Ulcerative Colitis: Nion-Larmurier I

Sokol H, Seksik P, Furet JP, Firmesse O, Nion-Larmurier I, Beaugerie L, Cosnes J, Corthier G, Marteau P, Doré J. · UEPSD, INRA, Jouy-en-Josas, France. · Inflamm Bowel Dis. · Pubmed #19235886 No free full text.

Abstract: BACKGROUND: The intestinal microbiota is suspected to play a role in colitis and particularly in inflammatory bowel disease (IBD) pathogenesis. The aim was to compare the fecal microbiota composition of patients with colitis to that of healthy subjects (HS). METHODS: fecal samples from 22 active Crohn's disease (A-CD) patients, 10 CD patients in remission (R-CD), 13 active ulcerative colitis (A-UC) patients, 4 UC patients in remission (R-UC), 8 infectious colitis (IC) patients, and 27 HS were analyzed by quantitative real-time polymerase chain reaction (PCR) targeting the 16S rRNA gene. Bacterial counts were transformed to logarithms (Log(10) CFU) for statistical analysis. RESULTS: Bacteria of the phylum Firmicutes (Clostridium leptum and Clostridium coccoides groups) were less represented in A-IBD patients (9.7; P = 0.004) and IC (9.4; P = 0.02), compared to HS (10.8). Faecalibacterium prausnitzii species (a major representative of the C. leptum group) had lower counts in A-IBD and IC patients compared to HS (8.8 and 8.3 versus 10.4; P = 0.0004 and P = 0.003). The Firmicutes/Bacteroidetes ratio was lower in A-IBD (1.3; P = 0.0001) and IC patients (0.4; P = 0.002). Compared to HS, Bifidobacteria were less represented in A-IBD and IC (7.9 and 7.7 versus 9.2; P = 0.001 and P = 0.01). CONCLUSIONS: The fecal microbiota of patients with IBD differs from that of HS. The phylum Firmicutes and particularly the species F. prausnitzii, are underrepresented in A-IBD patients as well as in IC patients. These bacteria could be crucial to gut homeostasis since lower counts of F. prausnitzii are consistently associated with a reduced protection of the gut mucosa.

Cacheux W, Seksik P, Lemann M, Marteau P, Nion-Larmurier I, Afchain P, Daniel F, Beaugerie L, Cosnes J. · Department of Gastroenterology, Assistance Publique des Hôpitaux de Paris (AP-HP), Saint-Antoine Hospital, Paris, France. · Am J Gastroenterol. · Pubmed #18047542 No free full text.

Abstract: OBJECTIVES: Cyclosporine is an effective rescue therapy in steroid-refractory ulcerative colitis (UC) and may avoid immediate colectomy. However, the individual's response to cyclosporine is poorly predictable. The aim of this study was to identify predictive factors of the response to cyclosporine in steroid-refractory UC. METHODS: One hundred thirty-five patients with steroid-refractory UC, admitted consecutively between 1992 and 2004, were included. Data were collected on the first day of the cyclosporine therapy. Colonoscopy was performed within 2 days preceding or following the cyclosporine treatment in 118 patients for assessing the presence of severe endoscopic lesions. RESULTS: The actuarial rate of colectomy was 0.45 at 6 months. Cox analysis in the whole population selected three predictive criteria of colectomy: body temperature >37.5 degrees C (adjusted hazard ratio = 1.94, 95% confidence interval 1.51-2.49), heart rate >90 bpm (1.86, 1.45-2.38), and C-reactive protein (CRP) >45 mg/L (1.70, 1.34-2.16). In the 118 patients who underwent colonoscopy, the presence of severe endoscopic lesions was an independent predictive factor of colectomy (2.38, 1.80-3.14). Colonoscopy was decisive and changed the therapeutic decision in patients with one or two criteria: 71% of the patients with severe endoscopic lesions were colectomized versus 17% of the patients without severe endoscopic lesions (P < 0.001). Finally, the clinical, biological, and endoscopic criteria allowed the classification of the patients into two different groups (80%vs 20% colectomy at 6 months). CONCLUSION: In patients with steroid-refractory UC, the combination of simple criteria is useful to predict the response to cyclosporine. Colonoscopy is crucial in patients with intermediate clinical and biological severity.

Cosnes J, Seksik P, Nion-Larmurier I, Beaugerie L, Gendre JP. · Service de Gastroentérologie et Nutrition, hôpital St-Antoine, 184 rue du Faubourg St-Antoine, 75571 Paris cedex 12, France. · World J Gastroenterol. · Pubmed #16534877 links to  free full text

Abstract: AIM: To determine whether prior appendectomy modifies the phenotype and severity of Crohn's disease. METHODS: Appendectomy status and smoking habits were specified by direct interview in 2838 patients consecutively seen between 1995 and 2004. Occurrence of complications and therapeutic needs were reviewed retrospectively. Additionally, annual disease activity was assessed prospectively between 1995 and 2004 in patients who had not had ileocecal resection and of a matched control group. RESULTS: Compared to 1770 non-appendectomized patients, appendectomized patients more than 5 years before Crohn's disease diagnosis (n=716) were more often females, smokers, with ileal disease. Cox regression showed that prior appendectomy was positively related to the risk of intestinal stricture (adjusted hazard ratio, 1.24; 95% confidence interval, 1.13 to 1.36; P=0.02) and inversely related to the risk of perianal fistulization (adjusted hazard ratio, 0.75; 95% confidence interval, 0.68 to 0.83; P=0.002). No difference was observed between the two groups regarding the therapeutic needs, except for an increased risk of surgery in appendectomized patients, attributable to the increased prevalence of ileal disease. Between 1995 and 2004, Crohn's disease was active during 50% of years in appendectomized patients (1318 out of 2637 patient-years) and 51% in non-appendectomized patients (1454 out of 2841 patient-years; NS). CONCLUSION: Prior appendectomy is associated with a more proximal disease and has an increased risk of stricture and a lesser risk of anal fistulization. However, the severity of the disease is unaffected.

Cosnes J, Nion-Larmurier I, Afchain P, Beaugerie L, Gendre JP. · Hôpital Saint-Antoine, 184 rue du Faubourg St-Antoine, 75571 Paris cedex 12, France. · Clin Gastroenterol Hepatol. · Pubmed #15017631 No free full text.

Abstract: BACKGROUND AND AIMS: The aim of this study was to examine in parallel the effect of smoking on ulcerative colitis and Crohn's colitis and assess the effect of gender on the response of colitis to smoking. METHODS: Medical charts of 1784 adult consecutive patients (978 patients, ulcerative colitis; 118 patients, indeterminate colitis; and 688 patients, Crohn's colitis), whose smoking habits were specified by direct interview, were reviewed. RESULTS: The proportion of ever smokers was 42% in ulcerative colitis, 43% in indeterminate colitis, and 61% in Crohn's colitis. Smoking cessation preceded the onset of colitis in 279 patients with ulcerative colitis or indeterminate colitis (61%) and only 52 patients (12%) with Crohn's colitis. In ulcerative colitis and indeterminate colitis, current smoking delayed mean age at disease onset in men (from 32 to 41 yr; P < 0.001), but not women (from 33 to 33 yr), and decreased the need for immunosuppressants in men (10-yr cumulative risk, 26% +/- 4% in nonsmokers vs. 8% +/- 4% in smokers; P < 0.01), but not significantly in women. Conversely, in Crohn's colitis, current smoking hastened disease onset in women (from 35 to 29 yr; P < 0.001), but not men (from 32 to 31 yr), and increased the need for immunosuppressants in women (10-yr cumulative risk, 48% +/- 5% in nonsmokers vs. 58% +/- 4% in smokers; P < 0.01), but not men. CONCLUSIONS: The dual effects of smoking in colitis, beneficial in ulcerative colitis and harmful in Crohn's colitis, are modulated importantly by gender, with women having more disadvantage than men.