学術雑誌リスト

There is growing interest in dietary interventions, particularly gerobiotics, that directly target aging. Several single-strain gerobiotics have proven to be beneficial in alleviating aging and age-related functional declines across species, but multistrain/multispecies gerobiotics have been proven even more advantageous due to the potential synergy and additive effects among individual isolates. However, there is very limited research on how multistrain/multispecies gerobiotic combinations or cocktails extend healthy longevity. This study comprehensively analyzed probiotic bacteria from traditionally fermented Barnyard millet and compared their efficacy in promoting healthy longevity under various combinations using Caenorhabditis elegans. We have shown that dramatic lifespan extension can be achieved by combining gerobiotics, and the effect was found to be strictly strain-specific. Among the 120 combinations tested, we identified two synergistic gerobiotic combinations, cocktail 55 (combination of B. licheniformis PS70, L. delbrueckii subsp. bulgaricus PS77, and L. amylovorus PS60) and cocktail 112 (combination of L. delbrueckii subsp. bulgaricus PS77, L. lactis PS10, and P. pentosaceus PS91), extending the mean lifespan of C. elegans by up to 46.2% and 53.1%, respectively. Our mechanistic study showed that the life-promoting effect of cocktail 55 relied on the p38 MAPK-SKN-1 pathway, while cocktail 112 acted on multiple signaling pathways, including IIS, β-catenin, and TGF-β pathways, to achieve its impact on the host. Moreover, feeding gerobiotic cocktails improved several healthspan markers reported to decline with age. These observations showed that the gerobiotic cocktails target different subsets of the gene regulatory network controlling the aging process in C. elegans, thereby extending healthy longevity.

Antibiotic-associated diarrhea is mediated by antibiotic treatment and is usually caused by the disruption of the intestinal barrier, gut microbiota, and metabolic balance. To identify a dietary strategy that can mitigate the side effects of antibiotics, this study investigated the effect of tangeretin on antibiotic-associated diarrhea in C57BL/6 mice. The results revealed that dietary tangeretin significantly ameliorated symptoms of antibiotic-associated diarrhea, as evidenced by the decreased diarrhea status scores, the reduced fecal water content, the decreased caecum/body weight ratio, and the alleviated colonic tissue damage. Dietary tangeretin also exhibited a protective effect on the intestinal barrier function by upregulating the mRNA and protein expression of claudin-1 and ZO-1. Furthermore, analysis of the gut microbiota using 16S rRNA gene sequencing indicated that dietary tangeretin modulated the gut microbiota of mice with antibiotic-associated diarrhea via increasing the gut microbiota diversity and the abundance of beneficial bacteria, e.g., Lactobacillaceae and Ruminococcaceae, and decreasing the abundance of harmful bacteria, e.g., Enterococcus and Terrisporobacter. Additionally, dietary tangeretin restored the levels of short-chain fatty acids and modulated metabolic pathways by enriching purine metabolism, bile acid metabolism, ABC transporters, and choline metabolism in cancer. Collectively, these findings provide a solid scientific basis for the rational use of tangeretin as a preventive and therapeutic agent for antibiotic-associated diarrhea.

Gut microbiota are closely related to lipopolysaccharide (LPS)-induced acute lung injury (ALI). Akkermansia muciniphila (A. muciniphila) maintains the intestinal barrier function and regulates the balance of reduced glutathione/oxidized glutathione. However, it may be useful as a treatment strategy for LPS-induced lung injury. Our study aimed to explore whether A. muciniphila could improve lung injury by affecting the gut microbiota. The administration of A. muciniphila effectively attenuated lung injury tissue damage and significantly decreased the oxidative stress and inflammatory reaction induced by LPS, with lower levels of myeloperoxidase (MDA), enhanced superoxide dismutase (SOD) activity, decreased pro-inflammatory cytokine levels, and reduced macrophage and neutrophil infiltration. Moreover, A. muciniphila maintained the intestinal barrier function, reshaped the disordered microbial community, and promoted the secretion of short-chain fatty acids (SCFAs). A. muciniphila significantly downregulated the expression of TLR2, MyD88 and NF-kappa B (P < 0.05). Butyrate supplementation demonstrated a significant improvement in the inflammatory response (P < 0.05) and mitigation of histopathological damage in mice with ALI, thereby restoring the intestinal butyric acid concentration. In conclusion, our findings indicate that A. muciniphila inhibits the accumulation of inflammatory cytokines and attenuates the activation of the TLR2/Myd88/NF-κB pathway due to exerting anti-inflammatory effects through butyrate. This study provides an experimental foundation for the potential application of A. muciniphila and butyrate in the prevention and treatment of ALI.

Pectin, a kind of dietary fiber, has attracted much attention owing to its beneficial effect on human health in recent years. In this study, the effects of both ‘Ganzhou’ navel orange peel pectin (GOP) and modified GOP (MGOP) on type 2 diabetes (T2DM) were investigated. The results indicated that GOP and MGOP intervention had positive effects on T2DM in C57BL/6 mice. After modification, pectin can be changed into low methoxy pectin (LMP) and the content of GalA can increase, which endow MGOP with significant effects on improving lipid metabolism (TC, TG, and LDL-C decreased by 30.46%, 50%, and 37.56%, respectively, and HDL-C increased by 56%) and OGTT, further reducing insulin resistance (insulin decreased by 74.35%). In addition, MGOP was superior to GOP in improving oxidative stress (GSH and GSH-Px increased by 52.05% and 29.08% respectively, and MDA decreased by 84.02%), inhibiting inflammation and promoting SCFA synthesis. 16S rRNA analysis showed that MGOP changed the composition of intestinal microbiota in diabetic mice, decreased the abundance of Alistipes, Helicobacter and Oscillibacter, and increased the relative abundance of Dubosiella, Akkermansiaceae, and Atopobiaceae. The phenotypes of the gut microbiome also changed accordingly, which showed that MGOP significantly inhibited the growth of Gram-negative bacteria and potential pathogenic bacteria and reversed the related complications. Taken together, our findings revealed that MGOP intake regulated lipid metabolism and oxidative stress and improved the gut health of mice, with promising effects against T2DM and related complications.

Constipation is a prevalent gastrointestinal (GI) problem affecting a large number of individuals. This study aimed to investigate peristalsis-promoting potential characteristics of Ligilactobacillus acidipiscis YJ5 and the underlying molecular mechanism. The study demonstrated the relieving effect of L. acidipiscis YJ5 on constipation in both zebrafish and mouse models. L. acidipiscis YJ5 intervention significantly increased intestinal peristalsis by reducing the peak time and increasing the fluorescence disappearance rate in the zebrafish model. In the mouse model, the symptoms of constipation relief induced by L. acidipiscis YJ5 included a shortened first black stool time, an increased number of defecation particles, an accelerated propulsion rate of the small intestine, and an increase in fecal water content. L. acidipiscis YJ5 was found to reduce the expression of colonic aquaporins to normalize the colonic water transport system of constipated mice. Additionally, L. acidipiscis YJ5 reversed loperamide-induced morphological damage in the ileum and colon and increased the colonic mucosal barrier. The results of the 16S rRNA gene analysis indicated that L. acidipiscis YJ5 could reverse the structure of gut microbiota to a near-normal group, including levels of β-diversity, phylum, family, and genus. Furthermore, the fermentation supernatant of L. acidipiscis YJ5 was shown to relieve constipation, and metabolomics analysis revealed that these positive effects were related to its metabolites like malic acid and heliangin.

Tropomyosin (TM) is the major allergen in shrimp that is known to be the primary trigger for shrimp-induced food allergy. Our previous reports suggest that glycation could reduce the allergenicity of TM and the reduction of allergenicity is largely dependent on the sources of saccharides. This investigation aimed to investigate the glycation of TM by glucose and maltotriose as well as the effects of glycation on the allergenicity of TM. Compared to TM, the IgG-binding capacity and IgE-binding capacity of tropomyosin glycated by glucose (TM-G) was greatly reduced with a longer glycation time, the release of allergic mediators from RBL-2H3 mast cells was reduced in a time-dependent manner, and weaker allergic reactions were induced in BALB/c mice. Conversely, tropomyosin glycated by maltotriose (TM-MTS) exhibited a stronger allergenicity after 48 hours of glycation due to the generation of neoallergens that were derived from the advanced glycation end products (AGEs). In conclusion, glucose could be used to desensitize the shrimp TM-induced food allergy via glycation, which could significantly reduce the allergenicity and alleviate allergic symptoms. This work could provide a novel approach to reduce the allergenicity of shrimp tropomyosin and prevent the shrimp tropomyosin-induced food allergy.

Intestinal mucosal barrier damage is closely associated with the development of several intestinal inflammatory diseases. Isoquercitrin (IQ) is a natural flavonoid compound derived from plants, which exhibits high antioxidant and anti-inflammatory activity with minimal side effects in humans. Therefore, it shows great potential for preventing and treating intestinal mucosal barrier damage. This study aims to investigate the ameliorative effect and mechanism of IQ on lipopolysaccharide (LPS)-induced intestinal mucosal barrier damage in mice. The mice were treated with IQ for 7 days and then injected with LPS to induce intestinal mucosal barrier damage. The results revealed that IQ treatment alleviated LPS-induced intestinal mucosal barrier damage in mice, which can be evidenced by the improvements in intestinal morphology and the promotion of expression in intestinal tight junctions (ZO-1, Claudin-1, and Occludin), as well as MUC2 mucin. IQ also attenuated intestinal inflammatory responses by inhibiting the TLR4/MyD88/NF-κB signaling pathway and reducing the expression and plasma levels of IL-6, IL-1β, and TNF-α. Furthermore, IQ significantly increased the relative abundance of beneficial bacteria, including Dubosiella, Akkermansia muciniphila and Faecalibaculum rodentium, while suppressing the growth of harmful bacteria such as Mucispirillum schaedleri in the intestinal flora of mice. Consequently, IQ can alleviate the LPS-induced intestinal mucosal barrier damage in mice by inhibiting the TLR4/MyD88/NF-κB signaling pathway and modulating the intestinal flora.

Food allergy (FA) has become a prominent problem in public health. 2′-Fucosyllactose (2′-FL) was reported to alleviate FA symptoms; however, the regulatory mechanism is still unclear. This study evaluated the 2′-FL antiallergic potential in an ovalbumin (OVA)-sensitized mouse model and explored the systemic effects of 2′-FL on gut microecology and the intestinal immune barrier. The results showed that 2′-FL alleviated allergy symptoms, decreased serum allergic indicator levels, enhanced the intestinal barrier, and attenuated low-grade inflammation. The up-regulation of G protein-coupled receptors (GPRs) was associated with higher levels of short-chain fatty acids (SCFAs) in 2′-FL intervention mice. 2′-FL also improved the intestinal microbiota diversity and increased the abundance of Akkermansia, Lachnospiraceae UCG-006, and Ruminococcaceae while suppressing Muribaculaceae, Desulfovibrionaceae, and Erysipelotrichaceae. Additionally, 2′-FL ameliorated the imbalance of Th2/Th1, mainly by decreasing Th2-type immune response and enhanced CD4 + Foxp3 + Treg immunoreaction. These results suggest that 2′-FL restores intestinal barrier defects, gut microbiota disorder, and immune impairment while alleviating ovalbumin-induced allergic symptoms in FA mice.

Idiopathic pulmonary fibrosis (IPF) is a life-threatening disease that leads to dyspnea and progressive loss of lung function. This study aimed to investigate the protective effect of betanin (BET), the major pigment in red beetroot, on pulmonary fibrosis induced by bleomycin (BLM) in rats and to assess the underlying mechanisms. In this view, total and differential cell counts and LDH activity in bronchoalveolar lavage fluid were estimated. Furthermore, MDA and GSH contents in the lungs were colorimetrically measured, while hydroxyproline, NLRP3, ASC, caspase-1, TGF-β1, and vimentin levels in lung tissue were evaluated using the ELISA technique. Moreover, IL-1β, E-cadherin, and α-SMA expressions were analyzed by immunostaining of lung specimens. BET treatment protects against pulmonary fibrosis as indicated by the reduction in total and differential cell counts, LDH activity, hydroxyproline, NLRP3, ASC, caspase-1, IL-1β, and TGF-β1 levels. MDA content was also decreased following BET administration, while GSH content was elevated. Additionally, BET suppressed the EMT process as evidenced by an increase in E-cadherin expression besides the reduction in vimentin and α-SMA expressions. To conclude, these results revealed the protective effect of BET against pulmonary fibrosis that might be attributed to the attenuation of the NLRP3/IL-1β/TGF-β1 signaling pathway and EMT process.

Hyperlipidemia is a common clinical disorder of lipid metabolism in modern society and is considered to be one of the major risk factors leading to cardiovascular-related diseases. Germinated brown rice (GBR) is a typical whole grain food. The lipid-lowering effect of GBR has received increasing attention, but its mechanism of action is not fully understood. The gut microbiota has been proposed as a novel target for the treatment of hyperlipidemia. The aim of this study was to investigate the effects of GBR on the gut microbiota and lipid metabolism in high-fat diet (HFD)-fed C57BL/6J mice. The effect of GBR on hyperlipidemia was evaluated by measuring blood lipid levels and by pathological examination. The gut microbiota was detected by 16S rRNA sequencing, and the protein and mRNA expression levels involved in cholesterol metabolism were detected by western blotting and RT-qPCR to find potential correlations. The results showed that GBR supplementation could effectively reduce the levels of TC, TG, LDL-C and HDL-C in the serum and alleviate the excessive accumulation of fat droplets caused by HFD. Moreover, GBR intervention improved HFD-fed gut microbiota disorder via increasing the diversity of the gut microbiota, reducing the Firmicutes/Bacteroidetes ratio, and improving gut barrier damage. In addition, GBR could inhibit endogenous cholesterol synthesis and promote cholesterol transport and excretion. These findings suggest that GBR may be a competitive candidate for the development of functional foods to prevent abnormal lipid metabolism.