Male circumcision significantly reduces prevalence and load of genital anaerobic bacteria

Abstract

Male circumcision reduces female-to-male HIV transmission. Hypothesized mechanisms for this protective effect include decreased HIV target cell recruitment and activation due to changes in the penis microbiome. We compared the coronal sulcus microbiota of men from a group of uncircumcised controls (n = 77) and from a circumcised intervention group (n = 79) at enrollment and year 1 follow-up in a randomized circumcision trial in Rakai, Uganda. We characterized microbiota using16S rRNA gene-based quantitative PCR (qPCR) and pyrosequencing, log response ratio (LRR), Bayesian classification, nonmetric multidimensional scaling (nMDS), and permutational multivariate analysis of variance (PerMANOVA). At baseline, men in both study arms had comparable coronal sulcus microbiota; however, by year 1, circumcision decreased the total bacterial load and reduced microbiota biodiversity. Specifically, the prevalence and absolute abundance of 12 anaerobic bacterial taxa decreased significantly in the circumcised men. While aerobic bacterial taxa also increased postcircumcision, these gains were minor. The reduction in anaerobes may partly account for the effects of circumcision on reduced HIV acquisition.

Importance: The bacterial changes identified in this study may play an important role in the HIV risk reduction conferred by male circumcision. Decreasing the load of specific anaerobes could reduce HIV target cell recruitment to the foreskin. Understanding the mechanisms that underlie the benefits of male circumcision could help to identify new intervention strategies for decreasing HIV transmission, applicable to populations with high HIV prevalence where male circumcision is culturally less acceptable.

Figures

FIG 1

Changes in the coronal sulcus bacterial load as measured by the log response ratio for the uncircumcised (Contr.; in red) versus the circumcised (Interv.; in orange) men, shown by group (top panel) and by individual (bottom panel). In the group comparison, the box of each box plot denotes the interquartile range (IQR) (quartile 1 [Q1] to Q3) and the corresponding median, whereas the whiskers signify the upper and lower 1.5× IQR. Outliers are shown as open symbols in each box plot. There was a statistically significant reduction in bacterial load for the circumcised men compared to that for the uncircumcised men (P = 0.048). As shown in the scatter plot in the bottom panel, although a decrease was observed for many individuals from both groups, more circumcised men showed decreases (i.e., negative log response ratios) (62/79, 78.5%) than did those that remained uncircumcised (51/77, 66.2%).

FIG 2

The nonmetric multidimensional scaling (nMDS) ordination plots enable the visualization of individuals’ microbiota over time. In nMDS plots, each data point represents an individual’s microbiota at one time point. The centroids and 95% confidence ellipses for each study group are as shown. Here, the coronal sulcus microbiota in men that remained uncircumcised showed minor variations from enrollment (in blue) to year-1 (in orange) (Fig. 2A). In contrast, significant shifts were seen in the circumcised men (Fig. 2B).