Polyphenols non-covalently bound to artificial plant cell walls are readily accessible to fecal microbiota and transiently alter fermentation activity
Plant-based foods support gut microbiota metabolism by providing a wide variety of non-digestible dietary fibers (DFs) and secondary metabolites such as polyphenols (PPs). Upon mastication or food processing, PPs get entrapped within the plant cell wall polysaccharides, forming covalent interactions that are strong enough to alter the PP profiles and lead to lower bioavailability in the upper gut and preserve their integrity to reach the colon. In the colon, PPs are metabolized by the microbiota, releasing bioactive metabolites and contributing to microbiota composition and function. As such, DFs and PPs may interact with the gut microbiota independently or in combination. However, most research focuses on their independent effects overlooking their interactions, which are more representative of real-life scenarios. As such, this study investigated the three-way interaction among DFs, PPs, and the gut microbiota at physiologically relevant concentrations (0.8 g/L). In vitro testing, using fecal microbiota batch fermentation from five donors (aged 20-49 years), was utilized to analyze a three-component bacterial cellulose analogue of the apple cell wall (aACW) soaked in a PP extract from apples (aACW + PP) on gut microbiota responses at 0, 5, 24, and 48 h. The in vitro fecal fermentation results showed that several flavonoids were detected early but were rapidly metabolized, with differences observed between individual fecal microbiota. Beta-diversity analysis revealed a donor-dependant variance and individuality as a stronger determinant of microbiota composition than the treatment itself. After 5 hours, aACW-bound PPs increased the fermentation activity, producing more acetic acid and lower formic acid levels. Lastly, the baseline differences between the microbiota composition from the different donors appeared to be a major factor in shaping PP metabolism and microbial community trajectories under the tested concentrations.
Key takeaways:
- The study investigated the interactions between DFs and PPs at concentrations reflecting actual dietary habits and their synergistic effects on gut microorganisms using an apple pomace (aACW) as model system in an in vitro analysis.
- Using two treatments, aACW alone or aACW combined with PP at 0.8 g/L, a physiologically relevant concentration, revealed a donor-dependent response in microbiota shifts rather than a not treatment-dependent effect.
- The aACW with PP showed a transient but significant rise in acetic acid levels at the 5-hour point compared to the control (only aACW), but no sustained overall short-chain fatty acid increase at later timepoints.
Access the study: https://pubmed.ncbi.nlm.nih.gov/40795553/
Reference: Bechtner, J. D., Lopez-Rodulfo, I. M., Gallego-Lobillo, P., Hosek, J., Schwab, C., & Martinez, M. M. (2025). Polyphenols non-covalently bound to artificial plant cell walls are readily accessible to fecal microbiota and transiently alter fermentation activity. Food chemistry, 493(Pt 2), 145817. Advance online publication. https://doi.org/10.1016/j.foodchem.2025.145817.
Effects of maternal allergy and supplementation with ω-3 fatty acid and probiotic on human milk oligosaccharides
Human milk oligosaccharides (HMOs) are complex carbohydrates that are largely indigestible and have prebiotic properties, supporting the neonate’s gut microbial colonization and immune development. To date, over 200 structurally distinct HMOs have been identified. Maternal-related factors such as genetics, diet, and overall health status contribute to HMO levels. This study investigated the effects of supplementing with omega-3 polyunsaturated fatty acids (omega-3 PUFA) and Limosilactobacillus reuteri on HMO levels in colostrum and mature milk. It also examined differences in HMO levels between allergic and non-allergic mothers, exploring the potential correlation with secretory immunoglobulin A (SIgA) in milk and allergy development during the first two years of life. One-hundred and thirty-six mothers provided milk samples, receiving either: 1) Omega-3 PUFA + L. reuteri, 2) Omega-3 PUFA + Placebo, 3) Placebo + L. reuteri, or 4) Placebo + Placebo. Omega-3 PUFA capsules were administered to the pregnant women from gestational week 20 through three months postpartum, receiving three capsules (containing 640 mg omega-3 PUFAs, with 35% eicosapentaenoic acid and 25% docosahexaenoic acid) twice daily. L. reuteri was taken in oil format, with the pregnant mothers using 10 drops twice daily (equivalent to 109 colony forming units (CFUs) per serving) from gestational week 20 until delivery. Newborns received 5 drops daily (equivalent to 108 CFUs per serving) during the first year of life. The placebo was olive oil. HMOs were measured in colostrum and mature milk collected three months postpartum and SIgA in colostrum at 1-, 2-, 3-, and 4-month milk. While the supplements did not cause a change in HMO levels in the colostrum or mature milk, maternal intake of omega-3 PUFA had a decreased HMO diversity over time. L. reuteri had no significant effect on HMO levels or diversity. In addition, significantly lower levels of several HMOs were noted in the allergic mothers compared to non-allergic mothers, and SIgA positively correlated with fucosylated and negatively with sialylated HMOs, suggesting an interplay between immune factors and milk composition.
Key takeaways:
- The role of maternal health and diet in shaping the bioactive components in breast milk and their influence on infant immunity is a topic of interest in research.
- This study examined the effects of maternal supplementation with omega-3 PUFA and the probiotic L. reuteri on HMOs composition between allergic and non-allergic mothers and their correlation with SIgA.
- While both omega-3 PUFA and L. reuteri had no significant change over HMO levels, omega-3 PUFA reduced the HMO diversity over time.
- Future research should explore the mechanisms underlying the omega-3 PUFA-induced reduction in HMO diversity and the biological pathways connecting HMOs, SIgA, and maternal gut interactions.
Access the study: https://pubmed.ncbi.nlm.nih.gov/40747696/
Reference: Al-Kaabawi, A., Landberg, E., Martí, M., Severin, E., Tingö, L., Duchén, K., & Jenmalm, M. C. (2025). Effects of maternal allergy and supplementation with ω-3 fatty acid and probiotic on human milk oligosaccharides. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology, 36(8), e70162. https://doi.org/10.1111/pai.70162.
A human milk oligosaccharide alters the microbiome, circulating hormones, and metabolites in a randomized controlled trial of older adults
HMOs are well studied for their various benefits in shaping the infant gut microbiome, supporting immune development, and protecting against pathogens. However, HMOs are largely under-studied in adult humans. This 6-week randomized controlled trial evaluated the effects of the HMO 2’-fucosyllactose (2’-FL) on improving gut microbiota and immune function in healthy adults. A total of 89 healthy adults (aged 60-84 years) were randomized to one of three arms: 1) 5 g/day 2′-FL, 2) 1 g/day 2′-FL, or 3) glucose placebo for six weeks. While the primary outcome of change in the cytokine response score showed no statistical difference with 2’-FL supplementation, 2′-FL appeared to transiently but significantly increase Bifidobacterium levels at week 3, with increases also detected in serum insulin, high-density lipoprotein (HDL) cholesterol, and fibroblast growth factor 21 (FGF21) hormone. Notably, the subjects that showed a response to the change in Bifidobacterium also experienced additional metabolic and proteomic changes and performed better on a cognitive test of visual memory. Subjects that showed no response to the Bifidobacterium change were more likely to lack the bacterium in their gut microbiota at the start of the intervention. Multi-omics analysis uncovered a systemic response to 2’-FL, detectable in blood and urine, which showcase this prebiotic’s potential to provide diverse benefits for healthy aging. Lastly, previous research has shown that Bifidobacterium can stimulate the release of glucagon-like peptide-1 (GLP-1) in the gut, which in turn, promotes insulin secretion, linking the microbiota changes to improved metabolic outcomes such as increased fasting insulin and HDL cholesterol levels.
Key takeaways:
- HMOs, especially 2′-FL, are well known for their role in shaping the infant gut microbiome and immune system, but their effects in older adults remain largely unexplored.
- This randomized, placebo-controlled trial assessed the safety, tolerability, and impact of 2′-FL supplementation on the gut microbiome, immune markers, and metabolic outcomes in healthy adults aged 60 years and older.
- 2′-FL induced a transient but significant increase in Bifidobacterium abundance at week 3, with increases in fasting insulin, HDL cholesterol, and FGF21, though no significant group-level changes were seen in the primary outcome of cytokine response score.
- Future research should explore the mechanisms of action and evaluate personalized responses to 2′-FL supplementation.
Access the study: https://pubmed.ncbi.nlm.nih.gov/40738103/
Reference: Carter, M. M., Demis, D., Perelman, D., St Onge, M., Petlura, C., Cunanan, K., Mathi, K., Maecker, H. T., Chow, J. M., Robinson, J. L., Sabag-Daigle, A., Sonnenburg, E. D., Buck, R. H., Gardner, C. D., & Sonnenburg, J. L. (2025). A human milk oligosaccharide alters the microbiome, circulating hormones, and metabolites in a randomized controlled trial of older adults. Cell reports. Medicine, 6(8), 102256. https://doi.org/10.1016/j.xcrm.2025.102256.
Gut microbiota-targeted dietary supplementation with fermentable fibers and polyphenols prevents hypobaric hypoxia-induced increases in intestinal permeability
As a potential mediator of host responses to environmental stressors, the gut microbiota is said to interact with the intestinal barrier, contributing to the pathophysiology of high-altitude illnesses. This study investigated the effects of dietary supplementation with a blend of fermentable fibers and polyphenols, designed to target the gut microbiota during hypobaric hypoxia exposure. This study employed a randomized, placebo-controlled crossover design in which healthy adults (aged 18-39 years) were assigned to receive either a blend of fermentable fibers and polyphenols (FP; containing oligofructose-enriched inulin, galactooligosaccharide, high-amylose corn starch, cocoa, green tea and cranberry extracts, and blueberry powder), or a placebo (PL; maltodextrin) daily for three 2-week phases separated by washout periods of at least one week. During the final 36 hours of each phase, participants were put under hypobaric conditions simulating low (LA; 500 m) or high (HA; 4300 m) altitude, creating three experimental conditions: PL + LA, PL + HA, and FP + HA. Twenty-six participants completed at least one study phase and 13 (12 male; aged 21 ± 3 years) completed all three phases. FP mitigated the hypoxia-induced increase in intestinal permeability in the small intestine and proximal colon. It also increased the relative abundance of Bifidobacterium and decreased alpha diversity of the gut microbiota and colonic pH. Notably, changes in the Bifidobacterium and colonic pH were associated with the improved intestinal permeability. However, the FP supplementation did not alter the fecal short-chain fatty acid levels and was associated with increased gastrointestinal symptoms during hypobaric hypoxia exposure. Altogether, these findings support the emerging concept of utilizing the gut microbiota as a modifiable factor to influence physiological responses under austere conditions.
Key takeaways:
- The gut microbiota plays a key role in various host physiological responses to environmental stressors.
- This study investigated whether a dietary supplement blend of fermentable fibers and polyphenols could modulate the microbiota to prevent increases in intestinal permeability during hypobaric hypoxia conditions.
- The study supports the potential of novel dietary interventions that target the gut microbiota to promote performance in challenging environments such as high terrestrial altitudes.
Access to the study: https://pubmed.ncbi.nlm.nih.gov/40701649/
Reference: Karl, J. P., Fagnant, H. S., Radcliffe, P. N., Wilson, M., Karis, A. J., Sayers, B., Wijeyesekera, A., Gibson, G. R., Lieberman, H. R., Giles, G. E., & Soares, J. W. (2025). Gut microbiota-targeted dietary supplementation with fermentable fibers and polyphenols prevents hypobaric hypoxia-induced increases in intestinal permeability. American journal of physiology. Regulatory, integrative and comparative physiology, 329(3), R378–R399. https://doi.org/10.1152/ajpregu.00109.2025.