Gut microbiota trajectory in early life may predict development of celiac disease

Marta Olivares, Alan W. Walker, Amalia Capilla, Alfonso Benitez-Paez, Francesc Palau, Julian Parkhill, Gemma Castillejo, Yolanda Sanz

Research output: Contribution to journalArticle

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Abstract

Background To investigate whether alterations in the developing intestinal microbiota and immune markers precede celiac disease (CD) onset in infants at familial risk of developing the disease. Methods A nested case-control study was carried out as part of a larger prospective cohort study, which included healthy full-term newborns (> 200) with at least one first relative with biopsy-verified CD. The present study includes cases of CD (n = 10) and the best-matched controls (n = 10) who did not develop the disease after 5-year follow-up. Fecal microbiota, assessed by high-throughput 16S rRNA gene amplicon sequencing, and immune parameters were profiled at 4 and 6 months of age and related to CD onset. Results The microbiota of infants who remained healthy showed an increase in bacterial diversity over time, characterized by increases in Firmicutes families, but not those who developed CD. Infants who subsequently developed CD showed a significant reduction in sIgA levels over time, while those who remained healthy showed increases in TNF-α correlated to Bifidobacterium spp. An increased relative abundance of Bifidobacterium longum was associated with control children while increased proportions of Bifidobacterium breve and Enterococcus spp. were associated with CD development. Conclusion The findings suggest that alterations in the early trajectory of gut microbiota in infants at CD risk could influence the immune maturation process and predispose to CD, although larger population studies are warranted to confirm this hypothesis.
Original languageEnglish
Article number36
JournalMicrobiome
Volume6
DOIs
Publication statusPublished - 20 Feb 2018

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Celiac Disease
Microbiota
Gastrointestinal Microbiome
Bifidobacterium
Enterococcus
rRNA Genes
Case-Control Studies
Cohort Studies
Biomarkers
Newborn Infant
Prospective Studies
Biopsy

Keywords

  • Celiac Disease
  • intestinal microbiology
  • HLA genes

Cite this

Olivares, M., Walker, A. W., Capilla, A., Benitez-Paez, A., Palau, F., Parkhill, J., ... Sanz, Y. (2018). Gut microbiota trajectory in early life may predict development of celiac disease. Microbiome, 6, [36]. https://doi.org/10.1186/s40168-018-0415-6

Gut microbiota trajectory in early life may predict development of celiac disease. / Olivares, Marta; Walker, Alan W.; Capilla, Amalia; Benitez-Paez, Alfonso; Palau, Francesc; Parkhill, Julian; Castillejo, Gemma; Sanz, Yolanda.

In: Microbiome, Vol. 6, 36, 20.02.2018.

Research output: Contribution to journalArticle

Olivares, M, Walker, AW, Capilla, A, Benitez-Paez, A, Palau, F, Parkhill, J, Castillejo, G & Sanz, Y 2018, 'Gut microbiota trajectory in early life may predict development of celiac disease' Microbiome, vol. 6, 36. https://doi.org/10.1186/s40168-018-0415-6
Olivares, Marta ; Walker, Alan W. ; Capilla, Amalia ; Benitez-Paez, Alfonso ; Palau, Francesc ; Parkhill, Julian ; Castillejo, Gemma ; Sanz, Yolanda. / Gut microbiota trajectory in early life may predict development of celiac disease. In: Microbiome. 2018 ; Vol. 6.
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abstract = "Background To investigate whether alterations in the developing intestinal microbiota and immune markers precede celiac disease (CD) onset in infants at familial risk of developing the disease. Methods A nested case-control study was carried out as part of a larger prospective cohort study, which included healthy full-term newborns (> 200) with at least one first relative with biopsy-verified CD. The present study includes cases of CD (n = 10) and the best-matched controls (n = 10) who did not develop the disease after 5-year follow-up. Fecal microbiota, assessed by high-throughput 16S rRNA gene amplicon sequencing, and immune parameters were profiled at 4 and 6 months of age and related to CD onset. Results The microbiota of infants who remained healthy showed an increase in bacterial diversity over time, characterized by increases in Firmicutes families, but not those who developed CD. Infants who subsequently developed CD showed a significant reduction in sIgA levels over time, while those who remained healthy showed increases in TNF-α correlated to Bifidobacterium spp. An increased relative abundance of Bifidobacterium longum was associated with control children while increased proportions of Bifidobacterium breve and Enterococcus spp. were associated with CD development. Conclusion The findings suggest that alterations in the early trajectory of gut microbiota in infants at CD risk could influence the immune maturation process and predispose to CD, although larger population studies are warranted to confirm this hypothesis.",
keywords = "Celiac Disease, intestinal microbiology, HLA genes",
author = "Marta Olivares and Walker, {Alan W.} and Amalia Capilla and Alfonso Benitez-Paez and Francesc Palau and Julian Parkhill and Gemma Castillejo and Yolanda Sanz",
note = "This work was supported by grants AGL2011-25169, AGL2014-52101-P and AGL2007-66126-C03-03/ALI (YS and FP) from the Spanish Ministry of Economy and Competitiveness (MINECO). Funding for AWW. JP and 16S rRNA gene sequencing was provided by Wellcome Trust (Grant 098051); AWW and The Rowett Institute, University of Aberdeen, receive core funding support from the Scottish Government Rural and Environmental Science and Analysis Service (RESAS). The scholarship to MO from CSIC (JAEpre) and the contract to ABP from the European Union’s Seventh Framework Program under the grant agreement no 613979 (MyNewGut) are also fully acknowledged.",
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T1 - Gut microbiota trajectory in early life may predict development of celiac disease

AU - Olivares, Marta

AU - Walker, Alan W.

AU - Capilla, Amalia

AU - Benitez-Paez, Alfonso

AU - Palau, Francesc

AU - Parkhill, Julian

AU - Castillejo, Gemma

AU - Sanz, Yolanda

N1 - This work was supported by grants AGL2011-25169, AGL2014-52101-P and AGL2007-66126-C03-03/ALI (YS and FP) from the Spanish Ministry of Economy and Competitiveness (MINECO). Funding for AWW. JP and 16S rRNA gene sequencing was provided by Wellcome Trust (Grant 098051); AWW and The Rowett Institute, University of Aberdeen, receive core funding support from the Scottish Government Rural and Environmental Science and Analysis Service (RESAS). The scholarship to MO from CSIC (JAEpre) and the contract to ABP from the European Union’s Seventh Framework Program under the grant agreement no 613979 (MyNewGut) are also fully acknowledged.

PY - 2018/2/20

Y1 - 2018/2/20

N2 - Background To investigate whether alterations in the developing intestinal microbiota and immune markers precede celiac disease (CD) onset in infants at familial risk of developing the disease. Methods A nested case-control study was carried out as part of a larger prospective cohort study, which included healthy full-term newborns (> 200) with at least one first relative with biopsy-verified CD. The present study includes cases of CD (n = 10) and the best-matched controls (n = 10) who did not develop the disease after 5-year follow-up. Fecal microbiota, assessed by high-throughput 16S rRNA gene amplicon sequencing, and immune parameters were profiled at 4 and 6 months of age and related to CD onset. Results The microbiota of infants who remained healthy showed an increase in bacterial diversity over time, characterized by increases in Firmicutes families, but not those who developed CD. Infants who subsequently developed CD showed a significant reduction in sIgA levels over time, while those who remained healthy showed increases in TNF-α correlated to Bifidobacterium spp. An increased relative abundance of Bifidobacterium longum was associated with control children while increased proportions of Bifidobacterium breve and Enterococcus spp. were associated with CD development. Conclusion The findings suggest that alterations in the early trajectory of gut microbiota in infants at CD risk could influence the immune maturation process and predispose to CD, although larger population studies are warranted to confirm this hypothesis.

AB - Background To investigate whether alterations in the developing intestinal microbiota and immune markers precede celiac disease (CD) onset in infants at familial risk of developing the disease. Methods A nested case-control study was carried out as part of a larger prospective cohort study, which included healthy full-term newborns (> 200) with at least one first relative with biopsy-verified CD. The present study includes cases of CD (n = 10) and the best-matched controls (n = 10) who did not develop the disease after 5-year follow-up. Fecal microbiota, assessed by high-throughput 16S rRNA gene amplicon sequencing, and immune parameters were profiled at 4 and 6 months of age and related to CD onset. Results The microbiota of infants who remained healthy showed an increase in bacterial diversity over time, characterized by increases in Firmicutes families, but not those who developed CD. Infants who subsequently developed CD showed a significant reduction in sIgA levels over time, while those who remained healthy showed increases in TNF-α correlated to Bifidobacterium spp. An increased relative abundance of Bifidobacterium longum was associated with control children while increased proportions of Bifidobacterium breve and Enterococcus spp. were associated with CD development. Conclusion The findings suggest that alterations in the early trajectory of gut microbiota in infants at CD risk could influence the immune maturation process and predispose to CD, although larger population studies are warranted to confirm this hypothesis.

KW - Celiac Disease

KW - intestinal microbiology

KW - HLA genes

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VL - 6

JO - Microbiome

JF - Microbiome

SN - 2049-2618

M1 - 36

ER -