Lactobacillus plantarum TW1-1 Alleviates Diethylhexylphthalate-Induced Testicular Damage in Mice by Modulating Gut Microbiota and Decreasing Inflammation

Abstract
Diethylhexylphthalate (DEHP), acting as an endocrine disruptor, disturbed reproductive health. Here, we evaluated the effects of Lactobacillus plantarum TW1-1 (L. plantarum TW1-1) on DEHP-induced testicular damage in adult male mice. Results showed that oral supplementation of L. plantarum TW1-1 significantly increased the serum testosterone concentration, enhanced the semen quality, and attenuated gonad development defects in DEHP-exposed mice. L. plantarum TW1-1 also alleviated DEHP-induced oxidative stress and inflammatory responses by decreasing the mRNA expression and serum protein concentration of different inflammatory factors [tumor necrosis factor-α, interleukin (IL)-1β and IL-6]. Furthermore, L. plantarum TW1-1 significantly reduced DEHP-induced intestinal hyper-permeability and the increase in the serum lipopolysaccharide level. Gut microbiota diversity analysis revealed that L. plantarum TW1-1 shifted the DEHP-disrupted gut microbiota to that of the control mice. At phylum level, L. plantarum TW1-1 reversed DEHP-induced Bacteroidetes increase and Firmicutes decrease, and restored Deferribacteres in DEHP-exposed mice. Spearman's correlation analysis showed that Bacteroidetes, Deferribacteres, and Firmicutes were associated with DEHP-induced testicular damage. In addition, the ratio of Firmicutes to Bacteroidetes (Firm/Bac ratio) significantly decreased from 0.28 (control group) to 0.13 (DEHP-exposed group), which was restored by L. plantarum TW1-1 treatment. Correlation analysis showed that the Firm/Bac ratio was negatively correlated with testicular damage and inflammation. These findings suggest that L. plantarum TW1-1 prevents DEHP-induced testicular damage via modulating gut microbiota and decreasing inflammation.