Large-Scale Study Finds Healthy Lifestyle Associated with Lover Rates of Diverticulitis Regardless of Genetic Risk
Lifestyle factors and genetic predisposition contribute to the development of diverticulitis, a gastrointestinal disorder characterized by the inflammation of abdominal pouches in the large intestine that can cause intense pain, fever and other intestinal complications.
Previous studies have shown that both lifestyle factors—smoking, obesity, lack of physical activity and a diet high in red and processed meats and low in fiber—as well as genetic factors contribute to the development of diverticulitis.
However, no study has examined whether making lifestyle changes can counteract genetic predisposition, or how genetic predisposition and lifestyle factors interact to influence diverticulitis risk.
A new study in Gut, led by researchers from Mass General Brigham, provides consistent evidence across a large-scale, diverse population that a healthy lifestyle score is associated with lower rates of diverticulitis, even among those with a genetic predisposition for the disease.
“These results suggest that most individuals, regardless of genetic risk, could achieve similar relative benefits in reducing the risk of diverticulitis by adopting a healthy lifestyle,” said first author Wenjie Ma, PhD, an investigator in the Clinical and Translational Epidemiology Unit at Massachusetts General Hospital (MGH), a founding member of the Mass General Brigham healthcare system.
The researchers first analyzed genetic and detailed lifestyle data from approximately 180,000 participants in the Nurses’ Health Study (I and II) and the Health Professionals Follow-Up Study to create a five-part healthy lifestyle score based on smoking history, body mass index, physical activity, dietary fiber intake and total red meat consumption. (Genetic risk was assessed in 36,077 people with available genotype information).
Participants received a score of 1 for each component if they met the low-risk lifestyle criteria (such as never having smoked or having a BMI less than 25 kg/m2); and a score of 0 if they did not.
The researchers separately validated the healthy lifestyle score in the Southern Community Cohort Study (SCCS). Two-thirds of the SCCS cohort are self-reported non-Hispanic Black participants. Gene and lifestyle associations were further validated in the Mass General Brigham Biobank.
Over a monitoring period of 20 years, 10,299 new cases of diverticulitis were recorded among the 180,000 participants in the three cohorts.
The researchers found that people with a higher healthy lifestyle score were much less likely to get diverticulitis. For example, those who scored a 5 had half the risk of developing the disorder compared to those who scored a 0.
The individual lifestyle risk factors tracked by the researchers had different impacts among individual population cohorts. In women from the NHS and NHSII cohorts, the more physically active they were, the less likely they were to develop diverticulitis—and this decrease happened at a steady, predictable rate.
In men (HPFS), however, only vigorous physical activity showed a significant association with a decreased risk.
Overweight and obesity appeared to be a more important risk factor in women, whereas diet showed a stronger association with diverticulitis in men.
“These differences may reflect variation in the relative contribution of potential mechanisms, such as metabolic dysfunction or inflammation, in the development of diverticulitis across populations,” said senior author Andrew Chan, MD, MPH, chief of the Clinical and Translational Epidemiology Unit at MGH.
The healthy lifestyle was associated with a reduced risk of diverticulitis similarly across genetic risk categories. For example, among individuals with high genetic risk, each point increase in the healthy lifestyle score was associated with 13% reduction in the risk.
Authorship: In addition to Ma and Chan, Mass General Brigham authors include Jane Ha, Jonathan M. Downie, and Magdalena Sevilla-Gonzalez.
Disclosures: ATC served as a consultant for Pfizer Inc., Bayer Pharma AG, and Boehringer Ingelheim and received grants from Pfizer Inc., Zoe Ltd, and Freenome for work unrelated to the topic. LLS is on Data Monitoring Committee for Medtronic for work unrelated to the topic. Other authors have no conflicts of interest to disclose.
Funding: This work is supported by the National Institutes of Health (NIH) grants UM1 CA186107, R01 CA49449, U01 CA176726, R01 CA67262, U01 CA167552, U01 CA202979, R01 DK101495 (ELG, LLS, ATC), R01 DK131694 (LLS), the American Gastroenterological Association Research Foundation’s Research Scholar Awards AGA2021-13-01 (WM), NIH 1K01DK135854-01A1 (WM), and Massachusetts General Hospital (MGH) Claflin Distinguished Scholar Award (WM). ATC is an American Cancer Society Clinical Research Professor. MSG is supported by the American Diabetes Association grant 9-22-PDFPM-04 and by the NIH grant 5U24DK132733-02. JMD is supported by the MGH Research Training in Digestive Diseases training grant (NIH grant T32 DK007191) and the NIH Loan Repayment Program (L30DK137289). LHM is supported by NIH grant 1K08DK124687. CJN is supported by American Society of Colon and Rectal Surgeons Surgery Resident Research Initiation Grant. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.
Paper cited: Ma W et. al. “Lifestyle factors, genetic susceptibility and risk of incident diverticulitis: an integrated analysis of four prospective cohort studies and electronic health records-linked biobank” Gut
DOI: 10.1136/gutjnl-2025-335364