Oral administration of heat-killed Lactobacillus brevis SBC8803 elevates the ratio of acyl/des-acyl ghrelin in blood and increases short-term food intake

Abstract

It is known that gastrointestinal microbiota, probiotics and heat-killed microbes can regulate intestinal immunity; however, their effect on the secretion of gastrointestinal hormones is unclear. The secretion of gastrointestinal hormones can be mediated by the elevation of intracellular Ca2+ concentration, suggesting that these hormones may act through common mechanisms. We have previously shown that heat-killed Lactobacillus brevis SBC8803 (hk-SBC8803) induced the secretion of serotonin and elevated intracellular Ca2+ concentration in serotonin-producing RIN-14B cells, suggesting that hk-SBC8803 could potentially cause the same effect on other gastrointestinal hormones, including hunger hormone ghrelin. Here, we tested this hypothesis by treating cultured cells and experimental animals with hk-SBC8803 and assessing ghrelin secretion, expression of ghrelin-related genes, and food intake. The results indicated that hk-SBC8803 treatment for 30 min significantly upregulated the secretion of acyl ghrelin (active form) (P=0.046) and mRNA expression of the Syt3 (synaptotagmin 3) gene related to ghrelin exocytosis (P<0.05) in primary mouse stomach cells. In addition, oral administration of 500 mg/kg hk-SBC8803 to rats tended to upregulate acyl ghrelin concentration (P=0.10) and significantly increased the ratio of acyl to des-acyl (inactive) ghrelin (P=0.027) in blood, which corresponded to a tendency of stimulating food intake (P=0.087) at 30 min post-treatment. However, when in order to minimise individual differences we normalised the data on food intake to those on one-day food intake prior to food deprivation, the resultant food intake ratio showed a significant increase (by 5% compared to control; P=0.032) at 30 min after hk-SBC8803 treatment, indicating that hk-SBC8803 administration stimulated rats to take more food during the first meal after fasting. These results suggest that hk-SBC8803 induces short-term ghrelin secretion and transiently increases appetite, which is an important effect for individuals with low energy intake.