Objective: To reveal the effect of foods with different natures on cold or hot syndrome and gastrointestinal bacterial community structure in mice.Methods: Forty-five 6-week-old male ICR Kunming mice of clean grade were divided into 5 groups,9 per group,including the control (CK),hot nature herb medicine (HM),Hong Qu glutinous rice wine (RW),tea rice wine (TW),and cold nature herb medicine (CM) groups.Distilled water or corresponding herbs were administered to mice (0.01 mL/g body weight) in the 5 groups by gastric infusion respectively,once daily for 28 d.Appearance,behavior,and serum biochemical indicators,including 5-hydroxytryptamine (5-HT),thyroid stimulating hormone (TSH),noradrenaline (NE),cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP),the hot nature index,as well as the gastrointestinal bacterial community structure were analyzed in all groups after treatment.Results: After supplementation for 28 d,CM and TW mice showed different degrees of cold syndrome,and HM and RW mice showed different degrees of hot syndrome.Compared with the HM and RW mice,the TSH,NE,cAMP levels and hot nature indices in the CM and TW mice were significantly decreased and 5-HT and cGMP levels were significantly increased (P＜0.05).There was no obvious change in appearance or behavior in CK mice.Results of clustering analysis showed that the gastrointestinal bacterial community structures were highly similar in TW and CM mice as well as in RW and HM mice,and that they were from the same branch,respectively,when the distance was 0.02.The key microbes associated with cold syndrome were Lachnospiraceae uncultured,Lactococcus,etc.,and the key microbes associated with hot syndrome were S24-7 norank,Ruminococcaceae uncultured,etc.Conclusion: The interventions with different nature foods could change cold or hot syndrome in mice,leading to changes in gastrointestinal bacterial community structure.