Whipworm-associated intestinal microbiome members consistent across both human and mouse hosts

Authors: ROSA, BRUCE - Washington University School Of Medicine; SNOWDEN, CAROLINE - Washington University School Of Medicine; MARTIN, JOHN - Washington University School Of Medicine; FISHER, KERSTIN - Washington University School Of Medicine; KUPRITZ, JONAH - Washington University School Of Medicine; Beshah, Ethiopia; SUPALI, TANIAWATI - Washington University School Of Medicine; GANKPALA, LINCOLN - Washington University School Of Medicine; FISHER, PETER - Washington University School Of Medicine; Urban, Joseph; MITREVA, MAKEDONKA - Washington University School Of Medicine

Submitted to: Frontiers in Cellular and Infection Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/20/2021
Publication Date: 3/11/2021
Citation: Rosa, B.A., Snowden, C., Martin, J., Fisher, K., Kupritz, J., Beshah, E., Supali, T., Gankpala, L., Fisher, P.U., Urban Jr, J.F., Mitreva, M. 2021. Whipworm-associated intestinal microbiome members consistent across both human and mouse hosts. Frontiers in Cellular and Infection Microbiology. https://doi.org/10.3389/fcimb.2021.637570.
DOI: https://doi.org/10.3389/fcimb.2021.637570

Interpretive Summary: Parasitic nematodes (worms) that infect livestock reduce production of meat, milk, fiber and compromise health. They also have deleterious effects on the health of humans in areas of the world were these infections are common. The human whipworm, Trichuris trichiura, infects close to 800 million people worldwide and is difficult to eliminate, resulting in high reinfection rates. The mouse whipworm, Trichuris muris, has been used as laboratory model to study the intricacies of the parasite and host interface. There is general interest in the bacteria that inhabit the intestinal microbiome of both livestock and humans because of the role in digestion, development and health. Recent studies in mice indicate that the intestinal microbiome is a potential novel target for infection control or prevention but the analyses used are very complicated and inconsistent methodology limits the interpretation of results and potential usefulness. This study used a common molecular analysis to evaluate both human and mouse whipworm infections to identify bacterial groups that are significantly associated with infection by comparing the microbiome of human and mice both before and after infection with whipworm and before and after drug treatment to reduce the infection. Significant common positive and negative associations were made for several groups of bacteria in both humans and mice. This approach targets bacterial populations that can be added or reduced from the microbiome to modulate the severity of whipworm infection and also validates the mouse animal model as being applicable for comparisons to human whipworm infections. Overall, this novel cross-species analysis provides valuable tools for future whipworm-gut microbiome interaction studies. The work strongly supports the need for more investigation of these types of interactions by research scientists and clinicians to reduce debilitating infectious diseases in humans and agricultural animals.

Technical Abstract: The human whipworm Trichuris trichiura infects 795 million people worldwide, resulting in substantial morbidity. Whipworm infections are difficult to treat due to low cure rates and high reinfection rates. Interactions between the whipworm and its host's gut 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 use a combined 16S OTU analysis approach (QIIME2) spanning both human and mouse whipworm infections, to identify for the first time, bacterial taxa that are consistently significantly associated with infection spanning host species and infection status using four independent comparisons (baseline infected vs uninfected, before vs after deworming, humans and mice). Using these four comparisons, we identify 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's internal microbiome. We additionally identify significant negative associations for five taxa including four members of the order Clostridiales, two of which were from the family Lachnospiraceae, including Blautia which was previously identified as positively associated with whipworm in independent human and mouse studies. Using this approach, in addition to identifying bacterial taxa of interest for future association and mechanistic studies, we validate the mouse animal model as being applicable for comparisons to human whipworm infections, in terms of the gut microbiome disruption and subsequent restoration following deworming. Overall, the novel cross-species analysis approach utilized here provides valuable results for future whipworm-gut microbiome interaction studies.