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

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

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.

Original language	English
Article number	234
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-27925-x
State	Published - Dec 2022

Bibliographical note

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

Funding

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.

Funders	Funder number
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

ASJC Scopus subject areas

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41467-021-27925-x

Cite this

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), Article 234. https://doi.org/10.1038/s41467-021-27925-x

@article{f9d228e32fa8406e8cfdd66be645854d,

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.",

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

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1038/s41467-021-27925-x",

language = "English",

volume = "13",

number = "1",

}

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, no. 1, 234. https://doi.org/10.1038/s41467-021-27925-x

TY - JOUR

T1 - Reduced infant rhesus macaque growth rates due to environmental enteric dysfunction and association with histopathology in the large intestine

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.

PY - 2022/12

Y1 - 2022/12

N2 - 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.

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.

UR - http://www.scopus.com/inward/record.url?scp=85122799976&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85122799976&partnerID=8YFLogxK

U2 - 10.1038/s41467-021-27925-x

DO - 10.1038/s41467-021-27925-x

M3 - Article

C2 - 35017515

AN - SCOPUS:85122799976

SN - 2041-1723

VL - 13

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 234

ER -

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

Abstract

Bibliographical note

Funding

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this