Gut simulation expands health benefits of HMOs in adults
Using systems such as the Simulator of the Human Intestinal Microbial Ecosystem (SHIME), cell lines, and human gut-on-chips, scientists report that 2’-FL (2’-fucosyllactose) alone of combined with lacto-N-neotetraose (LNnT) led to reductions in gut permeability and an upregulation in tight junction proteins, which support their role in strengthening gut barrier function in adults.
“With the demonstrated safety, tolerance, and impact of HMOs on the adult gut microbiota in clinical trials, this study supports the potential use of HMOs as a novel strategy to restore or promote gut barrier function in adults,” wrote scientists from Quadram Institute Bioscience, Glycom A/S, Prodigest Bv, Emulate Inc., National and Kapodistrian University of Athens in the journal Nutrients.
HMOs are unique carbohydrates that make up about 10% of the dry weight of mother’s milk. HMOs are not easily digested, so experts postulate that their purpose is to jump-start the infant’s microbiome.
There are about 200 different HMOs, and 2’-FL (2’-fucosyllactose) is the most abundant. As a result, it’s the most studied, and the one that is already commercially available from a number of different suppliers. Glycom, which provided the 2’-FL and LNnT used, is a leading producer of HMOs of synthetic origin. The company was acquired by DSM earlier this year.
While the majority of the science to date has focused on infants (see fact box below), there is data published in the scientific literature on the potential benefits in adults, with a 2016 study published in the British Journal of Nutrition (Elison et al. Vol. 116, pp. 1356-1368) concluding: “HMO supplementation specifically modified the adult gut microbiota with the primary impact being substantial increases in relative abundance of Actinobacteria and Bifidobacterium in particular and a reduction in relative abundance of Firmicutes and Proteobacteria.”
At the other end of the age spectrum, the bifidogenic effects of HMOs may also make these prebiotics interesting to aging populations, which are characterized by declining Bifidobacteria levels.
The new study used fecal samples from five different adult donors to simulate the adult microbiota in SHIME. Short-term (48 hours) colonic simulations revealed that differences between the donors did not change the results, allowing the researchers to randomly select the samples from one of the donors for a prolonged (three week) study. The data supported the Bifidogenic effects of 2’FL, LNnT, and a combination of them, and this was accompanied by increases in short chain fatty acid (SCFA). Butyrate was particularly increased with 2’-FL, said the researchers.
Additional experiments using Caco2 cell lines, and human intestinal gut organoid-on-chips revealed that 2’-FL reduced permeability on the cell monolayers, while the tight junction proteins called claudin-8 and claudin-5 were upregulated.
“Taken together, these data show that, in addition to their bifidogenic activity, HMOs have the capacity to modulate immune function and the gut barrier, supporting the potential of HMOs to provide health benefits in adults,” concluded the researchers.
FACT BOX: Data from infants
As stated earlier in this article, the majority of the science with HMOs has focused on infants, with a study published in Gut (He et al., 2016, Vol. 65, pp. 33–46) by scientists from Harvard Medical School indicating that 2’-FL could reduce the inflammatory response to pathogenic bacteria.
In addition, a 2017 paper in the Journal of Pediatric Gastroenterology and Nutrition (Puccio et al., Vol. 64, pp. 624–631) reported that infants fed formula with 2′-FL and lacto-N-neotetraose (LNnT), another HMO, had lower levels of bronchitis and required fewer antibiotics.
Results of a study published in the Journal of Nutrition in 2016 by scientists at Abbott Nutrition found that infants fed a formula with 2’-FL had levels of inflammatory cytokines similar to those observed for breast feeding, and significantly lower than those observed for infants fed a control formula containing no 2’-FL.
Such reports have created buzz in the marketplace around HMOs and 2-‘FL in particular, and the global HMO market size is estimated to already be worth almost US$20 million, according to Grandview Research.
2020, 12(9), 2808; doi: 10.3390/nu12092808
“Effects of Human Milk Oligosaccharides on the Adult Gut Microbiota and Barrier Function”
Authors: T. Šuligoj et al.