Authors: Wenjie Ma, Jane Ha, Christopher J. Neylan, Heather Munro, Duncan Skerrett, Jonathan M. Downie, Magdalena Sevilla-González, Mark Steinwandel, Michael Mumma, Wei Zheng, Lillias H. Maguire, Edward L. Giovannucci, Lisa L. Strate, Andrew T. Chan
Journal: Gut
Year: 2025
Volume: 74
Pages: 2004–2011
DOI: 10.1136/gutjnl-2025-335364
Study at a glance
- Study type: Integrated analysis of prospective cohorts and biobank data
- Number of studies: Four cohorts analysed
- Participants: 179,564 in main cohort analysis (NHS, NHSII, HPFS); 30,750 validation cohort (SCCS); 36,077 with genetic data; further validation in MGBB
- Population studied: Health professionals (NHS, NHSII, HPFS), predominantly non-Hispanic Black and lower-income participants (SCCS), biobank patients (MGBB)
- Intervention or approach studied: Healthy lifestyle score comprising smoking, body mass index, physical activity, fibre intake, and red meat intake
- Comparison group: Participants with unhealthy versus healthy lifestyle scores; low versus high genetic risk
- Follow-up duration: Average 20 years (NHS, NHSII, HPFS); 11.9 years (SCCS)
- Main outcome(s): Incident diverticulitis
Why was this study done?
Diverticulitis occurs when small pouches in the colon wall become inflamed, causing pain, fever, and sometimes complications requiring hospitalisation or surgery. Previous research identified lifestyle factors (smoking, obesity, low physical activity, dietary patterns) and genetic variants as contributors to diverticulitis risk. However, whether lifestyle modification could reduce risk in people with high genetic susceptibility remained unclear. Ma and colleagues examined whether maintaining a healthy lifestyle could reduce diverticulitis risk regardless of genetic predisposition.
How was the study performed?
The main analysis included 179,564 participants from three US health professional cohorts (Nurses’ Health Study, Nurses’ Health Study II, Health Professionals Follow-up Study) who completed questionnaires every two to four years. A healthy lifestyle score (0-5 points) was created from five factors: never smoking, BMI below 25, regular physical activity, high fibre intake, and low red meat consumption. Findings were validated in 30,750 participants from the Southern Community Cohort Study (two-thirds non-Hispanic Black).
For genetic analysis, 36,077 participants with DNA samples were assessed using a polygenic risk score combining multiple genetic variants. Results were validated in the Mass General Brigham Biobank. Follow-up averaged 20 years in health professional cohorts and 12 years in the Southern Community Cohort Study. Diverticulitis cases were identified through questionnaires and validated against medical records.
What did the researchers find?
Over follow-up, 10,299 new diverticulitis cases occurred. Each lifestyle factor associated with risk: overweight participants had 32% higher risk, obese participants 44% higher risk. Smokers had elevated risk, whilst higher physical activity and fibre intake showed lower risk. Higher red meat intake linked to increased risk.
For each one-point increase in lifestyle score, risk decreased 12%. Participants scoring five had half the risk of those scoring zero. This pattern was consistent across all cohorts. In the Southern Community Cohort Study, the healthiest lifestyle showed 31% lower risk, similar in White and Black participants.
Higher genetic risk strongly associated with diverticulitis (58% increase per standard deviation in polygenic risk score), particularly in those under 60 years. Crucially, healthy lifestyle reduced risk similarly across all genetic risk groups, potentially preventing 23-42% of diverticulitis cases. People with highest genetic risk and least healthy lifestyles had nearly five times the risk compared to those with lowest genetic risk and healthiest lifestyles. The Mass General Brigham Biobank confirmed genetic associations and showed higher BMI linked to increased risk at all genetic susceptibility levels.
What did the authors conclude?
The authors concluded that maintaining a healthy lifestyle was associated with reduced diverticulitis risk regardless of population differences and genetic susceptibilities. Benefits were consistent across diverse populations, including predominantly Black cohorts. Even individuals with high genetic risk could substantially reduce their likelihood of developing diverticulitis through lifestyle modification. The findings have direct implications for clinical practice and public health, indicating most people can achieve similar relative benefits irrespective of genetic background.
Key takeaways
- A healthy lifestyle score combining five factors (not smoking, healthy weight, regular physical activity, high fibre intake, and low red meat consumption) was associated with half the risk of diverticulitis compared to an unhealthy lifestyle.
- The lifestyle benefit was consistent across diverse populations, including predominantly non-Hispanic Black participants in the Southern Community Cohort Study.
- Higher genetic risk was strongly associated with increased diverticulitis risk, but healthy lifestyle behaviours reduced risk similarly across all genetic risk categories.
- Maintaining a healthy lifestyle could potentially prevent between one-quarter and two-fifths of diverticulitis cases, regardless of genetic predisposition.
- Individuals with the highest genetic risk and least healthy lifestyles had nearly five times the risk compared to those with the lowest genetic risk and healthiest behaviours.
This Scientific Publication Summary is an objective summary of the published study for personal and educational use. It does not constitute medical advice, endorsement of the intervention, or a recommendation to alter clinical practice.