Differential Effects of Two Common Antiparasitics on Microbiota Resilience.

BACKGROUND: Parasitic infections challenge vertebrate health worldwide, and off-target effects of antiparasitic treatments may be an additional obstacle to recovery. However, there have been few investigations of the effects of antiparasitics on the gut microbiome in the absence of parasites. METHODS: We investigated whether two common antiparasitics-albendazole (ALB) and metronidazole (MTZ)-significantly alter the gut microbiome of parasite-free mice. We treated mice with ALB or MTZ daily for 7 days and sampled the fecal microbiota immediately before and after treatment and again after a two-week recovery period. RESULTS: ALB did not immediately change the gut microbiota, while MTZ decreased microbial richness by 8.5% and significantly changed community structure during treatment. The structural changes caused by MTZ included depletion of the beneficial family Lachnospiraceae, and predictive metagenomic analysis revealed that these losses likely depressed microbiome metabolic function. Separately, we compared the fecal microbiotas of treatment groups after recovery, and there were minor differences in community structure between the ALB, MTZ, and sham-treated control groups. CONCLUSIONS: These results suggest that a healthy microbiome is resilient after MTZ-induced depletions of beneficial gut microbes, and ALB may cause slight, latent shifts in the microbiota but does not deplete healthy gut microbiota diversity.

PINWORMS ARE ASSOCIATED WITH TAXONOMIC BUT NOT FUNCTIONAL DIFFERENCES IN THE GUT MICROBIOME OF WHITE-THROATED WOODRATS (NEOTOMA ALBIGULA).

Vertebrates rely on their gut microbiome for digestion, and changes to gut microbial communities can impact host health. Past work, primarily in model organisms, has revealed that endoparasites disrupt the gut microbiome. Here, using wild-caught white-throated woodrats (Neotoma albigula), we tested whether naturally acquired parasite infections are associated with different microbiome structure and function. We surveyed wild N. albigula in eastern Utah for gastrointestinal parasites in the spring and fall of 2019, using traditional fecal float methods and testing a PCR-based approach to detect infection. We tested whether the host gut microbiome structure and function differed based on infection with the most prevalent parasite, the pinworm Lamotheoxyuris ackerti. In spring, infected and uninfected animals had significantly different microbiomes, but these differences were not detected in the fall. However, for both sampling periods, infection was associated with differences in particular microbial taxa determined by differential abundance analysis. As N. albigula rely on their microbiomes to digest both fiber and the plant defensive compound oxalate, we compared microbiome function by measuring dry matter digestibility and oxalate intake in infected and uninfected animals. Although we expected infected animals to have reduced fiber degradation and oxalate intake, we found no difference in microbiome function using these assays. This work suggests that parasite effects on the microbiome may be difficult to detect in complex natural systems, and more studies in wild organisms are warranted.

Toxin tolerance across landscapes: Ecological exposure not a prerequisite.

Little is known about the tolerances of mammalian herbivores to plant specialized metabolites across landscapes.We investigated the tolerances of two species of herbivorous woodrats, Neotoma lepida (desert woodrat) and Neotoma bryanti (Bryant's woodrat) to creosote bush (Larrea tridentata), a widely distributed shrub with a highly toxic resin. Woodrats were sampled from 13 locations both with and without creosote bush across a 900 km transect in the US southwest. We tested whether these woodrat populations consume creosote bush using plant metabarcoding of feces and quantified their tolerance to creosote bush through feeding trials using chow amended with creosote resin.Toxin tolerance was analyzed in the context of population structure across collection sites with microsatellite analyses. Genetic differentiation among woodrats collected from different locations was minimal within either species. Tolerance differed substantially between the two species, with N. lepida persisting 20% longer than N. bryanti in feeding trials with creosote resin. Furthermore, in both species, tolerance to creosote resin was similar among woodrats near or within creosote bush habitat. In both species, woodrats collected greater than 25 km from creosote had markedly lower tolerances to creosote resin compared to animals from within the range of creosote bush.The results imply that mammalian herbivores are adapted to the specialized metabolites of plants in their diet, and that this tolerance can extend several kilometers outside of the range of dietary items. That is, direct ecological exposure to the specialized chemistry of particular plant species is not a prerequisite for tolerance to these compounds. These findings lay the groundwork for additional studies to investigate the genetic mechanisms underlying toxin tolerance and to identify how these mechanisms are maintained across landscape-level scales in mammalian herbivores.