記述言語：英語   掲載種別：研究論文（学術雑誌）  

Exopolysaccharides (EPS) produced by lactic acid bacteria (LAB) contribute to the texture of fermented foods and offer potential health benefits. In this study, a ropy Lactiplantibacillus plantarum strain, KY5-ES5, was isolated from shibazuke, Japanese traditional fermented pickles. The strain exhibited significantly higher viscosity in synthetic medium compared to the non-ropy type strain L. plantarum JCM1149T. EPS extracted from KY5-ES5 contained glucose, galactose, and glycerol, a composition not previously reported. Structural analysis using NMR spectroscopy revealed a complex and heterogeneous polysaccharide structure with multiple glycosidic linkages, including α-1,4, α-1,6, β-1,3, and β-1,4 bonds. Glycerol residues possibly randomly modify the sugar residues as a 2-glycerol phosphate rather than being part of the main sugar chain. These findings highlight the unique composition and structural complexity of KY5-ES5 EPS, expanding the understanding of LAB-derived polysaccharides. The potential functional properties of this novel EPS, particularly its role in food texture modification and human health, warrant further investigation.

DOI： 10.1038/s41598-025-29706-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

This study explored sclerotia-forming strains from industrial Aspergillus oryzae strains, focusing on factors contributing to sclerotial morphological diversity. Using rice bran medium, ten MAT1-1 industrial strains capable of producing sclerotia were newly identified. Phylogenetic analysis revealed that strains in the specific clade are particularly prone to sclerotia formation under the conditions tested. Controlled environmental conditions, including specific CO2 concentrations and incubation periods, facilitated the development of novel internal structures that have not been previously reported in A. oryzae. Although these internal structures resemble ascocarps found in other Aspergillus species, no evidence related to reproduction was identified. Further studies are necessary to elucidate the roles of these internal structures. The findings of this study provide a foundation for future research into the cryptic sexual reproduction of A. oryzae.

DOI： 10.1016/j.funbio.2025.101669

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Black Ivory Coffee (BIC), produced through the digestion of Arabica coffee beans by Asian elephants, is recognized for its smooth, chocolaty flavor and low bitterness. However, the biological mechanisms underlying its unique taste remain poorly understood. In this study, we conducted a preliminary analysis of the gut microbiome of BIC-producing elephants and compared it with that of control elephants. 16S rRNA gene sequencing analysis revealed significant differences in microbial community structure, including the enrichment of specific bacterial genera such as Acinetobacter and family such as Izemoplasmataceae in the BIC group. Functional prediction using PICRUSt2 indicated that the BIC elephant gut microbiome harbors key enzymes involved in the degradation and utilization of pectin and cellulose-major components of coffee cherries and beans. Notably, genes related to pectin transport and downstream metabolism, including K08191 and K01812, were significantly more abundant in BIC elephants. These pathways may contribute to the degradation of specific compounds, such as 2-furfuryl furan, which has been previously shown to decrease after gastrointestinal passage. Comparative analysis with other animals revealed that only elephants harbored a complete set of pectin-degrading genes. Our findings suggest that the gut microbiota of BIC elephants facilitates microbial fermentation of coffee components, potentially influencing the chemical profiles of Black Ivory Coffee.

DOI： 10.1038/s41598-025-24196-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: Arteriosclerosis is a condition that leads to coronary artery disease (CAD) and stroke. Basic and clinical studies have suggested a link between the gut microbiota and various diseases, including atherosclerosis. Therefore, we focused on gut microbiota and aimed to develop a probiotic-based treatment for atherosclerosis. METHOD: From 6 to 14 weeks of age, apoE-deficient mice, a mouse model of atherosclerosis, were orally administered with Phocaeicola dorei and Phocaeicola vulgatus or saline five times/week. The diet was changed to a western diet at eight weeks of age. Finally, the mice were sacrificed at 14 weeks of age, and the atherosclerotic lesion area was evaluated. RESULT: Previous studies have shown that atherosclerosis is suppressed by the administration of live type strains (TS) of P. dorei and P. vulgatus in apoE-deficient mice. In this study, we isolated P. vulgatus AF299, which highly expresses commensal colonization factors. Oral administration of P. dorei TS and AF299 to model mice further suppressed atherosclerosis compared to the administration of P. dorei TS and P. vulgatus TS. Genetic analysis of lesion tissues showed that the expression levels of genes associated with inflammatory responses were significantly reduced in mice treated with P. dorei TS and AF299. Moreover, gene expression related to immune response and IgA secretion was increased in the ileum. CONCLUSION: Our results suggest that the bacteria-induced immune response in the gut leads to the suppression of the inflammatory response in atherosclerotic lesions. These results indicate the potential for the development of prophylactic drugs for atherosclerosis.

DOI： 10.5551/jat.65460

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Acute post-streptococcal glomerulonephritis (APSGN) is traditionally classified as an intrinsic form of acute kidney injury (AKI). However, previous reports suggest that its pathophysiology may resemble prerenal AKI, particularly regarding low fractional excretion of sodium (FENa) in the acute phase. This study aimed to evaluate the paradoxical coexistence of reduced renal blood flow and fluid overload in APSGN. METHODS: We retrospectively analyzed patients with APSGN (≤15 years old) hospitalized between 2010 and 2019 who exhibited ≥5% weight gain and brain natriuretic peptide (BNP) ≥100 pg/mL. The acute phase was divided into three periods: peak (3 days), early recovery (2 days), and late recovery (up to 30 days). Patients with FENa and BNP recorded in at least two periods were included. RESULTS: Among 10 patients (median age: 7 years, interquartile range: 5-7), BNP levels peaked during the acute phase and decreased in the recovery phases. Conversely, FENa was low during the peak phase but increased during recovery, despite decreasing BNP levels. CONCLUSIONS: In APSGN, FENa remained paradoxically low during the peak phase despite fluid overload (indicated by high BNP). These findings suggest that the acute phase of APSGN involves transient renal hypoperfusion and renin-angiotensin-aldosterone system activation, leading to sodium retention and volume overload. This mechanism supports the hypothesis that APSGN exhibits characteristics of prerenal AKI in its early stage.

DOI： 10.31662/jmaj.2025-0069

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Chronic kidney disease (CKD) is a life-threatening condition, and constipation is a progressive risk factor. We evaluated changes in uremic toxins, renal function, and the safety of lubiprostone, a selective chloride channel activator, in patients with CKD. In this phase 2, randomized, double-blind, placebo-controlled trial across nine centers in Japan, 150 patients with stage IIIb-IV CKD received lubiprostone (8 or 16 micrograms) or placebo for 24 weeks. The primary end point was change in indoxyl sulfate levels. Secondary end points included other uremic toxins and renal function markers. Lubiprostone did not alter uremic toxin levels but improved or preserved estimated glomerular filtration rate and its slope in the 16-microgram group. Mild-to-moderate gastrointestinal events occurred in the placebo and 16-microgram groups. Multiomics analysis revealed that lubiprostone modulated the gut microbial agmatine pathway and increased spermidine levels, thereby improving renal mitochondrial function. Lubiprostone is a previously unknown and safe therapeutic option to mitigate renal decline in CKD.

DOI： 10.1126/sciadv.adw3934

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The association between intestinal microbiota, dietary and lifestyle habits, and colorectal cancer (CRC) development is not fully understood. This study aimed to assess the association between intestinal microbiota composition and CRC risk across clinical stages, accounting for dietary and lifestyle factors. This cross-sectional study conducted in Japan included 499 participants who underwent colonoscopies. The study included 212 healthy controls, 107 patients with advanced adenoma, 109 with stage I/II CRC, and 71 with stage III/IV CRC. Multinomial logistic regression was used to evaluate the association between six specific intestinal bacteria, including Fusobacterium nucleatum, Solobacterium moorei, Gemella morbillorum, Parvimonas micra, Peptostreptococcus stomatis, and Peptostreptococcus anaerobius, and the risk of advanced adenoma and CRC. We conducted univariable and multivariable models, adjusting for potential confounding dietary and lifestyle factors. The risk of developing advanced adenoma significantly increased with a higher relative abundance of F. nucleatum, S. moorei, G. morbillorum, and P. stomatis. In stages I/II and III/IV CRC, all six bacteria demonstrated a substantial increase in risk, becoming more pronounced as the CRC stage progressed. F. nucleatum exhibited the highest odds ratio (8.92, 95% confidence interval: 3.59-22.14). Notably, even after adjusting for dietary and lifestyle factors, the observed associations remained consistent. This study highlights the differential impact of particular intestinal microbiota on the probability of advanced adenoma and CRC while also considering dietary and lifestyle factors. F. nucleatum exhibited a significant stage-dependent increase in the risk of CRC.

DOI： 10.1097/CEJ.0000000000000974

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

UNLABELLED: Lactic acid bacteria (LAB) are pivotal in food preservation and exhibit immunomodulatory effects on interleukin-10 (IL-10) and interleukin-12 (IL-12) production. Lactiplantibacillus plantarum (L. plantarum) and Lactiplantibacillus pentosus (L. pentosus) from fermented food are known for their effect; however, a comprehensive comparative genome analysis is needed to identify the linked genes. Here, we investigated the immunomodulatory capability at the genome level of L. plantarum and L. pentosus strains isolated from Japanese pickles at the genome level, and we further identified their immunomodulation-associated genes using the potential-gene (PG) index derived from the Calinski-Harabasz (CH) index. The results revealed an immunostimulatory clade with strain-specific IL-10 and IL-12 induction and identified key genes via the PG index. Both genes across two species were shown to encode the enzyme TagF2, which is crucial for synthesizing poly-glycerol-3-phosphate type wall teichoic acid (poly-GroP WTA), indicating that TagF2 plays a potential role as an effective microbe-associated-molecular-pattern. In vivo analyses confirmed the IL-10-inducing ability of one strain, reinforcing the IL-10-stimulating capacity of its poly-GroP WTA. Subpotential genes in L. plantarum TagF2-possessing strains were linked to host‒cell interactions, suggesting that such strains play potential probiotic roles. Collectively, the PG index effectively identified immunomodulation-related genes, thus paving the way for the use of the PG index to detect potential health benefit-associated genes in other LAB species. IMPORTANCE: Lactic acid bacteria are pivotal in food preservation and exhibit immunomodulatory effects on interleukin-10 (IL-10) and interleukin-12 (IL-12) production. Lactiplantibacillus plantarum and Lactiplantibacillus pentosus from fermented food are known for such effect, yet comprehensive comparative genome analysis is needed to elucidate the linked genes of the two species. The significance of our research is in observing the immunostimulatory clade with strain-specific cytokine induction and identifying key immunostimulation-related genes encoding enzymes that are crucial for synthesizing a potentially effective microbe-associated-molecular-pattern using the potential-gene index across two species. The further in vivo validation reinforced the interleukin-10-stimulating capacity of the identified pattern, and the detected sub-potential genes in Lactiplantibacillus plantarum key-gene possessing strains implied the utility of potential-gene index in detecting potential health-benefit-associated genes in other lactic acid bacteria species.

DOI： 10.1128/msystems.01575-24

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIMS: Clinical applications of fecal microbiota transplantation (FMT) for treating ulcerative colitis (UC) have shown promising results. However, whether the beneficial effects of FMT are due to the transfer and colonization of donor-derived species in patients remains unclear. Here, we investigated the factors affecting the efficacy of the administration of triple antibiotics (A-FMT) and the criteria for appropriate donor and patient-donor matching. METHODS: Ninety-seven patients with active UC who were enrolled between March 2014 and October 2019 underwent FMT. The clinical features were assessed based on a reduction in Lichtiger's clinical activity index 4 weeks after A-FMT, with long-term responders (LTR) defined as those with no increase or intensification within 12 months after A-FMT. Microbiome analysis was performed on 147 fecal samples (pre-A-FMT, post-A-FMT, and donor) from 49 patient-donor combinations that were assigned using the one-patient-to-one-donor strategy. RESULTS: Of the 97 patients, 61 achieved a clinical response, and of those, 35 were classified as having clinical remission. The efficacy of A-FMT was affected by UC severity and previous administration of steroids (P = .027), immunosuppressants (P = .049), and biologics (P = .029). Effective donors were rich in taxa such as Bacteroidota, which are lost in UC, and the abundances of "patient-origin" and "new-amplicon sequence variant" taxa were significantly lower in Responders compared to Nonresponders (Remission; P = .03, LTR; P = .05). "Donor-derived" amplicon sequence variant sequences, Oscillospiraceae UCG-002 and Alistipes, were significantly enriched in Responders (P < .05). Our results showed that the taxonomic composition of patients and the similarity of Bacteroides and butyric-acid-producing bacteria in the patient-donor microbiota significantly influenced A-FMT efficacy (P < .05). CONCLUSIONS: This study provides important insights for developing patient-tailored FMT-based therapies for UC.

DOI： 10.1093/ecco-jcc/jjaf054

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

MOTIVATION: Progress in sequencing technology has led to determination of large numbers of protein sequences, and large enzyme databases are now available. Although many computational tools for enzyme annotation were developed, sequence information is unavailable for many enzymes, known as orphan enzymes. These orphan enzymes hinder sequence similarity-based functional annotation, leading gaps in understanding the association between sequences and enzymatic reactions. RESULTS: Therefore, we developed DeepES, a deep learning-based tool for enzyme screening to identify orphan enzyme genes, focusing on biosynthetic gene clusters and reaction class. DeepES uses protein sequences as inputs and evaluates whether the input genes contain biosynthetic gene clusters of interest by integrating the outputs of the binary classifier for each reaction class. The validation results suggested that DeepES can capture functional similarity between protein sequences, and it can be implemented to explore orphan enzyme genes. By applying DeepES to 4744 metagenome-assembled genomes, we identified candidate genes for 236 orphan enzymes, including those involved in short-chain fatty acid production as a characteristic pathway in human gut bacteria. AVAILABILITY AND IMPLEMENTATION: DeepES is available at https://github.com/yamada-lab/DeepES. Model weights and the candidate genes are available at Zenodo (https://doi.org/10.5281/zenodo.11123900).

DOI： 10.1093/bioinformatics/btaf053

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objectives: The pathophysiological mechanism of abdominal aortic aneurysm (AAA) remains unclear. We previously reported that Bifidobacterium adolescentis levels were reduced in the feces of patients with AAA by 16S ribosomal ribonucleic acid (RNA) gene sequencing. In this study, we increased the number of cases and conducted metagenomic analyses to examine bacterial genes associated with the pathophysiology of AAA. Methods: For gut microbiota data, feces from 55 patients with AAA and 52 patients with no history of AAA, lower extremity artery disease, or coronary artery disease (control group) were collected. Metagenomic analysis was performed by collecting raw stool samples from patients. For intestinal microbiota analysis, metagenomic analysis of the fecal samples was performed. Results: Oral bacteria, including Actinomyces oris (p <0.0001), Streptococcus salivarius (p <0.001), Lactobacillus salivarius (p <0.001), and Streptococcus sp. (p <0.001), were increased in the feces of patients with AAA. In addition, bacterial genes related to alpha lipoic acid (ALA) biosynthesis (M00882, M00883, and M00884, p <0.0001) were decreased in patients with AAA. Conclusions: In the feces of patients with AAA, there was an increase in oral bacteria, and the expression of bacterial genes related to ALA biosynthesis was reduced. The results suggest the possibility of developing gut microbial drug treatments for AAA.

DOI： 10.3400/avd.oa.24-00105

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出版者・発行元：Cold Spring Harbor Laboratory  

The exponential growth of biomedical data has created an urgent need for efficient integration and analysis of heterogeneous sample metadata across studies. However, current methods for harmonizing and standardizing these metadata are largely manual, time-consuming, and prone to inconsistencies. Here, we present a novel computational framework that leverages large language models (LLMs) to automate the harmonization and large-scale integration of diverse biomedical sample metadata. Our approach combines semantic clustering techniques with LLM-driven natural language processing to extract, interpret, and standardize metadata from various sources, including research papers, supplementary tables, and text data from public databases. We demonstrate the efficacy of our framework by applying it to thousands of human gut microbiome papers, successfully extracting and integrating metadata from over 400,000 samples. Our method achieved a 50% recovery rate of manually curated metadata, significantly outperforming traditional rule-based methods. Furthermore, our framework enabled the creation of a unified, searchable database of standardized metadata, facilitating cross-study analyses and revealing previously obscured patterns in microbiome composition across diverse populations and conditions. The scalability and adaptability of our approach suggest its potential applicability to a wide range of biomedical fields, potentially accelerating meta-analyses and fostering new insights from existing data. This work represents a significant advancement in biomedical data integration, offering a powerful tool for researchers to unlock the full potential of accumulated scientific knowledge.

DOI： 10.1101/2024.10.26.620145

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担当区分：責任著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.isci.2024.110181

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

This hospital-based, cross-sectional study aimed to explore the association between diet and fluctuating intestinal bacteria in early-stage colorectal cancer (CRC) (Atopobium parvulum, Actinomyces odontolyticus, Solobacterium moorei, and Bifidobacterium longum). Healthy participants (n = 212) who underwent total colonoscopy at National Cancer Center Hospital (Tokyo, Japan) were divided into two groups according to the relative abundance of bacteria in their feces: those in the top 25% of relative bacterial abundance as cases and the bottom 25% as controls. The participants were divided into three groups (low, medium, and high) according to their intake of food groups associated with CRC. Multivariable logistic regression analysis was conducted to estimate the association between dietary intake and higher relative abundance of bacteria. Dairy products were inversely associated with a higher relative abundance of A. parvulum, A. odontolyticus, and S. moorei, with odds ratios (high vs. low) and 95% confidence interval as follows: 0.16 (0.06-0.44), 0.25 (0.08-0.82), and 0.29 (0.11-0.78), respectively. Additionally, dietary fiber was inversely associated with a higher relative abundance of S.moorei (0.29 [0.11-0.78]). No association was observed between diet and B.longum. In conclusion, healthy adults with a higher intake of dairy products and fiber had lower odds of having a higher relative abundance of CRC-associated microbiota.

DOI： 10.1080/01635581.2024.2344257

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