Dynamic changes in human-gut microbiome in relation to a placebo-controlled anthelminthic trial in Indonesia

Abstract

BackgroundMicrobiome studies suggest the presence of an interaction between the human gut microbiome and soil-transmitted helminth. Upon deworming, a complex interaction between the anthelminthic drug, helminths and microbiome composition might occur. To dissect this, we analyse the changes that take place in the gut bacteria profiles in samples from a double blind placebo controlled trial conducted in an area endemic for soil transmitted helminths in Indonesia.MethodsEither placebo or albendazole were given every three months for a period of one and a half years. Helminth infection was assessed before and at 3 months after the last treatment round. In 150 subjects, the bacteria were profiled using the 454 pyrosequencing. Statistical analysis was performed cross-sectionally at pre-treatment to assess the effect of infection, and at post-treatment to determine the effect of infection and treatment on microbiome composition using the Dirichlet-multinomial regression model.ResultsAt a phylum level, at pre-treatment, no difference was seen in microbiome composition in terms of relative abundance between helminth-infected and uninfected subjects and at post-treatment, no differences were found in microbiome composition between albendazole and placebo group. However, in subjects who remained infected, there was a significant difference in the microbiome composition of those who had received albendazole and placebo. This difference was largely attributed to alteration of Bacteroidetes. Albendazole was more effective against Ascaris lumbricoides and hookworms but not against Trichuris trichiura, thus in those who remained infected after receiving albendazole, the helminth composition was dominated by T. trichiura.DiscussionWe found that overall, albendazole does not affect the microbiome composition. However, there is an interaction between treatment and helminths as in subjects who received albendazole and remained infected there was a significant alteration in Bacteroidetes. This helminth-albendazole interaction needs to be studied further to fully grasp the complexity of the effect of deworming on the microbiome.Trial registrationISRCTN Registy, ISRCTN83830814.

The immune response and microbiota profiles during co-infection withP. vivaxand soil-transmitted helminths

“…This suggests that the environment in which the microbiota and STH exist (all the other co-factors, such as the diet, age, lifestyle, and other previous and current infections of the human host) may determine whether or not STH affect the gut microbiota. This could explain why the effects of STH on the gut microbiome have not been consistent between studies, even when examining the same STH species Rosa et al 2018;Martin et al 2018;Cooper et al 2013). Thereby we conclude that the effects of STH infections on the microbiota are dependent on the context of infection.…”

The mixed model for the analysis of a repeated‐measurement multivariate count data

“…Details of the study can be found elsewhere. 8 In a previous paper, 5 we identified an effect of treatment on the microbiome composition in subjects who were infected at baseline and at follow up. This relationship was studied in the post-treatment samples, whereas the microbiome composition at baseline was not used.…”

“…Here, parameter is unidentifiable. Similar to (5), we apply the parameterization in the work of Guimarães and Lindrooth, 12 where the overdispersion is absorbed in the grand mean 0 such that −1 exp( 0 ) = −1 0 in the reference category. In contrast to the nonoverdispersed multinomial model, the intercepts of the overdispersed multinomial model do not cancel out.…”

“…It has been shown previously that treatment had an effect on the composition at post-treatment in infected subjects who remained infected (condition 4). 5 Here, we want to reanalyze this data set by using a joint model for the microbiome data at pre-and post-treatment to assess the treatment effect in the infected subjects who remained infected. Additionally, we want to estimate the time effect while adjusting for other variables such as infection status and treatment allocation.…”

“…Our work is motivated by the microbiome measurements from an epidemiological study carried out in a helminth endemic rural area in Indonesia. 5 The primary research question of this study is to analyze the joint effect of helminth infections and albendazole treatment on the microbial composition comprising multiple bacterial taxa. It has been hypothesized that the presence of helminths is linked with the microbial dysbiosis.…”