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

Sara M. Hendrickson; Archana Thomas; Kamm Prongay; Andrew J. Haertel; Laura M. Garzel; Leanne Gill; Tasha Barr; Nicholas S. Rhoades; Rachel Reader; Mark Galan; Julie M. Carroll; Charles T. Roberts; Lina Gao; Ian J. Amanna; Ilhem Messaoudi; Mark K. Slifka

doi:10.1038/s41467-021-27925-x

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

Sara M. Hendrickson
, Archana Thomas
, Kamm Prongay
, Andrew J. Haertel
, Laura M. Garzel
, Leanne Gill
, Tasha Barr
, Nicholas S. Rhoades
, Rachel Reader
, Mark Galan
, Julie M. Carroll
, Charles T. Roberts
, Lina Gao
, Ian J. Amanna
, Ilhem Messaoudi
, Mark K. Slifka

Producción científica: Article › revisión exhaustiva

13 Citas (Scopus)

Resumen

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.

Idioma original	English
Número de artículo	234
Publicación	Nature Communications
Volumen	13
N.º	1
DOI	https://doi.org/10.1038/s41467-021-27925-x
Estado	Published - dic 2022

Nota bibliográfica

Publisher Copyright:
© 2022, The Author(s).

Financiación

We thank A. Lewis, A. Johnson, and the ONPRC Pathology Core for preparing samples for histology, and David Erikson and the ONPRC Endocrine Technologies Support Core (ETSC) at the Oregon National Primate Research Center for developing LC-MS/MS assays to measure serum tryptophan and kynurenine levels. This work was supported by a Bill & Melinda Gates Foundation grant (OPP1149233) to MKS and US National Institute of Health grants P51 OD011092 for the operation of the ONPRC and P51 OD011107 for the operation of the CNPRC. N S R was supported by an NIH IMSD fellowship (GM055246). Funding to digitize images of histology slides archived at the Washington University Digital Pathology Exchange (WUPAX) was provided by the Bill & Melinda Gates Foundation.

Financiadores	Número del financiador
National Institutes of Health (NIH)	GM055246
NIH Office of the Director	P51OD011092, P51 OD011107
Bill and Melinda Gates Foundation	OPP1149233
California National Primate Research Center
Oregon National Primate Research Center

ODS de las Naciones Unidas

Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

Good health and well being

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General
General Physics and Astronomy

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10.1038/s41467-021-27925-x

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Hendrickson, S. M., Thomas, A., Prongay, K., Haertel, A. J., Garzel, L. M., Gill, L., Barr, T., Rhoades, N. S., Reader, R., Galan, M., Carroll, J. M., Roberts, C. T., Gao, L., Amanna, I. J., Messaoudi, I., & Slifka, M. K. (2022). Reduced infant rhesus macaque growth rates due to environmental enteric dysfunction and association with histopathology in the large intestine. Nature Communications, 13(1), Artículo 234. https://doi.org/10.1038/s41467-021-27925-x

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title = "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.",

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Hendrickson, SM, Thomas, A, Prongay, K, Haertel, AJ, Garzel, LM, Gill, L, Barr, T, Rhoades, NS, Reader, R, Galan, M, Carroll, JM, Roberts, CT, Gao, L, Amanna, IJ, Messaoudi, I & Slifka, MK 2022, 'Reduced infant rhesus macaque growth rates due to environmental enteric dysfunction and association with histopathology in the large intestine', Nature Communications, vol. 13, n.º 1, 234. https://doi.org/10.1038/s41467-021-27925-x

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AU - Hendrickson, Sara M.

AU - Thomas, Archana

AU - Prongay, Kamm

AU - Haertel, Andrew J.

AU - Garzel, Laura M.

AU - Gill, Leanne

AU - Barr, Tasha

AU - Rhoades, Nicholas S.

AU - Reader, Rachel

AU - Galan, Mark

AU - Carroll, Julie M.

AU - Roberts, Charles T.

AU - Gao, Lina

AU - Amanna, Ian J.

AU - Messaoudi, Ilhem

AU - Slifka, Mark K.

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AB - 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.

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

Resumen

Nota bibliográfica

Financiación

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ASJC Scopus subject areas

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