Probiotics Combined with Metformin Improves Sperm Parameters in Obese Male Mice through Modulation of Intestinal Microbiota Equilibrium.

Abstract

The decline in sperm parameters among obese males has attracted significant scholarly interest. The intestinal microbiota plays a crucial role in obesity, and investigating the intestinal-reproductive axis may offer a novel molecular approach to addressing the decline in male sperm parameters caused by obesity. To clarify whether probiotics, either alone or in conjunction with metformin, can enhance sperm parameters in obese male mice and assess the underlying mechanisms involved. 6-week-old male mice were constructed as obese models. Probiotics and metformin were used as intervention conditions. Changes in inflammatory factors and ROS content were detected by ELISA, morphological changes in testicular and colon tissues were observed by H&E staining, changes in intestinal microbiota abundance were detected by 16SrRNA gene sequencing, and changes in metabolites such as blood glucose, blood lipids, and lipopolysaccharide were detected by biochemical testing to investigate the mechanism of probiotics, metformin, and their combination to ameliorate reproductive impairment in obese male mice. Our results revealed that high-fat diet would result in reduced testicular spermatogenic tubule hierarchy, decreased spermatogenic cell counts, decreased sperm concentration and motility, and altered abundance of intestinal microbiota, whereas the combination of probiotics and metformin could restore high-fat-mediated pathophysiological alterations thereby ameliorating spermatogenic disorders in mice. The combination of probiotics and metformin can attenuate inflammation and oxidative stress, while enhancing androgen production to improve testicular spermatogenic function by re-construction intestinal microbiota equilibrium in HFD mice.