2'-fucosyllactose alone or combined with resistant starch increases circulating short-chain fatty acids in lean men and men with prediabetes and obesity

Emanuel E Canfora; Lars M M Vliex; Taojun Wang; Arjen Nauta; Freek G Bouwman; Jens J Holst; Koen Venema; Erwin G Zoetendal; Ellen E Blaak

doi:10.3389/fnut.2023.1200645

2'-fucosyllactose alone or combined with resistant starch increases circulating short-chain fatty acids in lean men and men with prediabetes and obesity

Front Nutr. 2023 Jul 17:10:1200645. doi: 10.3389/fnut.2023.1200645. eCollection 2023.

Authors

Emanuel E Canfora¹, Lars M M Vliex¹, Taojun Wang², Arjen Nauta³, Freek G Bouwman¹, Jens J Holst⁴, Koen Venema⁵, Erwin G Zoetendal², Ellen E Blaak¹

Affiliations

¹ Human Biology, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center+, Maastricht, Netherlands.
² Laboratory of Microbiology, Wageningen University and Research, Wageningen, Netherlands.
³ FrieslandCampina, Amersfoort, Netherlands.
⁴ NovoNordisk Center for Basic Metabolic Research and Department of Biomedical Sciences, Faculty of Health and Medical Sciences University of Copenhagen, Copenhagen, Denmark.
⁵ Maastricht University-Campus Venlo, Centre for Healthy Eating and Food Innovation, Venlo, Netherlands.

Abstract

Background: Infusion of short-chain fatty acids (SCFA) to the distal colon beneficially affects human substrate and energy metabolism. Here, we hypothesized that the combination of 2'-fucosyllactose (2'-FL) with resistant starch (RS) increases distal colonic SCFA production and improves metabolic parameters.

Methods: In this randomized, crossover study, 10 lean (BMI 20-24.9 kg/m²) and nine men with prediabetes and overweight/obesity (BMI 25-35 kg/m²) were supplemented with either 2'-FL, 2'-FL+RS, or placebo one day before a clinical investigation day (CID). During the CID, blood samples were collected after a overnight fast and after intake of a liquid high-fat mixed meal to determine plasma SCFA (primary outcomes). Secondary outcomes were fasting and postprandial plasma insulin, glucose, free fatty acid (FFA), glucagon-like peptide-1, and peptide YY concentrations. In addition, fecal SCFA and microbiota composition, energy expenditure and substrate oxidation (indirect calorimetry), and breath hydrogen excretion were determined.

Results: In lean men, supplementation with 2'-FL increased postprandial plasma acetate (P = 0.017) and fasting H₂ excretion (P = 0.041) compared to placebo. Postprandial plasma butyrate concentration increased after 2'-FL and 2'-FL+RS as compared to placebo (P < 0.05) in lean men and men with prediabetes and overweight/obesity. Additionally, 2'-FL+RS decreased fasting and postprandial plasma FFA concentrations compared to placebo (P < 0.05) in lean men.

Conclusion: Supplementation of 2'-FL with/without RS the day before investigation increased systemic butyrate concentrations in lean men as well as in men with prediabetes and obesity, while acetate only increased in lean men. The combination of 2'-FL with RS showed a putatively beneficial metabolic effect by lowering plasma FFA in lean men, indicating a phenotype-specific effect.

Clinical trial registration: nr. NCT04795804.

Keywords: human milk oligosaccharides; obesity; prediabetes; short-chain fatty acids; substrate metabolism.

Associated data

ClinicalTrials.gov/NCT04795804

Grants and funding

Research of this work was performed in the public–private partnership CarboKinetics coordinated by the Carbohydrate Competence Center (CCC, www.cccresearch.nl). CarboKinetics is financed by participating industrial partners Agrifirm Innovation Center B.V., Cooperatie AVEBE U.A., DSM Food Specialties B.V., FrieslandCampina Nederland B.V., Nutrition Sciences N.V., Sensus B.V., and VanDrie Holding N.V. under allowances of The Netherlands Organisation for Scientific Research (NWO). JH was supported by the NovoNordisk Foundation.