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Protective effects of Lactococcus lactis subsp. lactis HFY14 supplementation on the brain, intestines, and motor function of antibiotic-treated mice

Yang Yang,Zhao Yuanji,Lei Huan

Introduction: This study aimed to explore the anti-oxidative and anti-inflammatory properties of Lactococcus lactis subsp. lactis HFY14 (LLSLHFY14) and investigate its effects on the intestinal barrier, cranial nerve, and motor function in mice treated with antibiotics.Methods: Mice were administered an antibiotic mixture (neomycin 5 mg/mL, vancomycin 25 mg/mL, amphotericin B 0.1 mg/mL, ampicillin 10 mg/mL, metronidazole file 5 mg/mL, and lipopolysaccharide 1.5 μg/mL) intraperitoneally, and oxidative stress and inflammatory markers in the serum and brain tissues, and liver index were measured. H&E staining was performed to detect pathological alterations in brain tissues. The expression of intestinal-barrier-related genes and that of genes involved in inflammatory pathways in the brain were detected using polymerase chain reaction (PCR).Results: LLSLHFY14 administration extended the weight-loaded swimming and running times of mice and decreased the liver index. Moreover, the levels of malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) in the serum and brain tissue were reduced, whereas those of superoxide dismutase (SOD), glutathione (GSH), and interleukin-10 (IL-10) were elevated. Elevated brain expression of the protein kinase B (AKT)/cAMP-response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF)/extracellular signal-regulated kinase 1 (ERK1) pathway, decreased brain expression of the IL-6 gene, and elevated cecum expression of zonula occludens-1 (ZO-1), occludin-1, and claudin-1 genes were noted. LLSLHFY14 supplementation significantly increased Bacteroidetes expression but decreased Firmicutes expression, thus increasing the Bacteroidetes/Firmicutes ratio.Discussion: Overall, LLSLHFY14 supplementation ameliorated antibiotic-induced oxidative stress and inflammation in the mouse central nervous system, intestinal barrier dysfunction, and increased motor function, thus confirming its potential application as probiotics.