Effects of antibiotic cocktail on the fecal microbiota and their potential correlation of local immune response.

BACKGROUND

The guts of mammals are home to trillions of microbes, forming a complex and dynamic ecosystem. Gut microbiota is an important biological barrier for maintaining immune homeostasis. Recently, the use of antibiotics to clear gut microbiota has gained popularity as a low cost and easy-to-use alternative to germ-free animals. However, the effect of the duration of the antibiotic cocktail on the gut microbiome is unclear, and more importantly, the effect of dramatic changes in the gut microbiota on intestinal tissue morphology and local immune response is rarely reported.

RESULTS

We observed a significant reduction in fecal microbiota species and abundance after 1 week of exposure to an antibiotic cocktail, gavage twice daily by intragastric administration. In terms of composition, Bacteroidetes and Firmicutes were replaced by Proteobacteria. Extending antibiotic exposure to 2-3 weeks did not significantly improve the overall efficiency of microbiotal consumption. No significant histomorphological changes were observed in the first 2 weeks of antibiotic cocktail exposure, but the expression of inflammatory mediators in intestinal tissue was increased after 3 weeks of antibiotic cocktail exposure. Mendelian randomization analysis showed that Actinobacteria had a significant causal association with the increase of IL-1β (OR = 1.65, 95% CI = 1.23 to 2.21, P = 0.007) and TNF-α (OR = 1.81, 95% CI = 1.26 to 2.61, P = 0.001).

CONCLUSIONS

Our data suggest that treatment with an antibiotic cocktail lasting 1 week is sufficient to induce a significant reduction in gut microbes. 3 weeks of antibiotic exposure can lead to the colonization of persistant microbiota and cause changes in intestinal tissue and local immune responses.