Human-Microbial Molecular Interactions
Mahesh Desai, Ph.D., research associate at the center for systems biomedicine at the University of Luxembourg, presented his results with a microfluidics system called HuMiX, which he described as “a microfluidics-based in vitro co-culture device for investigating human-microbial molecular interactions.”
The main goal of Dr. Desai’s research is to understand how the different microbial communities (human microbiome) that inhabit our gastrointestinal tract interact and influence our health status.
“We have now seen that the microbes in our intestinal system have ten times more genes than our own body cells,” explained Dr. Desai.
Current work has identified differences in the human microbiome between healthy versus diseased individuals. However, it is still difficult to establish a causal link regarding what makes healthy people sick, he pointed out.
“The field is in desperate need of in vivo and in vitro methods that can study interactions of human bacteria and human body cells. We need to develop an individual system that can look at these interactions,” continued Dr. Desai.
“Therefore, we are designing a microfluidic system, HuMiX, to study human cell and microbial communities. This microfluidic system can combine models to test several hypotheses.”
HuMiX is a modular microfluidics-based device where human epithelial cell lines and human microbial communities can be grown in individual chambers, separated by a semi-permeable membrane. Their close proximity allows for molecular interactions between the two cell populations to occur and to be studied.
The device consists of three separate chambers (top, central, and bottom). The central chamber hosts the human epithelial cell lines, while the bottom chamber holds the microbial community. The upper chamber acts as a perfusion system and is separated from the middle chamber by a microporous membrane, which facilitates diffusion-based perfusion between chambers.
“The human contingents are perfused with standard human cell culture medium using a programmable syringe pump. The synthetic gut microbial communities are introduced in the bottom chamber after the epithelial cells undergo an enterocytic differentiation mimicking the intestinal epithelial cell barrier,” said Dr. Desai.
The device’s architecture allows researchers “to establish in vitro models for the human proximal colon, the entire human gastrointestinal tract, and human gastro-intestinal tissues,” allowing for the co-culture and study of human cells or tissues and their naturally co-existing mixed microbial communities. These cultures are further studied via microscopy and metabolomics approaches before an actual experiment is performed.
“Once both contingents reach a steady state, they are exposed to a particular experimental regime, and the devices are snap frozen and the respective cell contingents undergo omic analyses,” according to Dr. Desai.
In the near future, Dr. Desai aims to use HuMiX to address the role of microbial dysbiosis in the pathogenesis of different diseases.