Reduced infant rhesus macaque growth rates due to environmental enteric dysfunction and association with histopathology in the large intestine.
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ABSTRACT:
SUBMITTER: Hendrickson SM
PROVIDER: S-EPMC8752659 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Antimicrobial peptides are secreted by small intestinal Paneth cells as components of innate immunity. To investigate the role of alpha-defensins in enteric host defenses in nonhuman primates, alpha-defensin cDNAs were isolated, alpha-defensin peptides were purified from rhesus macaque small bowel, and the bactericidal activities of the peptides were measured. Six rhesus enteric alpha-defensin (RED) cDNAs, RED-1 to RED-6, were identified in a jejunum cDNA library; the deduced RED peptides exhibited extensive diversity relative to the primary structures of rhesus myeloid alpha-defensins. RED-4 was purified from monkey jejunum, and N-terminal peptide sequencing of putative RED-4 peptides identified two N termini, RTCYCRTGR. and TCYCRTGRC.; these corresponded to alternative N termini for the RED-4 molecules, as deduced from their molecular masses and RED cDNAs. In situ hybridization experiments localized RED mRNAs exclusively to small intestinal Paneth cells. Recombinant RED-1 to RED-4 were purified to homogeneity and shown to be microbicidal in the low micromolar range (</=10 micro g/ml) against gram-positive and gram-negative bacteria, with individual peptides exhibiting variable target cell specificities. Thus, compared to myeloid alpha-defensins from rhesus macaques, enteric alpha-defensin peptides are highly variable in both primary structure and activity. These studies should facilitate further analyses of the role of alpha-defensins in primate enteric immunity.
| S-EPMC356057 | biostudies-literature
Project description:Infant temperament is theorized to lay the foundation for adult personality; however, many questions remain regarding personality in infancy, including the number of dimensions, extent to which they are adult-like, and their relation to other outcomes, such as mental and physical health. Here we tested whether adult-like personality dimensions are already present in infancy in a nonhuman primate species. We measured personality and subjective well-being in 7-month-old rhesus macaques (N = 55) using the Hominoid Personality Questionnaire and Subjective Well-Being Questionnaire, both of which were developed for adult primates based on human measures. Multiple human raters, who provided infants with daily care since birth, independently rated each infant. We found high interrater reliability. Results from a parallel analysis and scree plot indicated a five component structure, which, using principal components analysis, we found to be comprised of dimensions relating to Openness (e.g., curiosity, inquisitive, playfulness), Assertiveness (e.g., dominance, bullying, aggressive), Anxiety (e.g., vigilance, fearful), Friendliness (e.g., sociable, affectionate, sympathetic), and Intellect (e.g., organized, not erratic). These components are largely analogous to those in adult macaques, suggesting remarkably stable structural personality components across the lifespan. Infant macaques' subjective well-being positively correlates with Openness and Assertiveness and negatively correlated with Anxiety, similar to findings in adult macaques and other primates. Together, these findings suggest that, in macaques, infant personality dimensions may be conceptually related to adult personality and challenge the view that infant temperament may be disorganized and not as meaningful as adult personality. Further research is necessary to explore the antecedents, predictive validity, and stability of these personality components across situations and with development.
| S-EPMC6922351 | biostudies-literature
Project description:BACKGROUND Cystic fibrosis (CF) has multiple effects on the gastrointestinal system, including altered motility. The Cftr knockout mouse model of CF has impaired small intestinal transit but the mechanism is unknown. METHODS Behaviour of circular smooth muscle was studied in an organ bath. Expression levels of prostaglandin (PG) degradative genes were measured by quantitative RT-PCR, and PGE(2) levels were measured by enzyme immunoassay. KEY RESULTS Cystic fibrosis circular muscle activity was erratic and had variable frequency of contractions, as compared to WT. The CF tissue was non-responsive to cholinergic stimulation or direct KCl depolarization. PGE(2) and PGF(2alpha) are significantly elevated in the CF mouse small intestine, and we hypothesized these contribute to impaired smooth muscle activity. After inhibition of PG synthesis, the CF circular muscle exhibited greater cholinergic responsiveness, which was reversed by exogenous PGE(2). PGF(2alpha) enhanced activity of CF tissue only after inhibition of PG synthesis. The enteric microbiota was implicated in PGE(2)-mediated dysmotility because broad spectrum antibiotic treated WT mice, which have slowed transit, exhibit impaired circular muscle activity. This was accompanied by decreased expression of PG degradative genes and increased intestinal PGE(2) levels. Furthermore, administration of oral laxative, which eradicates bacterial overgrowth and improves transit in CF mice, increased expression of PG degradative genes, decreased PGE(2) levels, and improved CF muscle activity. CONCLUSIONS & INFERENCES These results suggest that the enteric microbiota modulates PGE(2) levels in a complex manner, which affects enteric smooth muscle activity and contributes to slower small intestinal transit in CF.
| S-EPMC3756681 | biostudies-literature
Project description:There is a growing appreciation for the specific health benefits conferred by commensal microbiota on their hosts. Clinical microbiota analysis and animal studies in germ-free or antibiotic-treated mice have been crucial for improving our understanding of the role of the microbiome on the host mucosal surface; however, studies on the mechanisms involved in microbiome-host interactions remain limited to small animal models. Here, we demonstrated that rhesus monkeys under short-term broad-spectrum antibiotic treatment could be used as a model to study the gut mucosal host-microbiome niche and immune balance with steady health status. Results showed that the diversity and community structure of the gut commensal bacteria in rhesus monkeys were both disrupted after antibiotic treatment. Furthermore, the 16S rDNA amplicon sequencing results indicated that Escherichia-Shigella were predominant in stool samples 9 d of treatment, and the abundances of bacterial functional genes and predicted KEGG pathways were significantly changed. In addition to inducing aberrant morphology of small intestinal villi, the depletion of gut commensal bacteria led to increased proportions of CD3 + T, CD4 + T, and CD16 + NK cells in peripheral blood mononuclear cells (PBMCs), but decreased numbers of Treg and CD20 + B cells. The transcriptome of PBMCs from antibiotic-treated monkeys showed that the immune balance was affected by modulation of the expression of many functional genes, including IL-13, VCAM1, and LGR4.
| S-EPMC6956715 | biostudies-literature
Project description:Renal pigmentation due to the administration of exogenous compounds is an uncommon finding in most species. This report describes renal pigmentation and intranuclear inclusions of the proximal convoluted tubules due to chronic bismuth administration in a rhesus macaque. An 11-year-old Indian-origin rhesus macaque with a medical history of chronic intermittent vomiting had been treated with bismuth subsalicylate, famotidine, and omeprazole singly or in combination over the course of 8 years. At necropsy, the renal cortices were diffusely dark green to black. Light and electron microscopy revealed intranuclear inclusions within the majority of renal proximal tubular epithelial cells. These inclusions appeared magenta to brown when stained with hematoxylin and eosin and were negative by the Ziehl-Neelsen acid-fast stain. Elemental analysis performed on frozen kidney measured bismuth levels to be markedly elevated at 110.6 ppm, approximately 500 to 1000 times acceptable limits. To our knowledge, this is the first report of renal bismuth deposition in a rhesus macaque resulting in renal pigmentation and intranuclear inclusions.
| S-EPMC4285376 | biostudies-literature
Project description:Backgroundα-Tocopherol (αT) in its natural form [2'R, 4'R, 8'R αT (RRR-αT)] is more bioactive than synthetic α-tocopherol (all rac-αT). All rac-αT is widely used in infant formulas, but its accretion in formula-fed infant brain is unknown.ObjectiveWe sought to compare αT and stereoisomer status in infant rhesus macaques (Macaca mulatta) fed infant formula (RRR-αT or all rac-αT) with a reference group fed a mixed diet of breast milk and maternal diet.MethodsFrom 1 d after birth until 6 mo of age, infants (n = 23) were either nursery reared and exclusively fed 1 of 2 formulas by staff personnel or were community housed with their mothers and consumed a mixed reference diet of breast milk (69 mL/d at 6 mo) transitioning to monkey diet at ∼2 mo (MF; n = 8). Formulas contained either 21 μmol RRR-αT/L (NAT-F; n = 8) or 30 μmol all rac-αT/L (SYN-F; n = 7). Total αT and αT stereoisomers were analyzed in breast milk at 2, 4, and 6 mo and in monkey plasma and liver and 6 brain regions at 6 mo of age. α-Tocopherol transfer protein (α-TTP), lipoprotein αT, and urinary α-carboxyethyl-hydroxychroman (α-CEHC) were measured. One-way ANOVA with Tukey's post-hoc test was used for analysis.ResultsAt study termination, plasma, liver, lipoprotein, and brain total αT did not differ between groups. However, the NAT-F-fed group had higher RRR-αT than the SYN-F-fed group (P < 0.01) and the MF group (P < 0.0001) in plasma (1.7- and 2.7-fold) and brain (1.5- and 2.5-fold). Synthetic αT 2R stereoisomers (SYNTH-2R) were generally 3- and 7-fold lower in brain regions of the NAT-F group compared with those of the SYN-F and MF groups (P < 0.05). SYNTH-2R stereoisomers were 2-fold higher in MF than SYN-F (P < 0.0001). The plasma percentage of SYNTH-2R was negatively correlated with the brain percentage of RRR-αT (r = -0.99, P < 0.0001). Brain αT profiles were not explained by α-TTP mRNA or protein expression. Urine α-CEHC was 3 times higher in the NAT-F than in the MF group (P < 0.01).ConclusionsConsumption of infant formulas with natural (NAT-F) compared with synthetic (SYN-F) αT differentially impacted brain αT stereoisomer profiles in infant rhesus macaques. Future studies should assess the functional implications of αT stereoisomer profiles on brain health.
| S-EPMC7467853 | biostudies-literature
Project description:Virome biogeography in the primate lower gastrointestinal tract
| PRJNA491509 | ENA
Project description: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.
| S-EPMC6709555 | biostudies-literature
Project description:Sixteen individual rhesus macaque genomes were compared to a reference macaque genome (R354) on custom-designed sure-print 1M oligonucleotide microarray Agilent (Agilent Technologies) aCGH slide per manufacturer’s recommendations.
2011-05-11 | GSE19881 | GEO
Project description:Self-injurious behavior (SIB) is a common comorbidity of psychiatric disorders but there is a dearth of information about neurological mechanisms underlying the behavior, and few animal models exist. SIB in humans is characterized by any intentional self-directed behavior that leads to wounds, whereas in macaques it is not always accompanied by wounds. We describe a cohort of rhesus macaques displaying SIB as adults, in which changes within the central nervous system were associated with the SIB. In these macaques, increases in central nervous system striatal dopamine (DA) receptor binding (BPND) measured by positron emission tomography (PET) [11C]raclopride imaging correlated with severity of wounding (rs=0.662, P=0.014). Furthermore, utilizing standardized cognitive function tests, we showed that impulsivity (stop signal reaction time, SSRT) and deficits in attentional set shifting (intra-/extradimensional shift) were correlated with increased severity of SIB (rs=0.563, P=0.045 and rs=0.692, P=0.009, respectively). We also tested the efficacy of guanfacine, an α2A adrenergic agonist that acts to improve postsynaptic transmission of neuronal impulses, in reducing SIB. A subset of these animals were enrolled in a randomized experimenter-blinded study that demonstrated guanfacine decreased the severity of wounding in treated animals compared with vehicle-only-treated controls (P=0.043), with residual beneficial effects seen for several weeks after cessation of therapy. Animals with the highest severity of SIB that received guanfacine also showed the most significant improvement (rs=-0.761, P=0.009). The elevated PET BPND was likely due to low intrasynaptic DA, which in turn may have been improved by guanfacine. With underlying physiology potentially representative of the human condition and the ability to affect outcome measures of disease using pharmacotherapy, this model represents a unique opportunity to further our understanding of the biology and treatment of SIB in both animals and humans.
| S-EPMC4471292 | biostudies-other