Different gut microbial communities correlate with efficacy of albendazole-ivermectin against soil-transmitted helminthiases

Abstract

Soil-transmitted helminth infections represent a large burden with over a quarter of the world’s population at risk. Low cure rates are observed with standard of care (albendazole); therefore, a more effective combination therapy (albendazole and ivermectin) is being investigated but showed variable treatment efficacies without evidence of intrinsic parasite resistance. Here, we analyzed the microbiome of Trichuris trichiura and hookworm-infected patients and found an association of different enterotypes with treatment efficacy. 80 T. trichiura-infected patients with hookworm co-infections from Pak-Khan, Laos, received either albendazole (n = 41) or albendazole and ivermectin combination therapy (n = 39). Pre-/post-treatment stool samples were collected to monitor treatment efficacy and microbial communities were profiled using 16S rRNA gene sequencing, qPCR, and shotgun sequencing. We identified three bacterial enterotypes and show that pre-treatment enterotype is associated with efficacy of the combination treatment for both T. trichiura (CRET1 = 5.8%; CRET2 = 16.6%; CRET3 = 68.8%) and hookworm (CRET1 = 31.3%; CRET2 = 16.6%; CRET3 = 78.6%). This study shows that pre-treatment enterotype enables predicting treatment outcome of combination therapy for T. trichiura and hookworm infections.Trial registration: ClinicalTrials.gov, NCT03527732. Registered 17 May 2018, https://clinicaltrials.gov/ct2/show/NCT03527732.

Species interactions, stability, and resilience of the gut microbiota - helminth assemblage in horses

“…Additionally, the administration of strict anaerobes Clostridiales could grant rapid recovery of the ecosystem properties and holobiont tness after acute insults like drug treatment. As such, our ndings complement past observations on the impact of gut microbiota on treatment outcomes in humans [77]. Combined with good management practices, strategic diet manipulation could be part of the helminths control program [29].…”

Effects of helminths on the human immune response and the microbiome

“…Most of the work in this area involves describing associations between intestinal helminths and fecal samples by 16S ribosomal sequencing analysis in endemic populations. These include cross-sectional (n = 12) 53,[133][134][135][136][137][138][139][140][141][142][143][144][145][146][147] and longitudinal studies (n = 10) [148][149][150][151][152][153][154][155][156][157][158][159] , but the conclusions are often divergent, due to differences in the prevalence of helminths and study population for each analysis (see below). A common feature observed from some cross-sectional studies is increased gut microbial diversity in helminth-infected individuals 133,138,142,[144][145][146]151,153,159 ; however, some other studies showed either reduced diversity 146 or no significant differences in microbial diversity in infected individuals 134,135,139,140,143,148,…”

“…As the gut microbiota varies across geography, ethnicity and mode of subsistence 161 , in studies conducted in various continents including South America 53,141,157 , North America 136,147 , Africa 133,138,139,148,153,154,156 , Europe 151 , and Asia 134,135,140,[142][143][144][145][146]149,150,152,153,155,158,159 , it is not surprising to have divergent findings. In addition, studies have focused on different parasites, based on the study population including T. trichiura 133,144,149,155,157 , A. lumbricoides 147 , S. haematobium 139,156 , S. mansoni 154 S. japonicum 134 , Strongyloides stercoralis 151 , Clonorchis sinensis 142 , Haplorchis taichui 146 , E. vermicularis 159 , or mixed infections 136,138,140,141,143,145...…”

“…While some studies observed differences in gut microbial diversity following deworming treatment 148,151,155 , others observed no impact from treatment 152,154,157 . The microbiota may also affect treatment efficacy, as the treatment outcome of the combination of albendazole and ivermectin was associated with pre-treatment enterotype, with increased egg reduction in Enterotype 3, which is enriched with Ruminococcus torques & Eubacterium coprostanoligenes 158 .…”

“…For example, the bioinformatic approach used for the microbiota analysis can introduce technical limitations. Most studies utilize 16S rRNA sequencing , while a few have utilized shotgun metagenomics 138,140,153,158 . 16S sequencing only provides a portion of the gut microbiota profile 162 and does not provide genome data to infer microbial functional, which can be generated by metagenomics.…”