools assess alterations beyond GE, such as muscular electrical activity and pyloric tone. These modalities have the potential to characterize the pathophysiology of gastroparesis, identifying patients who may benefit from targeted therapies. The aim of this review is to provide an overview of the current knowledge on diagnostic pathways in GP, with a focus on the association between diagnosis, symptoms, and treatment.

Exploring the Underlying Mechanism of Alpinia officinarum Hance Ameliorating Diabetic Gastroparesis through Combining Network Pharmacology, Molecular Docking, and in Vivo Experimental Verification.

Alpinia officinarum Hance (AOH) has a long history in China as a Chinese medicine and exerts the pharmacological effects of antidiabetic and gastrointestinal protection. In traditional Chinese medicine theory, AOH is often combined with other Chinese medicines for the treatment of diabetic gastroparesis (DGP). However, the molecular mechanisms, potential targets, and bioactive ingredients of AOH that act against DGP are yet to be elucidated. In this study, network pharmacology, molecular docking, and experimental study were used to predict the therapeutic effects and the potential molecular mechanism of AOH in DGP. Network pharmacology analysis was performed to acquire information on the active chemical ingredients, DGP-related target proteins in AOH, and potential signaling pathway. In addition, molecular docking approach was used to simulate the binding of drugs and targets. Finally, DGP-mice model was used for experimental verification in vivo. Results: Through the network pharmacological research, AKT1 was found to be the core protein in AOH for the treatment of DGP and was mainly involved in the PI3K-AKT signaling pathway. Additionally, the interactions between bioactive compounds and target proteins (PIK3CA and AKT1) were analyzed using molecular docking, which verified the results of network pharmacology. Further in vivo studies indicated that AOH could reduce fasting blood glucose levels, improve gastric emptying rate, and ameliorate biochemical indicators in DGP mice. Moreover, AOH could increase the expressions and phosphorylation levels of PI3K and AKT in the stomach to regulate oxidative stress. The study has shown that AOH may play a protective role on DGP through mediation of the PI3K-AKT signaling pathway to regulate oxidative stress.

An overview of systematic reviews of acupuncture for diabetic gastroparesis.

To date, several systematic reviews and/or meta-analyses (SRs/MAs) on the topic of acupuncture as a treatment for diabetic gastroparesis (DGP) have been published. However, whether acupuncture is an effective and safe treatment for DGP remains controversial. In this study, we aimed to determine whether the methodology and results of previously published SRs/MAs of acupuncture as a treatment for DGP were of sufficient quality to be considered reliable. We extensively searched seven databases, including PubMed, EMBASE, Cochrane Library, Web of Science, China National Knowledge, Wan Fang, and Chongqing VIP, for SRs/MAs published before or on September 16, 2022. The SRs/MAs that met the inclusion criteria were evaluated for the quality of the methodology and results using the Assessing the Methodological Quality of Systematic Reviews Two (AMSTAR-2) and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tools. A re-meta-analysis of primary outcome indicators was also performed. Ten SRs/MAs that met the inclusion criteria were obtained. Using the AMSTAR-2, which is a methodological quality assessment tool, two MAs were rated as low quality, and eight SRs/MAs were rated as extremely low quality. Assessment with the GRADE tool revealed that, among 20 results, 4 were of moderate quality, 10 were of low quality, and 6 were of very low quality. Re-meta-analysis of primary outcome indicators revealed that, in terms of total efficiency, all types of acupuncture interventions, such as acupuncture, electroacupuncture, and acupoint injection, performed better than the controls, such as gastroprokinetic agents and sham acupuncture. Moreover, in the treatment of DGP, acupuncture exhibited fewer side effects compared to the controls. Acupuncture appears to improve the symptoms of patients with DGP, and the side effects of acupuncture as a treatment for DGP are inferior to those of the controls. However, owing to the low quality of the methodology and results of the SRs/MAs, these findings cannot be considered reliable and need to be validated by additional studies with rigorous standards of experimental design and protocols and larger sample sizes.

A Randomized, Controlled Trial of Efficacy and Safety of Cannabidiol in Idiopathic and Diabetic Gastroparesis

Cannabis (delta-9-tetrahydrocannabinol), a nonselective cannabinoid-receptor agonist, relieves nausea and pain. Cannabidiol (CBD), a cannabinoid receptor 2 inverse agonist with central effects, also reduces gut sensation and inflammation. We compared the effects of 4 weeks of treatment with pharmaceutical CBD vs placebo in patients with idiopathic or diabetic (diabetes mellitus) gastroparesis. We performed a randomized, double-blinded, placebo-controlled study of CBD twice daily (Epidiolex escalated to 20 mg/kg/d; Jazz Pharmaceuticals, Dublin, Ireland) in patients with nonsurgical gastroparesis with delayed gastric emptying of solids (GES). Symptoms were assessed by the Gastroparesis Cardinal Symptom Index Daily Diary. After 4 weeks of treatment, we measured GES, gastric volumes, and Ensure (Abbott Laboratories, Abbott Park, IL) satiation test (1 kcal/mL, 30 mL/min) to assess volume to comfortable fullness and maximum tolerance. Patients underwent specific FAAH and CNR1 genotyping. Statistical analysis compared 2 treatments using analysis of variance including baseline measurements and body mass index as covariates. Among 44 patients (32 idiopathic, 6 diabetes mellitus type 1, and 6 diabetes mellitus type 2), 5 patients did not tolerate full-dose escalation; 3 withdrew before completing 4 weeks of treatment (2 placebo, 1 CBD); 95% completed 4 weeks of treatment and diaries. Compared with placebo, CBD reduced the total Gastroparesis Cardinal Symptom Index score (P= .008), inability to finish a normal-sized meal (P= .029), number of vomiting episodes/24 hours (P= .006), and overall symptom severity (P= .034). Patients treated with CBD had a higher volume to comfortable fullness and maximum tolerance and slower GES. FAAH rs34420 genotype significantly impacted nutrient drink ingestion. The most common adverse events reported were diarrhea (14 patients), fatigue (8 patients), headache (8 patients), and nausea (7 patients). CBD provides symptom relief in patients with gastroparesis and improves the tolerance of liquid nutrient intake, despite slowing of GES. gov NCT #03941288.

Involvement of Rictor/mTORC2/Akt/GLUT4 pathway in the regulation of energy metabolism in the gastric smooth muscle of diabetic rats.

Diabetes mellitus can be accompanied by a variety of complications. The purpose of the present study was to characterize the Rictor/mTOR complex 2 (mTORC2)/Akt/glucose transporter 4 (GLUT4) pathway and its effects on energy metabolism in the gastric smooth muscle of diabetic rats. Diabetes was induced in rats using streptozotocin and their phenotype was compared with untreated rats. The relationship between gastric motility and energy metabolism was analyzed by comparing the contraction and ATP metabolism of muscle strips. Western blotting was used to detect the expression of key proteins in the pathway. The diabetic rats demonstrated less frequent and less powerful gastric smooth muscle contractions. The concentrations of ADP, AMP, and ATP, and the energy charge in gastric smooth muscle changed in different periods of diabetes, and these changes were consistent with changes in mechanistic target of rapamycin (mTOR) protein content. The expression of the key intermediates in signal transduction in the Rictor/mTORC2/Akt/GLUT4 pathway also underwent significant changes. Rictor protein expression increased during the development of diabetes, but the activation of mTORC2 did not increase with the increase in Rictor expression. GLUT4 translocation is regulated by Akt and its expression change during the development of diabetes. These findings suggest that altered energy metabolism is present in gastric smooth muscle that is associated with changes in the Rictor/mTORC2/Akt/GLUT4 pathway. Rictor/mTORC2/Akt/GLUT4 pathway may be involved in the regulation of energy metabolism in the gastric smooth muscle of diabetic rats and the development of diabetic gastroparesis.

Association between Gastroparesis and Rheumatoid Arthritis: A US Population-Based Study.

Patients with rheumatoid arthritis (RA) have a high prevalence of nausea, vomiting, postprandial fullness, and abdominal pain; these are symptoms that are similar to those in gastroparesis (GP). The aim of this study was to assess the association between GP and RA and the determinants of GP. We identified patients with RA and patients with GP from the 2012-2014 National Inpatient Sample database. The t test and the χ2 test were used for continuous and categorical variables, respectively. We determined the association between RA and GP and independent predictors of GP by multivariate analysis. Of 1,514,960 patients with RA, there were 1070 hospitalizations in which a primary diagnosis of GP was identified. The GP odds ratio in RA was found to be 1.36 and the 95% confidence interval was 1.24 to 1.49 (P < 0.0001). The variables increasing the odds of GP were age intervals of 18 to 35 years, 36 to 50 years, and 51 to 65 years; being female, White, or Black; a median household income in the 26th to 50th and the 51st to 75th percentiles; having diabetes mellitus; and having RA. An increased likelihood of 36% of GP among patients with RA was determined. White and Black patients younger than age 65 showed a greater risk of developing GP.

RWD44 Use of Real-World Data for Hard-to-Identify Patient Population: Methodology and a Case Study

Real-world data (RWD) provides complimentary and supplemental data to discern effectiveness and value of therapeutic interventions. Fragmented data ecosystems remain a challenge for developing real-world evidence (RWE). In particular, medications dispensed via specialty pharmacies (SP) may not be well captured in traditional claims databases or, if captured, may represent a subgroup of patients. We sought to identify whether tokenization and matching between SP data and administrative claims data was feasible and representative for a nasal formulation of metoclopramide (nasal MCP) using the treatment of for diabetic gastroparesis (DGP).

Gastroparesis: Myths, Misconceptions, and Management.

Gastroparesis (GP), a historically vexing disorder characterized by symptoms of nausea, vomiting, abdominal pain, early satiety, and/or bloating, in the setting of an objective delay in gastric emptying, is often difficult to treat and carries a tremendous burden on the quality of patients' lives, as well as the healthcare system in general. Though the etiology of GP has been fairly well defined, much work has been done recently to better understand the pathophysiology of GP, as well as to identify novel effective and safe treatment options. As our understanding of GP has evolved, many myths and misconceptions still abound in this rapidly changing field. The goal of this review is to identify myths and misconceptions regarding the etiology, pathophysiology, diagnosis, and treatment of GP, in the context of the latest research findings which have shaped our current understanding of GP. Recognition and dispelling of such myths and misconceptions is critical to moving the field forward and ultimately advancing the clinical management of what will hopefully become a better understood and more manageable disorder in the future.

New insights into muscularis macrophages in the gut: from their origin to therapeutic targeting.

Muscularis macrophages, as the most abundant immune cells in the intestinal muscularis externa, exhibit tissue protective phenotype in the steady state. Owing to tremendous advances in technology, we now know the fact that muscularis macrophages are a heterogeneous population of cells which could be divided into different functional subsets depending on their anatomic niches. There is emerging evidence showing that these subsets, through molecular interactions with their neighbours, take part in a wide range of physiological and pathophysiological processes in the gut. In this review, we summarize recent progress (particularly over the past 4 years) on distribution, morphology, origin and functions of muscularis macrophages and, where possible, the characteristics of specific subsets in response to the microenvironment they occupy, with particular emphasis on their role in muscular inflammation. Furthermore, we also integrate their role in inflammation-related gastrointestinal disorders, such as post-operative ileus and diabetic gastroparesis, in order to propose future therapeutic strategies.

Role of Mfge8 in the reduced contractility of diabetic gastroparesis

Coordinated gastric contractility is imperative for ideal digestion and absorption of nutrients. This is impaired during diabetic gastroparesis, a disorder characterized by abnormal gastric smooth muscle contractions leading to delayed gastric emptying. The objective of this research was to further the understanding of the gastric smooth muscle contraction regulatory mechanisms and how these cascades are affected by diabetes. In addition to its anti-inflammatory properties, it has been shown that milk fat globule-epidermal growth factor 8 (Mfge8) binding to ɑ8β1 integrin decreases murine gastric contractile activity by reducing the inhibitory phosphorylation of MLCP, resulting in MLCP activation and reduced myosin phosphorylation. Additionally, Mfge8 is elevated in human serum from type 2 diabetic individuals compared to non-diabetic individuals. It is hypothesized that elevated levels of Mfge8 in smooth muscle tissue will lead to decreased contractility strength, a phenomenon that would resemble gastroparesis secondary to diabetes. We analyzed the contractility and Mfge8 expression of human gastric antrum smooth muscles from obese diabetic and obese non-diabetic individuals who elected to undergo sleeve gastrectomy surgery for weight loss. Short strips of gastric muscle were stimulated to contract with serial concentrations of carbachol and contractile activity was measured with AcqKnowledge software. Mfge8 protein expression was then analyzed using a Wes Simple western instrument. We report that human gastric antrum smooth muscle tissue levels of Mfge8 are elevated in diabetic obese individuals (n=22) compared to non-diabetic obese individuals (n=37, P=0.004). However, we show that the contractile activity of antrum smooth muscle from diabetic obese individuals (n=38) is not dependent on Mfge8 levels and is not significantly different from the contractility of non-diabetic obese individuals (n=38). The rate of contraction, rate of relaxation, and overall tension ( P=0.40) produced by the muscle tissues from the two groups did not significantly differ from each other. It is possible that Mfge8 was not elevated enough to cause reduced contractility, or that those with elevated Mfge8 had not yet developed symptoms of gastroparesis. Mfge8 may serve as a biomarker for diabetic gastroparesis in the future, and additional research is required to determine the pathologic significance of elevated Mfge8 levels in obese diabetic human gastric antrum smooth muscle. This research was supported by a National Institute of Diabetes and Digestive and Kidney Diseases Diabetic Complications Consortium (DiaComp, http://www.diacomp.org ) Grant DK076169, a Takeda Pharmaceuticals Innovation Center Grant to BP, and a UNRSOM Office of Medical Research Grant FD110-PG08935 to DD. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Gastroparesis: The Complex Interplay with Microbiota and the Role of Exogenous Infections in the Pathogenesis of the Disease.

Gastroparesis (GP) is a disorder of gastric functions that is defined by objective delayed gastric emptying in the absence of mechanical obstruction. This disease is characterized by symptoms such as nausea, post-prandial fullness, and early satiety. GP significantly impacts patients' quality of life and contributes to substantial healthcare expenses for families and society. However, the epidemiological burden of GP is difficult to evaluate, mainly due its significant overlap with functional dyspepsia (FD). GP and FD represent two similar diseases. The pathophysiology of both disorders involves abnormal gastric motility, visceral hypersensitivity, and mucosal inflammation. Moreover, both conditions share similar symptoms, such as epigastric pain, bloating, and early satiety. The latest evidence reveals that dysbiosis is directly or indirectly connected to gut-brain axis alterations, which are the basis of pathogenesis in both FD and GP. Furthermore, the role of microbiota in the development of gastroparesis was demonstrated by some clinical studies, which found that the use of probiotics is correlated with improvements in the gastric emptying time (GET). Infections (with viruses, bacteria, and protozoa) represent a proven etiology for GP but have not been sufficiently considered in current clinical practice. Previous viral infections can be found in about 20% of idiopathic GP cases. Moreover, delayed gastric emptying during systemic protozoal infections represents a huge concern for compromised patients, and few data exist on the topic. This comprehensive narrative review analyzes the relationship between microorganisms and GP. We explore, on the one hand, the correlation between gut microbiota dysbiosis and GP pathogenesis, including treatment implications, and, on the other hand, the association between exogenous infections and the etiology of the disease.

A Case Study of Gastro Paresis in a Patient with New Corona Virus Infection after Rectal Cancer Surgery

Background: In the face of the COVID-19 pandemic, surgical personnel and patients experience many diagnosis and treatment-related challenges. COVID-19 is highly virulent, and thus, immediate, safe, and effective solutions to the patients’ management are required. Research collaboration and knowledge dissemination are necessary to optimize medical and surgical approaches to the individual patients’ needs.&#x0D; Gastric manifestations of SARS-CoV-2 infection are not uncommon and may even precede respiratory symptoms. Common gastrointestinal symptoms include loss of appetite, diarrhea, nausea, vomiting and abdominal pain.&#x0D; Case Presentation: A 50-year-old male patient complained of "blood in the stool and tenesmus for half a year" and was admitted to the hospital on March 2, 2023. Half a year ago, the patient had blood in the stool without obvious incentives, the bleeding was bright red, the habit of defecation changed, the stool became thinner, and the frequency of defecation increased, 3-5 times a day, and the amount was not much. At that time, he went to a regular medical institution for any treatment measures.