Mixtures of Milkweed Cardenolides Protect Monarch Butterflies against Parasites.

Plants have evolved a diverse arsenal of defensive secondary metabolites in their evolutionary arms race with insect herbivores. In addition to the bottom-up forces created by plant chemicals, herbivores face top-down pressure from natural enemies, such as predators, parasitoids and parasites. This has led to the evolution of specialist herbivores that do not only tolerate plant secondary metabolites but even use them to fight natural enemies. Monarch butterflies (Danaus plexippus) are known for their use of milkweed chemicals (cardenolides) as protection against vertebrate predators. Recent studies have shown that milkweeds with high cardenolide concentrations can also provide protection against a virulent protozoan parasite. However, whether cardenolides are directly responsible for these effects, and whether individual cardenolides or mixtures of these chemicals are needed to reduce infection, remains unknown. We fed monarch larvae the four most abundant cardenolides found in the anti-parasitic-milkweed Asclepias curassavica at varying concentrations and compositions to determine which provided the highest resistance to parasite infection. Measuring infection rates and infection intensities, we found that resistance is dependent on both concentration and composition of cardenolides, with mixtures of cardenolides performing significantly better than individual compounds, even when mixtures included lower concentrations of individual compounds. These results suggest that cardenolides function synergistically to provide resistance against parasite infection and help explain why only milkweed species that produce diverse cardenolide compounds provide measurable parasite resistance. More broadly, our results suggest that herbivores can benefit from consuming plants with diverse defensive chemical compounds through release from parasitism.

Translocation of gut commensal bacteria to the brain.

The gut-brain axis, a bidirectional signaling network between the intestine and the central nervous system, is crucial to the regulation of host physiology and inflammation. Recent advances suggest a strong correlation between gut dysbiosis and neurological diseases, however, relatively little is known about how gut bacteria impact the brain. Here, we reveal that gut commensal bacteria can translocate directly to the brain when mice are fed an altered diet that causes dysbiosis and intestinal permeability, and that this also occurs without diet alteration in distinct murine models of neurological disease. The bacteria were not found in other systemic sites or the blood, but were detected in the vagus nerve. Unilateral cervical vagotomy significantly reduced the number of bacteria in the brain, implicating the vagus nerve as a conduit for translocation. The presence of bacteria in the brain correlated with microglial activation, a marker of neuroinflammation, and with neural protein aggregation, a hallmark of several neurodegenerative diseases. In at least one model, the presence of bacteria in the brain was reversible as a switch from high-fat to standard diet resulted in amelioration of intestinal permeability, led to a gradual loss of detectable bacteria in the brain, and reduced the number of neural protein aggregates. Further, in murine models of Alzheimer's disease, Parkinson's disease, and autism spectrum disorder, we observed gut dysbiosis, gut leakiness, bacterial translocation to the brain, and microglial activation. These data reveal a commensal bacterial translocation axis to the brain in models of diverse neurological diseases.