Increased prevalence of pathogenic bacteria in the gut microbiota of infants at risk of developing celiac disease: The PROFICEL study

ABSTRACT

Celiac disease (CD) is an immune-mediated enteropathy involving genetic and environmental factors, whose interaction influences disease risk. The intestinal microbiota, including viruses and bacteria, could play a role in the pathological process leading to gluten intolerance. In this study, we investigated the prevalence of pathogens in the intestinal microbiota of infants at familial risk of developing CD. We included 127 full-term newborns with at least one first-degree relative with CD. Infants were classified according to milk-feeding practice (breastfeeding or formula feeding) and HLA-DQ genotype (low, intermediate or high genetic risk). The prevalence of pathogenic bacteria and viruses was assessed in the faeces of the infants at 7 days, 1 month and 4 months of age. The prevalence of Clostridium perfringens was higher in formula-fed infants than in breast-fed over the study period, and that of C. difficile at 4 months. Among breastfed infants, a higher prevalence of enterotoxigenic E. coli (ETEC) was found in infants with the highest genetic risk compared either to those with a low or intermediate risk. Among formula-fed infants, a higher prevalence of ETEC was also found in infants with a high genetic risk compared to those of intermediate risk. Our results show that specific factors, such as formula feeding and the HLA-DQ2 genotype, previously linked to a higher risk of developing CD, influence the presence of pathogenic bacteria differently in the intestinal microbiota in early life. Further studies are warranted to establish whether these associations are related to CD onset later in life.

KEYWORDS:

• celiac disease
• gut microbiota
• HLA genotype
• pathogenic bacteria
• PCR

Abbreviations

APC	=	Antigen presenting cells
CD	=	Celiac disease
CECT	=	Spanish Type Culture Collection
CRT	=	Classification and Regression Trees
EPEC	=	Enteropathogenic E. coli
ETEC	=	Enterotoxigenic coli
PCR-SSP	=	Polymerase Chain Reaction-Sequence Specific Primers

Contributors

YS conceived the study design, MO and AB-P performed the experimental work, MO and AB-P analysed the data, GDP created the data base, EN, GC, VV, AM, JAG, IP, ED, CR-K, CC and LO recruited and followed-up the infants, AC and FP genotyped the infants, MO and YS drafted the manuscript and all authors read and approved its final version.

Footnotes

AC currently works in the Center for regenerative medicine, Boston university school of medicine, Boston (United States). JAG currently works in the Laboratorio de Genética, Servicio de Análisis Clínicos, Hospital Universitario Rio Hortega y Grupo de Inmunidad de las Mucosas, Facultad de Medicina-IBGM, Universidad de Valladolid (Spain). FP currently works in the Institut de Recerca Sant Joan de Déu and CIBERER, Hospital Sant Joan de Déu, Barcelona (Spain).

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Acknowledgments

We thank Laura Barrios working at the Departmet of Statistics from the Spanish National Research Council (CSIC) for her help with statistical assistance.

Additional information

Funding

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). 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.