Our gut microbiota provide a number of important functions, one of which is the metabolism of dietary fiber and other macronutrients that are undigested by the host. The main products of this fermentation process are short-chain fatty acids (SCFAs) and other intermediate metabolites including lactate and succinate. Production of these metabolites is dependent on diet and gut microbiota composition. There is increasing evidence for the role of SCFAs in host physiology and metabolic processes as well as chronic inflammatory conditions such as allergic disease and obesity. We aimed to investigate differences in fecal SCFAs and intermediate metabolites in 163 infants at 3–5 months of age according to breastfeeding status. Compared to no exposure to human milk at time of fecal sample collection, exclusive breastfeeding was associated with lower absolute concentrations of total SCFAs, acetate, butyrate, propionate, valerate, isobutyrate, and isovalerate, yet higher concentrations of lactate. Further, the relative proportion of acetate was higher with exclusive breastfeeding. Compared to non-breastfed infants, those exclusively breastfed were four times more likely (aOR 4.50, 95% CI 1.58–12.82) to have a higher proportion of acetate relative to other SCFAs in their gut. This association was independent of birth mode, intrapartum antibiotics, infant sex, age, recruitment site, and maternal BMI or socioeconomic status. Our study confirms that breastfeeding strongly influences the composition of fecal microbial metabolites in infancy.

Morphologic and functional similarities between the lymphoid tissues of the gut and lung have shown that a common mucosal immune system is involved in the protection of mucosal sites (1). Several studies have demonstrated the relevance of antibody, particularly IgA, in mucosal immunity. However, less attention has been directed to the role of cell-mediated immunity. The recent development of methods for the isolation of mucosal Iymphoid cells (2-7) has facilitated the analysis of cytotoxic functions of lymphocytes from intestine and lung. Thus, it has been shown that guinea pig and human lymphocytes from the intestinal mucosa exert mitogeninduced, antibody-dependent, and spontaneous cellular cytotoxicity (6-8). Spontaneous cytotoxic activity of cells from the mouse lung (9) and gut (10) has many characteristics of natural killer (NK) 1 cytotoxicity.The main effector cells of NK activity in human (11), rat (12), and mouse (13) are large granular lymphocytes (LGL) with a high cytoplasmic/nuclear ratio and azurophilic granules in the cytoplasm. Because large lymphocytes with cytoplasmic granules are abundant in the mammalian intestinal mucosa (2), we postulated that gut granulated lymphocytes (gGL) might be the NK effector cells at that site (10). Thus, we initiated a study to clarify the relationship between gGL and gut NK cytotoxicity. In an attempt to define the phenotype Of gu t NK cells and their lineage, experiments with sera against various surface markers were performed. Moreover, spleni c and gut NK activity were compared in C57BL/6-bg/bg (beige) mice, a mouse strain with very low NK activity (14), and in WBB6F1-W/W v mice, a hybrid mouse deficient in hemopoietic stem cells and mast cell precursors (15). The results obtained in this and previous studies (10) suggest that gut NK cells in the mouse are lymphocytes of the T cell lineage, similar but not identical to splenic NK cells. Materials and MethodsMice. Inbred CBA/J mice of both sexes were obtained from The Jackson Laboratory, Bar Harbor, ME. C57BL/6-bg/bg (beige) mice were bred in McMaster University from heter-* Supported by a fellowship from the Associazion Italiana per la Ricerca sul Cancro. Present address:

Fibrotic lung tissue shows increased connective tissue deposition and fibroblast proliferation and in addition a substantial increase in mast cell numbers in and around the fibrotic area. To elucidate the question ofwhether products of mast cells affect the proliferative behaviour of structural cells in the lung and thereby contribute to fibrogenesis, the effect of histamine, a prominent mast cell derived mediator, on the in vitro proliferation of primary cultures of normal adult human lung fibroblasts was studied. Histamine enhanced fibroblast proliferation in a dose dependent manner, with an optimum effect at a physiological concentration of 10 -' mol/l. This effect occurred when cells were exposed to histamine at restricted times during cell growth and was shown to depend in part on the stage of the cell cycle reached by the fibroblasts. The histamine induced proliferation was mediated through an H2 histamine receptor on the fibroblast, being inhibited by cimetidine, an H, antagonist, and not by pyrilamine maleate, an antagonist of the H, receptor. Mast cell products such as histamine may interact with and promote the increased fibroblast proliferation found in pulmonary fibrosis.

Increasing evidence suggests that neuropeptides may be important stimuli for mast cell secretion. Neuropeptide-induced histamine secretion from rat mast cells was inhibited by a variety of clinical and experimental antiallergic agents. The profile of responsiveness to this panel of drugs exhibited by peritoneal (PMC) and intestinal mucosal mast cells (IMC) was similar to that previously reported when histamine release was immunologically induced. Thus, cromoglycate, theophylline and Ro 22–3747 inhibited peptide-induced secretion from PMC but not from IMC. In contrast, doxantrazole was effective against PMC and IMC. Differences between IMC and PMC could not be attributed to the IMC isolation procedure. The results confirm the heterogeneity of responsiveness to antiallergic drugs exhibited by these mast cell subpopulations and indicate that it is not limited to immunologically induced secretion but also occurs when a neuropeptide is the secretory stimulus.

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