While the gut has dominated microbiome research and innovation, the oral cavity—the second most diverse microbiome in the human body—is emerging as both a critical gateway to systemic health and a fertile ground for innovation.
Speaking at the conference, Marco Pane, chief scientific officer at Probiotical, said new research on the oral microbiome marks an important shift in how the industry thinks about traditional microbial research methods.
“In the last 20 years, microbiome science has focused mostly on s**t,” he told delegates in Dublin. “It is like all the microbial studies have been really led by the emergency exit of our bodies.”
“This makes me think a lot about the value of studies that focus just on stool. Stool samples are convenient and non-invasive […], and there is a lot of biological material that you can use, but we only get a picture specifically of the last part of the journey from the mouth to the intestine. So I’m glad that our colleagues and speakers are starting to look at different body sites.”
New evidence linking oral dysbiosis to gastrointestinal and inflammatory conditions is reshaping how researchers think about microbial translocation and disease origins, while advances in sampling, strain discovery and biotic formats are expanding what is technically and commercially possible.
Together, these developments signal a broader evolution in the microbiome field: one that moves beyond the gut, embraces next-generation biotics and applies precision engineering to unlock targeted, stable and scalable health solutions.
The mouth as the ‘gateway’ to the body
Home to an estimated 20 billion bacteria at any given time, including 16 phyla, 230 genera and 770 species, the oral microbiome is made up of anatomically diverse micro-environments, with different communities living on the teeth, tongue, cheeks and gums.
In a healthy state, these microbes live in balance, protecting the host, but when this balance becomes disrupted, pathogens and other harmful bacteria can multiply, leading to dysbiosis.
Several lifestyle factors can cause oral dysbiosis, including diet, stress, poor oral hygiene, medical interventions and hormonal changes, which can have a significant impact on health. This is a pressing issue, given that an estimated 3.5 billion people are affected by oral diseases worldwide and the burden is increasing, particularly in low- and middle-income countries.
“The mouth is the gateway to our body,” said Dr. John Hale, chief technology officer at New Zealand-based oral probiotic company BLIS, during his presentation on the oral cavity’s link to health. “It is one of the primary orifices for bacteria to enter your body […] and it connects your body down to the GI tract, but also to your eustachian tubes, up to your ears, and your respiratory tract.”
This means that a problem in the mouth does not stay in the mouth, and Dr. Hale presented research showing that oral dysbiosis can cause both local and systemic diseases. For example, strep throat can lead to scarlet fever, toxic shock syndrome, nephritis, psoriasis and even pediatric autoimmune conditions, such as PANS/PANDAS.
These conditions are often caused by bacterial translocation—when pathogens move from the mouth into other areas of the body. Simon Yersin, a PhD candidate at the University of Lausanne, presented research showing that the duodenum (the first section of the small intestine) and the jejunum (middle section) often contain similar taxa to that of the mouth.
Multiple studies have identified a link in people with diseases such as colorectal cancer, liver disease, undernutrition and IBD, who often have an increased abundance of oral bacteria in the small intestine and the colon. In fact, Yersin’s team has uncovered a secondary form of small intestinal bacterial overgrowth (SIBO) called small intestinal oral bacterial overgrowth (SIOBO) that can have pathophysiological effects including lipid malabsorption, leaky gut and inflammation.
Yersin’s research suggests that translocation of oral bacteria may be caused by impaired host filtering, such as decreased gastric acidity or lower antimicrobial compounds levels, or that some bacterial strains are able to attach to the mucus or cell layer in the intestinal tract, enhancing their ability to translocate. However, knowledge gaps persist.
“We are still missing a proper description and characterization of a healthy small intestine microbiome,” he said. “There are also some controversies about the level of translocation of oral strains to the gastrointestinal tract. While it’s more and more clear in disease contexts, we don’t know if the strains, these oral taxa, are able to establish in healthy people.”
One of the main challenges in understanding the small intestinal microbiome lies in sampling techniques. Since fecal samples predominantly give an indication of the large intestine microbiota, researchers have historically been left with two options: performing an endoscopy (which is uncomfortable and can lead to contamination) or utilizing ileostomy pouches (which limits samples to people who have existing health issues).
Promisingly, however, novel techniques are being developed. For example, U.S.-based start-up Microvitality—which was selected as one of this year’s Probiota Pioneers—has developed an ingestible capsule designed to access the small intestine, allowing for previously unreported biomarker discovery and therapeutic developments.
“Proxies such as breath testing and stool sampling […] lack accuracy and give us limited diagnostic capabilities,” said Zoe Watson, co-founder and CEO of Microvitality. “What we are designing at Microvitality is direct sampling with the ability to identify specific microbes present that can then diagnose and treat patients.”
Novel techniques such as this are expected to enable repeated sampling of specific sections of the digestive tract, allowing for longitudinal analyses and the identification of characteristics across geographies, age groups, diets and disease status.
Oral microbiome solutions for whole-body health
As companies begin to harness the knowledge of upstream microbiomes, a swathe of novel solutions are coming to market. For example, Probiota Pioneer LuvBiotics recently launched a range of probiotic toothpastes, mouthwashes and lozenges which aim to restore the oral microbiome to a harmonious state.
“The traditional market is concentrated on killing everything in the mouth, or disinfecting the mouth, so we wanted to develop a product to balance the ecosystem in our bodies,” said Samanji Wigesena, co-founder of LuvBiotics, during her presentation. “We have seen consumer expectations evolve, but the products on the market haven’t.”
Anti-bacterial products still lead the oral health market, but Nick Stene, senior global insight manager of consumer health at Euromonitor, identified the oral microbiome as “the next frontier for commercial strain growth.”
In the last few decades, several probiotic strains specifically designed for oral health have been commercialized and patented, such as BLIS’s daily K12 strain. First introduced to the European market in 2011, BLIS K12 has been shown to reduce the risk of tonsilitis, oral thrush and otitis media (ear infections). There is also evidence that it reduces the risk of respiratory infections and lowers psoriasis severity scores compared to placebo.
BioGrowing Probiotics also has several probiotic strains for oral health in its product portfolio, including five patents in China, the United States, Europe, Japan and Australia.
While the company’s research efforts have predominantly focused on probiotic solutions for halitosis, inflammation, gingivitis and dental plaque, BioGrowing has also begun exploring postbiotic solutions. For example, LPc-G110, in both its live and inactivated form has shown significant effects in downregulating cellular inflammatory cytokines and suppressing inflammation in oral fibroblasts, opening up opportunities for innovative delivery formats, such as gummies, and the company’s patented ‘OralBubble’, a microbubble lozenge.
As the scientific evidence and market expands, Hale said oral probiotics could be the ‘next wave’ of biotic solutions—and even traditional, colonic microbiome experts are expressing interest in further study.
“I think I’m becoming a convert here towards the oral microbiome after this session, and I might need to readjust my research focus a little bit,” said Professor Marcus Claesson, associate professor at University College Cork, during a ‘gums to bums’ panel discussion. “All the samples we have been taking are biopsies from stool, but as lots of other people have shown, there is a clear impact of the oral microbiome further down. ”
Opportunities in strain optimization
Despite these advances, the vast majority of probiotics solutions on the market are focused on the colonic microbiome. The colon has historically been the main area of focus for researchers due to its high microbial density, its role in fermentation and SCFA production and accessibility for sampling (through the stool).
Advances in omics, sequencing, screening and genetic engineering are now creating novel opportunities in the field, particularly when it comes to bacterial strain optimization.
Dr. Sarah O’Flaherty, a senior research scholar at North Carolina State University, said CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) represents the future of engineering. Essentially, CRISPR systems act as an adaptive immune system for bacteria and archaea against invaders such as bacteriophages and plasmids, and can be programmed to target specific stretches of genetic code and edit DNA at precise locations.
In the microbiome field, this technology is being used to create practical products, such as baby formula and women’s health solutions. Dr. O’Flaherty’s team has used the technology to produce HMOs from a gold standard probiotic by cloning the HMO biosynthesis pathway and ‘deleting’ a specific gene that usually eats sugar, forcing the bacteria to use that sugar to build HMOs instead.
North Carolina State University is also working with start-up Ancilia Biosciences to develop the next generation of bacterial therapies for women’s health via natural CRISPR immunity. For example, they are developing a ‘super CRISPR array’ which enables probiotic strains to be immune to the vast majority of viruses in disease contexts such as bacterial vaginosis.
Other companies are using gene editing tools to preserve the unique character of certain strains and avoid transgenic modifications. For example, Carlsberg spin-off Traitomic is using a new tool, dubbed FIND-IT (Fast Identification of Nucleotide variants by droplet) to improve bacterial strains that are fundamental for brewing.
This technology is making it possible to identify optimized versions of probiotic strains with new and desirable properties, without impacting favorable characteristics and functionalities. It is also enabling the identification of plants with specific traits, such as those with high yields, improved flavor and better resistance to heat and drought.
During his presentation, Dr. Wilbert Sybesma, the founder of Microbiome Solutions, also discussed how gene-edited cultures could enhance fermentation performance, as well as the flavor, texture and safety of foods.
Large companies such as Nestlé and BioGaia are already using such technologies to optimize probiotic strains. For example, Nestlé has used sequential heat shocks to enable probiotics to survive during spray drying and storage. Meanwhile, BioGaia optimized its flagship L. reuteri strain by removing resistant plasmids that carried antibiotic resistance genes while ensuring the new strain maintained growth and adhesion.
Dr. Sybesma cautioned that there is still a long way to go when it comes to consumer acceptance of engineered probiotics, noting that public acceptance will only improve when communication focuses on measurable health benefits rather than technical descriptions of genetic modification.
Postbiotics: The next big thing?
Although the postbiotic concept emerged in the early 20th century, multiple speakers referred to this biotic format as the next ‘big thing’ in the microbiome field.
“It’s important to say that we’re thinking about next-gen biotics as opposed to [next-gen] probiotics—for ADM, that really means postbiotics and bacteriophages,” said Dr. Richard Day, vice president of medical affairs at biotic manufacturer and supplier ADM.
ADM, which recently established a research facility in Spain dedicated to postbiotic research, has launched a number of postbiotic solutions in the last few years, predominantly targeting stress, mood and sleep.
Other global ingredient companies are following suit, with Danone recently acquiring the Akkermansia Company to incorporate its postbiotic ingredient into food products. This is creating novel opportunities in the field, given that heat-killed microbes do not require refrigeration or specialized encapsulation techniques.
Ingredient supplier dsm-firmenich has also commercialized its Humiome postbiotic ingredient, derived from two Lactobacillus strains. The company’s research shows that the ingredient may also offer benefits beyond gut health, including reduced stress and improved muscle function (although these studies are pre-clinical). DSM is also currently exploring the role of postbiotics in healthy aging.
Postbiotics are still considered a novel, emerging category, despite their long history, and have only recently been defined by leading biotic organizations, such as the International Scientific Association for Probiotics and Prebiotics (ISAPP) and the International Probiotics Association (IPA).
Even now, definitions differ. The IPA defines postbiotics as “products of microbial metabolism followed by inactivation and/or inactivation and then separation of cell fragments or metabolites, which can exert beneficial physiological effects.”
This differs from the ISAPP definition which refers to postbiotics as “inanimate” rather than inactive. Professor Colin Hill, professor of microbiology at University College Cork, who co-authored the ISAPP consensus paper, said this is an important distinction given that the term “inactive” implies a lack of effect, which contradicts the core requirement of a postbiotic.
He added that postbiotics can perform most of the functions of probiotics, while having significant advantages given their safety profile, stability and potential use alongside antibiotics.
“You can co-administer with antibiotics without any fear of the antibiotic killing the probiotic because it’s already inanimate,” he said. “They are much more stable, of course, with longer shelf life and higher storage temperatures.”
As the scientific evidence base expands, postbiotics are expected to become more mainstream, but one of the most important things to consider, according to ADM’s Dr. Day, is that inactivating a known probiotic does not automatically create a valid postbiotic.
“Whichever definition you’re looking at, you need to have the health benefit,” he said. “Just because you see a health benefit in a live probiotic and then you inactivate it somehow does not mean you will necessarily see a health benefit.”
While the industry is clearly eager to explore the new opportunities this field has to offer, postbiotics still represent a miniscule segment of the market, with consumer understanding still fairly limited.
Euromonitor’s Stene presented data which showed that the term ‘postbiotic’ features on just 0.2% of dietary supplement products on the global market. This compares to 2% for prebiotics and roughly 10% for probiotics. Yet while product mentions are small, postbiotics have a rapidly rising presence in most global markets.
“We’ve got this pattern of constant growth, rapid growth, but this is still at a very low level,” he said. “If I look at the pattern, this is more of a support message on SKUs than the hero message.”
