Dynamics of the bacterial gut microbiota during controlled human infection with Necator americanus larvae

Gut Microbes. 2020 Nov 9;12(1):1-15. doi: 10.1080/19490976.2020.1840764.

Abstract

Hookworms are soil-transmitted helminths that use immune-evasive strategies to persist in the human duodenum where they are responsible for anemia and protein loss. Given their location and immune regulatory effects, hookworms likely impact the bacterial microbiota. However, microbiota studies struggle to deconvolute the effect of hookworms from confounders such as coinfections and malnutrition. We thus used an experimental human hookworm infection model to explore temporal changes in the gut microbiota before and during hookworm infection. Volunteers were dermally exposed to cumulative dosages of 50, 100 or 150 L3 Necator americanus larvae. Fecal samples were collected for microbiota profiling through 16S rRNA gene amplicon sequencing at weeks zero, four, eight, fourteen and twenty. During the acute infection phase (trial week zero to eight) no changes in bacterial diversity were detected. During the established infection phase (trial week eight to twenty), bacterial richness (Chao1, p = .0174) increased significantly over all volunteers. No relation was found between larval dosage and diversity, stability or relative abundance of individual bacterial taxa. GI symptoms were associated with an unstable microbiota during the first eight weeks and rapid recovery at week twenty. Barnesiella, amongst other taxa, was more abundant in volunteers with more GI symptoms throughout the study. In conclusion, this study showed that clinical GI symptoms following N. americanus infection are associated with temporary microbiota instability and relative abundance of specific bacterial taxa. These results suggest a possible role of hookworm-induced enteritis on microbiota stability.

Keywords: Necator americanus; Gut microbiota; controlled human infection; helminth; hookworm; longitudinal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Bacteria / classification*
  • Bacteria / genetics
  • Bacteria / isolation & purification*
  • Enteritis / microbiology
  • Enteritis / parasitology
  • Female
  • Gastrointestinal Microbiome / physiology*
  • Humans
  • Male
  • Middle Aged
  • Necator americanus / embryology
  • Necator americanus / genetics
  • Necator americanus / immunology*
  • Necatoriasis / immunology*
  • RNA, Ribosomal, 16S / genetics
  • Young Adult

Substances

  • RNA, Ribosomal, 16S

Grants and funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. EK is supported by an unrestricted grant from Vedanta Biosciences Inc. The original clinical trial was funded by a grant from Dioraphte Foundation. The funder had no influence on study design, data interpretation or preparation of the manuscript; Dioraphte Foundation.