Recent International Journal of Impotence Research The study confirmed the possible association between gut microflora and erectile dysfunction (ED), which is one of the most common sexual disorders in men.
Study: Causal Effects of Gut Microbiota on Erectile Dysfunction Risk: A Mendelian Randomization Study. Image credit: Prostock-studio/Shutterstock.com
Record
Patients with ED cannot maintain or achieve an erection for successful intercourse. Studies have shown that the prevalence of DM could be as high as 64% and that it increases with age. Therefore, early treatment of DM is important for individual well-being.
Emerging observational research has suggested a possible association between ED and the gut microbiota, which includes the vast diversity of microorganisms in the gastrointestinal tract.
However, such studies have important limitations, including unmeasured confounders and reverse causality.
A different method of data analysis, eg, Mendelian randomization (MR), estimates the causal relationship between the outcome variable and the exposure of interest by developing genetic variation as an instrumental variable (IV).
About the study
Here, summary statistics from two comprehensive genome-wide association studies (GWAS) were pooled. These studies specifically focus on the relationship between ED and the gut microbiota. Gut microbiota profiles were obtained from 18,340 participants.
MRI analyzes were used to study the data, which helped establish a causal relationship between ED and gut microbiota.
For successful MRI trials, certain conditions must be met, namely the existence of an association between exposure and IV, the absence of association between IV and confounding variables, and the ability of IV to affect the outcome through exposure alone. .
Regarding IV, a special focus was given to single nucleotide polymorphisms (SNPs) strongly associated with gut microbiota. Several sensitivity analyzes were performed to ensure the robustness of the results.
Important findings
Extensive evaluation of the causal relationship between ED and the gut microbiota led to the detection of six taxa of nominal importance. The genus Ruminococcaceae UCG-013 was associated with a reduced risk of DM.
In contrast, the genus Oscillibacter, the genus Erysipelotrichaceae UCG-003, the family Lachnospiraceae, the genus LachnospiraceaeNC2004group and the genus Tyzzerella3 showed an increased risk of ED.
In sensitivity analyses, horizontal pleiotropy and heterogeneity did not affect MRI results for these six species. The findings documented here are exciting as they open a new avenue for the treatment and prevention of EDs.
Previous research shows a significant correlation between the likelihood of developing DM and a high abundance of specific gut microbes. Specifically, Alistipes showed an association with a reduced risk of DM. In contrast, an increased risk was demonstrated by Clostridium XVIII.
There are some discrepancies between previous findings and those documented here, but these could be attributed to the highly complex nature of the interactions between gut microbiota. To combine 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 affects ED. However, it does provide some indirect clues.
It is possible that the secretion of lipopolysaccharide (LPS) by the gut microflora leads to the release of several inflammatory factors, e.g. IL-1, IL-2 and IL-10. Previous studies have firmly documented the role of these inflammatory factors in DM.
Another possible mechanism could work through the regulation of serum levels of trimethylamine N-oxide (TMAO) by the gut microbiota. TMAO has been shown to enhance vascular inflammation.
Vascular inflammation could damage smooth muscle cells and cavernous endothelium, which ultimately results in the development of DM.
conclusions
In summary, this study is the first to investigate a causal relationship between DM and gut microbiota composition and approach it using a genetic prognostic framework.
It also documents six gut microbiomes, which could be very important. This opens a new avenue for future research on ED prevention and management.
It should be noted, however, that this study also has limitations. The main limitation is that the data are from GWAS, which mainly includes European nationals.
This raises questions about the generalizability of the findings and extension to non-European populations.
Journal Reference:
Xu, R. et al. (2024) Causal effects of gut microbiota on erectile dysfunction risk: Mendelian randomization study. International Journal of Impotence Research. 1-6. doi: https://doi.org/10.1038/s41443-024-00824-7.