Whipworm-Associated Intestinal Microbiome Members Consistent Across Both Human and Mouse Hosts

Abstract

The human whipworm Trichuris trichiura infects 289 million people worldwide, resulting in substantial morbidity. Whipworm infections are difficult to treat due to low cure rates and high reinfection rates. Interactions between whipworm and its host’s intestinal microbiome present a potential novel target for infection control or prevention but are very complicated and are identified using inconsistent methodology and sample types across the literature, limiting their potential usefulness. Here, we used a combined 16S rRNA gene OTU analysis approach (QIIME2) for samples from humans and mice infected with whipworm (T. trichiura and T. muris, respectively) to identify for the first time, bacterial taxa that were consistently associated with whipworm infection spanning host species and infection status using four independent comparisons (baseline infected vs uninfected and before vs after deworming for both humans and mice). Using these four comparisons, we identified significant positive associations for seven taxa including Escherichia, which has been identified to induce whipworm egg hatching, and Bacteroides, which has previously been identified as a major component of the whipworm internal microbiome. We additionally identified significant negative associations for five taxa including four members of the order Clostridiales, two from the family Lachnospiraceae, including Blautia which was previously identified as positively associated with whipworm in independent human and mouse studies. Using this approach, bacterial taxa of interest for future association and mechanistic studies were identified, and several were validated by RT-qPCR. We demonstrate the applicability of a mouse animal model for comparison to human whipworm infections with respect to whipworm-induced intestinal microbiome disruption and subsequent restoration following deworming. Overall, the novel cross-species analysis approach utilized here provides a valuable research tool for studies of the interaction between whipworm infection and the host intestinal microbiome.

Mucin-degrading gut bacteria promote anti-parasitic immunity

“…Although previous studies have reported noticeable changes in the gut microbial taxa in mice with conventional gut microbiota after worm infection, these changes are described at broader level of microbial taxonomy [23][24][25][26][27][28] . It also remains to be studied which precise microbial species respond most to worm infection particularly during a longitudinal course of the worm infection both during chronic and acute phases of infection.…”

“…T. muris has been shown to broadly alter the host's gut microbiome composition [23][24][25][26][27][28] , but our longitudinal characterization of the gut microbiome provides explicit details about how the microbial shifts are characterized by distinct phases and specific microbial species based on their functional roles (Fig. 6).…”

Association between clinical and environmental factors and the gut microbiota profiles in young South African children

“…A study performed on South African infants determined that Haemophilus was a candidate gut pathogen associated with respiratory disease in infants 19 , but the clinical significance of Haemophilus outside of specific disease contexts is unknown. Further, we were only able to include 59 of 115 children in this analysis due to discrepant answers on the questionnaires, and did not evaluate the helminth infection status, which has been associated with specific microbiome profiles 61 . The numerous benefits of deworming in child health, such as control of anaemia and a lower risk of stunting and malnutrition, must also be considered and may mediate perceived negative microbiome effects.…”

The interplay between Trichuris and the microbiota

“…A recent study in Tanzania, was one of the first to identify a reduction in the abundance of gut bacteria: Bacteroidetes, Proteobacteria and Actinobacteria associated with a cohort of women and children solely infected with T. trichuria (Chen et al ., 2021 ); which is similar to the microbial changes reported in mouse studies (Holm et al ., 2015 ; Houlden et al ., 2015 ). Parallels between human and mouse studies were further addressed by identifying bacterial taxa that increased in both T. trichuria -only infected Indonesian individuals and T. muris -infected mice, these genera included Bacteroides , Collinsella , Subdoligranulum , Escherichia / Shigella , Prevetoella and Streptococcus (Rosa et al ., 2021 ). There has also been the development of a mouse model to partially address the discrepancy in human and mouse data that involves a trickle model of T. muris infection, where mice are routinely (weekly) infected with low doses of embryonated eggs, thereby closely mimicking the low-dose chronic human infection by T. trichiura (Glover et al ., 2019 ).…”