Ulcerative Colitis: Seksik P

Marteau P, Seksik P, Beaugerie L, Bouhnik Y, Reimund JM, Gambiez L, Flourié B, Godeberge P. · Service d'hépato-gastroentérologie, Hôpital Européen Georges Pompidou, 75015 Paris. · Gastroenterol Clin Biol. · Pubmed #15672566 No free full text.

This publication has no abstract.

Seksik P, Dray X, Sokol H, Marteau P. · AP-HP, Hôpital Saint-Antoine, Gastroenterology and Nutrition Department, University Pierre et Marie Curie, Paris, France. · Mol Nutr Food Res. · Pubmed #18384087 No free full text.

Abstract: The pathogenesis of inflammatory bowel disease (IBD) involves an interaction between genetically determined host susceptibility, dysregulated immune response, and the enteric microbiota. Ecological treatments including probiotics, prebiotics, and synbiotics are actively studied in Crohn's disease (CD), ulcerative colitis (UC) and pouchitis. We review herein the literature on the rational use of probiotics in IBD considering efficacy (as evaluated in randomized controlled trials), mechanisms of action and safety issues. A probiotic effect is strictly restricted to one defined strain and cannot be generalized from one to another. There is evidence of efficacy of some probiotic drugs in pouchitis (VSL#3), and in the prevention of recurrence of UC (Escherichia coli Nissle 1917). However, the evidence for efficacy of probiotic drugs in CD is still low as well as that of dietary ecological treatments. Despite an ecological (hopefully nutritional) treatment of IBD is promising, many questions remain unanswered and further clinical and fundamental studies are needed.

Sokol H, Lay C, Seksik P, Tannock GW. · Gastroenterology and Nutrition Unit, Saint-Antoine Hospital, APHP, Paris, France. · Inflamm Bowel Dis. · Pubmed #18275077 links to  free full text

Abstract: The bacterial community, in whole or in part, resident in the bowel of humans is considered to fuel the chronic immune inflammatory conditions characteristic of Crohn's disease and ulcerative colitis. Chronic or recurrent pouchitis in ulcerative colitis patients is responsive to antibiotic therapy, indicating that bacteria are the etiological agents. Microbiological investigations of the bacterial communities in stool or of biopsy-associated bacteria have so far failed to reveal conclusively the existence of pathogens or bacterial communities of consistently altered composition in IBD patients relative to control subjects. Confounding factors need to be eliminated from future studies by using better-defined patient populations of newly diagnosed and untreated individuals and by improved sampling procedures.

Seksik P, Contou JF, Ducrotté P, Faucheron JL, de Parades V. · Service d'hépato-gastroentérologie, Hôpital Européen Georges Pompidou, 75015 Paris. · Gastroenterol Clin Biol. · Pubmed #15672568 No free full text.

This publication has no abstract.

Seksik P, Marteau P. · Service de Gastro-Entérologie, Hôpital Européen Georges Pompidou, Paris, France. · Therapie. · Pubmed #15199674 No free full text.

Abstract: Probiotics may modulate intestinal flora and immunity and are therefore studied in an attempt to modulate experimental colitis or human inflammatory bowel disease. We analysed randomised controlled trials performed using probiotics in humans with Crohn's disease, ulcerative colitis and pouchitis. Perspectives include the use of genetically modified micro-organisms to deliver anti-inflammatory agents to the gastrointestinal tract.

Marteau P, Seksik P, Shanahan F. · Gastroenterology Department, European Hospital Georges Pompidou, AP-HP & Paris V University, France. · Best Pract Res Clin Gastroenterol. · Pubmed #12617882 No free full text.

Abstract: In this chapter we summarize the clinical and experimental data which indicate that bacteria, especially from the endogenous microflora, play a role in the pathogenesis of Crohn's disease, ulcerative colitis and pouchitis. We review the clinical trials, focusing on randomized controlled trials which used antibiotics or probiotics to treat situations of IBD or prevent recurrence, and we discuss the future of this approach.

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.

Branche J, Cortot A, Bourreille A, Coffin B, de Vos M, de Saussure P, Seksik P, Marteau P, Lemann M, Colombel JF. · Service des Maladies de l'Appareil Digestif et de la Nutrition, Hôpital Huriez, CHU Lille, Lille, France. · Inflamm Bowel Dis. · Pubmed #19137604 No free full text.

Abstract: BACKGROUND: Cyclosporine is considered a safe and effective treatment of severe steroid-refractory ulcerative colitis (UC). However, few data are available concerning its safety profile in pregnant women. We report here the experience of 5 GETAID centers. METHODS: In a retrospective study data on patients with severe UC treated with cyclosporine during pregnancy were extracted from medical records of consecutive patients treated between 2001 and 2007. RESULTS: Eight patients (median age 30.5 years old) were identified. At the time of flare-up the median duration of pregnancy was 11.5 weeks of gestation (range 4-25). Seven patients had pancolitis. All patients had more than 3 commonly used clinical and biological severity criteria. Three patients had severe endoscopic lesions and 5 patients had not. All patients received intravenous corticosteroids for at least 7 days before introduction of cyclosporine. Two patients received azathioprine during treatment with cyclosporine. No severe infections or other complications due to treatment were observed. Treatment was effective in 7/8 patients. One patient received infliximab due to cyclosporine therapy failure with a good outcome. No colectomy was performed during pregnancy. Seven pregnancies were conducted to term, but 1 in utero death occurred due to maternal absence of S-protein. Two newborns were premature, including 1 case of hypotrophy. No malformations were observed. CONCLUSIONS: In our experience, treatment with cyclosporine for steroid-refractory UC during pregnancy can be considered safe and effective.

Seksik P. · Service de gastro-entérologie et nutrition, hôpital Saint-Antoine, 184, rue du faubourg-Saint-Antoine, 75571 Paris cedex 12, France. · Gastroenterol Clin Biol. · Pubmed #19013043 No free full text.

This publication has no abstract.

Farhi D, Cosnes J, Zizi N, Chosidow O, Seksik P, Beaugerie L, Aractingi S, Khosrotehrani K. · Department of Dermatology, Hôpital Tenon, AP-HP, Paris, France. · Medicine (Baltimore). · Pubmed #18794711 No free full text.

Abstract: Erythema nodosum and pyoderma gangrenosum are the most common cutaneous manifestations in inflammatory bowel diseases (IBD). We conducted the current study to assess the cumulative prevalence of erythema nodosum and pyoderma gangrenosum in patients with IBD and to appraise their association with demographic, clinical, and prognostic factors related to IBD. Between 2000 and 2005, data for all patients with IBD at our gastroenterology department were prospectively and systematically collected using a standardized protocol.Among 2402 patients (1521 diagnosed with Crohn disease [63.3%] and 744 with ulcerative colitis [31.0%]), 140 (5.8%) had at least 1 skin manifestation. The most frequent dermatologic symptoms were erythema nodosum (4.0%) and pyoderma gangrenosum (0.75%). In multivariate analyses, erythema nodosum was significantly and independently associated with a diagnosis of Crohn disease (p < 0.001), female sex (p < 0.001), eye and joint involvement (p < 0.001), and pyoderma gangrenosum (p < 0.0001).Among patients with Crohn disease, erythema nodosum was associated with isolated colonic involvement (p = 0.0001). Pyoderma gangrenosum was significantly and independently associated with black African origin (p = 0.003), familial history of ulcerative colitis (p = 0.0005), uninterrupted pancolitis as the initial location of IBD (p = 0.03), permanent stoma (p = 0.002), eye involvement (p = 0.001), and erythema nodosum (p < 0.0001). It is noteworthy that the association between pyoderma gangrenosum and permanent stoma persisted after exclusion of patients with peristomal pyoderma gangrenosum (p = 0.07).In conclusion, neither erythema nodosum nor pyoderma gangrenosum was significantly associated with the severity criteria in IBD; however, their occurrence may reflect a peculiar phenotype among affected patients.

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.

Daniel F, Loriot MA, Seksik P, Cosnes J, Gornet JM, Lémann M, Fein F, Vernier-Massouille G, De Vos M, Boureille A, Treton X, Flourié B, Roblin X, Louis E, Zerbib F, Beaune P, Marteau P. · Department of Gastroenterology, Assistance Publique des Hôpitaux de Paris (AP-HP), Hôpital Européen Georges Pompidou, Paris, France. · Inflamm Bowel Dis. · Pubmed #17206635 links to  free full text

Abstract: BACKGROUND: Cyclosporine A (CsA) is inconstantly effective in inducing remission in acute attacks of ulcerative colitis (UC) not responding to steroids. This study aimed to establish whether multidrug resistance gene (MDR)1 polymorphisms would be associated with CsA failure. PATIENTS AND METHODS: The distribution of the different genotypes of single nucleotide polymorphisms (SNP) G2677T/A and C3435T of MDR1 exons 21 and 26, respectively, was studied in 154 patients (mean age, 44 yr) who had received CsA to treat severe attacks of steroid resistant UC in 11 centers in France and Belgium. Patients were classified as CsA failure (n = 50) when they needed colectomy within 30 days after CsA initiation. The SNPs were detected by use of a 5' nuclease allelic discrimination assay. RESULTS: There was a significant association between the G2677T/A polymorphism distribution (exon 21) and the risk for CsA failure (P = 0.0001). The TT genotype of exon 21 was significantly associated with the risk compared with the two other genotypes (odds ratio, 3.77; 95% confidence interval, 1.42-9.97, P = 0.007). There was no significant association between the genotype C3435T distribution (exon 26) and the risk of CsA failure (P = 0.23). CONCLUSION: The TT genotype of exon 21 MDR1 polymorphisms is associated with a higher risk of CsA failure in patients with steroid resistant UC. Further studies should be performed to establish whether other treatments could be more efficient to avoid surgery in this subset of patients.

Sokol H, Lepage P, Seksik P, Doré J, Marteau P. · INRA, UEPSD, CR de Jouy-en-Josas, 78352 Jouy-en-Josas, France. · J Clin Microbiol. · Pubmed #16954244 links to  free full text

Abstract: Previous studies of the endogenous microbiota in patients with ulcerative colitis (UC) have not taken bacterial activity into account, yet bacteria with high transcriptional activity might have a more important pathophysiological role than inactive bacteria. We therefore analyzed the biodiversity of active bacteria in the fecal microbiota of UC patients, in comparison with that of healthy subjects. Feces were collected from nine patients with active UC and from nine healthy controls. Total DNA and RNA were extracted, and 16S ribosomal DNA and RNA were amplified by PCR and reverse transcription-PCR, respectively. Amplification products were compared by means of temporal temperature gradient gel electrophoresis (TTGE). Bands of interest were excised, sequenced, and identified by comparison with the GenBank database (NCBI). The dominant-species diversity based on RNA-derived TTGE profiles was significantly lower for UC patients than for healthy controls (P = 0.01). The mean similarity index between the "present" and "active" microbiota was 74% +/- 18% for UC patients. Comparison of the individual "active" microbiota identified a band that was present for eight UC patients and only two controls (89% versus 22%; P = 0.008). The band was sequenced for 6 patients and always corresponded to Escherichia coli. The biodiversity of active bacteria in the dominant fecal microbiota of patients with UC is lower than that of healthy subjects. E. coli is more represented in the active microbiota of UC patients. The possible pathophysiological role of this difference remains to be determined.

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.

Sokol H, Seksik P, Rigottier-Gois L, Lay C, Lepage P, Podglajen I, Marteau P, Doré J. · Unité d'Ecologie et Physiologie du Système Digestif, INRA Research Center, Jouy-En-Josas, France. · Inflamm Bowel Dis. · Pubmed #16432374 links to  free full text

Abstract: BACKGROUND: Abnormalities have been described in the fecal microbiota of patients with IBD, but it is not known whether they are specific for inflammatory bowel disease (IBD) or to some extent common to other forms of colitis. The aim of this study was to compare the bacterial composition of the dominant fecal microbiota in patients with Crohn's disease (CD), ulcerative colitis (UC), infectious colitis (IC), and in healthy subjects (HS). METHODS: Fluorescent in situ hybridization adapted to flow cytometry was used to analyze the bacterial composition of fecal samples from 13 patients with active CD, 13 patients with active UC, 5 patients with IC, and 13 HS. We used 6 group-specific probes targeting 16S rRNA and spanning the main phylogenetic groups of the fecal microbiota. RESULTS: A significantly higher proportion of the total fecal bacteria were recognized by the 6 probes in HS (86.6%+/-12.7) and in IC (84.0%+/-11.7) than in patients with IBD (70.9%+/-15 in CD and 60.1%+/-25.7 in UC). The Clostridium coccoides group was reduced in UC (20.0%+/-13.3 versus 42.0%+/-12.0 in HS; P<.001), whereas the C leptum group was reduced in CD (13.1%+/-11.9 versus 25.2%+/-14.2 in HS; P=.002). The Bacteroides group was more abundant in IC (36.4%+/-22.9) than in the other 3 groups (13.8%+/-11.8 in CD, 11.7%+/-11.7 in UC, 12.1%+/-7.0 in HS; P<.001 for all 3 comparisons). CONCLUSIONS: In IBD the dominant fecal microbiota comprises unusual bacterial species. Moreover, CD and UC fecal microbiota harbor specific discrepancies and differ from that of IC and healthy subjects.

Lepage P, Seksik P, Sutren M, de la Cochetière MF, Jian R, Marteau P, Doré J. · National Institute for Agromonic Research, Digestive Tract Ecology and Physiology Unit, Research Center, Jouy en Josas, France. · Inflamm Bowel Dis. · Pubmed #15867587 No free full text.

Abstract: BACKGROUND: The mucosa-associated microbiota, being very close to the inflammatory process associated with inflammatory bowel disease (IBD), may have a pathogenic role. We used a culture-independent method to analyze the mucosa-associated microbiota in IBD patients at various points of the distal digestive tract. METHODS: Thirty-five patients (20 with Crohn's disease, 11 with ulcerative colitis, and 4 controls) underwent colonoscopy. Biopsies (n = 126) were taken from 4 sites: the ileum, right colon, left colon, and rectum. Fecal samples were also obtained from 7 individuals. Temporal temperature gradient gel electrophoresis (TTGE) of 16S rDNA was used to evaluate dominant species diversity. TTGE profiles were compared using software that measures the degree of similarity. RESULTS: In a given individual, the overall similarity percentage between the 4 segments of the distal digestive tract was 94.7 +/- 4.0%, regardless of clinical status. The average similarity of all profiles for a given segment was 59.3 +/- 18.3% in the overall population. Dendrogram analysis showed that TTGE profiles did not cluster with clinical status. Differences were observed between the dominant fecal microbiota and the mucosa-associated microbiota of all 4 sites, with similarity percentages less than 92%. CONCLUSIONS: These results confirm that the dominant species differ between the mucosa-associated and fecal microbiota. They also show that, in a given individual, the microbiota is relatively stable along the distal digestive tract, showing a slight evolution in dominant species diversity from the ileum to the rectum, in both healthy subjects and patients with IBD.

Lemann M, Beaugerie L, Bouhnik Y, Flourié B, Reimund JM, Seksik P, Marteau P. · Service de gastroentérologie, Hôpital Saint Louis, 75010 Paris. · Gastroenterol Clin Biol. · Pubmed #15672574 No free full text.

This publication has no abstract.

Marteau P, Beaugerie L, Bouhnik Y, Flourié B, Gambiez L, Reimund JM, Seksik P. · Service d'hépato-gastroentérologie, Hôpital Européen Georges Pompidou, 75015 Paris. · Gastroenterol Clin Biol. · Pubmed #15672567 No free full text.

This publication has no abstract.

Godeberge P, Desreumaux P, Slim K, Dupas JL, Marteau P, Beaugerie L, Bouhnik Y, Flourié B, Gambiez L, Reimund JM, Seksik P. · Département médico-chirurgical de pathologie digestive, Institut Mutualiste Montsouris, 75014 Paris. · Gastroenterol Clin Biol. · Pubmed #15672565 No free full text.

This publication has no abstract.

Daniel F, Seksik P, Cacheux W, Jian R, Marteau P. · Département d'Hepato-Gastroentŕologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France. · Inflamm Bowel Dis. · Pubmed #15290921 No free full text.

Abstract: Derivatives of 5-aminosalicylic acid (5-ASA) used for the treatment of inflammatory bowel disease may induce acute pancreatitis of immunoallergic origin. 4-aminosalicylic acid (4-ASA) differs from its 5-ASA counterpart by the position of the NH2 group and has shown efficacy in ulcerative colitis. The risk of cross intolerance reaction between 5-ASA and 4-ASA has currently never been evaluated. We report three cases of 5-ASA-induced pancreatitis, with no recurrence of pancreatitis during subsequent treatment with 4-ASA enemas. We conclude that 4-ASA enemas are a safe and well-tolerated therapeutic alternative whenever 5-ASA-induced pancreatitis occurs.

Marteau P, Seksik P. · Service d'Hépato-Gastroentérologie, Hôpital Européen Georges Pompidou, 20 rue Leblanc, 75908 Paris. · Gastroenterol Clin Biol. · Pubmed #11787388 No free full text.

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Seksik P, Gozlan J, Guitton C, Galula G, Maury E, Offenstadt G. · Medical Intensive Care Unit, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, France. · Intensive Care Med. · Pubmed #10342519 No free full text.

Abstract: Herpes simplex virus hepatitis (HSV hepatitis) is an uncommon and severe complication of HSV type 1 and HSV type 2 infection. HSV hepatitis affects mostly immunocompromised patients. We report the case of a young man without any previous known immunodeficiency who developed fatal HSV hepatitis in the first 8 days of oral corticotherapy given for ulcerative colitis. A prompt diagnosis was possible because HSV was recovered from peripheral blood leukocytes.

Sokol H, Lepage P, Seksik P, Doré J, Marteau P. · No affiliation provided · Gut. · Pubmed #17172591 No free full text.

This publication has no abstract.