NIZO microbiome expert: We must reach 'mechanistic understanding' in nutrition-related gut health

The Dutch-based food and health research firm, specialized in a range of research topics, including proteins, fermentation and microbiomics, works with an in vitro​ gut-like system 'Microcolon' for rapid screening of probiotics, prebiotics and other ingredients and an in silico​ predictive computer model for in-depth microbiome data analysis.

Speaking to NutraIngredients, Michiel Wels, expertise group leader for microbiomics at NIZO, said both systems will assist industry in pushing forward with nutrition-related microbiome understanding.

“If you look at more health-related topics, in many cases people have an ingredient or strain from the microbiome and have some evidence that there's a reduction in a specific discomfort or disease. But, when it comes to having a direct link on what the organism does in the microbiome or how it changes and what this change mechanistically means, that's lacking in many, many different cases,”​ Wels said.

“If you want to have a successful product on the market, you really need to know what's going on – what the mechanism of action is. In many cases, there are not even causal relationships in the change in microbiome, there's just a correlation. You need to go from correlation to mechanisms. We're sort of at the boundary between correlation and causal; not at the mechanistic understanding yet.”​

Identifying and understanding the mechanism of action is, by far, the most complicated and costly step and can often take years, he said, but it is important industry starts to collaborate and work towards this.

'There's a lot of knowledge we're gaining at the moment'​

Through Microcolon faecal analysis, NIZO is learning increasing amounts about colon microbiomics, Wels said, looking at a range of biomarkers to measure things like composition and functionality of the microbiome. 

“The amount of organisms in the colon is much larger than in the small intestine and a lot of the food structure that cannot be digested by your own system can be digested by the organisms in your colon and they also produce all kinds of compounds that can still be utilised. There's a lot of knowledge we're gaining there at the moment.”​

What NIZO is trying to do now, he said, is shift from composition analysis and microbiome profiling to functional analysis with genomics. Its in silico ​analysis model aims to capture data and look at specific genomes and mechanisms to target function-related questions, he said.

“If you want to do microbiome research, you don't want to focus too much on the general pathways, you have to have a specific research question. It really requires you to go down to individual processes or individual mechanisms of action, and this requires you to summarise this mechanism of action in some kind of model in order not to get drowned in all the data.”​

Industry now has a good understanding on nutrition-related health effects on the colon, particularly related to discomfort or common diseases, he said, but research is now advancing towards the interaction of the colon with other systems in the body, like the brain and vascular system.

There are some “hints”,​ Wels said, on how probiotics, for example, influence mood or brain disorders and it's believed the microbiome probably interacts with both the body and the brain. As research continues, he said it could be possible to eventually target some of these disorders through the microbiome, “but there's no clue yet on which ones and how”.​

The small intestine's 'really big role'​

What is clear, however, is the small intestine will have a “really big role” ​in this research because the microbiome here get first access to a lot of ingredients, Wels said.

“There is more and more evidence coming out that, especially in the small intestine, a lot is happening, especially if you look at what ingredients are doing. Most of the ingredients are being processed in your small intestine and not in your large intestine. To look at the small intestine for many ingredients would be a very beneficial thing.”​

Measuring microbiome activity in the small intestine, however, is no easy task, Wels said, and ideally needs to be done with a sampling device in vivo​.

Back in 2013, NIZO teamed up with biotech firm Medimetrics on 'The IntelliCap' system​ ​– a non-invasive capsule developed as a drug delivery system that both firms wanted to use for in vivo ​microbiome testing in the small intestine. ​However, Wels said the IntelliCap service was discontinued although NIZO remains committed to advancing its research in nutrition-related microbiome activity.

According to bankruptcy case website FaillissementsDossier, Medimetrics Personalized Drug Delivery B.V. was declared bankrupt by a Netherlands court in May, last year.​​

Wels said that whilst NIZO doesn't currently have access to any suitable in vivo​ sampling technology for small intestine research, it remains interested in partnering with companies that have such capabilities.