Co-occurrence of Campylobacter Species in Children From Eastern Ethiopia, and Their Association With Environmental Enteric Dysfunction, Diarrhea, and Host Microbiome

Yitagele Terefe; Loïc Deblais; Mostafa Ghanem; Yosra A. Helmy; Bahar Mummed; Dehao Chen; Nitya Singh; Vida Ahyong; Katrina Kalantar; Getnet Yimer; Jemal Yousuf Hassen; Abdulmuen Mohammed; Sarah L. McKune; Mark J. Manary; Maria Isabel Ordiz; Wondwossen Gebreyes; Arie H. Havelaar; Gireesh Rajashekara

doi:10.3389/fpubh.2020.00099

Co-occurrence of Campylobacter Species in Children From Eastern Ethiopia, and Their Association With Environmental Enteric Dysfunction, Diarrhea, and Host Microbiome

Yitagele Terefe, Loïc Deblais, Mostafa Ghanem, Yosra A. Helmy, Bahar Mummed, Dehao Chen, Nitya Singh, Vida Ahyong, Katrina Kalantar, Getnet Yimer, Jemal Yousuf Hassen, Abdulmuen Mohammed, Sarah L. McKune, Mark J. Manary, Maria Isabel Ordiz, Wondwossen Gebreyes, Arie H. Havelaar, Gireesh Rajashekara

Veterinary Science

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

32 Scopus citations

Abstract

High Campylobacter prevalence during early childhood has been associated with stunting and environmental enteric dysfunction (EED), especially in low resource settings. This study assessed the prevalence, diversity, abundance, and co-occurrence of Campylobacter spp. in stools from children in a rural area of eastern Ethiopia and their association with microbiome, diarrhea, and EED in children. Stool samples (n = 100) were collected from randomly selected children (age range: 360–498 days) in five kebeles in Haramaya District, Ethiopia. Diarrhea, compromised gut permeability, and gut inflammation were observed in 48, 45, and 57% of children, respectively. Campylobacter prevalence and species diversity were assessed using PCR and meta-total RNA sequencing (MeTRS). The prevalence of Campylobacter spp. in the children's stools was 50% (41–60%) by PCR and 88% (80–93.6%) by MeTRS (P < 0.01). Further, seven Campylobacter species (Campylobacter jejuni, Campylobacter upsaliensis, Campylobacter hyointestinalis, Campylobacter coli, Campylobacter sp. RM6137, uncultured Campylobacter sp., and Campylobacter sp. RM12175) were detected by MeTRS in at least 40% of children stools in high abundance (>1.76-log read per million per positive stool sample). Four clusters of Campylobacter species (5–12 species per cluster) co-occurred in the stool samples, suggesting that Campylobacter colonization of children may have occurred through multiple reservoirs or from a reservoir in which several Campylobacter species may co-inhabit. No associations between Campylobacter spp., EED, and diarrhea were detected in this cross-sectional study; however, characteristic microbiome profiles were identified based on the prevalence of Campylobacter spp., EED severity, and diarrhea. Forty-seven bacterial species were correlated with Campylobacter, and 13 of them also correlated with gut permeability, gut inflammation and/or EED severity. Forty-nine species not correlated with Campylobacter were correlated with gut permeability, gut inflammation, EED severity and/or diarrhea. This study demonstrated that (1) in addition to C. jejuni and C. coli, multiple non-thermophilic Campylobacter spp. (i.e., Campylobacter hyointestinalis, Campylobacter fetus, and Campylobacter concisus) were frequently detected in the children's stools and (2) the Campylobacter, gut permeability, gut inflammation, EED severity, and diarrhea were associated with characteristic microbiome composition. Additional spatial and longitudinal studies are needed to identify environmental reservoirs and sources of infection of children with disparate Campylobacter species and to better define their associations with EED in low-income countries.

Original language	English
Article number	99
Journal	Frontiers in Public Health
Volume	8
DOIs	https://doi.org/10.3389/fpubh.2020.00099
State	Published - Apr 15 2020

Bibliographical note

Funding Information:
We thank Chan Zuckerberg Biohub, San Francisco, CA, USA and Chan Zuckerberg Initiative, Redwood City, CA, USA for their support with sequencing of total RNA and the bioinformatics analysis of the MeTRS data. We thank Drs. Volker Mai and Nigel French for their critical reading of the manuscript. We also thank Ame Yousuf, Beyan Abdullahi, Yeharerwork Abebaw, Yenenesh Elias Ahmed, Ibsa Ahmed, Jafer Amin, Seyum Tezera, Dr. Nigussie Bussa, and Ibsa Usmane at Haramaya University, and Jenna Daniels and Anna Rabil at University of Florida for their contributions to the project. We thank Srevi Devaraj (Clinical Chemistry and POCT, Texas Children's Hospital, Baylor College of Medicine, Houston, TX) for analysis of sugars in the dual sugar absorption test. The study would not have been possible without cooperation of study communities and local administration of the study kebeles. We would like to express our appreciation for the study households and all who supported the study directly or otherwise. Funding. The CAGED project was funded by the Bill & Melinda Gates Foundation to address food insecurity issues in Ethiopia and Burkina Faso through the project Equip - Strengthening Smallholder Livestock Systems for the Future (grant number OPP11755487). These funds are administered by the Feed the Future Innovation Lab for Livestock Systems, which was established by funding from the United States Agency for International Development (USAID) and is co-led by the University of Florida's Institute of Food and Agricultural Sciences and the International Livestock Research Institute. Support for the Feed the Future Innovation Lab for Livestock Systems is made possible by the generous support of the American people through USAID. The contents are the responsibility of the authors and do not necessarily reflect the views of USAID or the United States Government. REDCap is hosted at the University of Florida Clinical and Translational Science Institute (CTSI), supported by NIH National Center for Advancing Translational Sciences grant UL1 TR000064. The CAGED is a collaborative project between University of Florida, The Ohio State University, Washington University, and Haramaya University (Ethiopia). The CAGED project was supported by a Technical Advisory Group consisting of Eric F?vre (University of Liverpool and International Livestock Research Institute), Nigel French (Massey University), Aulo Gelli (International Food Policy Research Institute), Andrew Jones (University of Michigan), Vivek Kapur (Penn State University), Nick Juleff and Supriya Kumar (Bill & Melinda Gates Foundation) and James Platts-Mills (University of Virginia).

Funding Information:
The CAGED project was funded by the Bill & Melinda Gates Foundation to address food insecurity issues in Ethiopia and Burkina Faso through the project Equip - Strengthening Smallholder Livestock Systems for the Future (grant number OPP11755487). These funds are administered by the Feed the Future Innovation Lab for Livestock Systems, which was established by funding from the United States Agency for International Development (USAID) and is co-led by the University of Florida’s Institute of Food and Agricultural Sciences and the International Livestock Research Institute. Support for the Feed the Future Innovation Lab for Livestock Systems is made possible by the generous support of the American people through USAID. The contents are the responsibility of the authors and do not necessarily reflect the views of USAID or the United States Government. REDCap is hosted at the University of Florida Clinical and Translational Science Institute (CTSI), supported by NIH National Center for Advancing Translational Sciences grant UL1 TR000064. The CAGED is a collaborative project between University of Florida, The Ohio State University, Washington University, and Haramaya University (Ethiopia). The CAGED project was supported by a Technical Advisory Group consisting of Eric Fèvre (University of Liverpool and International Livestock Research Institute), Nigel French (Massey University), Aulo Gelli (International Food Policy Research Institute), Andrew Jones (University of Michigan), Vivek Kapur (Penn State University), Nick Juleff and Supriya Kumar (Bill & Melinda Gates Foundation) and James Platts-Mills (University of Virginia).

Publisher Copyright:
© Copyright © 2020 Terefe, Deblais, Ghanem, Helmy, Mummed, Chen, Singh, Ahyong, Kalantar, Yimer, Yousuf Hassen, Mohammed, McKune, Manary, Ordiz, Gebreyes, Havelaar and Rajashekara.

Funding

The CAGED project was funded by the Bill & Melinda Gates Foundation to address food insecurity issues in Ethiopia and Burkina Faso through the project Equip - Strengthening Smallholder Livestock Systems for the Future (grant number OPP11755487). These funds are administered by the Feed the Future Innovation Lab for Livestock Systems, which was established by funding from the United States Agency for International Development (USAID) and is co-led by the University of Florida’s Institute of Food and Agricultural Sciences and the International Livestock Research Institute. Support for the Feed the Future Innovation Lab for Livestock Systems is made possible by the generous support of the American people through USAID. The contents are the responsibility of the authors and do not necessarily reflect the views of USAID or the United States Government. REDCap is hosted at the University of Florida Clinical and Translational Science Institute (CTSI), supported by NIH National Center for Advancing Translational Sciences grant UL1 TR000064. The CAGED is a collaborative project between University of Florida, The Ohio State University, Washington University, and Haramaya University (Ethiopia). The CAGED project was supported by a Technical Advisory Group consisting of Eric Fèvre (University of Liverpool and International Livestock Research Institute), Nigel French (Massey University), Aulo Gelli (International Food Policy Research Institute), Andrew Jones (University of Michigan), Vivek Kapur (Penn State University), Nick Juleff and Supriya Kumar (Bill & Melinda Gates Foundation) and James Platts-Mills (University of Virginia). We thank Chan Zuckerberg Biohub, San Francisco, CA, USA and Chan Zuckerberg Initiative, Redwood City, CA, USA for their support with sequencing of total RNA and the bioinformatics analysis of the MeTRS data. We thank Drs. Volker Mai and Nigel French for their critical reading of the manuscript. We also thank Ame Yousuf, Beyan Abdullahi, Yeharerwork Abebaw, Yenenesh Elias Ahmed, Ibsa Ahmed, Jafer Amin, Seyum Tezera, Dr. Nigussie Bussa, and Ibsa Usmane at Haramaya University, and Jenna Daniels and Anna Rabil at University of Florida for their contributions to the project. We thank Srevi Devaraj (Clinical Chemistry and POCT, Texas Children's Hospital, Baylor College of Medicine, Houston, TX) for analysis of sugars in the dual sugar absorption test. The study would not have been possible without cooperation of study communities and local administration of the study kebeles. We would like to express our appreciation for the study households and all who supported the study directly or otherwise. Funding. The CAGED project was funded by the Bill & Melinda Gates Foundation to address food insecurity issues in Ethiopia and Burkina Faso through the project Equip - Strengthening Smallholder Livestock Systems for the Future (grant number OPP11755487). These funds are administered by the Feed the Future Innovation Lab for Livestock Systems, which was established by funding from the United States Agency for International Development (USAID) and is co-led by the University of Florida's Institute of Food and Agricultural Sciences and the International Livestock Research Institute. Support for the Feed the Future Innovation Lab for Livestock Systems is made possible by the generous support of the American people through USAID. The contents are the responsibility of the authors and do not necessarily reflect the views of USAID or the United States Government. REDCap is hosted at the University of Florida Clinical and Translational Science Institute (CTSI), supported by NIH National Center for Advancing Translational Sciences grant UL1 TR000064. The CAGED is a collaborative project between University of Florida, The Ohio State University, Washington University, and Haramaya University (Ethiopia). The CAGED project was supported by a Technical Advisory Group consisting of Eric Fèvre (University of Liverpool and International Livestock Research Institute), Nigel French (Massey University), Aulo Gelli (International Food Policy Research Institute), Andrew Jones (University of Michigan), Vivek Kapur (Penn State University), Nick Juleff and Supriya Kumar (Bill & Melinda Gates Foundation) and James Platts-Mills (University of Virginia).

Funders	Funder number
Vivek Kapur
United States Agency for International Development
Bill and Melinda Gates Foundation	OPP11755487
National Center for Advancing Translational Sciences (NCATS)	UL1 TR000064
Ohio State University
Indiana Clinical and Translational Sciences Institute
Texas Children's Hospital
University of Michigan Hospital
Florida A and M University
The George Washington University
Baylor College of Medicine
University of Florida Institute of Food and Agricultural Sciences
The Pennsylvania State University
University of Virginia
Clinical and Translational Science Institute, University of Florida
Massey University
Haramaya University
International Livestock Research Institute

Keywords

Campylobacter
diarrhea
EED
livestock reservoirs
malnutrition
MeTRS
non-thermotolerant Campylobacter
stunting

ASJC Scopus subject areas

Public Health, Environmental and Occupational Health

UN SDGs

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

Access to Document

10.3389/fpubh.2020.00099

Cite this

Terefe, Y., Deblais, L., Ghanem, M., Helmy, Y. A., Mummed, B., Chen, D., Singh, N., Ahyong, V., Kalantar, K., Yimer, G., Yousuf Hassen, J., Mohammed, A., McKune, S. L., Manary, M. J., Ordiz, M. I., Gebreyes, W., Havelaar, A. H., & Rajashekara, G. (2020). Co-occurrence of Campylobacter Species in Children From Eastern Ethiopia, and Their Association With Environmental Enteric Dysfunction, Diarrhea, and Host Microbiome. Frontiers in Public Health, 8, Article 99. https://doi.org/10.3389/fpubh.2020.00099

@article{4ee6ef9fbc7e4bd594be04e4bff76fce,

title = "Co-occurrence of Campylobacter Species in Children From Eastern Ethiopia, and Their Association With Environmental Enteric Dysfunction, Diarrhea, and Host Microbiome",

abstract = "High Campylobacter prevalence during early childhood has been associated with stunting and environmental enteric dysfunction (EED), especially in low resource settings. This study assessed the prevalence, diversity, abundance, and co-occurrence of Campylobacter spp. in stools from children in a rural area of eastern Ethiopia and their association with microbiome, diarrhea, and EED in children. Stool samples (n = 100) were collected from randomly selected children (age range: 360–498 days) in five kebeles in Haramaya District, Ethiopia. Diarrhea, compromised gut permeability, and gut inflammation were observed in 48, 45, and 57% of children, respectively. Campylobacter prevalence and species diversity were assessed using PCR and meta-total RNA sequencing (MeTRS). The prevalence of Campylobacter spp. in the children's stools was 50% (41–60%) by PCR and 88% (80–93.6%) by MeTRS (P < 0.01). Further, seven Campylobacter species (Campylobacter jejuni, Campylobacter upsaliensis, Campylobacter hyointestinalis, Campylobacter coli, Campylobacter sp. RM6137, uncultured Campylobacter sp., and Campylobacter sp. RM12175) were detected by MeTRS in at least 40% of children stools in high abundance (>1.76-log read per million per positive stool sample). Four clusters of Campylobacter species (5–12 species per cluster) co-occurred in the stool samples, suggesting that Campylobacter colonization of children may have occurred through multiple reservoirs or from a reservoir in which several Campylobacter species may co-inhabit. No associations between Campylobacter spp., EED, and diarrhea were detected in this cross-sectional study; however, characteristic microbiome profiles were identified based on the prevalence of Campylobacter spp., EED severity, and diarrhea. Forty-seven bacterial species were correlated with Campylobacter, and 13 of them also correlated with gut permeability, gut inflammation and/or EED severity. Forty-nine species not correlated with Campylobacter were correlated with gut permeability, gut inflammation, EED severity and/or diarrhea. This study demonstrated that (1) in addition to C. jejuni and C. coli, multiple non-thermophilic Campylobacter spp. (i.e., Campylobacter hyointestinalis, Campylobacter fetus, and Campylobacter concisus) were frequently detected in the children's stools and (2) the Campylobacter, gut permeability, gut inflammation, EED severity, and diarrhea were associated with characteristic microbiome composition. Additional spatial and longitudinal studies are needed to identify environmental reservoirs and sources of infection of children with disparate Campylobacter species and to better define their associations with EED in low-income countries.",

keywords = "Campylobacter, diarrhea, EED, livestock reservoirs, malnutrition, MeTRS, non-thermotolerant Campylobacter, stunting",

author = "Yitagele Terefe and Lo{\"i}c Deblais and Mostafa Ghanem and Helmy, {Yosra A.} and Bahar Mummed and Dehao Chen and Nitya Singh and Vida Ahyong and Katrina Kalantar and Getnet Yimer and {Yousuf Hassen}, Jemal and Abdulmuen Mohammed and McKune, {Sarah L.} and Manary, {Mark J.} and Ordiz, {Maria Isabel} and Wondwossen Gebreyes and Havelaar, {Arie H.} and Gireesh Rajashekara",

note = "Funding Information: We thank Chan Zuckerberg Biohub, San Francisco, CA, USA and Chan Zuckerberg Initiative, Redwood City, CA, USA for their support with sequencing of total RNA and the bioinformatics analysis of the MeTRS data. We thank Drs. Volker Mai and Nigel French for their critical reading of the manuscript. We also thank Ame Yousuf, Beyan Abdullahi, Yeharerwork Abebaw, Yenenesh Elias Ahmed, Ibsa Ahmed, Jafer Amin, Seyum Tezera, Dr. Nigussie Bussa, and Ibsa Usmane at Haramaya University, and Jenna Daniels and Anna Rabil at University of Florida for their contributions to the project. We thank Srevi Devaraj (Clinical Chemistry and POCT, Texas Children's Hospital, Baylor College of Medicine, Houston, TX) for analysis of sugars in the dual sugar absorption test. The study would not have been possible without cooperation of study communities and local administration of the study kebeles. We would like to express our appreciation for the study households and all who supported the study directly or otherwise. Funding. The CAGED project was funded by the Bill & Melinda Gates Foundation to address food insecurity issues in Ethiopia and Burkina Faso through the project Equip - Strengthening Smallholder Livestock Systems for the Future (grant number OPP11755487). These funds are administered by the Feed the Future Innovation Lab for Livestock Systems, which was established by funding from the United States Agency for International Development (USAID) and is co-led by the University of Florida's Institute of Food and Agricultural Sciences and the International Livestock Research Institute. Support for the Feed the Future Innovation Lab for Livestock Systems is made possible by the generous support of the American people through USAID. The contents are the responsibility of the authors and do not necessarily reflect the views of USAID or the United States Government. REDCap is hosted at the University of Florida Clinical and Translational Science Institute (CTSI), supported by NIH National Center for Advancing Translational Sciences grant UL1 TR000064. The CAGED is a collaborative project between University of Florida, The Ohio State University, Washington University, and Haramaya University (Ethiopia). The CAGED project was supported by a Technical Advisory Group consisting of Eric F?vre (University of Liverpool and International Livestock Research Institute), Nigel French (Massey University), Aulo Gelli (International Food Policy Research Institute), Andrew Jones (University of Michigan), Vivek Kapur (Penn State University), Nick Juleff and Supriya Kumar (Bill & Melinda Gates Foundation) and James Platts-Mills (University of Virginia). Funding Information: The CAGED project was funded by the Bill & Melinda Gates Foundation to address food insecurity issues in Ethiopia and Burkina Faso through the project Equip - Strengthening Smallholder Livestock Systems for the Future (grant number OPP11755487). These funds are administered by the Feed the Future Innovation Lab for Livestock Systems, which was established by funding from the United States Agency for International Development (USAID) and is co-led by the University of Florida{\textquoteright}s Institute of Food and Agricultural Sciences and the International Livestock Research Institute. Support for the Feed the Future Innovation Lab for Livestock Systems is made possible by the generous support of the American people through USAID. The contents are the responsibility of the authors and do not necessarily reflect the views of USAID or the United States Government. REDCap is hosted at the University of Florida Clinical and Translational Science Institute (CTSI), supported by NIH National Center for Advancing Translational Sciences grant UL1 TR000064. The CAGED is a collaborative project between University of Florida, The Ohio State University, Washington University, and Haramaya University (Ethiopia). The CAGED project was supported by a Technical Advisory Group consisting of Eric F{\`e}vre (University of Liverpool and International Livestock Research Institute), Nigel French (Massey University), Aulo Gelli (International Food Policy Research Institute), Andrew Jones (University of Michigan), Vivek Kapur (Penn State University), Nick Juleff and Supriya Kumar (Bill & Melinda Gates Foundation) and James Platts-Mills (University of Virginia). Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2020 Terefe, Deblais, Ghanem, Helmy, Mummed, Chen, Singh, Ahyong, Kalantar, Yimer, Yousuf Hassen, Mohammed, McKune, Manary, Ordiz, Gebreyes, Havelaar and Rajashekara.",

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day = "15",

doi = "10.3389/fpubh.2020.00099",

language = "English",

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}

Terefe, Y, Deblais, L, Ghanem, M, Helmy, YA, Mummed, B, Chen, D, Singh, N, Ahyong, V, Kalantar, K, Yimer, G, Yousuf Hassen, J, Mohammed, A, McKune, SL, Manary, MJ, Ordiz, MI, Gebreyes, W, Havelaar, AH & Rajashekara, G 2020, 'Co-occurrence of Campylobacter Species in Children From Eastern Ethiopia, and Their Association With Environmental Enteric Dysfunction, Diarrhea, and Host Microbiome', Frontiers in Public Health, vol. 8, 99. https://doi.org/10.3389/fpubh.2020.00099

TY - JOUR

T1 - Co-occurrence of Campylobacter Species in Children From Eastern Ethiopia, and Their Association With Environmental Enteric Dysfunction, Diarrhea, and Host Microbiome

AU - Terefe, Yitagele

AU - Deblais, Loïc

AU - Ghanem, Mostafa

AU - Helmy, Yosra A.

AU - Mummed, Bahar

AU - Chen, Dehao

AU - Singh, Nitya

AU - Ahyong, Vida

AU - Kalantar, Katrina

AU - Yimer, Getnet

AU - Yousuf Hassen, Jemal

AU - Mohammed, Abdulmuen

AU - McKune, Sarah L.

AU - Manary, Mark J.

AU - Ordiz, Maria Isabel

AU - Gebreyes, Wondwossen

AU - Havelaar, Arie H.

AU - Rajashekara, Gireesh

N1 - Funding Information: We thank Chan Zuckerberg Biohub, San Francisco, CA, USA and Chan Zuckerberg Initiative, Redwood City, CA, USA for their support with sequencing of total RNA and the bioinformatics analysis of the MeTRS data. We thank Drs. Volker Mai and Nigel French for their critical reading of the manuscript. We also thank Ame Yousuf, Beyan Abdullahi, Yeharerwork Abebaw, Yenenesh Elias Ahmed, Ibsa Ahmed, Jafer Amin, Seyum Tezera, Dr. Nigussie Bussa, and Ibsa Usmane at Haramaya University, and Jenna Daniels and Anna Rabil at University of Florida for their contributions to the project. We thank Srevi Devaraj (Clinical Chemistry and POCT, Texas Children's Hospital, Baylor College of Medicine, Houston, TX) for analysis of sugars in the dual sugar absorption test. The study would not have been possible without cooperation of study communities and local administration of the study kebeles. We would like to express our appreciation for the study households and all who supported the study directly or otherwise. Funding. The CAGED project was funded by the Bill & Melinda Gates Foundation to address food insecurity issues in Ethiopia and Burkina Faso through the project Equip - Strengthening Smallholder Livestock Systems for the Future (grant number OPP11755487). These funds are administered by the Feed the Future Innovation Lab for Livestock Systems, which was established by funding from the United States Agency for International Development (USAID) and is co-led by the University of Florida's Institute of Food and Agricultural Sciences and the International Livestock Research Institute. Support for the Feed the Future Innovation Lab for Livestock Systems is made possible by the generous support of the American people through USAID. The contents are the responsibility of the authors and do not necessarily reflect the views of USAID or the United States Government. REDCap is hosted at the University of Florida Clinical and Translational Science Institute (CTSI), supported by NIH National Center for Advancing Translational Sciences grant UL1 TR000064. The CAGED is a collaborative project between University of Florida, The Ohio State University, Washington University, and Haramaya University (Ethiopia). The CAGED project was supported by a Technical Advisory Group consisting of Eric F?vre (University of Liverpool and International Livestock Research Institute), Nigel French (Massey University), Aulo Gelli (International Food Policy Research Institute), Andrew Jones (University of Michigan), Vivek Kapur (Penn State University), Nick Juleff and Supriya Kumar (Bill & Melinda Gates Foundation) and James Platts-Mills (University of Virginia). Funding Information: The CAGED project was funded by the Bill & Melinda Gates Foundation to address food insecurity issues in Ethiopia and Burkina Faso through the project Equip - Strengthening Smallholder Livestock Systems for the Future (grant number OPP11755487). These funds are administered by the Feed the Future Innovation Lab for Livestock Systems, which was established by funding from the United States Agency for International Development (USAID) and is co-led by the University of Florida’s Institute of Food and Agricultural Sciences and the International Livestock Research Institute. Support for the Feed the Future Innovation Lab for Livestock Systems is made possible by the generous support of the American people through USAID. The contents are the responsibility of the authors and do not necessarily reflect the views of USAID or the United States Government. REDCap is hosted at the University of Florida Clinical and Translational Science Institute (CTSI), supported by NIH National Center for Advancing Translational Sciences grant UL1 TR000064. The CAGED is a collaborative project between University of Florida, The Ohio State University, Washington University, and Haramaya University (Ethiopia). The CAGED project was supported by a Technical Advisory Group consisting of Eric Fèvre (University of Liverpool and International Livestock Research Institute), Nigel French (Massey University), Aulo Gelli (International Food Policy Research Institute), Andrew Jones (University of Michigan), Vivek Kapur (Penn State University), Nick Juleff and Supriya Kumar (Bill & Melinda Gates Foundation) and James Platts-Mills (University of Virginia). Publisher Copyright: © Copyright © 2020 Terefe, Deblais, Ghanem, Helmy, Mummed, Chen, Singh, Ahyong, Kalantar, Yimer, Yousuf Hassen, Mohammed, McKune, Manary, Ordiz, Gebreyes, Havelaar and Rajashekara.

PY - 2020/4/15

Y1 - 2020/4/15

N2 - High Campylobacter prevalence during early childhood has been associated with stunting and environmental enteric dysfunction (EED), especially in low resource settings. This study assessed the prevalence, diversity, abundance, and co-occurrence of Campylobacter spp. in stools from children in a rural area of eastern Ethiopia and their association with microbiome, diarrhea, and EED in children. Stool samples (n = 100) were collected from randomly selected children (age range: 360–498 days) in five kebeles in Haramaya District, Ethiopia. Diarrhea, compromised gut permeability, and gut inflammation were observed in 48, 45, and 57% of children, respectively. Campylobacter prevalence and species diversity were assessed using PCR and meta-total RNA sequencing (MeTRS). The prevalence of Campylobacter spp. in the children's stools was 50% (41–60%) by PCR and 88% (80–93.6%) by MeTRS (P < 0.01). Further, seven Campylobacter species (Campylobacter jejuni, Campylobacter upsaliensis, Campylobacter hyointestinalis, Campylobacter coli, Campylobacter sp. RM6137, uncultured Campylobacter sp., and Campylobacter sp. RM12175) were detected by MeTRS in at least 40% of children stools in high abundance (>1.76-log read per million per positive stool sample). Four clusters of Campylobacter species (5–12 species per cluster) co-occurred in the stool samples, suggesting that Campylobacter colonization of children may have occurred through multiple reservoirs or from a reservoir in which several Campylobacter species may co-inhabit. No associations between Campylobacter spp., EED, and diarrhea were detected in this cross-sectional study; however, characteristic microbiome profiles were identified based on the prevalence of Campylobacter spp., EED severity, and diarrhea. Forty-seven bacterial species were correlated with Campylobacter, and 13 of them also correlated with gut permeability, gut inflammation and/or EED severity. Forty-nine species not correlated with Campylobacter were correlated with gut permeability, gut inflammation, EED severity and/or diarrhea. This study demonstrated that (1) in addition to C. jejuni and C. coli, multiple non-thermophilic Campylobacter spp. (i.e., Campylobacter hyointestinalis, Campylobacter fetus, and Campylobacter concisus) were frequently detected in the children's stools and (2) the Campylobacter, gut permeability, gut inflammation, EED severity, and diarrhea were associated with characteristic microbiome composition. Additional spatial and longitudinal studies are needed to identify environmental reservoirs and sources of infection of children with disparate Campylobacter species and to better define their associations with EED in low-income countries.

AB - High Campylobacter prevalence during early childhood has been associated with stunting and environmental enteric dysfunction (EED), especially in low resource settings. This study assessed the prevalence, diversity, abundance, and co-occurrence of Campylobacter spp. in stools from children in a rural area of eastern Ethiopia and their association with microbiome, diarrhea, and EED in children. Stool samples (n = 100) were collected from randomly selected children (age range: 360–498 days) in five kebeles in Haramaya District, Ethiopia. Diarrhea, compromised gut permeability, and gut inflammation were observed in 48, 45, and 57% of children, respectively. Campylobacter prevalence and species diversity were assessed using PCR and meta-total RNA sequencing (MeTRS). The prevalence of Campylobacter spp. in the children's stools was 50% (41–60%) by PCR and 88% (80–93.6%) by MeTRS (P < 0.01). Further, seven Campylobacter species (Campylobacter jejuni, Campylobacter upsaliensis, Campylobacter hyointestinalis, Campylobacter coli, Campylobacter sp. RM6137, uncultured Campylobacter sp., and Campylobacter sp. RM12175) were detected by MeTRS in at least 40% of children stools in high abundance (>1.76-log read per million per positive stool sample). Four clusters of Campylobacter species (5–12 species per cluster) co-occurred in the stool samples, suggesting that Campylobacter colonization of children may have occurred through multiple reservoirs or from a reservoir in which several Campylobacter species may co-inhabit. No associations between Campylobacter spp., EED, and diarrhea were detected in this cross-sectional study; however, characteristic microbiome profiles were identified based on the prevalence of Campylobacter spp., EED severity, and diarrhea. Forty-seven bacterial species were correlated with Campylobacter, and 13 of them also correlated with gut permeability, gut inflammation and/or EED severity. Forty-nine species not correlated with Campylobacter were correlated with gut permeability, gut inflammation, EED severity and/or diarrhea. This study demonstrated that (1) in addition to C. jejuni and C. coli, multiple non-thermophilic Campylobacter spp. (i.e., Campylobacter hyointestinalis, Campylobacter fetus, and Campylobacter concisus) were frequently detected in the children's stools and (2) the Campylobacter, gut permeability, gut inflammation, EED severity, and diarrhea were associated with characteristic microbiome composition. Additional spatial and longitudinal studies are needed to identify environmental reservoirs and sources of infection of children with disparate Campylobacter species and to better define their associations with EED in low-income countries.

KW - Campylobacter

KW - diarrhea

KW - EED

KW - livestock reservoirs

KW - malnutrition

KW - MeTRS

KW - non-thermotolerant Campylobacter

KW - stunting

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UR - http://www.scopus.com/inward/citedby.url?scp=85083980270&partnerID=8YFLogxK

U2 - 10.3389/fpubh.2020.00099

DO - 10.3389/fpubh.2020.00099

M3 - Article

AN - SCOPUS:85083980270

VL - 8

JO - Frontiers in Public Health

JF - Frontiers in Public Health

M1 - 99

ER -

Co-occurrence of Campylobacter Species in Children From Eastern Ethiopia, and Their Association With Environmental Enteric Dysfunction, Diarrhea, and Host Microbiome

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