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The gut microbiota response to helminth infection depends on host sex and genotype

Abstract

Vertebrates’ gut microbial communities can be altered by the hosts’ parasites. Helminths inhabiting the gut lumen can interact directly with their host’s microbiota via physical contact, chemical products, or competition for nutrients. Indirect interactions can also occur, for instance when helminths induce or suppress host immunity in ways that have collateral effects on the microbiota. If there is genetic variation in host immune responses to parasites, we would expect such indirect effects to be conditional on host genotype. To test for such genotype by infection interactions, we experimentally exposed Gasterosteus aculeatus to their naturally co-evolved parasite, Schistocephalus solidus. The host microbiota differed in response to parasite exposure, and between infected and uninfected fish. The magnitude and direction of microbial responses to infection differed between host sexes, and also differed between variants at autosomal quantitative trait loci. These results indicate that host genotype and sex regulate the effect of helminth infection on a vertebrate gut microbiota. If this result holds in other taxa, especially humans, then helminth-based therapeutics for dysbiosis might need to be tailored to host genotype and sex.

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Fig. 1: Microbiota community structure of stickleback differs between cestode exposure versus infection.
Fig. 2: Many microbial Orders (N = 84, found in a minimum of 20 stickleback) exhibit significant effects of infection or fish characteristics.
Fig. 3: Examples of how the gut microbiota composition depends on host sex, genotype (cross), and infection status, focusing on the relative abundance of microbial Orders.
Fig. 4: Linear discriminant analysis of the top 50 unweighted PCoA axes of microbial composition reveals effects of host sex, host cross type, and infection status.
Fig. 5: QTL map of Fusobacteriales relative abundance (with nonparametric statistical tests) reveals two autosomal QTL plus an association with the X chromosome.
Fig. 6: A summary of the locations of QTL affecting the relative abundance of individual microbial Order.

Data availability

Sequence data have been deposited in the Sequence Read Database (SRA) under project IDs SRP115642 (BioProject PRJNA398629) and SRP115678 (BioProject PRJNA398630) for experimental 1 and 2, respectively. All other relevant data are available in this article and its Supplementary Information files, or from the corresponding authors upon request.

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Acknowledgements

We thank the Genome Sequencing and Analysis Facility (GSAF) at the University of Texas at Austin for sequencing support, and the Texas Advanced Computing Center (TACC) and High Performance Computing platform of Northwest A&F University for computational resources. This research was supported by funding from National Natural Science Foundation of China to FL, NSFC(Grant 31672680), and the Howard Hughes Medical Institute to DB, NIH (Grant 1R01AI123659-01A1).

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Ling, F., Steinel, N., Weber, J. et al. The gut microbiota response to helminth infection depends on host sex and genotype. ISME J 14, 1141–1153 (2020). https://doi.org/10.1038/s41396-020-0589-3

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