[ TMC3115 Promotes Early Life Intestinal Microbiota Building to Alleviate Symptoms of Inflammatory Bowel Disease].

OBJECTIVE

To investigate the effects of using TMC3115 in early life on intestinal microbiota and immune functions and the long-term impact on inflammatory bowel disease.

METHODS

Fourteen pregnant BALB/c mice were purchased and 84 newborn BALB/c mice were subsequently obtained. Then, the newborn mice were randomly assigned to a normal saline (NS) group and a TMC3115 group, given via oral gavage normal saline and TMC3115, respectively, at a daily volume of 0.2 mL for each mouse. About 42 mice were assigned to each group. The gavage was stopped after 3 weeks. At this point, half of the mice in each group were sacrificed, and then the remaining mice in each group were randomly divided into NS-water group, NS-DSS group, TMC3115-water group, and TMC3115-DSS group, with about 10 mice in each group. The mice were given regular feed until the end of week 6 when they were given 3% dextran sulphate sodium (DSS) for 4 days to establish the enteritis model, while the non-modeling groups were given pure water . The experiment ended after 6 weeks and 4 days. The weekly body mass changes of the mice were documented. The intestinal tissue at the end of the experiment and the fecal samples, spleen and serum of the mice at 3 weeks and at the end of the experiment were collected to determine the pathology scores of colonic inflammation, the composition of fecal gut microbiota, spleen organ index and the mass concentration of serum cytokines.

RESULTS

1. At the end of the experiment, the inflammatory pathology score was significantly lower in the TMC3115-DSS group compared with that of the Saline-DSS group ( <0.05), with less disruption of colonic crypt structures and other structures, less inflammatory infiltration, and more intact epithelial structures. 2) At 3 weeks, in comparison with those of the NS group, the relative abundance of was significantly higher in the feces of the TMC3115 ( <0.05), the relative abundance of both and was lower ( <0.05), the splenic organ index was significantly higher ( <0.05), and interleukin (IL)-10 was significantly decreased ( <0.05), while there was no significant change in IL-6 or TNF-α ( >0.05). At the end of the experiment, in comparison with those of the NS-DSS group that undergone DSS induction, the TMC3115-DSS group had reduced relative abundance of , and / in the feces ( <0.05), while the splenic organ index was significantly higher ( <0.05), and there were no significant changes in IL-6 or TNF-α ( >0.05).

CONCLUSION

The use of TMC3115 in early life promotes the construction of gut microbiota in neonatal mice, thereby producing a long-term effect that alleviates colitis in mice, but the mechanisms involved are still not fully understood.