Markus Gerhard

• Professor
• Deputy Director at Technical University of Munich

Helicobacter pylori γ-glutamyltransferase (gGT) is a virulence factor that promotes bacterial colonization and immune tolerance. Although some studies addressed potential functional mechanisms, the supportive role of gGT for in vivo colonization remains unclear. Additionally, it is unknown how different gGT expression levels may lead to compensator...

Introduction: Immunomodulating effects of Helicobacter pylori (H. pylori) have been shown to inhibit antitumor immunity. Resistance to immune checkpoint inhibitor (ICI)-based therapies is common among patients with hepatocellular carcinoma (HCC). This study aimed to assess the effect of H. pylori on the outcomes of ICI in patients with HCC. Methods...

Kidney transplantation (KT) is the best treatment for end-stage kidney disease, with graft survival critically affected by the recipient's immune response. The role of the gut microbiome in modulating this immune response remains underexplored. Our study investigates how microbiome alterations might associate with allograft rejection by analyzing t...

Gastric cancer is a leading cause of cancer-related deaths in China. Affecting more than 40% of the world’s population, Helicobacter pylori is a major risk factor for gastric cancer. While previous clinical trials indicated that eradication of H. pylori could reduce gastric cancer risk, this remains to be shown using a population-based approach. We...

Objective Screening and early diagnosis of gastric cancer (GC) are crucial for improved prognosis. However, gastroscopic screening is not feasible in large populations due to its high cost and invasive nature. The detection of circulating cell‐free DNA (cfDNA) provides an attractive minimally‐invasive alternative for screening of GC. In this system...

Background: Kidney transplantation (KT) is the optimal treatment for end-stage kidney disease, with graft survival critically affected by the recipient's immune response. The role of the gut microbiome in modulating this immune response remains underexplored. Our study investigates how microbiome alterations might associate with allograft rejection...

Helicobacter pylori gamma;-glutamyltransferase (gGT) is a virulence factor that promotes bacterial colonization and immune tolerance. Although some studies addressed potential functional mechanisms, the supportive role of gGT for in-vivo colonization remains unclear. Additionally, it is unknown how different gGT expression levels may lead to compen...

Somatic mutations in the tumor suppressor Ring finger protein 43 (RNF43) were frequently found in colitis-associated cancer (CAC) and related to the duration of chronic inflammation, but their significance in inflammation and inflammation-associated carcinogenesis remained elusive. We assessed the onset of RNF43 mutations at different stages of hum...

Infecting about half of the world´s population, Helicobacter pylori is one of the most prevalent bacterial infections worldwide and the strongest known risk factor for gastric cancer. Although H. pylori colonizes exclusively the gastric epithelium, the infection has also been associated with various extragastric diseases, including colorectal cance...

Effective screening and early detection are critical to improve the prognosis of gastric cancer (GC). Our study aims to explore noninvasive multianalytical biomarkers and construct integrative models for preliminary risk assessment and GC detection. Whole genomewide methylation marker discovery was conducted with CpG tandems target amplification (C...

Objectives: Early diagnosis is important in controlling Helicobacter pylori-induced gastritis and progression to gastric malignancy. Serological testing is an efficient non-invasive diagnostic method, but currently does not allow differentiation between active and past infections. To fill this diagnostic gap we investigated the diagnostic value of...

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide. While a close correlation between chronic Helicobacter pylori infection and CRC has been reported, the role of the virome has been overlooked. Here, we infected Apc-mutant mouse models and C57BL/6 mice with H. pylori and conducted a comprehensive metagenomics analysis...

Mammalian cells synthesize the antioxidant glutathione (GSH) to shield cellular biomolecules from oxidative damage. Certain bacteria, including the gastric pathogen Helicobacter pylori, can perturb host GSH homeostasis. H. pylori infection significantly decreases GSH levels in host tissues, which has been attributed to the accumulation of reactive...

ABSTRACT Metabolites and their interactions with microbiota may be involved in Helicobacter pylori-associated gastric lesion development. This study aimed to explore metabolite alterations upon H. pylori eradication and possible roles of microbiota-metabolite interactions in progression of precancerous lesions. Targeted metabolomics assays and 16S...

Objective: Helicobacter pylori infection is the most prevalent bacterial infection worldwide. Besides being the most important risk factor for gastric cancer development, epidemiological data show that infected individuals harbour a nearly twofold increased risk to develop colorectal cancer (CRC). However, a direct causal and functional connection...

The gram-negative bacterium Helicobacter pylori is the most common chronic bacterial infection and the main cause of gastric cancer. Due to the increasing antimicrobial resistance of H. pylori, the development of an efficacious vaccine is a valid option to protect from disease or infection and ultimately prevent gastric cancer. However, despite mor...

Helicobacter pylori has developed several strategies using its diverse virulence factors to trigger and, at the same time, limit the host’s inflammatory responses in order to establish a chronic infection in the human stomach. One of the virulence factors that has recently received more attention is a member of the Helicobacter outer membrane prote...

The ability of antibodies to neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important correlate of protection. For routine evaluation of protection, however, a simple and cost-efficient anti-SARS-CoV-2 serological assay predictive of serum neutralizing activity is needed. We analyzed clinical epidemiological data and...

Helicobacter pylori is a prevalent pathogen, which affects more than 40% of the global population. It colonizes the human stomach and persists in its host for several decades or even a lifetime, if left untreated. The persistent infection has been linked to various gastric diseases, including gastritis, peptic ulcers, and an increased risk for gast...

Background & aims: Infection with Helicobacter pylori strongly impacts global health by causing chronic gastritis, ulcer disease and gastric cancer. Although extensive research into the strong immune response against this persistently colonizing bacterium exists, the specific role of CD8+ T cells remains elusive. Methods: We comprehensively char...

Persistent chemosensory dysfunction (PCD) is a common symptom of long-COVID. Chemosensory dysfunction (CD) as well as SARS-CoV-2-specific antibody levels and CD8+ T-cell immunity were investigated in a cohort of 44 healthcare workers up to a median of 721 days after a positive PCR test. CD was assessed using questionnaires and psychophysical screen...

Helicobacter (H.) pylori -induced gastritis is a risk factor for gastric cancer (GC). Deleted-in-liver-cancer-1 (DLC1/ARHGAP7) inhibits RHOA, a downstream mediator of virulence factor cytotoxin-A (CagA) signalling and driver of consensus-molecular-subtype-2 diffuse GC. DLC1 located to enterochromaffin-like and MIST1+ stem/chief cells in the stomach...

The understanding of gut virome and its role in Helicobacter pylori-driven colorectal cancer (CRC), as well as the long-term impact of H. pylori eradication via antibiotic treatment on it could contribute to better understanding the mechanisms of the disruption of gut bacteriome homeostasis involved in H. pylori-driven colorectal carcinogenesis and...

OBJECTIVE H. pylori infection is the most prevalent bacterial infection worldwide. Besides being the most important risk factor for gastric cancer development, epidemiological data show that infected individuals harbor a nearly two-fold increased risk to develop colorectal cancer (CRC). However, a direct causal and functional connection between H....

Background COVID-19 has so far affected more than 250 million individuals worldwide, causing more than 5 million deaths. Several risk factors for severe disease have been identified, most of which coincide with advanced age. In younger individuals, severe COVID-19 often occurs in the absence of obvious comorbidities. Guided by the finding of cytome...

Helicobacter pylori infection induces a number of pro-inflammatory signaling pathways contributing to gastric inflammation and carcinogenesis and has been identified as a major risk factor for the development of gastric cancer (GC). Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling mediates immune regulatory process...

Background: Murine Helicobacter species have gained increasing awareness in mouse facilities over the last years. Infections with Helicobacter species may have an impact effect on the health of mice and might pose a zoonotic risk to researchers. To minimize the interference with experiments and hence contribute to the 3Rs, a reliable method of mon...

Anti-viral immunity continuously declines over time after SARS-CoV-2 infection. Here, we characterize the dynamics of anti-viral immunity during long-term follow-up and after BNT162b2 mRNA-vaccination in convalescents after asymptomatic or mild SARS-CoV-2 infection. Virus-specific and virus-neutralizing antibody titers rapidly declined in convalesc...

Background: COVID-19 has so far affected more than 250 million individuals worldwide, causing more than 5 million deaths. Several risk factors for severe disease have been identified, most of which coincide with advanced age. In younger individuals, severe COVID-19 often occurs in the absence of obvious comorbidities. Guided by the finding of cytom...

Background Molecular features underlining the multistage progression of gastric lesions and development of early gastric cancer (GC) are poorly understood, restricting the ability to GC prevention and management. Methods We portrayed proteomic landscape and explored proteomic signatures associated with progression of gastric lesions and risk of ea...

T cell immunity is crucial for the control of SARS-CoV-2 infections and has been widely studied on a quantitative level. However, quality of responses, in particular of CD8⁺ T cells, has only been marginally investigated so far. Here, we isolate T cell receptor (TCR) repertoires specific for immunodominant SARS-CoV-2 epitopes restricted to common H...

Deficiencies in smell and taste are common symptoms of COVID-19. Quantitative losses are well surveyed. This study focuses on qualitative changes such as phantosmia (hallucination of smell), parosmia (alteration of smell), and dysgeusia (alteration of taste) and possible connections with the adaptive immune system. Subjective experience of deficien...

Helicobacter pylori is the most prevalent bacterial infection, affecting half of the world's population, with a high morbidity and mortality rate.1,2 Several invasive and noninvasive testing procedures are available, and their selective use serves the specific needs of diverse clinical scenarios. For gastric cancer prevention, mass screening is nec...

The gastric pathogen Helicobacter pylori infects half of the world’s population and is a major risk factor for gastric cancer development. In order to attach to human gastric epithelial cells and inject the oncoprotein CagA into host cells, H. pylori utilizes the outer membrane protein HopQ that binds to the cell surface protein CEACAM, which can b...

T cell immunity is crucial for the control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and has been widely characterized on a quantitative level. In contrast, the quality of such T cell responses has been poorly investigated, in particular in the case of CD8+ T cells. Here, we explored the quality of SARS-CoV-2-specif...

Infection with the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is controlled by the host´s immune response1-4, but longitudinal follow-up studies of virus-specific immunity to evaluate protection from re-infection are lacking. Here, we report the results from a prospective study that started during the first wave of the COVID-19 pa...

In this study, we analyzed NoV evolution in sequential samples of 6 chronically infected patients. The capsid gene was amplified from stool samples and deep sequencing was performed. The role of amino acid flexibility in structural changes and ligand binding was studied with molecular dynamics (MD) simulations. Concentrations of capsid-specific ant...

State-subsidized programs develop medical data integration centers in Germany. To get infection disease (ID) researchers involved in the process of data sharing, common interests and minimum data requirements were prioritized. In 06/2019 we have initiated the German Infectious Disease Data Exchange (iDEx) project. We have developed and performed an...

In addition to Helicobacter pylori (H.pylori), gastric microbiota may be involved in carcinogenesis process. However, the longitudinal study to assess changes in the gastric microbiota associated with the development of gastric carcinogenesis is still limited. The aim of this study is to explore dynamic microbial alterations in gastric cancer (GC)...

Background & Aims RING finger protein 43 (RNF43) is a tumor suppressor that frequently is mutated in gastric tumors. The link between RNF43 and modulation of WNT signaling has not been shown clearly in the stomach. Because mutations in RNF43 are highly enriched in microsatellite-unstable gastric tumors, which show defects in DNA damage response (DD...

HopQ is an outer-membrane protein of Helicobacter pylori that binds to human carcinoembryonic antigen-related cell-adhesion molecules (CEACAMs) with high specificity. We aimed to investigate fluorescence targeting of CEACAM-expressing colorectal tumors in patient-derived orthotopic xenograft (PDOX) models with fluorescently labeled recom-binant Hop...

Background: Asymptomatic C. difficile colonization is believed to predispose to subsequent C. difficile infection (CDI). While emerging insights into the role of the commensal microbiota in mediating colonization resistance against C. difficile have associated CDI with specific microbial components, corresponding prospectively collected data on co...

Background and Aims Reg3 lectins are antimicrobial peptides at mucosal surfaces of the gut, whose expression is regulated by pathogenic gut microbes via IL-22- or TLR signaling. In addition to antimicrobial effects, tissue protection is hypothesized, but poorly investigated in the gut. Methods We applied antibiotic-induced microbiota perturbatio...

BACKGROUND AND AIMS: Reg3 lectins are antimicrobial peptides at mucosal surfaces of the gut, whose expression is regulated by pathogenic gut microbes via IL-22- or TLR signaling. In addition to antimicrobial effects, tissue protection is hypothesized, but poorly investigated in the gut. METHODS: We applied antibiotic-induced microbiota perturbation...

Attachment to the host gastric mucosa is a key step in Helicobacter pylori infection. Recently, a novel adhesin, HopQ, was shown to bind distinct host CEACAM proteins—an interaction that was found to be essential for the translocation of CagA, a key virulence factor of H. pylori. The HopQ–CEACAM1 co-crystal structure revealed a binding mode depende...

Objective Gastrointestinal microbiota may be involved in Helicobacter pylori- associated gastric cancer development. The aim of this study was to explore the possible microbial mechanisms in gastric carcinogenesis and potential dysbiosis arising from H. pylori infection. Design Deep sequencing of the microbial 16S ribosomal RNA gene was used to in...

Vaccination is the most effective method to prevent infectious diseases. However, approaches to identify novel vaccine candidates are commonly laborious and protracted. While surface proteins are suitable vaccine candidates and can elicit antibacterial antibody responses, systematic approaches to define surfomes from gram-negatives have rarely been...

Noroviruses (NoV) cause the majority of non-bacterial gastroenteritis cases worldwide, with genotype II.4 being the most common. The aim of our study was to quantitate norovirus-specific IgG in immunocompromised patients before and after laboratory-confirmed norovirus infection. A quantitative ELISA was developed by coating ELISA plates with recomb...

Helicobacter pylori colonizes the stomach of around 50% of humans. This chronic infection can lead to gastric pathologic conditions such as gastric ulcers and gastric adenocarcinomas. The strong inflammatory response elicited by H. pylori is characterized by the induction of the expression of several cytokines. Among those, IL-18 is found highly up...

Helicobacter pylori chronically colonizes the stomach and is strongly associated with gastric cancer. Its concomitant occurrence with helminths such as schistosomes has been linked to reduced cancer incidence, presumably due to suppression of H. pylori-associated pro-inflammatory responses. However, experimental evidence in support of such a causal...

Helicobacter pylori infection induces a number of pro-inflammatory signaling pathways contributing to gastric inflammation and carcinogenesis. Among those, NF-κB signaling plays a pivotal role during infection and malignant transformation of the gastric epithelium. However, deficiency of the adaptor molecule myeloid differentiation primary response...

The E3 ubiquitin ligase ring finger protein 43 (RNF43) is frequently mutated in gastric tumors and loss of RNF43 expression was suggested to be one of the key events during the transition from adenoma to gastric carcinoma. Functional studies on RNF43 have shown that it acts as a tumor suppressor by negatively regulating Wnt signaling. Interestingly...

We previously showed that the colorectal cancer colonizing bacterium Fusobacterium nucleatum protects tumors from immune cell attack via binding of the fusbacterial Fap2 outer-membrane protein to TIGIT, a checkpoint inhibitory receptor expressed on T cells and NK cells. Helicobacter pylori, the causative agent for peptic ulcer disease, is associate...

Ring Finger Protein 43 (RNF43) is an E3 ubiquitin ligase that has been described to be frequently mutated in gastrointestinal cancers. RNF43 downregulation was associated with distant metastasis, TNM stage and poorer survival in patients with gastric and colorectal cancers. Functional analysis has shown that overexpressed RNF43 negatively regulates...

Eradication of Helicobacter pylori has been found to be effective for gastric cancer prevention, but uncertainties remain about the possible adverse consequences such as the potential microbial dysbiosis. In our study, we investigated the association between gut microbiota and H. pylori-related gastric lesions in 47 subjects by deep sequencing of m...

The human gastric pathogen Helicobacter pylori is a major causative agent of gastritis, peptic ulcer disease, and gastric cancer. As part of its adhesive lifestyle, the bacterium targets members of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family by the conserved outer membrane adhesin HopQ. The HopQ-CEACAM1 interaction i...

Background Clostridium difficile infection (CDI) is a major cause of hospital-acquired diarrhea. Secondary bile acids were shown to confer resistance to colonization by C. difficile. 7α-dehydroxylation is a key step in transformation of primary to secondary bile acids and required genes have been located in a single bile acid-inducible (bai) operon...

Reproducibility of 16S rDNA copy number density by rtPCR. S1A Fig: A serial dilution starting with 108 copies to 102 copies of the standard (complete 16S gene Escherichia coli ATCC 25922) was used to determine the reproducibility of the 16S PCR assay as a double determination on three different days. Non-template controls (NTC) were included in all...

Establishment of a species-specific primer PCR against non-target test bacteria. S3A Fig: Cross-reaction experiments with 10 ng DNA of different bacterial strains (red) demonstrated primer specificity for the baiCD genes of C. scindens (blue) and C. hiranonis (blue) with Ct values of 16.64 (C. scindens) and 18.01 (C. hiranonis), respectively. Yello...

Alignment with annotated sequences of the baiCD genes. Pairwise comparison of different baiCD gene cluster sequences. Red colors showed highly (> 96%) matched sequences in comparison to the less well matched blue fields of sequences. The strains of C. scindens VPI 12708 and C. scindens VE202-05 were different, but the baiCD gene cluster sequence is...

Background The intestinal microbiota plays a major role in modulating the interaction between the gastrointestinal (GI) epithelium and the immune system. Increasing evidence suggests that inflammatory bowel disease is associated with gut microbiota disturbances. Such a microbial dysbiosis can affect immune signalling, but also gut epithelial homeos...

Background Clostridium difficile infection (CDI) poses an increased risk to patients with inflammatory bowel disease. Preconditions are colonisation with C. difficile, but also a breakdown of the colonisation resistance, of which secondary bile acids are believed to constitute a decisive component. 7α-dehydroxylation is one of the key steps in prim...

The spread of infectious diseases and vaccination history are common subjects of epidemiological and immunological research studies. Multiplexed serological assays are useful tools for assessing both current and previous infections as well as vaccination efficacy. We developed a serological multi-pathogen assay for hepatitis A, B and C virus, cytom...

Helicobacter pylori γ-glutamyl transferase (gGT) is a key bacterial virulence factor that is not only important for bacterial gastric colonization but also related to the development of gastric pathology. Despite accumulating evidence for pathogenic and immunologic functions of H. pylori gGT, it is still unclear how it supports gastric colonization...

Infection with Helicobacter pylori (H. pylori) occurs in 50% of the world population, and is associated with the development of ulcer and gastric cancer. Serological diagnostic tests indicate an H. pylori infection by detecting antibodies directed against H. pylori proteins. In addition to line blots, multiplex assay platforms provide smart solutio...

Helicobacter pylori infection shows a worldwide prevalence of around 50%. However, only a minority of infected individuals develop clinical symptoms or diseases. The presence ofH. pylorivirulence factors, such as CagA and VacA, has been associated with disease development, but assessment of virulence factor presence requires gastric biopsies. Here,...

The performance of diagnostic tests in intervention trials of Helicobacter pylori (H.pylori) eradication is crucial, since even minor inaccuracies can have major impact. To determine the cut-off point for 13C-urea breath test (13C-UBT) and to assess if it can be further optimized by serologic testing, mathematic modeling, histopathology and serolog...

Helicobacter pylori infection is commonly acquired during childhood, can persist lifelong if not treated, and can cause different gastric pathologies, including chronic gastritis, peptic ulcer disease, and eventually gastric cancer. H. pylori has developed a number of strategies in order to cope with the hostile conditions found in the human stomac...

Supplementary Table 1. Study Populations. Supplementary Figure 1. The result of five representative recomLine tests incubated with individual patient sera are shown (LHP13 − LHP17). The assignment of the bands is given in the cartoon above. The test score calculation is given beside the recomLine tests. LHP 16 shows only a CagA band and thus repres...

The Gram-negative bacterium Helicobacter pylori is predominantly known for its pathogenic role inducing peptic ulcer disease and gastric cancer. However, a considerable number of reports have linked H. pylori infection with the development of as well as protection from extra-gastrointestinal immunological disorders. Thus, recent epidemiological and...

Various gram-negative pathogens express type IV secretion systems (T4SSs) which translocate bacterial virulence factors into host target cells to hijack cellular processes for their own benefit and causing disease. The pathology of Helicobacter pylori, the causative agent of chronic gastritis, peptic ulcer disease, and gastric cancer in humans, str...

Erratum: Helicobacter pylori adhesin HopQ engages in a virulence-enhancing interaction with human CEACAMs Anahita Javaheri, Tobias Kruse, Kristof Moonens, Raquel Mejías-Luque, Ayla Debraekeleer, Carmen I. Asche, Nicole Tegtmeyer, Behnam Kalali, Nina C. Bach, Stephan A. Sieber, Darryl J. Hill, Verena Königer, Christof R. Hauck, Roman Moskalenko, Rai...