Targeting the gut-liver axis in cirrhosis
How would you propose to improve gut hyperpermeability by targeting the intestinal barrier with the goal to ameliorate the outcome of liver disease?
Antonio Filareto
Sr Principal Scientist
Cardio-Renal-Metabolic Diseases
Ines Truebenbach
Principal Scientist
Cardio-Renal-Metabolic Diseases
Bernhard Texler
Sr Scientist
Cardio-Renal-Metabolic Diseases
Call for proposals: All incoming answers accompanied by a collaboration proposal will be evaluated by a scientific jury, and, upon selection, chosen proposals are pursued through a joint collaboration with the successful applicants. Initial funding of up to 200,000 euros will be available for proposals that will receive support by our review team.
More information
Chronic liver damage in patients with cirrhosis is accompanied by increased intestinal hyperpermeability. Through the portal circulation, the gut and the liver are connected, forming the gut-liver axis. Therefore, everything that crosses the intestinal barrier reaches the liver, where it can be metabolized or interact with the immune and resident cells. Increased translocation of bacteria and bacterial products and other pathogenic substances from the intestine to the liver can trigger systemic inflammatory responses and recruitment of systemic leukocytes, resulting in hepatocyte apoptosis/necrosis as well as activation of hepatic stellate cells that can promote fibrosis. This is a self-perpetuating spiral ultimately promoting decompensation events and worse outcomes in patients. Throughout progression of liver disease, the intestine is subjected to subclinical inflammation, leading to impaired dendritic cell activity, expansion of pro-inflammatory lymphocytes and depletion of anti-inflammatory T helper cells, thereby further increasing the permeability of the gut barrier, leading to more inflammation to the liver and subsequently also to the gut.
As part of this opnMe call, we are exploring targeting the intestinal hyperpermeability to reduce inflammation as a driver of liver cirrhosis.
Hence, we are inviting scientists to submit research proposals that showcase novel ways to address this problem and deliver new potential therapeutic targets (genes, proteins, pathways) for restoring the gut barrier hereby using suitable cellular models or assays to show efficacy.
- Mechanisms that aim to target the epithelial barrier, either by regenerating/protecting intestinal epithelial cells (IECs), improving tight junction function, and/or improving goblet cell function and mucus layer integrity.
- Mechanism that indirectly affect gut hyperpermeability e.g., improving liver sinusoidal endothelial cells (LSEC) function
- Preliminary data showing that the proposed mechanism of action/target is supported by in vitro and/or in vivo genetic or pharmacological data, and the presence of human disease link (human genetic and/or altered target in patient tissues) would strengthen the proposal.
- Innovative methods to measure gut hyperpermeability metabolites and gut derived products.
- Innovative validated preclinical models (in vitro/ex vivo/in vivo) that could serve for target identification and validation.
- Proposals that solely target the microbiome, virome, or mycobiome
- Proposals including Fecal microbiota transplantation (FMT), antibiotics, probiotics, or dietary interventions
- Proposals that solely target cholangiocytes, bile-acid, or farsenoid X receptor (FxR) signaling
- Proposals focused on exosomes approaches
- Proposals that solely focus on IBD induced gut barrier damage
- Proposals addressing early steatotic liver disease
- Proposals that focus on incretin approaches
- Proposal lacking translatability to human
If your project is selected, you will have the opportunity to directly collaborate with the Cardiovascular-Renal-Metabolic Diseases Research team of Boehringer Ingelheim. You can expect appropriate funding for the prospective collaboration period. Your exact funding request should be outlined in your proposal. As a framework, we suggest that your initial funding request is structured in milestone and does not exceed 200,000 euros per submitted project in total.
The opportunity for a funded stay at Boehringer Ingelheim for technology exchange / training is potentially available, as is the availability of custom biological tools and reagents.
Our collaboration agreement will provide full transparency about each partner’s rights & obligations (including intellectual property rights). As part of the agreement, you will be encouraged to publish following the collaboration agreement (to be negotiated in good faith).
We are seeking research collaboration proposals that contain:
- A well-structured proposal outlining a new and compelling scientific approach.
- Outlining of the technical feasibility, and potentially existing data or previous publications that support feasibility / experience with outlined technology, based on existing techniques and established assays.
- Your exact funding request should be outlined in your proposal based on a well-thought-through project. The project should be structured in milestones and planned with key decision points (clear Go/No-Go criteria). The funding request for the initial milestones resulting in a Go/No-Go decision should not exceed 200,000 euros per submitted project in total.
- Proven track record in the required field of expertise.
- Ability to implement the outlined solution as part of a scientific collaboration project with Boehringer Ingelheim including access to a laboratory.
Please use our answer submission template to provide a 2–3 page non-confidential proposal (available for download here).
If confidential data exists that would strengthen the proposal, please indicate that information is available to share under a Confidential Disclosure Agreement (CDA). If we find the non-confidential concept proposal sufficiently interesting, we will execute a CDA for confidential discussions.
We are currently seeking answers for the following scientific question: How would you propose to improve gut hyperpermeability by targeting the intestinal barrier with the goal to ameliorate the outcome of liver disease?
All incoming answers accompanied by a collaboration proposal will be evaluated by a scientific jury, and, upon selection, chosen proposals are pursued through a joint collaboration with the successful applicants. Initial funding of up to 200,000 euros will be available for proposals that will receive support by our review team.
We can only accept research proposals if they arrive no later than March 26, 2025, 11:59 pm PST.
