Changes in intestinal bacteria and imbalances of metabolites induced in the intestines of pancreatic ductal adenocarcinoma patients in a Japanese population: a preliminary result.

BACKGROUND: The relationship between pancreatic ductal adenocarcinoma (PDAC) and the intestinal environment is not fully understood. The purpose of this study was to elucidate the characteristics of the intestinal environment in PDAC. METHODS: We performed a case-control study of 5 Japanese patients with unresectable PDAC located in the body or tail (PDAC-bt). The number of patients analyzed was limited for this preliminary study. We included 68 healthy subjects, herein control, of pre-printed study in the preliminary study. 16S rRNA amplicon sequencing and metabolomic analysis were performed using fecal samples from the subjects. RESULTS: There was no difference in the Shannon index and Principal Coordinate Analysis between PDAC-bt and the control. However, a significant increase in oral-associated bacteria (Actinomyces, Streptococcus, Veillonella, Lactobacillus) was observed. A significant decrease of Anaerostipes was demonstrated in the feces of PDAC-bt compared with the control. The intestinal propionic acid and deoxycholic acid were significantly lower in PDAC-bt compared with the control. CONCLUSIONS: We showed that the intestinal environment of PDAC-bt is characterized by an increase in oral-associated bacteria and an imbalance of metabolites but without changes in alpha and beta diversity of the gut microbiota profiles.Clinical Trial Registration: www.umin.ac.jp, UMIN 000041974, 000023675, 000023970.

Effect of urolithin A on the improvement of vascular endothelial function depends on the gut microbiota.

Background: Urolithin A (UA) is a metabolite produced by gut microbiota from ingested ellagic acid. Although the effect of ellagic acid intake on vascular endothelial function (VEF) improvement has been reported, the effect of UA intake on VEF improvement remains obscure. In addition, UA has been reported to improve the intestinal barrier function, and UA may have improved VEF by gut microbiome alteration. Objective: In this study, we conducted a clinical trial to explore and analyze the effects of UA intake on vascular endothelial function (VEF) and characteristics of the intestinal environment, such as gut microbiome profiling and organic acid composition. Methods: A placebo-controlled, randomized, double-blinded, parallel group trial was conducted on participants who could metabolize small amounts of UA from ellagic acid (non-UA producers) and had relatively poor VEF. VEF was assessed using the flow-mediated vasodilatation (FMD) score. Participants were administered placebo, UA 10 mg/day, or UA 50 mg/day for 12 weeks. FMD was measured and fecal samples were collected at 0, 4, 8, and 12 weeks of treatment. Gut microbiome analysis and organic acid level measurements were performed to evaluate the effects of UA intake on the intestinal environment. This clinical trial is publicly registered at the UMIN-CTR, trial number: UMIN000042014. Results: The gut microbiota of the UA 50 mg/day group showed a significant increase in alpha diversity (Faith's phylogenetic diversity). Four and nine microbial genera were significantly altered in the UA 10 mg/day and UA 50 mg/day groups, respectively (p < 0.05, not corrected). Participants whose FMD scores improved with UA intake had poor baseline FMD values as well as a low Bacillota/Bacteroidota ratio. Conclusion: Urolithin A intake alters the gut microbiota and improves their alpha diversity. In addition, the effect of UA on VEF correlated with the individual gut microbiota. Our results have practical implications for a new approach to providing healthcare that focuses on intestinal environment-based diet therapy.

Development of a Novel Web Camera-Based Contact-Free Major Depressive Disorder Screening System Using Autonomic Nervous Responses Induced by a Mental Task and Its Clinical Application.

BACKGROUND: To increase the consultation rate of potential major depressive disorder (MDD) patients, we developed a contact-type fingertip photoplethysmography-based MDD screening system. With the outbreak of SARS-CoV-2, we developed an alternative to contact-type fingertip photoplethysmography: a novel web camera-based contact-free MDD screening system (WCF-MSS) for non-contact measurement of autonomic transient responses induced by a mental task. METHODS: The WCF-MSS measures time-series interbeat intervals (IBI) by monitoring color tone changes in the facial region of interest induced by arterial pulsation using a web camera (1920 × 1080 pixels, 30 frames/s). Artifacts caused by body movements and head shakes are reduced. The WCF-MSS evaluates autonomic nervous activation from time-series IBI by calculating LF (0.04-0.15 Hz) components of heart rate variability (HRV) corresponding to sympathetic and parasympathetic nervous activity and HF (0.15-0.4 Hz) components equivalent to parasympathetic activities. The clinical test procedure comprises a pre-rest period (Pre-R; 140 s), mental task period (MT; 100 s), and post-rest period (Post-R; 120 s). The WCF-MSS uses logistic regression analysis to discriminate MDD patients from healthy volunteers via an optimal combination of four explanatory variables determined by a minimum redundancy maximum relevance algorithm: HF during MT (HF MT ), the percentage change of LF from pre-rest to MT (%ΔLF(Pre-R⇒MT) ), the percentage change of HF from pre-rest to MT (%ΔHF(Pre-R⇒MT) ), and the percentage change of HF from MT to post-rest (%ΔHF(MT⇒Post-R) ). To clinically test the WCF-MSS, 26 MDD patients (16 males and 10 females, 20-58 years) were recruited from BESLI Clinic in Tokyo, and 27 healthy volunteers (15 males and 12 females, 18-60 years) were recruited from Tokyo Metropolitan University and RICOH Company, Ltd. Electrocardiography was used to calculate HRV variables as references. RESULT: The WCF-MSS achieved 73% sensitivity and 85% specificity on 5-fold cross-validation. IBI correlated significantly with IBI from reference electrocardiography (r = 0.97, p < 0.0001). Logit scores and subjective self-rating depression scale scores correlated significantly (r = 0.43, p < 0.05). CONCLUSION: The WCF-MSS seems a promising contact-free MDD screening apparatus. This method enables web camera built-in smartphones to be used as MDD screening systems.