Project

Exploring the relationship between small intestinal microbiota and immune system. A multi –omix explorative approach

Background:

Regardless the increasing interest and characterization of the faecal microbiota and its association with health and disease, little is known on its small intestine counterpart. This is mainly due to the challenging and invasive sampling procedure needed. The small intestine is oxygenated, rich in nutrients with high amount of pancreatic and biliary secretion, and rapid motility. Thus, it is not surprising that the small intestinal microbiota is radically different from the faecal microbiota. Small intestinal bacterial population sizes increase from 104-5 CFU/mL in the duodenum to 107-8 CFU/mL in the distal ileum. Despite being difficult to reach, studying the ecosystem of the small intestine is of extreme interest not only because the duodenum and the jejunum are the major assimilator of nutrients in the human body, but also because there is a significant host-microbes/microbes-nutrient interaction.

Cohort study

The project uses a small cohort of ileostomy patients. The subjects are healthy, but their large intestines were surgically removed. An opening in the abdomen was made to bring a piece of the ileum outside the abdominal wall to create a stoma. Through the stoma digested food passes into an external pouching system. This allows us to obtain small intestinal content without any invasive procedure.

Sixteen ileostoma volunteers were recruited and the two following sampling schemes were adopted:

Scheme one:

9 small size ileostomy effluent have been collected per participant during a 100 days period. Samples were prepared for microbiota composition analysis (16S amplicon sequencing).

Scheme two:

During 3 visits, 1 every second week, the following samples were taken from each individual:

1. Urine for metabolite analyses.

2. Blood samples for PBMCs transcriptome analyses, biomarkers profiling, metabolome analyses and immune responsiveness (cytokine profiling after ex-vivo stimulus, 6 stimuli + 1 control).

3. Ileostomy samples for metatranscriptome analyses and SCFA composition.

Aim of the study

This project aims to have a better understanding of the small intestinal microbial community and its impact on human physiology. This project offers a unique combination of datasets from a still undiscovered ecosystem.

Moreover, for most of the above datasets, data are available both in raw, semi-process/process form. Thus no computer programming skills are required for data mining. This project will allow the student to explore the world of –omix with a diverse, challenging, but rewarding project.

 contact: edoardo.zaccaria@wur.nl