Bifidobacteria are assumed to exert colonization resistance to enteric pathogens. We associated C3H germfree mice with either Bifidobacterium longum or Escherichia coli or both strains and studied how they settled in the gut and the lymphoid organs as well as their effect on mucus composition. Within 24 hE. coli colonized the gut of germfree or B. longum ex-germfree mice. In contrast,B. longum was established in the intestine of E. coli ex-germfree mice only 1 month after inoculation whereas it colonized the germfree gut within 24 h. Although B. longum did not exert colonization resistance to E. coli, the establishing of bifidobacteria in the gut partly prevented changes in the E. coli cell wall. After colonization of the germfree or B. longum mono-associated mice, E. coli lipopolysaccharide exhibited a higher concentration of Kdo and the O-antigen side chain disappeared. A reduction in Kdo content was observed within 1 month in E. coli-B. longum diassociated mice whereas it remained at a high level in E. coli mono-associated mice. Association in a second step with B. longum led to Kdo reduction. Changes in E. coli LPS might be related to mucus modification. Inoculation of either bacterium led to a slow increase in mucus protein content which was however twice as high after E. coli implantation. Inoculation of B. longum in a second step led to a reduction in protein content before B. longum colonized the intestine at a high level suggesting that the protein concentration in the mucus was controlled by the host itself. A new glycoprotein of 200-230 kDa detected during the period preceeding colonization seemed to be broken down by B. longum. The resulting end product might participate in the restoration of E. coli LPS. Finally,B. longum inoculation led to the disappearance of E. coli from kidneys, liver, spleen and lung. The organs were cleared of E. coli before B. longum highly colonized the intestine suggesting that high intestinal colonization by B. longum was not required. Regulation of E. coli invasion seemed to depend on the ability of B. longum to stimulate the immune system.