Introduction: Inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), exhibits a multifactorial pathogenesis influenced by genetic and environmental factors. Antibiotic usage has been implicated in modifying the gut microbiome, potentially leading to dysbiosis and contributing to IBD risk. Despite existing literature, the relationship remains inconclusive. This meta-analysis aimed to evaluate the association between prior antibiotic use and the onset of IBD. Methods: A systematic literature search in PubMed was conducted to identify studies exploring the link between antibiotic use and subsequent IBD diagnosis. Studies reporting CD, UC, or both as primary outcomes were included. The meta-analysis, performed according to PRISMA guidelines, summarized risk estimates, represented as odds ratios (ORs), and corresponding confidence intervals (CIs). Subgroup analyses involved the categorization of antibiotics and the determination of the minimum number of antibiotic therapy courses administered. Results: Out of 722 publications, 31 studies comprising 102,103 individuals met eligibility criteria. The pooled OR for IBD in those with prior antibiotic exposure was 1.40 (95% CI: 1.25–1.56). Antibiotic use was associated with an increased risk of IBD (OR: 1.52, 95% CI: 1.19–1.94). Notably, this association was confined to CD (OR: 1.50, 95% CI: 1.27–1.77), while no significant association was observed with UC (OR: 1.21, 95% CI: 1.00–1.47). Risk augmentation for IBD correlated positively with the number of antibiotic courses (OR: 1.08, 95% CI: 1.05–1.12). Conclusion: Previous antibiotic use is associated with the later development of CD. A positive dose-response effect was also observed. Against this background, antibiotics should be used rationally.

1.
Glassner
KL
,
Abraham
BP
,
Quigley
EMM
.
The microbiome and inflammatory bowel disease
.
J Allergy Clin Immunol
.
2020
;
145
(
1
):
16
27
.
2.
Piovani
D
,
Danese
S
,
Peyrin-Biroulet
L
,
Nikolopoulos
GK
,
Lytras
T
,
Bonovas
S
.
Environmental risk factors for inflammatory bowel diseases: an umbrella review of meta-analyses
.
Gastroenterology
.
2019
;
157
(
3
):
647
59 e4
.
3.
Nguyen
LH
,
Örtqvist
AK
,
Cao
Y
,
Simon
TG
,
Roelstraete
B
,
Song
M
, et al
.
Antibiotic use and the development of inflammatory bowel disease: a national case-control study in Sweden
.
Lancet Gastroenterol Hepatol
.
2020
;
5
(
11
):
986
95
.
4.
Niu
J
,
Miao
J
,
Tang
Y
,
Nan
Q
,
Liu
Y
,
Yang
G
, et al
.
Identification of environmental factors associated with inflammatory bowel disease in a southwestern highland region of China: a nested case-control study
.
PLoS One
.
2016
;
11
(
4
):
e0153524
.
5.
Yang
AZ
,
Jostins-Dean
L
.
Environmental variables and genome-environment interactions predicting IBD diagnosis in large UK cohort
.
Sci Rep
.
2022
;
12
(
1
):
10890
.
6.
Han
DY
,
Fraser
AG
,
Dryland
P
,
Ferguson
LR
.
Environmental factors in the development of chronic inflammation: a case-control study on risk factors for Crohn’s disease within New Zealand
.
Mutat Res
.
2010
;
690
(
1–2
):
116
22
.
7.
Shaw
SY
,
Blanchard
JF
,
Bernstein
CN
.
Association between the use of antibiotics and new diagnoses of Crohn’s disease and ulcerative colitis
.
Am J Gastroenterol
.
2011
;
106
(
12
):
2133
42
.
8.
Ungaro
R
,
Bernstein
CN
,
Gearry
R
,
Hviid
A
,
Kolho
KL
,
Kronman
MP
, et al
.
Antibiotics associated with increased risk of new-onset Crohn's disease but not ulcerative colitis: a meta-analysis
.
Am J Gastroenterol
.
2014
;
109
(
11
):
1728
38
.
9.
Page
MJ
,
McKenzie
JE
,
Bossuyt
PM
,
Boutron
I
,
Hoffmann
TC
,
Mulrow
CD
, et al
.
The PRISMA 2020 statement: an updated guideline for reporting systematic reviews
.
Syst Rev
.
2021
;
10
(
1
):
89
.
10.
Egger
M
,
Davey Smith
G
,
Schneider
M
,
Minder
C
.
Bias in meta-analysis detected by a simple, graphical test
.
BMJ
.
1997
;
315
(
7109
):
629
34
.
11.
Balduzzi
S
,
Rucker
G
,
Schwarzer
G
.
How to perform a meta-analysis with R: a practical tutorial
.
Evid Based Ment Health
.
2019
;
22
(
4
):
153
60
.
12.
McGuinness
LA
,
Higgins
JPT
.
Risk-of-bias VISualization (robvis): an R package and Shiny web app for visualizing risk-of-bias assessments
.
Res Synth Methods
.
2021
;
12
(
1
):
55
61
.
13.
Troelsen
FS
,
Jick
S
.
Antibiotic use in childhood and adolescence and risk of inflammatory bowel disease: a case-control study in the UK clinical practice research datalink
.
Inflamm Bowel Dis
.
2020
;
26
(
3
):
440
7
.
14.
Ng
SC
,
Tang
W
,
Leong
RW
,
Chen
M
,
Ko
Y
,
Studd
C
, et al
.
Environmental risk factors in inflammatory bowel disease: a population-based case-control study in Asia-Pacific
.
Gut
.
2015
;
64
(
7
):
1063
71
.
15.
Ko
Y
,
Kariyawasam
V
,
Karnib
M
,
Butcher
R
,
Samuel
D
,
Alrubaie
A
, et al
.
Inflammatory bowel disease environmental risk factors: a population-based case-control study of middle eastern migration to Australia
.
Clin Gastroenterol Hepatol
.
2015
;
13
(
8
):
1453
63 e1
.
16.
Castiglione
F
,
Diaferia
M
,
Morace
F
,
Labianca
O
,
Meucci
C
,
Cuomo
A
, et al
.
Risk factors for inflammatory bowel diseases according to the “hygiene hypothesis”: a case-control, multi-centre, prospective study in Southern Italy
.
J Crohns Colitis
.
2012
;
6
(
3
):
324
9
.
17.
Hildebrand
H
,
Malmborg
P
,
Askling
J
,
Ekbom
A
,
Montgomery
SM
.
Early-life exposures associated with antibiotic use and risk of subsequent Crohn’s disease
.
Scand J Gastroenterol
.
2008
;
43
(
8
):
961
6
.
18.
Card
T
,
Logan
RFA
,
Rodrigues
LC
,
Wheeler
JG
.
Antibiotic use and the development of Crohn’s disease
.
Gut
.
2004
;
53
(
2
):
246
50
.
19.
Taylor
MT
,
Margolis
DJ
,
Kwatra
SG
,
Barbieri
JS
.
A propensity score matched cohort study identifying an association of acne, but not oral antibiotic or isotretinoin use, with risk of incident inflammatory bowel disease
.
J Am Acad Dermatol
.
2023
;
88
(
4
):
841
7
.
20.
Kronman
MP
,
Zaoutis
TE
,
Haynes
K
,
Feng
R
,
Coffin
SE
.
Antibiotic exposure and IBD development among children: a population-based cohort study
.
Pediatrics
.
2012
;
130
(
4
):
e794
803
.
21.
Margolis
DJ
,
Fanelli
M
,
Hoffstad
O
,
Lewis
JD
.
Potential association between the oral tetracycline class of antimicrobials used to treat acne and inflammatory bowel disease
.
Am J Gastroenterol
.
2010
;
105
(
12
):
2610
6
.
22.
Faye
AS
,
Allin
KH
,
Iversen
AT
,
Agrawal
M
,
Faith
J
,
Colombel
JF
, et al
.
Antibiotic use as a risk factor for inflammatory bowel disease across the ages: a population-based cohort study
.
Gut
.
2023
;
72
(
4
):
663
70
.
23.
Mark-Christensen
A
,
Lange
A
,
Erichsen
R
,
Frøslev
T
,
Esen
,
Sørensen
HT
, et al
.
Early-life exposure to antibiotics and risk for Crohn’s disease: a nationwide Danish birth cohort study
.
Inflamm Bowel Dis
.
2022
;
28
(
3
):
415
22
.
24.
Ortqvist
AK
,
Lundholm
C
,
Halfvarson
J
,
Ludvigsson
JF
,
Almqvist
C
.
Fetal and early life antibiotics exposure and very early onset inflammatory bowel disease: a population-based study
.
Gut
.
2019
;
68
(
2
):
218
25
.
25.
Li
WQ
,
Cho
E
,
Khalili
H
,
Wu
S
,
Chan
AT
,
Qureshi
AA
.
Rosacea, use of tetracycline, and risk of incident inflammatory bowel disease in women
.
Clin Gastroenterol Hepatol
.
2016
;
14
(
2
):
220
5.e53
. e1-3.
26.
Hviid
A
,
Svanstrom
H
,
Frisch
M
.
Antibiotic use and inflammatory bowel diseases in childhood
.
Gut
.
2011
;
60
(
1
):
49
54
.
27.
Lee
TW
,
Russell
L
,
Deng
M
,
Gibson
PR
.
Association of doxycycline use with the development of gastroenteritis, irritable bowel syndrome and inflammatory bowel disease in Australians deployed abroad
.
Intern Med J
.
2013
;
43
(
8
):
919
26
.
28.
Torres
J
,
Gomes
C
,
Jensen
CB
,
Agrawal
M
,
Ribeiro-Mourão
F
,
Jess
T
, et al
.
Risk factors for developing inflammatory bowel disease within and across families with a family history of IBD
.
J Crohns Colitis
.
2023
;
17
(
1
):
30
6
.
29.
Canova
C
,
Ludvigsson
JF
,
Di Domenicantonio
R
,
Zanier
L
,
Barbiellini Amidei
C
,
Zingone
F
.
Perinatal and antibiotic exposures and the risk of developing childhood-onset inflammatory bowel disease: a nested case-control study based on a population-based birth cohort
.
Int J Environ Res Public Health
.
2020
;
17
(
7
):
2409
.
30.
Shimodaira
Y
,
Watanabe
K
,
Iijima
K
.
The risk of antibiotics and enterocolitis for the development of inflammatory bowel disease: a Japanese administrative database analysis
.
Sci Rep
.
2022
;
12
(
1
):
7604
.
31.
Lee
WS
,
Song
ZL
,
Wong
SY
,
Gan
CW
,
Koay
ZL
,
Em
JM
, et al
.
Environmental risk factors for inflammatory bowel disease: a case control study in Southeast Asian children
.
J Paediatr Child Health
.
2022
;
58
(
5
):
782
90
.
32.
Bernstein
CN
,
Burchill
C
,
Targownik
LE
,
Singh
H
,
Roos
LL
.
Events within the first year of life, but not the neonatal period, affect risk for later development of inflammatory bowel diseases
.
Gastroenterology
.
2019
;
156
(
8
):
2190
7 e10
.
33.
Aniwan
S
,
Tremaine
WJ
,
Raffals
LE
,
Kane
SV
,
Loftus
EV
Jr
.
Antibiotic use and new-onset inflammatory bowel disease in olmsted county, Minnesota: a population-based case-control study
.
J Crohns Colitis
.
2018
;
12
(
2
):
137
44
.
34.
Bernstein
CN
,
Burchill
C
,
Targownik
LE
,
Singh
H
,
Ghia
JE
,
Roos
LL
.
Maternal infections that would warrant antibiotic use antepartum or peripartum are not a risk factor for the development of IBD: a population-based analysis
.
Inflamm Bowel Dis
.
2017
;
23
(
4
):
635
40
.
35.
Virta
L
,
Auvinen
A
,
Helenius
H
,
Huovinen
P
,
Kolho
KL
.
Association of repeated exposure to antibiotics with the development of pediatric Crohn’s disease: a nationwide, register-based Finnish case-control study
.
Am J Epidemiol
.
2012
;
175
(
8
):
775
84
.
36.
Shaw
SY
,
Blanchard
JF
,
Bernstein
CN
.
Association between the use of antibiotics in the first year of life and pediatric inflammatory bowel disease
.
Am J Gastroenterol
.
2010
;
105
(
12
):
2687
92
.
37.
Gearry
RB
,
Richardson
AK
,
Frampton
CM
,
Dodgshun
AJ
,
Barclay
ML
.
Population-based cases control study of inflammatory bowel disease risk factors
.
J Gastroenterol Hepatol
.
2010
;
25
(
2
):
325
33
.
38.
Wurzelmann
JI
,
Lyles
CM
,
Sandler
RS
.
Childhood infections and the risk of inflammatory bowel disease
.
Dig Dis Sci
.
1994
;
39
(
3
):
555
60
.
39.
Zou
Y
,
Wu
L
,
Xu
W
,
Zhou
X
,
Ye
K
,
Xiong
H
, et al
.
Correlation between antibiotic use in childhood and subsequent inflammatory bowel disease: a systematic review and meta-analysis
.
Scand J Gastroenterol
.
2020
;
55
(
3
):
301
11
.
40.
Dar
SH
,
Maniya
MT
,
Merza
N
,
Musheer
A
,
Zahid
M
,
Ahmed
F
, et al
.
The association of antibiotic exposure with new-onset inflammatory bowel disease: a systematic review and meta-analysis
.
Clin Res Hepatol Gastroenterol
.
2023
;
47
(
6
):
102129
.
41.
Mizoguchi
A
,
Mizoguchi
E
.
Animal models of IBD: linkage to human disease
.
Curr Opin Pharmacol
.
2010
;
10
(
5
):
578
87
.
42.
Kiesler
P
,
Fuss
IJ
,
Strober
W
.
Experimental models of inflammatory bowel diseases
.
Cell Mol Gastroenterol Hepatol
.
2015
;
1
(
2
):
154
70
.
43.
Chiotos
K
,
Tamma
PD
,
Gerber
JS
.
Antibiotic stewardship in the intensive care unit: challenges and opportunities
.
Infect Control Hosp Epidemiol
.
2019
;
40
(
6
):
693
8
.
44.
Suez
J
,
Zmora
N
,
Zilberman-Schapira
G
,
Mor
U
,
Dori-Bachash
M
,
Bashiardes
S
, et al
.
Post-antibiotic gut mucosal microbiome reconstitution is impaired by probiotics and improved by autologous FMT
.
Cell
.
2018
;
174
(
6
):
1406
23.e16
.
45.
Ianiro
G
,
Tilg
H
,
Gasbarrini
A
.
Antibiotics as deep modulators of gut microbiota: between good and evil
.
Gut
.
2016
;
65
(
11
):
1906
15
.
46.
Fang
H
,
Fu
L
,
Wang
J
.
Protocol for fecal microbiota transplantation in inflammatory bowel disease: a systematic review and meta-analysis
.
BioMed Res Int
.
2018
;
2018
:
8941340
.
47.
Holstiege
J
,
Garbe
E
.
Systemic antibiotic use among children and adolescents in Germany: a population-based study
.
Eur J Pediatr
.
2013
;
172
(
6
):
787
95
.
48.
Sartor
RB
.
Microbial influences in inflammatory bowel diseases
.
Gastroenterology
.
2008
;
134
(
2
):
577
94
.
49.
Axelrad
JE
,
Olén
O
,
Askling
J
,
Lebwohl
B
,
Khalili
H
,
Sachs
MC
, et al
.
Gastrointestinal infection increases odds of inflammatory bowel disease in a nationwide case-control study
.
Clin Gastroenterol Hepatol
.
2019
;
17
(
7
):
1311
22.e7
.
50.
García Rodríguez
LA
,
Ruigómez
A
,
Panés
J
.
Acute gastroenteritis is followed by an increased risk of inflammatory bowel disease
.
Gastroenterology
.
2006
;
130
(
6
):
1588
94
.
51.
Gradel
KO
,
Nielsen
HL
,
Schønheyder
HC
,
Ejlertsen
T
,
Kristensen
B
,
Nielsen
H
.
Increased short- and long-term risk of inflammatory bowel disease after salmonella or campylobacter gastroenteritis
.
Gastroenterology
.
2009
;
137
(
2
):
495
501
.
52.
Porter
CK
,
Tribble
DR
,
Aliaga
PA
,
Halvorson
HA
,
Riddle
MS
.
Infectious gastroenteritis and risk of developing inflammatory bowel disease
.
Gastroenterology
.
2008
;
135
(
3
):
781
6
.
53.
Higgins
JPTTJ
,
Chandler
J
,
Cumpston
M
,
Li
T
,
Page
MJ
,
Welch
VA
, editors.
Cochrane handbook for systematic reviews of interventions
. 2nd ed.
Chichester (UK)
:
John Wiley & Sons
;
2019
.
54.
Sterne
JA
,
Hernán
MA
,
Reeves
BC
,
Savović
J
,
Berkman
ND
,
Viswanathan
M
, et al
.
ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions
.
BMJ
.
2016
;
355
:
i4919
.
55.
Molodecky
NA
,
Soon
IS
,
Rabi
DM
,
Ghali
WA
,
Ferris
M
,
Chernoff
G
, et al
.
Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review
.
Gastroenterology
.
2012
;
142
(
1
):
46
e42
; quiz e30.
56.
Ng
SC
,
Shi
HY
,
Hamidi
N
,
Underwood
FE
,
Tang
W
,
Benchimol
EI
, et al
.
Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies
.
Lancet
.
2017
;
390
(
10114
):
2769
78
.
57.
Kaplan
GG
.
The global burden of IBD: from 2015 to 2025
.
Nat Rev Gastroenterol Hepatol
.
2015
;
12
(
12
):
720
7
.
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