Abstract
Introduction: The aim of this study was to investigate the association between helminth infections and celiac disease (CeD), examining various demographic and clinical factors in CeD cases compared to controls. Methods: We conducted a retrospective case-control study utilizing Leumit Health Care Services’ electronic health records. The study encompassed individuals with CeD and a matched control group. We analyzed demographic and clinical characteristics, examining their association with helminth infections. Results: We observed CeD cases and controls had similar mean ages (17.8 years vs. 18.0 years, p = 0.565) and gender distributions (64.0% females in both groups, p = 0.999). There were no significant differences in socioeconomic status and ethnic distribution between the two groups. Most of the helminthiases in the CeD group were due to intestinal helminthiases, and most of the intestinal helminthiases were nematode (roundworm) infections. Enterobiasis (the pinworm Enterobius vermicularis) is involved in most cases (odds ratio 1.32, 95% confidence interval 1.20–1.45, p < 0.001). While the prevalence of ascariasis and anisakiasis was also higher in the CeD group, these differences were not statistically significant (p = 0.115 and p = 0.174, respectively). No significant differences were found in the prevalence of other specific helminth infections, such as echinococcosis, cestode infections, and strongyloidiasis. Conclusions: This study reveals an unexpected association between CeD and helminth infections, challenging prevailing hypotheses, particularly within the context of the hygiene hypothesis. These findings warrant further investigation to elucidate the mechanisms underlying this intriguing relationship.
Journal Section:
Nutrition and Probiotics: Research Article
References
1.
Sollid
LM
, Jabri
B
. Is celiac disease an autoimmune disorder
. Curr Opin Immunol
. 2005
;17
(6
):595
–600
. 2.
Mamone
G
, Di Stasio
L
, Vitale
S
, Picascia
S
, Gianfrani
C
. Analytical and functional approaches to assess the immunogenicity of gluten proteins
. Front Nutr
. 2022
;9
:1049623
. 3.
Catassi
C
, Verdu
EF
, Bai
JC
, Lionetti
E
. Coeliac disease
. Lancet
. 2022
;399
(10344
):2413
–26
. 4.
Jansson-Knodell
CL
, Celdir
MG
, Hujoel
IA
, Lyu
R
, Gardinier
D
, Weekley
K
, et al. Relationship between gluten availability and celiac disease prevalence: a geo-epidemiologic systematic review
. J Gastroenterol Hepatol
. 2023
;38
(10
):1695
–709
. 5.
Simón
E
, Molero-Luis
M
, Fueyo-Díaz
R
, Costas-Batlle
C
, Crespo-Escobar
P
, Montoro-Huguet
MA
. The gluten-free diet for celiac disease: critical insights to better understand clinical outcomes
. Nutrients
. 2023
;15
(18
):4013
. 6.
Cardo
A
, Churruca
I
, Lasa
A
, Navarro
V
, Vázquez-Polo
M
, Perez-Junkera
G
, et al. Nutritional imbalances in adult celiac patients following a gluten-free diet
. Nutrients
. 2021
;13
(8
):2877
. 7.
Patriarca
G
, Pogna
N
, Cammarota
G
, Schiavino
D
, Lombardo
C
, Pollastrini
E
, et al. An attempt of specific desensitising treatment with gliadin in celiac disease
. Int J Immunopathol Pharmacol
. 2005
;18
(4
):709
–14
. 8.
Rossi
M
. Vaccination and other antigen-specific immunomodulatory strategies in celiac disease
. Dig Dis
. 2015
;33
(2
):282
–9
. 9.
Murdaca
G
, Greco
M
, Borro
M
, Gangemi
S
. Hygiene hypothesis and autoimmune diseases: a narrative review of clinical evidences and mechanisms
. Autoimmun Rev
. 2021
;20
(7
):102845
. 10.
Croese
J
, Giacomin
P
, Navarro
S
, Clouston
A
, McCann
L
, Dougall
A
, et al. Experimental hookworm infection and gluten microchallenge promote tolerance in celiac disease
. J Allergy Clin Immunol
. 2015
;135
(2
):508
–16
. 11.
Croese
J
, Miller
GC
, Marquart
L
, Llewellyn
S
, Gupta
R
, Becker
L
, et al. Randomized, placebo controlled trial of experimental hookworm infection for improving gluten tolerance in celiac disease
. Clin Transl Gastroenterol
. 2020
;11
(12
):e00274
. 12.
Sobotková
K
, Parker
W
, Levá
J
, Růžková
J
, Lukeš
J
, Jirků Pomajbíková
K
. Helminth therapy: from the parasite perspective
. Trends Parasitol
. 2019
;35
(7
):501
–15
. 13.
Rubio-Tapia
A
, Hill
ID
, Kelly
CP
, Calderwood
AH
, Murray
JA
. American College of Gastroenterology. ACG clinical guidelines: diagnosis and management of celiac disease
. Am J Gastroenterol
. 2013
;108
(5
):656
–76
. 14.
Burkhart
CN
, Burkhart
CG
. Assessment of frequency, transmission, and genitourinary complications of enterobiasis (pinworms)
. Int J Dermatol
. 2005
;44
(10
):837
–40
. 15.
Kubiak
K
, Dzika
E
, Paukszto
Ł
. Enterobiasis epidemiology and molecular characterization of Enterobius vermicularis in healthy children in north-eastern Poland
. Helminthologia
. 2017
;54
(4
):284
–91
. 16.
Tomaso
H
, Dierich
MP
, Allerberger
F
. Helminthic infestations in the tyrol, Austria
. Clin Microbiol Infect
. 2001
;7
(11
):639
–41
. 17.
Rubio-Tapia
A
, Hill
ID
, Semrad
C
, Kelly
CP
, Greer
KB
, Limketkai
BN
, et al. American college of gastroenterology guidelines update: diagnosis and management of celiac disease
. Am J Gastroenterol
. 2023
;118
(1
):59
–76
. 18.
Ottesen
EA
, Hiatt
RA
, Cheever
AW
, Sotomayor
ZR
, Neva
FA
. The acquisition and loss of antigen-specific cellular immune responsiveness in acute and chronic schistosomiasis in man
. Clin Exp Immunol
. 1978
;33
(1
):37
–47
.19.
Maizels
RM
, Bundy
DA
, Selkirk
ME
, Smith
DF
, Anderson
RM
. Immunological modulation and evasion by helminth parasites in human populations
. Nature
. 1993
;365
(6449
):797
–805
. 20.
Maizels
RM
, Yazdanbakhsh
M
. Immune regulation by helminth parasites: cellular and molecular mechanisms
. Nat Rev Immunol
. 2003
;3
(9
):733
–44
. 21.
Weiss
ST
. Eat dirt: the hygiene hypothesis and allergic diseases
. N Engl J Med
. 2002
;347
(12
):930
–1
. 22.
Quinnell
RJ
, Bethony
J
, Pritchard
DI
. The immunoepidemiology of human hookworm infection
. Parasite Immunol
. 2004
;26
(11–12
):443
–54
. 23.
Wilson
MS
, Taylor
MD
, Balic
A
, Finney
CAM
, Lamb
JR
, Maizels
RM
. Suppression of allergic airway inflammation by helminth-induced regulatory T cells
. J Exp Med
. 2005
;202
(9
):1199
–212
. 24.
Stene
LC
, Honeyman
MC
, Hoffenberg
EJ
, Haas
JE
, Sokol
RJ
, Emery
L
, et al. Rotavirus infection frequency and risk of celiac disease autoimmunity in early childhood: a longitudinal study
. Am J Gastroenterol
. 2006
;101
(10
):2333
–40
. 25.
Zanoni
G
, Navone
R
, Lunardi
C
, Tridente
G
, Bason
C
, Sivori
S
, et al. In celiac disease, a subset of autoantibodies against transglutaminase binds toll-like receptor 4 and induces activation of monocytes
. PLoS Med
. 2006
;3
(9
):e358
. 26.
Gaze
S
, McSorley
HJ
, Daveson
J
, Jones
D
, Bethony
JM
, Oliveira
LM
, et al. Characterising the mucosal and systemic immune responses to experimental human hookworm infection
. PLoS Pathog
. 2012
;8
(2
):e1002520
. 27.
Maizels
RM
, Gause
WC
. Targeting helminths: the expanding world of type 2 immune effector mechanisms
. J Exp Med
. 2023
;220
(10
):e20221381
. 28.
Yang
CA
, Liang
C
, Lin
CL
, Hsiao
CT
, Peng
CT
, Lin
HC
, et al. Impact of Enterobius vermicularis infection and mebendazole treatment on intestinal microbiota and host immune response
. PLoS Negl Trop Dis
. 2017
;11
(9
):e0005963
. 29.
Akobeng
AK
, Singh
P
, Kumar
M
, Al Khodor
S
. Role of the gut microbiota in the pathogenesis of coeliac disease and potential therapeutic implications
. Eur J Nutr
. 2020
;59
(8
):3369
–90
. 30.
Cataldo
F
, Montalto
G
. Celiac disease in the developing countries: a new and challenging public health problem
. World J Gastroenterol
. 2007
;13
(15
):2153
–9
. 31.
Ludvigsson
J
, Jones
MP
, Faresjö
Å
. Worm infestations and development of autoimmunity in children: the ABIS study
. PLoS One
. 2017
;12
(3
):e0173988
. 32.
Daveson
AJ
, Jones
DM
, Gaze
S
, McSorley
H
, Clouston
A
, Pascoe
A
, et al. Effect of hookworm infection on wheat challenge in celiac disease: a randomised double-blinded placebo controlled trial
. PLoS One
. 2011
;6
(3
):e17366
. 33.
Finlay
CM
, Walsh
KP
, Mills
KH
. Induction of regulatory cells by helminth parasites: exploitation for the treatment of inflammatory diseases
. Immunol Rev
. 2014
;259
(1
):206
–30
. 34.
Ni
Y
, Xiong
R
, Zhu
Y
, Luan
N
, Yu
C
, Yang
K
, et al. A target-based discovery from a parasitic helminth as a novel therapeutic approach for autoimmune diseases
. EBioMedicine
. 2023
;95
:104751
. 35.
Jo
EK
. Interplay between host and pathogen: immune defense and beyond
. Exp Mol Med
. 2019
;51
(12
):1
–3
. 36.
Cassin Sackett
L
. Does the host matter? Variable influence of host traits on parasitism rates
. Int J Parasitol
. 2018
;48
(1
):27
–39
. 37.
Smallwood
TB
, Giacomin
PR
, Loukas
A
, Mulvenna
JP
, Clark
RJ
, Miles
JJ
. Helminth immunomodulation in autoimmune disease
. Front Immunol
. 2017
;8
:453
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