Fecal transplantation and butyrate improve neuropathic pain, modify immune cell profile, and gene expression in the PNS of obese mice.

Obesity affects over 2 billion people worldwide and is accompanied by peripheral neuropathy (PN) and an associated poorer quality of life. Despite high prevalence, the molecular mechanisms underlying the painful manifestations of PN are poorly understood, and therapies are restricted to use of painkillers or other drugs that do not address the underlying disease. Studies have demonstrated that the gut microbiome is linked to metabolic health and its alteration is associated with many diseases, including obesity. Pathologic changes to the gut microbiome have recently been linked to somatosensory pain, but any relationships between gut microbiome and PN in obesity have yet to be explored. Our data show that mice fed a Western diet developed indices of PN that were attenuated by concurrent fecal microbiome transplantation (FMT). In addition, we observed changes in expression of genes involved in lipid metabolism and calcium handling in cells of the peripheral nerve system (PNS). FMT also induced changes in the immune cell populations of the PNS. There was a correlation between an increase in the circulating short-chain fatty acid butyrate and pain improvement following FMT. Additionally, butyrate modulated gene expression and immune cells in the PNS. Circulating butyrate was also negatively correlated with distal pain in 29 participants with varied body mass index. Our data suggest that the metabolite butyrate, secreted by the gut microbiome, underlies some of the effects of FMT. Targeting the gut microbiome, butyrate, and its consequences may represent novel viable approaches to prevent or relieve obesity-associated neuropathies.

Variation in Trematode Infection in Snails Associated with Land Cover and Water Chemistry in the Central Illinois River Watershed.

Parasites can affect animal populations and communities in aquatic ecosystems. However, greater understanding is needed for the distributions and drivers of parasite infection levels in many areas. This study focuses on parasite prevalence (percent infected hosts) of an important class of parasites, trematodes, in 2 species of snail first intermediate hosts (Planorbella trivolvis and Physa sp.) in the Illinois River watershed, which has been impacted by human development. We hypothesized that trematode prevalence depends on local (e.g., water chemistry) and landscape (e.g., proximity to the Illinois River and land cover) factors. To test our hypotheses, we collected at least 20 individuals of 1 or both species of snails from 28 ponds within the watershed, and we made water-quality measurements and recorded habitat characteristics at each site. We then screened the snails for infections in the laboratory and identified the trematode cercariae that emerged based on morphological and molecular techniques. We found 5 cercariae morphotypes, including important parasites of wildlife, such as Echinostoma sp. and Ribeiroia ondatrae. Our results indicate that proximity to the Illinois River and open water or wetlands was positively associated with trematode prevalence in both snail species, whereas water chemistry (higher pH, lower calcium concentration, and lower specific conductance) was associated with increased prevalence, but only in Physa. Our findings offer increased understanding of potential environmental drivers underlying trematode distributions, with implications for wildlife health.

Effects of vertical position on trematode parasitism in larval anurans.

Spatial distributions of animals can affect interactions with their natural enemies, such as parasites, and thus have important implications for host-parasite dynamics. While spatial variation in infection risk has been explored in many systems at the landscape scale, less attention has been paid to spatial structure at smaller scales. Here, we explore a hypothesized relationship between a common spatial variable, vertical position, and risk of parasite infection in a model aquatic system, larval frogs (Rana) and trematode (Digenea) parasites. Vertical position is relevant to this system given evidence that the densities of snail first intermediate hosts, tadpole second intermediate hosts, and trematode infective stages can vary with depth. To test the effects of depth on infection risk of larval frogs by trematodes, we performed two enclosure experiments, one in the laboratory and one in the field, in which larval frogs in cages just below the water surface or near the bottom of the water column were exposed to parasites. Compared with near-surface cages, mean infection load (number of cysts) in tadpoles in near-bottom cages was 83% higher after 48-h exposures in the laboratory and 730% higher after 10-day exposures in the field. Our findings thus indicate that infection risk depends on depth, which may have adaptive significance, as tadpoles have previously been shown to change vertical position in response to parasite presence. These results motivate future work examining vertical variation in infection risk and may have broader implications for host-parasite dynamics and evolution of host and parasite behavior.