Bacterial translocation is a unique physiologic event, which is increased during pregnancy and lactation in rodents. Human breast milk cells contain a limited number of viable bacteria but a range of bacterial DNA signatures, as also found in maternal peripheral blood mononuclear cells. Those peripheral blood mononuclear cells showed greater biodiversity than did peripheral blood mononuclear cells from control women. Taken together, our results suggest that intestinally derived bacterial components are transported to the lactating breast within mononuclear cells. We speculate that this programs the neonatal immune system to recognize specific bacterial molecular patterns and to respond appropriately to pathogens and commensal organisms.

The clinical response to oral polymeric diet CT3211 is associated with mucosal healing and a down regulation of mucosal pro-inflammatory cytokine mRNA in both the terminal ileum and colon. In the ileum there was also an increase in transforming growth factor beta1 mRNA.

Because of the lack of data that convincingly show immunomodulatory properties of lactic acid bacteria in humans, a study was performed in which healthy volunteers were divided into two groups and given a fermented milk product supplemented with Lactobacillus acidophilus strain La1 or Bifidobacterium bifidum strain Bb 12 for 3 wk. Blood was sampled throughout the study to assess changes in lymphocyte subsets or leukocyte phagocytic activity following consumption of the fermented products. No modifications of lymphocyte subpopulations were detected. In contrast, phagocytosis of Escherichia coli sp. in vitro was enhanced after the administration of both fermented products. The increment in phagocytosis was coincident with fecal colonization by the lactic acid bacteria and persisted for 6 wk after ingestion of the fermented products. By this time, the fecal lactobacilli and bifidobacteria had returned to concentrations prior to consumption. Nonspecific, anti-infective mechanisms of defense can be enhanced by the ingestion of specific lactic acid bacteria strains. These strains can be used as nutritional supplements to improve the immune function of particular age groups, i.e., the neonate or the elderly, for which these functions are diminished.

Little is known about innate immunity to bacteria after birth in the hitherto sterile fetal intestine. Breast-feeding has long been associated with a lower incidence of gastrointestinal infections and inflammatory and allergic diseases. We found in human breast milk a 48-kD polypeptide, which we confirmed by mass spectrometry and sequencing to be a soluble form of the bacterial pattern recognition receptor CD14 (sCD14). Milk sCD14 (m-sCD14) concentrations were up to 20-fold higher than serum sCD14 from nonpregnant, pregnant, or lactating women. In contrast, lipopolysaccharide (LPS)-binding protein was at very low levels. Mammary epithelial cells produced 48-kD sCD14. m-sCD14 mediated activation by LPS and whole bacteria of CD14 negative cells, including intestinal epithelial cells, resulting in release of innate immune response molecules. m-sCD14 was undetectable in the infant formulas and commercial (cows') milk tested, although it was present in bovine colostrum. These findings indicate a sentinel role for sCD14 in human milk during bacterial colonization of the gut, and suggest that m-sCD14 may be involved in modulating local innate and adaptive immune responses, thus controlling homeostasis in the neonatal intestine.

Lactic acid bacteria in food can transiently colonize the intestine and exert beneficial effects (probiotic). Survival during intestinal transit or adhesion to epithelium or both seem to be important for modifying the host's immune reactivity. Because Lactobacillus acidophilus strain La1 is adherent to enterocytes in vitro, we hypothesize that contact with immune cells may occur in vivo. However, Bifidobacterium bifidum strain Bb12, which shows high fecal colonization, is another potential immunomodulator. Twenty-eight volunteers were divided into two groups and given a fermented product containing one of the two strains. Lymphocyte subsets and leukocyte phagocytic activity were studied in blood. No modifications were detected in lymphocyte subsets. In contrast, phagocytosis of Escherichia coli ssp. was enhanced in both groups (P < 0.001 for both). Bacterial adhesion to enterocytes, fecal colonization, or both seem to be valuable selection criteria for immunomodulation. Antiinfective mechanisms of defense can be enhanced after ingestion of specific lactic acid bacteria strains.