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The significance of less abundant genera within the gut microbiota, such as Parabacteroides, remains largely unexplored. Despite its low levels, Parabacteroides is highly conserved and potentially beneficial across populations. This trial aimed to evaluate whether a four-week intake of glucolacto-oligosaccharides (GLO), previously reported as an enhancer of Parabacteroides, improves defecation frequency as the primary outcome. It also assessed holistic gut health and underlying microbiota-based mechanisms. In this randomized, double-blind, placebo-controlled trial, 50 healthy Japanese participants with a defecation frequency of five or fewer times per week were enrolled. The mean (±SE) weekly defecation frequency in the GLO group was 3.2 ± 0.2 at baseline, increasing to 5.8 ± 0.6 at week 4, whereas that in the placebo group was 3.4 ± 0.3 at baseline, increasing to 4.4 ± 0.3 at week 4. The time-dependent weekly defecation frequency was significantly higher in the GLO group than in the placebo group (p = 0.029). Changes in the relative abundance of the genus Parabacteroides significantly increased in the GLO group compared with in the placebo group. Changes in fecal bile acid composition were also confirmed in the GLO group compared with the placebo group, which was thought to be due to the unique features of Parabacteroides. Furthermore, changes in alpha diversity indices were significantly higher in the GLO group than in the placebo group (Simpson, p = 0.041; Pielou, p = 0.022). Additional analysis demonstrated that the increase in alpha diversity in the GLO group was significantly correlated with the increase in the relative abundance of Parabacteroides (p = 0.006), which tended to be associated with decreases in serum gamma-glutamyltransferase (p = 0.089) and serum triglyceride (p = 0.075) levels. These data suggest that GLO intake improved defecation status, selectively increased Parabacteroides, and harmonized the gut environment. Full article

Background/Objectives: Oligosaccharides, such as fructooligosaccharides (FOS), have long been used to promote human health due to their beneficial effects on the intestinal environment and their anti-inflammatory properties. Recent advances in manufacturing technologies have enabled the production of novel oligosaccharides derived from rare sugars. These compounds may exert unique health benefits; however, their physiological functions remain largely unexplored. Because sleep is a conserved, lifespan-linked physiological phenotype governed by metabolic and stress-response pathways that oligosaccharides can influence, we evaluated sleep alongside lifespan to capture systemic functional effects. Methods: Using the model organism Drosophila melanogaster, we investigated the effects of 4-galactosylkojibiose (4-GK), a promising new oligosaccharide, on sleep and lifespan. We also conducted RNA sequencing following 4-GK or FOS application. Results: Our results demonstrated that both 4-GK and FOS extended lifespan, with 4-GK showing comparable or numerically greater efficacy than FOS. While the addition of 4-GK or FOS to sucrose diet did not affect overall sleep or activity levels, 4-GK alone without sucrose decreased sleep compared to sucrose alone. Furthermore, RNA-seq analysis revealed upregulation of gene groups associated with longevity in both the 4-GK and FOS treatment groups, particularly genes encoding heat shock proteins. Conclusions: 4-GK promotes longevity in D. melanogaster and activates stress-response programs, suggesting a health-promoting role comparable to FOS. Sleep effects were diet-context dependent, unchanged when added to sucrose but reduced when given without sucrose. These findings suggest a novel potential role for 4-GK in promoting longevity. Full article