Fucosyllactose prebiotic may protect intestines from injury: Mouse data

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Supplementation with human milk oligosaccharides (HMOs) in adulthood may balance the gut microbiome and prevent intestinal inflammation, says a new study that sheds light on the potential mechanisms of action of HMOs.

Writing in mBio, researchers from Vanderbilt University in Tennessee reported that 2’-FL (2’-fucosyllactose), the most abundant HMO in breastmilk, could rectify dysregulated microbial metabolism in lab mice transplanted with fecal microbiota from animals with ulcerative colitis.

Focusing on the gut microbe Bifidobacterium infantis, the researchers also found that 2′-FL-enriched the production of specific metabolites, including a compound called pantothenol.

"This work demonstrated that the 2-FL-modulated gut microbial community plays significant roles in mitigating intestinal injury and colitis in adult mice and identified a metabolic mechanism involved in this effect," they wrote.

"By using B. infantis as a 2′-FL consumption bacterial model, we found pantothenol as a novel 2′-FL-derived secreted metabolite that can maintain intestinal barrier integrity and protect against colon injury and inflammation."

HMOs

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 over 200 different HMOs. 2’FL is the most abundant and is therefore the most studied. It is already commercially available from several different suppliers. Other HMOs have also been released onto the market, such as 3-fucosyllactose (3-FL), 3’-sialyllactose (3’-SL), 6’-sialyllactose (6’-SL) and lacto-N-neotetraose (LNnT).

While the majority of the science to date has focused on infants, there is data published in the scientific literature on the potential benefits in adults. For example, a 2016 study published in the British Journal of Nutrition (Elison et al. Vol. 116, pp. 1356-1368) concluded: “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.”

Study details

In the current study, the Vanderbilt researchers noted: "Although the correlation between 2′-FL and its beneficial health effects has been recognized, the mechanism(s) by which 2′-FL protects intestinal homeostasis remain unclear. Particularly, the contribution of the 2′-FL and HMO-modulated gut microbial community to the biological effects in infancy and adulthood remains largely unclear."

According to their findings, adult mice that consumed 2′-FL had higher abundances of several beneficial genera in the gut microbiota, including Bifidobacterium and Lactobacillus, and these HMO-modulated gut microbial communities exerted beneficial effects in mice treated with a specific chemical to induce colitis.

Additional studies using B. infantis showed an increase in the production of pantothenol by the bacteria, and this compound was associated with protecting the intestinal barrier in the mice and reducing colitis.

Commenting on the importance of their findings, the researchers noted their work "demonstrates a previously unrecognized role of pantothenate in significantly protecting the intestinal barrier against oxidative stress and mitigating colitis in adult mice".

"Remarkably, 2′-FL-enhanced bacterial metabolic pathways are found to be dysregulated in the fecal microbiota of ulcerative colitis patients," they reported. "These novel metabolic pathways underlying the bioactivities of 2′-FL may lay a foundation for applying individual oligosaccharides for prophylactic intervention for diseases associated with impaired intestinal homeostasis."

Source: mBio

Published online ahead of print, doi: 10.1128/mbio.00298-24

“A human milk oligosaccharide prevents intestinal inflammation in adulthood via modulating gut microbial metabolism”

Authors: K.M. Schalich et al.