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

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.

Interactions between parasitic helminths and gut microbiota in wild tropical primates from intact and fragmented habitats

“…Nematode presence (strongylid nematodes, Strongyloides ) was also associated with lower bacterial richness in red colobus, but in PF. Although studies of the interactions between helminths and microbiota in wild animal populations are still relatively new, we speculate that the discrepancy found here may derive from a temporary instability in microbiota composition as a result of helminth infections which may recover over time, as already found in humans under controlled settings 17 . Further longitudinal studies on the same wild populations could help to fulfil this gap and reveal the actual influence of each gut component over time.…”

Unbalanced relationships: insights into the interaction between gut microbiota, geohelminths, and schistosomiasis

“…(2014) found that experimental administration of N. americanus to healthy individuals did not affect fecal microbiota, but they did not reject the possibility of having minor changes to microbiota at the site of infection. Ducarmon et al (2020) showed an increase in the species richness of the gut microbiota among all volunteers during an established infection, but the diversity and stability were almost unchanged. Even the group with many symptoms was characterized by transient microbiota instability and subsequent recovery.…”

Effects of helminths on the human immune response and the microbiome

“…A study on 8 healthy volunteers infected with 20 L3 larvae found no major impact on the gut microbiota at 8 weeks post infection 167 . A more recent study on 20 healthy young volunteers with higher dosages (i.e., 50, 100, or 150) of L3 found that the bacterial richness increased significantly during the established infection phase (week 8-20), but not during the acute infection phase (trial week 0-8) 168 . As hookworm resides in the small intestine, these results are consistent with deworming studies indicating that these worms may not alter the gut microbiota significantly, especially in the first 8 weeks after the infection.…”

“…Controlled experimental challenge infections may be an approach to minimize confounding factors and determine more direct effects of helminths on the microbiome and mucosal responses. The hookworm, N. americanus infection studies have been conducted on healthy individuals 167,168 , participants with relapsing multiple sclerosis 169 , and coeliac disease 170 . A study on 8 healthy volunteers infected with 20 L3 larvae found no major impact on the gut microbiota at 8 weeks post infection 167 .…”