SUMMARY Intestinal peristalsis is a dynamic physiologic process influenced by dietary and microbial changes. It is tightly regulated by complex cellular interactions; however, our understanding of these controls is incomplete. A distinct population of macrophages is distributed in the intestinal muscularis externa. We demonstrate that in the steady state muscularis macrophages regulate peristaltic activity of the colon. They change the pattern of smooth muscle contractions by secreting bone morphogenetic protein 2 (BMP2), which activates BMP receptor (BMPR) expressed by enteric neurons. Enteric neurons, in turn, secrete colony stimulatory factor 1 (CSF1), a growth factor required for macrophage development. Finally, stimuli from microbial commensals regulate BMP2 expression by macrophages and CSF1 expression by enteric neurons. Our findings identify a plastic, microbiota-driven, crosstalk between muscularis macrophages and enteric neurons, which controls gastrointestinal motility.

These results indicate that triggering of an anaphylactic response requires two phases (1) sensitization by aggregates through Peyer's patches and (2) efficient transfer of soluble protein across the epithelial barrier. As the majority of common food allergens tend to form aggregates, this may be of clinical importance.

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Use of the nonpathogenic yeastSaccharomyces boulardii is a thermophilic, nonpathogenic yeast administered in Western Europe for the prevention and treatment of a variety of diarrheal diseases (17, 29). However, the mechanisms by which S. boulardii controls diarrhea remain elusive. The efficacy of this yeast has been attributed to several of its properties, such as its effect on the mucosa leading to an increase in dissaccharidase activity (8) or stimulation of the immune response (7). In animals, administration of S. boulardii provides protection against intestinal lesions caused by several diarrheal pathogens (10,33). In vitro studies have demonstrated that S. boulardii exerts antagonistic activity against various bacterial pathogens (6). Recent studies have reported the adhesion of the Salmonella enterica serovars Typhimurium and Enteritis and of enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli to S. boulardii (24,25).EPEC is a major cause of diarrhea in the developing world (31, 34). The pathogenesis of EPEC infections involves a three-stage process. (i) EPEC adheres initially to intestinal epithelial cells in a pattern described as localized adherence (36). This pattern of adherence, characterized by microcolonies of bacteria associated with the epithelial cells, is dependent on the expression of the bacterial type IV bundle-forming pilus (BFP) (3). (ii) Next, the bacteria induce signal transduction pathways in host cells, leading to an elevation in the intracellular levels of Ca 2ϩ and inositol triphosphate (16, 23) and the phosphorylation of cellular proteins (4, 35, 41). (iii) These signaling events culminate in the formation of attachingand-effacing lesions which are characterized by localized degeneration of the microvilli, intimate contact between the bacteria and the infected cell, and the assembly of highly organized cytoskeletal structures in the epithelial cells just beneath the attached bacteria, forming cuplike pedestals (22,27,30). EPEC is also able to induce its internalization by nonphagocytic epithelial cells (2, 15).The aim of our study was to investigate in vitro the effect of S. boulardii against EPEC infection using the T84 cell line derived from a colon carcinoma. This cell line has been extensively used to elucidate the mechanism of EPEC-induced diarrhea. EPEC infection results in a modification of the T84 barrier function, characterized by a drop in transepithelial resistance, an increase in permeability, and modification of the distribution of the tight junction-associated protein 37). Our study reveals that S. boulardii maintains the barrier function and the viability of EPEC-infected T84 cells. Although the yeast does not modify the number of cell-associated bacteria, it reduces the number of intracellular bacteria. The phosphorylation of several proteins induced by EPEC in T84 cells is diminished in the presence of S. boulardii. Finally, the yeast interferes with the ERK1/2 mitogen-activated protein (MAP) kinase pathway that, as demonstrated in this study, is ...