Less than half of all patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) respond to chemotherapy, and the prognosis of PDAC is poor, which may be mediated by the gut microbiota. We investigated the clinical improvement effects of 1-kestose, a fructooligosaccharide, on PDAC chemotherapy in this single-center, randomized, controlled pilot trial conducted at Fujita Health University Hospital, which enrolled patients with PDAC. The trial included 1-kestose administration and non-administration groups. The 1-kestose group received 9 g of 1-kestose daily for 12 weeks, and their blood markers, imaging studies, physical findings, and gut microbiota were evaluated. In the 1-kestose administration group, the cancer marker CA19-9 significantly decreased, and there was a reduction in the neutrophil-to-lymphocyte ratio (NLR). There was also suppression of the reduction of albumin levels and of an increase in C-reactive protein. Additionally, Escherichia coli, which typically increases in PDAC, significantly decreased in the 1-kestose group. Thus, 1-kestose altered the gut microbiota and improved the prognostic factors for PDAC. Large-scale, long-term trials of 1-kestose interventions for PDAC are thus warranted to improve the prognosis of PDAC.

Recent studies have linked Ruminococcus gnavus to inflammatory bowel disease and Fusobacterium nucleatum to various cancers. Agarooligosaccharides (AOS), derived from the acid hydrolysis of agar, have shown significant inhibitory effects on the growth of R. gnavus and F. nucleatum at concentrations of 0.1 and 0.2%, respectively. RNA sequencing and quantitative reverse-transcription PCR analyses revealed the downregulation of fatty acid biosynthesis genes (fab genes) in these bacteria when exposed to 0.1% AOS. Furthermore, AOS treatment altered the fatty acid composition of R. gnavus cell membranes, increasing medium-chain saturated fatty acids (C8, C10) and C18 fatty acids while reducing long-chain fatty acids (C14, C16). In contrast, no significant growth inhibition was observed in several strains of Bifidobacteria and Lactobacillales at AOS concentrations of 0.2 and 2%, respectively. Co-culture experiments with R. gnavus and Bifidobacterium longum in 0.2% AOS resulted in B. longum dominating the population, constituting over 96% post-incubation. In vivo studies using mice demonstrated a significant reduction in the Lachnospiraceae family, to which R. gnavus belongs, following AOS administration. Quantitative PCR also showed lower levels of the nan gene, potentially associated with immune disorders, in the AOS group. These findings suggest that AOS may introduce a novel concept in prebiotics by selectively inhibiting potentially pathogenic bacteria while preserving beneficial bacteria such as Bifidobacteria and Lactobacillales.

The gut microbiota has been implicated in the modulation of food allergies. Building on previous studies on the preventive effects of combining short-chain fructan 1-kestose (Kes) and long-chain fructan inulin (Inu) in food allergies, we investigated their therapeutic effects in an ovalbumin (OVA)-induced food allergy mouse model. Following OVA sensitization, the mice received 5% Kes and Inu, either individually or a combined 2.5% dose of each, for 4 wk. We assessed allergy-related markers, such as OVA-specific serum IgE (OVA-sIgE) levels, in the blood and monitored changes in the gut microbiome. The intake of fructans ameliorated allergic symptoms and stabilized rectal temperatures, with a significant reduction in OVA-sIgE levels only in the combined Kes and Inu group (Kes+Inu), p<0.05. Gut microbiota diversity analysis revealed significant differences in beta diversity between the groups not receiving fructans and those receiving Kes, Inu, or Kes+Inu (p<0.01 each). Specifically, in the Kes+Inu group, the abundance of the genus UBA7173 belonging to the family Muribaculaceae significantly increased. Additionally, acetate levels were significantly elevated only in the Kes+Inu group and correlated positively with the presence of the genus UBA7173. These findings indicated that the combined intake of Kes and Inu improves allergic outcomes, positively affects the gut microbiome, and enhances the production of acetate.

Prebiotics, such as short- and long-chain fructans, beneficially modulate the microbiota; however, individual variability in response remains unclear....

Background: Agaro-oligosaccharides (AOS) have been shown to modulate the gut microbiota in in vitro and animal studies; however, human evidence remains scarce. Methods: Herein, we conducted a four-week open-label, single-arm, non-randomized pilot trial in 18 healthy Japanese adults to examine the association of AOS intake at 200 mg/day with gut microbiota composition and bowel condition. Fecal samples collected before and after the intervention were analyzed using QIIME2-based 16S rRNA sequencing, and bowel condition was assessed with the Bristol Stool Form Scale. This study was registered in the UMIN Clinical Trials Registry (UMIN000056992). Results: AOS intake was not associated with significant changes in bowel condition. Gut microbiota analysis showed no significant alterations in overall community structure but revealed taxon-specific trends in the relative abundance of several bacterial taxa. Notably, nominal changes were observed in the abundance of the Ruminococcus gnavus group and Bacteroides uniformis after the intervention. In addition, quantitative PCR analysis showed an increase in 3,6-anhydro-L-galactose cycloisomerase (ACI) gene abundance after the intervention. Conclusions: These findings suggest that, in this exploratory pilot study, AOS intake was associated with a taxon-specific pattern in the gut microbiota. Further randomized controlled studies are needed to clarify the microbiota-related effects of AOS in humans.

Background/Objectives: Nopalea cochenillifera (L.) Salm-Dyck cladodes are rich in dietary fiber, polyphenols, and minerals, which are known to exert antioxidant and immunomodulatory effects. However, the mechanisms and active constituents have not been fully elucidated. In this study, we investigated the effects of continuous N. cochenillifera consumption on lipid metabolism, immune function, and the gut microbiota in mice. Methods: The feed was made using freeze-dried and powdered cladodes of N. cochenillifera. Male C57BL/6J mice were assigned to four groups: control diet (C), control diet plus 10% N. cochenillifera (CN), high-fat diet (FC), and high-fat diet plus 10% N. cochenillifera (FN). Results: Cactus supplementation reduced the body and liver weights that were elevated by the high-fat diet. Serum total cholesterol and free fatty acids were increased in the FC group compared with the C group, while cactus intake lowered these levels and enhanced fecal cholesterol excretion. Cactus consumption also elevated fecal total IgA and mucin contents. IL-4 expression in Peyer’s patches was significantly increased in the FN group compared with the FC group. Gut microbiota analysis showed significant differences in β-diversity, along with increased α-diversity and higher abundance of Lachnospiraceae, following cactus intake. Conclusions: These findings suggest that N. cochenillifera intake increases gut microbiota diversity, which enhances intestinal barrier function and thereby contributes to improved lipid metabolism and immune regulation.