Relating gut microbiome composition and life history metrics for pronghorn (Antilocapra americana) in the Red Desert, Wyoming.

Host microbial communities (hereafter, the 'microbiome') are recognized as an important aspect of host health and are gaining attention as a useful biomarker to understand the ecology and demographics of wildlife populations. Several studies indicate that the microbiome may contribute to the adaptive capacity of animals to changing environments associated with increasing habitat fragmentation and rapid climate change. To this end, we investigated the gut microbiome of pronghorn (Antilocapra americana), an iconic species in an environment that is undergoing both climatic and anthropogenic change. The bacterial composition of the pronghorn gut microbiome has yet to be described in the literature, and thus our study provides important baseline information about this species. We used 16S rRNA amplicon sequencing of fecal samples to characterize the gut microbiome of pronghorn-a facultative sagebrush (Artemisia spp.) specialist in many regions where they occur in western North America. We collected fecal pellets from 159 captured female pronghorn from four herds in the Red Desert of Wyoming during winters of 2013 and 2014. We found small, but significant differences in diversity of the gut microbiome relative to study area, capture period, and body fat measurements. In addition, we found a difference in gut microbiome composition in pronghorn across two regions separated by Interstate 80. Results indicated that the fecal microbiome may be a potential biomarker for the spatial ecology of free-ranging ungulates. The core gut microbiome of these animals-including bacteria in the phyla Firmicutes (now Bacillota) and Bacteroidota-remained relatively stable across populations and biological metrics. These findings provide a baseline for the gut microbiome of pronghorn that could potentially be used as a target in monitoring health and population structure of pronghorn relative to habitat fragmentation, climate change, and management practices.

Spatial models can improve the experimental design of field-based transplant gardens by preventing bias due to neighborhood crowding.

Field-based transplant gardens, including common and reciprocal garden experiments, are a powerful tool for studying genetic variation and gene-by-environment interactions. These experiments assume that individuals within the garden represent independent replicates growing in a homogenous environment. Plant neighborhood interactions are pervasive across plant populations and could violate assumptions of transplant garden experiments. We demonstrate how spatially explicit models for plant-plant interactions can provide novel insights on genotypes' performance in field-transplant garden designs. We used individual-based models, based on data from a sagebrush (Artemisia spp.) common garden, to simulate the impact of spatial plant-plant interactions on between-group differences in plant growth. We found that planting densities within the range of those used in many common gardens can bias experimental outcomes. Our results demonstrate that higher planting densities can lead to inflated group differences and may confound genotypes' competitive ability and genetically underpinned variation. Synthesis. We propose that spatially explicit models can help avoid biased results by informing the design and analysis of field-based transplant garden experiments. Alternately, including neighborhood effects in post hoc analyses of transplant garden experiments is likely to provide novel insights into the roles of biotic factors and density dependence in genetic differentiation.

Los experimentos de trasplante de especies en parcelas de campo experimentales, tanto bajo condiciones ambientales comunes ("common gardens") como diferentes ("reciprocal gardens"), son una poderosa herramienta que permite estudiar la variación genética y la interacción entre el genoma y el medio ambiente. Dichos experimentos asumen que los individuos dentro de una misma parcela representan réplicas independientes creciendo bajo condiciones ambientales homogéneas. Las interacciones entre plantas vecinas están omnipresentes en las dinámicas poblaciones y pueden suponer una violación de dichas asunciones. Sin embargo, enfoques cuantitativos que permitan evaluar la adecuación del diseño experimental son escasos. Nosotros demostramos cómo los modelos espacialmente explícitos para las interacciones planta­planta pueden proporcionar nuevos hallazgos sobre el rendimiento genotípico en el diseño de experimentos de trasplante. Utilizamos modelos basados en individuos, junto con datos de "artemisa" (Artemisia spp.) procedentes de un "common garden," para simular el impacto de las interacciones planta­planta sobre las diferencias de crecimiento entre grupos. Encontramos que la densidad de siembra utilizada con frecuencia en muchos "common gardens" puede sesgar la estimación de la variación entre grupos. Nuestros resultados demuestran que una mayor densidad de siembra puede inflar las diferencias entre grupos, confundir la habilidad competitiva de los genomas y la variabilidad sustentada genéticamente, introduciendo así un sesgo en el experimento. Proponemos que los modelos espacialmente explícitos pueden ayudar a evitar el sesgo en los resultados mediante el apoyo en el diseño y análisis de experimentos de trasplante. Incluir efectos de vecindad en el análisis a posteriori de experimentos puede proporcionar nuevos hallazgos sobre el papel de los factores bióticos y densidad­dependientes en la diferenciación genética.

A haploid pseudo-chromosome genome assembly for a keystone sagebrush species of western North American rangelands.

Increased ecological disturbances, species invasions, and climate change are creating severe conservation problems for several plant species that are widespread and foundational. Understanding the genetic diversity of these species and how it relates to adaptation to these stressors are necessary for guiding conservation and restoration efforts. This need is particularly acute for big sagebrush (Artemisia tridentata; Asteraceae), which was once the dominant shrub over 1,000,000 km2 in western North America but has since retracted by half and thus has become the target of one of the largest restoration seeding efforts globally. Here, we present the first reference-quality genome assembly for an ecologically important subspecies of big sagebrush (A. tridentata subsp. tridentata) based on short and long reads, as well as chromatin proximity ligation data analyzed using the HiRise pipeline. The final 4.2-Gb assembly consists of 5,492 scaffolds, with nine pseudo-chromosomal scaffolds (nine scaffolds comprising at least 90% of the assembled genome; n = 9). The assembly contains an estimated 43,377 genes based on ab initio gene discovery and transcriptional data analyzed using the MAKER pipeline, with 91.37% of BUSCOs being completely assembled. The final assembly was highly repetitive, with repeat elements comprising 77.99% of the genome, making the Artemisia tridentata subsp. tridentata genome one of the most highly repetitive plant genomes to be sequenced and assembled. This genome assembly advances studies on plant adaptation to drought and heat stress and provides a valuable tool for future genomic research.

Food quality, security, and thermal refuge influence the use of microsites and patches by pygmy rabbits (Brachylagus idahoensis) across landscapes and seasons.

How intensely animals use habitat features depends on their functional properties (i.e., how the feature influences fitness) and the spatial and temporal scale considered. For herbivores, habitat use is expected to reflect the competing risks of starvation, predation, and thermal stress, but the relative influence of each functional property is expected to vary in space and time. We examined how a dietary and habitat specialist, the pygmy rabbit (Brachylagus idahoensis), used these functional properties of its sagebrush habitat-food quality, security, and thermal refuge-at two hierarchical spatial scales (microsite and patch) across two seasons (winter and summer). At the microsite and patch scales, we determined which plant functional traits predicted the number of bites (i.e., foraging) by pygmy rabbits and the number of their fecal pellets (i.e., general habitat use). Pygmy rabbits used microsites and patches more intensely that had higher crude protein and aerial concealment cover and were closer to burrows. Food quality was more influential when rabbits used microsites within patches. Security was more influential in winter than summer, and more at Cedar Gulch than Camas. However, the influence of functional properties depended on phytochemical and structural properties of sagebrush and was not spatiotemporally consistent. These results show function-dependent habitat use that varied according to specific activities by a central-place browsing herbivore. Making spatially explicit predictions of the relative value of habitat features that influence different types of habitat use (i.e., foraging, hiding, and thermoregulating) will improve how we predict patterns of habitat use by herbivores and how we monitor and manage functional traits within habitats for wildlife.

Where to forage when afraid: Does perceived risk impair use of the foodscape?

The availability and quality of forage on the landscape constitute the foodscape within which animals make behavioral decisions to acquire food. Novel changes to the foodscape, such as human disturbance, can alter behavioral decisions that favor avoidance of perceived risk over food acquisition. Although behavioral changes and population declines often coincide with the introduction of human disturbance, the link(s) between behavior and population trajectory are difficult to elucidate. To identify a pathway by which human disturbance may affect ungulate populations, we tested the Behaviorally Mediated Forage-Loss Hypothesis, wherein behavioral avoidance is predicted to reduce use of available forage adjacent to disturbance. We used GPS collar data collected from migratory mule deer (Odocoileus hemionus) to evaluate habitat selection, movement patterns, and time-budgeting behavior in response to varying levels of forage availability and human disturbance in three different populations exposed to a gradient of energy development. Subsequently, we linked animal behavior with measured use of forage relative to human disturbance, forage availability, and quality. Mule deer avoided human disturbance at both home range and winter range scales, but showed negligible differences in vigilance rates at the site level. Use of the primary winter forage, sagebrush (Artemisia tridentata), increased as production of new annual growth increased but use decreased with proximity to disturbance. Consequently, avoidance of human disturbance prompted loss of otherwise available forage, resulting in indirect habitat loss that was 4.6-times greater than direct habitat loss from roads, well pads, and other infrastructure. The multiplicative effects of indirect habitat loss, as mediated by behavior, impaired use of the foodscape by reducing the amount of available forage for mule deer, a consequence of which may be winter ranges that support fewer animals than they did before development.

Conservation Genomics in the Sagebrush Sea: Population Divergence, Demographic History, and Local Adaptation in Sage-Grouse (Centrocercus spp.).

Sage-grouse are two closely related iconic species of the North American West, with historically broad distributions across sagebrush-steppe habitat. Both species are dietary specialists on sagebrush during winter, with presumed adaptations to tolerate the high concentrations of toxic secondary metabolites that function as plant chemical defenses. Marked range contraction and declining population sizes since European settlement have motivated efforts to identify distinct population genetic variation, particularly that which might be associated with local genetic adaptation and dietary specialization of sage-grouse. We assembled a reference genome and performed whole-genome sequencing across sage-grouse from six populations, encompassing both species and including several populations on the periphery of the species ranges. Population genomic analyses reaffirmed genome-wide differentiation between greater and Gunnison sage-grouse, revealed pronounced intraspecific population structure, and highlighted important differentiation of a small isolated population of greater sage-grouse in the northwest of the range. Patterns of genome-wide differentiation were largely consistent with a hypothesized role of genetic drift due to limited gene flow among populations. Inferred ancient population demography suggested persistent declines in effective population sizes that have likely contributed to differentiation within and among species. Several genomic regions with single-nucleotide polymorphisms exhibiting extreme population differentiation were associated with candidate genes linked to metabolism of xenobiotic compounds. In vitro activity of enzymes isolated from sage-grouse livers supported a role for these genes in detoxification of sagebrush, suggesting that the observed interpopulation variation may underlie important local dietary adaptations, warranting close consideration for conservation strategies that link sage-grouse to the chemistry of local sagebrush.

Preferences of Specialist and Generalist Mammalian Herbivores for Mixtures Versus Individual Plant Secondary Metabolites.

Herbivores that forage on chemically defended plants consume complex mixtures of plant secondary metabolites (PSMs). However, the mechanisms by which herbivores tolerate mixtures of PSMs are relatively poorly understood. As such, it remains difficult to predict how PSMs, singly or as complex mixtures, influence diet selection by herbivores. Although relative rates of detoxification of PSMs have been used to explain tolerance of PSMs by dietary specialist herbivores, few studies have used the rate of detoxification of individual PSMs to understand dietary preferences of individual herbivores for individual versus mixtures of PSMs. We coupled in vivo experiments using captive feeding trials with in vitro experiments using enzymatic detoxification assays to evaluate the dietary preferences and detoxification capacities of pygmy rabbits (Brachylagus idahoensis), dietary specialists on sagebrush (Artemisia spp.), and mountain cottontails (Sylvilagus nuttallii), dietary generalists. We compared preference for five single PSMs in sagebrush compared to a mixture containing those same five PSMs. We hypothesized that relative preference for individual PSMs would coincide with faster detoxification capacity for those PSMs by specialists and generalists. Pygmy rabbits generally showed little preference among individual PSMs compared to mixed PSMs, whereas mountain cottontails exhibited stronger preferences. Pygmy rabbits had faster detoxification capacities for all PSMs and consumed higher concentrations of individual PSMs versus a mixture than cottontails. However, detoxification capacity for an individual PSM did not generally coincide with preferences or avoidance of individual PSMs by either species. Cottontails avoided, but pygmy rabbits preferred, camphor, the PSM with the slowest detoxification rate by both species. Both species avoided ß-pinene despite it having one of the fastest detoxification rate. Taken together our in vivo and in vitro results add to existing evidence that detoxification capacity is higher in dietary specialist than generalist herbivores. However, results also suggest that alternative mechanisms such as absorption and the pharmacological action of individual or mixtures of PSMs may play a role in determining preference of PSMs within herbivore species.

Seasonal temperature acclimatization in a semi-fossorial mammal and the role of burrows as thermal refuges.

Small mammals in habitats with strong seasonal variation in the thermal environment often exhibit physiological and behavioral adaptations for coping with thermal extremes and reducing thermoregulatory costs. Burrows are especially important for providing thermal refuge when above-ground temperatures require high regulatory costs (e.g., water or energy) or exceed the physiological tolerances of an organism. Our objective was to explore the role of burrows as thermal refuges for a small endotherm, the pygmy rabbit (Brachylagus idahoensis), during the summer and winter by quantifying energetic costs associated with resting above and below ground. We used indirect calorimetry to determine the relationship between energy expenditure and ambient temperature over a range of temperatures that pygmy rabbits experience in their natural habitat. We also measured the temperature of above- and below-ground rest sites used by pygmy rabbits in eastern Idaho, USA, during summer and winter and estimated the seasonal thermoregulatory costs of resting in the two microsites. Although pygmy rabbits demonstrated seasonal physiological acclimatization, the burrow was an important thermal refuge, especially in winter. Thermoregulatory costs were lower inside the burrow than in above-ground rest sites for more than 50% of the winter season. In contrast, thermal heterogeneity provided by above-ground rest sites during summer reduced the role of burrows as a thermal refuge during all but the hottest periods of the afternoon. Our findings contribute to an understanding of the ecology of small mammals in seasonal environments and demonstrate the importance of burrows as thermal refuge for pygmy rabbits.

Interacting effects of ambient temperature and food quality on the foraging ecology of small mammalian herbivores.

Both temperature and diet quality play an important role in the time and energy budgets of small mammalian herbivores. However, little is known about how temperature and diet quality interact to influence diet selection, nutrient extraction, and energetics, and how these effects might differ among species. Therefore, we examined the effects of diet quality and temperature on aspects of the foraging ecology of two species of lagomorphs, pygmy rabbits (Brachylagus idahoensis), which are small dietary specialists, and mountain cottontail rabbits (Sylvilagus nuttallii), which are larger dietary and habitat generalists. In a series of feeding experiments, we investigated 1) the effects of temperature on selection of plant fiber and the plant secondary metabolite 1,8 cineole in their diets, 2) effects of temperature and plant fiber on daily intake, digestion, and passage of food, 3) effects of plant fiber and 1,8 cineole on resting metabolic rate, and 4) how these interactions differ between the rabbit species. Both species chose to eat more total food and a greater proportion of high fiber food that passed more quickly through the digestive system in colder temperatures. However, temperature did not affect how much 1,8 cineole the rabbits consumed nor how thoroughly they digested food. Food quality affected how well they digested the dry matter in the food, but not their resting metabolic rate. Understanding how the interactions between ambient temperature and food quality affect selection of diets and intake by small mammalian herbivores, and the physiological mechanisms governing these choices, is useful for predicting how these species might respond to changes in both temperature and food quality and inform conservation and restoration strategies.

Evaluation of micro-GPS receivers for tracking small-bodied mammals.

GPS telemetry markedly enhances the temporal and spatial resolution of animal location data, and recent advances in micro-GPS receivers permit their deployment on small mammals. One such technological advance, snapshot technology, allows for improved battery life by reducing the time to first fix via postponing recovery of satellite ephemeris (satellite location) data and processing of locations. However, no previous work has employed snapshot technology for small, terrestrial mammals. We evaluated performance of two types of micro-GPS (< 20 g) receivers (traditional and snapshot) on a small, semi-fossorial lagomorph, the pygmy rabbit (Brachylagus idahoensis), to understand how GPS errors might influence fine-scale assessments of space use and habitat selection. During stationary tests, microtopography (i.e., burrows) and satellite geometry had the largest influence on GPS fix success rate (FSR) and location error (LE). There was no difference between FSR while animals wore the GPS collars above ground (determined via light sensors) and FSR generated during stationary, above-ground trials, suggesting that animal behavior other than burrowing did not markedly influence micro-GPS errors. In our study, traditional micro-GPS receivers demonstrated similar FSR and LE to snapshot receivers, however, snapshot receivers operated inconsistently due to battery and software failures. In contrast, the initial traditional receivers deployed on animals experienced some breakages, but a modified collar design consistently functioned as expected. If such problems were resolved, snapshot technology could reduce the tradeoff between fix interval and battery life that occurs with traditional micro-GPS receivers. Our results suggest that micro-GPS receivers are capable of addressing questions about space use and resource selection by small mammals, but that additional techniques might be needed to identify use of habitat structures (e.g., burrows, tree cavities, rock crevices) that could affect micro-GPS performance and bias study results.

Occurrence of Triclocarban and Triclosan in an Agro-ecosystem Following Application of Biosolids.

Triclocarban (TCC) and triclosan (TCS), two of the most commonly used antimicrobial compounds, can be introduced into ecosystems by applying wastewater treatment plant biosolids to agricultural fields. Concentrations of TCC and TCS were measured in different trophic levels within a terrestrial food web encompassing land-applied biosolids, soil, earthworms (Lumbricus), deer mice (Peromyscus maniculatus), and eggs of European starlings (Sturnus vulgaris) and American kestrels (Falco sparverius) at an experimental site amended with biosolids for the previous 7 years. The samples from this site were compared to the same types of samples from a reference (biosolids-free) agricultural site. Inter-site comparisons showed that concentrations of both antimicrobials were higher on the experimental site in the soil, earthworms, mice (livers), and European starling eggs, but not American kestrel eggs, compared to the control site. Inter-species comparisons on the experimental site indicated significantly higher TCC concentrations in mice (TCC: 12.6-33.3 ng/g) and in starling eggs (TCC: 15.4-31.4 ng/g) than in kestrel eggs (TCC: 3.6 ng/g). Nesting success of kestrels only was significantly lower on the experimental site compared to the reference site due to nest abandonment. This study demonstrates that biosolids-derived TCC and TCS are present throughout the terrestrial food web, including secondary (e.g., starlings) and tertiary (i.e., kestrels) consumers, after repeated, long-term biosolids application.

Selection of food patches by sympatric herbivores in response to concealment and distance from a refuge.

Small herbivores face risks of predation while foraging and are often forced to trade off food quality for safety. Life history, behaviour, and habitat of predator and prey can influence these trade-offs. We compared how two sympatric rabbits (pygmy rabbit, Brachylagus idahoensis; mountain cottontail, Sylvilagus nuttallii) that differ in size, use of burrows, and habitat specialization in the sagebrush-steppe of western North America respond to amount and orientation of concealment cover and proximity to burrow refuges when selecting food patches. We predicted that both rabbit species would prefer food patches that offered greater concealment and food patches that were closer to burrow refuges. However, because pygmy rabbits are small, obligate burrowers that are restricted to sagebrush habitats, we predicted that they would show stronger preferences for greater cover, orientation of concealment, and patches closer to burrow refuges. We offered two food patches to individuals of each species during three experiments that either varied in the amount of concealment cover, orientation of concealment cover, or distance from a burrow refuge. Both species preferred food patches that offered greater concealment, but pygmy rabbits generally preferred terrestrial and mountain cottontails preferred aerial concealment. Only pygmy rabbits preferred food patches closer to their burrow refuge. Different responses to concealment and proximity to burrow refuges by the two species likely reflect differences in perceived predation risks. Because terrestrial predators are able to dig for prey in burrows, animals like pygmy rabbits that rely on burrow refuges might select food patches based more on terrestrial concealment. In contrast, larger habitat generalists that do not rely on burrow refuges, like mountain cottontails, might trade off terrestrial concealment for visibility to detect approaching terrestrial predators. This study suggests that body size and evolutionary adaptations for using habitat, even in closely related species, might influence anti-predator behaviors in prey species.

Phytochemistry predicts habitat selection by an avian herbivore at multiple spatial scales.

Animal habitat selection is a process that functions at multiple, hierarchically. structured spatial scales. Thus multi-scale analyses should be the basis for inferences about factors driving the habitat selection process. Vertebrate herbivores forage selectively on the basis of phytochemistry, but few studies have investigated the influence of selective foraging (i.e., fine-scale habitat selection) on habitat selection at larger scales. We tested the hypothesis that phytochemistry is integral to the habitat selection process for vertebrate herbivores. We predicted that habitats selected at three spatial scales would be characterized by higher nutrient concentrations and lower concentrations of plant secondary metabolites (PSMs) than unused habitats. We used the Greater Sage-Grouse (Centrocercus urophasianus), an avian herbivore with a seasonally specialized diet of sagebrush, to test our hypothesis. Sage-Grouse selected a habitat type (black sagebrush, Artemisia nova) with lower PSM concentrations than the alternative (Wyoming big sagebrush, A. tridentata wyomingensis). Within black sagebrush habitat, Sage-Grouse selected patches and individual plants within those patches that were higher in nutrient concentrations and lower in PSM concentrations than those not used. Our results provide the first evidence for multi-scale habitat selection by an avian herbivore on the basis of phytochemistry, and they suggest that phytochemistry may be a fundamental driver of habitat selection for vertebrate herbivores.

PharmEcology: A pharmacological approach to understanding plant-herbivore interactions: an introduction to the symposium.

A central goal in understanding the ecology and evolution of animals is to identify factors that constrain or expand breadth of diet. Selection of diet in many animals is often constrained by chemical deterrents (i.e., secondary metabolites) in available food items. The integration of chemistry and ecology has led to a significant understanding of the chemical complexity of prey (e.g., animals, plants, and algae) and the resultant foraging behavior of consumers. However, most of the literature on chemical defenses of marine and terrestrial prey lacks a mechanistic understanding of how consumers tolerate, or avoid, chemically-defended foods. In order to understand ecological patterns of foraging and co-evolutionary relationships between prey and consumers, we must advance our understanding of the physiological mechanisms responsible for chemical interactions. Such mechanistic studies require the integration of the discipline of pharmacology with ecology, which we call "PharmEcology." Pharmacology provides the tools and insight to investigate the fate (what the body does to a chemical) and action (what a chemical does to the body) of chemicals in living organisms, whereas ecology provides the insight into the interactions between organisms (e.g., herbivores) and their environment (e.g., plants). Although, the general concepts of pharmacology were introduced to ecologists studying plant-herbivore interactions over 30 years ago, the empirical use of pharmacology to understand mechanisms of chemical interactions has remained limited. Moreover, many of the recent biochemical, molecular and technical advances in pharmacology have yet to be utilized by ecologists. The PharmEcology symposium held at a meeting of the Society for Integrative and Comparative Biology in January of 2009 was developed to define novel research directions at the interface of pharmacology and ecology.

Revisiting the dietary niche: When is a mammalian herbivore a specialist?

Understanding dietary specialization in herbivores has theoretical and practical implications in ecology, yet defining niche breadth consistently has been problematic. To increase clarity and communication among ecologists and among disciplines (i.e., chemists, pharmacologists), we propose a specialization key for mammalian herbivores that assigns "obligatory" and "facultative" modifiers to the terms "specialist" and "generalist". These modifiers are assigned based on (1) relative breadth of the animal's realized niche and diet (what it eats), (2) relative breadth of the fundamental niche and available diet (what it could eat), (3) the extent of chemical or physical characteristics, termed "difficulty", that make food items either low in value or unpalatable to most herbivores, and (4) relevant temporal and spatial scales at which diets and niche breadth were measured. Obligatory specialists always have a narrow realized niche consisting of difficult food items, and morphological adaptations and/or the loss of redundant behavioral flexibility that effectively limit their fundamental niches, precluding them from expanding their diet under changed environmental conditions. Facultative specialists have a consistently narrow realized niche for difficult foods during at least one spatial or temporal scale, but have a broad enough fundamental niche to allow them to expand their diet to include less difficult foods when environmental conditions allow. Facultative generalists have the broadest fundamental niche, allowing them to consume a wide variety of foods. However, they may occasionally demonstrate a narrow realized niche, focused on less difficult plants than is the case with specialists. Finally, the obligatory generalists always have a wide realized niche because of a relatively narrow fundamental niche, precluding them from eating much of any difficult plant. We summarize hypothesized characteristics of mammalian herbivores in each of the four categories of specialization. We demonstrate the need for further work on defining the realized and fundamental niches, comparing among herbivores across categories conducted under similar conditions, and understanding the nature of trade-offs required for specialization and generalization for both community and phylogenetically based analyses.

Exploitation of secondary metabolites by animals: A response to homeostatic challenges.

We propose that the exploitation of the bioactive properties of secondary metabolites (SMs) by animals can provide a "treatment" against various challenges that perturb homeostasis in animals. The unified theoretical framework for the exploitation of SMs by animals is based on a synthesis of research from a wide range of fields and although it is focused on providing generalized predictions for herbivores that exploit SMs of plants, predictions can be applied to understand the exploitation of SMs by many animals. In this review, we argue that the probability of SM exploitation is determined by the relative difference between the cost of a homeostatic challenge and the toxicity of the SM and we provide various predictions that can be made when considering behavior under a homeostatic perspective. The notion that animals experience and respond to costly challenges by exploiting therapeutic SMs provides a relatively novel perspective to explain foraging behavior in herbivores, specifically, and behavior of animals in general. We provide evidence that animals can exploit the biological activity of SMs to mitigate the costs of infection by parasites, enhance reproduction, moderate thermoregulation, avoid predation, and increase alertness. We stress that a better understanding of animal behavior requires that ecologists look beyond their biases that SMs elicit punishment and consider a broader view of avoidance or selection of SMs relative to the homeostatic state. Finally, we explain how understanding exploitation of SMs by animals could be applied to advance practices of animal management and lead to discovery of new drugs.