This is one of the focuses of an ongoing study by AMILI, a biotech startup that was founded by gut microbiome experts from the National University of Singapore (NUS).
The study is funded by dsm-firmenich, an ingredients company that awarded a €50,000 (USD52,749) Nutrition Research Grant to each of the five recipients. This is to advance understanding of gut health in Asia, whose populations are currently under-represented in terms of research data.
The gut microbiome is influenced by diet and the environment. Since most microbiome studies were conducted in North America and Europe, available research information would not be representative of the Asian population, said Associate Professor Jeremy Lim of NUS, who is also the CEO and co-founder of AMILI.
Additionally, while HMOs have been shown to provide crucial health benefits during early life, there is limited data on the prebiotic potential and health benefits of HMOs in adults.
Therefore, the key objective of this study – along with the other four research proposals funded by the grant – is whether HMOs can benefit the Asian adult gut microbiome through supplementation.
“Even in infants, HMOs require specific gut microbes to break them down into useful components and metabolites. So, our focus is to determine if Asian adults can have the necessary microbes to unlock the benefits of HMOs,” said AMILI’s lead scientist Dr Germaine Yong.
If the findings are positive, this could pave the way for HMOs to emerge as a new prebiotic category.
Testing for a new generation of prebiotics
Currently, galacto-oligosaccharides (GOS) and fructo-oligosaccharides (FOS) are the most common prebiotics found in a wide range of supplements and functional foods globally.
Dr Yong refers to HMOs as “the next-generation prebiotics” – not just boosting gut health but also driving the production of key metabolites like GABA, tryptophan, and serotonin, which can impact neurological, immune, and metabolic health.
Metabolites can originate from both microbes and diet, but the study specifically tracks how HMOs impact their production in the gut.
The analysis will rely on metagenomic data, which involves sequencing the genetic material of entire microbial communities to identify their composition and functional potential. Dr Yong emphasised that their findings are currently inferred from this data and serve as a precursor for future clinical validation.
For neurological health, the study will track microbial metabolites like GABA and serotonin, which influence mood, stress, and sleep.
As for immune health, the team will monitor metabolites that influence allergic responses, providing insights into how the microbiome can either trigger or mitigate such reactions.
For metabolic health, they will focus on cardiovascular disease and Type 2 diabetes. Microbial metabolites like trimethylamine (TMA), linked to cardiovascular risk, and those affecting insulin secretion are key targets.
These broader systemic effects highlight HMOs as a new frontier in prebiotic science.
While the HMOs being tested in this study are already approved and commercially available, they are primarily used in infant formulas due to their well-established benefits for early gut health. However, their potential as prebiotics for adults remains largely untapped.
HMOs can be categorised into three main groups – neutral HMOs, fucosylated HMOs, and sialylated HMOs. AMILI will test across all three groups to understand their diverse effects on gut microbes, particularly in Asian adults.
The researchers will conduct low-dose in vitro tests, using less than 5 grams per serving, on stool samples from six donors between 40–60 years old, selected from AMILI’s multi-ethnic Asian stool biobank.
“Our study aims to answer two key questions: first, whether Asian populations experience similar or distinct beneficial effects; and second, whether lower doses can still deliver these benefits,” said Dr Yong.
Cost and practicality are key challenges in HMO applications.
Higher doses of 5 grams or more used in western studies have been shown to provide benefits like increased levels of Bifidobacterium species in the gut and increased production of short-chain fatty acids.
However, higher doses are expensive and difficult to incorporate into foods or supplements without affecting taste or requiring multiple tablets.
This research therefore focuses on developing low-dose solutions to ensure their benefits are both accessible and cost-effective, particularly for underserved markets.
Broader implications for market use
While this research can help guide which HMOs are suitable for specific target populations in Asia, it will be critical to further evaluate and verify clinical efficacy in human studies, particularly for HMOs that do not yet have regulatory clearance, clarified Dr Yong.
“For the HMOs that are already in the market, our results can help support provide scientific evidence to support soft claims for health indications of interest to consumers,” Dr Yong said as she highlighted two categories of soft claims.
The first “low hanging fruit” is the primary objective of demonstrating a prebiotic effect – specifically, how certain HMOs increase the abundance of beneficial microbes like Bifidobacterium. These claims align with existing regulatory guidelines in markets like Singapore.
Secondary soft claims include microbial metabolite production and its role in gut, brain, immune, and metabolic health. Such claims are less strictly regulated and often substantiated through observational data rather than full clinical trials.
Prof Lim added that AMILI’s screening process enables quick and cost-effective evaluation, reducing the typical timeline of 12–18 months for such studies to as short as three months.
This is significant, as narrowing down promising ingredients for further testing is critical and costly in pharmaceutical development. A shorter process means faster market entry.
The screening uses a plate-based system with customised media to simulate gut microbial diversity.
“This allows us to observe how introducing HMOs alters the microbial community, both in terms of the types of microbes present and their functional activity,” said Dr Yong.
When asked if there are plans to conduct studies with larger sample sizes, Dr Yong acknowledged this possibility, given the current sample size may not fully represent the Southeast Asian population.
However, the research will provide valuable insights into how HMOs impact Asian populations, as faecal samples provide the richest and most accessible source of gut microbiome data. The gut microbiome plays a central role in key areas like metabolism, immune function, and the gut-brain axis, making it the most scientifically significant focus for studying health impacts, said Prof Lim.
“Once we receive the metagenomic data from the lab experiments, we analyse which microbes and functions are impacted. We then compare these findings to our multi-ethnic Asian database to determine how a specific test compound or HMO might be functionally relevant to different target segments within that population. This step is crucial and sets our work apart,” said Dr Yong.
