The Impact of Anthelmintic Treatment on Human Gut Microbiota Based on Cross-Sectional and Pre- and Postdeworming Comparisons in Western Kenya

Abstract

Murine studies suggest that the presence of some species of intestinal helminths is associated with changes in host microbiota composition and diversity. However, studies in humans have produced varied conclusions, and the impact appears to vary widely depending on the helminth species present. To demonstrate how molecular approaches to the human gut microbiome can provide insights into the complex interplay among disparate organisms, DNA was extracted from cryopreserved stools collected from residents of 5 rural Kenyan villages prior to and 3 weeks and 3 months following albendazole (ALB) therapy. Samples were analyzed by quantitative PCR (qPCR) for the presence of 8 species of intestinal parasites and by MiSeq 16S rRNA gene sequencing. Based on pretreatment results, the presence of neither Ascaris lumbricoides nor Necator americanus infection significantly altered the overall diversity of the microbiota in comparison with age-matched controls. Following ALB therapy and clearance of soil-transmitted helminths (STH), there were significant increases in the proportion of the microbiota made up by Clostridiales (P = 0.0002; average fold change, 0.57) and reductions in the proportion made up by Enterobacteriales (P = 0.0004; average fold change, −0.58). There was a significant posttreatment decrease in Chao1 richness, even among individuals who were uninfected pretreatment, suggesting that antimicrobial effects must be considered in any posttreatment setting. Nevertheless, the helminth-associated changes in Clostridiales and Enterobacteriales suggest that clearance of STH, and of N. americanus in particular, alters the gut microbiota. IMPORTANCE The gut microbiome is an important factor in human health. It is affected by what we eat, what medicines we take, and what infections we acquire. In turn, it affects the way we absorb nutrients and whether we have excessive intestinal inflammation. Intestinal worms may have an important impact on the composition of the gut microbiome. Without a complete understanding of the impact of mass deworming programs on the microbiome, it is impossible to accurately calculate the cost-effectiveness of such public health interventions and to guard against any possible deleterious side effects. Our research examines this question in a “real-world” setting, using a longitudinal cohort, in which individuals with and without worm infections are treated with deworming medication and followed up at both three weeks and three months posttreatment. We quantify the impact of roundworms and hookworms on gut microbial composition, suggesting that the impact is small, but that treatment of hookworm infection results in significant changes. This work points to the need for follow-up studies to further examine the impact of hookworm on the gut microbiota and determine the health consequences of the observed changes.

Linking the effects of helminth infection, diet and the gut microbiota with human whole-blood signatures

“…While albendazole treatment may have had some effect on the microbiome, we believe that this is likely limited. Recent studies in Indonesia and Kenya found statistically significant but small changes in the microbiome that could have been a direct result of albendazole treatment [56, 57]. Since prevalence in our study site was so high (96%) that we did not have an uninfected post-deworming control group, we believe the strongest evidence of changes resulting from worm clearance are those where changes are correlated with the decrease in egg burden ( Fig 4 ) and those in which the post-deworming phenotype reverts to a more urban-like phenotype ( Fig 5 ).…”

Host–microbiota interactions in immune-mediated diseases

“…www.nature.com/nrmicro microbiota, leading to increases in SCFA production and pulmonary T reg cells 118 . Associative studies suggest that helminth infection encourages gut bacterial diversity that is protective against asthma in humans [118][119][120] . The hygiene hypothesis in atopic diseases may thus relate to both protective colonization and infections that mediate immune-microorganism interactions in local and distant tissues.…”

Impact of intestinal parasites on microbiota and cobalamin gene sequences: a pilot study

“…Gastrointestinal parasites may modulate intestinal inflammation, malabsorption, and microbiome changes [22][23][24][25][26]. The microbiome is associated with digestion, nutrition and health, but alterations in biodiversity can increase disease states and induce intestinal inflammation [27].…”