Freising, Germany

Annual Meeting German Society of Neurogastroenterology & Motility (DGNM)

We would like to draw your attention to the next German annual meeting in Freising, which, in addition to a varied programme, has a special highlight in store:

On the occasion of the upcoming retirement of Thomas Frieling, long-time DGNM member and founder of the Neurogastroenterology Foundation, we are presenting a high-calibre international symposium in Freising. International companions of Thomas will present their research findings and perspectives on neurogastroenterology, including Hannah Carey, Maggy Curras, David Grundy, Jeff Palmer, Jan Tack and Paul Wade. This symposium is designed as a surprise for Thomas Freiling, which is why he is not aware of it yet. The detailed programme can be found on the website of our European umbrella organisation, the ESNM.

Interested participants still have time until Sunday, 31 December 2023, to submit their abstracts for the next annual conference. As a specialist society affiliated with the German Society for Gastroenterology, Digestive and Metabolic Diseases (DGVS), we would like to encourage young doctors and researchers in particular to present their results and take the opportunity for intensive networking - the abstract portal is open.

International Symposium

Presentations at the Symposium on
“Neurogastroenterology - 20 years Foundation of Neurogastroenterology”

  1. David Grundy, Sheffield, U.K.
    Title: The Birth of Neurogastroenterology.
  2. Fievos Christofi, Columbus, USA
    Title: Use of Human Gut Samples in Translational Neurogastroenterology
  3. Jan Tack, Leuven, Belgium
    Title: Relation between Pathophysiology and Symptoms in Functional Dyspepsia
  4. Paul Wade, Philadelphia, USA
    Title: Drug Discovery in Functional Gut Diseases
  5. Jeffrey Palmer, Philadelphia, USA
    Title: Enteric Host-Parasite Interactions: Models for Exploring Mechanisms of Inflammation and Neuroimmune Interactions in Bowel Disorders
  6. Magarita Curras-Collazo. Riverside, USA
    Title: Microbiota-Gut-Brain Interactions May Contribute to Pathophysiology in Chronic Multi-Symptom Illness
  7. Hannah Carey, Sacramento, USA
    Title: Sharing Resources During Lean Times: How Hibernators and their Gut Symbionts Work Together During Winter Fasting


DGNM is looking forward to meeting you!


The Birth of Neurogastroenterology. David Grundy

I graduated in physiology from the University of London where I had the privilege to being lectured to by Andrew Huxley and Bernard Katz. They had each received the Nobel Prize for their work in neurophysiology. It was there I developed an interest in electrophysiology which I pursued during my PHD with Joe Davison in Dundee. My project was to record afferent and efferent nerve traffic passing along the vagus nerve to the gastrointestinal track. Back then this was a pretty niche subject and I more or less had the field to myself. Unlike now where the vagus is a "hot" topic implicated as a superhighway for mind-gut communication regulating not only GI function but mood, depression, eating behaviour and inflammation.

After moving to Sheffield I teamed up with Nick Read, a clinical gastroenterologist, and we started to apply basic science understanding to clinical investigations. At the time the focus was on gut motility related issues because it was possible to record gut contractile activity and neural signalling in real time. The research circles that we moved in were related to GI motility and enteric neuroscience. Nick and I had published a book with Blackwell's publishers and in the 1980. We were sounded out by Peter Saugman,  their commissioning editor, about the possibility of establishing a Journal of Gastrointestinal Motility. We were enthusiastic about this because we lacked a natural home for our papers. Basic science went to physiology and pharmacology journals while clinical science went to Gut or Gastroenterology. Having both under one "roof" was appealing and the journal was launched in 1989, with Nick as clinical editor and me covering the basic science. At the time we hadn't anticipated the political minefield we had stepped into. This was finally resolved when Juan Malagelada became the chair of the editorial board and brokered a deal with the American and European GI motility working groups joining the editorial board. At that time they weren't formal societies, but loosely affiliated around a biannual meeting. With a journal to get behind the societies became formalised and the journal their official journal.

Even at the outset it was apparent that GI motility didn't encompass the breadth of the field. GI secretions, hormones, blood flow, immune function all fell under the umbrella. So when David Wingate took over from Nick Read as clinical editor, we took the opportunity to canvass opinion on a change of name. Enteric Neurology was discussed as an option but deemed too narrow. Neurogastroenteroly, proposed by David Wingate, was the clear favourite and so it was in 1994, the journal of GI motility became Neurogastroenterology and Motility, motility was retained as a link to its history. The societies followed suit with American, European and International Neurogastroenterolgy and Motility Societies, with many more regional socities doing the same. The "Arbeitskreis Gastrointestinale Moiutlität" founded by Martin Weinbeck in 1981 became the German Society of Neurogastroenterology and Motility. Around this time the "Little Brain Big Brain" group of young investigators was also getting going led by Michael Schemann and Paul Enck and still thrives today. Thomas Freiling was at the inaugural meeting of LBBB and is where he and I first met. Tom subsequently established a charity and young investigator prize, Stiftung für Neurogastroenterologie in 2004 and there have now been 19 recipients of the award, recognised as rising stars who, Tom has helped along the way.

Neurogastroenterology is now a dynamic community with societies, journals, working groups and Institutes all operating under its name, with twitter feed and facebook bringing it into the realm of social media. It has been a privilege and joy to see the field evolve to become the dynamic one it has become today.


Relation between pathophysiology and symptoms in functional dyspepsia. Jan Tack,

Functional dyspepsia (FD), a disorder thought to originate from the gastroduodenum, is one of the most prevalent functional gastrointestinal disorders. According to the Rome IV consensus, FD is subdivided into epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS). PDS is characterized by postprandial fullness and early satiation) while EPS is characterized by epigastric pain and burning.

The underlying pathophysiology of functional dyspepsia is probably multifactorial, involving multiple mechanisms. Traditional views have implicated disordered gastric sensorimotor function, more in particular visceral hypersensitivity, delayed gastric emptying and impaired gastric accommodation in the pathophysiology of FD. These abnormalities are all present in a subset of patients, show some association with the symptom pattern and have been used as therapeutic target. Nevertheless, targeting these abnormalities has generated limited progress in clinical management and the origin of these alterations remained unclarified.

More recent studies have unraveled low-grade inflammatory changes in the duodenum, with increased numbers of mast cells and eosinophils, and increased mucosal permeability, in FD. These findings are associated with PDS symptoms.. How low-grade inflammation may lead to gastric sensorimotor dysfunction, and how it can be targeted therapeutically is a topic of ongoing research. In addition, cognitive-affective processes including anticipation of pain and its associated anxiety interfere with pain modulatory mechanisms in the brain in FD, leading to increased pain sensitivity and symptom levels. The basis for these duodenal changes is unclear, but candidate mechanisms are duodenal acid exposure, bile acid exposure, stress, reactions to food allergens and changes in duodenal microbiota

Recent studies have focused on food as a trigger of FD symptoms, acting through increased mucosal permeability in the duodenum to trigger local immune activation via an IgE-independent pathway, with modulation through duodenal acid exposure, the bile salt pool and an altered duodenal microbiota composition. Ongoing research evaluates mucosal integrity, low-grade inflammation, diet and microbiota as targets for novel therapeutic interventions.


Drug discovery in functional gut disorders. Paul Wade

Significant advances in the basic biology of regulatory systems involved in ordered gastrointestinal motility and secretion (e.g. the enteric nervous system, interstitial cells of Cajal, sensory pathways, neuroimmune interactions, etc.) have been made over the past 20 years.  Conversely, successes in the applied sciences of discovery and development of novel drugs for the treatment of functional gastrointestinal disorders (FGIDs) have been somewhat limited.  This status quo exists from one end of the gut to the other.  Thus, patients with esophageal motility disorders are frequently treated with calcium channel blockers, smooth muscle relaxants, anticholinergics, and antianxiety medications; however, none of these drugs were discovered in the past 20 years and a novel drug for the treatment of esophageal motility disorders has not been approved.  There is significant overlap in the signs and symptoms of gastroesophageal reflux disease (GERD) with functional dyspepsia (FD), and although there is no currently approved medicine to treat FD, four drugs have been approved over the past 20 years to treat GERD, yet two of the three are combination products including omeprazole, the proton pump-inhibiting drug discovered in 1978 and first approved in 1988.  Drugs used to treat nausea and vomiting include the class of NK1/Substance P antagonists, the first of which was approved by the FDA in 2003 and the transdermal patch reformulation of granisetron, a selective 5-HT3 antagonist discovered in 1985.  Drug discovery for the treatment diarrhea over the past 20 years has run the gamut from antibiotics (rifaximin, 2004) to vaccines (Rotarix, 2008), to fecal microbiota spores (Vowst, 2023); however only two drugs are approved to treat diarrhea-predominate irritable bowel syndrome (IBS-D):  rifaximin and the mixed opioid (µ- and κ- agonist/δ – antagonist) eluxadoline.  Constipation in various FGIDs (including, e.g. chronic idiopathic constipation, IBS-C, opioid-induced constipation) can now be treated with medicines discovered and developed largely in the last two decades.  In addition to the 5-HT4 agonist prucalopride (a drug discovered last century, EMA-approved in 2009, and FDA-approved in 2018), other drug discovery targets e.g., opioid receptors, epithelial guanylate cyclase, and the sodium-proton antiporter NHE3 have been developed into treatments for constipation in FGIDs.

Reasons for this relatively slow pace of drug discovery and development in FGIDs are many and varied, but include:  multifaceted pathophysiology such that targeting a single gene product in discovery results in lack of efficacy in clinical development;  challenges related to animal models used in discovery;  missteps in clinical trial design;  regulatory decisions not always rooted in good science;  the fickle nature of pharmaceutical drug development; and the perception by developers and regulators that FGIDs are not real diseases or are ‘only’ quality of life disorders.  Three drugs will serve as examples of such hurdles in bringing novel, safe and effective medicines to physicians for the treatment of FGIDs in their patients - from drug discovery (eluxadoline) to drug development (felcisetrag), to expanding access (prucalopride approval in the US).


Enteric host-parasite interactions: Models for exploring mechanisms of inflammation and neuroimmune interactions in bowel disorders. Jeffrey Palmer

Enteric helminths have a significant impact on the structure, function, and neural control of the gastrointestinal (GI) tract of the host. Interactions between the host's nervous and immune systems redirect activity in neuronal circuits intrinsic to the gut into an alternative repertoire of defensive and adaptive motor programs. Gut inflammation and activation of the enteric neuroimmune axis play integral roles in the dynamic interaction between host and parasite that occurs at the mucosal surface. Three inter-related themes underscore the pivotal role that neural control mechanisms play in the host's GI tract functional responses to enteric parasitism: 1) signaling molecules of both parasite and host origin can reorient the dynamic ecology of enteric host-parasite interactions; 2) altered gut propulsive and secretomotor reflex activities occur during enteric parasitic infections and the emerging picture indicates that intrinsic nerves help facilitate and orchestrate long-term functional reorganization of the parasitized gut; 3) enteric parasitism has a significant impact on nerve cell function and neurotransmission pathways in both the enteric and central nervous systems of the host (ie, the gut-brain axis). Complex multi-layered mechanisms underly the integrative neuroimmunophysiological responses to the presence of both invasive and noninvasive enteric helminths. The focus of our work for many years has been to explore the effects of inflammation and immunity on enteric nervous system function and behavior during and after infection with the nematode parasite, Trichinella spiralis. Results obtained from studies with this experimental model have demonstrated significant changes in electrical and synaptic behavior, neuro-immune signaling pathways, the occurrence of excitation-transcription coupling, and activation of a key intracellular second messenger signaling pathway in enteric neurons during host-parasite interactions. Taken together, the results provide an opportunity to develop a unifying mechanistic algorithm as the basis for further elucidation of the integrative interactions between hosts and parasites in the GI tract.


Microbiota-Gut-Brain Interactions May Contribute to Pathophysiology in Chronic Multi-Symptom Illness. Margarita Curras-Collazo.

Thirty years after the Persian Gulf War veterans continue to suffer from Gulf War Illness (GWI) characterized by cognitive deficit, fatigue and gastrointestinal problems. Using a mouse model that manifests these varied symptoms after exposure to Gulf War agents, our lab has reported impaired learning/memory, exercise intolerance, metabolic disturbance, gut dysbiosis and deregulation of neuroinflammatory genes, suggesting a possible microbiota-gut-brain interaction in GWI pathology (Kozlova et a., 2022a; 2022b). Subsequent study showed concomitant brain and gut proinflammatory profiles. More recently, we tested the hypothesis that probiotic treatment (P) prevents GWI symptoms. Adult male C57Bl/6N mice were separated into 4 groups (n=16/group): GW group was exposed to 8.7 mg/kg/d pyridostigmine bromide (PB) in saline (po, 150uL/30g bw), 1.3 mg/kg PER in 100% DMSO, and 33% DEET in 70% EtOH for 28 d (5 d/wk). CON/S group received vehicle. All groups received restraint stress (5 min/d, 28 d). CON/S+P and GW+P groups were treated with a gut-protective probiotic (P) cocktail of L. reuteri, L. rhamnosus, L. casei, B. longum (po, 108 CFU/mL, 3 times/wk) for 2 wk prior to and during GW agent treatment and until sacrifice 5 months later. Fecal RT-qPCR showed colonization of all strains except L. rhamnosus after 6-7 doses when compared to saline sham. Colonization after GW agent exposure was strain-specific and varied with time post exposure.

On an exercise endurance (EE) test GW (but not GW+P) mice tired faster relative to CON/S at PT56 (p<0.05) but not at PT150. Repeat testing on the passive avoidance apparatus (15 wk after previous test) showed that GW but not GW+P mice displayed reduced latency to enter aversive chamber on day 1 of acquisition trials, indicating deficient memory (p<0.05). Depressive-like behavior (mean percent time spent mobile) on tail suspension test (TST) was significantly lower for GW (p<0.05) but not GW+P mice at PT50 (but not at PT150). Probiotics protected against the GW-induced rise in liver C-reactive protein (CRP) (p<0.05) and brain interleukin-6 (IL-6) (p<0.05). Immunofluorescence probing in the hippocampal CA1 and dentate gyrus showed significantly greater count of Iba-1 positive cells in GW (but not GW+P) vs CON/S (p<0.05). NeuN immunostaining on the same sections showed abnormal neuronal phenotype characterized by stain-free loci in nuclei, indicative of reorganized RNA. In the gut, M1 proinflammatory macrophages appeared to be more abundant in GW (but not GW+P) vs CON/S (p<0.05). Ongoing experiments are designed to explore the effect of deafferentation of gut nerve fibers in the vagus nerve. In combination, our findings indicate that GW mice can be used to model exercise fatigue, cognitive deficit and mood alterations found in multi-symptom illness and suggest that underlying pathophysiology may involve gut and central neuro-inflammation. Importantly, microbiota may contribute since GW agents produce dysbiosis and probiotic treatment protects against all GWI symptom domains, suggesting potential therapeutic benefit of probiotic therapy in chronic illness. Further study is needed to uncover physiological pathways through which the microbiota-gut-brain axis impacts gut and brain health in toxicant-induced challenge. Supported by Department of Defense grant W81XWH-19-1-0802


Sharing Resources During Lean Times: How Hibernators and their Gut Symbionts Work Together During Winter Fasting. Hannah Carey


Abundant fat stores and metabolic plasticity enable mammalian hibernators to cease feeding during seasons when food is scarce and low temperatures increase energy demands. However, prolonged fasting markedly alters the gut environment both structurally and functionally, with implications for the hibernator hosts, their microbiotas, and the symbiotic relationship between the two. This presentation uses hibernation to explore tasks that still need doing when guts are “on holiday”, away from their typical jobs processing and absorbing food. We’ll touch on key epithelial functions that are retained despite mucosal atrophy; the maintenance of intestinal barrier function; the remodeled intestinal immune system; how the food-free winter environment reshapes the microbiota, and how some microbes collaborate with their hibernating hosts to recycle urea nitrogen, promoting protein synthesis when dietary nitrogen is absent. Pathways by which this natural system readily adapts to alternating periods of normal feeding and extended fasting, which also occurs in species like migrating whales and breeding penguins, may lead to therapeutic interventions in pathologic states when the gut of continuous feeders (such as humans) is deprived of enteral nutrition for prolonged periods of time.


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