{"title":"Anti-Adipogenic Effects of Probiotic Lactiplantibacillus pentosus THF59 via Inhibition of Differentiation and Promotion of Apoptosis in 3T3-L1 Cells.","authors":"Qiwen Zheng, Trang Thi Minh Nguyen, Xiangji Jin, Gyeong-Seon Yi, Tae-Hoo Yi","doi":"10.1007/s12602-025-10663-7","DOIUrl":"https://doi.org/10.1007/s12602-025-10663-7","url":null,"abstract":"<p><p>This study investigated the probiotic properties and anti-adipogenic activities of Lactiplantibacillus pentosus THF59, isolated from blueberries. THF59 exhibited several probiotic traits, including antimicrobial activity, tolerance to simulated gastric juice and bile salts, non-pathogenicity, and strong adhesion to intestinal epithelial Caco-2 cells. To evaluate its anti-adipogenic potential, MDI-induced 3T3-L1 preadipocytes were treated with THF59 cell-free supernatant (CFS). At the highest tested concentration (100 μg/mL), THF59 CFS significantly reduced intracellular lipid accumulation by 68.40%, as evidenced by Oil Red O staining. It also decreased intracellular reactive oxygen species (ROS) levels by 27.45%, potentially suppressing adipogenic differentiation by disrupting ROS-mediated early signaling events. Moreover, THF59 alleviated MDI-induced S-phase cell cycle arrest, suggesting interference with early-stage preadipocyte differentiation. At this concentration, THF59 CFS significantly downregulated key adipogenic transcription factors involved in various stages of differentiation, including SREBP-1 (68.91%), PPARγ (50.75%), C/EBPα (41.99%), and AP-2 (37.44%). These findings indicate that THF59 suppressed adipogenesis through multi-level regulatory interference, from early commitment to terminal differentiation. Notably, THF59 also promoted late-stage apoptosis in mature adipocytes by 6.55%, representing an additional lipid-lowering mechanism through the removal of lipid-storing cells. In conclusion, THF59 exerted anti-adipogenic effects in MDI-induced 3T3-L1 preadipocytes by inhibiting differentiation and promoting apoptosis, supporting its potential as a functional probiotic candidate for obesity prevention.</p>","PeriodicalId":20506,"journal":{"name":"Probiotics and Antimicrobial Proteins","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144609191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Antibacterial Efficacy of Chlamydomonas reinhardtii-Expressed Enterocin RM6 Against Gram-Positive and Gram-Negative Bacteria.","authors":"Yan-Xia Liu, Yuan-Yuan Zhang, Zhen-Chuan Fan","doi":"10.1007/s12602-025-10641-z","DOIUrl":"https://doi.org/10.1007/s12602-025-10641-z","url":null,"abstract":"<p><p>In 2013, enterocin RM6, an antimicrobial peptide, was isolated from Enterococcus faecalis in raw milk. This antimicrobial peptide exhibits certain antibacterial activity against Listeria monocytogenes. However, since its discovery, its antibacterial activity remains uninvestigated. In this study, we utilized the green algae Chlamydomonas reinhardtii to express N-terminal hemagglutinin and 6 × His double-tagged triple tandem repeats of enterocin RM6 (3 × Enterocin RM6). The expression of 3 × Enterocin RM6 remained stable after continuously passaging transgenic cells for 6 months; this yielded 0.45% of total soluble proteins. C. reinhardtii-expressed enterocin RM6 inhibited the growth of six bacterial strains, encompassing both gram-positive and gram-negative strains. The minimum inhibitory concentrations were 25-70 μg/mL. Recombinant 3 × Enterocin RM6 exhibited significant stability across a broad spectrum of temperatures and pH levels, exhibited tolerance to proteolytic enzymes, displayed minimal hemolytic activity against rabbit erythrocytes, and demonstrated low cytotoxicity toward Vero, BHK21, HEK293, and MDBK cell lines. In addition, C. reinhardtii-expressed 3 × Enterocin RM6 exhibited effective cell membrane penetration and caused morphological disruption in the targeted bacterial cells. Our study results indicate that C. reinhardtii is a viable host for producing bioactive enterocin RM6.</p>","PeriodicalId":20506,"journal":{"name":"Probiotics and Antimicrobial Proteins","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144609192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bifidobacterium's Influential Role in the Battle Against Obesity: Going Beyond Probiotics.","authors":"Nazanin Daneshpour, Mahsa Rajabi, Nima Zafari","doi":"10.1007/s12602-025-10645-9","DOIUrl":"https://doi.org/10.1007/s12602-025-10645-9","url":null,"abstract":"<p><p>Obesity has emerged as a major global health concern, contributing to the development of many chronic illnesses and metabolic conditions. Recent studies underscore the critical role that gut bacteria play in controlling the body's metabolism, with Bifidobacterium species gaining prominence for their diverse effects on the management of obesity. This review considers the knowledge currently accessible about the processes that how Bifidobacterium affects obesity, extending beyond the conventional understanding of probiotics. We explore the probiotic characteristics of Bifidobacterium, which encompass the enhancement of gut homeostasis, the strengthening of intestinal barrier integrity, the mitigation of inflammation as a key factor in obesity pathogenesis, and various other widely recognized beneficial effects. In addition, we discuss the role of Bifidobacterium in metabolic functions and its effects on weight management and associated mechanisms. This review also addresses Bifidobacterium and the multiple elements that lead to obesity, including the interaction with dietary and nutritional elements, the effects of exercise and lifestyle choices, and the consideration of impacts from both the environment and genetics. The evidence and mechanisms presented highlight the beneficial role of Bifidobacterium in managing obesity; however, there remain significant gaps in our comprehensive understanding of its impact on obesity, which we have aimed to address in this review.</p>","PeriodicalId":20506,"journal":{"name":"Probiotics and Antimicrobial Proteins","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144609193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yu Yang, Jing Sui, Wang Liao, Shaokang Wang, Da Pan, Guiju Sun, Peng Gao, Xuesong Xiang, Hui Xia
{"title":"Clinical Evidence on the Health Benefits and Safety of Probiotic Lacticaseibacillus rhamnosus: A Systematic Review.","authors":"Yu Yang, Jing Sui, Wang Liao, Shaokang Wang, Da Pan, Guiju Sun, Peng Gao, Xuesong Xiang, Hui Xia","doi":"10.1007/s12602-025-10646-8","DOIUrl":"https://doi.org/10.1007/s12602-025-10646-8","url":null,"abstract":"<p><p>In recent years, the health benefits of probiotics have received increasing attention. As one of the most common probiotics, the health efficacy and safety of Lacticaseibacillus rhamnosus (L. rhamnosus) have become the research focus. For this reason, the review aimed to comprehensively evaluate the impact of L. rhamnosus on human health and various diseases. PubMed, Embase, Cochrane Library, and Web of Science databases were searched for randomized controlled trials (RCTs) investigating the effect of L. rhamnosus and multiple diseases. A digital search was conducted following systematic review guidelines, and 51 studies met inclusion criteria from a total of 1595 articles. The results of this review indicate that L. rhamnosus provides potential health benefits in various diseases. For example, studies have shown that it may alleviate clinical symptoms of atopic dermatitis in children, modulate gut microbiota to improve symptoms in patients with irritable bowel syndrome (IBS), and potentially reduce the incidence of gestational diabetes mellitus. L. rhamnosus is generally considered safe for healthy individuals, with no serious adverse events commonly reported in the general population. However, occasional adverse effects have been documented in special populations such as critically ill patients, pregnant women, and infants, and caution is advised when used in these groups. Future studies investigating the health benefits of L. rhamnosus still need to design more comprehensive RCTs and expand the sample size to better study the impact of L. rhamnosus on various diseases.</p>","PeriodicalId":20506,"journal":{"name":"Probiotics and Antimicrobial Proteins","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144609194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ting Liu, Qiang Meng, Yijun Zhang, Jianming Ye, Yingju Shang, Wei Song, Yane Luo
{"title":"Enhancing the Adhesion/Colonization Efficacy of Probiotics by Polysaccharide Surface Decoration for Remission from Ulcerative Colitis.","authors":"Ting Liu, Qiang Meng, Yijun Zhang, Jianming Ye, Yingju Shang, Wei Song, Yane Luo","doi":"10.1007/s12602-025-10653-9","DOIUrl":"https://doi.org/10.1007/s12602-025-10653-9","url":null,"abstract":"<p><p>Ulcerative colitis (UC) is a chronic inflammatory disease in the colon, with a rising global incidence. Probiotics have been explored for treat UC due to their regulation roles on the gut microbiota. However, issues such as low survival rate, limited colonization time, and poor therapeutic effects have been observed following the oral administration of free probiotics. Thus, techniques for surface modification of probiotics have emerged to enhance the adhesion of encapsulation materials at inflammation sites, thereby to improve the retention time of probiotics and their therapeutic effects on UC. Here, we investigated the altered physio-biochemistry environments in the gastrointestinal tract of UC patients, and the factors influencing the molecular interactions between probiotics and the mucosa. We also clarified that encapsulation materials such as chitosan, sodium alginate, and thiolated hyaluronic acid could target the colon wall through electrostatic adsorption, hydrogen bonding, or the formation of disulfide bonds, thereby elongating the adhesion time of probiotics in the intestine. Additionally, the degradation patterns, potential beneficial or harmful impacts of these encapsulation materials were summarized. Finally, the current status of probiotics and polysaccharide-based treatments for UC in clinical trials were discussed. This research will facilitate the preparation of probiotic microcapsules with colon adhesion properties and also provide recommendations for the clinical application of encapsulation materials.</p>","PeriodicalId":20506,"journal":{"name":"Probiotics and Antimicrobial Proteins","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144609195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yiqin Deng, Liwen Xu, Keng Yang, Ziyang Lin, Shujun Zang, Kui Jiang, Wangdong Li, Nabil A Ibrahim, Hongling Ma, Changhong Cheng, Juan Feng
{"title":"The Time Reliable Effect of Probiotic Clostridium butyricum on the Growth of Spotted Sea Bass (Lateolabrax maculatus).","authors":"Yiqin Deng, Liwen Xu, Keng Yang, Ziyang Lin, Shujun Zang, Kui Jiang, Wangdong Li, Nabil A Ibrahim, Hongling Ma, Changhong Cheng, Juan Feng","doi":"10.1007/s12602-025-10652-w","DOIUrl":"https://doi.org/10.1007/s12602-025-10652-w","url":null,"abstract":"<p><p>Probiotic Clostridium butyricum has been demonstrated to enhance the growth of spotted sea bass (Lateolabrax maculatus). However, the time reliable effect of C. butyricum application for L. maculatus growth promotion is poorly understood, limiting our ability to make informed decisions about when the C. butyricum should be added and why. To address this, we employed multidisciplinary approach to investigate the growth response (including growth performance, intestinal morphology, digestive enzyme activities, and gut microbiome) of L. maculatus to C. butyricum supplementation throughout the entire breeding cycle (from juvenile to marketable size). The C. butyricum supplementation significantly increased the weight of L. maculatus during its early life stages. Correspondingly, 16S rRNA sequence showed that C. butyricum addition increased probiotic bacteria (including Lactobacillales), decreased pathogenic bacteria (including Enterobacterales, Burkholderiales, and Fusobacteriales), and reduced bacterial virulence processes (including quorum sensing, biofilm formation, and bacterial secretion systems) of gut microbiota in L. maculatus. Concurrently, C. butyricum supplementation increased intestinal villus height (up to 32.1%), muscle thickness (up to 115.8%), and digestive enzyme activities (up to 77.8%). Nevertheless, during the later stages of incubation, treatment with C. butyricum did not result in further improvements or even showed similar outcomes to the non-supplemented treatment. These findings emphasize that C. butyricum supplementation during the early breeding stage can significantly benefit L. maculatus growth, rather than adding it during later stages. This study provides evidence on the appropriate timing for C. butyricum supplementation in L. maculatus culture, offering timely information and technical support for its culture management.</p>","PeriodicalId":20506,"journal":{"name":"Probiotics and Antimicrobial Proteins","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144601284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Role of Akkermansia muciniphila in Disease Regulation.","authors":"Yingying Ding, Yingjian Hou, Xingzhen Lao","doi":"10.1007/s12602-025-10642-y","DOIUrl":"https://doi.org/10.1007/s12602-025-10642-y","url":null,"abstract":"<p><p>In recent years, Akkermansia muciniphila (A. muciniphila), as a representative of the core gut commensal bacteria, has shown outstanding therapeutic potential in the field of microecological interventions due to its unique mucin degrading ability and host-interaction mechanism. A. muciniphila is first isolated from human feces in 2004. It colonizes the intestinal mucus layer, utilizing mucin secreted by goblet cells as its primary carbon and nitrogen source. In 2013, researchers found that supplementation with A. muciniphila could improve obesity, demonstrating the potential of A. muciniphila in the treatment of disease. Recent studies show that A. muciniphila strengthens intestinal barrier integrity, improves metabolic diseases, and mitigates inflammation through multiple mechanisms, including adenosine monophosphate-activated protein kinase (AMPK) pathway activation via Toll-like receptor (TLR) 2 stimulation and NOD-like receptor family, pyrin domain containing 3 (NLRP3) activation. A. muciniphila and its derivatives also exhibit potent anti-tumor effects. They induce tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL) upregulation, triggering extrinsic (death receptor-mediated) and intrinsic (mitochondrial) apoptosis pathways in tumor cells. Additionally, A. muciniphila promotes M1-like tumor-associated macrophages (TAMs) through NLRP3 activation and remodels the tumor microenvironment via metabolic crosstalk with intratumoral microbiota. Notably, A. muciniphila combined with programmed death-1 (PD-1) antibody boost CD8<sup>+</sup> T cell infiltration, thereby overcoming host resistance to PD-1 blockade. Moreover, A. muciniphila contributes to the growth of butyric acid-producing bacteria and suppresses the growth of specific bacterial populations, playing an important role in the gut microbiome network. This review evaluates recent discoveries regarding A. muciniphila's multifaceted roles in maintaining intestinal barrier integrity, ameliorating metabolic and inflammatory disorders, and enhancing anti-tumor immune responses. We also discuss its ecological effect on the gut microbiota flora and point out the therapeutic limitations and prospect which provides theoretical references to promote the development of Akkermansia muciniphila in clinical diseases, especially in tumor therapy.</p>","PeriodicalId":20506,"journal":{"name":"Probiotics and Antimicrobial Proteins","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Selin Kalkan, Şirin Yilmaz Çopur, Selahaddin Batuhan Akben, Mustafa Remzi Otağ, Mehmet Soner Engin
{"title":"Effect of Incorporation of Mix Probiotic Culture in Sodium Alginate Film Characteristics: Antimicrobial, Physiochemical, Mechanical, and Barrier Properties.","authors":"Selin Kalkan, Şirin Yilmaz Çopur, Selahaddin Batuhan Akben, Mustafa Remzi Otağ, Mehmet Soner Engin","doi":"10.1007/s12602-025-10651-x","DOIUrl":"https://doi.org/10.1007/s12602-025-10651-x","url":null,"abstract":"<p><p>This study investigates the characterization and antimicrobial properties of sodium alginate (SA) films enriched with probiotic microorganisms, including Bifidobacterium animalis ssp. lactis B94, Lacticaseibacillus rhamnosus GG, and kefir cultures. The films were evaluated for their physicochemical, mechanical, and bioactive properties. The results showed that the addition of probiotics significantly influenced the films' thickness, moisture content, density, and water vapor permeability (WVP). Films containing a combination of kefir, B. lactis, and L. rhamnosus (SA-KLB) exhibited the highest thickness (100.00 ± 0.02 µm) and WVP (2.11 ± 0.00 g mm/h m<sup>2</sup> kPa), while control films (SA-C) had the lowest thickness (50.00 ± 0.00 µm) and WVP (1.45 ± 0.00 g mm/h m<sup>2</sup> kPa). The moisture content of probiotic films ranged from 20.28 ± 3.69% to 28.81 ± 0.61%, with SA-KLB showing the highest moisture retention. Mechanical properties, including tensile strength (TS) and elongation at break (E), were also affected by probiotic addition, with TS values ranging from 0.42 ± 0.06 to 1.49 ± 0.20 MPa and E values from 20.45 ± 3.60 to 28.62 ± 4.40%. Antimicrobial activity tests revealed that the films effectively inhibited pathogenic bacteria, with the strongest effect against Staphylococcus aureus (inhibition zones of 23.00 ± 1.41 to 24.75 ± 1.77 mm) and the weakest against Escherichia coli (15.50 ± 0.71 to 19.00 ± 1.41 mm). The viability of probiotics in the films after drying ranged from 81.79 to 90.57%, indicating good stability during the drying process. These findings suggest that probiotic-enriched SA films have potential as functional packaging materials, offering both extended shelf life and health benefits by delivering viable probiotics to consumers.</p>","PeriodicalId":20506,"journal":{"name":"Probiotics and Antimicrobial Proteins","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Probiotics Modulate the Ruminal Microbiome and Metabolite Availability to Enhance Rumen Barrier Function and Growth Performance in Goats Fed a High-Concentrate Diet.","authors":"Xinhong Zhou, Xiaoyun Shen","doi":"10.1007/s12602-025-10647-7","DOIUrl":"https://doi.org/10.1007/s12602-025-10647-7","url":null,"abstract":"<p><p>The purpose of this study was to evaluate the effects of probiotics supplementation on goats fed a high-concentrate diet in terms of growth performance, rumen fermentation, microbiome and metabolite, and barrier function. Twelve 5-month-old goats (22.74 ± 0.31 kg) were randomly assigned to two groups. The control group (CON) was given a basal diet, whereas the experimental group (PRB) was provided with a diet supplemented with 2 g/kg of a probiotics for 60 days. The results indicated that the final weight (FW) and average daily gain (ADG) were significantly increased in the PRB group compared to the CON group (p < 0.05). Rumen fluid in the PRB group showed significantly elevated levels of butyrate, ammonia nitrogen, propionate, acetate, and total volatile fatty acids, with a significantly reduced acetate/propionate (p < 0.05). Additionally, the PRB group demonstrated significant increases in rumen papilla width and density of gastric papillae (p < 0.05). The mRNA relative expression of tight junction proteins Claudin-4, Claudin-1, Occludin, and ZO-1 in the rumen epithelium was significantly upregulated (p < 0.05). Furthermore, the mRNA relative expression of the anti-inflammatory factor IL-10 was significantly elevated, whereas the pro-inflammatory factors IL-1β and TNF-α were significantly reduced (p < 0.05). 16S rDNA sequencing revealed enrichment of beneficial microbes, such as Lachnospiraceae_NK4A136_group, Christensenellaceae_R-7_group, Monoglobus, Parabacteroides, Bacteroides, and Roseburia, which promoted fiber degradation and volatile fatty acid production. Elevated metabolites, including 2-lysophosphatidylcholin, PC(18:0/0:0), tryptophol, 5-hydroxy-6-methoxyindole glucuronide, and mevalonic acid, contribute to epithelial repair, barrier function, and fermentation. Additionally, 4-nitrocatechol was associated with improved rumen papillae structure and anti-inflammatory effects. In conclusion, probiotics supplementation enhanced rumen fermentation, microbial composition, and barrier function while alleviating inflammation, ultimately improving growth performance and rumen health in goats on a high-concentrate diet.</p>","PeriodicalId":20506,"journal":{"name":"Probiotics and Antimicrobial Proteins","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Engineered Clostridium butyricum-pMTL007-GLP-1 Delays Neurodegeneration in Prnp-SNCA*A53T Transgenic Mice Model by Suppressing Astrocyte Senescence.","authors":"Bin Liao, Leiping Ding, Wenjing Chen, Mengyun Yue, Yun Wang, Daojun Hong, Tingtao Chen, Xin Fang","doi":"10.1007/s12602-025-10638-8","DOIUrl":"https://doi.org/10.1007/s12602-025-10638-8","url":null,"abstract":"<p><p>Astrocyte senescence has been identified as a factor in the progression of Parkinson's disease (PD) and the onset of age-related cognitive decline. Glucagon-like peptide-1 (GLP-1) has developed into a novel neuroprotective strategy for PD. However, the effects of GLP-1 on astrocyte senescence in PD remain to be elucidated. In our research, we developed an engineered strain of Clostridium butyricum-pMTL007-GLP-1 that continuously expresses GLP-1 and has demonstrated neuroprotective effects in PD. We utilized the Prnp-SNCA*A53T transgenic mouse model to better replicate the degenerative characteristics of PD. Our findings indicated that C. butyricum-GLP-1 reduced misfolded α-synuclein (α-syn), prevented dopaminergic (DAergic) neuron loss, mitigated neuroinflammation, and enhanced motor function impairments in A53T mouse. Additionally, C. butyricum-GLP-1 crossed the blood-brain barrier (BBB) and bound to GLP-1 receptors, reducing the build-up of senescent astrocytes, as evidenced by increased expression of Lamin B1, decreased levels of the senescence biomarker p21, and decreased levels of the pro-inflammatory senescence-associated secretory phenotype (SASP). Moreover, C. butyricum-GLP-1 mitigated oxidative stress-induced senescence by regulating the Nrf2/HO-1 axis and enhancing antioxidant efficacy. 16S rRNA analysis indicated that C. butyricum-GLP-1 strengthened the gastrointestinal barrier, restored gut microbiota homeostasis, and upregulated the abundance of C. butyricum. In summary, the results of this study suggested that C. butyricum-GLP-1 inhibited p53/p21 pathway, mitigated oxidative stress by targeting astrocyte senescence, and regulated gut microbiota, suggesting it may represent a therapeutic approach that brings renewed hope to patients with age-related diseases, such as PD.</p>","PeriodicalId":20506,"journal":{"name":"Probiotics and Antimicrobial Proteins","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}