Digestive Diseases and Sciences

, Volume 63, Issue 12, pp 3434–3441 | Cite as

Microbial Biomarkers in Patients with Nonresponsive Celiac Disease

  • Liisa Viitasalo
  • Kalle KurppaEmail author
  • Merja Ashorn
  • Päivi Saavalainen
  • Heini Huhtala
  • Sara Ashorn
  • Markku Mäki
  • Tuire Ilus
  • Katri Kaukinen
  • Sari Iltanen
Original Article


Background and Aims

In nonresponsive celiac disease (NRCD), the symptoms and duodenal damage persist despite a gluten-free diet. Celiac disease patients with persistent symptoms are found to have a dysbiotic microbiota. We thus hypothesized that increased seroreactivity to the serum gluten-sensitive microbial antibodies Saccharomyces cerevisiae (ASCA), Pseudomonas fluorescens-associated sequence (I2), and Bacteroides caccae TonB-linked outer membrane protein (OmpW) is associated with NRCD.


ASCA, I2 and OmpW were measured in 20 seronegative CD patients with persistent villous damage despite strict dietary treatment (NRCD group). Fifty-eight responsive patients served as CD controls (55 on gluten-free treatment) and 80 blood donors as non-CD controls.


At least one microbial marker was positive in 80% of NRCD patients, in 97% of untreated CD and 87% of treated CD patients, and in 44% of controls. NRCD patients had the highest frequency of ASCA positivity (65% vs 52, 20, and 0%, respectively) and also significantly higher ASCA IgA (median 14.5 U/ml) and IgG (32.5 U/ml) titers than treated CD patients (7.0 U/ml, 13.0 U/ml) and non-CD controls (4.5 U/ml, 5.8 U/ml). The frequencies of I2 and OmpW were lower in NRCD than in untreated CD (65% and 45% vs 86% and 59%, respectively), and I2 titers were higher in NRCD (median absorbance 0.76) and untreated (1.0) and treated (0.83) CD than controls (0.32). OmpW was elevated in untreated (1.1) and treated (0.94) CD patients compared with controls (0.79).


Seropositivity and high titers of ASCA are associated with NRCD and might serve as an additional follow-up tool in CD.


Nonresponsive celiac disease Microbiota Saccharomyces cerevisiae Pseudomonas fluorescence Bacteroides caccae 



We would like to acknowledge Jonathan Braun, M.D., Ph.D, Professor and Chair, Pathology and Laboratory Medicine, UCLA David Geffen School of Medicine, UCLA Health System for his support.


This study was supported by the Academy of Finland, the Sigrid Juselius Foundation, the Päivikki and Sakari Sohlberg Foundation, the Competitive State Research Financing of the Expert Area of Tampere University Hospital, the Foundation for Pediatric Research, the Yrjö Jahnsson Foundation and State fund, Grant number Y1023G2017.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Tampere Center for Child Health ResearchUniversity of Tampere and Tampere University HospitalTampereFinland
  2. 2.Department of Clinical Genetics and Laboratory of Genetics, HUSLABUniversity of Helsinki and Helsinki University HospitalHelsinkiFinland
  3. 3.Research Programs Unit, Immunobiology, and Department of Medical and Clinical GeneticsUniversity of HelsinkiHelsinkiFinland
  4. 4.Faculty of Social SciencesUniversity of TampereTampereFinland
  5. 5.Department of Gastroenterology and Alimentary Tract SurgeryTampere University HospitalTampereFinland
  6. 6.Celiac Disease Research Center, Faculty of Medicine and Life SciencesUniversity of TampereTampereFinland
  7. 7.Department of Internal MedicineTampere University HospitalTampereFinland
  8. 8.Lapland Central HospitalRovaniemiFinland

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