PubMed · 14094084
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E GILBRIN. 1963-10-10. [BLIND LOOPS].. https://pubmed.ncbi.nlm.nih.gov/14094084/
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BACKGROUND AND AIMS: The involvement of bacteria in the pathogenesis of inflammatory bowel disease has been discussed for several years. In this study we evaluated the ability of E. coli isolates from inflamed and noninflamed colonic mucosa to activate NF-kappaB. MATERIALS AND METHODS: Fifteen bacterial strains from inflamed and six from noninflamed colonic tissues from IBD patients. Their ability to induce NF-kappaB activation was examined in vitro by gel-shift assays. The activation of the TNF-alpha promoter was determined by reporter gene assays. Bacterial isolates were characterized by invasion assays, electron microscopy, and PCR. RESULTS: Four of 15 E. coli bacterial isolates from inflamed IBD tissues induced NF-kappaB activity in intestinal epithelial cells as determined by gel-shift assays. NF-kappaB activation was only seen with living bacteria but not with heat-inactivated cells. Isolates from noninflamed tissues and a wild-type E. coli control strain induced a weaker or no activation. Reporter gene assays with a construct comprising a luciferase gene driven by the TNF-alpha promoter revealed that isolates from Crohn's disease patients induced a stronger activation of the TNF-alpha gene than isolates from ulcerative colitis patients. The isolated bacteria invaded HT-29 cells, although typical virulence genes for enteropathogenic, enterhemorrhagic, or enteroinvasive E. coli, i.e., eae, tir, EspA, Per (A-C), ipaC, were not detected in these cells. Bacterial invasion was additionally confirmed by electron microscopy examination. CONCLUSION: Our results indicate that E. coli strains can be found in the mucosa of some IBD patients which are able to activate NF-kappaB similar to known pathogenic strains. The absence of several virulence genes in these cells suggests that they are members of the luminal flora which acquire as yet unidentified virulence determinants and are therefore involved in the pathophysiology of IBD.
BACKGROUND: The ability to discern ancestral relationships between individual human colon crypts is limited. Widely separated crypts likely trace their common ancestors to a time around birth, but closely spaced adult crypts may share more recent common ancestors if they frequently divide by fission to form clonal patches. Alternatively, adult crypts may be long-lived structures that infrequently divide or die. METHODS: Methylation patterns (the 5' to 3' order of methylation) at CpG sites that exhibit random changes with aging were measured from isolated crypts by bisulfite genomic sequencing. This epigenetic drift may be used to infer ancestry because recently related crypts should have similar methylation patterns. RESULTS: Methylation patterns were different between widely separated ("unrelated") crypts greater than 15 cm apart. Evidence for a more recent relationship between directly adjacent or branched crypts could not be found because their methylation pattern distances were not significantly different than widely separated crypt pairs. Methylation patterns are essentially equally different between two adult human crypts regardless of their relative locations. CONCLUSIONS: Methylation patterns appear to record somatic cell trees. Starting from a single cell at conception, sequences replicate and may drift apart. Most adult human colon crypts appear to be long-lived structures that become mosaic with respect to methylation during aging.
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