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Opportunistic pathogens (the bad bugs) acquire features that allow them to grow out, increase in density and spread. This outgrowth is often directly dependent on the composition of the microbiota and can upset the delicate balance for example in our gut, tipping the scales towards infection and disease. This relationship between disease and the microbe community within our bodies, is an emerging hot area of discussion and research.

Studying changes in our microbiome

As a clinical immunologist (Helen Leavis) and expert in antimicrobial resistance (Rob Willems), we’ve combined our strengths and established a facility to identify and help decipher how changes in the human microbiota can affect a patient’s health treatment or vice versa, how a procedure can affect a patient’s microbiota with an impact on health status.

Within the Exposome Hub, we’re establishing a new facility to explore internal exposures to the microbiome and host factors that are related to inflammation, oxidative stress and various metabolic pathways that are the result of microbiome-host interactions. Evaluation of these requires a variety of omics’ analysis, including microbiomics, genomics, proteomics and metabolomics. The strength of the Utrecht Exposome Hub is that all of these techniques are well-established, and we aim to expand our capacity, both within Utrecht and outside.  

Some examples of projects we’re working on include transfer of resistance between animals and humans; changes in the gut microbiota in patients experiencing graft-vs-host disease and inflammatory bowel disease; on colonization resistance for example, the role of the microbiota in preventing acquisition and intestinal outgrowth of (multidrug-resistant) opportunistic pathogens in critically ill patients; and on developing novel metagenomic technologies to study the composition and function of the human microbiome. Other groups within the hub also look at the interaction between chemical exposures and for example, the gut and respiratory microbiome. This interface between external and internal factors potentially mediated by the microbiome is currently at the forefront of exposome research.

Case study: is weight loss because of surgery, or because of microbiota changes?

It’s becoming more apparent that surgical procedures themselves, may affect a patient’s clinical outcome or road to recovery. Take, for example, bariatric surgery, which is often a last resort for weight loss. There are two types of surgery, one involves physically reducing the size of the stomach by a gastric band or removing part of the stomach, and the other consists of bypassing the stomach by re-connecting the small intestine to a small stomach pouch. Currently, it’s up to the surgeon and patient to decide which procedure to use and often depends on what the patient wants and the estimated surgical operation risk.

It’s becoming more apparent that surgical procedures themselves, may affect a patient’s clinical outcome or road to recovery.

Together with a surgeon at the Catharina Hospital in Eindhoven, we wondered whether parts of the procedures had an effect on composition of the microbiome. Before patients undergo surgery, they must follow a strict crash diet plan, which can also affect the microbiome, and this factor is almost never studied. We collected samples from patient 40 patients before, during and for six months after the procedure (including crash diet) and analyzed them.

As expected, the microbiome was a complete mess right after the crash diet, but this was not a long-lasting effect. Our most dramatic analysis was a total change of the microbiome only two weeks after surgery, regardless of surgery type. This is of particular interest, because within that short time frame, patients see no relevant weight loss changes. We speculate that changes in anatomy or bowel movement velocity facilitate an almost immediate long lasting metabolic change, reflected by the almost immediate change in the microbiome, such that even as a patient loses weight, the newly adjusted microbiome stabilizes long-term.

This leads to questions about whether a non-surgical procedure, such as fecal transplant (transplant of fecal bacteria from a healthy donor into a patient) can induce a microbiome change (or perhaps long lasting metabolic changes) that more naturally aids weight loss.  

Investigating inside, and out

The Utrecht Exposome Hub creates a diverse community through which we have readily access to many different types of expertise, ranging from fundamental science, to new technologies, to preclinical and clinical application. We’re well-positioned to investigate important questions about our internal microbiome and ultimately, by understanding the molecular underpinnings these environments, we hope to restore a healthy balance by preventing the bad bugs from taking over.

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Department  of Medical Microbiology
UMC Utrecht