Objectives: The goal of this study was to evaluate the modulatory effect of chitosan oligosaccharidenisin conjugate (CON-C) on intestinal microbiota of human flora-associated (HFA) mice and also reveal its effect towards the high-fat diet (HFD)-induced obesity. Both Chitosan oligosaccharides and nisin showed great potential in modulating the intestinal microbiota, so it is worth to explore whether the modulation effect of chitosan oligosaccharide could be improved by covalently binding with nisin. 

Materials and Methods: CON-C was prepared by heating the mixed solution of chitosan oligosaccharide and nisin at 80°C and pH 2.0 for 24h. The structure of CON-C were analyzed by Fourier transform-infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). The CON-C’s antiobesity effect and modulatory effect toward intestinal microbiota were analyzed using human flora-associated (HFA) mice model. 

Results: CON-C could alleviated HFD-induced gut dysbiosis, by significantly decreasing the numbers of Bifidobacterium and Lactobacillus/Enterococcus spp., and increasing the numbers of Bacteroides–Prevotella and Clostridium groups. CON-C could also enriched the most differentially expressed genes through KEGG pathways of biosynthesis of amino acids, two-component system, and ATP binding cassette (ABC) transporters. 

Conclusions: The improved therapeutic effect of CON-C against HFD-induced obesity has been approved, and hence, CON-C has a great potential to be utilized as a functional food ingredient in reducing body weight.