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Reduced infant rhesus macaque growth rates due to environmental enteric dysfunction and association with histopathology in the large intestine.

ABSTRACT: Environmental enteric dysfunction is associated with malnutrition as well as infant growth stunting and has been classically defined by villous blunting, decreased crypt-to-villus ratio, and inflammation in the small intestine. Here, we characterized environmental enteric dysfunction among infant rhesus macaques that are naturally exposed to enteric pathogens commonly linked to human growth stunting. Remarkably, despite villous atrophy and histological abnormalities observed in the small intestine, poor growth trajectories and low serum tryptophan levels were correlated with increased histopathology in the large intestine. This work provides insight into the mechanisms underlying this disease and indicates that the large intestine may be an important target for therapeutic intervention.

SUBMITTER: Hendrickson SM

PROVIDER: S-EPMC8752659 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Reduced infant rhesus macaque growth rates due to environmental enteric dysfunction and association with histopathology in the large intestine.

Hendrickson Sara M SM Thomas Archana A Prongay Kamm K Haertel Andrew J AJ Garzel Laura M LM Gill Leanne L Barr Tasha T Rhoades Nicholas S NS Reader Rachel R Galan Mark M Carroll Julie M JM Roberts Charles T CT Gao Lina L Amanna Ian J IJ Messaoudi Ilhem I Slifka Mark K MK

Nature communications 20220111 1

Environmental enteric dysfunction is associated with malnutrition as well as infant growth stunting and has been classically defined by villous blunting, decreased crypt-to-villus ratio, and inflammation in the small intestine. Here, we characterized environmental enteric dysfunction among infant rhesus macaques that are naturally exposed to enteric pathogens commonly linked to human growth stunting. Remarkably, despite villous atrophy and histological abnormalities observed in the small intesti ...[more]

PMID: 35017515

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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.

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.

Dataset Information

Reduced infant rhesus macaque growth rates due to environmental enteric dysfunction and association with histopathology in the large intestine.

Publications

Reduced infant rhesus macaque growth rates due to environmental enteric dysfunction and association with histopathology in the large intestine.

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