[Alleviation and recovery effects of Lactobacillus on the antibiotic-induced intestinal dysbiosis in early life stages of mice]

Objective: To investigate the effects of Lactobacillus on the alleviation and recovery of ceftriaxone-induced intestinal dysbiosis in early life stages of mice, and the possible effect on immunity of the host.

Methods: A total of 48 four-week-old Balb/c male mice were randomly divided into four groups, with 12 in each group. The experiment lasted for four weeks. In the first week, mice were given normal saline, ceftriaxone, ceftriaxone plus Lactobacillus rhamnosus GG, ceftriaxone plus direct vat set pickle(PC) by gavage respectively in the control group(ctrl), ceftriaxone group(ceftri), PC group and LGG group. The PC group and LGG group were given PC and LGG respectively for the last three weeks. The feces were collected once a week, and the profile composition of fecal bacteria were analyzed by next-generation sequencing. The mRNA expression levels of interleukin-6(IL-6), IL-12 and tumor necrosis factor α(TNF-α) in the spleen were analysed using quantitative real-time PCR.

Results: In the first week, the simpson index decreased significantly in the ceftri group(P<0. 001), but not in PC and LGG groups. At week four, the observed-species index in the PC group increased significantly(P<0. 001) and the simpson index increased in both LGG group and ceftri group(P<0. 01). As for the flora structure, in the first week, the ctrl group differed from the other three groups significantly(P<0. 05) while no differences were found between the PC group and the LGG group. The firmicutes/bacteroides(F/B) ratio of three ceftriaxone-treated groups increased while the abundance of Akkermansia decreased, particularly in the ceftri group. In the fourth week, the intestinal flora structure were different between four groups(P<0. 05) and the F/B ratio and Akkermansia abundance recovered. Ruminococcaceae, Bacteroidaceae and Tannerellacea appeared in the ceftri group, while Lactobacillus was dominant in the PC group, and Akkermansia was the characteristic species of the LGG group. Weight lost was found in ceftriaxone-treated groups(P<0. 05) and the PC group recovered first. IL-12 and TNF-α mRNA expression of the spleen were lower in PC and LGG groups compared with the ceftri group(P<0. 01). IL-6 mRNA expression level in the LGG group were lower than the ctrl group(P<0. 01).

Conclusion: The administration of antibiotics in the early life stage might inhibit weight gain, reduce the diversity of intestinal flora, damage functional bacteria and cause long-term inflammation, even though self-recovery ability exist. Lactobacillus might be helpful to alleviate the damage of antibiotics. But no therapeutic effect has been found.