A recent International Journal of Impotence Research study has validated the potential association between gut microbiota and erectile dysfunction (ED), which is one of the most prevalent sexual disorders in men.
Study: Causal effects of gut microbiota on the risk of erectile dysfunction: a Mendelian randomization study. Image Credit: Prostock-studio/Shutterstock.com
Background
Patients of ED are unable to sustain or attain an erection for successful sexual intercourse. Studies have shown that the prevalence of ED could be as high as 64% and that it increases with age. Therefore, early management of ED is important for individual well-being.
Emerging observational research has suggested a potential association between ED and the gut microbiota, encompassing the huge variety of microorganisms in the gastrointestinal tract.
However, such studies have major limitations, including unmeasured confounders and reverse causality.
A different method of data analysis, i.e., Mendelian randomization (MR), estimates the causal link between the outcome variable and the exposure of interest by deploying genetic variation as the instrumental variable (IV).
About the study
Here, summary statistics were gathered from two comprehensive genome-wide association studies (GWAS). These studies focus specifically on the relationship between ED and the gut microbiota. Gut microbiota profiles from 18,340 participants were obtained.
MR analyses were used to study the data, which aided in establishing a causal relationship between ED and the gut microbiota.
For successful MR trials, certain conditions must be met, namely, the existence of a correlation between the exposure and the IV, the absence of a correlation between the IV and confounding variables, and the ability of the IV to affect the outcome through exposure solely.
Concerning the IV, a specific focus was laid on single nucleotide polymorphisms (SNPs) strongly associated with gut microbiota. Several sensitivity analyses were conducted to ensure the robustness of the results.
Key findings
The extensive assessment of the causal link between ED and the gut microbiota led to the detection of six taxa of nominal significance. The genus Ruminococcaceae UCG-013 was linked to a reduced risk of ED.
On the contrary, the genus Oscillibacter, the genus Erysipelotrichaceae UCG-003, the family Lachnospiraceae, the genus LachnospiraceaeNC2004group, and the genus Tyzzerella3 exhibited an augmented risk of ED.
In sensitivity analyses, horizontal pleiotropy and heterogeneity did not influence the MR results for these six taxa. The findings documented here are compelling, as they pave a novel avenue for ED treatment and prevention.
Prior research shows a significant correlation between the likelihood of developing ED and a high abundance of specific gut microbiota. Specifically, Alistipes showed a correlation with a reduced risk of ED. On the contrary, an augmented risk was demonstrated by Clostridium XVIII.
There are some discrepancies between the previous findings and those documented here, but these could be attributed to the extremely complex nature of the interactions among the gut microbiota. To reconcile these findings, more prospective randomized controlled trials should be conducted.
This study does not shed light on the exact mechanism by which the gut microbiota influences ED; however, it provides some indirect indications.
It could be that the secretion of lipopolysaccharide (LPS) by the gut microbiota leads to the release of several inflammatory factors, e.g., IL-1, IL-2, and IL-10. Previous studies have firmly established the role of these inflammatory factors in ED.
Another potential mechanism could operate through regulating serum trimethylamine N-oxide (TMAO) levels by the gut microbiota. TMAO has been seen to enhance vascular inflammation.
Vascular inflammation could impair smooth muscle cells and the cavernous endothelium, which eventually culminates in the development of ED.
Conclusions
In sum, this study is the first to explore a causal link between ED and the gut microbiota composition and approaches this using a genetic predictive framework.
It also documents six gut microbiota, which could be very significant. This paves a novel avenue for future research on ED prevention and management.
It must, however, be mentioned that this study has limitations as well. The key limitation is that the data was sourced from GWAS, which comprises mainly European nationals.
This raises questions about the generalizability of the findings and the extension to non-European populations.
Study reveals variability in polygenic risk scores for predicting heart disease