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Previously, a polysaccharide produced by <i>Chaetomium</i><i>globosum</i> CGMCC 6882 was found to have antibacterial activity, but its toxic effects on body health and gut microbiota were concealed. Recent results showed that this polysaccharide was safe to Caco-2 cells and mice, while it reduced the body weight gain of mice from 10.5 ± 1.21 g to 8.4 ± 1.17 g after 28 days administration. Acetate, propionate, butyrate and total short-chain fatty acids concentrations increased from 23.85 ± 1.37 μmol/g, 10.23 ± 0.78 μmol/g, 7.15 ± 0.35 μmol/g and 41.23 ± 0.86 μmol/g to 42.77 ± 1.29 μmol/g, 20.03 ± 1.44 μmol/g, 12.06 ± 0.51 μmol/g and 74.86 ± 2.07 μmol/g, respectively. Furthermore, this polysaccharide enriched the abundance of gut microbiota and the <i>Firmicutes</i>/<i>Bacteroidetes</i> ratio was increased from 0.5172 to 0.7238. Overall, this study provides good guidance for the promising application of polysaccharides as preservatives in foods and in other fields in the future.