Pankaj J. Pasricha

Johns Hopkins University | JHU

Background Breath testing for small intestinal bacterial overgrowth (SIBO) is typically performed using clinic-based equipment or single-use test kits. Aims This study aimed to evaluate the utility of a portable, point-of-care breath analysis device (AIRE®, FoodMarble) in patients suspected to have SIBO. A technical assessment including a comparis...

COVID-19 increases the risk of neurological and gastrointestinal sequelae, but it is unclear if it does so more than other infections. Using a multicenter record network, we matched 649,478 COVID-19 patients to negative controls (NCs) and patients infected with influenza, human herpesvirusses, and lyme's disease (LD) to compare new-onset gastrointe...

Introduction We examined autoimmunity markers (AIM) and autonomic dysfunction in patients with chronic neurogastroenterological symptoms and their relationship to joint hypermobility/hypermobility spectrum disorder (JH/HSD). Methods AIM positivity was defined as a diagnosis of known autoimmune/autoinflammatory disorder (AIDX) with at least one pos...

Patients with gastroparesis (Gp) often have diets deficient in calories, electrolytes, and vitamins. Vitamin D levels have been reported to be low in some patients with Gp but has not been systematically studied. Aims To determine vitamin D levels and relationships among symptoms, gastric emptying and gastric myoelectrical activity (GMA) in patien...

The proper organization of the enteric nervous system (ENS) is critical for normal gastrointestinal (GI) physiology. Inflammatory bowel disease (IBD) dysregulates GI physiology, including bowel movements (motility), but in many IBD patients, GI motility disorders persist in remission through a poorly understood pathological process. Here we uncover...

Gastrointestinal immune cells, particularly muscularis macrophages (MM) interact with the enteric nervous system and influence gastrointestinal motility. Here we determine the human gastric muscle immunome and its changes in patients with idiopathic gastroparesis (IG). Single cell sequencing was performed on 26,000 CD45⁺ cells obtained from the gas...

The pathogenesis of irritable bowel syndrome (IBS) is multifactorial, characterized in part by increased intestinal permeability and visceral hypersensitivity. Increased permeability is associated with IBS severity and abdominal pain. Tenapanor is FDA-approved for the treatment of IBS with constipation (IBS-C) and has demonstrated improvements in b...

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 com...

Objective Autoantibodies are clinically useful in phenotyping patients with systemic sclerosis (SSc). Gastrointestinal (GI) function is regulated by the enteric nervous system (ENS) and commonly impaired in SSc, suggesting that the SSc autoimmune response may target ENS antigens. We sought to identify novel anti‐ENS autoantibodies with an aim to cl...

Background and aims We examined autoimmunity markers (AIMs) in patients with unexplained gastrointestinal symptoms, their relationship to joint hypermobility/hypermobility spectrum disorder (JH/HSD) and the response to intravenous immunoglobulin (IVIG). Methods The study comprised of three cohorts, consisting of adolescent or adult patients with g...

Background: Gastroparesis (GP) is characterized by delayed gastric emptying in the absence of mechanical obstruction. Objective: Genetic predisposition may play a role; however, investigation at the genome-wide level has not been performed. Methods: We carried out a genome-wide association study (GWAS) meta-analysis on (i) 478 GP patients from...

Objective Braak’s hypothesis states that Parkinson’s disease (PD) originates in the gastrointestinal (GI) tract, and similar associations have been established for Alzheimer’s disease (AD) and cerebrovascular diseases (CVD). We aimed to determine the incidence of GI syndromes and interventions preceding PD compared with negative controls (NCs), AD...

Introduction: Gastric emptying scintigraphy (GES) measures total gastric retention after a solid meal, and can assess intragastric meal distribution (IMD). Water load satiety test (WLST) measures gastric capacity. Both IMD immediately after meal ingestion (ratio of proximal gastric counts after meal ingestion to total gastric counts at time 0 [IMD...

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 com...

Unlabelled: : Patients with gastroparesis (Gp) not meeting nutritional needs orally, may need enteral nutrition (EN) or total parenteral nutrition (TPN). Among patients with gastroparesis, we aimed to: 1) Identify the frequency of EN and TPN use; and 2) Explore characteristics of patients with EN/TPN to those using oral nutrition (ON) including ch...

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 com...

Objective Up to 50% of patients with systemic sclerosis (SSc) experience slow colonic transit, which may be associated with severe outcomes. Our objective, therefore, was to identify specific clinical features associated with slow colonic transit in SSc. Methods SSc patients with gastrointestinal symptoms were prospectively enrolled and completed...

Background: RYGB surgery has significant weight loss and improvement in glycemia, attributed predominantly to duodenal exclusion. To mimic this effect non-invasively, we developed oral, gut-restricted, inert polymer (GLY-POL) that interacts with mucus in the proximal small intestine to form a dynamic barrier excluding the duodenal lining from lumin...

Background Patients with gastroparesis (GP) and functional dyspepsia (FD) have similar symptoms, but the pathophysiology of postprandial symptoms remains uncertain. Aims To compare symptoms and gastric myoelectrical activity (GMA) after liquid and solid test meals in patients with GP and FD. Methods Patients enrolled in the Gastroparesis Clinical...

Abstract We sought to quantify the characteristics of acid reflux episodes in patients with extraesophageal GERD symptoms (EES), hiatal hernia (HH), and erosive esophagitis (EroE) using multichannel intraluminal impedance pH (MII‐pH) and investigate the correlation between impedance parameters and high resolution esophageal manometry (HREM). This w...

Objectives: Gastroparesis is a common complication of systemic sclerosis (SSc). We sought to determine the degree of overlap between gastroparesis and dysmotility in other areas of the gut, correlate our findings with GI symptoms, and examine associations between gastroparesis and SSc features. Methods: Whole gut scintigraphy was performed on SS...

Objective Systemic sclerosis (SSc)–associated gastrointestinal (GI) complications are attributed to a variety of factors, including diet, microbiota dysbiosis, or GI transit abnormalities. Our objective was to examine the contribution of abnormal GI transit to SSc Medsger GI severity scores and/or University of California Los Angeles Scleroderma Cl...

Background Autoimmunity may play a role in the pathogenesis of gastroparesis in a subset of patients. Antinuclear antibody (ANA) testing is often used to screen for autoimmune disorders. Aims 1) Determine prevalence of a positive ANA in patients with gastroparesis; 2) Describe characteristics of idiopathic gastroparesis patients with positive ANA....

Background The use of domperidone (DOM), for gastroparesis (GP) remains controversial and limited. We aimed to present outcomes of DOM therapy for treatment of patients participating in the multicenter NIDDK Gastroparesis Clinical Research Consortium (GPCRC) Registries (GpR). Methods The GpCRC cohort consisted of GP (75%) and GP-like symptoms pati...

Background: Roux-en-Y gastric bypass surgery produces significant weight loss and improvement in T2D and insulin resistance, attributed predominantly to duodenal exclusion. To mimic this effect non-invasively, we developed an oral, gut-restricted, inert polymer (GLY-POL) that interacts with mucus in the proximal small intestine to form a dynamic ba...

Background The aim of this study was to clarify the pathophysiology of functional dyspepsia (FD), a highly prevalent gastrointestinal syndrome, and its relationship with the better-understood syndrome of gastroparesis. Methods Adult patients with chronic upper gastrointestinal symptoms were followed up prospectively for 48 weeks in multi-center re...

Background Understanding factors that impair quality of life (QOL) in gastroparesis is important for clinical management. Aims: (a) Determine QOL in patients with gastroparesis; (b) Determine factors that impair QOL. Methods Gastroparetic patientsAQ6 underwent history and questionnaires assessing symptoms (PAGI‐SYM and Rome III), QOL (SF‐36v2 and...

Background & Aims Constipation can be an important symptom in some patients with gastroparesis. The aims were to: 1) Determine prevalence of constipation and delayed colonic transit in patients with symptoms of gastroparesis; 2) Correlate severity of constipation to severity of symptoms of gastroparesis; and 3) Relate severity of constipation to GI...

Background The classic clinical picture of gastroparesis is a symptomatic patient losing weight. In addition, a number of patients with delayed gastric emptying are obese and/or gaining weight. Our aim was to investigate the factors impacting body weight in patients with idiopathic gastroparesis. Methods In patients with idiopathic gastroparesis,...

The enteric nervous system (ENS), a collection of neurons 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 embryonic neural crest and remains largely unchanged thereafter. Here, we show that the compos...

Acetylcholine induces robust electrogenic anion secretion in mammalian intestine and it has long been hypothesized that it mediates the epithelial response through the M3 and, to a lesser extent, the M1 muscarinic receptors in the mouse. However, nicotinic receptors have recently been identified in intestinal enterocytes by qRT-PCR/RNAseq, although...

Background & Aims The enteric nervous system (ENS) exists in close proximity to luminal bacteria. Intestinal microbes regulate ENS development, but little is known about their effects on adult enteric neurons. We investigated whether intestinal bacteria or their products affect the adult ENS via toll like receptors (TLRs) in mice. Methods We perfo...

Background: Macrophage-based immune dysregulation plays a critical role in development of delayed gastric emptying in diabetic mice. Loss of anti-inflammatory macrophages and increased expression of genes associated with pro-inflammatory macrophages has been reported in full thickness gastric biopsies from gastroparesis patients. Aim: We aimed t...

Background: The lymphatic system is involved in metastasis in pancreatic cancer progression. In cancer staging, lymphatic spread has been used to assess the invasiveness of tumor cells. However, from the endothelium's perspective, the analysis downplays the peri-lesional activities of lymphatic vessels. This unintended bias is largely due to the l...

Analysis of human pathology led Braak to postulate that α-synuclein (α-syn) pathology could spread from the gut to brain via the vagus nerve. Here, we test this postulate by assessing α-synucleinopathy in the brain in a novel gut-to-brain α-syn transmission mouse model, where pathological α-syn preformed fibrils were injected into the duodenal and...

Functional gastrointestinal disorders (FGIDs) are characterized by dysregulated gut-brain interactions. Emerging evidence shows that low-grade mucosal inflammation and immune activation contribute to FGIDs, including functional dyspepsia (FD). Stress plays an important role in the onset of FD symptoms. In human subjects with FD, presence of gastric...

Abstract Background Cellular changes described in human gastroparesis have revealed a role for immune dysregulation, however, a mechanistic understanding of human gastroparesis and the signaling pathways involved are still unclear. Methods Diabetic gastroparetics, diabetic non-gastroparetic controls, idiopathic gastroparetics and non-diabetic non-g...

Erratic blood glucose levels can be a cause and consequence of delayed gastric emptying in patients with diabetes. It is unknown if better glycemic control increases risks of hypoglycemia or improves hemoglobin A1c levels and gastrointestinal symptoms in diabetic gastroparesis. This study investigated the safety and potential efficacy of continuous...

This file includes Tables A, B, C, D, E, and F. (PDF)

This file includes Institutional Review Board approval information for each site. (PDF)

This file includes the initial study protocol dated August 12, 2009. (PDF)

This file includes the TREND checklist. (PDF)

This file includes the amended study protocol dated March 16, 2011. (PDF)

This file includes the amended study protocol dated April 16, 2013. (PDF)

Background & aims: Chronic pancreatitis (CP) is characterized by pancreatic inflammation and fibrosis, associated with increased pancreatic expression of transforming growth factor beta (TGFB). It is not clear how these might contribute to pain. We investigated whether TGFB signaling via SMAD induces sensitization of pancreatic sensory neurons to...

Introduction Individuals with diabetes are at increased risk for complications, including gastroparesis. Type 1 diabetes mellitus (T1DM) is an autoimmune disorder resulting in decreased beta-cell function. Glutamic acid decarboxylase-65 antibody (GADA) is the most commonly used test to assess autoimmunity while C-peptide level is used to assess bet...