Work Package 4

Microbiome modulation in vitro

General aim

To develop and validate in vitro models for Host-Microbiome Interactions (HMI) that can be used to predict the impact of interventions on the physiological balance between the host and its microbes in the oral cavity and in the gut as the key arena’s for the interplay between the host, its microbiome and diet.

Objectives

To develop an oral and a gut HMI model that allow analysis of microbial and host-contributions to homeostasis and study mechanisms involved in maintaining homeostasis.
To describe the immune fitness in in vitro HMI models.
To evaluate the effect of microbially derived metabolites, most notably short chain fatty acids on the immune fitness in HMI models.
To study the role of known variations in dietary fibers, oligosaccharides, pre- and probiotics in the oral and gut HMI.
To assist in silico modeling (WP3) at different stages during the WP through iterative cycles of in vitro and in silico modeling of set variables.
To translate designated interventions (WP5) in testable variables in in vitro HMI models and predict their value in strengthening oral and gut homeostasis in the first 1000 days.
To disseminate achieved outputs during and at the end of the work package.

Active period

Year 3-8

Members of WP4

Rob van Dalen

Bastiaan Krom

Leader WP4

Dongmei Deng

Stanley Brul

Jianbo Zhang

Meike Wortel

Coen Berns

Sofía Jiménez Ochoa

Aliki Antoniou

Applicants

ACTA, AUMC/Tytgat, WUR, UvA-SILS.

Cooperation partners/co-funders

NIBI, Bètapartners, BaseClear.

Progress

Update: March 2025

WP4 has successfully hired 3 PhD students that all started their projects on January 1st 2025. The first concrete plans are made to commence with the practical work. The first experiments will focus on generating experimental data for a set of microbes to allow Genome Scale Metabolic Modelling. In addition, a joint review paper is being drafted as introduction to the subject.

A paper was published before the start of the WP.

The human gut harbors native microbial communities, forming a highly complex ecosystem. Synthetic microbial communities (SynComs) of the human gut are an assembly of microorganisms isolated from human mucosa or fecal samples. In recent decades, the ever-expanding culturing capacity and affordable sequencing, together with advanced computational modeling, started a ‘‘golden age’’ for harnessing the beneficial potential of SynComs to fight gastrointestinal disorders, such as infections and chronic inflammatory bowel diseases. Read more

As simplified and completely defined microbiota, SynComs offer a promising reductionist approach to understanding the multispecies and multikingdom interactions in the microbe–host-immune axis. However, there are still many challenges to overcome before we can precisely construct SynComs of designed function and efficacy that allow the translation of scientific findings to patients’ treatments. Here, we discussed the strategies used to design, assemble, and test a SynCom, and address the significant challenges, which are of microbiological, engineering, and translational nature, that stand in the way of using SynComs as live bacterial therapeutics.