In milk fermented with Lactobacillus helveticus, a lactic acid bacterium with potent proteolytic activity, valyl-prolyl-proline and isoleucyl-prolyl-proline are produced. These two peptides have been shown to have an inhibitory effect on angiotensin-converting enzyme, which converts angiotensin I to angiotensin II, a strong vasoconstrictor. Pre-clinical and in vitro studies suggest an orally ingested dose of these peptides can be absorbed in an intact form from the gastrointestinal tract, and can inhibit the renin-angiotensin system, producing significant reductions in blood pressure. In our human studies, fermented milk containing these peptides significantly decreased systolic and diastolic blood pressure in hypertensive subjects. Inhibitors of angiotensin-converting enzyme increase bradykinin, which in turn increases nitric oxide production, improving endothelial function. These peptides improved acetylcholine-induced vascular reactivity in rats administered NG-nitro-L-arginine methyl ester hydrochloride, an inhibitor of nitric oxide production. Furthermore, we measured the reactive hyperemia of the human upper forearm using plethysmography as an index of vascular endothelial function, and observed that casein hydrolysate containing the peptides significantly increased the forearm blood flow with no change in systemic blood pressure, indicating the improvement in vascular endothelial function, attributable to the tripeptides, was independent of hemodynamic changes. These results suggest that valyl-prolyl-proline and isoleucyl-prolyl-proline contribute to reducing the risk of metabolic syndrome by modulating vascular endothelial function as well as blood pressure.

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We have demonstrated that lactic acid bacteria (LAB), especially some selected strains, might possess health promoting effects for serum cholesterol and lipid metabolisms in vitro, and in animal and human clinical studies. Some studies have indicated that dairy products have anti-obesity effects in which Ca may play an important role. A preparation of fermented milk with LAB strains, originally selected to improve serum lipid metabolism, significantly stimulated the anti-obesity effects of high Ca-supplemented fermented milk. In light of these recent findings, the present article discusses the anti-obesity effect and the underlying mechanisms of probiotic strains and probiotics in fermented milk.

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The number of patients with diabetes mellitus and people with prediabetes has been rapidly increasing due to changes in life style and social environment in Japan. Type 2 diabetes, found in the majority of diabetes patients, is seen as a major cause of swelling healthcare cost. Therefore, the prevention of its onset and initial treatment are essential.
In recent years, it has been reported that many probiotics are effective in some diabetic animal models. However, the mechanism of their action is not clear, due to the complicated mechanism of the onset and exacerbation of type 2 diabetes itself. In this paper, we describe a possible mechanism of probiotic actions against diabetes such as improved fat metabolism, anti-inflammatory effects, and improvement of gut microbiota, and probiotics beneficial role in initial treatment and prophylaxis of diabetes.

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In vitro, animal and clinical studies have reported the effects of probiotics in the improvement of hypercholesterolemics. Several mechanisms of cholesterol reduction by probiotics have been suggested including removal of cholesterol by assimilation or conjugation with the cell surface, enzymatic deconjugation of bile acids, and inhibition of cholesterol synthesis by short-chain fat acids produced by probiotic bacteria in the gastrointestinal tract. Many clinical trials have shown the efficacy of probiotics in the improvement of serum lipid levels, especially those of bifidobacteria or lactobacilli with bile salt hydrolyzing activity, although there are also several reports of no effect. Recent studies have highlighted the role of gut microbiota in the development of obesity and metabolic syndrome. Progress in evaluating the role of probiotics and microbiota in metabolic disorders is garnering much attention.

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The anti-obesity action of lactic acid bacteria was evaluated using in vitro and in vivo assay systems. From 293 strains of lactic acid bacteria, several Lactobacillus strains showed strong inhibitory activity against pancreatic lipase. The effects of seven Lactobacillus strains on plasma triacylglycerol elevation in rats with oral lipid loading were examined. Rats administered the lipid emulsion containing Lactobacillus gasseri NLB367 showed lower plasma triacylglycerol levels than those fed the lipid emulsion only.
Lactobacillus gasseri NLB367 inhibited the hydrolysis of triacylglycerol by pancreatic lipase in vitro and elevation of the plasma triacylglycerol level after oral administration of the lipid emulsion in the rats. These results suggest that L.gasseri NLB367 might improve lipid metabolism as a probiotic.

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Bifidobacteria are obligately anaerobic, Gram-positive, rod-shaped bacteria which predominate in human intestinal microbiota during early infancy. Although they are considered to be “vertically” transferred from mother to infant, little is known to substantiate this view. In this context, we performed Pulsed-Field Gel Electrophoresis (PFGE) on strains of Bifidobacterium longum subsp. longum isolated from fecal samples of 5 mother-infant pairs. Our PFGE analysis revealed that strains isolated from 3 of the pairs had almost identical PFGE patterns within pairs. Subsequently, we investigated aerobic and microaerophilic survival of the maternal strains. The strains maintained their original population on agar plate medium for up to 6 h and 18 h under aerobic and microaerophilic conditions, respectively; they died out on a human palm within 3 h; and it took more than 24 h for them to die out, even under an aerobic condition, if they were desiccated. This evidence suggests that the vertical transfer of bifidobacteria occurs via the birth canal or surrounding atmosphere, equipment, or clothing rather than the hand or fingers.

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