A new platform for studying the effects of probiotics on the human gut

Traditional laboratory models do not accurately replicate the human gut. This is a challenge for research on gut health in general and probiotics in particular. To gain a better understanding of how probiotics interact with the gut as well as the implications for drug research, highlighting the importance of realistic gut models in scientific studies, stem cell scientists and microbiologists have teamed up and merged stem cell and microbial science.

Probiotics, the ‘good bacteria’ that can support healthy gut function, have become a common fixture in pharmacies and dairy aisles worldwide. But recent research indicates that the traditional methods used scientists in the industry have underestimated the intestinal responce to bacteria.

The article, published in Gut Microbes, lays out a novel technique that provides an effective method to create an intestinal epithelium in a dish to monitor microbial interactions.

“We are actually recreating the part of the gut that is exposed to all the microbes within our body,” says co-author Kim Bak Jensen, Professor and Director of the Novo Nordisk Foundation Center for Stem Cell Medicine, reNEW, at the University of Copenhagen.

Inside-out and inside again
The human digestive tract, an astounding 6 meters of fleshly tubes coiled inside our bodies, is extremely difficult for scientists to access while it is alive and functioning. Thus, in vitro models are essential for scientists hoping to gain further insight into the interactions between bacteria and the digestive system.

For decades, researchers have extensively used colorectal cancer cells for research. The downside of this is that cancer cells carry cancerous mutations that affect their behaviour and they therefore do not exactly resemble the cells we would normally observe in a healthy intestine. Pioneering advancements in the intestinal field overcame the normal restrictions on growing the healthy intestinal epithelial lining from stem cells, enabling researchers to make structures in a dish called organoids – or mini-guts.

‘This was a game-change for the field’, Jensen explains. Yet, there remains a problem given that organoids have their inner surface facing inwards, where they interact with microbes, which isn’t how it works in our bodies.

Expertise from industry in microbial biology and production
The study is done in collaboration with Adam Baker. He has a background in human medical genetics and is Director of Science for Future Labs at Novonesis, a Danish bioscience company. “We have the most extensive culture and enzyme range for microbes including cheese in the dairy world,” Baker says.

Cheesemaking is, after all, the art of using bacterial dairy husbandry. “That is something we are very good at – producing bacteria,” Baker explains. While Novonesis culture business has been active for 150 years, “we only started work with probiotic 25 years ago or so.”

Novonesis produces probiotic supplements and also sells its bacteria strains to many manufacturers. These strains ultimately make their way into cultured diary products. But with data lacking on how probiotics interact with the gut, Baker and Novonesis wanted to better understand how their pet bacterial strains perform.

In collaboration with reNEW and the Department of Biology, based at the University of Copenhagen, they set out to design a platform that would enable them to watch healthy cells respond to probiotics using stem cell derived intestinal organoids.

“We are getting a lot of interest from other companies that would like to identify ways to transfer something across the epithelial membrane,” Jensen says. “If you can get something efficiently transferred across, that will enable you to dose people with various drugs that just have to pass through the stomach.”

Detecting host responses to microbial stimulation using primary epithelial organoids” has been published in Gut Microbes. The research was funded by Innovation Fund Denmark, European Union’s Horizon 2020 research and innovation programme, Independent Research Fund Denmark | Medical Sciences, and the Novo Nordisk Foundation. The Novo Nordisk Foundation supports the Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW). Novonesis A/S funded the clinical trial.

We would like to acknowledge Science News, as the content of this article is based on their story.

Reprogrammed neurons may fool you!

Associate Professor Agnete Kirkeby, from reNEW Copenhagen, has published the paper Forced LMX1A expression induces dorsal neural fates and disrupts patterning of human embryonic stem cells into ventral midbrain dopaminergic neurons, in Stem Cell Reports.