The functional role of fungi in the gut, a branched story!

The human gut acts as a host to vast populations of microorganisms such as bacteria, viruses, archaea, and fungi. All these microorganisms together residing in the human gut are called the Human Gut Microbiome (HGM). Years of attention and research have already elucidated that the health of the HGM is tightly correlated with the overall health of the individual. Especially the commensal bacteria have shown to influence the food metabolism, nutrient uptake, energy homeostasis, epithelial barrier integrity, host immunological response, and the protection against colonization of pathogens.

The functional role of other key microorganisms in the HGM has, however, not been studied in as much detail, if at all. Fungi are often overlooked yet repeatedly found in observational studies. In this research, we aim to elucidate the functional role that some of the most common yeasts have in the HGM and how it affects the other microorganisms by using a synthetic consortium of HGM bacteria. Furthermore, to investigate the effect of these yeasts when combined with the synthetic consortium on the host, a novel gut on a chip model is used.

To understand the functional roles and interactions of the species in the synthetis consortium, we use both species interactions models and genome-scale metabolic models in addition to in vitro experiments. With species interaction model we identify complex structures from data of pairwise interactions. The genome-scale metabolic models are used to identify the metabolic potential of the different species, both to identify their nutrient requirements as to identify potential interactions.

Scientist involved in this project

Pim van Leeuwen
Meike Wortel
Stanley Brul
Jianbo Zhang
Jurgen Seppen (Amsterdam UMC)
Wouter de Jonge (Amsterdam UMC)


  1. Mechanistic insights into the adaptive evolvability of spore heat resistance in Bacillus cereus sensu lato.

    Khanal S, Kim TD, Begyn K, Duverger W, Kramer G, Brul S, Rajkovic A, Devlieghere F, Heyndrickx M, Schymkowitz J, Rousseau F, Broussolle V, Michiels C, Aertsen A.Int J Food Microbiol. 2024 Apr 15;418:110709. doi: 10.1016/j.ijfoodmicro.2024.110709. Online ahead of print.PMID: 38663147

  2. Germination and outgrowth of Bacillus mycoides KBAB4 spores are impacted by environmental pH, quantitatively analyzed at single cell level with sporetracker.

    Trunet C, Vischer N, Coroller L, Brul S.Food Microbiol. 2024 Aug;121:104509. doi: 10.1016/ Epub 2024 Mar 4.PMID: 38637073 Free article.

  3. Role of RelA-synthesized (p)ppGpp and ROS-induced mutagenesis in de novo acquisition of antibiotic resistance in E. coli.

    Qi W, Jonker MJ, de Leeuw W, Brul S, Ter Kuile BH.iScience. 2024 Mar 26;27(4):109579. doi: 10.1016/j.isci.2024.109579. eCollection 2024 Apr 19.PMID: 38617560 Free PMC article.

  4. Isolation and characterization of persisters of the pathogenic microorganism Staphylococcus aureus.

    Shiqi Liu, Paul Laman, Sean Jensen, Gertjan Kramer, Sebastian A.J. Zaat, Stanley Brul, iScience, May-2024, doi:10.1016/j.isci.2024.110002

  5. Model-driven approach for the production of butyrate from CO2 /H2 by a novel co-culture of C. authoethanogenum and C. beijerinckii.

    Sara Benito-Vaquerizo, Niels Nouse, Peter J. Schaap, Jeroen Hugenholtz, Stanley Brul, Ana Lopez-Contreras, Vitor A. P. Martins dos Santos, Maria Suarez-Diez ;Front. Microbiol. Sec. Microbiotechnology doi: 10.3389/fmicb.2022.1064013

  6. Heat activation and inactivation of bacterial spores. Is there an overlap?

    Wen J, Smelt JPPM, Vischer NOE, de Vos AL, Setlow P, Brul S. Appl Environ Microbiol. 2022 Jan 12:aem0232421. doi: 10.1128/aem.02324-21. Epub ahead of print. PMID: 35020450.

  7. History of fecal transplantation; camel feces contains limited amounts of Bacillus subtilis spores and likely has no traditional role in the treatment of dysentery.

    Koopman N, van Leeuwen P, Brul S, Seppen J (2022). PLOS ONE 17(8): e0272607.

  8. Changes in the Spore Proteome of Bacillus cereus in Response to Introduction of Plasmids.

    Gao, X.; Swarge, B.N.; Roseboom, W.; Wang, Y.; Dekker, H.L.; Setlow, P.; Brul, S.; Kramer, G. Microorganisms 2022, 10, 1695.

  9. Dynamics of Germinosome Formation and FRET-Based Analysis of Interactions between GerD and Germinant Receptor Subunits in Bacillus cereus Spores.

    Wang Y, Breedijk RMP, Hink MA, Bults L, Vischer NOE, Setlow P, Brul S. Int J Mol Sci. 2021 Oct 18;22(20):11230. doi: 10.3390/ijms222011230. PMID: 34681888; PMCID: PMC8539644.

  10. Identification of Native Cross-Links in Bacillus subtilis Spore Coat Proteins – PubMed

    Rick Ursem, Bhagyashree Swarge, Wishwas R Abhyankar, Hansuk Buncherd, Leo J de Koning, Peter Setlow, Stanley Brul, Gertjan Kramer. J. Proteome Res. 2021, 20, 3, 1809–1816