The Probiotic VSL#3 Has Anti-inflammatory Effects and Could Reduce Endoscopic Recurrence After Surgery for Crohn's Disease  Richard N. Fedorak, Brian G. Feagan, Naomi Hotte, Des Leddin, Levinus A. Dieleman, Denis M. Petrunia, Robert Enns, Alain Bitton, Naoki Chiba, Pierre Paré, Alaa Rostom, John Marshall, William Depew, Charles N. Bernstein, Remo Panaccione, Guy Aumais, A. Hillary Steinhart, Alan Cockeram, Robert J. Bailey, Paolo Gionchetti, Cindy Wong, Karen Madsen  Clinical Gastroenterology and Hepatology  Volume 13, Issue 5, Pages 928-935.e2 (May 2015) DOI: 10.1016/j.cgh.2014.10.031 Copyright © 2015 AGA Institute Terms and Conditions

Figure 1 Schematic diagram outlining the group of patients who received VSL#3 early after surgery (within the first 30 days after surgery, early VSL#3 treatment group, shaded bar) compared with those who received VSL#3 late (from days 91 to 365 after surgery, late VSL#3 treatment group, open hatched bar). The late VSL#3 treatment group included patients with no or mild endoscopic recurrence (Rutgeerts grade 0, 1, 2). Clinical Gastroenterology and Hepatology 2015 13, 928-935.e2DOI: (10.1016/j.cgh.2014.10.031) Copyright © 2015 AGA Institute Terms and Conditions

Figure 2 Percent severe endoscopic recurrence (Rutgeerts score i3, i4) at day 90 and day 365. Between day 0 and day 90, patients received either placebo (open bar) or early VSL#3 treatment (black bar). Between day 91 and day 365, all patients received VSL#3, defining a group who received early VSL#3 (early VSL#3 treatment group, black bar) and one who received VSL#3 late (ie, from days 91 to 365, late VSL#3 treatment group, open hatched bar). At day 90, the proportions of patients with severe endoscopic lesions did not differ significantly between VSL#3 and placebo. Similarly, the proportions of patients with non-severe lesions at day 90 who had severe endoscopic recurrence at day 365 were numerically but not statistically different in the early VSL#3 group (given VSL#3 for the entire 365 days) compared with the late VSL#3 group (given VSL#3 from days 90 through 365) (P = .09). Clinical Gastroenterology and Hepatology 2015 13, 928-935.e2DOI: (10.1016/j.cgh.2014.10.031) Copyright © 2015 AGA Institute Terms and Conditions

Figure 3 Mucosal expression of cytokines at day 90 as expressed as relative-fold change in early VSL#3 group compared with placebo group. For comparisons of relative expression, the housekeeping gene GAPDH was used to normalize each cytokine before calculating fold change. To show cytokine expression differences between the early VSL#3 and placebo groups at day 90, each patient was calibrated against the group average of the placebo group for each cytokine before averaging. Patients receiving VSL#3 from day 0 had overall reduced cytokine expression compared with the placebo group. *P < .05 compared with placebo group at day 90. IFN, interferon; IL, interleukin; TGF, transforming growth factor; TNF, tumor necrosis factor. Clinical Gastroenterology and Hepatology 2015 13, 928-935.e2DOI: (10.1016/j.cgh.2014.10.031) Copyright © 2015 AGA Institute Terms and Conditions

Supplementary Figure 1 Study participant flow. Clinical Gastroenterology and Hepatology 2015 13, 928-935.e2DOI: (10.1016/j.cgh.2014.10.031) Copyright © 2015 AGA Institute Terms and Conditions