Nestlé-funded research finds HMO blend mirrors breast milk-led gut development

The study focuses on 2′-fucosyllactose, 2′,3-di-fucosyllactose, lacto-N-tetraose, 3′-sialyllactose, and 6′-sialyllactose, as HMOS that promote higher bifidobacterial numbers and lower levels of toxigenic Clostridioides difficile.​

Writing in Frontiers in Nutrition, ​the Nestlé Nutrition-funded study, highlights the HMO’s “strong bifidogenic effect and less toxigenic C. difficile, which is expected to decrease the risk of diarrheal illness. ​

“The shift in the gut microbiota may mediate, to a certain extent, the effects that have been seen on intestinal immune response evidenced by the substantial increase in faecal secretory immunoglobulin A (SlgA).”​ (a marker of gut secretory immunity and barrier).

“Supplementing infant formula with our blend of five HMOs is therefore a promising and efficacious approach to support the gut microbiome and gut barrier and immune maturation during early infancy of formula-fed infants.”​

Study details ​

With assistance from Denmark-based Clinical Microbiomics, the study adopted a multicentre approach, in which healthy infants (seven to 21 days old) were randomly assigned to one study group.

Group members were asked to consume either a standard cow’s milk-based infant formula (control group, CG); the same formula with 1.5 grams per litre (g/L) HMOs (test group 1, TG1); or with 2.5 g/L HMOs (test group 2, TG2).

A human milk-fed group (HMG) was enrolled as a reference with faecal samples collected at baseline, age three and six months and analysed for microbiome metabolism, and biomarkers.

Findings revealed at both post-baseline visits, different microbiota compositions in the two test groups (TGs) compared to CG with coordinates closer to that of HMG.

The relative abundance of Bifidobacterium longum​ subsp. infantis (B. infantis​) was higher in TGs vs. CG (except at six months).

Bifidobacterium abundance was higher by around 45% in TGs vs. CG at six months approaching HMG.

Further discoveries revealed toxigenic Clostridioides difficile​ abundance was 75–85% lower in TGs vs. CG and comparable with HMG.

Faecal pH was significantly lower in TGs vs. CG, and the overall organic acid profile was different in TGs vs. CG, approaching HMG.

At three months, TGs (vs. CG) had higher secretory immunoglobulin A (sIgA) and lower alpha-1-antitrypsin.

At six months, sIgA in TG2 vs. CG remained higher and calprotectin was lower in TG1 vs. CG.

Decrease in inflammation marker​

“In our study, test groups had significantly higher abundance of these breastmilk-promoted Bifidobacterium species, indicating that the five-HMO blend likely increases the production of some immunomodulatory metabolites in formula-fed infants,”​ the research team suggests.

“We also found some indication that the HMO formulas contribute to the known decrease in the gut inflammation marker calprotectin in infants over time. ​

“Together, our faecal biomarker results indicate that HMO-supplemented formula may be supportive of the infant intestinal immune development and gut barrier function,”​ they conclude.

HMOs have been long recognised as drivers of the Bifidobacterium dominance in breastfed infants.

Bifidobacterium longum​ subsp. infantis (B. infantis)​ is known as a dedicated HMO consumer and able to proliferate in the presence of HMOs.

Additionally, a role of HMOs in immune protection has been demonstrated via anti-adhesive antimicrobial effects, regulation of intestinal epithelial cell response, and modulation of immune responses.

Furthermore, potential benefits of HMOs on brain development have been reported.

With more HMOs becoming available, it is possible to supplement formulas with blends of HMOs providing structurally diverse and complex oligosaccharides to formula-fed infants.

Clinical trials have demonstrated that infant formula with 2′FL and LNnT was shown to promote a microbiome more like the human milk-fed reference than formula not containing HMOs.

In another trial, infants fed a formula containing 2′FL and galacto-oligosaccharides had plasma and ex vivo​ inflammatory cytokine profiles more similar to the breastfed reference than control infants fed a formula with galacto-oligosaccharides alone.

Source: Frontiers in Nutrition​​

Published online: doi.org/10.3389/fnut.2022.920362​​

'Infant Formula With a Specific Blend of Five Human Milk Oligosaccharides Drives the Gut Microbiota Development and Improves Gut Maturation Markers: A Randomized Controlled Trial.'​

Authors: Miroslava Bosheva et al.