The macrophages exist in whole body tissues and maintain health condition and/or protect various diseases through appropriate their activations. We hypothesized that these macrophages formed network and this putative macrophages communication was termed a macrophage-network. Then to improve and/or maintain health status as far as possible, we focused on the some dietary-experienced Gram-negative bacteria with long experience of food production. We found a lipopolysaccharide (LPS) as macrophage-activating substances from water extract of wheat flour. This named it IP-PA1, immunopotentiator of Pantoea agglomerans which is the symbiotic Gram-negative bacteria of wheat.
While LPS is known as the strongest substance to activate macrophages, many people have prejudice against LPS as the toxin especially through intravenous route. Thus, nobody develop LPS as the medical drugs. Recently, the biological significance of LPS has been recognized as the regulator of homeostasis through signal transduction of TLR-4 in the body.
To apply the excellent function of LPS or LPS-containing materials for social health care, it is essential to investigate the basic science for the analysis of individual health maintenance system reevaluating biological significance of LPS based on the accumulation of scientific information about usefulness of LPS. To achieve these purposes, cooperation system with many specialists in different fields (university, industry, and government) should be needed.
Thus, we established an alliance composed of the, non profit organization (NPO) mainly for conduct of clinical trial with products containing LPS and evaluation of the various products in terms of both quality and quantity of LPS and its function, and university-led venture company mainly for transferring intellectual properties and for development and supply of new functional materials containing LPS derived from dietary-experienced Gram-negative bacteria including IP-PA1. In this manuscript, we introduce our concept for maintaining homeostasis based on the macrophage-network and processes in development of the product containing IP-PA1 which is a material from dietary-experienced Gram-negative bacteria to be applicable to health food.

At present, lifestyle-related diseases are one of the most critical health issues worldwide. It has been reported that lipopolysaccharide derived from a Gram-negative bacteria (IP-PA1) symbiotic with wheat exhibited several advantageous biological effects, such as the reduction of plasma glucose levels in NOD mice and low-density lipoprotein (LDL) levels in WHHL rabbits. In this study, the beneficial effects on plasma glucose and lipids of a tea (SI tea) consisting of IP-PA1 and Salacia (which contains an inhibitor of alpha-glucosidase) were investigated in the KK-Ay/TaJcl type 2 diabetic model mice and in human subjects with premetabolic syndrome in a double-blind, randomized study. SI tea significantly decreased plasma glucose levels in KK-Ay/TaJcl mice. A clinical trial of SI tea was performed with 41 subjects between the ages of 40 and 69, who belonged either to a high plasma glucose group (HG: FPG 100-125 mg/dl) or to a hyperlipidemia group (HL: TG > or = 150 mg/dl, or LDL > or = 120 mg/dl, or HDL < 40 mg/dl). These subjects ingested either Salacia without IP-PA1 (the control) or SI tea. Blood samples were collected at 0, 30, and 60 days after initiating SI tea treatment, and were measured for FPG, HbA1c, TG, LDL, and HDL. These results showed that SI tea reduced FPG and HbA1c more rapidly than the control in the HL group, and also significantly improved LDL and HDL levels in the HG group. Thus, SI tea may be helpful in preventing lifestyle-related diseases.
Animals ; Cholesterol ; Fasting ; Glucose ; Gram-Negative Bacteria ; Humans ; Hyperlipidemias ; Lipoproteins ; Mice ; Mice, Inbred NOD ; Plasma ; Rabbits ; Salacia ; Tea ; Triticum