Background Diarrhea is the second leading cause of death in children under 5 years of age. Enhanced understanding of causal pathways, pathogenesis, and sequelae of diarrhea is urgently needed. Although the gut microbiota is believed to play a role in susceptibility to diarrheal diseases, our understanding of this association remains incomplete. Infant rhesus macaques ( Macaca mulatta ) are susceptible to diarrhea making them an ideal model to address this question. Results The maturation of the infant rhesus macaque gut microbiome throughout the first 8 months of life occurs in a similar pattern as that described for human infants. Moreover, the microbiome of the captive reared infant rhesus macaque more closely resembles that of human infants in the developing world than in the western world. Importantly, prior to disease onset, the gut microbiome of infants that later develop diarrhea is enriched in pathways of immunomodulatory metabolite synthesis, while those of infants that remain asymptomatic are enriched in pathways for short-chain fatty acid production. We identify Prevotella strains that are more abundant at 1 month in infants that later develop diarrhea. At 8 months, the microbiomes of animals that experience diarrhea show increased abundance of Campylobacter and a reduction in Helicobacter macacae . Conclusion The composition of the microbial community could provide a phenotypic marker of an infant’s susceptibility to diarrheal disease. Given the significant physiological and immunological similarities between human and nonhuman primates, these findings provide potential markers of susceptibility to diarrhea that could be modulated to improve infant health, especially in the developing world. Electronic supplementary material The online version of this article (10.1186/s13059-019-1789-x) contains supplementary material, which is available to authorized users.

Inherited retinal degenerations are a common cause of untreatable blindness worldwide, with retinitis pigmentosa and cone dystrophy affecting approximately 1 in 3500 and 1 in 10,000 individuals, respectively. A major limitation to the development of effective therapies is the lack of availability of animal models that fully replicate the human condition. Particularly for cone disorders, rodent, canine, and feline models with no true macula have substantive limitations. By contrast, the cone-rich macula of a nonhuman primate (NHP) closely mirrors that of the human retina. Consequently, well-defined NHP models of heritable retinal diseases, particularly cone disorders that are predictive of human conditions, are necessary to more efficiently advance new therapies for patients. We have identified 4 related NHPs at the California National Primate Research Center with visual impairment and findings from clinical ophthalmic examination, advanced retinal imaging, and electrophysiology consistent with achromatopsia. Genetic sequencing confirmed a homozygous R565Q missense mutation in the catalytic domain of PDE6C, a cone-specific phototransduction enzyme associated with achromatopsia in humans. Biochemical studies demonstrate that the mutant mRNA is translated into a stable protein that displays normal cellular localization but is unable to hydrolyze cyclic GMP (cGMP). This NHP model of a cone disorder will not only serve as a therapeutic testing ground for achromatopsia gene replacement, but also for optimization of gene editing in the macula and of cone cell replacement in general.

Populations of wild lake trout Salvelinus namaycush have been extirpated from nearly all their historical habitats across the Great Lakes. Efforts to restore self-sustaining lake trout populations in U.S. waters have emphasized the stocking of coded-wire-tagged juveniles from six hatchery strains (Seneca Lake, Lewis Lake, Green Lake, Apostle Islands, Isle Royale, and Marquette) into vacant habitats. Strain-specific stocking success has historically been based on estimates of the survival and catch rates of coded-wire-tagged adults returning to spawning sites. However, traditional marking methods and estimates of relative strain abundance provide no means of assessing strain fitness (i.e., the realized contributions to natural recruitment) except by assuming that young-of-the-year production is proportional to adult spawner abundance. We used microsatellite genetic data collected from six hatchery strains with likelihood-based individual assignment tests (IA) and mixed-stock analysis (MSA) to identify the strain composition of young of the year recruited each year. We show that strain classifications based on IA and MSA were concordant and that the accuracy of both methods varied based on strain composition. Analyses of young-of-the-year lake trout samples from Little Traverse Bay (Lake Michigan) and Six Fathom Bank (Lake Huron) revealed that strain contributions differed significantly from estimates of the strain composition of adults returning to spawning reefs. The Seneca Lake strain contributed the majority of juveniles produced on Six Fathom Bank and more young of the year than expected within Little Traverse Bay. Microsatellite markers provided a method for accurately classifying the lake trout hatchery strains used for restoration efforts in the Great Lakes and for assessment of strain-specific reproductive success.

Nonhuman primates are the only mammals to possess a true macula similar to humans, and spontaneously develop drusenoid lesions which are hallmarks of age-related macular degeneration (AMD). Prior studies demonstrated similarities between human and nonhuman primate drusen based on clinical appearance and histopathology. Here, we employed fundus photography, spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), and infrared reflectance (IR) to characterize drusenoid lesions in aged rhesus macaques. Of 65 animals evaluated, we identified lesions in 20 animals (30.7%). Using the Age-Related Eye Disease Study 2 (AREDS2) grading system and multimodal imaging, we identified two distinct drusen phenotypes – 1) soft drusen that are larger and appear as hyperreflective deposits between the retinal pigment epithelium (RPE) and Bruch’s membrane on SD-OCT, and 2) hard, punctate lesions that are smaller and undetectable on SD-OCT. Both exhibit variable FAF intensities and are poorly visualized on IR. Eyes with drusen exhibited a slightly thicker RPE compared with control eyes (+3.4 μm, P=0.012). Genetic polymorphisms associated with drusenoid lesions in rhesus monkeys in ARMS2 and HTRA1 were similar in frequency between the two phenotypes. These results refine our understanding of drusen development, and provide insight into the absence of advanced AMD in nonhuman primates.