Dietary supplementation with (2'-FL) reduced fat mass and energy intake in high-fat fed mice.
2'-FL supplementation significantly decreased the HF-induced increase in fat mass and energy intake.
Intestinal permeability was significantly reduced with 2'-FL supplementation.
2'-FL significantly increased the expression of interleukin (IL)-22, which plays a protective role in the intestine.
Changes in gut microbiota composition and associated microbial metabolites were observed with 2'-FL.
Signaling in the vagal afferent pathway improved with 2'-FL supplementation, but cognitive function showed no significant change.
Simplified
(2'-FL) is one of the predominant oligosaccharides found in human milk and has several well-established beneficial effects in the host. It has previously been shown that 2'-FL can improve the metabolic phenotype in high-fat (HF)-fed mice. Here we investigated whether dietary supplementation with 2'-FL was associated with improved intestinal barrier integrity, signaling in the vagal afferent pathway and cognitive function. Mice were fed either a low-fat (LF, 10% fat per kcal) or HF (45% fat per kcal) diet with or without supplementation of 2'-FL (10% w/w) in the diet for 8 weeks. Body weight, energy intake, fat and lean mass, intestinal permeability (in Ussing chambers), lipid profiles, gut microbiome and microbial metabolites, and cognitive functions were measured. Vagal afferent activity was measuredimmunohistochemical detection of c-Fos protein in the brainstem in response to peripheral administration of cholecystokinin (CCK). 2'-FL significantly attenuated the HF-induced increase in fat mass and energy intake. 2'-FL significantly reduced intestinal permeability and significantly increased expression of interleukin (IL)-22, a cytokine known for its protective role in the intestine. Additionally, 2'-FL led to changes in the gut microbiota composition and in the associated microbial metabolites. Signaling in the vagal afferent pathway was improved but there was no effect on cognitive function. In conclusion, 2'-FL supplementation improved the metabolic profiles, gut barrier integrity, lipid metabolism and signaling in the vagal afferent pathway. These findings support the utility of 2'-FL in the control of gut barrier function and metabolic homeostasis under a metabolic challenge. ex vivo via
Key numbers
HF/2'-FL vs. HF/CON < 0.05
Decrease in Energy Intake
Energy intake was significantly reduced in 2'-FL supplemented mice on a high-fat diet.
2'-FL supplementation decreased paracellular and transcellular permeability
Improved Gut Barrier Function
2'-FL supplementation significantly improved gut barrier integrity in both diet groups.
Higher c-Fos expression in AP and NTS areas in HF/2'-FL
Activation
2'-FL-treated mice showed increased neuronal activation in response to CCK.
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HER, MG, SL, WV, MB have no financial or personal, or otherwise conflicts of interests. DB is the co-founder of Evolve Biosystems, a company focused on probiotics.
