Understanding Microbiome/ Host Interactions


Presentation Title
Bacteriophages Dynamically Modulate the Gut Microbiota and Metabolome

The human gut microbiome is comprised of densely colonizing micro-organisms in dynamic
interaction with each other and the host. While the bacterial component of the microbiome is under
intense investigation, far less is known about how bacteriophages impact bacterial communities in the
gut. We investigated the dynamic effects of phages on a model microbiome using gnotobiotic mice
colonized by human commensal bacteria and found that phage predation not only directly impacts
susceptible bacteria but also leads to cascading effects on other bacterial species via inter-bacterial
interactions. Using metabolomic profiling, we also found that the shifts in the microbiome caused by
phage predation have a direct consequence on the gut metabolome. Our work provides insight into
the ecological importance of phages as modulators of bacterial colonization, and additionally suggests
the potential impact of gut phages on the host with implications for the use of phages as therapeutic
tools to rationally and precisely modulate the microbiome.



Presentation Title
Quantitative Microbiome Profiling in Health and Disease.

Alterations in the gut microbiota have been linked to various pathologies, ranging from inflammatory
bowel disease and diabetes to cancer. Although large numbers of clinical studies aiming at
microbiome-based disease markers are currently being performed, our basic knowledge about the
normal variability of the human intestinal microbiota and its determining factors remains limited. Here,
I will discuss our findings studying a large-scale study (Flemish Gut Flora Project; n=3400) of the gut
microbiome variation in a geographically confined region (Flanders, Belgium), in which analysis of
microbiome variability in health identified the primary parameters associated to microbiome
composition. In this presentation, I will discuss our experiences in large-scale microbiome monitoring,
show how the development of dedicated computational approaches can assist in microbiome analysis
and interpretation, and which confounders are essential for inclusion in microbiome disease research.
In addition I will show how Quantitative Microbiome Profiling (QMP; Vandeputte et al. Nature 2017),
which combines microbiomics with flow cytometry-based cell counts, is profoundly changing our view
on gut microbiota variation and allowed the identification of an inflammation-associated, cross-
disease enterotype.



Presentation Title
The Early Life Mycobiome

The human gut contains a complex and diverse array of microbes from all three domains of life, with
fungi often being the principle representatives of the Eukarya. However, while the importance of gut
residing microbes in human health and disease is unquestioned, fungi are often overlooked due to
their relative low abundance. Despite this, fungi can nevertheless still have a significant impact,
especially on individuals who are either immunocompromised or receiving long-term antibiotic
treatment. In this presentation, I will focus on the young infant gut mycobiome, and look at how its first
established, develops over time and what influence it can have, both positively and negatively, upon
infant health.



Presentation Title
Understanding Human Microbiome Functionality & Immune Interactions Through Deep Learning

The human microbiome, the collection of bacteria and other microbes that colonize the human body,
has a profound impact on human physiology and disease state. Additionally, the interaction between
the host and the microbiome plays a major role in the development and functionality of the immune
system. These interactions are driven in large part by the metabolic processes of the bacterial
members of the microbiome. One of the mechanisms by which bacteria synthesize secondary
metabolites is through biosynthetic gene clusters (BGCs). BGCs are clusters of genes that are
physically co-localized in a bacterial genome and together encode the components required to
produce a metabolic product. Our group has enhanced the detection and analysis of BGCs through
the development of methods including DeepBGC, a BGC detection algorithm based on a long short-
term memory (LSTM) neural network. The use of these and other analytical tools in our microbiome
studies has allowed us to begin gaining unique insights into how the microbiome may impact immune
responses, and how that may be leveraged therapeutically to improve treatment efficacy.



Presentation Title
Bioinformatic analysis of microbial communities for novel live biotherapeutic product discovery and
patient stratification

Dysbiotic gut microbiota contribute to conditions of chronic inflammation caused by an overactive
immune system, such as IBD pathogenesis. Strategies to manipulate this dysbiosis range from Fecal
Microbiome Transplants to replacing strains decreased during inflammation, as determined via
comparative microbiome analysis between healthy individuals and patients. However, current
strategies do not consider recently observed microbial functional and metabolic alterations in IBD and
other diseases that are characterized by a gut microbiome-related compound.
To address this, we developed improved methods to analyze the composition and functional of the
gut microbiome of patients suffering from a range of conditions. Subsequently, we used these insights
(1) Improved stratification of patients, such as patients suffering from various diseases that classify
under IBD; or improved stratification of metastatic melanoma patients in responders and non-
responders to immune checkpoint inhibitor drugs;
(2) Rational design of live biotherapeutic products (LBPs) designed around missing functionalities
rather than missing bacterial species.
Using an experimental colitis model, a rationally designed LBP was successfully used to overcome
functional dysbiosis of the gut microbiome, resulting in inflammation control.



Presentation Title
Functional Metagenomics approaches to better understand Host-Microbiome interactions

The human intestinal microbiota has been considered as a true organ, playing major functions for its
host, however little is known on the underlying mechanisms. Indeed, very few specific effectors
interacting with the human host have been identified, probably due to the difficulties to cultivate most
commensal bacteria. We have developed a functional metagenomic approach to identify bacterial
genes and compounds regulating key signaling pathways or effector genes in human intestinal
epithelial cells. Metagenomic libraries were built by cloning metagenomic DNA from different donors
(healthy or with chronic diseases) in a fosmid vector and using E.coli as a host. A high throughput
screening platform was established permitting the identification of clones modulating pathways and

genes in human cells. This functional metagenomic strategy allowed the characterization of new
commensal bacteria genes and effector molecules that impact on host cellular functions with potential
influence on human health.

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