Chronic alcohol-induced dysbiosis of the gut microbiota and gut metabolites impairs sperm quality in mice

Abstract

Studies have indicated that the ethanol exposure impairs the gut microbiota, At the same time, high levels of alcohol exposure damage sperm in mice. However, whether the gut microbiota is involved in mediating the effects of alcohol on sperm quality remains unclear. This study aimed to assess the effect of chronic alcohol consumption on intestinal microbiota in mice and analyze the potential pathophysiological effect of altered intestinal microbiota on sperm quality. We established a mouse model of chronic alcohol consumption by allowing male C57 mice to freely ingest 10% ethanol for 10 weeks, and collected the fecal microbiota of the male mice in the chronic drinking group (alcohol) and the control group (control) and transplanted the specimens into the transplant groups (the alcohol-fecal microbiota transplantation [FMT] group and the control-FMT group). Sperm quality was significantly decreased in the alcohol-FMT group compared with the control-FMT group. Gut microbiota analysis revealed that the abundance of 11 operational taxonomic units (OTUs) was altered in the alcohol-FMT group. Nontargeted metabolomics identified 105 differentially altered metabolites, which were mainly annotated to amino acids, lipids, glycerophosphoethanolamine, organic oxygenic compounds, organic acids and their derivatives, steroids, and flavonoids. In particular, the oxidative phosphorylation pathway, which is the key to spermatogenesis, was significantly enriched in the alcohol-FMT group. Moreover, compared with the control-FMT group, the alcohol-FMT group presented significantly higher serum endotoxin and inflammatory cytokine levels, with more pronounced T cell and macrophage infiltration in the intestinal lamina propria and elevated levels of testicular inflammatory cytokines. In addition, RNA sequencing showed significant differences in the expression of testis-related genes between the alcohol-FMT group and the control-FMT group. In particular, the expression of genes involved in gamete meiosis, testicular mitochondrial function, and the cell division cycle was significantly reduced in alcohol-FMT mice. In conclusion, these findings indicated that intestinal dysbiosis induced by chronic alcohol consumption may be an important factor contributing to impaired sperm quality. Chronic alcohol consumption induces intestinal dysbiosis, which then leads to metabolic disorders, elevated serum endotoxin and inflammatory cytokine levels, testicular inflammation, abnormal expression of related genes, and ultimately, impaired sperm quality. These findings are potentially useful for the treatment of male infertility.

Inflammatory cytokines may mediate the causal relationship between gut microbiota and male infertility: a bidirectional, mediating, multivariate Mendelian randomization study

“…Gut microbes and their metabolites alter levels of various inflammatory cytokines ( 47 – 49 ). A study has shown that chronic alcohol consumption disrupts the gut microbial environment, leading to significant decreases in the levels of some of these key gut microbes (e.g., Helicobacter, a genus of Bacteroides), which in turn alters the body’s microenvironment, resulting in altered levels of inflammatory cytokines in the body, and ultimately an increased risk of infertility ( 50 ). Despite existing knowledge linking the gut microbiome to inflammatory cytokine levels, the exact mechanisms by which the gut microbiome affects inflammatory cytokine levels, especially HGF, remain unclear.…”

Short-chain-fatty acid valerate reduces voluntary alcohol intake in male mice

“…Previous research has demonstrated the involvement of gut microbiota in alcohol consumption, [ 8 – 10 ] and the disruption of gut microbiota through antibiotics has been shown to increase ethanol consumption in mice [ 33 ]. In agreement with this study, we found that Abx treatment significantly increased voluntary ethanol consumption levels in a binge-like ethanol drinking paradigm in mice.…”

“…Recent advances in the microbiome and alcohol research have shown that alcohol consumption can influence [ 6 ] or be influenced by the gut microbiome [ 7 ]. Acute or chronic alcohol consumption breaks down the homeostasis of gut microbiota, resulting in an overgrowth of harmful bacteria and a reduction in beneficial bacteria [ 8 – 10 ]. Dysbiosis of gut microbiota has been highlighted in the progression of alcoholic liver diseases [ 11 ].…”

Male infertility risk and gut microbiota: a Mendelian randomization study

“…An important risk factor for male infertility is poor sperm quality. In addition to overweight (Salas-Huetos et al, 2021 ), substance abuse (Gundersen et al, 2015 ), and testicular inflammation (Bryan et al, 2020 ), poor lifestyle habits such as smoking (Sharma et al, 2016 ), alcohol consumption (Li et al, 2022 ), and consumption of sugary beverages (Nassan et al, 2021 ) can affect sperm quality.…”