Small intestine microbiota and big omics challenges

Dr Tom van den Bogert focused his research on small intestinal microbiota combining cutting edge omics method like metagenomics. He accepted to give us more detailed information about his work conducted in TIFN framework. We advise our readers to follow him on twitter @TomvandenBogert.

What is your background?

My studies started in Rotterdam where I obtained a bachelor’s degree with a specialization in Medical Microbiology. The bachelor thesis was performed in a clinical setting at Erasmus MC in Rotterdam and focussed on characterization and dynamics of the bacterial flora in Barrett’s esophagus. My studies continued at Leiden University specializing on molecular and cellular biology. The final research thesis was conducted research in a company setting and focused on the effect of different dietary components on the human intestinal microbiota. Knowing that this was the field of interest, I started my PhD-research at the Laboratory of Microbiology at Wageningen University under the supervision of Dr. E.G. Zoetendal and Prof. Dr. M. Kleerebezem focusing on community and genomic analysis of the human small intestine microbiota in a TI Food and Nutrition funded project.

 

TI Food and nutrition

TI Food and Nutrition (http://www.tifn.nl/)

 

What is the context of your work?

Research focusing on the intestinal microbiota often use fecal samples as a representative of the bacteria that inhabit the end of the large intestine. These studies revealed that the intestinal bacteria contribute to our health, which has stimulated the interest in understanding their dynamics and activities. However, bacterial communities in fecal samples are different compared to microbial communities at other locations in the intestinal tract, such as the small intestine. Despite that the small intestine is the first region where our food and intestinal microbiota meet, we know little about the bacteria in the small intestine and how they influence our overall well-being. The work described the thesis provides an expansion to the accumulating knowledge on the human intestine microbiota by targeting the microbiota of the poorly proximal regions of the intestine.

What was the most challenging part of your work?

The challenging part of the work was integrating all the data from the different (meta)omics technologies, including microbial profiling (using microarrays or sequencing based platforms), metatranscriptomics, comparative genome analysis and immunesystem oriented studies. Nonetheless, without these approaches, I feel that biological understanding of the microbiota function cannot be achieved and highlights that microbiology PhD student need to have a firm grasp of bioinformatic tools to analyze these data.

 

Graphic representation of the small intestine provided by Tom van den Bogert

Graphic representation of the small intestine provided by Tom van den Bogert

 

What were main findings of your research?

Microbial profiling of small intestinal samples revealed that Streptococcus spp. were among the bacterial species that were detected in each ileostoma effluent sample, albeit that their abundance varied greatly between samples from the same subject as well as samples from different subjects. Veillonella spp. frequently co-occurred with Streptococcus spp., indicating that the Streptococcus and Veillonella populations play a prominent role in the human small intestine ecosystem. Cultivation and molecular typing methodologies of these groups revealed that the richness of the small intestinal streptococci strongly exceeded the diversity that could be estimated on basis of 16S rRNA analyses, and could be extended to the genomic lineage level (anticipated to resemble strain-level). Comparative analysis of the genomes of these streptococci revealed that their genomes encode different carbohydrate transporters and the necessary enzymes to metabolize different sugars, which was in excellent agreement with what carbohydrates could be used by representative strains of the Streptococcus lineages. Furthermore, the Streptococcus lineages differed significantly in their capacity to modulate cytokine responses of bloodmonocyte derived immature dendritic cells. Interestingly, pair-wise combinations of Streptococcus lineages and Veillonella from the small intestine were also tested for their combined immunomodulatory properties. This resulted in considerably different cytokine responses as those that could be predicted from the stimulations with either Streptococcus or Veillonella, indicating that it is not trivial to predict gut mucosal associated immune responses and that the composition of the intestinal microbiota as a whole may have a distinct influence on an individual’s immune status.

What are limitations?

The next challenge will be to identify mechanistic connections between multidisciplinary data sets from human intervention studies and to draw conclusions about the homeostatic relationship between diet, microbiota, and immune responses. The field of bioinformatics will be especially important to provide algorithms that reduce computational complexity for efficient data mining.

How your research could help clinicians in the future?

Ultimately, the research in this area can be exploited to guide the design of future studies that aim to elucidate the interplay between diet, microbiota and the mucosal tissues in the human small intestinal tract as well as open avenues towards rational design of food compositions that aim to modulate the small intestine microbiota composition and activity and thereby aiming to regulate mucosal (and systemic) immunity.

 

Selected publications :

GMFH Editing Team
GMFH Editing Team