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19 pages, 2396 KB  
Article
Alleviation of Ovalbumin-Allergic Reactions in Mice by Eucommia ulmoides Polysaccharides via Modulation of Intestinal Microbiota
by Xuelei Zhang, Ketong Bi, Chuansheng Zhao, Yuxin Cao, Yuxuan Yang, Jingxuan Jia, Yong Zhang, Dandan Zhai, Yu Yang and Peng Li
Foods 2025, 14(16), 2913; https://doi.org/10.3390/foods14162913 - 21 Aug 2025
Viewed by 390
Abstract
Food allergy represents a prevalent immunological disorder, with current clinical management primarily emphasizing allergen avoidance and emergency pharmacological intervention. Eucommia ulmoides polysaccharides, the principal bioactive constituents of the traditional Chinese medicinal plant Eucommia ulmoides, have demonstrated anti-inflammatory and antioxidant properties; however, their [...] Read more.
Food allergy represents a prevalent immunological disorder, with current clinical management primarily emphasizing allergen avoidance and emergency pharmacological intervention. Eucommia ulmoides polysaccharides, the principal bioactive constituents of the traditional Chinese medicinal plant Eucommia ulmoides, have demonstrated anti-inflammatory and antioxidant properties; however, their specific effects on food allergies remain inadequately characterized. A total of thirty-six female BALB/c mice were randomly allocated into three groups (n = 12 per group): the control group (CON group, receiving saline treatment), the allergic model group (OVA group, subjected to ovalbumin sensitization), and the intervention group (OVA+PS group, undergoing OVA sensitization followed by Eucommia ulmoides polysaccharides administration via gavage). The anti-allergic efficacy of Eucommia ulmoides polysaccharides was comprehensively evaluated through clinical allergy symptom scoring, histological and pathological tissue analysis, real-time fluorescence quantitative PCR (qRT-PCR) for the assessment of key gene expression, and 16S rDNA sequencing. The findings indicated the following: (1) The allergy scores in the OVA+PS group were significantly lower than those in the OVA group (p < 0.01). Following OVA stimulation, the rectal temperature of mice in the OVA group decreased sharply, whereas the temperature decline in the OVA+PS group was more gradual compared to the model group. (2) The liver, kidney, spleen, and intestinal tissues of mice in the OVA+PS group exhibited normal morphology, consistent with the CON group, which suggests that Eucommia ulmoides polysaccharides effectively mitigates the local inflammatory response induced by food allergy. (3) The expression of NICD in the spleen of mice in the OVA+PS group was significantly higher than in the OVA group (p < 0.05), while the expression of the Hes1 gene was significantly elevated in the OVA group compared to both the CON and OVA+PS groups (p < 0.05). In the OVA group, the expression level of Gata-3 was significantly elevated compared to both the CON group and the OVA+PS group (p < 0.05). Similarly, the expression of STAT5 in the OVA group was markedly higher than in the other groups (p < 0.05). (4) Eucommia ulmoides polysaccharides were found to modulate the intestinal microbiota composition in allergic mice, notably increasing the expression abundance of Enterobacter, Oscillibacter, and Butyricicoccus, while decreasing the expression abundance of Clostridium sensu stricto 1 and Turicibacter. (5) There was a correlation between alterations in the intestinal microbiota of mice and the expression of key genes. Specifically, the relative abundance of Blautia was negatively correlated with the expression of NICD and Gata-3 genes (p < 0.05), and the relative abundance of the Lachnospiraceae_FCS020_group was negatively correlated with the expression of the Hes1 gene (p < 0.05). In conclusion, Eucommia ulmoides polysaccharides demonstrate potential in alleviating allergic symptoms, providing a scientific foundation for the development of novel natural anti-allergic functional foods. Full article
(This article belongs to the Special Issue Natural Polysaccharides: Structure and Health Functions)
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12 pages, 1592 KB  
Article
Interconnection of Gut Microbiome and Efficacy of Immune Checkpoint Inhibitors in Inoperable Non-Small-Cell Lung Cancer
by Fedor Moiseenko, Andrey Kechin, Maksim Koryukov, Ulyana Boyarskikh, Albina Gabina, Ani Oganesian, Sergey Belukhin, Maria Makarkina, Ekaterina Elsakova, Elizaveta Artemeva, Alexander Myslik, Nikita Volkov, Alexey Bogdanov, Ekaterina Kuligina, Svetlana Aleksakhina, Aglaya Iyevleva, Alexander Ivantsov, Andrey Bogdanov, Sergey Sidorenko, Vladimir Gostev, Alexey Komissarov, Vasilisa Dudurich, Lavrenty Danilov, Evgeny Imyanitov and Vladimir Moiseyenkoadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2025, 26(16), 7758; https://doi.org/10.3390/ijms26167758 - 11 Aug 2025
Viewed by 331
Abstract
The efficacy of immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC) varies widely across patients. Growing evidence indicates that the gut microbiome, through its interaction with the tumor microenvironment, may influence the response to immunotherapy. To investigate this, we analyzed fecal and [...] Read more.
The efficacy of immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC) varies widely across patients. Growing evidence indicates that the gut microbiome, through its interaction with the tumor microenvironment, may influence the response to immunotherapy. To investigate this, we analyzed fecal and tumor samples from 63 patients with inoperable NSCLC undergoing ICI therapy. Based on microbiome profiling using 16S rRNA sequencing, patients were grouped according to treatment benefit, defined as progression-free survival (PFS) of six months or longer. Associations between α-diversity indices, microbial composition at the genus and phylum levels, and a composite Sum Index of Binary Abundance (SIBA) were examined in relation to clinical outcomes. Higher microbial α-diversity was linked to improved response to ICIs (p-value = 0.0078 for the Chao1 index). Multiple specific taxa, such as Ruminococcus gauvreauii (p-value = 2 × 10−4), Ruminiclostridium 9 (p-value = 8 × 10−4), and [Eubacterium] ventriosum (p-value = 9 × 10−4), were enriched in patients with favorable outcomes, whereas Oscillibacter and the Eubacterium hallii group were associated with disease progression (p-value = 2 × 10−3 and 9 × 10−3, respectively). The SIBA index, which reflects the absence of multiple beneficial bacterial taxa, proved to be a stronger predictor of treatment response than individual taxa alone. Median SIBA values were 18 vs. 24 in patients benefiting from IO therapy compared to non-responders (p-value = 9 × 10−7). These findings suggest that gut microbiome diversity and composition are closely tied to immunotherapy outcomes in NSCLC. Composite microbial metrics like SIBA may enhance predictive accuracy and inform personalized treatment approaches. Full article
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29 pages, 3012 KB  
Article
Investigating Multi-Omic Signatures of Ethnicity and Dysglycaemia in Asian Chinese and European Caucasian Adults: Cross-Sectional Analysis of the TOFI_Asia Study at 4-Year Follow-Up
by Saif Faraj, Aidan Joblin-Mills, Ivana R. Sequeira-Bisson, Kok Hong Leiu, Tommy Tung, Jessica A. Wallbank, Karl Fraser, Jennifer L. Miles-Chan, Sally D. Poppitt and Michael W. Taylor
Metabolites 2025, 15(8), 522; https://doi.org/10.3390/metabo15080522 - 1 Aug 2025
Viewed by 626
Abstract
Background: Type 2 diabetes (T2D) is a global health epidemic with rising prevalence within Asian populations, particularly amongst individuals with high visceral adiposity and ectopic organ fat, the so-called Thin-Outside, Fat-Inside phenotype. Metabolomic and microbiome shifts may herald T2D onset, presenting potential biomarkers [...] Read more.
Background: Type 2 diabetes (T2D) is a global health epidemic with rising prevalence within Asian populations, particularly amongst individuals with high visceral adiposity and ectopic organ fat, the so-called Thin-Outside, Fat-Inside phenotype. Metabolomic and microbiome shifts may herald T2D onset, presenting potential biomarkers and mechanistic insight into metabolic dysregulation. However, multi-omics datasets across ethnicities remain limited. Methods: We performed cross-sectional multi-omics analyses on 171 adults (99 Asian Chinese, 72 European Caucasian) from the New Zealand-based TOFI_Asia cohort at 4-years follow-up. Paired plasma and faecal samples were analysed using untargeted metabolomic profiling (polar/lipid fractions) and shotgun metagenomic sequencing, respectively. Sparse multi-block partial least squares regression and discriminant analysis (DIABLO) unveiled signatures associated with ethnicity, glycaemic status, and sex. Results: Ethnicity-based DIABLO modelling achieved a balanced error rate of 0.22, correctly classifying 76.54% of test samples. Polar metabolites had the highest discriminatory power (AUC = 0.96), with trigonelline enriched in European Caucasians and carnitine in Asian Chinese. Lipid profiles highlighted ethnicity-specific signatures: Asian Chinese showed enrichment of polyunsaturated triglycerides (TG.16:0_18:2_22:6, TG.18:1_18:2_22:6) and ether-linked phospholipids, while European Caucasians exhibited higher levels of saturated species (TG.16:0_16:0_14:1, TG.15:0_15:0_17:1). The bacteria Bifidobacterium pseudocatenulatum, Erysipelatoclostridium ramosum, and Enterocloster bolteae characterised Asian Chinese participants, while Oscillibacter sp. and Clostridium innocuum characterised European Caucasians. Cross-omic correlations highlighted negative correlations of Phocaeicola vulgatus with amino acids (r = −0.84 to −0.76), while E. ramosum and C. innocuum positively correlated with long-chain triglycerides (r = 0.55–0.62). Conclusions: Ethnicity drove robust multi-omic differentiation, revealing distinctive metabolic and microbial profiles potentially underlying the differential T2D risk between Asian Chinese and European Caucasians. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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20 pages, 12384 KB  
Article
Oxidative Stress Model of Lipopolysaccharide-Challenge in Piglets of Wuzhishan Miniature Pig
by Ruiying Bao, Pingfei Qiu, Yanrong Hu, Junpu Chen, Xiaochun Li, Qin Wang, Yongqiang Li, Huiyu Shi, Haiwen Zhang and Xuemei Wang
Vet. Sci. 2025, 12(8), 694; https://doi.org/10.3390/vetsci12080694 - 24 Jul 2025
Viewed by 399
Abstract
Oxidative stress (OS) is a major concern in young poultry and livestock, prompting extensive research on OS models. This study aimed to systematically investigate the dynamic effects and temporal trends of OS induced with lipopolysaccharide (LPS) over time. Twenty-eight piglets were randomly divided [...] Read more.
Oxidative stress (OS) is a major concern in young poultry and livestock, prompting extensive research on OS models. This study aimed to systematically investigate the dynamic effects and temporal trends of OS induced with lipopolysaccharide (LPS) over time. Twenty-eight piglets were randomly divided into four groups and equally intraperitoneally injected with LPS at doses of 0 μg/kg (control), 50 μg/kg (L-LPS), 100 μg/kg (M-LPS) and 150 μg/kg (H-LPS) body weight, respectively. The results showed that total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), and catalase (CAT) were decreased, while malondialdehyde (MDA), nitric oxide (NO), inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α), diamine oxidase (DAO) and D-lactic acid (D-LA) were increased in the M-LPS and H-LPS group on day 1 in comparison with the control group, but no differences were found among treatments on day 7. However, LPS treatments gave rise to varying degrees of pathological injury in the intestines, livers and spleens on day 7. Metabolomics analysis indicated that compared with the control group, glycyl-valine, histamine and lepidine F were decreased in the M-LPS group. Most differentially expressed metabolites were enriched in amino acid-related metabolism pathways on both day 1 and day 7. Microbiome analysis identified that Oscillibacter_sp._CAG:241 was decreased in the M-LPS group compared with the control group on day 1, while Bacteroides_thetaiotaomicron and Lactobacillus_amylovorus were reduced in the M-LPS group on day 7. Collectively, an LPS dose of 100 μg/kg body weight is optimal for inducing acute inflammation in Wuzhishan miniature pigs. These findings highlight the importance of considering both the duration of OS induction and the specific research objectives when establishing OS models. Full article
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17 pages, 7840 KB  
Article
Systemic and Retinal Protective Effects of Butyrate in Early Type 2 Diabetes via Gut Microbiota–Lipid Metabolism Interaction
by Haijun Gong, Haoyu Zuo, Keling Wu, Xinbo Gao, Yuqing Lan and Ling Zhao
Nutrients 2025, 17(14), 2363; https://doi.org/10.3390/nu17142363 - 18 Jul 2025
Viewed by 735
Abstract
Background: Early neurovascular unit (NVU) impairment plays a critical role in the pathogenesis of diabetic retinopathy (DR), often preceding clinically detectable changes. Butyrate, a short-chain fatty acid (SCFA) derived from gut microbiota, has shown promising metabolic and anti-inflammatory effects. Methods: This study [...] Read more.
Background: Early neurovascular unit (NVU) impairment plays a critical role in the pathogenesis of diabetic retinopathy (DR), often preceding clinically detectable changes. Butyrate, a short-chain fatty acid (SCFA) derived from gut microbiota, has shown promising metabolic and anti-inflammatory effects. Methods: This study investigated the protective potential of oral butyrate supplementation in a mouse model of early type 2 diabetes mellitus (T2DM) induced by a high-fat diet and streptozotocin. Mice (C57BL/6J) received sodium butyrate (5 g/L in drinking water) for 12 weeks. Retinal NVU integrity was assessed using widefield swept-source optical coherence tomography angiography (WF SS-OCTA), alongside evaluations of systemic glucose and lipid metabolism, hepatic steatosis, visual function, and gut microbiota composition via 16S rRNA sequencing. Results: Butyrate supplementation significantly reduced body weight, fasting glucose, serum cholesterol, and hepatic lipid accumulation. Microbiome analysis demonstrated a partial reversal of gut dysbiosis, characterized by increased SCFA-producing taxa (Ruminococcaceae, Oscillibacter, Lachnospiraceae) and decreased pro-inflammatory, lipid-metabolism-related genera (Rikenella, Ileibacterium). KEGG pathway analysis further revealed enrichment in microbial lipid metabolism functions (fabG, ABC.CD.A, and transketolase). Retinal vascular and neurodegenerative alterations—including reduced vessel density and retinal thinning—were markedly attenuated by butyrate, as revealed by WF SS-OCTA. OKN testing indicated partial improvement in visual function, despite unchanged ERG amplitudes. Conclusions: Butyrate supplementation mitigates early NVU damage in the diabetic retina by improving glucose and lipid metabolism and partially restoring gut microbial balance. This study also underscores the utility of WF SS-OCTA as a powerful noninvasive tool for detecting early neurovascular changes in DR. Full article
(This article belongs to the Section Nutrition and Diabetes)
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24 pages, 4132 KB  
Article
Metagenomic Insight into Cecal Microbiota Shifts in Broiler Chicks Following Eimeria spp. Vaccination
by Dimitrios Marinos Karadedos, Tilemachos Mantzios, Despoina Eugenia Kiousi, Margaritis Tsifintaris, Ilias Giannenas, Panagiotis Sakkas, Georgios A. Papadopoulos, Gunther Antonissen, Aglaia Pappa, Alex Galanis and Vasilios Tsiouris
Microorganisms 2025, 13(7), 1470; https://doi.org/10.3390/microorganisms13071470 - 24 Jun 2025
Viewed by 678
Abstract
Coccidiosis, caused by Eimeria spp., remains a major challenge in poultry production, significantly affecting poultry health and performance, leading to substantial economic losses. While its impact on gut health is well documented, the interplay of Eimeria spp. challenge and/or vaccination with the intestinal [...] Read more.
Coccidiosis, caused by Eimeria spp., remains a major challenge in poultry production, significantly affecting poultry health and performance, leading to substantial economic losses. While its impact on gut health is well documented, the interplay of Eimeria spp. challenge and/or vaccination with the intestinal microbiota remain insufficiently understood. Therefore, the aim of this study was to investigate the effects of Eimeria spp. (E. acervulina, E. maxima, and E. tenella) challenge, alone or in combination with a commercially available vaccine, on broiler performance, intestinal gross lesions, and cecal microbiota structure and function in experimentally challenged broiler chicks. A total of 216 Ross 308® broilers were randomly divided into three groups, with six replicates per group, according to the following experimental design: (A) negative control, (B) Eimeria spp.-challenged birds on day 16, and (C) Eimeria spp.-vaccinated and -challenged birds. Performance parameters were recorded on a weekly basis, coccidiosis gross lesions in the intestine were evaluated on days 23 and 29, and microbiota samples were collected on day 23. Broilers in the challenged group exhibited significantly (p ≤ 0.05) increased coccidiosis gross lesions in the intestine at both sampling periods (7 and 19 days post-infection, dpi), whereas vaccination significantly (p ≤ 0.05) minimized the severity of lesions at both time points. The challenged-only group showed significantly (p ≤ 0.05) lower average daily weight gain (ADWG) during the finisher phase and the overall experimental period compared to the vaccinated group. Additionally, average daily feed intake (ADFI) during the post-challenge period (22–29 dpi) was significantly (p ≤ 0.05) reduced in both challenged groups. Alpha diversity decreased in the challenged (p = 0.016) and vaccinated–challenged (p = 0.016) groups compared to control, Accordingly, beta diversity was reduced in groups B and C compared to the control group. This reduction was accompanied by an increased relative abundance of Proteobacteria (18, 71% in Group B and 10, 87% in Group C) and potentially pathogenic genera (Escherichia spp. and Shigella spp. p < 0.05), along with a decline in short-chain fatty acid (SCFA)-producing bacteria (Oscillibacter spp. and Eisenbergiella spp.) in groups B and C, respectively, compared to the control. Predictive functional metagenomics indicated disruptions in amino acid metabolism, nucleotide degradation, and lipid metabolism, potentially affecting gut integrity and nutrient absorption. Additionally, in the vaccinated group, gross lesions in the intestine were reduced in severity and microbial diversity was partially preserved, resulting in a microbiota composition more similar to that of the control group. Overall, these findings support that Eimeria spp. infection alters gut microbiota and function in broiler chicks, underscoring the need for further research into alternative strategies, such as probiotics and phytobiotics, to support gut health and disease resilience in poultry. Full article
(This article belongs to the Special Issue Microbiome Research for Animal, Plant and Environmental Health)
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14 pages, 998 KB  
Article
The Paradox of Clean Eating: Neuroactive Dysbiosis and Pesticide Residues in Fruit- and Vegetable-Based Diets
by Ramona Alina Tomuța, Andrada Florina Moldovan, Loredana Matiș, Lavinia Maris, Timea Claudia Ghitea and Florin Banica
Toxics 2025, 13(6), 504; https://doi.org/10.3390/toxics13060504 - 15 Jun 2025
Viewed by 700
Abstract
(1) Background: Exposure to pesticide residues through food remains a critical issue in public health, especially given their potential cumulative neurotoxic effects. (2) Methods: This study investigated the presence of pesticide residues in commonly consumed vegetables, fruits, and cereals based on official laboratory [...] Read more.
(1) Background: Exposure to pesticide residues through food remains a critical issue in public health, especially given their potential cumulative neurotoxic effects. (2) Methods: This study investigated the presence of pesticide residues in commonly consumed vegetables, fruits, and cereals based on official laboratory reports and evaluated the intestinal microbiome profiles of individuals whose diets consisted of over 50% plant-based foods. (3) Results: Analytical results from accredited laboratories in Romania demonstrated that all tested food samples were compliant with European regulations (Regulation (EC) 396/2005), with either undetectable or below-quantification-limit pesticide residues. However, organophosphates such as chlorpyrifos and diazinon were frequently tested, indicating persistent regulatory concern due to their known neurotoxic potential. A parallel analysis of stool samples revealed significant imbalances in neuroactive gut bacteria, including consistently low levels of Bifidobacterium and Lactobacillus species, and elevated levels of Oscillibacter and Alistipes, which are implicated in modulating GABA and serotonin pathways. Markers of proinflammatory activity, such as LPS-positive bacteria and histamine producers, were also elevated. (4) Conclusions: These findings suggest that even in diets rich in plant-based foods, microbial dysbiosis with neuroactive relevance can occur, potentially linked to environmental or dietary factors. The study underscores the need for a comprehensive evaluation of food safety and microbiome function as interconnected determinants of neurological health. Full article
(This article belongs to the Section Neurotoxicity)
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23 pages, 8037 KB  
Article
Alteration of Gastrointestinal Function and the Ameliorative Effects of Hericium erinaceus Polysaccharides in Tail Suspension Rats
by Peng Zang, Pu Chen, Junli Chen, Jingchao Sun, Haiyun Lan, Haisheng Dong, Wei Liu, Nan Xu, Weiran Wang, Lingwei Hou, Bowen Sun, Lujia Zhang, Jiaqiang Huang, Pengjie Wang, Fazheng Ren and Siyuan Liu
Nutrients 2025, 17(4), 724; https://doi.org/10.3390/nu17040724 - 18 Feb 2025
Cited by 1 | Viewed by 2178
Abstract
Background/Objectives: Long-term spaceflight in a microgravity environment frequently results in gastrointestinal dysfunction, presenting substantial challenges to astronauts’ health. Hericium erinaceus, a plant recognized for its dual use as food and medicine, contains a key functional component called Hericium erinaceus polysaccharide (HEP), [...] Read more.
Background/Objectives: Long-term spaceflight in a microgravity environment frequently results in gastrointestinal dysfunction, presenting substantial challenges to astronauts’ health. Hericium erinaceus, a plant recognized for its dual use as food and medicine, contains a key functional component called Hericium erinaceus polysaccharide (HEP), which is purported to promote gastrointestinal health. This study aims to investigate the protective effects of HEP against gastrointestinal disturbances induced by simulated weightlessness and to elucidate its regulatory mechanisms. Methods: Sprague Dawley rats subjected to a tail suspension model were administered either a standard diet or a diet supplemented with 0.125% HEP over a period of 4 weeks (the intake of HEP is approximately 157.5 mg/kg bw/d, n = 8), metagenomics and targeted metabolomics to investigate the effects of HEP on gastrointestinal hormone secretion disorders, gut microbiota dysbiosis, and intestinal barrier damage induced by simulated weightlessness. Results: Dietary supplementation with HEP was observed to significantly alleviate weightlessness-induced gastrointestinal hormone disruptions, enhancing motility and intestinal barrier function while reducing inflammation. In addition, HEP improved gut microbiota by boosting beneficial bacteria as Oscillibacter sp.1-3, Firmicutes bacterium ASF500, and Lactobacillus reuteri, while reducing harmful bacteria like Escherichia coli and Mucispirillum schaedleri at the species level. Furthermore, HEP altered the serum metabolic profile of the rats, reducing inflammation by upregulating the tryptophan metabolism pathway and enhancing the production of short-chain fatty acids. Conclusions: HEP effectively protects against gastrointestinal dysfunction induced by simulated weightlessness by regulating hormone secretion and maintaining intestinal homeostasis. Full article
(This article belongs to the Section Phytochemicals and Human Health)
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22 pages, 12777 KB  
Article
Effect of Food Matrix on Regulation of Intestinal Barrier and Microbiota Homeostasis by Polysaccharides Sulfated Carrageenan
by Xuke Shang, Juanjuan Guo and Peilin Chen
Foods 2025, 14(4), 635; https://doi.org/10.3390/foods14040635 - 14 Feb 2025
Cited by 1 | Viewed by 908
Abstract
Carrageenan (CGN) has side effects on the intestinal barrier. Damage to the intestinal barrier is associated with exposure to sulfate groups. Food matrix has significant influence on the exposure quantity of sulfate groups and conformation in κ-CGN, but the corresponding side effects are [...] Read more.
Carrageenan (CGN) has side effects on the intestinal barrier. Damage to the intestinal barrier is associated with exposure to sulfate groups. Food matrix has significant influence on the exposure quantity of sulfate groups and conformation in κ-CGN, but the corresponding side effects are not reported specifically. This study aimed to explore the regulatory effect of κ-CGN dissolved in aqueous (κ-CGN) and in 3% casein (κ-carrageenan-casein, κ-CC) on the intestinal barrier and microbiota homeostasis. Research has shown that both κ-CGN and κ-CC can induce different extents of intestinal barrier damage through disrupting microbiota homeostasis. Importantly, κ-CGN in casein with lower sulfate groups content was found to repair the intestinal barrier injury induced by an equivalent dose of κ-CGN aqueous through increasing the abundance of Oscillibacter and decreasing Weissella. These alleviating effects were reflected in lower levels of tumor necrosis factor (TNF)-α and C-reaction protein (CRP), higher levels of interleukin (IL)-10, raised secretion of mucus and goblet cells, and improved expression of epithelial cell compact proteins zonula occluden (ZO)-1 and mucin protein 2 (MUC2). This study states that κ-CGN in casein has a positive regulatory effect on the intestinal barrier damage compared to in aqueous solution, which can provide guidance for processing and utilization of CGN. Full article
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15 pages, 3447 KB  
Article
Therapeutic Potential of Cajanus cajan (L.) Millsp. Leaf Extract in Modulating Gut Microbiota and Immune Response for the Treatment of Inflammatory Bowel Disease
by Mingzhang Lin, Linghua Piao, Zhendong Zhao, Li Liao, Dayong Wang, Haiwen Zhang and Xiande Liu
Pharmaceuticals 2025, 18(1), 67; https://doi.org/10.3390/ph18010067 - 9 Jan 2025
Cited by 5 | Viewed by 1665
Abstract
Background/Objectives: Inflammatory bowel disease (IBD) is a persistent inflammatory condition affecting the gastrointestinal tract, distinguished by the impairment of the intestinal epithelial barrier, dysregulation of the gut microbiota, and abnormal immune responses. Cajanus cajan (L.) Millsp., traditionally used in Chinese herbal medicine [...] Read more.
Background/Objectives: Inflammatory bowel disease (IBD) is a persistent inflammatory condition affecting the gastrointestinal tract, distinguished by the impairment of the intestinal epithelial barrier, dysregulation of the gut microbiota, and abnormal immune responses. Cajanus cajan (L.) Millsp., traditionally used in Chinese herbal medicine for gastrointestinal issues such as bleeding and dysentery, has garnered attention for its potential therapeutic benefits. However, its effects on IBD remain largely unexplored. Methods: In this study, the major compounds from Cajanus cajan leaf extract (CCLE) were initially characterized by LCMS-IT-TOF. The IBD model was developed in C57BL/6 mice by administering continuous 4% (w/v) dextran sodium sulfate (DSS) aqueous solution over a period of seven days. The body weight, colon length, disease activity index (DAI), and histopathological examination using hematoxylin and eosin (H&E) staining were performed in the IBD model. The levels of the main inflammatory factors, specifically TNF-α, IL-1β, IL-6, and myeloperoxidase (MPO), were quantified by employing enzyme-linked immunosorbent assay (ELISA) kits. Additionally, the levels of tight junction proteins (ZO-1, Occludin) and oxidative stress enzymes (iNOS, SOD1, CAT) were investigated by qPCR. Subsequently, flow cytometry was employed to analyze the populations of various immune cells within the spleen, thereby assessing the impact of the CCLE on the systemic immune homeostasis of IBD mice. Finally, 16S rDNA sequencing was conducted to examine the composition and relative abundance of gut microbiota across different experimental groups. In addition, molecular docking analysis was performed to assess the interaction between the principal components of CCLE and the aryl hydrocarbon receptor (AHR). Results: We identified seven bioactive compounds in CCLE: catechin, cajachalcone, 2-hydroxy-4-methoxy-6-(2-phenylcinyl)-benzoic acid, longistylin A, longistylin C, pinostrobin, amorfrutin A, and cajaninstilbene acid. Our results demonstrated that oral administration of CCLE significantly alleviates gastrointestinal symptoms in DSS-induced IBD mice by modulating the balance of gut-derived pro- and anti-inflammatory cytokines. This modulation is associated with a functional correction in M1/M2 macrophage polarization and the Th17/Treg cell balance in splenic immune cells, as well as shifts in the populations of harmful bacteria (Erysipelatoclostridium and Staphylococcus) and beneficial bacteria (Odoribacter, unidentified Oscillospiraceae, Lachnoclostridium, and Oscillibacter) in the gut. Furthermore, cajaninstilbene acid, longistylin A, and longistylin C were identified as potential AhR agonists. Conclusions: The present results suggested that CCLE, comprising stilbenes like cajaninstilbene acid, longistylin A, and longistylin C, protects the epithelial barrier’s structure and function against DSS-induced acute IBD by restoring gut microbiota balance and systemic immune response as AhR agonists. Overall, CCLE represents a promising natural product-based therapeutic strategy for treating IBD by restoring gut microbiota balance and modulating systemic immune responses. Full article
(This article belongs to the Section Natural Products)
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21 pages, 6247 KB  
Article
The Interactive Effects of Nutrient Density and Breed on Growth Performance and Gut Microbiota in Broilers
by Meiting Jia, Jiaqi Lei, Yuanyang Dong, Yuming Guo and Bingkun Zhang
Animals 2024, 14(23), 3528; https://doi.org/10.3390/ani14233528 - 6 Dec 2024
Cited by 2 | Viewed by 1778
Abstract
This study investigated whether variations in growth response to low nutrient density across breeds are linked to microbiota regulation. Arbor Acres (AA) and Beijing-You (BY) were fed high- (HN) and low-nutrient (LN) diets from day [...] Read more.
This study investigated whether variations in growth response to low nutrient density across breeds are linked to microbiota regulation. Arbor Acres (AA) and Beijing-You (BY) were fed high- (HN) and low-nutrient (LN) diets from day (d) 0 to d42. Body weight, feed intake, and intestinal measurements were recorded, and microbiota from the ileum and cecum were analyzed on d7, d21, and d42. Results showed that AA broilers had greater growth performance with a lower feed conversion ratio (FCR) and greater average daily gain (ADG) than BY chickens. The LN diet negatively affected AA broiler growth due to impaired intestinal development, while BY chickens compensated by increasing feed intake. Microbiota composition was primarily affected by breed than by nutrient density, with AA broilers having more beneficial bacteria and BY chickens having more short-chain fatty acid (SCFA)-producing bacteria. The LN diets reduced anti-inflammatory bacteria such as Shuttleworthia and Eisenbergiella in the cecum on d7. By d21, LN diets decreased Lactobacillus and increased proinflammatory Marvinbryantia, potentially impairing growth. However, LN diets enriched SCFA-producing bacteria like Ruminococcaceae_UCG.013, Eisenbergiella, and Tyzzerella in BY chickens and Faecalitalea in AA broilers by d21, which may benefit gut health. By d42, LN diets reduced genera linked to intestinal permeability and fat deposition, including Ruminococcus_torques_group, Romboutsia, Erysipelatoclostridium, and Oscillibacter. Additionally, LN diets enriched Christensenellaceae_R-7_group in AA broilers, associated with intestinal barrier integrity, and increased anti-inflammatory bacteria Alistipes and Barnesiella in AA broilers and BY chickens, respectively, by d42. Overall, AA broilers were more susceptible to reduced nutrient density due to impaired intestinal development, while BY chickens adapted better by increasing feed intake. The microbiota responses to low nutrient density varied over time, potentially negatively affecting gut health in the early stage and growth in the middle stage but possibly improving lipid deposition and gut health in the middle and late stages. Full article
(This article belongs to the Special Issue Microbiome, Immune and Intestinal Health in Animals)
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21 pages, 1799 KB  
Article
Mediterranean Diet and Olive Oil Redox Interactions on Lactate Dehydrogenase Mediated by Gut Oscillibacter in Patients with Long-COVID-19 Syndrome
by Amanda Cuevas-Sierra, Victor de la O, Andrea Higuera-Gómez, Lourdes Chero-Sandoval, Begoña de Cuevillas, María Martínez-Urbistondo, Victor Moreno-Torres, Ilduara Pintos-Pascual, Raquel Castejón and J. Alfredo Martínez
Antioxidants 2024, 13(11), 1358; https://doi.org/10.3390/antiox13111358 - 6 Nov 2024
Cited by 3 | Viewed by 1921
Abstract
Chronic viral inflammation is associated with oxidative stress and changes in gut microbiota. The Mediterranean diet (MD), with recognized anti-inflammatory and antioxidant properties, modulates gut microorganisms, specifically on the interaction between extra virgin olive oil, a key component of the MD with well-documented [...] Read more.
Chronic viral inflammation is associated with oxidative stress and changes in gut microbiota. The Mediterranean diet (MD), with recognized anti-inflammatory and antioxidant properties, modulates gut microorganisms, specifically on the interaction between extra virgin olive oil, a key component of the MD with well-documented antioxidant effects. This study investigated the influence of adherence to MD and antioxidant-rich foods (extra virgin olive oil) on biochemical, inflammatory, and microbiota profiles in patients with chronic inflammation defined as a prolonged inflammatory response due to immune dysregulation following the acute phase of the viral infection. Participants were classified into low (n = 54) and high (n = 134) MD adherence groups (cut-off of 7 points based on previous studies utilizing the same threshold in the assessment of MD adherence). Gut microbiota was sequenced using the 16S technique, and the adherence to MD was assessed using a validated questionnaire for a Spanish population. High adherence to the MD was linked to significant improvements in inflammatory and oxidative stress markers, including reductions in LDL-cholesterol, glucose, and lactate dehydrogenase (LDH) levels, an indicative of redox balance, as well as a significant higher consumption of antioxidant foods. Moreover, gut microbiota analysis revealed distinct compositional shifts and a lower abundance of the Oscillibacter genus in the high adherence group. Notably, a significant interaction was observed between MD adherence and extra virgin olive oil consumption, with Oscillibacter abundance influencing LDH levels, suggesting that the MD antioxidant properties may modulate inflammation through gut microbiota-mediated mechanisms. These findings provide new evidence that adherence to the Mediterranean diet can reduce inflammatory markers in patients with long-COVID-19, a population that has not been extensively studied, while also highlighting the potential role of the bacterial genus Oscillibacter in modulating this effect. Full article
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12 pages, 6351 KB  
Brief Report
Uncovering a Causal Connection between Gut Microbiota and Six Thyroid Diseases: A Two-Sample Mendelian Randomization Study
by Jiahao Chen, Yu Wang, Hang Yao, Yuxin Li and Hong Song
Biology 2024, 13(9), 714; https://doi.org/10.3390/biology13090714 - 11 Sep 2024
Cited by 2 | Viewed by 2078
Abstract
Background: Recent studies have established associations between the gut microbiota (GM) and thyroid diseases (TDs). However, their causal relationships remain elusive. Methods: To investigate this causality, we conducted a two-sample Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data from MiBioGen and [...] Read more.
Background: Recent studies have established associations between the gut microbiota (GM) and thyroid diseases (TDs). However, their causal relationships remain elusive. Methods: To investigate this causality, we conducted a two-sample Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data from MiBioGen and FinnGen, with GM as the exposure and six TDs as outcomes. Results: We identified 32 microbial taxa linked to the risk of six TDs. The Clostridium innocuum group, Ruminiclostridium5, and Lachnoclostridium exhibited protective effects against nontoxic diffuse goiter (NDG). Conversely, an increased risk of NDG was associated with Ruminococcaceae UCG002, Alistipes, Methanobrevibacter, Marvinbryantia, and Ruminococcaceae UCG014. Bifidobacterium and Sutterella were protective against nontoxic multinodular goiter (NMG), while the Ruminococcus gauvreauii group and Rikenellaceae RC9 gut group heightened NMG risk. Protective effects against nontoxic single thyroid nodule (NSTN) were observed with Defluviitaleaceae UCG011, Ruminococcus1, and Ruminococcaceae UCG010, whereas increased risk was linked to Alistipes, the Ruminococcus gauvreauii group, and Lachnospiraceae UCG010. Ruminiclostridium9, Victivallis, and Butyricimonas offered protection against thyrotoxicosis with Graves’ Disease (GD), while the Eubacterium rectale group, Desulfovibrio, Bifidobacterium, Collinsella, Oscillospira, and Catenibacterium were risk factors. For thyrotoxicosis with Plummer Disease (PD), protective taxa included Butyricimonas and Lachnospira, whereas Dorea, Eggerthella, Odoribacter, Lactobacillus, Intestinimonas, and Phascolarctobacterium increased risk. Lastly, Parasutterella was protective against thyrotoxicosis with toxic single thyroid nodule (TSTN), while increased risk was associated with Sutterella, Oscillibacter, and Clostridium sensu stricto1. Conclusions: Our findings support a causal relationship between specific GM and TDs at the genetic level, laying the foundation for future research into potential mechanisms and the identification of novel therapeutic targets. Full article
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15 pages, 2487 KB  
Article
Specific Gut Microbiome Signatures in Children with Cow’s Milk Allergy
by Dafni Moriki, E. Daniel León, Gabriel García-Gamero, Nuria Jiménez-Hernández, Alejandro Artacho, Xavier Pons, Despoina Koumpagioti, Argirios Dinopoulos, Vassiliki Papaevangelou, Kostas N. Priftis, Konstantinos Douros and M. Pilar Francino
Nutrients 2024, 16(16), 2752; https://doi.org/10.3390/nu16162752 - 18 Aug 2024
Cited by 2 | Viewed by 2764
Abstract
Although gut dysbiosis is associated with cow’s milk allergy (CMA), causality remains uncertain. This study aimed to identify specific bacterial signatures that influence the development and outcome of the disease. We also investigated the effect of hypoallergenic formula (HF) consumption on the gut [...] Read more.
Although gut dysbiosis is associated with cow’s milk allergy (CMA), causality remains uncertain. This study aimed to identify specific bacterial signatures that influence the development and outcome of the disease. We also investigated the effect of hypoallergenic formula (HF) consumption on the gut microbiome of milk-allergic children. 16S rRNA amplicon sequencing was applied to characterize the gut microbiome of 32 milk-allergic children aged 5–12 years and 36 age-matched healthy controls. We showed that the gut microbiome of children with CMA differed significantly from that of healthy children, regardless of whether they consumed cow’s milk. Compared to that of healthy cow’s milk consumers, it was depleted in Bifidobacterium, Coprococcus catus, Monoglobus, and Lachnospiraceae GCA-900066575, while being enriched in Oscillibacter valericigenes, Negativibacillus massiliensis, and three genera of the Ruminococcaceae family. Of these, only the Ruminococcaceae taxa were also enriched in healthy children not consuming cow’s milk. Furthermore, the gut microbiome of children who developed tolerance and had received an HF was similar to that of healthy children, whereas that of children who had not received an HF was significantly different. Our results demonstrate that specific gut microbiome signatures are associated with CMA, which differ from those of dietary milk elimination. Moreover, HF consumption affects the gut microbiome of children who develop tolerance. Full article
(This article belongs to the Section Nutritional Immunology)
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16 pages, 2683 KB  
Article
The Effects of Caloric Restriction and Clinical Psychological Intervention on the Interplay of Gut Microbial Composition and Stress in Women
by Luise Bellach, Alexandra Kautzky-Willer, Kathrin Heneis, Michael Leutner and Alexander Kautzky
Nutrients 2024, 16(16), 2584; https://doi.org/10.3390/nu16162584 - 6 Aug 2024
Viewed by 2365
Abstract
Both mental and metabolic disorders are steadily becoming more prevalent, increasing interest in non-pharmacological lifestyle interventions targeting both types of disorders. However, the combined effect of diet and psychological interventions on the gut microbiome and mental health outcomes remains underexplored. Thus, in this [...] Read more.
Both mental and metabolic disorders are steadily becoming more prevalent, increasing interest in non-pharmacological lifestyle interventions targeting both types of disorders. However, the combined effect of diet and psychological interventions on the gut microbiome and mental health outcomes remains underexplored. Thus, in this study, we randomized 41 women into two caloric restriction (CR) dietary groups, namely very-low-calorie diet (VLCD) and F.X. Mayr diet (FXM). The patients were then further randomized to either receive clinical psychological intervention (CPI) or no CPI. Blood and fecal samples were collected before and after two weeks of CR. Psychometric outcomes were assessed using the Perceived Stress Scale (PSS), Brief Symptom Index (BSI), and Burnout Dimension Inventory (BODI). Stool samples underwent 16S-rRNA sequencing. Upon two weeks of CR, α-diversity decreased overall and longitudinal PERMANOVA models revealed significant shifts in β-diversity according to diet, CPI, age, and body-mass-index. Furthermore, Agathobacter, Fusicatenibacter, and Subdoligranulum decreased in abundance. However, the Oscillibacter genus was enriched solely in FXM. CPI had a negligible effect on the microbiome. Dimension reduction models revealed clusters of taxa which distinctly associated with psychometric outcomes. Members of the Oscillospiraceae family were linked to favorable psychometric outcomes after two weeks of CR. Despite α-diversity reductions after CR, enrichment of Oscillospiraceae spp., solely seen in FXM, correlated with improved psychometric outcomes. This study suggests a promising direction for future interventions targeting mental health through gut microbial modulation. Full article
(This article belongs to the Special Issue Nutrition and Food Safety in Pregnancy)
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