Case-control studyindependent cross-checkfull text checked★ key study I-ABX-06 in-depth review
Antibiotics and IBD in adults (Sweden)
Antibiotic use and the development of inflammatory bowel disease: a national case-control study in Sweden.
Overview
Nguyen LH et al.. Lancet Gastroenterol Hepatol 2020 · PMID 32818437 · DOI 10.1016/S2468-1253(20)30267-3
More antibiotic use was linked to IBD, also when compared with siblings.
Does the study support the specific claim? Partly · Methodological quality: high
Plain-language summary
Study explained simply
- What did the researchers want to find out?
Link.
- How was the study done?
Case-control with siblings.
- How many people, animals or samples were studied?
23,982 adult IBD cases, 117,827 controls, 28,732 siblings (Sweden 2007-2016).
- What was actually found?
More antibiotic prescriptions, especially broad-spectrum, were linked to higher odds of IBD: 3 or more vs none aOR 1.55 against the general population and 1.35 against siblings.
- How large was the observed effect?
aOR 1.55 (>=3 dispensations); 1.35 vs siblings; ever vs never 1.94.
- What do the results mean in everyday life?
Possible effect.
- What are the study's limitations?
Observational; reason for antibiotics unknown; adults only; no absolute risks.
- What does it say about Elawady's specific claim?
Supports association.
- Do the results apply to Germany and Europe?
High.
- What can explicitly not be concluded from this study?
Causation, absolute risk, or effects in children.
Scientific in-depth review
1. Full reference
- Authors
- Nguyen LH et al.
- Journal
- Lancet Gastroenterol Hepatol
- Year
- 2020
- Identifier
- PMID 32818437 DOI 10.1016/S2468-1253(20)30267-3
- Verification
- verified – PubMed efetch 2026-10-25
- Retracted
- no
- Corrections
- none
- Extent checked
- full text
- Conflicts of interest and funding
Funding: NIH (T32CA009001, Loan Repayment Program, K07CA218377, R00CA215314), Crohn's and Colitis Foundation, American Gastroenterological Association, MGH Steele award; funders had no role. Declarations: KS grants from AstraZeneca, Gelesis, Takeda and fees from Shire, Boston Pharmaceuticals, Arena (unrelated); HK unrelated grant/consulting from Pfizer and Takeda; JFL coordinates a separate SWIBREG study.
2. Research question
Antibiotics and incident IBD in adults
3. Study design and population
- Study design
- Case-control study – Nationwide population-based matched case-control study nested in ESPRESSO histopathology cohort with Swedish Patient and Prescribed Drug Registers; secondary comparison with unaffected full siblings
- Population
Swedish residents aged >=16 years with incident, histology-confirmed IBD (2007-2016), up to 5 general-population controls matched on age, sex, county and calendar year, plus IBD-free full siblings
- Country
Sweden
- Period
2007-2016
- Sample size
23,982 incident IBD cases (15,951 UC, 7,898 CD, 133 IBD-U); 117,827 matched controls; 28,732 full siblings (for 16,353 cases with >=1 sibling)
- Inclusion and exclusion criteria
Cases: histopathology compatible with IBD plus >=1 ICD code (PPV 95% on chart review of 100); excluded IBD before 2005; controls could later become cases
4. Methods and endpoints
- Exposure / intervention
Cumulative systemic antibiotic dispensations (ATC J01) from 2005 baseline up to 1 year before diagnosis/matching (0, 1, 2, >=3); also by spectrum and class
- Comparator
No prior antibiotic dispensation; matched population controls; siblings
- Endpoints
Incident IBD, UC, CD
- Statistical methods
Conditional logistic regression adjusted for matching factors, education and number of inpatient/outpatient encounters; sibling comparison by unconditional logistic regression adjusted for age, sex, year, county, education, health-care use; sensitivity: 2-year lead-in, ciprofloxacin/metronidazole composite, age strata
5. Actual results
- Results
Ever vs never antibiotics: aOR 1.94 (95% CI 1.85-2.03) for IBD (this full-text version; existing record cited 1.88). Dose-response vs none: 1 dispensation aOR 1.11 (1.07-1.15), 2: 1.38 (1.32-1.44), >=3: 1.55 (1.49-1.61) for IBD; >=3 for UC 1.47 (1.40-1.54), CD 1.64 (1.53-1.76); P-trend <0.0001. Two-year lead-in: >=3 aOR 1.47 (1.41-1.53). Each class associated (per-dispensation aOR 1.03-1.20; cephalosporins 1.20, 1.14-1.25); broad-spectrum higher than narrow-spectrum (P-interaction <0.0001); ciprofloxacin/metronidazole composite aOR 1.15 (1.11-1.20). Sibling referent: >=3 dispensations aOR 1.35 (1.28-1.43) for IBD; UC 1.29 (1.20-1.39); CD 1.46 (1.23-1.62).
- Absolute risks
Not estimable (case-control design; authors state that incidence rates and absolute risks could not be estimated)
- Authors' conclusion
Higher cumulative systemic antibiotic exposure, particularly broad-spectrum, may be associated with increased risk of new-onset IBD, UC and CD in adults; association not materially altered with sibling controls; residual confounding, confounding by indication and reverse causation cannot be fully excluded.
6. Strengths
- Very large nationwide sample with histology-confirmed incident cases
- 1-year (and 2-year) lead-in to reduce reverse causation
- Dose-response and spectrum analyses
- Sibling comparison for shared genetic/childhood factors
- Prospectively recorded dispensations (no recall bias)
7. Weaknesses
- Indication for antibiotics not available; confounding by indication (e.g. infections, prodromal GI symptoms) possible despite lead-in
- Residual confounding by health-care-seeking and comorbidity (adjusted only via encounter counts and education)
- Hospital-administered antibiotics not captured
- Sibling analysis unmatched and attenuated (OR 1.35)
- Adults >=16 years only (no direct evidence for children)
- No absolute risks; Swedish IBD and prescribing patterns may limit generalisability
- Several analyses reported as 'data not shown'
8. Risk of bias
- Orienting tool
- ROBINS-E
- Type of assessment
- structured assessment based on the full text by a single reviewer (no formal double review)
- Full formal assessment
- no
- Overall risk of bias
- some concerns
- Rationale
Single-reviewer structured ROBINS-E-oriented judgement based on the full text (PMC author manuscript); not formal (needs two independent reviewers and a protocol).
| Domain | Judgement | Rationale |
|---|---|---|
| Confounding | some concerns | Adjustment for education and health-care use; sibling comparison; but no indication data, smoking, diet or other lifestyle factors. |
| Measurement of exposure | low | Register-based dispensations with fixed lead-in; non-differential misclassification of adherence. |
| Selection of participants | low | All consecutive incident cases nationally; population controls matched by incidence density. |
| Post-exposure interventions | not applicable | Not relevant. |
| Missing data | low | Complete registers; education unknown category used. |
| Measurement of outcome | low | Histopathology plus diagnosis code, PPV 95%. |
| Selection of reported result | some concerns | Multiple subgroup analyses and several 'data not shown' results; ever-vs-never estimate differs between versions (1.94 here vs 1.88 in record). |
Full-text review (25 October 2026): Full text (author manuscript) gives ever-vs-never aOR 1.94 (1.85-2.03), not 1.88; added dose-response CIs, UC/CD estimates, 2-year lead-in, class and spectrum results, sibling UC/CD estimates, inclusion criteria (PPV 95%), funding/COI, inability to estimate absolute risk; ROBINS-E domains (overall unchanged).
9. Assessment of the statistical interpretation
Modest, graded associations (aOR 1.11-1.55; 1.35 vs siblings) with tight CIs; attenuation versus siblings indicates partial confounding by shared factors. OR approximates relative risk for a rare disease, but no absolute risks are available.
10. Relevance to the specific claim
C-ABX-07 (supports association).
11. Independent contrary findings
12. Transferability to Germany and Europe
High.
13. Overall methodological judgement
Strong, consistent evidence of a dose-dependent association between antibiotic dispensations and adult-onset IBD, partly persisting within families. Causality not established (indication, reverse causation). It concerns adults, not children, and the within-family estimate (about 35% higher odds with >=3 dispensations) is well below 'nearly doubling'.
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | high |
| Risk of bias | some concerns |
| Precision of results | high |
| Directness | direct |
| Reproducibility | partly replicated |
| Consistency with the overall evidence | consistent |
| Regional transferability | high |
| Adequacy of the interpretation (by the archive) | not applicable |
14. Open questions
Validation outside Sweden; indication-adjusted analyses; absolute risk; paediatric data from comparable designs.