New Study in Nature Journal: “Human Milk Oligosaccharides Modulate the Intestinal Microbiome of Healthy Adults”

Human Milk Oligosaccharides: A New Frontier in Adult Gut Health

A recent study titled “Human Milk Oligosaccharides Modulate the Intestinal Microbiome of Healthy Adults,” published in Scientific Reports (in the Nature family of journals), brings fascinating insights into how HMOs impact the gut microbiome of adults. While much research has focused on their role in infant gut development, this study expands the scope, exploring how this brand new gut health prebiotic influences adult gut health.

Robust Study Design

The study recruited 32 healthy adults to explore how varying doses of HMO-Concentrate, a mixture derived from donor human breast milk, affect gut microbiome composition. Participants received one of four doses (1.8g, 3.6g, 9g, or 18g) daily for seven days, with their gut microbiome monitored for 21 days after the treatment period. Fecal samples were collected and analyzed using 16S rRNA gene sequencing and metagenomics, a process that examines microbial diversity and function.

At the core of the research is the question of whether HMOs can alter microbial diversity and composition in the adult gut, which typically differs from the microbiome found in infants. The results show clear changes, particularly an increase in Bifidobacterium species, suggesting the potential HMO prebiotics have as a supplement for inflammation, gut health, and immunity in adult populations.

Reduced Diversity but Increased Bifidobacterium: Less bad guys, more good guys

One of the study’s main findings was a significant reduction in overall gut microbial diversity following HMO treatment. Microbial diversity, measured by the Shannon Index and Chao1 Index, dropped notably after seven days of HMO administration, especially at higher doses, but began recovering after 28. This might seem counterintuitive, as higher diversity is typically associated with better health. However, the decrease was not necessarily detrimental; it reflected a selective expansion of beneficial bacteria.

The most striking shift was the increased abundance of Bifidobacterium species, a hallmark of a healthy gut microbiome often associated with breastfed infants. Bifidobacterium was shown to expand in a dose-dependent manner, peaking at day seven and then gradually returning to baseline levels after HMO treatment ceased. This increase, particularly at the higher doses (3.6g and 18g), highlights HMOs' prebiotic potential, fostering the growth of beneficial bacteria even in adult guts, which typically have lower levels of these microbes compared to infants.

When measured on day 7, Five specific species of Bifidobacterium responded to the HMO treatment: B. adolescentis, B. longum, B. bifidum, B. catenulatum, and B. pseudocatenulatum. This was further validated by shotgun metagenomics, which offered species-level resolution.

Microbial Succession After HMO Treatment: Pathway to a Happy Future?

After the cessation of HMO administration, the gut microbiome did not simply return to its pre-treatment state. Instead, the study observed a notable microbial succession. Bifidobacterium gradually decreased, but other bacterial groups like Bacteroides expanded, particularly on day 14. This shift mirrors patterns seen in infants transitioning from breastfeeding, where Bacteroides gain dominance as Bifidobacterium subsides.

This finding is significant because Bacteroides play a vital role in breaking down complex polysaccharides and maintaining gut health in adults. Their expansion may suggest that after Bifidobacterium lays the groundwork for a healthier gut environment, other beneficial bacteria can flourish.

The microbial shifts seen in this study have important implications for how we understand gut microbiome dynamics in response to dietary interventions. Rather than simply boosting one type of bacteria, HMO consumption seems to set off a chain reaction, leading to more sustained changes in microbial composition.

Quantitative and Qualitative: Functional Changes

Beyond altering bacterial composition, HMO treatment also affected the functional capacity of the gut microbiome. Shotgun metagenomics revealed that HMO intake was associated with increased pathways involved in antibiotic synthesis and decreased pathways linked to antibiotic resistance. These findings suggest that HMOs may enhance the gut’s natural defenses against harmful microbes.

Moreover, the study found increases in short-chain fatty acids (SCFAs), particularly acetate and butyrate, in response to HMO treatment. SCFAs are crucial for maintaining gut health—they support the integrity of the gut barrier and have anti-inflammatory properties. Although the changes in SCFA levels did not reach statistical significance in this study, the trend is consistent with the known role of Bifidobacterium in producing SCFAs from complex sugars like HMOs.

This functional shift aligns with the broader changes in microbial composition, suggesting that HMOs not only reshape the bacterial population in the gut but also enhance its metabolic activity in ways that promote health.

Systemic Effects: Cytokines and Serum Metabolites

The study didn’t limit its observations to the gut. Blood samples revealed systemic changes as well. Notably, levels of the regulatory cytokine TGF-β increased after HMO treatment,

particularly in the highest dose group (18g). TGF-β is a key player in regulating immune responses and maintaining gut barrier function. Increased levels of this cytokine could indicate improved gut health and a lower risk of inflammation, although more research is needed to confirm this.

Interestingly, the study also found changes in circulating metabolites, with decreases in markers linked to metabolic diseases like succinate and sphingosine-1-phosphate. These metabolites are associated with obesity, insulin resistance, and cardiovascular risk. The reduction in these markers could suggest a protective effect of HMOs on metabolic health, though the clinical implications of these findings remain to be explored in future studies.

Why we love HMOs!

This study presents a compelling case for the use of HMOs as a tool to modulate the adult gut microbiome. By selectively promoting Bifidobacterium and facilitating positive microbial succession, HMOs offer benefits in maintaining or restoring a healthy gut environment. These effects, combined with changes in functional capacity, SCFA production, and systemic metabolites, back up HMOs as being on the forefront of prebiotics for inflammation, IBS, and immunity.

This research piles on top of a growing body of scholarship in support of HMOs. They are not just for infants—adults, too, can nurture their often forgotten microbiomes with this prebiotic fiber, whether as a supplement, or in a beverage (like bellie’s prebiotic herbal tea!). By improving gut health to potentially influencing metabolic and immune functions, HMOs stand out as some of the most promising and modern prebiotic fibers!

 

Jacobs, J.P., Lee, M.L., Rechtman, D.J. et al. Human milk oligosaccharides modulate the intestinal microbiome of healthy adults. Sci Rep 13, 14308 (2023). https://doi.org/10.1038/s41598-023-41040-5