Ulcerative Colitis: Doré J

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.

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.

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.

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

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