掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

DOI： 10.1016/j.jnutbio.2025.110039

PubMed

<p>腸溶型ラクトフェリンのネコへの安全性および動態を観察するため、健康なネコを対象に単回投与・反復投与試験を実施した。腸溶型ラクトフェリンの安全性が認められ、ラクトフェリンは血液循環には入らず腸で作用を示すことが示唆された。</p>

DOI： 10.11266/jpan.28.suppl_suppl_33

CiNii Research

掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

DOI： 10.1038/s41598-025-04339-z

PubMed

掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

DOI： 10.1038/s41598-025-01144-6

PubMed

掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

Aberrant activation of the stimulator of interferon genes (STING) pathway is a hallmark of autoinflammatory disorders such as STING-associated vasculopathy with onset in infancy (SAVI), characterized by systemic inflammation affecting blood vessels, skin, and lungs. Despite its clinical significance, the mechanisms linking STING activation to disease pathology remain poorly defined. In this study, we demonstrated that SAVI mice harboring the N153S STING mutation exhibit diverse disease phenotypes, with a subset developing severe colitis and diarrhea alongside exacerbated systemic inflammation. These diarrheal SAVI mice showed pronounced dysbiosis, marked by reduced short-chain fatty acid-producing bacteria and an enrichment of segmented filamentous bacteria. This microbial imbalance was accompanied by elevated levels of both microbial and host-derived cyclic dinucleotides (CDNs), potent activators of the STING pathway. Notably, antibiotic treatment ameliorated inflammation, underscoring the role of dysbiosis in driving STING-mediated autoinflammation. Furthermore, in SAVI patients, elevated systemic microbial and host-derived CDNs were observed. In conditions such as systemic lupus erythematosus (SLE)-a heterogeneous autoimmune disease with potential STING involvement-systemic microbial CDNs were significantly correlated with disease biomarkers, including type I interferon scores and anti-dsDNA antibodies. In contrast, no such correlations were observed in STING-independent conditions like rheumatoid arthritis (RA). Importantly, this study highlights that both microbial and host-derived CDNs are key drivers of STING activation, suggesting that personalized treatment strategies could target cGAS or the microbiome based on a patient's specific CDN profile. These findings position systemic CDNs as valuable biomarkers and therapeutic targets for STING-driven diseases.

DOI： 10.1016/j.jaut.2025.103434

PubMed

掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

Malnutrition is observed in approximately 20-50% of hospitals and long-term care facilities. We examined the effects of malted rice amazake beverage on the nutritional status and gut microbiome of older patients and residents in an integrated long-term care facility; 13 older patients and residents (84.6 ± 9.3 years) were prescribed 35 g of malted rice amazake daily for six weeks. Gut microbiome analysis, body composition and blood biochemistry test results, defecation surveys, dietary intake, and medications were recorded before and after the intervention. After the intervention, the Geriatric Nutritional Risk Index (GNRI) increased from 83.6 ± 9.1 points to 86.0 ± 9.8 points, and serum albumin increased from 3.3 ± 0.5 g/dL to 3.4 ± 0.5 g/dL. The α-diversity of gut bacteria increased from 390.1 ± 89.4 before to 447.2 ± 108.1, and the abundance of Desulfovibrio decreased from 0.76 ± 0.47% to 0.56 ± 0.60%. ΔGNRI showed a positive correlation with ΔBifidobacterium and ΔBarnesiella, but a negative correlation with ΔKlebsiella. Consumption of malted rice amazake for six weeks improved the GNRI and altered the gut microbiome of older patients and residents at moderate risk of nutritional disorders. Malted rice amazake may be a new way to improve nutrition because it has a high nutritional value, mainly in terms of carbohydrates, and improves the gut microbiome.

DOI： 10.1080/21551197.2024.2431283

PubMed

医薬基盤・健康・栄養研究所では,日本人の生活習慣や健康における腸内細菌叢の機能や役割を理解するため,日本人を対象とした大規模な腸内細菌調査に取り組んでいる.また,本研究領域の発展に貢献することを目的に,プロトコルの標準化や解析ツールの開発などを進め,他の研究機関への支援にも力を入れている.そのなかで,疫学と基礎を融合させた腸内細菌研究を推進し,肥満や糖尿病の予防や改善が期待できる腸内細菌の同定や作用機序の解明,腸内細菌が作り出すポストバイオティクスの探索や機能解析,腸内細菌叢の個人差に着目した個別化・層別化研究などを展開している.本稿では医薬基盤・健康・栄養研究所における腸内細菌研究の概要や最新の成果についてご紹介したい.(著者抄録)

<p>医薬基盤・健康・栄養研究所では，日本人の生活習慣や健康における腸内細菌叢の機能や役割を理解するため，日本人を対象とした大規模な腸内細菌調査に取り組んでいる．また，本研究領域の発展に貢献することを目的に，プロトコルの標準化や解析ツールの開発などを進め，他の研究機関への支援にも力を入れている．そのなかで，疫学と基礎を融合させた腸内細菌研究を推進し，肥満や糖尿病の予防や改善が期待できる腸内細菌の同定や作用機序の解明，腸内細菌が作り出すポストバイオティクスの探索や機能解析，腸内細菌叢の個人差に着目した個別化・層別化研究などを展開している．本稿では医薬基盤・健康・栄養研究所における腸内細菌研究の概要や最新の成果についてご紹介したい．</p>

DOI： 10.11209/jim.39.9

CiNii Research

掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

DOI： 10.3390/nu16223839

PubMed

掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

BACKGROUND: The incidence of pancreatic cancer is on the rise, and its prognosis remains poor. Recent reports have established a link between the gut and oral microbiome and pancreatic cancer. However, the intricacies of this association within the Japanese population remain unclear. In this study, we investigated the gut and oral microbiomes of Japanese patients with pancreatic cancer, comparing them with those of healthy individuals. METHODS: We recruited 30 patients with untreated pancreatic cancer and 18 healthy controls at Kyoto University Hospital (2018-2022). We performed a comprehensive 16S rRNA gene sequencing to analyze their gut and oral microbiomes. RESULTS: Analysis revealed that the diversity of the gut and oral microbiomes of patients with pancreatic cancer was reduced compared to that of the healthy controls. Specifically, we observed an increase in the genus Streptococcus in both the gut and oral microbiomes and a significant decrease in several butyrate-producing bacteria in fecal samples. Moreover, bacteria such as Streptococcus mitis and Holdemanella biformis were present in pancreatic cancer tissues, suggesting that they might influence the carcinogenesis and progression of pancreatic cancer. CONCLUSIONS: The gut and oral microbiome differed between patients with pancreatic cancer and healthy controls, with a notable decrease in butyrate-producing bacteria in the gut microbiome of the patients. This suggests that there may be a distinct microbial signature associated with pancreatic cancer in the Japanese population. Further studies are required to elucidate the microbiome's causal role in this cancer and help develop prognostic markers or targeted therapies.

DOI： 10.1016/j.pan.2024.09.002

PubMed

掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

Objective

Barley, abundant in β-glucan, a soluble dietary fiber, holds promise in obesity prevention. Given the microbial metabolism of dietary fiber in the gastrointestinal tract, we investigated the role of gut microbiota in non-obese individuals consuming high levels of barley.

Methods

Our study enrolled 185 participants from “The cohort study on barley and the intestinal environment (UMIN000033479).” Comprehensive physical examinations, including blood tests, were conducted, along with separate assessments of gut microbiome profiling and dietary intake. Participants were categorized into high and low barley consumption groups based on the median intake, with non-obese individuals in the high intake group identified as barley responders while participants with obesity were designated as non-responders. We compared the relative abundance of intestinal bacteria between these groups and used multivariate analysis to assess the association between intestinal bacteria and barley responders while controlling for confounding factors.

Results and discussion

Among the fermented food choices, responders exhibited notably higher consumption of natto (fermented soybeans) than non-responders. Moreover, after adjusting for confounders, Butyricicoccus and Subdoligranulum were found to be significantly more prevalent in the intestines of responders. Given natto’s inclusion of Bacillus subtilis, a glycolytic bacterium, and the butyrate-producing capabilities of Butyricicoccus and Subdoligranulum, it is hypothesized that fiber degradation and butyrate production are likely to be enhanced within the digestive tract of barley responders.

DOI： 10.3389/fnut.2024.1434150

PubMed

掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

DOI： 10.3390/nu16203546

PubMed

掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

OBJECTIVE: Food addiction is a multifactorial disorder characterised by a loss of control over food intake that may promote obesity and alter gut microbiota composition. We have investigated the potential involvement of the gut microbiota in the mechanisms underlying food addiction. DESIGN: We used the Yale Food Addiction Scale (YFAS) 2.0 criteria to classify extreme food addiction in mouse and human subpopulations to identify gut microbiota signatures associated with vulnerability to this disorder. RESULTS: Both animal and human cohorts showed important similarities in the gut microbiota signatures linked to food addiction. The signatures suggested possible non-beneficial effects of bacteria belonging to the Proteobacteria phylum and potential protective effects of Actinobacteria against the development of food addiction in both cohorts of humans and mice. A decreased relative abundance of the species Blautia wexlerae was observed in addicted humans and of Blautia genus in addicted mice. Administration of the non-digestible carbohydrates, lactulose and rhamnose, known to favour Blautia growth, led to increased relative abundance of Blautia in mice faeces in parallel with dramatic improvements in food addiction. A similar improvement was revealed after oral administration of Blautia wexlerae as a beneficial microbe. CONCLUSION: By understanding the crosstalk between this behavioural alteration and gut microbiota, these findings constitute a step forward to future treatments for food addiction and related eating disorders.

DOI： 10.1136/gutjnl-2023-331445

PubMed

掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

DOI： 10.1016/j.celrep.2024.114752

PubMed

担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

DOI： 10.3389/fmicb.2024.1415893

PubMed

掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

Abstract

This study investigated the effects of white meat, such as chicken, intake combined with resistance training on muscle mass and strength in the elderly women, and whether the underlying mechanism involves changes in the gut microbiota. Ninety‐three volunteers (age 59–79 years) were randomly allocated to sedentary control with placebo (Sed + PL) or chicken meat (Sed + HP) and resistance training with placebo (RT + PL) or chicken meat (RT + HP). Resistance training sessions were performed 3 d/week for 12 weeks using leg extensions and curls. Boiled chicken meat (110 g, containing 22.5 g protein) was ingested 3 d/week for 12 weeks. Maximal muscle strength and whole‐body lean mass increased significantly in the RT + PL group compared to the Sed + HP group, and the RT + HP group showed a significantly greater increase than the Sed + HP and RT + PL groups. Additionally, the gut microbiota composition did not change before or after the interventions in any of the four groups. Moreover, the individual comparison of gut bacteria using false discovery rate‐based statistical analysis showed no alterations before or after the interventions in the four groups. Resistance training combined with chicken meat intake may effective have increased muscle mass and strength without drastically modifying the gut microbiota composition in elderly women.

DOI： 10.14814/phy2.16100

PubMed

掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

Intestinal bacteria metabolize dietary substances to produce bioactive postbiotics, among which some are recognized for their role in promoting host health. We here explored the postbiotic potential of two omega-3 α-linolenic acid–derived metabolites: trans-10-cis-15-octadecadienoic acid (t10,c15-18:2) and cis-9-cis-15-octadecadienoic acid (c9,c15-18:2). Dietary intake of lipids rich in omega-3 α-linolenic acid elevated levels of t10,c15-18:2 and c9,c15-18:2 in the serum and feces of mice, an effect dependent on the presence of intestinal bacteria. Notably, t10,c15-18:2 mitigated skin inflammation in mice that became hypersensitive after exposure to 2,4-dinitrofluorobenzene, an experimental model for allergic contact dermatitis. In particular, t10,c15-18:2—but not c9,c15-18:2—attenuated ear swelling and edema, characteristic symptoms of contact hypersensitivity. The anti-inflammatory effects of t10,c15-18:2 were due to its ability to suppress the release of vascular endothelial growth factor A from keratinocytes, thereby mitigating the enhanced vascular permeability induced by hapten stimulation. Our study identified retinoid X receptor as a functional receptor that mediates the downregulation of skin inflammation upon treatment with t10,c15-18:2. Our results suggest that t10,c15-18:2 holds promise as an omega-3 fatty acid–derived postbiotic with potential therapeutic implications for alleviating the skin edema seen in allergic contact dermatitis–induced inflammation.

DOI： 10.3389/fcimb.2024.1355679

PubMed

掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

Despite accumulating evidence that suggests a unique gut microbiota composition in athletes, a comprehensive understanding of this phenomenon is lacking. Furthermore, seasonal variation in the gut microbiota of athletes, particularly during the off-season, remains underexplored. This study aimed to compare the gut microbiotas between athletic subjects (AS) and non-athletic subjects (NS), and to investigate variations between athletic and off-season periods. The data were derived from an observational study involving Japanese male handball players. The results revealed a distinct gut microbiota composition in AS compared with NS, characterized by significantly higher alpha-diversity and a greater relative abundance of Faecalibacterium and Streptococcus. Moreover, a comparative analysis between athletic and off-season periods in AS demonstrated a significant change in alpha-diversity. Notably, AS exhibited significantly higher alpha-diversity than NS during the athletic season, but no significant difference was observed during the off-season. This study demonstrates the characteristics of the gut microbiota of Japanese handball players and highlights the potential for changes in alpha-diversity during the off-season. These findings contribute to our understanding of the dynamic nature of the gut microbiota of athletes throughout the season.

DOI： 10.3390/microorganisms12040781

PubMed

掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

Lipopolysaccharide (LPS), a cell surface component of Gram-negative bacteria, activates innate immunity. Its active principle is the terminal glycolipid lipid A. Acetobacter pasteurianus is a Gram-negative bacterium used in the fermentation of traditional Japanese black rice vinegar (kurozu). In this study, we focused on A. pasteurianus lipid A, which is a potential immunostimulatory component of kurozu. The active principle structure of A. pasteurianus lipid A has not yet been identified. Herein, we first systematically synthesized three types of A. pasteurianus lipid As containing a common and unique tetrasaccharide backbone. We developed an efficient method for constructing the 2-trehalosamine skeleton utilizing borinic acid-catalyzed glycosylation to afford 1,1'-α,α-glycoside in high yield and stereoselectivity. A common tetrasaccharide intermediate with an orthogonal protecting group pattern was constructed via [2+2] glycosylation. After introducing various fatty acids, all protecting groups were removed to achieve the first chemical synthesis of three distinct types of A. pasteurianus lipid As. After evaluating their immunological function using both human and murine cell lines, we identified the active principles of A. pasteurianus LPS. We also found the unique anomeric structure of A. pasteurianus lipid A contributes to its high chemical stability.

DOI： 10.1002/anie.202402922

PubMed

マウスへの経鼻投与におけるアルカリゲネス属リピドA(ALA)とモノホスホリルリピドA(MPLA)のアジュバント活性を比較し、これらの効果の根底にあるメカニズムを調べた。ALAは化学的合成品を用いた。マウスの鼻腔にオボアルブミン(OVA)とALA/MPLAを投与した後、血清、鼻洗浄液、気管支肺胞洗浄液中のOVA特異的IgAとIgGをELISAで測定した。皮下投与については血清中の抗体を測定した。経鼻および皮下投与後、ALAはMPLAより高レベルの抗原特異的抗体分泌を誘導した。特に、ALAは経鼻ワクチン接種において優れた効果を発揮した。鼻腔内と全身のIgA産生に及ぼす効果と一致して、ALAは鼻咽頭関連リンパ組織(NALT)と頸部リンパ節(CLN)内の胚中心(GC)の形成を促進し、GC B細胞、IgA陽性B細胞、Tfh細胞集団を増加させた。経鼻ワクチンにおけるALAの優位性の根底にある可能性の高いメカニズムとしては、ALAが鼻腔組織における高度に活性化されたCD11b陽性の従来型2型樹状細胞(cDC2)の浸潤、特にcDC2A細胞数を増加させることが考えられた。さらに、ALAは鼻腔組織の間質細胞上のGM-CSFとCCL2の発現とCD45陽性免疫細胞上のCCL3とCCL4の発現を誘導した。これらのケモカインのうちCCL2とCCL3は鼻腔組織へのcDC2の動員を支援した。

日本の一般成人の骨格筋機能、量、質と関連する腸内細菌属を同定するため横断研究を実施した。都市在住の35-80歳の成人164例の糞便検体を収集し、16S rRNAアンプリコンシーケンス解析を行った。その結果、60歳以上の患者においてのみBacteroidesおよびPrevotella 9が脚伸展筋力(LEP)と有意に関連していた。BacteroidesとPrevotella 9の両方を同じ回帰モデルに含めた場合、Bacteroidesのみが有意にLEPと関連した。なお、骨格筋量、握力、位相角と、主要な腸内細菌属との間に有意な関連はみられなかった。以上より、日本の高齢者ではBacteroidesとLEPとの間に有意な正の関係が認められた。