Project results: Understanding gut microbiome imbalance

Evidence shows that microbial imbalance in the gastrointestinal system, also referred to as dysbiosis, is linked to colorectal cancer, diabetes and cardiovascular diseases. Even though dysbiosis can be treated by implementing lifestyle changes, the challenge of this condition lies in the diagnosis. The complex composition of the gut microbiota, that differs between individuals, makes it difficult to diagnose this multifactorial condition. Proteobacteria are shown to respond very strongly to dietary changes and have been proposed as a diagnostic marker of dysbiosis. Several studies have described that proteobacteria abundance increased in response to diets high in fat, sugar, and artificial sweeteners. A unique feature of proteobacteria is the presence of secretion systems by which the so-called ‘effector-proteins’ can be injected into the host’s cytosol (the aqueous portion of the cytoplasm in an intact cell, consisting of water, organic molecules and dissolved ions) to interact with host proteins and modulate molecular pathways. Understanding these effector-protein interactions provides more insights into the mechanism and diagnosis of dysbiosis. 

In the project ‘The role of diet-dependent human microbiome encoded T3SS-dependent effectors in modulating health’ (DIME), researchers from Germany, Austria and France collaborated to investigate how diet-responsive commensal gut microbes modulate human health by injecting microbial proteins into human cells to affect regulation and metabolism. The project ran between 2018-2022. The project was cofunded by the European Commission within the HDHL-INTIMIC cofunded call. 

Aim
The DIME project aimed to analyze the protein-protein interaction network of effector proteins from commensal microbes with the human host interactome to understand which processes and disease modules are targeted by this underexplored molecular mechanism.

Results
Amongst others, the research has revealed the widespread presence of secretion systems and effectors among human gut proteobacteria. These gut effectors have been found to target key immune signalling pathways and have the ability to modulate human immune signalling. Furthermore, it has been discovered that the host-targets of these effectors are genetically associated with microbiome-influenced traits and diseases. Additionally, it has been observed that effectors are enriched in the microbiomes of individuals with Inflammatory Bowel Disease. The project discovered significant proof  that backs up the initial theory that the microbiome may affect human health through mechanisms involving effector-proteins. Several resources were developed, such as a microbiome-human interaction map, that will benefit the research community.

Overall, the DIME consortium provided a better understanding of the mechanisms by which microbes can influence human molecular processes which will allow much more precise and informed health prevention and intervention strategies.

In total, 11 projects were funded within the HDHL-INTIMIC cofunded call. All results will be shared on our website. Stay tuned! See ‘more information’ below for already published project results. 

More information:

• HDHL-INTIMIC cofunded call
• Di-Mi-Liv project results
• FATMAL project results
• GUTMOM project results
• MICRODIET project results
• MeaTic project results
• EarlyFOOD project results
• TransMic project results
• OCTOPUS project results
• DiGuMet project results

Text: call secretariat INTIMIC cofunded call
Publication date: May 2023
Image by Freepik