Evaluation of the recovery effects of antibiotic-resistant lactiplantibacillus plantarum subsp. Plantarum ATCC14917 on the antibiotic-disturbed intestinal microbiota using a mice model.

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Supplementing Lactobacillus alongside antibiotic treatment was a curative strategy to modulate gut microbiota and alleviate antibiotic-associated dysbiosis. But the lactobacilli that are used as probiotics are sensitive or have a low level of resistance to antibiotics, so they usually cannot achieve their beneficial effect, since they are killed by the applied antibiotics. This work aimed to develop the highly resistant Lactiplantibacillus plantarum subsp. plantarum ATCC14917 to cephalexin and evaluate its recovery effects of antibiotic-resistant L. plantarum on the antibiotic-disturbed intestinal microbiota using a mice model. After successive growth in LSM broth containing a gradually increasing concentration of cephalexin for 70 days, the minimum inhibitory concentration (MIC) of L. plantarum ATCC14917 to cephalexin significantly increased from 16 μg·mL-1 to 8192 μg·mL-1, but stabilized on 4096 μg·mL-1. After sequencing and sequence analysis, no mutated genes were detected on mobile elements, showing that horizontal transfer of mutated genes could not occur. Compared to the control group (Con), feeding mice with cephalexin (1mg·mL-1; Cep) led to a decrease in alpha diversity. However, concurrently used cephalexin and L. plantarum (Cep+LpR) increased the alpha diversity in both microbial richness and diversity. The Cep+LpR group showed a lowest distance with the Con group than either Cep or Cep+LpS groups, suggesting that resistant L. plantarum treatment was more effective than the original strain for the recovery of intestinal microbiota. Compared to the cephalexin-treated group, concurrent ingestion of cephalexin together with resistant L. plantarum significantly increased the proportion of beneficial bacteria, decreased Firmicutes/Bacteroidetes ratio and abundance of potential pathogens. The use of antibiotic-resistant Lactiplantibacillus plantarum ATCC14917 contributed to a much faster and richer recovery of the gut microbiota disturbed by antibiotic treatment compared to original strain.