We appreciate Dr. Kawada’s interest in our study.1 Our data support an overall linear relationship between the inflammatory potential of diet and risk of diverticulitis.2 Although the linear trend was more evident among participants with a body mass index ≥ 25 kg/m2 or those performing vigorous activity, a formal test for statistical interaction was not significant. Thus, we were conservative about concluding whether there was a truly biologic difference in the association according to either body mass index or activity. We concur with Dr. Kawada that further studies are warranted to evaluate if specific subgroups would preferentially benefit from consuming an anti-inflammatory diet for prevention of diverticulitis.
A growing body of evidence suggests that chronic inflammation may play a role in the pathogenesis of diverticulitis, including 1) lifestyle and dietary risk factors for diverticulitis are closely related to chronic inflammation; 2) patients with diverticular disease demonstrate low-grade inflammatory features in both colonic mucosa and gut microbiota; and 3) associations between diverticular disease and cardiovascular disease indicate shared etiopathogenetic mechanisms. In our study, the positive associations for CRP and IL-6 were seen primarily by comparing the extreme categories. As Dr. Kawada points out, this might be owing to a lack of specificity of these markers for diverticulitis. Alternative circulating markers of gut-related inflammation and intestinal permeability, such as LPS binding protein (LBP) and soluble CD14 (sCD14),3,4 or mucosal or fecal markers of immune responses and inflammation such as fecal calprotectin,5 may yield better specificity for disease prediction. In addition, biomarkers in our study were measured only at baseline, and variation over time might have attenuated the associations. Thus, more specific markers of intestinal inflammation with repeated measurements prior to diverticulitis should be considered in future studies to further our understanding of the role of chronic inflammation in diverticulitis.
Acknowledgments
Funding: This work was supported by grants UM1 CA186107, R01 DK101495 and K24 DK098311 from the National Institutes of Health and MGH Executive Committee Tosteson & Fund for Medical Discovery Award. The funders had no role in study design, data collection and analysis, interpretation of data, writing of the report, and decision to submit the paper for publication.
Footnotes
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Declaration of interests: Andrew T. Chan receives consulting fees from Janssen, Pfizer Inc., and Bayer Pharma AG for work unrelated to the topic of this manuscript. The remaining authors have no conflicts of interest to disclose.
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