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Maleki M, MontazeriFar F, Payandeh A, Azadbakht Z. Prevalence of celiac disease and its related factors in children aged 2-6 years old: A case-control study. Nutr Health 2025; 31:247-254. [PMID: 37006133 DOI: 10.1177/02601060231167456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/04/2023]
Abstract
Background: Celiac disease (CD) is an immune-genetic disorder associated with the small intestine. Aim: The aim of this study was to determine the prevalence of CD and its related factors in children aged 2-6 years in southeastern Iran. Methods: In the present case-control research, the study groups were selected by convenience sampling method in Zahedan city, Sistan-and-Baluchestan province, southeastern Iran, from January 2021 till January 2022. Social-demographic status and personal information about the child, family, as well as the feeding pattern of children and mothers in the first six months of breastfeeding were examined. Frequency Food Questionnaire (FFQ) was also used for data collection. Results: The prevalence of CD was estimated at 9.2 per 10,000. Our findings showed that child age, birth weight, location of living, child birth type, child digestive disease, and child FFQ score played a significant role in the development of CD (p < 0.05). Children with CD consumed less bread and cereals, meat, eggs and legumes, dairy products, and fruits and vegetables (p = 0.004). In the first six months of breastfeeding, the mean intake of mothers with celiac children and mothers with healthy children was almost the same (p = 0.75). Conclusion: Nutrition in the first six months of lactation, gastrointestinal diseases, birth weight, and type of delivery played a significant role in causing CD in children aged 2-6 years, but mothers' diets in the first six months of lactation had no significant effect on CD incidence in their infants.
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Affiliation(s)
- Mohsen Maleki
- Student Research Committee, Department of Nutrition, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Farzaneh MontazeriFar
- Department of Nutrition, School of Medicine, Pregnancy Health Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Abolfazl Payandeh
- Department of Biostatistics and Epidemiology, School of Health, Infectious Diseases and Tropical Medicine Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Zahra Azadbakht
- Student Research Committee, Department of Nutrition, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
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Mouslih A, El Rhazi K, Bahra N, Lakhdar Idrissi M, Hida M. Celiac Disease in Moroccan Children: Diagnostic Characteristics and Determinants of Diagnosis Delay. Cureus 2023; 15:e50800. [PMID: 38125690 PMCID: PMC10731523 DOI: 10.7759/cureus.50800] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/19/2023] [Indexed: 12/23/2023] Open
Abstract
Advances in the field of celiac disease have led to a better understanding of the disease, but it remains underdiagnosed and poses a daily challenge to clinicians to make a timely diagnosis. This study aims to analyze and describe diagnosis characteristics, diagnosis delay, and the factors influencing this delay in Moroccan children. Our study included 324 children diagnosed during the study period from January 01, 2010, to December 30, 2019, at the Department of Pediatrics, Hassan II University Hospital in Fez, Morocco. Data were collected using a collection grid and then analyzed using SPSS 26 software (IBM Corp., Armonk, NY). The results showed a female predominance (n=197, 60.8%), with a diagnosis age of 73.8±46.8 months. The mean age onset of symptoms was 51.3±41.2 months, and the diagnosis delay was 22.2±22.6 months, with only 32.7% (n=106) diagnosed less than 12 months after symptom onset. The most common consultation reason was diarrhea (n=149, 46%) and growth delay (n=105, 32.4%) and 50.5% (n=98) of parents consulted a pediatrician first. The three clinical, serologic, and histologic criteria made it possible to agree on the diagnosis, with the clinical profile dominated by the digestive form at 84.9% (n=279), serologic with the presence of IgA transglutaminase antibodies (95.7%; n=310), and histologic with villous atrophy at 91.7% (n=297). Unfortunately, 14.8% (n=48) of the children were diagnosed with a celiac crisis. The multivariate logistic regression analysis showed that as symptoms onset age increased, so did the risk of late diagnosis (OR=0.96, 95% CI: 0.94 to 0.97, p<0.001). Age of diagnosis was also associated with delayed diagnosis (OR=19.68, 95% CI: 8.77 to 44.15, p<0.001). The combination of these variables and the diagnosis delay argues in favor of adopting a diagnosis strategy that includes raising awareness among healthcare professionals of the need to identify typical and atypical cases early in order to reduce the adverse effects of late diagnosis and the complications that can result. This methodology for improving diagnoses may also unearth previously unknown aspects of celiac disease in Moroccan children.
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Affiliation(s)
- Assia Mouslih
- Laboratory of Epidemiology and Health Research, Faculty of Medicine and Pharmacy, Sidi Mohammed Ben Abdellah University, Fez, MAR
| | - Karima El Rhazi
- Laboratory of Epidemiology and Health Research, Faculty of Medicine and Pharmacy, Sidi Mohammed Ben Abdellah University, Fez, MAR
| | - Nassiba Bahra
- Laboratory of Epidemiology and Health Research, Faculty of Medicine and Pharmacy, Sidi Mohammed Ben Abdellah University, Fez, MAR
| | - Mounia Lakhdar Idrissi
- Department of Pediatrics, Faculty of Medicine and Pharmacy/ Epidemiology and Health Science Research Laboratory, Hassan II University Hospital, Fez, MAR
- Laboratory of Epidemiology and Health Research, Faculty of Medicine and Pharmacy, Sidi Mohammed Ben Abdellah University, Fez, MAR
| | - Moustapha Hida
- Department of Pediatrics, Faculty of Medicine and Pharmacy/ Epidemiology and Health Science Research Laboratory, Hassan II University Hospital, Fez, MAR
- Laboratory of Epidemiology and Health Research, Faculty of Medicine and Pharmacy, Sidi Mohammed Ben Abdellah University, Fez, MAR
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Rossi RE, Dispinzieri G, Elvevi A, Massironi S. Interaction between Gut Microbiota and Celiac Disease: From Pathogenesis to Treatment. Cells 2023; 12:823. [PMID: 36980164 PMCID: PMC10047417 DOI: 10.3390/cells12060823] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 12/24/2022] [Accepted: 01/01/2023] [Indexed: 03/09/2023] Open
Abstract
Celiac disease (CD) is a common systemic disorder that results from an abnormal response of human immunity to gluten intake, affecting the small intestine. In individuals who carry a genetic susceptibility, CD is triggered by environmental factors, including viral infections and dysbiosis of the gut microbiota. The gut microbiome is essential in controlling the immune system, and recent findings indicate that changes in the gut microbiome may contribute to various chronic immune disorders, such as CD through mechanisms that still require further exploration. Some bacteria exhibit epitopes that mimic gliadin and may enhance an immune response in the host. Other bacteria, including Pseudomonas aeruginosa, may work in conjunction with gluten to trigger and escalate intestinal inflammation. The microbiota may also directly influence antigen development through the production of immunogenic or tolerogenic gluten peptides or directly influence intestinal permeability through the release of zonulin. Finally, the gut microbiome can impact intestinal inflammation by generating proinflammatory or anti-inflammatory cytokines and metabolites. It is crucial to consider the impact of genetic factors (specifically, HLA-DQ haplotypes), perinatal elements such as birth mode, type of infant feeding, and antibiotic and infection exposure on the composition of the early intestinal microbiome. According to the available studies, the gut microbiome alterations associated with CD tend to exhibit a decreased presence of beneficial bacteria, including some anti-inflammatory Bifidobacterium species. However, some controversy remains as some reports have found no significant differences between the gut microbiomes of individuals with and without CD. A better understanding of the gut microbiome's role in the development of CD would greatly benefit both prevention and treatment efforts, especially in complicated or treatment-resistant cases. Here, we have attempted to summarize the available evidence on the relationship between the gut microbiota and CD, with a particular focus on potential therapeutic targets.
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Affiliation(s)
- Roberta Elisa Rossi
- Gastroenterology and Endoscopy Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy
| | - Giulia Dispinzieri
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca and European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Via Pergolesi 33, 20900 Monza, Italy
| | - Alessandra Elvevi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca and European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Via Pergolesi 33, 20900 Monza, Italy
| | - Sara Massironi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca and European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Via Pergolesi 33, 20900 Monza, Italy
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Lal SB, Venkatesh V, Aneja A, Seetharaman K, Kumar Y, Prasad KK, Rana SS. Clinical spectrum & changing presentation of celiac disease in Indian children. Indian J Med Res 2023; 158:75-84. [PMID: 37602589 PMCID: PMC10550060 DOI: 10.4103/ijmr.ijmr_1102_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Indexed: 08/10/2023] Open
Abstract
Background & objectives Celiac disease (CD) is a genetic immune mediated disorder characterised by gluten intolerance. This single centre study, from north India was aimed to assess the clinical, serological and histological profile of CD in a large cohort of children and the changing trends in its presentation. Methods A review of clinical details of CD children diagnosed between 2000 and 2019 and currently on follow up was performed. Information on demography, symptoms, associated conditions, serology, biopsy findings and gluten-free diet were analyzed. Results The mean age (±standard deviation) of 891 children included in the study, at onset and at diagnosis was 4.0±2.7 and 6.2±3.1 yr, respectively. Growth faltering, abdominal pain, abdominal distension and diarrhoea were presenting symptoms in 70, 64.2, 61.2 and 58.2 per cent, respectively. A positive family history of CD was present in 14 per cent and autoimmune conditions in 12.3 per cent of children. Thyroid disorders were seen in 8.5 per cent of children and Type 1 diabetes mellitus (T1DM) in 5.7 per cent. The duration of breastfeeding had a weak positive correlation with age at onset and diagnosis of CD (P<0.001). Non-classical CD was significantly more common in children aged >10 yr and in those presenting after 2010 (P<0.01). T1DM and hypothyroidism occurred more frequently in non-compliant children. Interpretation & conclusions This was the largest single centre study, pertaining to the presentation and follow up of CD in children. Infants and young children were more likely to present with classical symptoms of diarrhoea, abdominal distension and growth failure while older children presented with non-classical CD. There was a trend towards non-classical forms of CD in recent years.
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Affiliation(s)
- Sadhna Bhasin Lal
- Division of Paediatric Gastroenterology & Hepatology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Vybhav Venkatesh
- Division of Paediatric Gastroenterology & Hepatology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Aradhana Aneja
- Division of Paediatric Gastroenterology & Hepatology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Keerthivasan Seetharaman
- Division of Paediatric Gastroenterology & Hepatology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Yashwant Kumar
- Department of Immunopathology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Kaushal Kishor Prasad
- Division of Gastroenterology Histopathology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Surinder Singh Rana
- Department of Gastroenterology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
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Pang Y, Ermann Lundberg L, Mata Forsberg M, Ahl D, Bysell H, Pallin A, Sverremark-Ekström E, Karlsson R, Jonsson H, Roos S. Extracellular membrane vesicles from Limosilactobacillus reuteri strengthen the intestinal epithelial integrity, modulate cytokine responses and antagonize activation of TRPV1. Front Microbiol 2022; 13:1032202. [PMID: 36466671 PMCID: PMC9712456 DOI: 10.3389/fmicb.2022.1032202] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Accepted: 10/24/2022] [Indexed: 09/05/2023] Open
Abstract
Bacterial extracellular membrane vesicles (MV) are potent mediators of microbe-host signals, and they are not only important in host-pathogen interactions but also for the interactions between mutualistic bacteria and their hosts. Studies of MV derived from probiotics could enhance the understanding of these universal signal entities, and here we have studied MV derived from Limosilactobacillus reuteri DSM 17938 and BG-R46. The production of MV increased with cultivation time and after oxygen stress. Mass spectrometry-based proteomics analyses revealed that the MV carried a large number of bacterial cell surface proteins, several predicted to be involved in host-bacteria interactions. A 5'-nucleotidase, which catalyze the conversion of AMP into the signal molecule adenosine, was one of these and analysis of enzymatic activity showed that L. reuteri BG-R46 derived MV exhibited the highest activity. We also detected the TLR2 activator lipoteichoic acid on the MV. In models for host interactions, we first observed that L. reuteri MV were internalized by Caco-2/HT29-MTX epithelial cells, and in a dose-dependent manner decreased the leakage caused by enterotoxigenic Escherichia coli by up to 65%. Furthermore, the MV upregulated IL-1β and IL-6 from peripheral blood mononuclear cells (PBMC), but also dampened IFN-γ and TNF-α responses in PBMC challenged with Staphylococcus aureus. Finally, we showed that MV from the L. reuteri strains have an antagonistic effect on the pain receptor transient receptor potential vanilloid 1 in a model with primary dorsal root ganglion cells from rats. In summary, we have shown that these mobile nanometer scale MV reproduce several biological effects of L. reuteri cells and that the production parameters and selection of strain have an impact on the activity of the MV. This could potentially provide key information for development of innovative and more efficient probiotic products.
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Affiliation(s)
- Yanhong Pang
- Department of Molecular Sciences, Uppsala BioCenter, Swedish University of Agricultural Sciences, Uppsala, Sweden
| | - Ludwig Ermann Lundberg
- Department of Molecular Sciences, Uppsala BioCenter, Swedish University of Agricultural Sciences, Uppsala, Sweden
- BioGaia AB, Stockholm, Sweden
| | - Manuel Mata Forsberg
- The Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden
| | - David Ahl
- Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden
| | | | - Anton Pallin
- Department of Molecular Sciences, Uppsala BioCenter, Swedish University of Agricultural Sciences, Uppsala, Sweden
| | - Eva Sverremark-Ekström
- The Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden
| | - Roger Karlsson
- Department of Clinical Microbiology, Sahlgrenska University Hospital, Gothenburg, Sweden
- Nanoxis Consulting AB, Gothenburg, Sweden
| | - Hans Jonsson
- Department of Molecular Sciences, Uppsala BioCenter, Swedish University of Agricultural Sciences, Uppsala, Sweden
| | - Stefan Roos
- Department of Molecular Sciences, Uppsala BioCenter, Swedish University of Agricultural Sciences, Uppsala, Sweden
- BioGaia AB, Stockholm, Sweden
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6
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Zhang X, Xu XF, Jin J. Rotavirus vaccination and the risk of type 1 diabetes and celiac disease: A systematic review and meta-analysis. Front Pediatr 2022; 10:951127. [PMID: 36090563 PMCID: PMC9459138 DOI: 10.3389/fped.2022.951127] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Accepted: 07/29/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Rotavirus vaccination has been proven to effectively protect against rotavirus gastroenteritis. However, there are concerns about the relationship between rotavirus vaccination and the risk of autoimmune disorders. Thus, we conducted a systematic review and meta-analysis to comprehensively assess the association between rotavirus vaccination and type 1 diabetes (T1D) or celiac disease (CD) risk. METHODS A systematic review and meta-analysis were conducted to evaluate the type 1 diabetes or celiac disease associated with rotavirus vaccination. The following journal databases were searched to identify potential studies for inclusion: PubMed, Embase, and Cochrane Library databases. RESULTS Seven articles involving more than 5,793,055 children were included. Our results showed that rotavirus vaccination does not alter the subsequent risk of T1D (RR 0.94, 95% CI: 0.82-1.09) or CD (RR 0.86, 95% CI: 0.64-1.17) after vaccination. Furthermore, the risk of T1D was not increased or decreased for children fully exposed to rotavirus vaccination (RR 0.86, 95% CI, 0.54-1.36) and for children partially exposed to rotavirus vaccination (RR 1.05, 95% CI, 0.87-1.26). However, younger (<5 years) vaccinated children at the end of study (RR 0.84, 95% CI = 0.75-0.95) may be at a lower risk for T1D than older (≥5 years) vaccinated children (RR 0.93, 95% CI, 0.81-1.07). CONCLUSION The findings of this study suggest that rotavirus vaccination does not appear to be associated with T1D or CD in children. The protective effect of rotavirus vaccination on T1D may be presented by time dependent.
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Affiliation(s)
- Xue Zhang
- Department of Infectious Diseases, The Affiliated Hangzhou First People's Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Xiang-Fei Xu
- Department of Infectious Diseases, The Affiliated Hangzhou First People's Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Jie Jin
- Department of Infectious Diseases, The Affiliated Hangzhou First People's Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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7
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Pourhoseingholi MA. Epidemiology and burden of gluten-related disorders. GLUTEN-RELATED DISORDERS 2022:59-81. [DOI: 10.1016/b978-0-12-821846-4.00011-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Cauble JS, Herman A, Wick J, Goetz J, Daley CM, Sullivan DK, Hull HR. A prenatal group based phone counseling intervention to improve breastfeeding rates and complementary feeding: a randomized, controlled pilot and feasibility trial. BMC Pregnancy Childbirth 2021; 21:521. [PMID: 34294051 PMCID: PMC8296528 DOI: 10.1186/s12884-021-03976-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Accepted: 06/04/2021] [Indexed: 11/29/2022] Open
Abstract
Background Despite numerous benefits for both mom and baby, few infants are exclusively breastfed for the recommended first six months. Additionally, infants are given solids too early. Prenatal education increases rates of breastfeeding initiation and we hypothesize it can also improve exclusive breastfeeding rates and prevent the early introduction of solids. We conducted a randomized controlled pilot and feasibility trial to understand the feasibility and maternal acceptance of a prenatal behavioral lifestyle intervention (PBLI) delivered via group based phone counseling (GBPC) and its effectiveness on rates of exclusive breastfeeding up to six months postpartum. Secondary aims included rates of any breastfeeding up to six months, rates of early introduction of solids, and infant feeding progression. Methods Forty-one pregnant women were recruited from a Kansas City Metropolitan Obstetrics and Gynecology office and randomly assigned to a usual care group or a PBLI. Women in the PBLI participated in six GBPC sessions where they learned about breastfeeding and introducing solids. Feeding questionnaires to assess breastfeeding and introduction of solids were sent at two weeks, two months, four months, and six months postpartum. Structured interviews were also conducted after the intervention and at six months postpartum to assess maternal acceptance and intervention feasibility. Results Participants overwhelmingly found the intervention acceptable and beneficial. Rates of exclusive breastfeeding and any breastfeeding did not differ between groups at any time point. No between group differences were found for early introduction of solids or infant feeding progression. Conclusions Mothers discontinue breastfeeding earlier than recommended despite high rates of initiation. A PBLI delivered via GBP is feasible, acceptable to participants, and showed positive impacts such as maternal empowerment for both breastfeeding and introducing solids. Future interventions should incorporate both prenatal and postpartum components. Trial registration Study protocols were approved by the University of Kansas Medical Center’s Human Subjects Committee (STUDY00140506) and registered at ClinicalTrials.gov on 02/22/2018 (NCT03442517, retrospectively registered). All participants gave written informed consent prior to data collection.
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Affiliation(s)
- Jennifer S Cauble
- School of Health Professions, Department of Dietetics & Nutrition, University of Kansas Medical Center, 3901 Rainbow BLVD, Mail Stop 4013, Kansas City, KS 66160, USA
| | - Amy Herman
- School of Health Professions, Department of Dietetics & Nutrition, University of Kansas Medical Center, 3901 Rainbow BLVD, Mail Stop 4013, Kansas City, KS 66160, USA
| | - Jo Wick
- School of Health Professions, Department of Dietetics & Nutrition, University of Kansas Medical Center, 3901 Rainbow BLVD, Mail Stop 4013, Kansas City, KS 66160, USA
| | - Jeannine Goetz
- School of Health Professions, Department of Dietetics & Nutrition, University of Kansas Medical Center, 3901 Rainbow BLVD, Mail Stop 4013, Kansas City, KS 66160, USA
| | - Christine M Daley
- School of Medicine, Department of Preventative Medicine and Public Health, University of Kansas Medical Center, Kansas City, USA
| | - Debra K Sullivan
- School of Health Professions, Department of Dietetics & Nutrition, University of Kansas Medical Center, 3901 Rainbow BLVD, Mail Stop 4013, Kansas City, KS 66160, USA
| | - Holly R Hull
- School of Health Professions, Department of Dietetics & Nutrition, University of Kansas Medical Center, 3901 Rainbow BLVD, Mail Stop 4013, Kansas City, KS 66160, USA.
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Olshan KL, Zomorrodi AR, Pujolassos M, Troisi J, Khan N, Fanelli B, Kenyon V, Fasano A, Leonard MM. Microbiota and Metabolomic Patterns in the Breast Milk of Subjects with Celiac Disease on a Gluten-Free Diet. Nutrients 2021; 13:nu13072243. [PMID: 34210038 PMCID: PMC8308312 DOI: 10.3390/nu13072243] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Revised: 06/14/2021] [Accepted: 06/25/2021] [Indexed: 12/30/2022] Open
Abstract
The intestinal microbiome may trigger celiac disease (CD) in individuals with a genetic disposition when exposed to dietary gluten. Research demonstrates that nutrition during infancy is crucial to the intestinal microbiome engraftment. Very few studies to date have focused on the breast milk composition of subjects with a history of CD on a gluten-free diet. Here, we utilize a multi-omics approach with shotgun metagenomics to analyze the breast milk microbiome integrated with metabolome profiling of 36 subjects, 20 with CD on a gluten-free diet and 16 healthy controls. These analyses identified significant differences in bacterial and viral species/strains and functional pathways but no difference in metabolite abundance. Specifically, three bacterial strains with increased abundance were identified in subjects with CD on a gluten-free diet of which one (Rothia mucilaginosa) has been previously linked to autoimmune conditions. We also identified five pathways with increased abundance in subjects with CD on a gluten-free diet. We additionally found four bacterial and two viral species/strains with increased abundance in healthy controls. Overall, the differences observed in bacterial and viral species/strains and in functional pathways observed in our analysis may influence microbiome engraftment in neonates, which may impact their future clinical outcomes.
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Affiliation(s)
- Katherine L. Olshan
- Division of Pediatric Gastroenterology and Nutrition, MassGeneral Hospital for Children, Harvard Medical School, Boston, MA 02114, USA; (K.L.O.); (A.R.Z.); (A.F.)
- Mucosal Immunology and Biology Research Center, MassGeneral Hospital for Children, Boston, MA 02129, USA;
- Department of Pediatrics, Harvard Medical School, Harvard University, Boston, MA 02115, USA
- Celiac Research Program, Harvard Medical School, Boston, MA 02115, USA
| | - Ali R. Zomorrodi
- Division of Pediatric Gastroenterology and Nutrition, MassGeneral Hospital for Children, Harvard Medical School, Boston, MA 02114, USA; (K.L.O.); (A.R.Z.); (A.F.)
- Mucosal Immunology and Biology Research Center, MassGeneral Hospital for Children, Boston, MA 02129, USA;
- Department of Pediatrics, Harvard Medical School, Harvard University, Boston, MA 02115, USA
- Celiac Research Program, Harvard Medical School, Boston, MA 02115, USA
| | | | - Jacopo Troisi
- Theoreo srl, University of Salerno, 84084 Salerno, Italy; (M.P.); (J.T.)
- Department of Medicine, Surgery and Dentistry, Scuola Medica Salernitana, University of Salerno, 84084 Salerno, Italy
- European Biomedical Research Institute of Salerno (EBRIS), Via S. De Renzi, 50, 84125 Salerno, Italy
| | - Nayeim Khan
- CosmosID Inc., Rockville, MD 20850, USA; (N.K.); (B.F.)
| | - Brian Fanelli
- CosmosID Inc., Rockville, MD 20850, USA; (N.K.); (B.F.)
| | - Victoria Kenyon
- Mucosal Immunology and Biology Research Center, MassGeneral Hospital for Children, Boston, MA 02129, USA;
- Celiac Research Program, Harvard Medical School, Boston, MA 02115, USA
| | - Alessio Fasano
- Division of Pediatric Gastroenterology and Nutrition, MassGeneral Hospital for Children, Harvard Medical School, Boston, MA 02114, USA; (K.L.O.); (A.R.Z.); (A.F.)
- Mucosal Immunology and Biology Research Center, MassGeneral Hospital for Children, Boston, MA 02129, USA;
- Department of Pediatrics, Harvard Medical School, Harvard University, Boston, MA 02115, USA
- Celiac Research Program, Harvard Medical School, Boston, MA 02115, USA
- Department of Medicine, Surgery and Dentistry, Scuola Medica Salernitana, University of Salerno, 84084 Salerno, Italy
| | - Maureen M. Leonard
- Division of Pediatric Gastroenterology and Nutrition, MassGeneral Hospital for Children, Harvard Medical School, Boston, MA 02114, USA; (K.L.O.); (A.R.Z.); (A.F.)
- Mucosal Immunology and Biology Research Center, MassGeneral Hospital for Children, Boston, MA 02129, USA;
- Department of Pediatrics, Harvard Medical School, Harvard University, Boston, MA 02115, USA
- Celiac Research Program, Harvard Medical School, Boston, MA 02115, USA
- Correspondence:
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10
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Contribution of Infectious Agents to the Development of Celiac Disease. Microorganisms 2021; 9:microorganisms9030547. [PMID: 33800833 PMCID: PMC8001938 DOI: 10.3390/microorganisms9030547] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 02/28/2021] [Accepted: 03/02/2021] [Indexed: 02/07/2023] Open
Abstract
The ingestion of wheat gliadin (alcohol-soluble proteins, an integral part of wheat gluten) and related proteins induce, in genetically predisposed individuals, celiac disease (CD), which is characterized by immune-mediated impairment of the small intestinal mucosa. The lifelong omission of gluten and related grain proteins, i.e., a gluten-free diet (GFD), is at present the only therapy for CD. Although a GFD usually reduces CD symptoms, it does not entirely restore the small intestinal mucosa to a fully healthy state. Recently, the participation of microbial components in pathogenetic mechanisms of celiac disease was suggested. The present review provides information on infectious diseases associated with CD and the putative role of infections in CD development. Moreover, the involvement of the microbiota as a factor contributing to pathological changes in the intestine is discussed. Attention is paid to the mechanisms by which microbes and their components affect mucosal immunity, including tolerance to food antigens. Modulation of microbiota composition and function and the potential beneficial effects of probiotics in celiac disease are discussed.
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11
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Villamil E, Rodríguez-Camejo C, Puyol A, Fazio L, Colistro V, Hernández A. Immune profiling of breast milk from mothers with treated celiac disease. Pediatr Res 2021; 89:488-495. [PMID: 32316028 DOI: 10.1038/s41390-020-0901-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2019] [Accepted: 04/01/2020] [Indexed: 11/09/2022]
Abstract
BACKGROUND The protective effect of breastfeeding on celiac disease (CD) onset is controversial. We studied a wide range of milk components in milk produced by celiac mothers following long-term gluten-free diet (GFD) in comparison to milk produced by healthy mothers. METHODS Breast-milk samples from celiac (n = 33) and healthy (n = 41) mothers were obtained during the first year of lactation. A panel of bioactive components was analyzed by enzyme-linked immunosorbent assay in the aqueous fraction. We studied molecules involved in defenses, immunoregulation, and strengthening of the gut-epithelial barrier. RESULTS During late lactation (from 6 to 12 months after delivery), the content of total immunoglobulin A (IgA) and IgM was significantly lower in the milk produced by celiac patients. Nevertheless, gliadin (GFD)-specific IgA relative contribution was higher in this group, in contrast to tetanus toxoid-specific antibodies. The balance between pro-inflammatory and anti-inflammatory molecules was different. While interleukin-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 were most frequently found in samples from celiac mothers, soluble Toll-like receptor-2 prevalence was lower. CONCLUSIONS We describe differences between the innate and adaptive immune profile of milk produced by celiac and healthy mothers. These results might explain previous controversial reports about breastfeeding and CD protection. IMPACT In spite of a long-term adherence to GFD, the milk produced by mothers with CD exhibit a different immune profile, in relation with some immunoregulatory factors and antibody content. This work shows a more comprehensive characterization of milk from celiac mothers, including macronutrients, lysozymes, growth factors, and immunoregulatory components that had not been studied before. The present study widens the available data regarding the characteristics of human milk of celiac mothers following GFD. Further follow-up studies of the health of children who were breastfed by celiac mothers will be necessary in order to also estimate the impact of the present results therein.
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Affiliation(s)
- Emilia Villamil
- Cátedra de Inmunología. Instituto de Química Biológica, Facultad de Ciencias/Departamento de Biociencias, Facultad de Química, Universidad de la República, Instituto de Higiene. Avda. Alfrado Navarro 3051, Montevideo, Uruguay
| | - Claudio Rodríguez-Camejo
- Cátedra de Inmunología. Instituto de Química Biológica, Facultad de Ciencias/Departamento de Biociencias, Facultad de Química, Universidad de la República, Instituto de Higiene. Avda. Alfrado Navarro 3051, Montevideo, Uruguay
| | - Arturo Puyol
- Banco de Leche Humana "Ruben Panizza", Centro Hospitalario Pereira Rossell, Administración de los Servicios de Salud del Estado, Montevideo, Uruguay
| | - Laura Fazio
- Banco de Leche Humana "Ruben Panizza", Centro Hospitalario Pereira Rossell, Administración de los Servicios de Salud del Estado, Montevideo, Uruguay
| | - Valentina Colistro
- Departamento de Métodos Cuantitativos, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay
| | - Ana Hernández
- Cátedra de Inmunología. Instituto de Química Biológica, Facultad de Ciencias/Departamento de Biociencias, Facultad de Química, Universidad de la República, Instituto de Higiene. Avda. Alfrado Navarro 3051, Montevideo, Uruguay.
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12
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Olshan KL, Leonard MM, Serena G, Zomorrodi AR, Fasano A. Gut microbiota in Celiac Disease: microbes, metabolites, pathways and therapeutics. Expert Rev Clin Immunol 2020; 16:1075-1092. [PMID: 33103934 DOI: 10.1080/1744666x.2021.1840354] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Current evidence supports a vital role of the microbiota on health outcomes, with alterations in an otherwise healthy balance linked to chronic medical conditions like celiac disease (CD). Recent advances in microbiome analysis allow for unparalleled profiling of the microbes and metabolites. With the growing volume of data available, trends are emerging that support a role for the gut microbiota in CD pathogenesis. AREAS COVERED In this article, the authors review the relationship between factors such as genes and antibiotic exposure on CD onset and the intestinal microbiota. The authors also review other microbiota within the human body (like the oropharynx) that may play a role in CD pathogenesis. Finally, the authors discuss implications for disease modification and the ultimate goal of prevention. The authors reviewed literature from PubMed, EMBASE, and Web of Science. EXPERT OPINION CD serves as a unique opportunity to explore the role of the intestinal microbiota on the development of chronic autoimmune disease. While research to date provides a solid foundation, most studies have been case-control and thus do not have capacity to explore the mechanistic role of the microbiota in CD onset. Further longitudinal studies and integrated multi-omics are necessary for investigating CD pathogenesis.
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Affiliation(s)
- Katherine L Olshan
- Division of Pediatric Gastroenterology and Nutrition, MassGeneral Hospital for Children, Harvard Medical School , Boston, MA, USA.,Mucosal Immunology and Biology Research Center, MassGeneral Hospital for Children, Harvard Medical School , Boston, MA, USA.,Celiac Research Program, Harvard Medical School , Boston, MA, USA
| | - Maureen M Leonard
- Division of Pediatric Gastroenterology and Nutrition, MassGeneral Hospital for Children, Harvard Medical School , Boston, MA, USA.,Mucosal Immunology and Biology Research Center, MassGeneral Hospital for Children, Harvard Medical School , Boston, MA, USA.,Celiac Research Program, Harvard Medical School , Boston, MA, USA
| | - Gloria Serena
- Division of Pediatric Gastroenterology and Nutrition, MassGeneral Hospital for Children, Harvard Medical School , Boston, MA, USA.,Mucosal Immunology and Biology Research Center, MassGeneral Hospital for Children, Harvard Medical School , Boston, MA, USA.,Celiac Research Program, Harvard Medical School , Boston, MA, USA
| | - Ali R Zomorrodi
- Division of Pediatric Gastroenterology and Nutrition, MassGeneral Hospital for Children, Harvard Medical School , Boston, MA, USA.,Mucosal Immunology and Biology Research Center, MassGeneral Hospital for Children, Harvard Medical School , Boston, MA, USA.,Celiac Research Program, Harvard Medical School , Boston, MA, USA
| | - Alessio Fasano
- Division of Pediatric Gastroenterology and Nutrition, MassGeneral Hospital for Children, Harvard Medical School , Boston, MA, USA.,Mucosal Immunology and Biology Research Center, MassGeneral Hospital for Children, Harvard Medical School , Boston, MA, USA.,European Biomedical Research Institute of Salerno (EBRIS) , Salerno, Italy
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13
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Logan K, Perkin MR, Marrs T, Radulovic S, Craven J, Flohr C, Bahnson HT, Lack G. Early Gluten Introduction and Celiac Disease in the EAT Study: A Prespecified Analysis of the EAT Randomized Clinical Trial. JAMA Pediatr 2020; 174:1041-1047. [PMID: 32986087 PMCID: PMC7522778 DOI: 10.1001/jamapediatrics.2020.2893] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
IMPORTANCE There are no strategies for the prevention of celiac disease (CD). Current guidelines stating that the age at gluten introduction does not affect the prevalence of CD are based on the results from several randomized clinical trials, but the doses of gluten and timing of its introduction varied. OBJECTIVE To determine whether early introduction of high-dose gluten lowers the prevalence of CD at age 3 years. DESIGN, SETTING, AND PARTICIPANTS The Enquiring About Tolerance (EAT) Study was an open-label randomized clinical trial. A total of 1303 children from the general population in England and Wales were recruited and followed up from November 2, 2009, to July 30, 2012. For the present study, samples were collected from November 1, 2012, to March 31, 2015, and data were analyzed from April 25, 2017, to September 17, 2018. INTERVENTIONS Infants were randomized to consume 6 allergenic foods (peanut, sesame, hen's egg, cow's milk, cod fish, and wheat) in addition to breast milk from age 4 months (early introduction group [EIG]) or to avoid allergenic foods and follow UK infant feeding recommendations of exclusive breastfeeding until approximately age 6 months (standard introduction group [SIG]). MAIN OUTCOMES AND MEASURES Evaluation of CD was an a priori secondary end point of the EAT Study, and at age 3 years, all children with available serum samples were tested for antitransglutaminase type 2 antibodies. Children with antibody levels greater than 20 IU/L were referred to independent gastroenterologists for further investigation. RESULTS Of the 1004 infants included in the analysis, 514 were male (51.2%). The mean (SD) quantity of gluten consumed between ages 4 and 6 months was 0.49 (1.40) g/wk in the SIG and 2.66 (1.85) g/wk in the EIG (P < .001). Mean (SD) weekly gluten consumption ranged from 0.08 (1.00) g/wk at age 4 months to 0.9 (2.05) g/wk at age 6 months in the SIG vs 1.3 (1.54) g/wk at age 4 months to 4.03 (2.40) g/wk at age 6 months in the EIG. Seven of 516 children from the SIG (1.4%) had a diagnosis of CD confirmed vs none of the 488 children in the EIG (P = .02, risk difference between the groups using the bootstrap, 1.4%; 95% CI, 0.6%-2.6%). CONCLUSIONS AND RELEVANCE In this analysis of infants in the EAT Study, the introduction of gluten from age 4 months was associated with reduced CD prevalence. These results suggest that early high-dose consumption of gluten should be considered as a strategy to prevent CD in future studies. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN14254740.
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Affiliation(s)
- Kirsty Logan
- The Paediatric Allergy Research Group, Department of Women and Children’s Health, School of Life Course Sciences, King’s College London, London, United Kingdom
| | - Michael R. Perkin
- The Population Health Research Institute, St George's, University of London, London, United Kingdom
| | - Tom Marrs
- The Paediatric Allergy Research Group, Department of Women and Children’s Health, School of Life Course Sciences, King’s College London, London, United Kingdom
| | - Suzana Radulovic
- The Paediatric Allergy Research Group, Department of Women and Children’s Health, School of Life Course Sciences, King’s College London, London, United Kingdom
| | - Joanna Craven
- The Paediatric Allergy Research Group, Department of Women and Children’s Health, School of Life Course Sciences, King’s College London, London, United Kingdom
| | - Carsten Flohr
- The St John’s Institute of Dermatology, Guy’s and St Thomas’ Hospital NHS Foundation Trust, London, United Kingdom
| | | | - Gideon Lack
- The Paediatric Allergy Research Group, Department of Women and Children’s Health, School of Life Course Sciences, King’s College London, London, United Kingdom
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14
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Leonard MM, Karathia H, Pujolassos M, Troisi J, Valitutti F, Subramanian P, Camhi S, Kenyon V, Colucci A, Serena G, Cucchiara S, Montuori M, Malamisura B, Francavilla R, Elli L, Fanelli B, Colwell R, Hasan N, Zomorrodi AR, Fasano A. Multi-omics analysis reveals the influence of genetic and environmental risk factors on developing gut microbiota in infants at risk of celiac disease. MICROBIOME 2020; 8:130. [PMID: 32917289 PMCID: PMC7488762 DOI: 10.1186/s40168-020-00906-w] [Citation(s) in RCA: 63] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Accepted: 08/10/2020] [Indexed: 05/28/2023]
Abstract
BACKGROUND Celiac disease (CD) is an autoimmune digestive disorder that occurs in genetically susceptible individuals in response to ingesting gluten, a protein found in wheat, rye, and barley. Research shows that genetic predisposition and exposure to gluten are necessary but not sufficient to trigger the development of CD. This suggests that exposure to other environmental stimuli early in life, e.g., cesarean section delivery and exposure to antibiotics or formula feeding, may also play a key role in CD pathogenesis through yet unknown mechanisms. Here, we use multi-omics analysis to investigate how genetic and early environmental risk factors alter the development of the gut microbiota in infants at risk of CD. RESULTS Toward this end, we selected 31 infants from a large-scale prospective birth cohort study of infants with a first-degree relative with CD. We then performed rigorous multivariate association, cross-sectional, and longitudinal analyses using metagenomic and metabolomic data collected at birth, 3 months and 6 months of age to explore the impact of genetic predisposition and environmental risk factors on the gut microbiota composition, function, and metabolome prior to the introduction of trigger (gluten). These analyses revealed several microbial species, functional pathways, and metabolites that are associated with each genetic and environmental risk factor or that are differentially abundant between environmentally exposed and non-exposed infants or between time points. Among our significant findings, we found that cesarean section delivery is associated with a decreased abundance of Bacteroides vulgatus and Bacteroides dorei and of folate biosynthesis pathway and with an increased abundance of hydroxyphenylacetic acid, alterations that are implicated in immune system dysfunction and inflammatory conditions. Additionally, longitudinal analysis revealed that, in infants not exposed to any environmental risk factor, the abundances of Bacteroides uniformis and of metabolite 3-3-hydroxyphenylproprionic acid increase over time, while those for lipoic acid and methane metabolism pathways decrease, patterns that are linked to beneficial immunomodulatory and anti-inflammatory effects. CONCLUSIONS Overall, our study provides unprecedented insights into major taxonomic and functional shifts in the developing gut microbiota of infants at risk of CD linking genetic and environmental risk factors to detrimental immunomodulatory and inflammatory effects. Video Abstract.
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Affiliation(s)
- Maureen M Leonard
- Division of Pediatric Gastroenterology and Nutrition, MassGeneral Hospital for Children, Harvard Medical School, Boston, MA, USA
- Mucosal Immunology and Biology Research Center, MassGeneral Hospital for Children, Boston, USA
- Harvard Medical School, Boston, MA, USA
- Celiac Research Program, Harvard Medical School, Boston, MA, USA
| | | | | | - Jacopo Troisi
- Theoreo srl, University of Salerno, Montecorvino Pugliano, Italy
- Department of Medicine, Surgery and Dentistry, Scuola Medica Salernitana, University of Salerno, Salerno, Italy
- European Biomedical Research Institute of Salerno (EBRIS), Via S. De Renzi, 50, 84125, Salerno, Italy
| | - Francesco Valitutti
- European Biomedical Research Institute of Salerno (EBRIS), Via S. De Renzi, 50, 84125, Salerno, Italy
- Pediatric Unit, Maternal and Child Health Department, AOU San Giovanni di Dio e Ruggi d'Aragona, Salerno, Italy
| | | | - Stephanie Camhi
- Mucosal Immunology and Biology Research Center, MassGeneral Hospital for Children, Boston, USA
- Celiac Research Program, Harvard Medical School, Boston, MA, USA
| | - Victoria Kenyon
- Mucosal Immunology and Biology Research Center, MassGeneral Hospital for Children, Boston, USA
- Celiac Research Program, Harvard Medical School, Boston, MA, USA
| | - Angelo Colucci
- Theoreo srl, University of Salerno, Montecorvino Pugliano, Italy
- Department of Medicine, Surgery and Dentistry, Scuola Medica Salernitana, University of Salerno, Salerno, Italy
| | - Gloria Serena
- Division of Pediatric Gastroenterology and Nutrition, MassGeneral Hospital for Children, Harvard Medical School, Boston, MA, USA
- Mucosal Immunology and Biology Research Center, MassGeneral Hospital for Children, Boston, USA
- Harvard Medical School, Boston, MA, USA
- Celiac Research Program, Harvard Medical School, Boston, MA, USA
| | | | - Monica Montuori
- Pediatric Gastroenterology, Sapienza University of Rome, Rome, Italy
| | - Basilio Malamisura
- Pediatric Unit, Maternal and Child Health Department, AOU San Giovanni di Dio e Ruggi d'Aragona, Pole of Cava de' Tirreni, Salerno, Italy
| | | | - Luca Elli
- Center for Prevention and Diagnosis of Celiac Disease Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | | | - Rita Colwell
- CosmosID Inc., Rockville, MD, USA
- Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD, USA
| | | | - Ali R Zomorrodi
- Division of Pediatric Gastroenterology and Nutrition, MassGeneral Hospital for Children, Harvard Medical School, Boston, MA, USA.
- Mucosal Immunology and Biology Research Center, MassGeneral Hospital for Children, Boston, USA.
- Harvard Medical School, Boston, MA, USA.
- Celiac Research Program, Harvard Medical School, Boston, MA, USA.
| | - Alessio Fasano
- Division of Pediatric Gastroenterology and Nutrition, MassGeneral Hospital for Children, Harvard Medical School, Boston, MA, USA.
- Mucosal Immunology and Biology Research Center, MassGeneral Hospital for Children, Boston, USA.
- Harvard Medical School, Boston, MA, USA.
- Celiac Research Program, Harvard Medical School, Boston, MA, USA.
- European Biomedical Research Institute of Salerno (EBRIS), Via S. De Renzi, 50, 84125, Salerno, Italy.
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15
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Popp A, Mäki M. Changing Pattern of Childhood Celiac Disease Epidemiology: Contributing Factors. Front Pediatr 2019; 7:357. [PMID: 31555624 PMCID: PMC6727179 DOI: 10.3389/fped.2019.00357] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Accepted: 08/15/2019] [Indexed: 12/14/2022] Open
Abstract
Up until the 1960s and 1970s, diarrhea, malabsorption syndrome, and failure to thrive were the presenting symptoms and signs of celiac disease (CD) in young infants; however this disease was also at the same time reported to be disappearing. Indeed, clinical childhood CD was seen to transform into a milder form, resulting in an upward shift in age at diagnosis during the 1970s (and years later for many countries). This changing pattern of CD presentation then altered the epidemiology of the disease, with major differences between and within countries observed. An awareness of the changing clinical nature of CD and use of case-finding tools to detect even clinically silent CD became an important factor in this changing epidemiology. Countries report both low and high prevalence but it seems to be on the increase resulting in a population-based level of 1-2%. This paper discusses the potential causes and environmental factors behind these observed clinical changes, identifying new clues from different studies published at the time this transformation took place. For instance, it was found that breastfeeding postponed the diagnosis of the disease but did not altogether prevent it. Moreover, gluten introduction at a young age, specifically at the mean age of 2 months, seemed to also have a clear impact in inducing malabsorption syndrome and failure to thrive in young infants in addition to other factors such as gluten intake volume and type of cereal present in the weaning food. Further, the impact of cow's milk and its high osmolarity might have played an important role; humanized milk formulas were not yet invented. Future epidemiological studies on the contributing environmental factors to the shift in CD presentation are thus recommended for countries in which these changing clinical features are still being observed.
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Affiliation(s)
- Alina Popp
- Faculty of Medicine and Health Technology, Tampere Center of Child Health Research, Tampere University and Tampere University Hospital, Tampere, Finland
- National Institute for Mother and Child Health “Alessandrescu-Rusescu”, University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania
| | - Markku Mäki
- Faculty of Medicine and Health Technology, Tampere Center of Child Health Research, Tampere University and Tampere University Hospital, Tampere, Finland
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16
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Barroso M, Beth SA, Voortman T, Jaddoe VWV, van Zelm MC, Moll HA, Kiefte-de Jong JC. Dietary Patterns After the Weaning and Lactation Period Are Associated With Celiac Disease Autoimmunity in Children. Gastroenterology 2018; 154:2087-2096.e7. [PMID: 29481779 DOI: 10.1053/j.gastro.2018.02.024] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2017] [Revised: 02/03/2018] [Accepted: 02/19/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS There have been many studies of associations between infant feeding practices and development of celiac disease during childhood, but few studies have focused on overall diets of young children after the weaning period. We aimed to examine the association between common dietary patterns in infants and the occurrence of celiac disease autoimmunity during childhood. METHODS We performed a prospective analysis of data from the Generation R Study that comprised 1997 children born from April 2002 through January 2006 in Rotterdam, the Netherlands. Food consumption around 1 year of age was assessed with a validated food-frequency questionnaire. Dietary data were examined using a priori (based on existing guidelines) and a posteriori (principal component analysis and reduced rank regression) dietary pattern analyses. Five dietary patterns were compared. Celiac disease autoimmunity, determined on the basis of serum concentration of transglutaminase-2 autoantibody (ie, TG2A) below or above 7 U/mL, was evaluated at 6 years. Associations between dietary pattern adherence scores and celiac disease autoimmunity were examined using multivariable logistic regression models. RESULTS Higher adherence to the a posteriori-derived prudent dietary pattern (high intake of vegetables, vegetable oils, pasta, and grains and low consumption of refined cereals and sweet beverages) at 1 year was significantly associated with lower odds of celiac disease autoimmunity at 6 years (odds ratio, 0.67; 95% confidence interval, 0.53-0.84). No significant associations were found for the 4 remaining dietary patterns. CONCLUSIONS In a prospective study of dietary patterns of young children in the Netherlands, we associated a dietary pattern characterized by high consumption of vegetables and grains and low consumption of refined cereals and sweet beverages, with lower odds of celiac disease autoimmunity. Early-life dietary patterns might therefore be involved in the development of celiac disease during childhood.
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Affiliation(s)
- Monica Barroso
- Generation R Study Group, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Pediatrics, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Sytske A Beth
- Generation R Study Group, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Pediatrics, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Trudy Voortman
- Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Vincent W V Jaddoe
- Generation R Study Group, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Pediatrics, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Menno C van Zelm
- Department of Immunology and Pathology, Central Clinical School, Monash University and Alfred Hospital, Melbourne, Victoria, Australia
| | - Henriette A Moll
- Department of Pediatrics, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Jessica C Kiefte-de Jong
- Department of Pediatrics, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands; Leiden University College, the Hague, the Netherlands.
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17
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Olivares M, Benítez-Páez A, de Palma G, Capilla A, Nova E, Castillejo G, Varea V, Marcos A, Garrote JA, Polanco I, Donat E, Ribes-Koninckx C, Calvo C, Ortigosa L, Palau F, Sanz Y. Increased prevalence of pathogenic bacteria in the gut microbiota of infants at risk of developing celiac disease: The PROFICEL study. Gut Microbes 2018; 9:551-558. [PMID: 29672211 PMCID: PMC6287676 DOI: 10.1080/19490976.2018.1451276] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
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.
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Affiliation(s)
- Marta Olivares
- Microbial Ecology, Nutrition & Health Research Unit. Institute of Agrochemistry and Food Technology, Spanish National Research Council (IATA-CSIC), Valencia, Spain,CONTACT Marta Olivares IATA-CSIC, C/Catedrático Agustín Escardino, 7. 46980, Paterna, Valencia, Spain
| | - Alfonso Benítez-Páez
- Microbial Ecology, Nutrition & Health Research Unit. Institute of Agrochemistry and Food Technology, Spanish National Research Council (IATA-CSIC), Valencia, Spain
| | - Giada de Palma
- Microbial Ecology, Nutrition & Health Research Unit. Institute of Agrochemistry and Food Technology, Spanish National Research Council (IATA-CSIC), Valencia, Spain
| | - Amalia Capilla
- Genetics and Molecular Medicine Unit. Institute of Biomedicine of Valencia, Spanish National Research Council (IBV-CSIC), Valencia, Spain
| | - Esther Nova
- Institute of Food Science, Technology and Nutrition, Spanish National Research Council (ICTAN-CSIC), Madrid, Spain
| | - Gemma Castillejo
- Universitary Hospital Sant Joan of Reus, URV, IISPV, Tarragona, Spain
| | - Vicente Varea
- Gastroenterología, Nutrición y Hepatología Pediátrica, Hospital Universitario Sant Joan de Deu, and Instituto de Gastroeneterología y Nutrición Pediátrica de Barcelona, Barcelona, Spain
| | - Ascensión Marcos
- Institute of Food Science, Technology and Nutrition, Spanish National Research Council (ICTAN-CSIC), Madrid, Spain
| | - José Antonio Garrote
- Research Unit and Paediatric Service, Hospital Clínico Universitario, Valladolid, Spain
| | - Isabel Polanco
- Servicio de Gastroenterología y Nutrición Pediátrica, Hospital Universitario La Paz, Madrid, Spain
| | - Ester Donat
- Unidad de Gastroenterología, Hospital Infantil Universitario La Fe, Valencia, Spain
| | | | - Carmen Calvo
- Research Unit and Paediatric Service, Hospital Clínico Universitario, Valladolid, Spain
| | - Luis Ortigosa
- Unidad de Gastroenterologia, Hepatología y Nutrición Pediátrica, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Canary Islands, Spain
| | - Francesc Palau
- Genetics and Molecular Medicine Unit. Institute of Biomedicine of Valencia, Spanish National Research Council (IBV-CSIC), Valencia, Spain
| | - Yolanda Sanz
- Microbial Ecology, Nutrition & Health Research Unit. Institute of Agrochemistry and Food Technology, Spanish National Research Council (IATA-CSIC), Valencia, Spain,Yolanda Sanz IATA-CSIC, C/Catedrático Agustín Escardino, 7. 46980, Paterna, Valencia, Spain
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18
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Girbovan A, Sur G, Samasca G, Lupan I. Is the evidence of breast feeding protection against coeliac disease real? Allergol Immunopathol (Madr) 2017; 45:616-618. [PMID: 28410871 DOI: 10.1016/j.aller.2017.01.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2016] [Accepted: 01/24/2017] [Indexed: 10/19/2022]
Abstract
Many recent studies discredit breastfeeding protection against coeliac disease. We will try to answer the question: "Is the evidence of breast feeding protection against coeliac disease real?"
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Abstract
The incidence of celiac disease (CD) has increased over the last half-century, resulting in rising interest in identifying risk factors for CD. The necessity of duodenal biopsies in the diagnosis of CD has recently been challenged. Areas covered: This review covers the recent literature regarding the role of infant feeding practices, including breastfeeding and timing of gluten introduction, and the microbiota in the development of CD. Additionally, the application of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for a non-biopsy approach to the diagnosis of CD is reviewed. Expert commentary: Recent investigations have not revealed any significant effect of breastfeeding or timing of gluten introduction on the risk of CD in at-risk populations. There are alterations in the microbiota of CD patients. However, the role of the microbiome and whether its manipulation has a clinical effect are unknown. Preliminary data suggests a non-biopsy approach to diagnosis of pediatric CD can be applied to several populations, although additional studies are needed. Prospective investigations are underway to examine the interplay of infant feeding practices and the microbiome and to identify particular CD-specific biomarkers that may aid in the diagnosis and ultimately prevention of CD.
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Affiliation(s)
- Grace J Lee
- a Division of Pediatric Gastroenterology, Department of Pediatrics and Communicable Diseases , C.S. Mott Children's Hospital, University of Michigan , Ann Arbor , MI , USA
| | - John Y Kao
- b Division of Gastroenterology, Department of Internal Medicine , University of Michigan , Ann Arbor , MI , USA
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Crespo-Escobar P, Mearin ML, Hervás D, Auricchio R, Castillejo G, Gyimesi J, Martinez-Ojinaga E, Werkstetter K, Vriezinga SL, Korponay-Szabo IR, Polanco I, Troncone R, Stoopman E, Kolaček S, Shamir R, Szajewska H, Koletzko S, Ribes-Koninckx C. The role of gluten consumption at an early age in celiac disease development: a further analysis of the prospective PreventCD cohort study. Am J Clin Nutr 2017; 105:890-896. [PMID: 28228423 DOI: 10.3945/ajcn.116.144352] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2016] [Accepted: 01/23/2017] [Indexed: 12/16/2022] Open
Abstract
Background: We previously found that the introduction of small quantities of gluten at 4-6 mo of age did not reduce the risk of celiac disease (CD) in a group of high-risk children. However, the consumption of high amounts of gluten early in life has been suggested to increase CD risk.Objective: The aim of this study was to evaluate this hypothesis by using data from the previous study of the PreventCD trial (www.preventcd.com).Design: Gluten intake was prospectively quantified by using specific food records between 11 and 36 mo of age in 715 children positive for the human leukocyte antigen (HLA)-DQ2 and/or HLA-DQ8 from 5 European countries. According to the PreventCD protocol, infants received 100 mg immunologically active gluten/d or placebo from 4 to 6 mo of age, with a stepwise and fixed gluten increase until age 10 mo and unrestricted intake thereafter. The primary outcome of the present study was the impact of the amount of gluten consumed from age 10 mo onward on CD development.Results: Mean daily gluten intakes from 10 mo onward were significantly different between countries for children at all ages (P < 0.001) but not between children who developed CD and those who did not within the same country (P > 0.05). The variables country, sex, intervention group, and gluten consumption pattern did not show significant associations with CD development risk (HRs not significant). In addition, the interaction between HLA risk group and gluten consumption pattern showed no significant risk on CD development, except for the DQ2.2/DQ7 haplotype (HR: 5.81; 95% CI: 1.18, 28.74; P = 0.031).Conclusions: Gluten consumption patterns as well as the amount of gluten consumed at 11-36 mo of age do not influence CD development for most related HLA genotypes in children with a genetic risk. This study reports the gluten consumption pattern in children at risk of CD from different European countries. This trial was registered at www.controlled-trials.com as ISRCTN74582487.
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Affiliation(s)
| | | | - David Hervás
- Biostatistics, Medical Research Institute La Fe, Valencia, Spain
| | - Renata Auricchio
- Department of Medical Translational Sciences and European Laboratory for the Investigation of Food-Induced Diseases, University Federico II, Naples, Italy
| | - Gemma Castillejo
- Department of Pediatrics, Hospital Universitari Sant Joan, Reus/Universitat Rovira i Virgili, Tarragona, Spain
| | - Judit Gyimesi
- Celiac Disease Center, Heim Pál Children's Hospital, Budapest, Hungary
| | - Eva Martinez-Ojinaga
- Department of Pediatric Gastroenterology and Nutrition, La Paz University Hospital, Madrid, Spain
| | - Katharina Werkstetter
- Department of Pediatric Gastroenterology and Hepatology, Dr. von Hauner Children's Hospital, Ludwig Maximilians University, Munich, Germany
| | | | | | - Isabel Polanco
- Department of Pediatric Gastroenterology and Nutrition, La Paz University Hospital, Madrid, Spain
| | - Riccardo Troncone
- Department of Medical Translational Sciences and European Laboratory for the Investigation of Food-Induced Diseases, University Federico II, Naples, Italy
| | - Els Stoopman
- Medical Statistics, Leiden University Medical Center, Leiden, Netherlands
| | - Sanja Kolaček
- Referral Center for Pediatric Gastroenterology and Nutrition, University Children's Hospital Zagreb, Zagreb, Croatia
| | - Raanan Shamir
- Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Hania Szajewska
- Department of Pediatrics, Medical University of Warsaw, Warsaw, Poland; and
| | - Sibylle Koletzko
- Department of Pediatric Gastroenterology and Hepatology, Dr. von Hauner Children's Hospital, Ludwig Maximilians University, Munich, Germany
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Venter C, Maslin K, Dean T, Arshad SH. Does concurrent breastfeeding alongside the introduction of solid food prevent the development of food allergy? J Nutr Sci 2016; 5:e40. [PMID: 27752307 PMCID: PMC5048184 DOI: 10.1017/jns.2016.31] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2016] [Revised: 06/21/2016] [Accepted: 07/20/2016] [Indexed: 11/21/2022] Open
Abstract
The timing of introduction of solid food on the subsequent development of food allergy is under debate and the role of concurrent breastfeeding is unclear. The aim of the present study was to investigate the role of solid food introduction whilst concurrently breastfeeding on food allergy outcome, with a specific focus on cows' milk allergy. Prospectively collected infant feeding data from a birth cohort were analysed. Participants with histories suggestive of food allergy underwent diagnostic food challenges. Children with food allergy were matched to control participants for age and sex. Mann-Whitney U tests, χ2, Fisher exact tests and logistic regression calculations were undertaken. A total of thirty-nine food-allergic children and seventy-eight matched controls were identified, including twenty-two cows' milk-allergic children and forty-four matched controls. The control group introduced solid food earlier than the food-allergic group (P < 0·05). There was no effect of concurrent breastfeeding alongside cows' milk introduction or other food allergens on the development of food allergy. Due to small numbers, it was not possible to explore differences for food allergy phenotype. We have therefore found no evidence that introducing solids, or food allergens, whilst breastfeeding has an allergy-preventative effect; however, the results should be interpreted with caution due to sample size. Recommendations regarding infant feeding and food allergy should be carefully considered. Although breastfeeding should be promoted for many health reasons, larger studies looking at the introduction of food allergens on the development of food allergy are needed to make a final conclusion.
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Affiliation(s)
- Carina Venter
- School of Health Sciences and Social Work, University of Portsmouth, Portsmouth, UK
- David Hide Asthma and Allergy Research Centre, Newport, Isle of Wight, UK
| | - Kate Maslin
- School of Health Sciences and Social Work, University of Portsmouth, Portsmouth, UK
- David Hide Asthma and Allergy Research Centre, Newport, Isle of Wight, UK
| | - Taraneh Dean
- School of Health Sciences and Social Work, University of Portsmouth, Portsmouth, UK
- David Hide Asthma and Allergy Research Centre, Newport, Isle of Wight, UK
| | - Syed Hasan Arshad
- David Hide Asthma and Allergy Research Centre, Newport, Isle of Wight, UK
- Clinical and Experimental Sciences, University of Southampton, Southampton, UK
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Boudet-Berquier J, Salanave B, de Launay C, Castetbon K. Introduction of complementary foods with respect to French guidelines: description and associated socio-economic factors in a nationwide birth cohort (Epifane survey). MATERNAL AND CHILD NUTRITION 2016; 13. [PMID: 27430649 DOI: 10.1111/mcn.12339] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/08/2015] [Revised: 04/15/2016] [Accepted: 04/19/2016] [Indexed: 01/16/2023]
Abstract
We described the introduction of complementary food (ICF) during the first year of life and identify associations observed with maternal and infant characteristics. We studied 3368 children included in the Epifane cohort, France, 2012. Maternal and infant characteristics and age at introduction of 28 complementary foods were collected at birth and at 1, 4, 8 and 12 months. Kaplan-Meier plots were used to represent probabilities of ICF. A score was used as tertiles in multinomial logistic regression to identify maternal and infant factors associated with ICF agreement with French recommendations. Median age of ICF was 152 days. While 12.6% of infants received complementary food before the age of 4 months, 95% of them were introduced after 7 months. Recommendations were generally followed, except for eggs and added fats, introduced in only 23.2% and 53.1% of 1-year-old infants, respectively. Factors significantly associated with the first ICF score tertile (low agreement with recommendations) vs. third tertile were as follows: maternal age 18-24 years (OR = 2.24 [1.49-3.35]) or 25-29 years (OR = 1.57 [1.21-2.04]), education less than or equal to high school graduation (OR = 1.94[1.51-2.48]), birthplace in France (OR = 2.13 [1.41-3.21]), three or more children (OR = 1.70 [1.15-2.51]), no follow-up antenatal classes (OR = 1.58 [1.22-2.04]), unemployment before and after pregnancy (OR = 1.64 [1.04-2.59]), unemployment before pregnancy and return to work within 12 months (OR = 2.06 [1.05-4.02]), no breastfeeding (OR = 2.08 [1.55-2.79]) or lasting <28 days (OR = 1.68 [1.22-2.31]) or 1-4 months (OR = 1.45 [1.08-1.96]). Recommendations concerning complementary food were generally followed. However, guidelines should be clarified and adapted to families who have difficulties in adopting them.
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Affiliation(s)
- Julie Boudet-Berquier
- Unité de Surveillance Périnatale et Nutritionnelle (USPEN), Institut de Veille Sanitaire, Université Paris 13, Centre de Recherche en Epidémiologie et Statistiques, COMUE Sorbonne Paris Cité, F-93017, Bobigny, France
| | - Benoit Salanave
- Unité de Surveillance Périnatale et Nutritionnelle (USPEN), Institut de Veille Sanitaire, Université Paris 13, Centre de Recherche en Epidémiologie et Statistiques, COMUE Sorbonne Paris Cité, F-93017, Bobigny, France
| | - Catherine de Launay
- Unité de Surveillance Périnatale et Nutritionnelle (USPEN), Institut de Veille Sanitaire, Université Paris 13, Centre de Recherche en Epidémiologie et Statistiques, COMUE Sorbonne Paris Cité, F-93017, Bobigny, France
| | - Katia Castetbon
- Unité de Surveillance Périnatale et Nutritionnelle (USPEN), Institut de Veille Sanitaire, Université Paris 13, Centre de Recherche en Epidémiologie et Statistiques, COMUE Sorbonne Paris Cité, F-93017, Bobigny, France
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Abstract
OBJECTIVE To review the evidence for the association of breast feeding, breastfeeding duration or the timing of gluten introduction and the later development of celiac disease (CD). DESIGN Systematic review. METHODS We searched MEDLINE, via PubMed, EMBASE and Web of Science, for studies published up to 31 August 2015 investigating the association of breastfeeding duration, breast feeding at the moment of gluten introduction or the timing of gluten introduction and the later development of CD. Prospective studies had to enrol infants/children at high risk of CD. For retrospective studies, participants had to be children or adults with CD. The paper quality was assessed by means of a GRADE score and the bias risk was assessed by the Newcastle-Ottawa Scale (for observational cohort studies) and Cochrane Collaboration's tool (for randomised trials). RESULTS Out of 149 retrieved papers, 48 were considered in depth and 16 were included in this review (9 were prospective and 2 were interventional). We found that neither duration of breastfeeding nor breastfeeding at time of gluten introduction nor the delayed introduction of gluten during weaning were effective in preventing later development of CD. CONCLUSIONS Currently, there is no evidence on the optimal breastfeeding duration or the effects of avoiding early (<4 months of age) or late (≥ 6 or even at 12 months) gluten introduction in children at risk of CD. Accordingly, no specific general recommendations about gluten introduction or optimal breastfeeding duration can be presently provided on evidence-based criteria in order to prevent CD.
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Affiliation(s)
- Marco Silano
- Unit of Human Nutrition and Health, Istituto Superiore di Sanità, Roma, Italy
| | - Carlo Agostoni
- Pediatric Clinic, Department of Clinical Sciences and Community Health, University of Milan, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - Yolanda Sanz
- Department of Microbial Ecology, Nutrition & Health Research Group, Institute of Agrochemistry and Food Technology, National Research Council (IATA-CSIC), Valencia, Spain
| | - Stefano Guandalini
- Section of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Chicago, Chicago, Illinois, USA
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Pinto-Sánchez MI, Verdu EF, Liu E, Bercik P, Green PH, Murray JA, Guandalini S, Moayyedi P. Gluten Introduction to Infant Feeding and Risk of Celiac Disease: Systematic Review and Meta-Analysis. J Pediatr 2016; 168:132-143.e3. [PMID: 26500108 DOI: 10.1016/j.jpeds.2015.09.032] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2015] [Revised: 07/30/2015] [Accepted: 09/09/2015] [Indexed: 10/22/2022]
Abstract
OBJECTIVE To assess the evidence regarding the effect of time of gluten introduction and breastfeeding on the risk of developing celiac disease (CD). STUDY DESIGN We included randomized controlled trials and observational studies evaluating the proper timing for introducing gluten to the infant diet, the appropriate quantity of gluten consumption at weaning, and the effect of breastfeeding on CD risk. Studies were located through the electronic databases Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), EMBASE (Ovid), and System for Information on Grey Literature in Europe (SIGLE). Two independent authors collected the data. RESULTS A total of 1982 studies were identified, 15 of which were eligible for data extraction. A meta-analysis was performed on 2 randomized controlled trials, 10 cohort studies, and 1 case-control study. There was a 25% increase in CD risk with late (>6 months) vs recommended (4-6 months) gluten introduction (risk ratio [RR], 1.25; 95% CI, 1.08-1.45). There was no significant effect of breastfeeding vs no breastfeeding on CD risk (OR, 0.55; 95% CI, 0.28-1.10), with substantial heterogeneity (I(2) = 92%) among studies. CONCLUSION There is currently no evidence to support that early introduction of gluten to the infant diet increases the risk of CD; however, late introduction of gluten may be associated with increased risk of CD. More studies are needed that control for potential confounders and that evaluate environmental factors in low-risk families.
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Affiliation(s)
- María Inés Pinto-Sánchez
- Department of Medicine, Farncombe Family Digestive Research Institute, McMaster University, Hamilton, Ontario, Canada.
| | - Elena F Verdu
- Department of Medicine, Farncombe Family Digestive Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Edwin Liu
- Colorado Center for Celiac Disease, Children's Hospital Colorado, Aurora, CO
| | - Premysl Bercik
- Department of Medicine, Farncombe Family Digestive Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Peter H Green
- Celiac Disease Center at Columbia University, New York, NY
| | - Joseph A Murray
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Stefano Guandalini
- Department of Pediatrics, Section of Gastroenterology, Hepatology and Nutrition, University of Chicago, Chicago, IL
| | - Paul Moayyedi
- Department of Medicine, Farncombe Family Digestive Research Institute, McMaster University, Hamilton, Ontario, Canada
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Abstract
This commentary by the leadership of the North American Society for the Study of Celiac Disease (NASSCD) concerns recent research findings regarding infant feeding practices. Celiac disease has increased markedly in recent decades, and seroprevalence studies indicate that this is a true rise, rather than one due to increased awareness and testing. Prior studies have suggested that infant feeding practices and timing of initial gluten exposure are central to the development of celiac disease. Two recent multicenter randomized trials tested strategies of early or delayed gluten introduction in infants, and neither strategy appeared to influence celiac disease risk. These studies also found that breastfeeding did not protect against the development of celiac disease. While disappointing, these results should spur the study of wider environmental risk factors beyond infant feeding, such as intrauterine and perinatal exposures as well as environmental influences later in life, including drug exposure, microbial infections, and the microbiome. Given that celiac disease can develop at any age, it is imperative to study these proposed triggers so as to elucidate the loss of tolerance to gluten and to develop future intervention strategies.
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26
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Pohl CS, Medland JE, Moeser AJ. Early-life stress origins of gastrointestinal disease: animal models, intestinal pathophysiology, and translational implications. Am J Physiol Gastrointest Liver Physiol 2015; 309:G927-41. [PMID: 26451004 PMCID: PMC4683303 DOI: 10.1152/ajpgi.00206.2015] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2015] [Accepted: 10/01/2015] [Indexed: 01/31/2023]
Abstract
Early-life stress and adversity are major risk factors in the onset and severity of gastrointestinal (GI) disease in humans later in life. The mechanisms by which early-life stress leads to increased GI disease susceptibility in adult life remain poorly understood. Animal models of early-life stress have provided a foundation from which to gain a more fundamental understanding of this important GI disease paradigm. This review focuses on animal models of early-life stress-induced GI disease, with a specific emphasis on translational aspects of each model to specific human GI disease states. Early postnatal development of major GI systems and the consequences of stress on their development are discussed in detail. Relevant translational differences between species and models are highlighted.
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Affiliation(s)
- Calvin S. Pohl
- 1Department of Large Animal Clinical Sciences, Michigan State University, East Lansing, Michigan; ,2Gastrointestinal Stress Biology Laboratory, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan; and
| | - Julia E. Medland
- 3Comparative Biomedical Sciences Program, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina
| | - Adam J. Moeser
- 1Department of Large Animal Clinical Sciences, Michigan State University, East Lansing, Michigan; ,2Gastrointestinal Stress Biology Laboratory, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan; and
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Silvester JA, Leffler DA. Recent Advances in Celiac Disease from TTG to Gluten in Pee. Clin Transl Gastroenterol 2015; 6:e125. [PMID: 26561989 PMCID: PMC4817408 DOI: 10.1038/ctg.2015.53] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Affiliation(s)
- J A Silvester
- Celiac Research Program, Harvard Medical School, Boston, Massachusetts, USA
- Celiac Center, Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Hospital, Boston, Massachusetts, USA
- Boston Children's Hospital, Boston, Massachusetts, USA
- Department of Paediatrics, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Daniel A Leffler
- Celiac Research Program, Harvard Medical School, Boston, Massachusetts, USA
- Celiac Center, Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Hospital, Boston, Massachusetts, USA
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The Role of Environmental Factors in the Development of Celiac Disease: What Is New? Diseases 2015; 3:282-293. [PMID: 28943625 PMCID: PMC5548256 DOI: 10.3390/diseases3040282] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2015] [Revised: 10/02/2015] [Accepted: 10/20/2015] [Indexed: 01/08/2023] Open
Abstract
Celiac disease (CD) is a systemic immune-mediated disorder caused by the ingestion of gluten-containing grains in genetically susceptible persons. It is one of the most common lifelong disorders, affecting approximately 1% of the general population. The prevalence of CD has increased in developed countries over recent decades, pointing to the role of additional environmental triggers other than gluten. It has been hypothesized that intestinal infections, the amount and quality of gluten, the intestinal microbiota, and early nutrition are all possible triggers of the switch from tolerance to an immune response to gluten. Two recent randomized controlled trials have been performed to clarify the relationship between the age at which gluten is introduced to a child’s diet and the risk of CD, showing that timing of gluten introduction does not modify the risk of CD. Both trials also showed that breastfeeding compared with no breastfeeding or breastfeeding duration or breastfeeding during gluten introduction have no effect on the risk of CD. The two trials, although not designed to address this issue, have shown that intestinal infections seem not to influence the risk of CD. Further studies are still needed to explore the missing environmental factors of CD for future prevention.
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30
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Diamanti A, Capriati T, Bizzarri C, Ferretti F, Ancinelli M, Romano F, Perilli A, Laureti F, Locatelli M. Autoimmune diseases and celiac disease which came first: genotype or gluten? Expert Rev Clin Immunol 2015; 12:67-77. [DOI: 10.1586/1744666x.2016.1095091] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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Frederiksen BN, Seifert J, Kroehl M, Lamb MM, Milne GL, Rewers M, Norris JM. Timing of solid food introduction is associated with urinary F2-isoprostane concentrations in childhood. Pediatr Res 2015; 78:451-6. [PMID: 26083762 PMCID: PMC4589419 DOI: 10.1038/pr.2015.116] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2014] [Accepted: 03/12/2015] [Indexed: 11/22/2022]
Abstract
BACKGROUND Timing of solid food introduction in infancy has been associated with several chronic diseases. To explore potential mechanisms, we investigated the relationship between timing of solid food introduction and F2-isoprostanes-a marker of oxidative stress. METHODS Urinary F2-isoprostanes were assessed in 336 healthy children aged less than 11.5 y with 1,266 clinic visits (mean = 3.8 visits per child) in the Diabetes Autoimmunity Study in the Young. We analyzed the association between F2-isoprostane concentrations and infant diet exposures using linear mixed models adjusted for age, age(2), HLA-DR3/4,DQB1*0302 genotype, first-degree relative with type 1 diabetes, maternal age, maternal education, sex, and exposure to in utero cigarette smoke. RESULTS Later solid food introduction was associated with lower F2-isoprostane concentrations in childhood (on average, 0.10 ng/mg per month of age at introduction; estimate: -0.10 (95% confidence interval (CI): -0.18, -0.02) P value = 0.02). Moreover, childhood F2-isoprostane concentrations were, on average, 0.24 ng/mg lower in individuals breastfed at solid food introduction (estimate: -0.24 (95% CI: -0.47, -0.01) P value = 0.04) compared with those who were not. Associations remained significant after limiting analyses to F2-isoprostanes after 2 y of age. CONCLUSION Our results suggest a long-term protective effect of later solid food introduction and breastfeeding at solid food introduction against increased F2-isoprostane concentrations throughout childhood.
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Affiliation(s)
- Brittni N. Frederiksen
- Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, CO, USA
| | - Jennifer Seifert
- Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, CO, USA
| | - Miranda Kroehl
- Department of Biostatistics & Informatics, Colorado School of Public Health, University of Colorado Denver, Aurora, CO, USA
| | - Molly M. Lamb
- Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, CO, USA
| | - Ginger L. Milne
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | | | - Jill M. Norris
- Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, CO, USA,Address correspondence to: Jill M. Norris, MPH, PhD, 13001 E. 17th Pl., Box B119, Aurora CO, 80045, , Telephone: 303-724-4428, Fax: 303-724-4489
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Freeman HJ. Celiac disease: a disorder emerging from antiquity, its evolving classification and risk, and potential new treatment paradigms. Gut Liver 2015; 9:28-37. [PMID: 25547088 PMCID: PMC4282854 DOI: 10.5009/gnl14288] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Celiac disease is a chronic genetically based gluten-sensitive immune-mediated enteropathic process primarily affecting the small intestinal mucosa. The disorder classically presents with diarrhea and weight loss; however, more recently, it has been characterized by subclinical occult or latent disease associated with few or no intestinal symptoms. Diagnosis depends on the detection of typical histopathological biopsy changes followed by a gluten-free diet response. A broad range of clinical disorders may mimic celiac disease, along with a wide range of drugs and other therapeutic agents. Recent and intriguing archeological data, largely from the Gobleki Tepe region of the Fertile Crescent, indicate that celiac disease probably emerged as humans transitioned from hunter-gatherer groups to societies dependent on agriculture to secure a stable food supply. Longitudinal studies performed over several decades have suggested that changes in the prevalence of the disease, even apparent epidemic disease, may be due to superimposed or novel environmental factors that may precipitate its appearance. Recent therapeutic approaches are being explored that may supplement, rather than replace, gluten-free diet therapy and permit more nutritional options for future management.
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Affiliation(s)
- Hugh J Freeman
- Department of Medicine, University of British Columbia, Vancouver, Canada
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33
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Mearin ML. The prevention of coeliac disease. Best Pract Res Clin Gastroenterol 2015; 29:493-501. [PMID: 26060113 DOI: 10.1016/j.bpg.2015.04.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2015] [Revised: 04/22/2015] [Accepted: 04/26/2015] [Indexed: 01/31/2023]
Abstract
Primary prevention of coeliac disease is currently not possible. Previously, a 'window of opportunity' was suggested for primary prevention, by introducing gluten between four and six months of age. However, results from recent prospective studies establish that the timing of gluten introduction and the duration or maintenance of breastfeeding do not influence the development of the disease. Secondary prevention is possible through early diagnosis and treatment. Since coeliac disease is severely underdiagnosed, the only way to achieve large-scale secondary prevention is by mass screening. Prospective studies indicate that important health problems, such as reduced foetal growth and birth weight, delayed growth in height and weight in children, and reduced bone mineral density in both children and adults can be prevented by mass screening. Adherence to a strict gluten-free diet may be considered as tertiary prevention.
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Affiliation(s)
- M Luisa Mearin
- Dept. of Paediatrics, Leiden University Medical Center, Leiden, The Netherlands.
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34
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Szajewska H, Shamir R, Chmielewska A, Pieścik-Lech M, Auricchio R, Ivarsson A, Kolacek S, Koletzko S, Korponay-Szabo I, Mearin ML, Ribes-Koninckx C, Troncone R. Systematic review with meta-analysis: early infant feeding and coeliac disease--update 2015. Aliment Pharmacol Ther 2015; 41:1038-54. [PMID: 25819114 DOI: 10.1111/apt.13163] [Citation(s) in RCA: 81] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2015] [Revised: 02/14/2015] [Accepted: 02/27/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND New evidence emerged on early feeding practices and the risk of coeliac disease. AIM To systematically update evidence on these practices to find out whether there is a need to revise current recommendations. METHODS MEDLINE, EMBASE and the Cochrane Library were searched from July 2012 (end of last search) to February 2015 for studies of any design that assessed the effect of gluten consumption and breastfeeding on the development of coeliac disease and/or coeliac disease-related autoimmunity. RESULTS We identified 21 publications, including two, new, large, randomised controlled trials performed in high-risk infants. Exclusive or any breastfeeding, as well as breastfeeding at the time of gluten introduction, did not reduce the risk of developing coeliac disease during childhood. For infants at high risk of developing coeliac disease, gluten introduction at 4 months of age in very small amounts, or at 6 or 12 months of age, resulted in similar rates of coeliac disease diagnosis in early childhood. Later gluten introduction was associated with later development of coeliac specific autoimmunity and coeliac disease during childhood, but not total risk reduction. Observational studies indicate that consumption of a higher amount of gluten at weaning may increase the risk for coeliac disease development. CONCLUSIONS Infant feeding practices (breastfeeding, time of gluten introduction) have no effect on the risk of developing coeliac disease during childhood (at least at specific timeframes evaluated in the included studies), necessitating an update of current European recommendations.
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Affiliation(s)
- H Szajewska
- The Medical University of Warsaw, Warsaw, Poland
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[The introduction of gluten into the infant diet. Expert group recommendations]. An Pediatr (Barc) 2015; 83:355.e1-7. [PMID: 25913122 DOI: 10.1016/j.anpedi.2015.03.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2015] [Accepted: 03/10/2015] [Indexed: 11/21/2022] Open
Abstract
At present there is a degree of uncertainty regarding when, how and in what form gluten should be introduced into the infant diet. For years the recommendations of the ESPGHAN Committee on Nutrition have prevailed, which include avoiding early introduction, before 4 months, and late, after 7 months, and gradually introducing gluten into the diet while the infant is being breastfed, with the aim of reducing the risk of celiac disease, diabetes and gluten allergy. However, 2 independent studies published in The New England Journal of Medicine in October 2014 reached the conclusion that the age of introduction of gluten does not modify the risk of developing celiac disease, and that breastfeeding at any age does not confer protection against celiac disease development. On the other hand, according to available scientific evidence, the introduction of foods other than breast milk or formula into the infants diet is generally recommended around 6 months of age, since the introduction before 4 months could be associated with an increased risk of food allergy and autoimmune diseases, and delaying it beyond 7 months would not have a protective effect. In this context, a group of experts has considered it appropriate to produce a consensus document based on the current scientific evidence and present general recommendations for daily clinical practice on the introduction of gluten into the diet.
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Alvisi P, Brusa S, Alboresi S, Amarri S, Bottau P, Cavagni G, Corradini B, Landi L, Loroni L, Marani M, Osti IM, Povesi-Dascola C, Caffarelli C, Valeriani L, Agostoni C. Recommendations on complementary feeding for healthy, full-term infants. Ital J Pediatr 2015; 41:36. [PMID: 25928205 PMCID: PMC4464122 DOI: 10.1186/s13052-015-0143-5] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2014] [Accepted: 04/23/2015] [Indexed: 01/24/2023] Open
Abstract
Weaning (or introduction of complementary feeding) is a special and important moment in the growth of a child, both for the family and the infant itself, and it can play a major role in the child’s future health. Throughout the years, various weaning modes have come in succession, the latest being baby-led weaning; the timing for introducing foods and the requirements of which sort of nutrient for weaning have also changed over time. Furthermore, the role played by nutrition, especially in the early stages of life, for the onset of later non-communicable disorders, such as diabetes, obesity or coeliac disease has also been increasingly highlighted. Members of Italian Society of Gastroenterology, Hepathology and Pediatric Nutrition (SIGENP) and the Italian Society of Allergology and Pediatric Immunology (SIAIP) Emilia Romagna here propose a practical approach for pediatricians to deal with daily practice. The four main areas for discussion were weaning in relation with the onset of allergic diseases, coeliac disease, diabetes and metabolic syndrome, the nutrition requirements to take into account for assessing the diet of infants under one year of age and about the practice of baby-led weaning focusing on limits and benefits, respectively.
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Affiliation(s)
- Patrizia Alvisi
- Department of Paediatrics, Ospedale Maggiore, Azienda USL, Bologna, Italy.
| | - Sandra Brusa
- Department of Paediatrics and Neonatology, Ospedale di Imola, Azienda USL, Imola, Italy.
| | | | - Sergio Amarri
- Department of Paediatrics, Arcispedale S. Maria Nuova, Azienda USL-IRCCS, Reggio Emilia, Italy.
| | - Paolo Bottau
- Department of Paediatrics and Neonatology, Ospedale di Imola, Azienda USL, Imola, Italy.
| | - Giovanni Cavagni
- Coordinator European Allergology Center - European Diagnostic Center Dalla Rosa Prati, Parma, Italy.
| | - Barbara Corradini
- Department of Dietetics and Clinical Nutrition, Ospedale Maggiore-Bellaria, Azienda USL, Bologna, Italy.
| | - Linda Landi
- Department of Paediatrics and Neonatology, Ospedale di Imola, Azienda USL, Imola, Italy.
| | - Leonardo Loroni
- Paediatrician, Ospedale privato Accreditato S. Francesco, Ravenna, Italy.
| | | | - Irene M Osti
- Department of Paediatrics and Neonatology, Ospedale di Imola, Azienda USL, Imola, Italy.
| | - Carlotta Povesi-Dascola
- Clinica Pediatrica, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy.
| | - Carlo Caffarelli
- Clinica Pediatrica, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy.
| | - Luca Valeriani
- Department of Dietetics and Clinical Nutrition, Ospedale Maggiore-Bellaria, Azienda USL, Bologna, Italy.
| | - Carlo Agostoni
- Department of Clinical and Community Sciences, University of Milano, IRCCS Fondazione Cà Granda, Ospedale Maggiore Policlinico, Milano, Italy.
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Mearin ML. Celiac disease: prevention in children. Dig Dis 2015; 33:162-166. [PMID: 25925918 DOI: 10.1159/000369539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Several studies have suggested a protective role of breastfeeding and/or the timing and quantity of gluten introduction in the subsequent development of celiac disease. Especially, prolonged breastfeeding during the introduction of gluten-containing feeding has been associated with a reduced risk of developing celiac disease in infancy. The mentioned results suggest the existence of a 'window of opportunity' between 4 and 6 months of age in which gluten can be introduced in small amounts. Therefore, the European Society for Pediatric Gastroenterology Hepatology and Nutrition recommends avoiding gluten introduction before the age of 4 months and after the age of 7 months and that gluten should be preferably introduced during ongoing breastfeeding. However, the influence of breastfeeding in the development of celiac disease is not clear, since some studies report prevention and others do not, and the studies reporting a protective effect of breastfeeding do not make clear if it concerns prevention of the disease or delays the onset of symptoms. In addition, most of the studies on this topic have been observational and retrospective. For these reasons, prospective studies are needed to understand the relationship between early nutrition in particular and environmental factors in general, concerning the development and possible prevention of celiac disease. Some of these studies are ongoing. One example is the European multicenter PreventCD project (www.preventcoeliacdisease.com) among infants with a first-degree family member with celiac disease carrying HLA-DQ2 and/or -DQ8, randomized to a double-blind dietary intervention with 100 mg of gluten daily or placebo between the age of 4-6 months. All included children are already 3 years old, and the first analyses are being prepared (http://www.trialregister.nl).
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Affiliation(s)
- M Luisa Mearin
- Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands
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Abstract
PURPOSE OF REVIEW Although many studies of the microbiota have been specific to the colonic or faecal microbiota, several studies are relevant to or directly address the small bowel microbiota in health and disease. A selection of recent landmark findings is addressed here. RECENT FINDINGS The complexity of host-microbe interactions is confirmed by unfolding evidence for signalling networks including microbe-macrophage-neuronal communication and several examples of diet-microbe-host metabolic exchanges. The contribution of the microbiota to several disorders, including celiac disease and inflammatory bowel disease, is increasingly evident and the importance of drug-bug interactions has been clarified. SUMMARY Despite difficulty accessing the small bowel microbiota, there is growing evidence for its role in development, homeostasis and a diversity of diseases.
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Nadhem ON, Azeez G, Smalligan RD, Urban S. Review and practice guidelines for celiac disease in 2014. Postgrad Med 2015; 127:259-65. [PMID: 25702766 DOI: 10.1080/00325481.2015.1015926] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Celiac disease, or gluten-sensitive enteropathy, is defined as a state of heightened immunologic responsiveness to ingested gluten (from wheat, barley, or rye) in genetically susceptible individuals. Ingestion of the offending proteins leads to inflammation and intestinal mucosal damage, which may result in a spectrum of gastrointestinal symptoms, nutritional abnormalities, and systemic complications ranging from anemia and osteoporosis to secondary autoimmunity and malignancy. The genetic influence in the pathogenesis of celiac disease is indicated by its familial occurrence. Celiac disease does not develop unless a person has alleles that encode for human leukocyte antigen DQ2 or DQ8 proteins. The clinical picture of celiac disease has changed considerably during the past 30 years. Diarrhea, which was the presenting symptom in > 90% of celiac disease patients before 1981, is now the chief complaint in < 40%. In contrast, the increased frequency of atypical celiac disease presentations, including anemia and bone disease, is revealed by the widespread availability of serologic testing. An association between celiac disease and autoimmune disorders, such as type 1 diabetes, autoimmune thyroid disease, and Sjögren's syndrome, has been well documented. The tissue transglutaminase immunoglobulin antibody and the endomysial immunoglobulin antibody are the most sensitive and specific serologic tests, respectively, for identifying individuals who need to undergo an intestinal biopsy. If the suspicion of celiac disease is high, intestinal biopsy should be pursued even if serologic tests are negative. The gold standard for the diagnosis of celiac disease is a small bowel biopsy showing villous atrophy. The treatment for celiac disease is lifelong adherence to a gluten-free diet (GFD). Despite the proven benefits of the GFD, it can be exceedingly difficult to completely avoid gluten-containing foods, and adherence to a GFD is estimated to be only 45% to 80%.
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Affiliation(s)
- Omar N Nadhem
- Internal Medicine Department, Texas Tech University Health Sciences Center/Amarillo , Amarillo, TX , USA
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Aronsson CA, Lee HS, Liu E, Uusitalo U, Hummel S, Yang J, Hummel M, Rewers M, She JX, Simell O, Toppari J, Ziegler AG, Krischer J, Virtanen SM, Norris JM, Agardh D. Age at gluten introduction and risk of celiac disease. Pediatrics 2015; 135:239-45. [PMID: 25601977 PMCID: PMC4306795 DOI: 10.1542/peds.2014-1787] [Citation(s) in RCA: 93] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/29/2014] [Indexed: 12/27/2022] Open
Abstract
OBJECTIVES The goal of this study was to determine whether age at introduction to gluten was associated with risk for celiac disease (CD) in genetically predisposed children. METHODS TEDDY (The Environmental Determinants of Diabetes in the Young) is a prospective birth cohort study. Newborn infants (N = 6436) screened for high-risk HLA-genotypes for CD were followed up in Finland, Germany, Sweden, and the United States. Information about infant feeding was collected at clinical visits every third month. The first outcome was persistent positive for tissue transglutaminase autoantibodies (tTGA), the marker for CD. The second outcome was CD, defined as either a diagnosis based on intestinal biopsy results or on persistently high levels of tTGA. RESULTS Swedish children were introduced to gluten earlier (median: 21.7 weeks) compared with children from Finland (median: 26.1 weeks), Germany, and the United States (both median: 30.4 weeks) (P < .0001). During a median follow-up of 5.0 years (range: 1.7-8.8 years), 773 (12%) children developed tTGA and 307 (5%) developed CD. Swedish children were at increased risk for tTGA (hazard ratio: 1.74 [95% CI: 1.47-2.06]) and CD (hazard ratio: 1.76 [95% CI: 1.34-2.24]) compared with US children, respectively (P < .0001).Gluten introduction before 17 weeks or later than 26 weeks was not associated with increased risk for tTGA or CD, adjusted for country, HLA, gender, and family history of CD, neither in the overall analysis nor on a country-level comparison. CONCLUSIONS In TEDDY, the time to first introduction to gluten introduction was not an independent risk factor for developing CD.
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Affiliation(s)
| | - Hye-Seung Lee
- Pediatrics Epidemiology Center, Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, Florida
| | - Edwin Liu
- Digestive Health Institute, University of Colorado, Children's Hospital Colorado, Denver, Colorado
| | - Ulla Uusitalo
- Pediatrics Epidemiology Center, Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, Florida
| | - Sandra Hummel
- Institute of Diabetes Research, Helmholtz Zentrum München, and Klinikum rechts der Isar, Technische Universität München, and Forschergruppe Diabetes e.V., Neuherberg, Germany
| | - Jimin Yang
- Pediatrics Epidemiology Center, Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, Florida
| | - Michael Hummel
- Institute of Diabetes Research, Helmholtz Zentrum München, and Klinikum rechts der Isar, Technische Universität München, and Forschergruppe Diabetes e.V., Neuherberg, Germany
| | - Marian Rewers
- Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, Colorado
| | - Jin-Xiong She
- Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Georgia Regents University, Augusta, Georgia
| | - Olli Simell
- Department of Pediatrics, Turku University Hospital, Turku, Finland
| | - Jorma Toppari
- Department of Physiology and Pediatrics, University of Turku, Turku, Finland
| | - Anette-G Ziegler
- Institute of Diabetes Research, Helmholtz Zentrum München, and Klinikum rechts der Isar, Technische Universität München, and Forschergruppe Diabetes e.V., Neuherberg, Germany
| | - Jeffrey Krischer
- Pediatrics Epidemiology Center, Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, Florida
| | - Suvi M Virtanen
- National Institutes for Health and Welfare, Nutrition Unit, Helsinki, Finland; School of Health Sciences, University of Tampere, Tampere, Finland; Research Center for Child Health, Tampere University and University Hospital and the Science Center of Pirkanmaa Hospital District, Tampere, Finland; and
| | - Jill M Norris
- Department of Epidemiology, Colorado School of Public Health, University of Colorado, Denver, Aurora, Colorado
| | - Daniel Agardh
- Department of Clinical Sciences, Lund University, Malmö, Sweden
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Schuppan D, Zimmer KP. The diagnosis and treatment of celiac disease. DEUTSCHES ARZTEBLATT INTERNATIONAL 2015; 110:835-46. [PMID: 24355936 DOI: 10.3238/arztebl.2013.0835] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/02/2013] [Revised: 09/11/2013] [Accepted: 09/11/2013] [Indexed: 12/18/2022]
Abstract
BACKGROUND Celiac disease is an inflammatory disease of, the small intestine with a prevalence of roughly 0.5%-1%. Its symptoms arise in response to gluten consumption by genetically predisposed persons (HLA-DQ2/8). The autoantigen tissue transglutaminase (TG2) plays an important role in the pathogenesis of celiac disease. METHOD Selective review of pertinent literature, including guidelines from Germany and abroad. RESULTS Celiac disease can present at any age with gastrointestinal or extraintestinal manifestations (e.g., malabsorption or Duhring's dermatitis herpetiformis); it can also be found in association with other (auto-)immune diseases, such as type 1 diabetes. Most cases are oligosymptomatic. The wide differential diagnosis includes food intolerances, intestinal infections, and irritable bowel syndrome, among other conditions. The definitive diagnosis requires the demonstration of celiac disease-specific autoantibody to TG2 (endomysium), which is over 90% sensitive and far over 90% specific, and the characteristic histologic lesions of the small-bowel mucosa and remission on a gluten-free diet. CONCLUSION An understanding of celiac disease ought to inform everyday clinical practice in all medical disciplines, because this is a common condition with diverse manifestations that can be effectively diagnosed and easily treated for the prevention of both acute and long-term complications. Patients should follow a strictly gluten-free diet for life.
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Affiliation(s)
- Detlef Schuppan
- Institute of Translational Immunology, Johannes Gutenberg University, Mainz, and Division of Gastroenterology, Beth Israel deaconess Medical Center, Harvard Medical School, Boston, MA, USA, Center for Pediatric and Adolescent Medicine, Justus Liebig University, Gießen
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Lionetti E, Castellaneta S, Francavilla R, Pulvirenti A, Tonutti E, Amarri S, Barbato M, Barbera C, Barera G, Bellantoni A, Castellano E, Guariso G, Limongelli MG, Pellegrino S, Polloni C, Ughi C, Zuin G, Fasano A, Catassi C. Introduction of gluten, HLA status, and the risk of celiac disease in children. N Engl J Med 2014; 371:1295-1303. [PMID: 25271602 DOI: 10.1056/nejmoa1400697] [Citation(s) in RCA: 312] [Impact Index Per Article: 28.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND The relationship between the risk of celiac disease and both the age at which gluten is introduced to a child's diet and a child's early dietary pattern is unclear. METHODS We randomly assigned 832 newborns who had a first-degree relative with celiac disease to the introduction of dietary gluten at 6 months (group A) or 12 months (group B). The HLA genotype was determined at 15 months of age, and serologic screening for celiac disease was evaluated at 15, 24, and 36 months and at 5, 8, and 10 years. Patients with positive serologic findings underwent intestinal biopsies. The primary outcome was the prevalence of celiac disease autoimmunity and of overt celiac disease among the children at 5 years of age. RESULTS Of the 707 participants who remained in the trial at 36 months, 553 had a standard-risk or high-risk HLA genotype and completed the study. At 2 years of age, significantly higher proportions of children in group A than in group B had celiac disease autoimmunity (16% vs. 7%, P=0.002) and overt celiac disease (12% vs. 5%, P=0.01). At 5 years of age, the between-group differences were no longer significant for autoimmunity (21% in group A and 20% in group B, P=0.59) or overt disease (16% and 16%, P=0.78 by the log-rank test). At 10 years, the risk of celiac disease autoimmunity was far higher among children with high-risk HLA than among those with standard-risk HLA (38% vs. 19%, P=0.001), as was the risk of overt celiac disease (26% vs. 16%, P=0.05). Other variables, including breast-feeding, were not associated with the development of celiac disease. CONCLUSIONS Neither the delayed introduction of gluten nor breast-feeding modified the risk of celiac disease among at-risk infants, although the later introduction of gluten was associated with a delayed onset of disease. A high-risk HLA genotype was an important predictor of disease. (Funded by the Fondazione Celiachia of the Italian Society for Celiac Disease; CELIPREV ClinicalTrials.gov number, NCT00639444.).
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Affiliation(s)
- Elena Lionetti
- From the Departments of Pediatrics (E.L.) and Clinical and Molecular Biomedicine (A.P.), University of Catania, the Department of Pediatrics, San Paolo Hospital (S.C.), and the Department of Developmental Biomedicine, University of Bari (R.F.), Bari, the Department of Immunopathology and Allergology, Udine Hospital, Udine (E.T.), the Department of Pediatrics, Azienda Ospedaliera IRCCS Santa Maria Nuova Hospital, Reggio Emilia (S.A.), the Department of Pediatrics, Sapienza University of Rome, Rome (M.B.), the Department of Pediatrics, University of Turin, Turin (C.B.), the Department of Pediatrics, San Raffaele Hospital (G.B.), and the Department of Pediatrics, Vittore Buzzi Children's Hospital, Milan (G.Z.), the Department of Pediatrics, Bianchi Melacrino Morelli Hospital, Reggio Calabria (A.B.), Pediatric Gastroenterology Unit, Giannina Gaslini Institute, Genoa (E.C.), the Department of Pediatrics, University of Padua, Padua (G.G.), the Department of Pediatrics, Federico II University of Naples, Naples (M.G.L.), Pediatric Gastroenterology and Cystic Fibrosis Unit, University Hospital Gaetano Martino, Messina (S.P.), the Department of Pediatrics, Rovereto Hospital, Rovereto (Trento) (C.P.), the Department of Pediatrics, University of Pisa, Pisa (C.U.), and the Department of Pediatrics, Marche Polytechnic University, Ancona (C.C.) - all in Italy; and the Division of Pediatric Gastroenterology and Nutrition and Center for Celiac Research, MassGeneral Hospital for Children (A.F.), and the Celiac Program, Harvard Medical School (A.F., C.C.) - both in Boston
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Vriezinga SL, Auricchio R, Bravi E, Castillejo G, Chmielewska A, Crespo Escobar P, Kolaček S, Koletzko S, Korponay-Szabo IR, Mummert E, Polanco I, Putter H, Ribes-Koninckx C, Shamir R, Szajewska H, Werkstetter K, Greco L, Gyimesi J, Hartman C, Hogen Esch C, Hopman E, Ivarsson A, Koltai T, Koning F, Martinez-Ojinaga E, te Marvelde C, Pavic A, Romanos J, Stoopman E, Villanacci V, Wijmenga C, Troncone R, Mearin ML. Randomized feeding intervention in infants at high risk for celiac disease. N Engl J Med 2014; 371:1304-15. [PMID: 25271603 DOI: 10.1056/nejmoa1404172] [Citation(s) in RCA: 300] [Impact Index Per Article: 27.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
BACKGROUND A window of opportunity has been suggested for reducing the risk of celiac disease by introducing gluten to infants at 4 to 6 months of age. METHODS We performed a multicenter, randomized, double-blind, placebo-controlled dietary-intervention study involving 944 children who were positive for HLA-DQ2 or HLA-DQ8 and had at least one first-degree relative with celiac disease. From 16 to 24 weeks of age, 475 participants received 100 mg of immunologically active gluten daily, and 469 received placebo. Anti-transglutaminase type 2 and antigliadin antibodies were periodically measured. The primary outcome was the frequency of biopsy-confirmed celiac disease at 3 years of age. RESULTS Celiac disease was confirmed by means of biopsies in 77 children. To avoid underestimation of the frequency of celiac disease, 3 additional children who received a diagnosis of celiac disease according to the 2012 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition diagnostic criteria (without having undergone biopsies) were included in the analyses (80 children; median age, 2.8 years; 59% were girls). The cumulative incidence of celiac disease among patients 3 years of age was 5.2% (95% confidence interval [CI], 3.6 to 6.8), with similar rates in the gluten group and the placebo group (5.9% [95% CI, 3.7 to 8.1] and 4.5% [95% CI, 2.5 to 6.5], respectively; hazard ratio in the gluten group, 1.23; 95% CI, 0.79 to 1.91). Rates of elevated levels of anti-transglutaminase type 2 and antigliadin antibodies were also similar in the two study groups (7.0% [95% CI, 4.7 to 9.4] in the gluten group and 5.7% [95% CI, 3.5 to 7.9] in the placebo group; hazard ratio, 1.14; 95% CI, 0.76 to 1.73). Breast-feeding, regardless of whether it was exclusive or whether it was ongoing during gluten introduction, did not significantly influence the development of celiac disease or the effect of the intervention. CONCLUSIONS As compared with placebo, the introduction of small quantities of gluten at 16 to 24 weeks of age did not reduce the risk of celiac disease by 3 years of age in this group of high-risk children. (Funded by the European Commission and others; PreventCD Current Controlled Trials number, ISRCTN74582487.).
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Jansen MAE, Tromp IIM, Kiefte-de Jong JC, Jaddoe VWV, Hofman A, Escher JC, Hooijkaas H, Moll HA. Infant feeding and anti-tissue transglutaminase antibody concentrations in the Generation R Study. Am J Clin Nutr 2014; 100:1095-101. [PMID: 25240074 DOI: 10.3945/ajcn.114.090316] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND Celiac disease (CD) has emerged as a common, but largely undiagnosed health problem. Numerous studies examined the influence of infant nutrition on the development of diagnosed CD. However, results are still inconsistent. In addition, the effect of infant feeding practices on the development of potential forms of CD might be different. OBJECTIVE The objective was to examine whether the timing of gluten introduction and breastfeeding duration are associated with CD autoimmunity (CDA) in children at the age of 6 y. DESIGN This study was embedded in the Generation R Study, a population-based prospective cohort study. Participants included 1679 Dutch children who were positive for human leukocyte antigen (HLA) DQ2/DQ8. Data on the timing of gluten introduction (<6 mo compared with ≥6 mo) and duration of breastfeeding (<6 mo compared with ≥6 mo) were obtained by questionnaire. Serum samples were analyzed for anti-tissue transglutaminase (anti-tTG) concentrations at age 6 y. Anti-tTG concentrations were categorized into negative (<7 U/mL) and positive (≥7 U/mL) values. Positive anti-tTG concentrations were further categorized based on ≥10 times the upper limit of normal (ULN) values of the test kit (≥7-70 and ≥70 U/mL). Multivariable logistic regression analyses were performed. RESULTS Positive anti-tTG concentrations were found in 43 children, 26 of whom had concentrations ≥10 times the ULN (≥70 IU/mL). The introduction of gluten from the age of 6 mo onward and breastfeeding for ≥6 mo were not significantly associated with positive anti-tTG concentrations. In addition, the timing of gluten introduction and duration of breastfeeding were not significantly associated with positive anti-tTG concentrations below or above 10 times the ULN. CONCLUSIONS Delayed introduction of gluten beyond the age of 6 mo does not increase the risk of CDA. In addition, breastfeeding for ≥6 mo does not decrease the risk of CDA in children at 6 y of age.
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Affiliation(s)
- Michelle A E Jansen
- From the Generation R Study Group (MAEJ, IIMT, and VWVJ) and the Departments of Pediatrics (MAEJ, IIMT, VWVJ, and HAM), Epidemiology (JCK-dJ, VWVJ, and AH), Pediatric Gastroenterology (JCE), and Immunology (HH), Erasmus MC, University Medical Center, Rotterdam, Netherlands
| | - Ilse I M Tromp
- From the Generation R Study Group (MAEJ, IIMT, and VWVJ) and the Departments of Pediatrics (MAEJ, IIMT, VWVJ, and HAM), Epidemiology (JCK-dJ, VWVJ, and AH), Pediatric Gastroenterology (JCE), and Immunology (HH), Erasmus MC, University Medical Center, Rotterdam, Netherlands
| | - Jessica C Kiefte-de Jong
- From the Generation R Study Group (MAEJ, IIMT, and VWVJ) and the Departments of Pediatrics (MAEJ, IIMT, VWVJ, and HAM), Epidemiology (JCK-dJ, VWVJ, and AH), Pediatric Gastroenterology (JCE), and Immunology (HH), Erasmus MC, University Medical Center, Rotterdam, Netherlands
| | - Vincent W V Jaddoe
- From the Generation R Study Group (MAEJ, IIMT, and VWVJ) and the Departments of Pediatrics (MAEJ, IIMT, VWVJ, and HAM), Epidemiology (JCK-dJ, VWVJ, and AH), Pediatric Gastroenterology (JCE), and Immunology (HH), Erasmus MC, University Medical Center, Rotterdam, Netherlands
| | - Albert Hofman
- From the Generation R Study Group (MAEJ, IIMT, and VWVJ) and the Departments of Pediatrics (MAEJ, IIMT, VWVJ, and HAM), Epidemiology (JCK-dJ, VWVJ, and AH), Pediatric Gastroenterology (JCE), and Immunology (HH), Erasmus MC, University Medical Center, Rotterdam, Netherlands
| | - J C Escher
- From the Generation R Study Group (MAEJ, IIMT, and VWVJ) and the Departments of Pediatrics (MAEJ, IIMT, VWVJ, and HAM), Epidemiology (JCK-dJ, VWVJ, and AH), Pediatric Gastroenterology (JCE), and Immunology (HH), Erasmus MC, University Medical Center, Rotterdam, Netherlands
| | - Herbert Hooijkaas
- From the Generation R Study Group (MAEJ, IIMT, and VWVJ) and the Departments of Pediatrics (MAEJ, IIMT, VWVJ, and HAM), Epidemiology (JCK-dJ, VWVJ, and AH), Pediatric Gastroenterology (JCE), and Immunology (HH), Erasmus MC, University Medical Center, Rotterdam, Netherlands
| | - Henriette A Moll
- From the Generation R Study Group (MAEJ, IIMT, and VWVJ) and the Departments of Pediatrics (MAEJ, IIMT, VWVJ, and HAM), Epidemiology (JCK-dJ, VWVJ, and AH), Pediatric Gastroenterology (JCE), and Immunology (HH), Erasmus MC, University Medical Center, Rotterdam, Netherlands
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Early microbial markers of celiac disease: is the microbiological fog clearing? J Clin Gastroenterol 2014; 48:579-81. [PMID: 24983539 DOI: 10.1097/mcg.0000000000000159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
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Tjernberg AR, Ludvigsson JF. Children with celiac disease are more likely to have attended hospital for prior respiratory syncytial virus infection. Dig Dis Sci 2014; 59:1502-1508. [PMID: 24510390 DOI: 10.1007/s10620-014-3046-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2013] [Accepted: 01/20/2014] [Indexed: 12/31/2022]
Abstract
BACKGROUND AND AIM The purpose of this study was to examine the association between celiac disease (CD) and prior respiratory syncytial virus (RSV) infection or any viral bronchiolitis. METHODS This was a retrospective case-control study. During 2006-2008 small intestinal biopsy data were collected from Sweden's 28 pathology departments. We identified 3,835 children diagnosed with CD (villous atrophy, Marsh stage 3) before the age of 2 years in 1987 or later. Using conditional logistic regression we calculated odds ratios (ORs) for having a prior diagnosis of respiratory syncytial virus or other viral bronchiolitis compared to 19,102 age- and sex-matched controls. RESULTS Of the 3,835 children with CD, 36 (0.9 %) had a prior diagnosis of RSV compared to 117/19,102 (0.6 %) matched controls. This corresponded to an OR of 1.46 (95 % CI 1.03-2.07). ORs were similar in girls and boys. The highest ORs were seen in children developing early CD (before 1 year of age (OR 1.82; 95 % CI 0.91-3.62). Prior record of any type of viral bronchiolitis was found in 3.4 % (132/3,835) of individuals with CD and in 2.0 % (390/19,102) of the matched controls corresponding to an OR of 1.60 (95 % CI 1.33-1.92). CONCLUSIONS Children with CD diagnosed <2 years of age were more likely to have attended hospital for a prior RSV infection or any viral bronchiolitis than other children.
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Abstract
Celiac disease (CD) is an autoimmune disorder caused by ingestion of gluten in genetically predisposed individuals. It is a chronic, multiorgan disease in which small-intestinal mucosal damage may lead to malabsorption of nutrients. In the last years, several studies suggested a protective role of breast-feeding and/or the timing and quantity of gluten introduction in the subsequent development of CD. Especially, prolonged breast feeding during the introduction of gluten-containing feeding has been associated with a reduced risk of developing CD in infancy. The focus of this review was to present the actual knowledge of the possible preventive influence of early nutrition on the risk to develop CD.
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Canova C, Zabeo V, Pitter G, Romor P, Baldovin T, Zanotti R, Simonato L. Association of maternal education, early infections, and antibiotic use with celiac disease: a population-based birth cohort study in northeastern Italy. Am J Epidemiol 2014; 180:76-85. [PMID: 24853109 DOI: 10.1093/aje/kwu101] [Citation(s) in RCA: 106] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
We conducted a population-based birth cohort study of approximately 203,000 babies born in northeastern Italy (1989-2012) to investigate perinatal variables, early infections leading to hospital admission, and antibiotic use in the first 12 months of life as possible risk factors for celiac disease (CD). Incident CD cases were identified from pathology reports, hospital discharge records, and exemptions from prescription charges for clinical tests. Multivariate Poisson regression models were fitted to estimate incidence rate ratios (IRRs). A total of 1,227 children had CD; CD was histopathologically confirmed in 866 (71%). Female sex, maternal age, and high maternal educational level were found to be significantly associated with CD. Gastrointestinal infections were strongly associated with a subsequent diagnosis of CD (IRR = 2.04, 95% confidence interval (CI): 1.30, 3.22). Antibiotic use was significantly associated with CD onset (IRR = 1.24, 95% CI: 1.07, 1.43), with a dose-response relationship for number of courses (P-trend < 0.01). Cephalosporin use strongly increased the risk of CD (IRR = 1.42, 95% CI: 1.18, 1.73). Use of antibiotics (supported by the dose-response relationship) and gastrointestinal infections in the first year of life may facilitate the early onset of CD by altering intestinal microflora and the gut mucosal barrier. Perinatal factors, including cesarean section, had little influence on the risk of childhood CD.
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Burden S, Langley-Evans S, Talley N. Coeliac disease: pathogenesis, prognosis and management. J Hum Nutr Diet 2014; 27:203-4. [DOI: 10.1111/jhn.12233] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- S. Burden
- Journal of Human Nutrition and Dietetics
| | | | - N. Talley
- Journal of Human Nutrition and Dietetics
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Gilissen LJ, van der Meer IM, Smulders MJ. Reducing the incidence of allergy and intolerance to cereals. J Cereal Sci 2014. [DOI: 10.1016/j.jcs.2014.01.005] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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