Yakult Central Institute

Occult bacteremia (OB), defined as blood stream micro-organisms confirmed by reverse transcriptase-quantitative polymerase chain reaction that target 16S or 23S ribosomal RNA, has been shown to increase the incidence of post-operative infections during pancreaticoduodenectomy. However, its impact on other surgical procedures remains unclear. This study aimed to evaluate the effect of pre-operative OB on post-operative surgical site infection (SSI) during esophageal cancer surgery. In this prospective observational study, 56 patients scheduled for esophagectomy were included. Pre-operative blood samples were tested for OB, and fecal samples were analyzed for microbiota. Ten patients (18%) exhibited pre-operative OB. These patients had more frequent SSIs than did those without OB (40% vs. 10.9%, p = 0.044). Other complications or clinical factors did not substantially differ between the OB-positive and OB-negative groups. Fecal samples from OB-positive patients presented a greater prevalence of Atopobium clusters. In addition, the same bacterial species were detected in both the blood and feces of five OB-positive patients, with Collinsella aerofaciens being the most commonly shared species among Atopobium clusters. Pre-operative OB increased the risk of SSI following esophagectomy. These findings emphasize the potential role of the gut microbiota, particularly Collinsella aerofaciens, in OB and subsequent infections.

This study aimed to identify gut microbiota-derived metabolites governing the activity of hepatic CYP3A in blood level. Indole propionic acid (IPA) and lithocholic acid, ligands of the pregnane X receptor, a transcriptional regulator of CYP3A, and various gut microbiota-derived metabolites in blood level were analyzed. Results revealed that IPA and lithocholic acid did not affect CYP3A activity, while indoxyl sulfate (IS), a uremic toxin, affected CYP3A across different cell lines. The effects of IS on primary hepatocytes from three donors were analyzed, and a concentration-dependent impact was observed, as the CYP3A activity decreased in one donor and increased in another. These findings offer initial insights into blood-level gut microbiota-derived metabolites influencing hepatic CYP3A. Furthermore, the study demonstrates that the response to IS, beyond its concentration, can cause variations in hepatic CYP3A activity among individuals. This study advocates accounting for the dual effects of IS and the benefits of personalized medicine.

The COVID-19 pandemic has significantly impacted our daily lives. Routine infection-control measures present an effective preventive strategy for a new infectious disease outbreak. Fucoidan, a fucose-rich sulfated polysaccharide found in brown algae, exhibits antiviral activity. Moreover, fucoidan exerts an antimicrobial effect; however, it requires considerably higher concentrations than those needed for its antiviral effect. In this study, we aimed to enhance the antimicrobial activity of fucoidan and prepared a fucoidan silver salt (Ag-Fuc) by incorporating silver ions into the sulfate groups of Yakult Fucoidan derived from Cladosiphon okamuranus Tokida. The fucoidan exhibited a weak inhibitory effect on Escherichia coli growth at significantly higher concentrations, whereas Ag-Fuc inhibited the growth of E. coli and Staphylococcus epidermidis at concentrations comparable to those required for its antiviral effects. Moreover, Ag-Fuc inhibited the growth of Cladosporium cladosporioides. Infections of human cells with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus were more effectively inhibited by lower concentrations of Ag-Fuc compared with fucoidan. Overall, silver ions added to the sulfate groups induced strong antimicrobial activity and enhanced the antiviral effect of fucoidan. We suggest a wide application of Ag-Fuc as a routine preventive material to avoid new infectious disease pandemics.

Lacticaseibacillus paracasei strain Shirota (LcS) modulates psychological homeostasis via the gut–brain axis. To explore the possible efficacy of LcS for improving daytime performance, we conducted a double-blind, randomized, crossover, placebo-controlled study of 12 healthy office workers with sleep complaints. The participants received fermented milk containing viable LcS (daily intake of 1 × 1011 colony-forming units) and non-fermented placebo milk, each for a 4-week period. In the last week of each period, the participants underwent assessments of their subjective mood and measurements of physiological state indicators via an electroencephalogram (EEG) and heart rate variability in the morning and afternoon. The attention score in the afternoon as assessed by the visual analog scale was higher in the LcS intake period than in the placebo intake period (p = 0.041). Theta power on EEG measured at rest or during an auditory oddball task in the afternoon was significantly lower in the LcS period than in the placebo period (p = 0.025 and 0.009, respectively). The change rate of theta power was associated with the change in attention score. Treatment-associated changes were also observed in heart rate and the sympathetic nerve activity index. These results indicate that LcS has possible efficacy for improving daytime performance, supported by observations of the related physiological state indicators.

Safer and more effective cow milk (CM)-oral immunotherapy that does not induce allergic reactions has not yet been standardised. We sought to explore the efficacy and feasibility of a combination of heat-killed Lactiplantibacillus plantarum YIT 0132 (LP0132) and oral immunotherapy for treating IgE-mediated cow milk allergy (CMA). We conducted a 24-week, double-blind, randomised (1:1), two-arm, parallel-group, placebo-controlled, phase 2 trial of LP0132 intervention for treating IgE-mediated CMA in children aged 1-18 years (n=60) from January 29, 2018 to July 12, 2019 in Tokyo, Japan. Participants were randomly assigned to the LP0132 group receiving citrus juice fermented with LP0132 or to the control group receiving citrus juice without. Both groups received low-dose slow oral immunotherapy with CM. The primary outcome was improved tolerance to CM, proven by the CM challenge test at 24 weeks. Secondary outcomes were changes in serum biomarkers of serum-specific β-lactoglobulin-IgE (sIgE) and β-lactoglobulin-IgG4 (sIgG4). Exploratory outcomes included changes in serum cytokine levels and gut microbiota composition. A total of 61 participants were included. Finally, 31 children were assigned to the LP0132 group and 30 to the control group, respectively. After the intervention, 41.4 and 37.9% of the participants in the LP0132 and control groups, respectively, showed improved tolerance to CM. In serum biomarkers after the intervention, the sIgG4 level was significantly higher, and interleukin (IL)-5 and IL-9 were significantly lower, in the LP0132 group than in the control group. In the gut microbiome, the α-diversity and Lachnospiraceae increased significantly in the LP0132 group, and Lachnospiraceae after the intervention was significantly higher in the LP0132 group than in the control group. In conclusion, low-dose oral immunotherapy with modulating gut microbiota might be a safer and more effective approach for treating cow's milk allergy.

This prospective study aimed to investigate the dynamic changes in the gut microbiota (GM) and associated intestinal environment, which were assessed by measuring fecal organic acid (OA) concentrations, during the early period after liver transplantation (LT). To understand the fundamental characteristics of the human GM, data obtained from living donors were also analyzed. Fixed-point observation was performed in 23 recipients and 21 donors for up to 2 weeks after LT. The GM and OA concentrations were investigated using ribosomal RNA-targeted reverse-transcription quantitative polymerase chain reaction and high-performance liquid chromatography, respectively. Before LT, the recipients exhibited remarkable dysbiosis and OA depletion, which were proportional to the model for end-stage liver disease score. Correlations between the abundances of some specific strains and OA concentrations were observed. After LT, while donor lobectomy caused only slight, transient and reversible changes in the GM and OA concentrations, recipients exhibited delayed recovery in these factors. However, no clear evidence of causality was observed between the GM or OA concentrations and LT outcomes. The GM and intestinal environment in LT recipients exhibited characteristics that were clearly different from those in donors. LT did not normalize but rather disrupted the GM during the early post-LT period, but its negative clinical impact could be minimized with perioperative management.