Impairment of spermatogenesis and sperm motility by the high-fat diet-induced dysbiosis of gut microbes

Abstract

ObjectiveHigh-fat diet (HFD)-induced metabolic disorders can lead to impaired sperm production. We aim to investigate if HFD-induced gut microbiota dysbiosis can functionally influence spermatogenesis and sperm motility.DesignFaecal microbes derived from the HFD-fed or normal diet (ND)-fed male mice were transplanted to the mice maintained on ND. The gut microbes, sperm count and motility were analysed. Human faecal/semen/blood samples were collected to assess microbiota, sperm quality and endotoxin.ResultsTransplantation of the HFD gut microbes into the ND-maintained (HFD-FMT) mice resulted in a significant decrease in spermatogenesis and sperm motility, whereas similar transplantation with the microbes from the ND-fed mice failed to do so. Analysis of the microbiota showed a profound increase in genus Bacteroides and Prevotella, both of which likely contributed to the metabolic endotoxaemia in the HFD-FMT mice. Interestingly, the gut microbes from clinical subjects revealed a strong negative correlation between the abundance of Bacteroides-Prevotella and sperm motility, and a positive correlation between blood endotoxin and Bacteroides abundance. Transplantation with HFD microbes also led to intestinal infiltration of T cells and macrophages as well as a significant increase of pro-inflammatory cytokines in the epididymis, suggesting that epididymal inflammation have likely contributed to the impairment of sperm motility. RNA-sequencing revealed significant reduction in the expression of those genes involved in gamete meiosis and testicular mitochondrial functions in the HFD-FMT mice.ConclusionWe revealed an intimate linkage between HFD-induced microbiota dysbiosis and defect in spermatogenesis with elevated endotoxin, dysregulation of testicular gene expression and localised epididymal inflammation as the potential causes.Trial registration numberNCT03634644.

Small intestinal bacterial overgrowth (SIBO) as a potential cause of impaired spermatogenesis

“…Pilot data from our group confirms a significant positive correlation between serum zonulin production and ME, while a negative correlation exist between these two markers of intestinal permeability and serum testosterone (figure 1, table 1). While neither zonulin nor ME are conclusive for the presence of SIBO, these observations in the context of Ding’s findings,1 certainly support the concept that bacterial overgrowth in the small intestine may trigger an increase in intestinal permeability and ME, which then impairs testicular function 5 6…”

“…We commend Ding and colleagues for their innovative work investigating how high-fat diet-induced changes to the gut microbiome can alter spermatogenesis 1. This link between the gut microbiome and testicular function had earlier been suggested by studies that reported the consumption of probiotic bacteria could improve spermatogenesis and testosterone production in both mice and men 2 3.…”

“…Obesity and its associated lifestyle (high fat diet, minimal exercise) primarily produce colonic dysbiosis, with bacterial numbers still remaining low in the small intestine due to the inhibitory action of gastric acid and bile 4. In the Ding paper1 the authors delivered large numbers of faecal bacteria direct to the small intestine by gastric lavage over a 15-week period. While this did modify the recipient’s faecal (colonic) microbiome, it also resulted in very significant small intestinal inflammation suggestive of small intestinal bacterial overgrowth (SIBO).…”

Diet and Nutritional Factors in Male (In)Fertility – Underestimated Factors

“…Moreover, the number of Bacteroides and Prevotella increased significantly. It has been suggested that the spermatogenesis deterioration may be caused by elevated blood endotoxin levels, epididitis and disturbances in gene expression in the testes [55].…”

Effects of high-fat diet-induced gut microbiota dysbiosis: far beyond the gut

“…We read with great interest the attractive study by Ding N et al ,1 which reported that the dysbiosis of gut microbiota induced by high-fat diet (HFD) was one of the primary causes for the impaired sperm production and motility. It is likely mediated by elevated blood endotoxin, epididymal inflammation and the dysregulation of testicular gene expressions.…”