The concept of prebiotics was established more than 30 years ago. While the prebiotic concept has now expanded thus includes non-carbohydrate substances and diverse categories other than foods, fructooligosaccharides (FOS) have still predominantly been used as pebiotics, because the effects of FOS exclusively act through the enrichment of Bifidobacterium and Lactobacillus spp., which have been classified as beneficial intestinal commensals so far. Now the commercially available FOS products are synthetic mixture of several kinds of FOS components including 1-kestose (GF₂), nystose (GF₃) and GF₄. In our previous studies, superiority of 1-kestose to the longer-chain FOS components such as nystose with regard to bifidogenic activity was clearly demonstrated. Recently, a broader range of beneficial bacteria including butyrate-producing indigenous bacteria have been recognized and expected to be new probiotic strains. Among them, resident Faecalibacterium prausnitzii is a butyrate producer with a significant anti-inflammatory effect thus expected to be useful as a next-generation probiotic. However, this bacterium is extremely oxygen-sensitive thus can be difficult to grow industrially. On the other hand, we have clearly demonstrated a significant prebiotic effect of 1-kestose, which is the smallest component of FOS, on F. prausnitzii in the gut of humans. These findings suggest that 1-kestose has impressive potential as a new prebiotic targeting F. prausnitzii, a next-generation probiotic strain, as well as bifidobacteria.

Insulin resistance leads to the onset of medical conditions such as type 2 diabetes, and its development is associated with the alteration in the gut microbiota. Although it has been demonstrated that supplementation with prebiotics modulates the gut microbiota, limited evidence is available for effects of prebiotics on insulin resistance, especially for humans. We investigated the prebiotic effect of 1-kestose supplementation on fasting insulin concentration in obesity-prone humans and rats. In the preliminary study using rats, the hyperinsulinemia induced by high-fat diet was suppressed by intake of water with 2% (w/v) 1-kestose. In the clinical study using obese-prone volunteers, the fasting serum insulin level was significantly reduced from 6.5 µU/mL (95% CI, 5.5–7.6) to 5.3 (4.6–6.0) by the 12-week intervention with supplementation of 10 g 1-kestose/day, whereas it was not changed by the intervention with placebo (6.2 µU/mL (5.4–7.1) and 6.5 (5.5–7.6) before and after intervention, respectively). The relative abundance of fecal Bifidobacterium was significantly increased to 0.3244 (SD, 0.1526) in 1-kestose-supplemented participants compared to that in control participants (0.1971 (0.1158)). These results suggest that prebiotic intervention using 1–kestose may potentially ameliorate insulin resistance in overweight humans via the modulation of the gut microbiota. UMIN 000028824.

Background Interventions targeting the gut microbiota for treating food allergy (FA) have been gaining much attention. Although several studies have examined the effects of probiotics, few have verified the effects of prebiotic intervention on FA in humans. Methods We conducted a preliminary open-label, parallel-group comparison trial in children diagnosed with severe cow’s milk allergy (CMA) who were instructed to ingest baked milk (BM; bread or cookies) daily. The subjects either received or did not receive the prebiotic 1-kestose (kestose) daily for 6 months. CMA symptoms and the threshold dose for milk protein were evaluated by oral food challenge with heated milk or BM. Blood and fecal samples were also collected for investigations of the antigen-specific immunoglobulin (Ig) E levels and microbiota composition. Results Kestose treatment significantly increased the threshold dose for milk protein, and decreased the milk- and casein-specific IgE levels in serum. In those treated with kestose, the abundance of Fusicatenibacter spp. significantly increased in the feces, and a significant inverse correlation was seen between the abundance of Fusicatenibacter spp. and the milk- and casein-specific IgE levels. Conclusion Kestose treatment induced some tolerance to milk protein via changes in the gut microbiota composition in children with FA. Impact A 6-month treatment with the prebiotic kestose increased the threshold dose for milk protein, and decreased the serum levels of milk- and casein-specific IgE in children diagnosed with cow’s milk allergy. The kestose treatment increased the abundance of Fusicatenibacter spp. in the gut, which was inversely correlated with the antigen-specific IgE levels. This is the first study to demonstrate that a prebiotic intervention induced some tolerance to an allergen in children with food allergy.

1-Kestose is a non-digestible oligosaccharide consisting of glucose linked to two fructose units. While 1-kestose is not digested in the small intestine of mammals, it is fermented in the ceca and colon, where the growth of bifidobacteria is promoted. In the present study, we assessed the threshold dose of dietary 1-kestose that increased cecal bifidobacterial levels in rats. Rats were fed experimental diets containing 0% to 0.3% 1-kestose for four weeks. The levels of the genus Bifidobacterium and total gut bacteria were significantly increased in cecal samples of rats fed the 0.3% 1-kestose diet. Further, a significant correlation between the dose of 1-kestose and the levels of cecal Bifidobacterium and total gut bacteria was observed. The minimum dose of dietary 1-kestose to induce significant bifidogenic activity in rats was 0.3% by weight in the diet.

Objectives: Hyperlipidemia is a risk factor for various diseases. Identifying food components that can help reduce the levels of blood lipids, such as cholesterol and triglycerides, is a global research priority. It has been reported that 1-Kestose, a fructooligosaccharide, can reduce blood cholesterol and triglyceride levels in rats; however, the underlying mechanisms remain unclear. Therefore, we aimed to elucidate the effects of 1-kestose supplementation on lipid metabolism and the gut environment in rats. Methods: Twenty male Sprague–Dawley rats (age 8 weeks) were provided 1-kestose-containing water and were maintained for two weeks. After dissection, the blood components, hepatic gene expression, gut microbiota, and bile acid composition in the cecal contents of the rats were analyzed. Results: The 1-Kestose intake reduced plasma cholesterol and triglyceride levels. Additionally, an increase in cytochrome P450 family 7 subfamily A member 1 mRNA expression, a key gene for bile acid synthesis in the liver, and a decrease in lipid synthesis-related mRNA expression were observed. In the cecum, the levels of deconjugated bile acids, which are involved in the regulation of lipid synthesis, were increased. Furthermore, the 1-kestose intake altered the gut microbiota in the cecum, leading to an increase in the abundance of specific bacteria, such as Bifidobacterium, which are involved in the deconjugation of conjugated bile acids. Conclusions: The intake of 1-kestose alters the gut microbiota and bile acid metabolism in the cecum, potentially influencing lipid metabolism in the host.

Constipation is common in children and can significantly affect quality of life. Prebiotics are reportedly helpful for constipation in adults, but few studies have examined their use in young children. In this study, the effect of 1-kestose (kestose), which has excellent bifidobacterial growth properties, on constipation in kindergarten children (n = 11) was compared with that of maltose (n = 12) in a randomized, double-blind study. Three grams of kestose per day for 8 weeks did not affect stool properties, but significantly increased the number of defecations per week (Median; 3 → 4 times/week, p = 0.017, effect size = 0.53). A significant decrease in Intestinibacter, a trend toward increased bifidobacteria, and a trend toward decreased Clostridium sensu stricto were observed after kestose ingestion, while concentrations of short-chain fatty acids in stools were unchanged.