Markus M. Lerch

Helicobacter pylori ( H. pylori ) infects the gastric epithelium of approximately half of the global population, and is a well-known risk factor for developing gastric cancer. Despite the clinical significance of H. pylori infection, many genetic factors that contribute to susceptibility remain unidentified. While it is well-established that H. pylori infection can result in gastritis and peptic ulcers, which may progress to gastric cancer, its causal link to other diseases remains unclear. We performed the genome-wide association study (GWAS) for anti- H. pylori IgG antibody titers, which were validated as a surrogate marker for H. pylori infection by the correlation with clinical traits, followed by gene-based and pathway analyses, involving up to 140,863 individuals. This included 56,967 in the discovery phase, and 68,211 in the replication phase from Japanese cohorts, and an additional 15,685 from European populations in a cross-ancestry meta-analysis. We reveal significant associations between H. pylori infection and polymorphisms in the Human Leukocyte Antigen (HLA) class II region within the Major Histocompatibility Complex (MHC), as well as genes related to innate immunity, including CCDC80 , NFKBIZ , TIFA , PSCA , and TRAF3 . Mendelian randomization (MR) analysis revealed that genetic liability to H. pylori infection has both positive and negative causal relationships with a variety of diseases, including autoimmune-related diseases such as Type 1 diabetes, Hashimoto’s disease, atopic dermatitis, as well as traits like body height and weight. These genetic findings strongly support the notion that genetic liability to H. pylori infection influences not only gastrointestinal diseases, but also a broader spectrum of health issues, thereby providing valuable insights for public health strategies and personalized medicine approaches.

INTRODUCTION: The exocrine pancreas is an important determinant of the intestinal microbiome composition and stability. Although chronic pancreatitis (CP) is known to severely affect the bacterial community, its impact on the intestinal mycobiome is currently unknown. METHODS: A total of 93 patients with clinical and imaging evidence of CP were prospectively recruited and compared with 2 equally sized matched control cohorts. One control group was matched for age, sex, body mass index, and smoking (Con-1), and the other additionally for exocrine pancreatic function (stool elastase) and diabetes (Con-2). Fecal samples were collected from all 279 individuals to determine the fecal mycobiome by internal transcribed spacer 2 sequencing. RESULTS: In CP patients, fungal reads were increased (3.7-fold and 2.0-fold) as compared with Con-1 and Con-2. In comparison with Con-1, CP patients demonstrated higher total abundance of Candida (4.5-fold, q = 0.009) and higher mean relative abundance (11.4% vs 1.0%, q = 0.014) and presence (25.8% vs 9.7%, q = 0.025) of Nakaseomyces. In contrast to Con-2, CP patients showed higher Candida total abundance (1.9-fold, P = 0.016) which was, however, not significant after correction for multiple testing (q = 0.056). DISCUSSION: Not only the microbiome but also the mycobiome in CP patients is characterized by distinct changes, with higher abundances of Candida or Nakaseomyces. Exocrine pancreatic dysfunction in CP patients likely contributes to this observation. This may result in increased rates of fungal infections, chronic inflammation, and could be contributing to the development of pancreatic cancer.

Zusammenfassung „Die Grenzen der Inneren Medizin“ bildeten das Kongressmotto des 128. Internistenkongresses im Jahr 2022 in Wiesbaden. In seiner Präsidentenrede ging Prof. Lerch auf vier Aspekte dieses Mottos ein: ärztliches Handeln am Lebensende, Lektionen aus der Coronapandemie, Defizite in der Digitalisierung des deutschen Gesundheitswesens und der deutsche Sonderweg beim Datenschutz in der Medizin. Anhand von Daten aus Kanada, der Schweiz und den Niederlanden, in denen Sterbehilfe praktiziert wird, appellierte Prof. Lerch an Internistinnen und Internisten – v. a. hausärztlich tätige –, sich nach dem Urteil des Bundesverfassungsgerichtes intensiv mit dieser Thematik auseinanderzusetzen. Mit Blick auf die Entwicklungen der Coronapandemie diskutierte er Gründe der fehlenden Impfbereitschaft in Teilen der Gesellschaft sowie die Frage, warum v. a. nicht klinisch tätige und kaum patientenversorgende Fächer die Diskussion um Coronaschutzmaßnahmen in Deutschland geprägt haben. Ein weiterer Schwerpunkt der Rede war die unzureichende Digitalisierung des deutschen Gesundheitswesens, das im Hinblick auf seine digitale Transformation im internationalen Vergleich deutlich zurückliegt. Ärztinnen und Ärzte müssten sich stärker in die digitale Transformation einbringen, um das Gesundheitswesen zum Wohle der Patienten umzugestalten. Der deutsche Sonderweg bei der Auslegung der Datenschutz-Grundverordnung (DSGVO) bedarf einer gesetzlichen Regelung, die eine pragmatische und fortschrittliche Nutzung von Patientendaten für die Krankenversorgung und die medizinische Forschung erlaubt.

Objective Changes of the pancreaticobiliary ducts herald disease. Magnetic resonance cholangiopancreatography (MRCP) allows accurate duct visualisation. Data on reliable upper reference ranges are missing. Design Cross-sectional whole body MRI data from the population-based Study of Health in Pomerania were analysed. The width of the common bile duct (CBD) and the pancreatic duct (PD) was determined. We aimed to describe the distribution of physiological duct diameters on MRCP in a population of healthy subjects and to identify factors influencing duct size. Results After excluding pre-existing pancreaticobiliary conditions, CBD and PD diameters from 938 and 774 healthy individuals, respectively, showed a significant increase with age (pConclusions This is the first population-based study delineating age-adjusted upper reference limits of CBD and PD on MRCP. We showed that up to 18.2% of healthy volunteers would have needed diagnostic workup, if the conventional reference values were used. The utilisation of the adapted reference levels may help to avoid unnecessary investigations and thus to reduce healthcare expenditure and test-related adverse events.