Role of Lactic Acid Bacteria-Myeloperoxidase Synergy in Establishing and Maintaining the Normal Flora in Man

Lactic acid bacteria (LAB) are incapable of cytochrome synthesis and lack the heme electron transport mechanisms required for efficient oxygen-based metabolism. Consequently, LAB redox activity is flavoenzyme-based and metabolism is fermentative, producing lactic acid, and in many cases, hydrogen peroxide (H2O2). Despite this seeming metabolic limitation, LAB dominate in the normal flora of the mouth, vagina and lower gastrointestinal tract in man. Myeloperoxidase (MPO) is produced by the neutrophil leukocytes and monocytes that provide the innate phagocyte defense against infecting pathogens. MPO is unique in its ability to catalyze the H2O2-dependent oxidation of chloride (Cl) to hypochlorite (OCl). In turn, this OCl directly reacts with a second H2O2 to produce singlet molecular oxygen ( 1 2 O  ), a metastable electronic excitation state of oxygen with a microsecond lifetime that restricts its combustive reactivity within a submicron radius of its point of generation. Each day a healthy human adult produces about a hundred billion neutrophils containing about 4 femtograms MPO per neutrophil. Inflammatory states and G-CSF treatment increase both neutrophil production and the quantity of MPO per neutrophil. After a short circulating lifetime, neutrophils leave the blood and migrate into body spaces including the mouth, vagina, urinary tract, and gastrointestinal tract. Greater than a hundred thousand neutrophils are lavaged from the mouths of healthy humans; the quantity lavaged is proportional to the blood neutrophil count. MPO selectively and avidly binds to most Gram-positive and all Gram-negative bacteria tested, but LAB do not show significant MPO binding. Neutrophils migrating to normal flora sites release MPO into the LAB-conditioned milieu containing adequate acidity and H2O2 to support extra-phagocyte MPO microbicidal action. In combination, LAB plus MPO exert a potent synergistic microbicidal action against high MPO-binding microbes. This LAB-MPO synergy provides a mechanism for the establishment and maintenance of LAB in the normal flora of man.