IFF backs probiotic strain quality over CFU counts, taps biomics to predict behavior

Amid a growing demand for probiotics, IFF underscores the importance of improving the inherent quality of strains used in supplements, rather than increasing their colony-forming units (CFU) count. CFUs are used to estimate the number of viable microbial cells in a product. 

Nutrition Insight meets with Dr. Arthur Ouwehand, a technical fellow at IFF, to discuss probiotic quality, research advances, and knowledge gaps. 

The company uses biomics to predict how a strain will behave in the human body. Biomics is the multidimensional analysis of biological data, Ouwehand explains. He says the analysis covers many aspects, such as metabolomics (analysis of metabolites), proteomics (proteins), and transcriptomics (RNA transcripts). 

“Biomics, in general, will not guarantee that a probiotic works, but it will help us make informed choices on what probiotic to test, for what potential health benefit,” he details. 

He adds that biomics may help researchers understand a probiotic’s mechanism of action.

“Traditionally, microbiologists want to know what microbes are there,” Ouwehand continues. “But, I think there is a realization that it could be more important to know what microbes are doing, especially for metagenomics.” 

Probiotic quality

Naming the specific probiotic strain on a product label, not just the species that is used, is an important indicator of quality, says Ouwehand. 

“There are many products on the market that say they contain Lactobacillus acidophilus, but that doesn’t say anything,” he cautions. “If it just reads the species, you don’t know what you’re getting, and that should ring an alarm bell.”

Biomics covers many aspects, such as metabolomics (analysis of metabolites), proteomics (proteins), and transcriptomics (RNA transcripts).“There are two other things that are important for quality,” Ouwehand adds. “One is the stability — the CFUs, and not at the time of manufacturing, but the CFUs that are guaranteed at the end of shelf life.”

Moreover, he notes that a product needs to include instructions on how to store it, usually somewhere cool and dry, to maintain stability. 

He says that CFUs are also important as they link back to the clinical research a company conducts that shows a certain benefit with a specific dose. “That is the dose you should be providing.”

The second quality measure, Ouwehand outlines, is documentation to indicate scientific evidence on a product’s health benefits. “What research has been done on the strain? You can sell a specific strain, define that, and write it on a label, but does it have any health benefits?”

He adds that research should be of a certain quality. For example, studies should involve an appropriate target population, use a sufficient size, and examine a valid marker.

Beyond CFU counts

Ouwehand observes an ongoing trend that “more is better” when it comes to CFUs in probiotics. However, he argues this is not always the case — as more CFUs don’t necessarily mean consumers get more benefits out of the product. 

“A couple of years ago I looked into that,” he tells us. “When you look at doses that have been tested for a certain health benefit and how big the effect is, in most cases it doesn’t really matter. More, in itself, is not better.”

However, he says there is one notable exception — antibiotic-associated diarrhea — where more is better. 

Further, he notes that products with many strains will need a higher total CFU count if a company wants to provide the strains in the product at the clinically tested dose.

Naming the specific probiotic strain on a product label, not just the species that is used, is an important indicator of quality, says Ouwehand.At the same time, he notes that more is not worse — it’s not dangerous to take very high levels of CFUs. “Probiotics are extremely safe.” 

The proof is in the pudding

Sequencing the genome of one microbe was a major achievement 15 or 20 years ago, he notes. “Today, you can sequence the whole genome of your whole microbiota if you want to. It’s not going to be cheap, but it is doable.”

Although genomics details what a microbe is capable of doing, Ouwehand cautions that the data doesn’t specify what it actually does. 

“We have all our probiotics sequenced, we know them inside out,” he adds. “Then you can go mining, and the question that always comes is ‘does it express that?’ It may have the capability to produce a certain enzyme that may be of relevance for certain health benefits, but there’s no guarantee it actually comes to expression.” 

Moreover, enzymes may be expressed in vitro, but that is no guarantee that this will also happen in animals or humans. 

Ouwehand explains that researchers can learn a lot about a microbe through biomics, which can help make informed decisions. However, he cautions: “the proof is in the pudding — you have to test it in humans.”

Biomics may also help to select microbes for further testing. For example, if it is lacking a certain gene then researchers know it will not make the related enzyme. Moreover, it can help researchers understand which enzymes play a role in its mechanism of action, which could benefit additional research. 

“It narrows things down, but you still have to make a decision. You may choose the wrong one.” 

“Genome mining also has a price tag,” Ouwehand adds. “Some easy in vitro tests are cheaper and faster than going for whole genome mining.” 

He says that when compared to animal research, genome mining is preferable, especially from ethical perspectives. 

Although genomics details what a microbe is capable of doing, Ouwehand cautions that the data doesn’t specify what it actually does.Meanwhile, regulatory requirements may still call for animal studies. “You have to do your safety assessments through short-term and long-term tox studies. But also, if you want to understand how a microbe interacts with the whole organism, you have to look at the whole thing.” 

Small intestine sampling

According to Ouwehand, gut microbiome research largely relies on fecal samples, which he calls a reasonable approximation of what’s happening in the colon. However, he says there are significant knowledge gaps regarding the small intestine, with most documented knowledge stemming from patients, sudden death cases, and animals. 

“What’s happening in the human small intestine needs to be investigated,” he underscores.

He notes that researchers have developed capsules that can take samples. For example, in 2025, a team developed an ingestible pill that can sample bacteria from the small intestine to map its microbiome, as did the company Nimble Science. 

“Increasingly, there are capsules that can measure different things, more than just pH, pressure, and temperature,” Ouwehand adds. “There’s a capsule that can measure redox potential, which is then linked to inflammation. There are also capsules being developed where you can measure certain enzyme activity.”

However, he cautions more research needs to be done on these products to determine their effectiveness and reliability. “But, if we look at where we come from, when it really was a black box, five or 10 years from now we will have a better understanding of what is going on in the small intestine.”

Moreover, Ouwehand says that many of the capsules taking samples use well-established technology and are relatively cheap, especially when compared to camera capsules that are used as an alternative to endoscopy. 

Gut models

Researchers and companies such as IFF also use gut models in biotics research. Ouwehand notes that, in most cases, these models simulate the microbiota quite well. 

“For instance, for prebiotic work, they’re pretty good. They’ll give you quite some information on what microbes will react, what metabolites will be formed,” he details. 

Ouwehand sees promise in in silico gut models, provided there is sufficient computing power.But he cautions that these models miss the host response. He suggests that researchers can harvest material and expose tissue-cultured cells to a simulated chyme (semi-digested food) from the intestine to provide an extra angle on how the immune system or the gut epithelium may react.

At the same time, Ouwehand also sees promise in in silico gut models, provided there is sufficient computing power. 

“If you have the genome of a microbe, you can understand its metabolism. With enough computing power, you can do that for hundreds or thousands of organisms, similar to what you have in your gut, and then suddenly you can simulate your gut in silico — this is when things become very interesting.”

He adds that researchers can also introduce antibiotics and probiotics to the model to see how microbes might react to these factors. “That is where I see the simulated gut going.” 

“We probably will continue to do some in vitro work, but I think in silico we can do more,” Ouwehand predicts. “Because, at some stage, you might be able to also simulate a host interaction with that, and then you can build much bigger.” 

“That will exponentially increase the amount of computing power, but I’m sure that will be possible in the future.”