The prevalence of acute respiratory infections and their impact on quality of life underlies the need for efficacious solutions that are safe, sustainable and economically viable. Polysaccharides in several (traditional) plant extracts have been shown to be immunostimulatory, and some studies suggest beneficial effects against respiratory infections. The aim of this study was to (i) identify the active polysaccharide constituents from affordable and renewable crops (bell pepper and carrot) using activity‐guided fractionation, (ii) evaluate in vitro effects on innate immune responses (phagocytosis and cytokine secretion), microbiota modulation and production of short chain fatty acids, followed by (iii) the evaluation of effects of a bell pepper extract enriched for the active component in a human proof of concept study. We identified rhamnogalacturonan‐I (RG‐I) as the nutricophore responsible for the immunostimulatory activity with substantial structural and functional equivalence between bell pepper (bp) and carrot (c). The in vitro studies showed that bpRG‐I and cRG‐I comprise similar immune‐ and microbiota modulatory potential and the human study demonstrated that bpRG‐I was well tolerated and enhanced innate immune responsiveness in vivo. This is an important step towards testing the efficacy of RG‐I from bpRG‐I or cRG‐I in an infection trial in humans.
- Innate immune response
- Microbiota modulation
- Rhamnogalacturonan‐I (RG‐I), bell pepper
- Short chain fatty acids (SCFA), immunity
- Viral infections