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BackgroundThe long-term natural history of microscopic colitis (MC) (collagenous colitis (CC), lymphocytic colitis (LC)), traditionally considered relapsing but non-progressive diseases, is poorly defined. Whether persistent histologic inflammation in such diseases is associated with an increased risk of colorectal neoplasia (CRN) or extracolonic cancers has not been robustly established.MethodsThis retrospective cohort included diagnosed with MC at a referral center. Rates of CRN and extracolonic cancer were compared to patients undergoing screening colonoscopy (n = 306) and to the United States population using data from the Surveillance, Epidemiology, and End-Results (SEER) program. Standardized incidence ratios (SIR) and 95% confidence intervals were calculated and multivariable regression models used to identify the effect of MC diagnosis and severity on cancer risk.ResultsOur study included 221 patients with microscopic colitis (112 CC, 109 LC) among whom 77% were women. Compared to the colonoscopy control population, MC was associated with similar odds of tubular adenoma (Odds ratio (OR) 1.07, 95% CI 0.69–1.66) or villous adenoma (OR 1.26, 95% CI 0.17–9.42). Compared to patients with a single episode of MC, those with 2 or more episodes had similar risk of colon cancer (OR 0.83, 95% CI 0.20–3.39) or tubular adenoma (OR 1.49 95% CI 0.83–2.67). We also identified no statistical increase in the rates of cancer in the MC population compared to US-SEER data.ConclusionMicroscopic colitis was not associated with increased risk of CRN and extracolonic cancers when compared to controls undergoing colonoscopy or the US SEER population.

SUMMARY Tropomyosins comprise a large family of actin binding proteins with critical roles in diverse actin-based processes [1], but our understanding of how they mechanistically contribute to actin filament dynamics has been limited. We addressed this question in S. cerevisiae, where tropomyosins (Tpm1 and Tpm2), profilin (Pfy1), and formins (Bni1 and Bnr1) are required for the assembly of an array of actin cables that facilitate polarized vesicle delivery and daughter cell growth. Formins drive cable formation by promoting actin nucleation and by accelerating actin filament elongation together with profilin [2]. In contrast, how tropomyosins contribute mechanistically to cable formation has been unclear, but genetic studies demonstrate that Tpm1 plays a more important role than Tpm2 [3, 4]. Here, we found that loss of TPM1 in strains lacking BNR1 but not BNI1 led to severe defects in cable formation, polarized secretion, and cell growth, suggesting TPM1 function is required for proper Bni1-mediated cable assembly. Further, in vitro TIRF microscopy demonstrated that Tpm1 strongly enhanced Bni1- but not Bnr1-mediated actin nucleation, without affecting filament elongation rate, whereas Tpm2 had no effects on Bni1 or Bnr1. Tpm1 stimulation of Bni1-mediated nucleation also required profilin and its interactions with both G-actin and formins. Together these results demonstrate that yeast Tpm1 works in concert with profilin to promote formin-dependent nucleation of actin cables, thus expanding our understanding of how specific tropomyosin isoforms influence actin dynamics.

Introduction Adipose tissue in mesenteric fat plays a key role in systemic and luminal inflammation. However, little is known about the role of visceral adipose tissue (VAT) and its interaction with genetic predisposition in Crohn’s disease (CD) progression. Methods Our study population included CD patients enrolled in Prospective Registry in Inflammatory Bowel Disease Study at Massachusetts General Hospital (PRISM). VAT volume was measured from CT scans using Aquarius 3D. We used logistic regression models to estimate the multivariable-adjusted odds ratio (MV-adjusted OR) and 95% confidence interval (CI). We tested for effect modification by genetic predisposition using the log-likelihood ratio test. Results Among 482 CD patients with available data on VAT, 174 developed penetrating disease, 132 developed stricturing disease, 147 developed perianal disease, and 252 required surgery. Compared to individuals in the lowest quartile of VAT volume, the MV-adjusted OR of surgery among individuals in the highest quartile was 2.02 (95% CI, 1.09 – 3.76; Ptrend = 0.006). Similarly, the risk of penetrating disease appeared to increase with greater VAT volume (Ptrend = 0.022) but not stricturing or perianal disease (all Ptrend > 0.23). The associations between VAT volume and CD complications were not modified by genetic predisposition (all Pinteraction > 0.12). Conclusions Visceral adiposity as measured by VAT volume may be associated with a significant increase in risk of penetrating disease and surgery in CD. Our data suggest that visceral adiposity as measured by VAT may negatively impact long-term progression of CD regardless of genetic predisposition.