Cessation of exclusive breastfeeding and seasonality, but not small intestinal bacterial overgrowth, are associated with environmental enteric dysfunction: A birth cohort study amongst infants in rural Kenya

<strong>Background</strong> Environmental Enteric Dysfunction (EED) is a chronic intestinal inflammatory disorder of unclear aetiology prevalent amongst children in low-income settings and associated with stunting. We aimed to characterise development of EED and its putative risk factors...

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Main Authors: Crane, RJ, Parker, EPK, Fleming, S, Gwela, A, Gumbi, W, Ngoi, JM, de Laurent, ZR, Nyatichi, E, Ngari, M, Wambua, J, Uhlig, HH, Berkley, JA
Format: Journal article
Language:English
Published: Elsevier 2022
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author Crane, RJ
Parker, EPK
Fleming, S
Gwela, A
Gumbi, W
Ngoi, JM
de Laurent, ZR
Nyatichi, E
Ngari, M
Wambua, J
Uhlig, HH
Berkley, JA
author_facet Crane, RJ
Parker, EPK
Fleming, S
Gwela, A
Gumbi, W
Ngoi, JM
de Laurent, ZR
Nyatichi, E
Ngari, M
Wambua, J
Uhlig, HH
Berkley, JA
author_sort Crane, RJ
collection OXFORD
description <strong>Background</strong> Environmental Enteric Dysfunction (EED) is a chronic intestinal inflammatory disorder of unclear aetiology prevalent amongst children in low-income settings and associated with stunting. We aimed to characterise development of EED and its putative risk factors amongst rural Kenyan infants. <br> <strong>Methods</strong> In a birth cohort study in Junju, rural coastal Kenya, between August 2015 and January 2017, 100 infants were each followed for nine months. Breastfeeding status was recorded weekly and anthropometry monthly. Acute illnesses and antibiotics were captured by active and passive surveillance. Intestinal function and small intestinal bacterial overgrowth (SIBO) were assessed by monthly urinary lactulose mannitol (LM) and breath hydrogen tests. Faecal alpha-1-antitrypsin, myeloperoxidase and neopterin were measured as EED biomarkers, and microbiota composition assessed by 16S sequencing. <br> <strong>Findings</strong> Twenty nine of the 88 participants (33%) that underwent length measurement at nine months of age were stunted (length-for-age Z score <-2). During the rainy season, linear growth was slower and LM ratio was higher. In multivariable models, LM ratio, myeloperoxidase and neopterin increased after cessation of continuous-since-birth exclusive breastfeeding. For LM ratio this only occurred during the rainy season. EED markers were not associated with antibiotics, acute illnesses, SIBO, or gut microbiota diversity. Microbiota diversified with age and was not strongly associated with complementary food introduction or linear growth impairment. <br> <strong>Interpretation</strong> Our data suggest that intensified promotion of uninterrupted exclusive breastfeeding amongst infants under six months during the rainy season, where rainfall is seasonal, may help prevent EED. Our findings also suggest that therapeutic strategies directed towards SIBO are unlikely to impact on EED in this setting. However, further development of non-invasive diagnostic methods for SIBO is required. <br> <strong>Funding</strong> This research was funded in part by the Wellcome Trust (Research Training Fellowship to RJC (103376/Z/13/Z)). EPKP was supported by the MRC/DfID Newton Fund (MR/N006259/1). JAB was supported by the MRC/DFiD/Wellcome Trust Joint Global Health Trials scheme (MR/M007367/1) and the Bill & Melinda Gates Foundation (OPP1131320). HHU was supported by the NIHR Oxford Biomedical Research Centre (IS-BRC-1215-20008).
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spelling oxford-uuid:b445dcc1-7b3f-43a6-bb59-801f6d33b6112022-05-16T14:20:43ZCessation of exclusive breastfeeding and seasonality, but not small intestinal bacterial overgrowth, are associated with environmental enteric dysfunction: A birth cohort study amongst infants in rural KenyaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b445dcc1-7b3f-43a6-bb59-801f6d33b611EnglishSymplectic ElementsElsevier2022Crane, RJParker, EPKFleming, SGwela, AGumbi, WNgoi, JMde Laurent, ZRNyatichi, ENgari, MWambua, JUhlig, HHBerkley, JA<strong>Background</strong> Environmental Enteric Dysfunction (EED) is a chronic intestinal inflammatory disorder of unclear aetiology prevalent amongst children in low-income settings and associated with stunting. We aimed to characterise development of EED and its putative risk factors amongst rural Kenyan infants. <br> <strong>Methods</strong> In a birth cohort study in Junju, rural coastal Kenya, between August 2015 and January 2017, 100 infants were each followed for nine months. Breastfeeding status was recorded weekly and anthropometry monthly. Acute illnesses and antibiotics were captured by active and passive surveillance. Intestinal function and small intestinal bacterial overgrowth (SIBO) were assessed by monthly urinary lactulose mannitol (LM) and breath hydrogen tests. Faecal alpha-1-antitrypsin, myeloperoxidase and neopterin were measured as EED biomarkers, and microbiota composition assessed by 16S sequencing. <br> <strong>Findings</strong> Twenty nine of the 88 participants (33%) that underwent length measurement at nine months of age were stunted (length-for-age Z score <-2). During the rainy season, linear growth was slower and LM ratio was higher. In multivariable models, LM ratio, myeloperoxidase and neopterin increased after cessation of continuous-since-birth exclusive breastfeeding. For LM ratio this only occurred during the rainy season. EED markers were not associated with antibiotics, acute illnesses, SIBO, or gut microbiota diversity. Microbiota diversified with age and was not strongly associated with complementary food introduction or linear growth impairment. <br> <strong>Interpretation</strong> Our data suggest that intensified promotion of uninterrupted exclusive breastfeeding amongst infants under six months during the rainy season, where rainfall is seasonal, may help prevent EED. Our findings also suggest that therapeutic strategies directed towards SIBO are unlikely to impact on EED in this setting. However, further development of non-invasive diagnostic methods for SIBO is required. <br> <strong>Funding</strong> This research was funded in part by the Wellcome Trust (Research Training Fellowship to RJC (103376/Z/13/Z)). EPKP was supported by the MRC/DfID Newton Fund (MR/N006259/1). JAB was supported by the MRC/DFiD/Wellcome Trust Joint Global Health Trials scheme (MR/M007367/1) and the Bill & Melinda Gates Foundation (OPP1131320). HHU was supported by the NIHR Oxford Biomedical Research Centre (IS-BRC-1215-20008).
spellingShingle Crane, RJ
Parker, EPK
Fleming, S
Gwela, A
Gumbi, W
Ngoi, JM
de Laurent, ZR
Nyatichi, E
Ngari, M
Wambua, J
Uhlig, HH
Berkley, JA
Cessation of exclusive breastfeeding and seasonality, but not small intestinal bacterial overgrowth, are associated with environmental enteric dysfunction: A birth cohort study amongst infants in rural Kenya
title Cessation of exclusive breastfeeding and seasonality, but not small intestinal bacterial overgrowth, are associated with environmental enteric dysfunction: A birth cohort study amongst infants in rural Kenya
title_full Cessation of exclusive breastfeeding and seasonality, but not small intestinal bacterial overgrowth, are associated with environmental enteric dysfunction: A birth cohort study amongst infants in rural Kenya
title_fullStr Cessation of exclusive breastfeeding and seasonality, but not small intestinal bacterial overgrowth, are associated with environmental enteric dysfunction: A birth cohort study amongst infants in rural Kenya
title_full_unstemmed Cessation of exclusive breastfeeding and seasonality, but not small intestinal bacterial overgrowth, are associated with environmental enteric dysfunction: A birth cohort study amongst infants in rural Kenya
title_short Cessation of exclusive breastfeeding and seasonality, but not small intestinal bacterial overgrowth, are associated with environmental enteric dysfunction: A birth cohort study amongst infants in rural Kenya
title_sort cessation of exclusive breastfeeding and seasonality but not small intestinal bacterial overgrowth are associated with environmental enteric dysfunction a birth cohort study amongst infants in rural kenya
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