Obesity and Weight Gain Since Early Adulthood Are Associated with a Lower Risk of Microscopic Colitis

Over the past several decades, the incidence of microscopic colitis has rapidly increased. Presumably, this trend is due in part to increased disease awareness, but it may also reflect changing environmental exposures, including smoking, medication, dietary and lifestyle factors. In particular, now that obesity is at epidemic levels, it may account at least in part for the increasing incidence of microscopic colitis.

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In the first prospective study of the association between obesity and risk of microscopic colitis, Po-Hong Liu, MD, MPH, academic investigator at the Clinical Translational Epidemiology Unit at Massachusetts General Hospital, Gastroenterologist Hamed Khalili, MD, MPH, and colleagues made a surprising discovery: Obesity and greater weight gain since early adulthood are actually associated with a lower risk of microscopic colitis in women. Their report is published in Clinical Gastroenterology and Hepatology.

Study Design

The researchers used data from two very large prospective cohorts, the Nurses' Health Study (NHS, initiated in 1976, female nurses 30 to 55 years old at baseline) and the parallel NHSII (initiated in 1989, female nurses 25 to 42 years old at baseline). 192,101 participants were eligible for this study, including 79,729 women in the NHS and 112,374 women in the NHSII.

Participants in both studies complete health questionnaires every two years. Biopsies for diagnosis of microscopic colitis were not performed routinely until the late 1980s, so for the current analysis, the study period was from 1986 to 2014 in the NHS and from 1991 to 2015 in the NHSII. Participants with a prior diagnosis of Crohn's disease, ulcerative colitis, celiac disease or cancer were excluded.

The researchers confirmed 244 cases of microscopic colitis over 4,223,868 person-years of follow-up (5.8 per 100,000 person-years).

BMI and Risk of Microscopic Colitis

Higher body mass index (BMI) was inversely associated with the risk of microscopic colitis (P < .001 for the trend). Compared with women whose BMI was 18.5 to 20.9 kg/m², the adjusted hazard ratios (aHRs) for microscopic colitis were:

• 1.14 (95% CI, 0.50–2.56) for women with BMI <18.5 kg/m²
• 0.80 (95% CI, 0.52–1.23) for women with BMI of 21–22.9 kg/m²
• 0.56 (95% CI, 0.35–0.88) for women with BMI of 23–24.9 kg/m²
• 0.61 (95% CI, 0.41–0.91) for women with BMI of 25–29.9 kg/m²
• 0.50 (95% CI, 0.32–0.79) for women with BMI ≥30 kg/m²

The inverse association appeared to be linear: each 5 kg/m² increase in BMI was associated with an aHR of 0.79 (95% CI, 0.69–0.90; P < .001 for the trend). The association between BMI and risk of microscopic colitis was not modified by cohort, age, physical activity or smoking status.

Weight Change and Risk of Microscopic Colitis

Compared with women who remained weight-neutral (weight change ≤5 kg since age 18), the aHRs for microscopic colitis were:

• 0.79 (95% CI, 0.54–1.16) for women who gained 5–9.9 kg since age 18
• 0.69 (95% CI, 0.49–0.98) for women who gained 10–19.9 kg
• 0.54 (95% CI, 0.37–0.78) for women who gained ≥20 kg

The aHR for every 10-kg increase in weight since age 18 was 0.85 (95% CI, 0.77–0.94; P = .001 for the trend).

There was no association between midlife weight change (since age 55) and the risk of microscopic colitis.

Research Implications

The pathophysiology of microscopic colitis remains largely unknown, so the biologic pathway underlying these associations is unclear, but at least two mechanisms are plausible.

First, because microscopic colitis principally affects postmenopausal women, the influence of BMI on changes in sex hormones during menopause may help explain the new findings. In previous explorations of NHS and NHSII published in Inflammatory Bowel Diseases, Dr. Khalili and colleagues found that endogenous testosterone levels are inversely associated with the risk of inflammatory bowel disease and, more specifically, published in Gastroenterology, that the use of menopausal hormone replacement therapy (which significantly lowers testosterone levels) is associated with an increased risk of microscopic colitis.

Another possibility is that microbial signatures associated with obesity or a lean phenotype may protect or increase, respectively, the risk of microscopic colitis. Additional research suggests that new-onset inflammatory bowel disease can be associated with a past history of bariatric surgery, and that this phenomenon may be related in part to changes in the gut microbiome. The potential interactions between the gut microbiome, obesity and microscopic colitis warrant further investigation.

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