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Du W, Zou ZP, Ye BC, Zhou Y. Gut microbiota and associated metabolites: key players in high-fat diet-induced chronic diseases. Gut Microbes 2025; 17:2494703. [PMID: 40260760 PMCID: PMC12026090 DOI: 10.1080/19490976.2025.2494703] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2025] [Revised: 02/26/2025] [Accepted: 04/11/2025] [Indexed: 04/24/2025] Open
Abstract
Excessive intake of dietary fats is strongly associated with an increased risk of various chronic diseases, such as obesity, diabetes, hepatic metabolic disorders, cardiovascular disease, chronic intestinal inflammation, and certain cancers. A significant portion of the adverse effects of high-fat diet on disease risk is mediated through modifications in the gut microbiota. Specifically, high-fat diets are linked to reduced microbial diversity, an overgrowth of gram-negative bacteria, an elevated Firmicutes-to-Bacteroidetes ratio, and alterations at various taxonomic levels. These microbial alterations influence the intestinal metabolism of small molecules, which subsequently increases intestinal permeability, exacerbates inflammatory responses, disrupts metabolic functions, and impairs signal transduction pathways in the host. Consequently, diet-induced changes in the gut microbiota play a crucial role in the initiation and progression of chronic diseases. This review explores the relationship between high-fat diets and gut microbiota, highlighting their roles and underlying mechanisms in the development of chronic metabolic diseases. Additionally, we propose probiotic interventions may serve as a promising adjunctive therapy to counteract the negative effects of high-fat diet-induced alterations in gut microbiota composition.
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Affiliation(s)
- Wei Du
- Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China
| | - Zhen-Ping Zou
- Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China
| | - Bang-Ce Ye
- Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China
| | - Ying Zhou
- Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China
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2
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Chikazawa M, Minato KI. Intestinal antibody repertoire is altered by diabetes and varies depending on the pathogenesis. Biochem Biophys Rep 2025; 42:101964. [PMID: 40114672 PMCID: PMC11923831 DOI: 10.1016/j.bbrep.2025.101964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 01/16/2025] [Accepted: 02/26/2025] [Indexed: 03/22/2025] Open
Abstract
Intestinal immunity is an important system for host defense and it is influenced by various factors such as diet and diseases. To elucidate the relationship between intestinal immunity and type 2 diabetes, we analyzed the effects of diabetes on intestinal antibody production and IgA repertoire using high-fat diet-fed mice and genetically diabetic KK-Ay mice model. The antibody level in the small intestine increased only in KK-Ay mice. We also confirmed that the IgA repertoire in both models experienced significant changes when compared to that in control mice, and no shared characteristics were observed between the two diabetic models. Antibody production in the intestine is influenced by stimuli associated with the onset of diabetes, and the types of induced IgA would differ depending on the process of disease onset.
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Affiliation(s)
- Miho Chikazawa
- Department of Applied Biological Chemistry, Faculty of Agriculture, Meijo University, 1-501 Shiogamaguchi, Nagoya, Japan
| | - Ken-Ichiro Minato
- Department of Applied Biological Chemistry, Faculty of Agriculture, Meijo University, 1-501 Shiogamaguchi, Nagoya, Japan
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3
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Chen Y, Wu N, Yan X, Kang L, Ou G, Zhou Z, Xu C, Feng J, Shi T. Impact of gut microbiota on colorectal anastomotic healing (Review). Mol Clin Oncol 2025; 22:52. [PMID: 40297498 PMCID: PMC12035527 DOI: 10.3892/mco.2025.2847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Accepted: 03/27/2025] [Indexed: 04/30/2025] Open
Abstract
Intestinal anastomosis is a critical procedure in both emergency and elective surgeries to maintain intestinal continuity. However, the incidence of anastomotic leakage (AL) has recently increased, reaching up to 20%, imposing major clinical and economic burdens. Substantial perioperative alterations in the intestinal microbiota composition may contribute to AL, particularly due to disruptions in key microbial populations essential for intestinal health and healing. The intricate interplay between the intestinal microbiota and the host immune system, along with microbial changes before and during surgery, significantly influences anastomotic integrity. Notably, specific pathogens such as Enterococcus and Pseudomonas aeruginosa have been implicated in AL pathogenesis. Preventive strategies including dietary regulation, personalized intestinal preparation, microbiota restoration and enhanced recovery after surgery protocols, may mitigate AL risks. Future research should focus on elucidating the precise mechanisms linking intestinal microbiota alterations to anastomotic healing and developing targeted interventions to improve surgical outcomes.
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Affiliation(s)
- Yangyang Chen
- General Surgery Department, Guiyang Public Health Clinical Center, Guiyang, Guizhou 550004, P.R. China
| | - Nian Wu
- Clinical Medical College, Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China
| | - Xin Yan
- Anesthesia Operating Room, Guiyang Public Health Clinical Center, Guiyang, Guizhou 550004, P.R. China
| | - Liping Kang
- General Surgery Department, Guiyang Public Health Clinical Center, Guiyang, Guizhou 550004, P.R. China
| | - Guoyong Ou
- General Surgery Department, Guiyang Public Health Clinical Center, Guiyang, Guizhou 550004, P.R. China
| | - Zhenlin Zhou
- General Surgery Department, Guiyang Public Health Clinical Center, Guiyang, Guizhou 550004, P.R. China
| | - Changbo Xu
- General Surgery Department, Guiyang Public Health Clinical Center, Guiyang, Guizhou 550004, P.R. China
| | - Jiayi Feng
- General Surgery Department, Guiyang Public Health Clinical Center, Guiyang, Guizhou 550004, P.R. China
| | - Tou Shi
- General Surgery Department, Guiyang Public Health Clinical Center, Guiyang, Guizhou 550004, P.R. China
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Jiang L, Lau HCH, Zeng R, Yu J. Diet, Gastric Microbiota, and Metabolites in Gastric Tumorigenesis. RESEARCH (WASHINGTON, D.C.) 2025; 8:0693. [PMID: 40357361 PMCID: PMC12067930 DOI: 10.34133/research.0693] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/26/2025] [Revised: 04/09/2025] [Accepted: 04/15/2025] [Indexed: 05/15/2025]
Abstract
Gastric cancer (GC) is one of the most common cancers worldwide particularly in Asian populations, and certain diets have been associated with increased risk of GC. Recent advances in microbial profiling technology have facilitated investigations on microbes residing on the gastric mucosa and increasing evidence has revealed the critical roles of non-Helicobacter pylori gastric microbes in gastric tumorigenesis. On the other hand, diets can affect microbial communities, causing compositional and functional shift of the microbiota. In this review, we summarize the influence of various diets including processed meat, salt-preserved food, high-fat diet, and alcohol on the development and progression of GC. We also explore microbial metabolites and host-microbe interactions in gastric tumorigenesis, alongside dietary interventions targeting the microbiota for the prevention and management against GC.
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Affiliation(s)
- Lanping Jiang
- Institute of Digestive Disease, Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Harry Cheuk-Hay Lau
- Institute of Digestive Disease, Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Ruijie Zeng
- Institute of Digestive Disease, Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Jun Yu
- Institute of Digestive Disease, Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
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Zeng X, Yu P, Li D, Li Y, Wang X, Yang X, Ren D. Structural characterization and alleviative effects of novel polysaccharides from Artemisia sphaerocephala Krasch seed on obese mice by regulating gut microbiota. Int J Biol Macromol 2025; 310:143407. [PMID: 40274139 DOI: 10.1016/j.ijbiomac.2025.143407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Revised: 04/07/2025] [Accepted: 04/20/2025] [Indexed: 04/26/2025]
Abstract
This study aimed to investigate the efficacy of polysaccharides from Artemisia sphaerocephala Krasch (ASK) seed in alleviating high fat diet (HFD) caused obesity. Here, three polysaccharide fractions (ASKP1, ASKP2 and ASKP3) were purified from ASK seed. Chemical characteristic analysis revealed that ASKP1 is a neutral heteropolysaccharide with the average molecular weight of 9.08 × 105 Da, while ASKP2 and ASKP3 are acidic heteropolysaccharides with the molecular weight of 9.39 × 105 and 8.41 × 105 Da, respectively. Animal experiment found that three ASKP fractions obviously relieved obesity and related metabolic disorders induced by HFD, while ASKP1 was more effective in reducing the blood glucose and serum LDL levels. 16S rDNA sequencing showed that ASKP fractions improved the gut microbiota imbalance of obese mice, and ASKP1 promoted the proliferation of beneficial bacterium Akkermansia more effectively than ASKP2 and ASKP3. Furthermore, ASKP fractions facilitated thermogenesis of brown adipose tissue (BAT) of obese mice, as evidenced by increased expression of thermogenic marker genes UCP1 in BAT, and the thermogenesis effect of ASKP1 was the most obvious. Taken together, our results show that ASKP1 is a novel prebiotic that may be used to treat obesity and its related abnormal metabolism.
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Affiliation(s)
- Xiaoqian Zeng
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710119, China
| | - Pinglian Yu
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710119, China; Key Laboratory of YunNan University for Plateau Characteristic Functional Food, School of Chemistry and Chemical Engineering, Zhaotong University, 657000, China.
| | - Donglu Li
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710119, China
| | - Yixiao Li
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710119, China
| | - Xuejie Wang
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710119, China
| | - Xingbin Yang
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710119, China
| | - Daoyuan Ren
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, and Shaanxi Key Laboratory for Hazard Factors Assessment in Processing and Storage of Agricultural Products, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710119, China.
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Emílio-Silva MT, Rodrigues VP, Fioravanti MM, Ruiz-Malagon AJ, Naia Fioretto M, Raimundo PR, Ohara R, Assunção R, Bueno G, Dario FL, Justulin LA, Rodríguez-Nogales A, da Rocha LRM, Gálvez J, Hiruma-Lima CA. Citral protects against metabolic endotoxemia, and systemic disorders caused by high-fat diet-induced obesity via intestinal modulation. Front Pharmacol 2025; 16:1567217. [PMID: 40260376 PMCID: PMC12009827 DOI: 10.3389/fphar.2025.1567217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2025] [Accepted: 03/24/2025] [Indexed: 04/23/2025] Open
Abstract
Background Obesity is a growing global epidemic associated with changes in the gut microenvironment and metabolic endotoxemia, which can exacerbate metabolic and inflammatory processes. Citral (CT), a monoterpene present in essential oils, has been investigated for its anti-inflammatory, antioxidant, and immunomodulatory properties. However, its role in modulating the gut axis during metabolic and inflammatory alterations in obesity remains unknown. In this study, we investigated the effects of CT on intestinal and metabolic impairment induced by lipopolysaccharide (LPS) and high-fat diet (HFD) in in vitro and in vivo models. Methods Male C57BL/6J mice were fed a standard diet and HFD for 17 weeks, with daily oral administration of CT treatment (25, 100, or 300 mg/kg) or vehicle. Morphological and histological parameters, lipid profiles, adipose index, cytokine levels, and colonic gene expression were determined. In vitro, murine rectal carcinoma (CMT-93) cells were stimulated with LPS (10 μg/mL) to assess tight junction and inflammatory protein expression. Results CT treatment showed anti-obesity activity against HFD-induced body mass gain in mice, which was attributed to a significant reduction in body fat, glycemia, and cholesterol levels. Systemic inflammation during obesity also decreased after CT treatment, with a significant reduction in serum levels of endotoxin, interleukin-1β, and tumor necrosis factor-α. Additionally, CT stimulation reduced inducible nitric oxide synthase expression and maintained ZO-1 levels in LPS-stimulated CMT-93 cells. Conclusion CT has anti-obesogenic, anti-inflammatory, and anti-hyperlipidemic properties mediated by its protective effects on the intestinal epithelium in obesity. Thus, our results highlight the promising preclinical results of CT treatment as a protective agent against the detrimental effects of HFD and LPS in mice.
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Affiliation(s)
- Maycon Tavares Emílio-Silva
- Department of Structural and Functional Biology, Physiology Sector, Institute of Bioscience, São Paulo State University (UNESP), Botucatu, Brazil
| | - Vinicius Peixoto Rodrigues
- Department of Structural and Functional Biology, Physiology Sector, Institute of Bioscience, São Paulo State University (UNESP), Botucatu, Brazil
| | - Mariana Moraes Fioravanti
- Department of Structural and Functional Biology, Physiology Sector, Institute of Bioscience, São Paulo State University (UNESP), Botucatu, Brazil
| | - Antonio Jesús Ruiz-Malagon
- Department of Pharmacology, Center for Biomedical Research (CIBM), University of Granada, Granada, Spain
| | - Matheus Naia Fioretto
- Department of Structural and Functional Biology, Morphology Sector, Institute of Bioscience, São Paulo State University, (UNESP), Botucatu, Brazil
| | - Priscila Romano Raimundo
- Department of Structural and Functional Biology, Physiology Sector, Institute of Bioscience, São Paulo State University (UNESP), Botucatu, Brazil
| | - Rie Ohara
- Department of Structural and Functional Biology, Physiology Sector, Institute of Bioscience, São Paulo State University (UNESP), Botucatu, Brazil
| | - Renata Assunção
- Department of Structural and Functional Biology, Physiology Sector, Institute of Bioscience, São Paulo State University (UNESP), Botucatu, Brazil
| | - Gabriela Bueno
- Department of Structural and Functional Biology, Physiology Sector, Institute of Bioscience, São Paulo State University (UNESP), Botucatu, Brazil
| | - Felipe Lima Dario
- Department of Structural and Functional Biology, Physiology Sector, Institute of Bioscience, São Paulo State University (UNESP), Botucatu, Brazil
| | - Luis Antonio Justulin
- Department of Structural and Functional Biology, Morphology Sector, Institute of Bioscience, São Paulo State University, (UNESP), Botucatu, Brazil
| | - Alba Rodríguez-Nogales
- Department of Pharmacology, Center for Biomedical Research (CIBM), University of Granada, Granada, Spain
| | - Lucia Regina Machado da Rocha
- Department of Structural and Functional Biology, Physiology Sector, Institute of Bioscience, São Paulo State University (UNESP), Botucatu, Brazil
| | - Júlio Gálvez
- Department of Pharmacology, Center for Biomedical Research (CIBM), University of Granada, Granada, Spain
- CIBER de Enfermedades Hepáticas y Digestivas (CIBER-EHD), Instituto de Salud Carlos III, Madrid, Spain
| | - Clélia Akiko Hiruma-Lima
- Department of Structural and Functional Biology, Physiology Sector, Institute of Bioscience, São Paulo State University (UNESP), Botucatu, Brazil
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Babakhani K, Kucinskas AL, Ye X, Giles ED, Sun Y. Aging immunity: unraveling the complex nexus of diet, gut microbiome, and immune function. IMMUNOMETABOLISM (COBHAM, SURREY) 2025; 7:e00061. [PMID: 40352822 PMCID: PMC12063687 DOI: 10.1097/in9.0000000000000061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/13/2024] [Accepted: 03/28/2025] [Indexed: 05/14/2025]
Abstract
Aging is associated with immune senescence and gut dysbiosis, both of which are heavily influenced by the diet. In this review, we summarize current knowledge regarding the impact of diets high in fiber, protein, or fat, as well as different dietary components (tryptophan, omega-3 fatty acids, and galacto-oligosaccharides) on the immune system and the gut microbiome in aging. Additionally, this review discusses how aging alters tryptophan metabolism, contributing to changes in immune function and the gut microbiome. Understanding the relationship between diet, the gut microbiome, and immune function in the context of aging is critical to formulate sound dietary recommendations for older individuals, and these personalized nutritional practices will ultimately improve the health and longevity of the elderly.
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Affiliation(s)
| | - Amanda L. Kucinskas
- Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA
| | - Xiangcang Ye
- Department of Nutrition, Texas A&M University, College Station, TX, USA
| | - Erin D. Giles
- School of Kinesiology, University of Michigan, Ann Arbor, MI, USA
| | - Yuxiang Sun
- Department of Nutrition, Texas A&M University, College Station, TX, USA
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Kovynev A, Charchuta MM, Begtašević A, Ducarmon QR, Rensen PCN, Schönke M. Combination of dietary fiber and exercise training improves fat loss in mice but does not ameliorate MASLD more than exercise alone. Am J Physiol Gastrointest Liver Physiol 2025; 328:G399-G410. [PMID: 40033967 DOI: 10.1152/ajpgi.00317.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Revised: 01/02/2025] [Accepted: 02/20/2025] [Indexed: 03/05/2025]
Abstract
Lifestyle interventions, such as diet and exercise, are currently the main therapies against metabolic dysfunction-associated steatotic liver disease (MASLD). However, not much is known about the combined impact of fiber and exercise on the modulation of gut-liver axis and MASLD amelioration. Here, we studied the impact of the combination of exercise training and a fiber-rich diet on the amelioration of MASLD. Male APOE*3-Leiden.CETP mice were fed a high-fat high-cholesterol diet with or without the addition of fiber (10% inulin) and exercise trained on a treadmill, or remained sedentary. Exercise training and fiber supplementation reduced fat mass gain and lowered plasma glucose levels. Only the combination treatment, however, induced fat loss and decreased plasma triglyceride and cholesterol levels compared with sedentary control mice. Exercise training with and without the addition of fiber had a similar ameliorating effect on the MASLD score. Only exercise without fiber decreased the hepatic expression of inflammatory markers. Fiber diet was mainly responsible for remodeling the gut microbial composition, with an increase in the relative abundance of the short-chain fatty acid (SCFA)-producing genera Anaerostipes and Muribaculaceae, whereas, surprisingly, exercise training alone and with fiber resulted in the highest increase of SCFA production. Overall, the combination of exercise training and dietary fiber decreases fat mass and improves glucose and lipid homeostasis but does not have an additional synergistic positive effect on liver health compared with exercise training alone.NEW & NOTEWORTHY The combination of dietary fiber intake and exercise training has a synergetic beneficial effect on the metabolic health, resulting in fat loss, lowered blood glucose, and lowered plasma lipid levels in mice with steatotic liver disease. However, fiber supplementation, despite a positive remodulation of the gut-liver axis, does not have an additional positive effect on liver health compared with exercise training alone.
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Affiliation(s)
- Artemiy Kovynev
- Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
- Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Mikołaj M Charchuta
- Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
- Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Amina Begtašević
- Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
- Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Quinten R Ducarmon
- Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands
| | - Patrick C N Rensen
- Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
- Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Milena Schönke
- Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
- Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
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Mendez-Hernandez R, Braga I, Bali A, Yang M, de Lartigue G. Vagal Sensory Gut-Brain Pathways That Control Eating-Satiety and Beyond. Compr Physiol 2025; 15:e70010. [PMID: 40229922 DOI: 10.1002/cph4.70010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2025] [Revised: 03/20/2025] [Accepted: 03/31/2025] [Indexed: 04/16/2025]
Abstract
The vagus nerve is the body's primary sensory conduit from gut to brain, traditionally viewed as a passive relay for satiety signals. However, emerging evidence reveals a far more complex system-one that actively encodes diverse aspects of meal-related information, from mechanical stretch to nutrient content, metabolic state, and even microbial metabolites. This review challenges the view of vagal afferent neurons (VANs) as simple meal-termination sensors and highlights their specialized subpopulations, diverse sensory modalities, and downstream brain circuits, which shape feeding behavior, metabolism, and cognition. We integrate recent advances from single-cell transcriptomics, neural circuit mapping, and functional imaging to examine how VANs contribute to gut-brain communication beyond satiety, including their roles in food reward and memory formation. By synthesizing the latest research and highlighting emerging directions for the field, this review provides a comprehensive update on vagal sensory pathways and their role as integrators of meal information.
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Affiliation(s)
- Rebeca Mendez-Hernandez
- Monell Chemical Senses Center, Philadelphia, Pennsylvania, USA
- Department of Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Isadora Braga
- Monell Chemical Senses Center, Philadelphia, Pennsylvania, USA
- Department of Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Avnika Bali
- Monell Chemical Senses Center, Philadelphia, Pennsylvania, USA
- Department of Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Mingxin Yang
- Monell Chemical Senses Center, Philadelphia, Pennsylvania, USA
- Department of Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Guillaume de Lartigue
- Monell Chemical Senses Center, Philadelphia, Pennsylvania, USA
- Department of Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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10
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Wang G, Wang B, Zhou Q, Cheng Z, Liu L, Zhang S, Zhou S, Luo P. Puerarin combined with Hericium erinaceus insoluble dietary fiber alleviates obesity induced by high-fat diet through regulating the glycerophospholipid metabolism pathway influenced by gut microbiota. Appl Environ Microbiol 2025; 91:e0237624. [PMID: 39976439 PMCID: PMC11921353 DOI: 10.1128/aem.02376-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Accepted: 01/19/2025] [Indexed: 02/21/2025] Open
Abstract
The purpose of this study was to evaluate the combined effects of puerarin (Pue) and insoluble dietary fiber from Hericium erinaceus (HEIDF) on obesity induced by a high-fat diet (HFD) in mice, focusing on their effects on lipid and glucose metabolism, gut microbiota (GM), and serum metabolites. Glucose tolerance, tissue pathology, and serum biochemical levels were conducted to assess the effects of puerarin combined with Hericium Erinaceus insoluble dietary fiber (LH) on glucose and lipid metabolism. 16S rRNA sequencing and untargeted metabonomics were employed to explore the underlying mechanisms. The results showed that the LH group significantly reduced body weight and hepatic and adipose lipid accumulation, and improved glucose tolerance and dyslipidemia compared to the Pue or HEIDF groups alone. Moreover, the LH group exhibited enhanced regulation of GM, including increased microbial diversity, higher abundance of beneficial bacteria such as g__Lactobacillus and g__Bacillus, and a decreased Firmicutes-to-Bacteroidota ratio. In addition, the LH group ameliorated HFD-induced serum metabolite changes and promoted the activation of tryptophan and glycerophospholipid metabolism pathways. The combination of Pue and HEIDF exhibits a synergistic anti-obesity effect by modulating specific GM (g__Lactobacillus and g__Bacillus) and serum metabolites.IMPORTANCEThe combination of HEIDF and Pue holds significant importance in the context of obesity. This synergistic effect not only aids in weight management but may also enhance metabolic health through various mechanisms, including increased satiety and promotion of fat oxidation. Therefore, incorporating these two components into the daily diet could offer effective strategies for the prevention and intervention of obesity and its related diseases.
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Affiliation(s)
- Guoze Wang
- The Affiliated Hospital of Guizhou Medical University, Guizhou Provincial Engineering Research Center of Ecological Food Innovation, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang, China
| | - Binbin Wang
- The Affiliated Hospital of Guizhou Medical University, Guizhou Provincial Engineering Research Center of Ecological Food Innovation, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang, China
| | - Qin Zhou
- The Affiliated Hospital of Guizhou Medical University, Guizhou Provincial Engineering Research Center of Ecological Food Innovation, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang, China
| | - Zhimei Cheng
- The Affiliated Hospital of Guizhou Medical University, Guizhou Provincial Engineering Research Center of Ecological Food Innovation, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang, China
| | - Li Liu
- The Affiliated Hospital of Guizhou Medical University, Guizhou Provincial Engineering Research Center of Ecological Food Innovation, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang, China
- The Key Laboratory of Precision Nutrition and Health of Ministry of Education, Harbin Medical University, Harbin, China
| | - Shuai Zhang
- The Affiliated Hospital of Guizhou Medical University, Guizhou Provincial Engineering Research Center of Ecological Food Innovation, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang, China
| | - Shi Zhou
- The Affiliated Hospital of Guizhou Medical University, Guizhou Provincial Engineering Research Center of Ecological Food Innovation, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang, China
| | - Peng Luo
- The Affiliated Hospital of Guizhou Medical University, Guizhou Provincial Engineering Research Center of Ecological Food Innovation, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang, China
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11
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Fan K, Hua X, Wang S, Efferth T, Tan S, Wang Z. A promising fusion: Traditional Chinese medicine and probiotics in the quest to overcome osteoporosis. FASEB J 2025; 39:e70428. [PMID: 40047492 DOI: 10.1096/fj.202403209r] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Revised: 01/23/2025] [Accepted: 02/19/2025] [Indexed: 05/13/2025]
Abstract
Botanical drugs and probiotic supplements present safer alternative options for the prevention and treatment of osteoporosis (OP). However, pathological disorders of the gut microbiota and the specific properties of probiotics and traditional Chinese medicine (TCM) significantly limit their therapeutic efficacy. Given the favorable synergistic and complementary effects between probiotics and herbal medicines, a creative combination of these approaches may address the issue of their current limited efficacy. A comprehensive analysis is necessary to provide a detailed review of their potential for combination, the mechanisms behind their synergy, scientific applications, and future developments. There exists a complex relationship between gut microbiota and OP, and the underlying regulatory mechanisms are multidimensional, involving the production of pro-inflammatory metabolites, immune system disruption, and the impairment of the intestinal mucosal barrier. Furthermore, we analyzed the complex mechanisms and potential connections between probiotics, TCM, and their combined applications. We highlighted the principle of complementary gain and the substantial therapeutic potential of their organic combination, which facilitates the release of active substances in TCM, increases the bioavailability of TCM, enhances probiotic delivery efficiency, and exerts synergistic effects. The combined use of probiotics and TCM offers a safe and effective strategy for managing OP and presents an innovative and promising direction for the future development of modern phytomedicine.
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Affiliation(s)
- Kangcheng Fan
- College of Exercise and Health, Shenyang Sport University, Shenyang, China
| | - Xin Hua
- Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou, China
| | - Shuwan Wang
- College of Exercise and Health, Shenyang Sport University, Shenyang, China
| | - Thomas Efferth
- Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany
| | - Shengnan Tan
- Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou, China
| | - Zhuo Wang
- College of Exercise and Health, Shenyang Sport University, Shenyang, China
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12
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Jack BU, Dias S, Pheiffer C. Comparative Effects of Tumor Necrosis Factor Alpha, Lipopolysaccharide, and Palmitate on Mitochondrial Dysfunction in Cultured 3T3-L1 Adipocytes. Cell Biochem Biophys 2025; 83:905-918. [PMID: 39269560 PMCID: PMC11870959 DOI: 10.1007/s12013-024-01522-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/29/2024] [Indexed: 09/15/2024]
Abstract
We have previously reported that dysregulated lipid metabolism and inflammation in 3T3-L1 adipocytes is attributed to tumor necrosis factor alpha (TNFα) rather than lipopolysaccharide (LPS) and palmitate (PA). In this study, we further compared the modulative effects of TNFα, LPS, and PA on mitochondrial function by treating 3T3-L1 adipocytes with TNFα (10 ng/mL), LPS (100 ng/mL), and PA (0.75 mM) individually or in combination for 24 h. Results showed a significant reduction in intracellular adenosine triphosphate (ATP) content, mitochondrial bioenergetics, total antioxidant capacity, and the mRNA expression of citrate synthase (Cs), sirtuin 3 (Sirt3), protein kinase AMP-activated catalytic subunit alpha 2 (Prkaa2), peroxisome proliferator-activated receptor gamma coactivator 1 alpha (Ppargc1α), nuclear respiratory factor 1 (Nrf1), and superoxide dismutase 1 (Sod1) in cells treated with TNFα individually or in combination with LPS and PA. Additionally, TNFα treatments decreased insulin receptor substrate 1 (Irs1), insulin receptor substrate 2 (Irs2), solute carrier family 2, facilitated glucose transporter member 4 (Slc2a4), and phosphoinositide 3 kinase regulatory subunit 1 (Pik3r1) mRNA expression. Treatment with LPS and PA alone, or in combination, did not affect the assessed metabolic parameters, while the combination of LPS and PA increased lipid peroxidation. These results show that TNFα but not LPS and PA dysregulate mitochondrial function, thus inducing oxidative stress and impaired insulin signaling in 3T3-L1 adipocytes. This suggests that TNFα treatment can be used as a basic in vitro model for studying the pathophysiology of mitochondrial dysfunction and related metabolic complications and screening potential anti-obesity therapeutics in 3T3-L1 adipocytes.
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Affiliation(s)
- Babalwa Unice Jack
- Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, Cape Town, 7505, South Africa.
- Centre for Cardiometabolic Research in Africa, Division of Medical Physiology, Stellenbosch University, Tygerberg, Cape Town, 7505, South Africa.
| | - Stephanie Dias
- Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, Cape Town, 7505, South Africa
| | - Carmen Pheiffer
- Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, Cape Town, 7505, South Africa
- Department of Obstetrics and Gynaecology, Faculty of Health Sciences, University of Pretoria, Pretoria, 0001, South Africa
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13
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Zhang H, Tian Y, Xu C, Chen M, Xiang Z, Gu L, Xue H, Xu Q. Crosstalk between gut microbiotas and fatty acid metabolism in colorectal cancer. Cell Death Discov 2025; 11:78. [PMID: 40011436 DOI: 10.1038/s41420-025-02364-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 01/30/2025] [Accepted: 02/17/2025] [Indexed: 02/28/2025] Open
Abstract
Colorectal cancer (CRC) is the third most common malignancy globally and the second leading cause of cancer-related mortality. Its development is a multifactorial and multistage process influenced by a dynamic interplay between gut microbiota, environmental factors, and fatty acid metabolism. Dysbiosis of intestinal microbiota and abnormalities in microbiota-associated metabolites have been implicated in colorectal carcinogenesis, highlighting the pivotal role of microbial and metabolic interactions. Fatty acid metabolism serves as a critical nexus linking dietary patterns with gut microbial activity, significantly impacting intestinal health. In CRC patients, reduced levels of short-chain fatty acids (SCFAs) and SCFA-producing bacteria have been consistently observed. Supplementation with SCFA-producing probiotics has demonstrated tumor-suppressive effects, while therapeutic strategies aimed at modulating SCFA levels have shown potential in enhancing the efficacy of radiation therapy and immunotherapy in both preclinical and clinical settings. This review explores the intricate relationship between gut microbiota, fatty acid metabolism, and CRC, offering insights into the underlying mechanisms and their potential translational applications. Understanding this interplay could pave the way for novel diagnostic, therapeutic, and preventive strategies in the management of CRC.
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Affiliation(s)
- Hao Zhang
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China
| | - Yuan Tian
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China
| | - Chunjie Xu
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China
| | - Miaomiao Chen
- Department of Radiology, Huashan Hospital, National Center for Neurological Disorders, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, 200040, PR China
| | - Zeyu Xiang
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China
| | - Lei Gu
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.
| | - Hanbing Xue
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
| | - Qing Xu
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.
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14
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Wang X, Zhang J, Zhong R, Chen G, Qi H, Cao Y, Lan Y. Consumption of oleogel alleviates lipid metabolism disorders in high-fat diet-fed rats by inhibiting LPS-induced gut microbiota-mediated inflammation. Food Funct 2025; 16:1130-1141. [PMID: 39831811 DOI: 10.1039/d4fo02974g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2025]
Abstract
This study investigated the effect of oleogel consumption on lipid metabolism, gut microbiota and low-grade inflammation in rats fed with a high-fat diet. Male SD rats received either a control diet or high-fat diets for six weeks. The high-fat diets included a regular high-fat diet and high-fat diets in which lard was replaced with pure sunflower oil, un-gelled sunflower oil containing a dispersed gelator, or gelled sunflower oil with the gelator (oleogel). Results showed that compared to regular fat, pure sunflower oil and un-gelled sunflower oil consumption, oleogel consumption significantly suppressed weight gain and adipose tissue accumulation as well as serum and liver lipid accumulation. Microscopic observations further confirmed that oleogel intake alleviated white adipose tissue and liver steatosis caused by high-fat diet. Ex vivo biodistribution studies indicated an increased movement of TAGs toward the large intestine in the oleogel group. In the meantime, the dysregulation of gut microbiota was restored by reducing the Firmicutes/Bacteroidetes ratio and the relative abundance of Desulfobacterota and Proteobacteria. The oleogel group also exhibited reduced LPS levels in faeces, serum and liver. Furthermore, oleogel consumption alleviated inflammation, including decreased gene expression of pro-inflammatory cytokines, such as IL-6 and TNF-α, as well as suppressed protein expression of TLR4 and NF-κB in the liver. These results provide theoretical guidance for the regulation of oleogel properties and the potential application of oleogels as healthy fat replacers in high-fat diets.
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Affiliation(s)
- Xin Wang
- Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, College of Food Science, South China Agricultural University, Guangzhou, Guangdong, P.R. China.
| | - Jing Zhang
- Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, College of Food Science, South China Agricultural University, Guangzhou, Guangdong, P.R. China.
| | - Ruimin Zhong
- Guangdong Provincial Key Laboratory of Utilization and Conservation of Food and Medicinal Resources in Northern Region, Shaoguan, Guangdong, P.R. China
| | - Gangchao Chen
- Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, College of Food Science, South China Agricultural University, Guangzhou, Guangdong, P.R. China.
| | - Hongjin Qi
- Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, College of Food Science, South China Agricultural University, Guangzhou, Guangdong, P.R. China.
| | - Yong Cao
- Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, College of Food Science, South China Agricultural University, Guangzhou, Guangdong, P.R. China.
| | - Yaqi Lan
- Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, College of Food Science, South China Agricultural University, Guangzhou, Guangdong, P.R. China.
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15
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Siguenza N, Bailey S, Sadegi M, Gootin H, Tiu M, Price JD, Ramer-Tait A, Zarrinpar A. Gut Competition Dynamics of Live Bacterial Therapeutics Are Shaped by Microbiome Complexity, Diet, and Therapeutic Transgenes. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2025.01.21.634159. [PMID: 39896492 PMCID: PMC11785071 DOI: 10.1101/2025.01.21.634159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 02/04/2025]
Abstract
Competitive exclusion is conventionally believed to prevent the establishment of a secondary strain of the same bacterial species in the gut microbiome, raising concerns for the deployment of live bacterial therapeutics (LBTs), especially if the bacterial chassis is a strain native to the gut. In this study, we investigated factors influencing competition dynamics in the murine gut using isogenic native Escherichia coli strains. We found that competition outcomes are context-dependent, modulated by microbiome complexity, LBT transgene expression, intestinal inflammation, and host diet. Furthermore, we demonstrated that native LBTs can establish long-term engraftment in the gut alongside a parental strain, with transgene-associated fitness effects influencing competition. We identified various interventions, including strategic dosing and dietary modulation, that significantly enhanced LBT colonization levels by 2 to 3 orders of magnitude. These insights provide a framework for optimizing LBT engraftment and efficacy, supporting their potential translation for human therapeutic applications.
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Affiliation(s)
- Nicole Siguenza
- Division of Gastroenterology, University of California, San Diego, La Jolla, CA, USA
- Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA, USA
| | - Sharyl Bailey
- Division of Gastroenterology, University of California, San Diego, La Jolla, CA, USA
| | - Mohammad Sadegi
- Division of Gastroenterology, University of California, San Diego, La Jolla, CA, USA
| | - Hanna Gootin
- Division of Gastroenterology, University of California, San Diego, La Jolla, CA, USA
| | - Maria Tiu
- Division of Gastroenterology, University of California, San Diego, La Jolla, CA, USA
| | - Jeffrey D. Price
- Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE, USA
| | - Amanda Ramer-Tait
- Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE, USA
- Nebraska Food for Health Center, University of Nebraska-Lincoln, Lincoln, NE, USA
| | - Amir Zarrinpar
- Division of Gastroenterology, University of California, San Diego, La Jolla, CA, USA
- Division of Gastroenterology, Jennifer Moreno Department of Veterans Affairs Medical Center, La Jolla, CA, USA
- The Moores Cancer Center, University of California San Diego, La Jolla, CA, USA
- Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA
- Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, CA, USA
- Synthetic Biology Institute, University of California San Diego, La Jolla, CA, USA
- Institute of Diabetes and Metabolic Health, University of California San Diego, La Jolla, CA, USA
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16
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Borrego-Ruiz A, Borrego JJ. Human gut microbiome, diet, and mental disorders. Int Microbiol 2025; 28:1-15. [PMID: 38561477 PMCID: PMC11775079 DOI: 10.1007/s10123-024-00518-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Revised: 03/15/2024] [Accepted: 03/22/2024] [Indexed: 04/04/2024]
Abstract
Diet is one of the most important external factor shaping the composition and metabolic activities of the gut microbiome. The gut microbiome plays a crucial role in host health, including immune system development, nutrients metabolism, and the synthesis of bioactive molecules. In addition, the gut microbiome has been described as critical for the development of several mental disorders. Nutritional psychiatry is an emerging field of research that may provide a link between diet, microbial function, and brain health. In this study, we have reviewed the influence of different diet types, such as Western, Mediterranean, vegetarian, and ketogenic, on the gut microbiota composition and function, and their implication in various neuropsychiatric and psychological disorders.
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Affiliation(s)
- Alejandro Borrego-Ruiz
- Departamento de Psicología Social y de las Organizaciones, Universidad Nacional de Educación a Distancia (UNED), Madrid, Spain
| | - Juan J Borrego
- Departamento de Microbiología, Universidad de Málaga. Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina BIONAND, Málaga, Spain.
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17
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Yarahmadi A, Afkhami H, Javadi A, Kashfi M. Understanding the complex function of gut microbiota: its impact on the pathogenesis of obesity and beyond: a comprehensive review. Diabetol Metab Syndr 2024; 16:308. [PMID: 39710683 PMCID: PMC11664868 DOI: 10.1186/s13098-024-01561-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Accepted: 12/15/2024] [Indexed: 12/24/2024] Open
Abstract
Obesity is a multifactorial condition influenced by genetic, environmental, and microbiome-related factors. The gut microbiome plays a vital role in maintaining intestinal health, increasing mucus creation, helping the intestinal epithelium mend, and regulating short-chain fatty acid (SCFA) production. These tasks are vital for managing metabolism and maintaining energy balance. Dysbiosis-an imbalance in the microbiome-leads to increased appetite and the rise of metabolic disorders, both fuel obesity and its issues. Furthermore, childhood obesity connects with unique shifts in gut microbiota makeup. For instance, there is a surge in pro-inflammatory bacteria compared to children who are not obese. Considering the intricate nature and variety of the gut microbiota, additional investigations are necessary to clarify its exact involvement in the beginnings and advancement of obesity and related metabolic dilemmas. Currently, therapeutic methods like probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), dietary interventions like Mediterranean and ketogenic diets, and physical activity show potential in adjusting the gut microbiome to fight obesity and aid weight loss. Furthermore, the review underscores the integration of microbial metabolites with pharmacological agents such as orlistat and semaglutide in restoring microbial homeostasis. However, more clinical tests are essential to refine the doses, frequency, and lasting effectiveness of these treatments. This narrative overview compiles the existing knowledge on the multifaceted role of gut microbiota in obesity and much more, showcasing possible treatment strategies for addressing these health challenges.
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Affiliation(s)
- Aref Yarahmadi
- Department of Biology, Khorramabad Branch, Islamic Azad University, Khorramabad, Iran
| | - Hamed Afkhami
- Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran.
- Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran.
- Department of Medical Microbiology, Faculty of Medicine, Shahed University, Tehran, Iran.
| | - Ali Javadi
- Department of Medical Sciences, Faculty of Medicine, Qom Medical Sciences, Islamic Azad University, Qom, Iran.
| | - Mojtaba Kashfi
- Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran.
- Fellowship in Clinical Laboratory Sciences, Mashhad University of Medical Sciences, Mashhad, Iran.
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18
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Kovynev A, Ying Z, Zhang S, Olgiati E, Lambooij JM, Visentin C, Guigas B, Ducarmon QR, Rensen PCN, Schönke M. Timing Matters: Late, but Not Early, Exercise Training Ameliorates MASLD in Part by Modulating the Gut-Liver Axis in Mice. J Pineal Res 2024; 76:e70003. [PMID: 39539028 DOI: 10.1111/jpi.70003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Revised: 10/10/2024] [Accepted: 10/21/2024] [Indexed: 11/16/2024]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) affects two billion people worldwide and is currently mostly treatable via lifestyle interventions, such as exercise training. However, it is unclear whether the positive effects of exercise are restricted to unique circadian windows. We therefore aimed to study whether the timing of exercise training differentially modulates MASLD development. Twenty weeks old male APOE*3-Leiden.CETP mice were fed a high fat-high cholesterol diet to induce MASLD and treadmill-trained for 1 h five times per week for 12 weeks either early (ZT13; E-RUN) or late (ZT22; L-RUN) in the dark phase while corresponding sedentary groups (E-SED and L-SED) did not. Late, but not early exercise training decreased the MASLD score, body weight, fat mass, and liver triglycerides, accompanied by an altered composition of the gut microbiota. Specifically, only late exercise training increased the abundance of short-chain fatty acid-producing bacterial families and genera, such as Akkermansia, Lachnospiraceae, and Rikenella. To assess the role of the gut microbiota in training-induced effects, the study was repeated and trained (ZT22 only, RUN) or sedentary mice (SED) served as fecal donors for sedentary recipient mice (RUN FMT and SED FMT). Fecal microbiota transplantation reduced liver weight and plasma triglycerides in RUN FMT compared to SED FMT and tended to lower the MASLD score and liver triglycerides. Timing of exercise training is a critical factor for the positive effect on MASLD in this preclinical model, and the effect of late exercise is partially mediated via the gut-liver axis.
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Affiliation(s)
- Artemiy Kovynev
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
- Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Zhixiong Ying
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
- Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Sen Zhang
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
- Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Emanuele Olgiati
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
- Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Joost M Lambooij
- Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center, Leiden, The Netherlands
- Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands
| | - Clara Visentin
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
- Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Bruno Guigas
- Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center, Leiden, The Netherlands
| | - Quinten R Ducarmon
- Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center, Leiden, The Netherlands
| | - Patrick C N Rensen
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
- Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Milena Schönke
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
- Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
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19
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Cruz-Muñoz JR, Valdez-Morales EE, Barajas-Espinosa A, Barrios-García T, Liñán-Rico A, Guerrero-Alba R. Gene expression alterations of purinergic signaling components in obesity-associated intestinal low-grade inflammation in type 2 diabetes. Purinergic Signal 2024; 20:629-643. [PMID: 38587723 PMCID: PMC11555165 DOI: 10.1007/s11302-024-10006-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Accepted: 03/26/2024] [Indexed: 04/09/2024] Open
Abstract
Intestinal low-grade inflammation induced by a high-fat diet has been found to detonate chronic systemic inflammation, which is a hallmark of obesity, and precede the apparition of insulin resistance, a key factor for developing type 2 diabetes (T2D). Aberrant purinergic signaling pathways have been implicated in the pathogenesis of inflammatory bowel disease and other gastrointestinal diseases. However, their role in the gut inflammation associated with obesity and T2D remains unexplored. C57BL/6 J mice were fed a cafeteria diet for 21 weeks and received one injection of streptozotocin in their sixth week into the diet. The gene expression profile of purinergic signaling components in colon tissue was assessed by RT-qPCR. Compared to control mice, the treated group had a significant reduction in colonic length and mucosal and muscular layer thickness accompanied by increased NF-κB and IL-1β mRNA expression. Furthermore, colonic P2X2, P2X7, and A3R gene expression levels were lower, while the P2Y2, NT5E, and ADA expression levels increased. In conclusion, these data suggest that these purinergic signaling components possibly play a role in intestinal low-grade inflammation associated with obesity and T2D and thus could represent a novel therapeutic target for the treatment of the metabolic complications related to these diseases.
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Affiliation(s)
- José R Cruz-Muñoz
- Departamento de Fisiología y Farmacología, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, Aguascalientes, Ags, México
| | - Eduardo E Valdez-Morales
- Departamento de Fisiología y Farmacología, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, Aguascalientes, Ags, México
| | - Alma Barajas-Espinosa
- Escuela Superior de Huejutla, Universidad Autónoma del Estado de Hidalgo, Huejutla de Reyes, Hidalgo, México
| | - Tonatiuh Barrios-García
- Departamento de Fisiología y Farmacología, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, Aguascalientes, Ags, México
| | - Andrómeda Liñán-Rico
- Centro Universitario de Investigaciones Biomédicas. Consejo Nacional de Humanidades, Ciencia y Tecnología (CONAHCYT), Universidad de Colima, Colima, México.
| | - Raquel Guerrero-Alba
- Departamento de Fisiología y Farmacología, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, Aguascalientes, Ags, México.
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20
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Gopal RK, Ganesh PS, Pathoor NN. Synergistic Interplay of Diet, Gut Microbiota, and Insulin Resistance: Unraveling the Molecular Nexus. Mol Nutr Food Res 2024; 68:e2400677. [PMID: 39548908 DOI: 10.1002/mnfr.202400677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Revised: 10/04/2024] [Indexed: 11/18/2024]
Abstract
This comprehensive review explores the intricate relationship between gut microbiota, diet, and insulin resistance, emphasizing the novel roles of diet-induced microbial changes in influencing metabolic health. It highlights how diet significantly influences gut microbiota composition, with different dietary patterns fostering diverse microbial communities. These diet-induced changes in the microbiome impact human metabolism by affecting inflammation, energy balance, and insulin sensitivity, particularly through microbial metabolites like short-chain fatty acids (SCFAs). Focusing the key mediators like endotoxemia and systemic inflammation, and introduces personalized microbiome-based therapeutic strategies, it also investigates the effects of dietary components-fiber, polyphenols, and lipids-on microbiota and insulin sensitivity, along with the roles of protein intake and amino acid metabolism. The study compares the effects of Western and Mediterranean diets on the microbiota-insulin resistance axis. Therapeutic implications, including probiotics, fecal microbiota transplantation (FMT), and personalized diets, are discussed. Key findings reveal that high-fat diets, especially those rich in saturated fats, contribute to dysbiosis and increased intestinal permeability, while high-fiber diets promote beneficial bacteria and SCFAs. The review underscores the future potential of food and microbiota interventions for preventing or managing insulin resistance.
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Affiliation(s)
- Rajesh Kanna Gopal
- Department of Microbiology, Centre for Infectious Diseases, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University (Deemed to be University), Chennai, Tamil Nadu, 600077, India
| | - Pitchaipillai Sankar Ganesh
- Department of Microbiology, Centre for Infectious Diseases, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University (Deemed to be University), Chennai, Tamil Nadu, 600077, India
| | - Naji Naseef Pathoor
- Department of Microbiology, Centre for Infectious Diseases, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University (Deemed to be University), Chennai, Tamil Nadu, 600077, India
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21
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Xu H, Xue Z, Wang P, Lee Q, Chen Z, Liu B, Liu X, Zeng F. Edible fungi polysaccharides modulate gut microbiota and lipid metabolism: A review. Int J Biol Macromol 2024; 283:137427. [PMID: 39537059 DOI: 10.1016/j.ijbiomac.2024.137427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Revised: 11/04/2024] [Accepted: 11/06/2024] [Indexed: 11/16/2024]
Abstract
Edible fungi polysaccharides (EFPs) and gut microbiota (GM) play an important role in lipid metabolism. The structure of GM is complex and can be dynamically affected by the diet. EFPs can be used as dietary intervention to improve lipid metabolism directly, or by regulate the GM to participate in the host lipid metabolism by a complex mechanism. In this paper, we reviewed that EFPs regulate the balance of GM by increasing the number of beneficial bacteria and decreasing the number of harmful bacteria in the intestinal tract. The metabolites of GM are mainly bile acids (BAs), short-chain fatty acids (SCFAs), and lipopolysaccharides (LPS). EFPs can promote the synthesis of BAs and increase the content of SCFAs that produced by GM fermented EFPs, but reduce the content of LPS to regulate lipid metabolism. This review provides a valuable reference for further elucidation of the relationship between EFPs-GM-lipid metabolism and EFPs targeted regulation of GM to improve public health.
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Affiliation(s)
- Huanyi Xu
- College of Food Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China
| | - Zhixiang Xue
- Engineering Research Center of Fujian Subtropical Fruit and Vegetable Processing, Fuzhou 350002, China; National Engineering Research Center of JUNCAO Technology, Fuzhou 350002, China
| | - Pengyi Wang
- College of Food Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China
| | - Quancen Lee
- College of Food Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China
| | - Zihui Chen
- College of Food Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China
| | - Bin Liu
- College of Food Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China; Engineering Research Center of Fujian Subtropical Fruit and Vegetable Processing, Fuzhou 350002, China; National Engineering Research Center of JUNCAO Technology, Fuzhou 350002, China
| | - Xiaoyan Liu
- Beijing Engineering and Technology Research Center of Food Additives, School of Food and Health, Beijing Technology and Business University, Beijing 100048, China
| | - Feng Zeng
- College of Food Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China; Engineering Research Center of Fujian Subtropical Fruit and Vegetable Processing, Fuzhou 350002, China.
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22
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Hua Y, Zhou C, Fan R, Benazzouz S, Shen J, Xiao R, Ma W. Altered intestinal microbiota induced by high-fat diets affect cognition differently in mice. Nutr Res 2024; 132:67-84. [PMID: 39500027 DOI: 10.1016/j.nutres.2024.09.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Revised: 09/29/2024] [Accepted: 09/29/2024] [Indexed: 12/14/2024]
Abstract
The role of the gut microbiota in the association between high-fat diet and cognition is not clear. We hypothesized that a high-fat diet may influence cognition by altering the intestinal microbiota. Fecal microbiota isolated from male C57BL/6J mice feeding on various high-fat diets and a control basic diet were transplanted to antibiotic-treated recipient mice. The measurement of weight and plasma lipids, novel object recognition test, 16S rRNA gene sequencing of feces, and hematoxylin-eosin staining of the hippocampal cornu ammonis 1 and cornu ammonis 3 areas were performed for all mice. Compared with those in the control and n-3 polyunsaturated fatty acid (n-3 PUFA) groups, donor obese mice fed with diets high in long-chain saturated fatty acids, n-6 polyunsaturated fatty acids (n-6 PUFAs), and trans fatty acids exhibited significant cognitive impairment (all P < .05). There were fewer neurons in the hippocampal area in the n-6 PUFA group than in the n-3 PUFA group (P < .05). Similar effect on cognition and neurons in hippocampal area in corresponding recipient mice were revealed after fecal microbiota transplantation. In addition, the composition of intestinal microbiota differed among recipient mice after fecal microbiota transplantation from donor mice. According to these results, it was concluded that diets rich in long-chain saturated fatty acids, n-6 PUFAs, and trans fatty acids may lead to cognitive impairment by damaging the structure of the hippocampus through influencing the intestinal microbiota in mice, whereas a diet high in n-3 PUFAs may exhibit a beneficial effect.
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Affiliation(s)
- Yinan Hua
- School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China
| | - Cui Zhou
- School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China
| | - Rong Fan
- School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China
| | - Sara Benazzouz
- Laboratory of cellular and molecular biology, Faculty of biological sciences, University of Science and Technology Houari Boumediene, Bab Ezzouar, 16111, Algeria
| | - Jingyi Shen
- School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China
| | - Rong Xiao
- School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China
| | - Weiwei Ma
- School of Public Health, Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China.
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23
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Joshi DD, Deb L, Kaul K, Somkuwar BG, Rana VS, Singh R. Relevance of Indian Traditional Herbal Brews for Gut Microbiota Balance. Indian J Microbiol 2024; 64:1425-1444. [PMID: 39678955 PMCID: PMC11645388 DOI: 10.1007/s12088-024-01251-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Accepted: 03/02/2024] [Indexed: 12/17/2024] Open
Abstract
The considerable changes in lifestyle patterns primarily affect the human gut microbiota and result in obesity, diabetes, dyslipidemia, renal complications, etc. though there are few traditional safeguards such as herbal brews to maintain the ecological stability under intestinal dysbiosis. The present article is designed to collect all the scientific facts in a place to decipher the role of the Indian traditional herbal brews used to balance gut health for centuries. Computerized databases, commercial search engines, research papers, articles, and books were used to search by using different keywords to select the most appropriate published articles from 2000 onward to September 2023. A total of 1907 articles were scrutinized, 46 articles were finally selected from the 254 screened, and targeted information was compiled. Interaction of herbal brews to the gut microflora and resulting metabolites act as prebiotics due to antimicrobial, anti-inflammatory, and antioxidant properties, and modulate the pH of the gut. The effect of brews on gut microbiota has a drastic impact on various gut-related diseases and has gained popularity as an alternative to antibiotics against bacteria, fungi, viruses, parasites, and boosting the immune system and strengthening the intestinal barrier. Berberine, kaempferol, piperine, and quercetin have been found in more than one brew discussed in the present article. Practically, these brews balance the gut microbiota, prevent chronic and degenerative diseases, and reduce organ inflammation, though, there is a knowledge gap on the molecular mechanism to explain their efficacy. Indian traditional herbal brews used to reboot and heal the gut microbiota since centuries-old practice with successful history without toxicity. The systematic consumption of these brews under specific dietary prescriptions has a hope of arrays for a healthy human gut microbiome in the present hasty lifestyle with overall health and well-being. Graphical Abstract
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Affiliation(s)
- Devi Datt Joshi
- Amity Food and Agriculture Foundation, Amity University Uttar Pradesh, Noida, Sector-125, J-1 Block, Noida, UP 201313 India
| | - Lokesh Deb
- Institute of Bioresources and Sustainable Development (IBSD)-Regional Centre, Sikkim, 5th Mile, Tadong, Gangtok, Sikkim 737102 India
| | - Kanak Kaul
- Amity Institute of Microbial Technology, Amity University Uttar Pradesh, Noida, Sector-125, E-2 Block, Noida, UP 201313 India
| | - Bharat G. Somkuwar
- Institute of Bioresources and Sustainable Development (IBSD), Node Mizoram, A-1, C/O P. Lalthangzauva Building, Chawnga Road, Nursery Veng, Aizawl, Mizoram 796005 India
| | - Virendra Singh Rana
- Division of Agricultural Chemicals, ICAR-Indian Agricultural Research Institute (IARI), Pusa Campus, New Delhi, 110 012 India
| | - Rajni Singh
- Amity Institute of Microbial Technology, Amity University Uttar Pradesh, Noida, Sector-125, E-2 Block, Noida, UP 201313 India
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24
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Zeng F, He S, Sun Y, Li X, Chen K, Wang H, Man S, Lu F. Abnormal enterohepatic circulation of bile acids caused by fructooligosaccharide supplementation along with a high-fat diet. Food Funct 2024; 15:11432-11443. [PMID: 39450588 DOI: 10.1039/d4fo03353a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2024]
Abstract
Fructooligosaccharide (FOS) is a widely used prebiotic and health food ingredient, but few reports have focused on its risk to specific populations. Recently, it has been shown that the intake of inulin, whose main component is FOS, can lead to cholestasis and induce hepatocellular carcinoma in mice fed a high-fat diet (HFD); however, the molecular mechanism behind this is not clear. This study found that FOS supplementation induced abnormal enterohepatic circulation of bile acids in HFD-fed mice, which showed a significant increase in bile acid levels in the blood and liver, especially the secondary bile acids with high cytotoxicity, such as deoxycholic acid. The abundance of Clostridium, Bacteroides, and other bacteria in the gut microbiota also increased significantly. The analysis of the signaling pathway involved in regulating the enterohepatic circulation of bile acids showed that the weakening of the feedback inhibition of FXR-FGF15 and FXR-SHP signalling pathways possibly induced the enhancement of CYP7A1 activity and bile acid reabsorption in the blood and liver and led to an increase in bile acid synthesis and accumulation in the liver, increasing the risk of cholestasis. This study showed the risk of health damage caused by FOS supplementation in HFD-fed mice, which is caused by gut microbiota dysfunction and abnormal enterohepatic circulation of bile acids. Therefore, the application of FOS should be standardized to avoid the health risks of unreasonable FOS use in specific populations.
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Affiliation(s)
- Fang Zeng
- Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, The College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P. R. China.
| | - Shi He
- Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, The College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P. R. China.
| | - Ying Sun
- Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, The College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P. R. China.
| | - Xue Li
- Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, The College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P. R. China.
| | - Kaiyang Chen
- Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, The College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P. R. China.
| | - Hongbin Wang
- Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, The College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P. R. China.
| | - Shuli Man
- Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, The College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P. R. China.
| | - Fuping Lu
- Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, The College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P. R. China.
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25
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Yun SW, Shin YJ, Ma X, Kim DH. Lactobacillus plantarum and Bifidobacterium longum Alleviate High-Fat Diet-Induced Obesity and Depression/Cognitive Impairment-like Behavior in Mice by Upregulating AMPK Activation and Downregulating Adipogenesis and Gut Dysbiosis. Nutrients 2024; 16:3810. [PMID: 39599597 PMCID: PMC11597813 DOI: 10.3390/nu16223810] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 11/01/2024] [Accepted: 11/04/2024] [Indexed: 11/29/2024] Open
Abstract
Background/Objective: Long-term intake of a high-fat diet (HFD) leads to obesity and gut dysbiosis. AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism. Herein, we investigated the impacts of Lactobacillus (Lactiplantibacillus) plantarum P111 and Bifidobacterium longum P121, which suppressed dexamethasone-induced adipogenesis in 3T3 L1 cells and increased lipopolysaccharide-suppressed AMPK activation in HepG2 cells, on HFD-induced obesity, liver steatosis, gut inflammation and dysbiosis, and depression/cognitive impairment (DCi)-like behavior in mice. Methods: Obesity is induced in mice by feeding with HFD. Biomarker levels were measured using immunoblotting, enzyme-linked immunosorbent assay, and immunofluorescence staining. Results: Orally administered P111, P121, or their mix LpBl decreased HFD-induced body weight gain, epididymal fat pad weight, and triglyceride (TG), total cholesterol (TC), and lipopolysaccharide levels in the blood. Additionally, they downregulated HFD-increased NF-κB activation and TNF-α expression in the liver and colon, while HFD-decreased AMPK activation was upregulated. They also suppressed HFD-induced DCi-like behavior and hippocampal NF-κB activation, NF-κB-positive cell population, and IL-1β and TNF-α levels, while increasing the hippocampal BDNF-positive cell population and BDNF level. The combination of P111 and P122 (LpBl) also improved body weight gain, liver steatosis, and DCi-like behavior. LpBl also mitigated HFD-induced gut dysbiosis: it decreased Desulfovibrionaceae, Helicobacteriaceae, Coriobacteriaceae, and Streptococcaceae populations and lipopolysaccharide production, which were positively correlated with TNF-α expression; and increased Akkermansiaceae, Bifidobacteriaceae, and Prevotellaceae populations, which were positively correlated with the BDNF expression. Conclusions: P111 and/or P121 downregulated adipogenesis, gut dysbiosis, and NF-κB activation and upregulatde AMPK activation, leading to the alleviation of obesity, liver steatosis, and DCi.
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Affiliation(s)
- Soo-Won Yun
- Neurobiota Research Center, College of Pharmacy, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea; (S.-W.Y.); (Y.-J.S.); (X.M.)
| | - Yoon-Jung Shin
- Neurobiota Research Center, College of Pharmacy, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea; (S.-W.Y.); (Y.-J.S.); (X.M.)
| | - Xiaoyang Ma
- Neurobiota Research Center, College of Pharmacy, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea; (S.-W.Y.); (Y.-J.S.); (X.M.)
| | - Dong-Hyun Kim
- Neurobiota Research Center, College of Pharmacy, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea; (S.-W.Y.); (Y.-J.S.); (X.M.)
- PBLbioLab, Inc., Seoul 03174, Republic of Korea
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26
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Liu CY, Chen YW, Tsai TY, Liu TH, Chang TC, Tsao CW. Lactiplantibacillus plantarum 1008 Enhances Testicular Function and Spermatogenesis via the Modulation of Gut Microbiota in Male Mice with High-Fat-Diet-Induced Obesity. BIOLOGY 2024; 13:890. [PMID: 39596845 PMCID: PMC11592197 DOI: 10.3390/biology13110890] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Revised: 10/26/2024] [Accepted: 10/29/2024] [Indexed: 11/29/2024]
Abstract
Our study was designed to investigate the Lactiplantibacillus plantarum 1008 (LP1008) on testicular antioxidant capacity, spermatogenesis, apoptosis, autophagy, and metabolic function in male mice with high-fat-diet-induced obesity. A total of thirty-six male C57BL/6 mice were fed a normal diet (denoted as the NC group) or a high-fat control diet (denoted as the HFC group) for 16 weeks, then half of the HFC group was randomly chosen and subsequently fed with LP1008 for the final 8 weeks (high-fat diet + LP1008; denoted as the HFP group). The HFP group expressed improved blood cholesterol, insulin resistance, hepatic function, and lipopolysaccharide (LPS) levels compared to the HFC group. Meanwhile, the HFC group displayed decreased testicular testosterone levels, sperm quality, and 17β-HSD protein expression, which were rescued after LP1008 treatment. Moreover, the HFC group had lower superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) enzyme activities. After LP1008 treatment, enhanced antioxidative activities and decreased lipid peroxidation were observed. The HFC group also exhibited aggravated apoptosis, inflammation, and autophagy proteins in the testis, which were ameliorated by LP1008 supplementation. Furthermore, the gut microbiota analysis results revealed that the Firmicutes/Bacteroidetes ratio was significantly elevated in the HFC and HFP groups compared to the NC group and that LP1008 treatment diminished Ruminococcaceae and enhanced Bifidobacteriaceae diversity. In summary, LP1008 treatment strengthened antioxidative enzyme levels and regulated microbiota-ameliorated HFC-induced oxidative stress, apoptosis, inflammation, and autophagy, and thus improved testicular function and semen quality.
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Affiliation(s)
- Chin-Yu Liu
- Department of Nutritional Science, Fu Jen Catholic University, New Taipei City 242062, Taiwan; (C.-Y.L.); (Y.-W.C.); (T.-C.C.)
| | - Yi-Wen Chen
- Department of Nutritional Science, Fu Jen Catholic University, New Taipei City 242062, Taiwan; (C.-Y.L.); (Y.-W.C.); (T.-C.C.)
| | - Tsung-Yu Tsai
- Department of Food Science, Fu Jen Catholic University, New Taipei City 242062, Taiwan; (T.-Y.T.); (T.-H.L.)
| | - Te-Hua Liu
- Department of Food Science, Fu Jen Catholic University, New Taipei City 242062, Taiwan; (T.-Y.T.); (T.-H.L.)
| | - Ting-Chia Chang
- Department of Nutritional Science, Fu Jen Catholic University, New Taipei City 242062, Taiwan; (C.-Y.L.); (Y.-W.C.); (T.-C.C.)
| | - Chih-Wei Tsao
- Division of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 114202, Taiwan
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27
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Wang Q, Huang H, Yang Y, Yang X, Li X, Zhong W, Wen B, He F, Li J. Reinventing gut health: leveraging dietary bioactive compounds for the prevention and treatment of diseases. Front Nutr 2024; 11:1491821. [PMID: 39502877 PMCID: PMC11534667 DOI: 10.3389/fnut.2024.1491821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Accepted: 10/07/2024] [Indexed: 11/08/2024] Open
Abstract
The human gut harbors a complex and diverse microbiota essential for maintaining health. Diet is the most significant modifiable factor influencing gut microbiota composition and function, particularly through bioactive compounds like polyphenols, dietary fibers, and carotenoids found in vegetables, fruits, seafood, coffee, and green tea. These compounds regulate the gut microbiota by promoting beneficial bacteria and suppressing harmful ones, leading to the production of key microbiota-derived metabolites such as short-chain fatty acids, bile acid derivatives, and tryptophan metabolites. These metabolites are crucial for gut homeostasis, influencing gut barrier function, immune responses, energy metabolism, anti-inflammatory processes, lipid digestion, and modulation of gut inflammation. This review outlines the regulatory impact of typical bioactive compounds on the gut microbiota and explores the connection between specific microbiota-derived metabolites and overall health. We discuss how dietary interventions can affect disease development and progression through mechanisms involving these metabolites. We examine the roles of bioactive compounds and their metabolites in the prevention and treatment of diseases including inflammatory bowel disease, colorectal cancer, cardiovascular diseases, obesity, and type 2 diabetes mellitus. This study provides new insights into disease prevention and underscores the potential of dietary modulation of the gut microbiota as a strategy for improving health.
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Affiliation(s)
- Qiurong Wang
- Chengdu Medical College, Chengdu, China
- Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Hui Huang
- Chengdu Medical College, Chengdu, China
- Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Ying Yang
- Chengdu Medical College, Chengdu, China
| | - Xianglan Yang
- Pengzhou Branch of the First Affiliated Hospital of Chengdu Medical College, Pengzhou Second People’s Hospital, Chengdu, China
| | - Xuemei Li
- Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Wei Zhong
- Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Biao Wen
- Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Feng He
- Chengdu Medical College, Chengdu, China
- Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Jun Li
- Chengdu Medical College, Chengdu, China
- Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
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28
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Tagliatti E, Bizzotto M, Morini R, Filipello F, Rasile M, Matteoli M. Prenatal drivers of microglia vulnerability in the adult. Immunol Rev 2024; 327:100-110. [PMID: 39508795 DOI: 10.1111/imr.13418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2024]
Abstract
Environmental insults during early development heavily affect brain trajectories. Among these, maternal infections, high-fat diet regimens, and sleep disturbances pose a significant risk for neurodevelopmental derangements in the offspring. Notably, scattered evidence is starting to emerge that also paternal lifestyle habits may impact the offspring development. Given their key role in controlling neurogenesis, synaptogenesis and shaping neuronal circuits, microglia represent the most likely suspects of mediating the detrimental effects of prenatal insults. For some of these environmental triggers, like maternal infections, ample literature evidence demonstrates the central role of microglia, also delineating the specific transcriptomic and proteomic profiles induced by these insults. In other contexts, the analysis of microglia is still in its infancy. Fostering these studies is needed to define microglia as potential therapeutic target in the frame of disorders consequent to maternal immune activation.
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Affiliation(s)
| | | | | | | | - Marco Rasile
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Michela Matteoli
- IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
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29
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Wang T, Zhang X, Fan L, Zhao Y, Zhang Z, Cao Z, Xu Y, Lee S, Lim C, Zhang S. Complete genome sequence and anti-obesity potential of Lactiplantibacillus plantarum HOM2217 in 3T3-L1 cells and high-fat diet-fed rats. Front Microbiol 2024; 15:1436378. [PMID: 39323881 PMCID: PMC11422070 DOI: 10.3389/fmicb.2024.1436378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Accepted: 08/27/2024] [Indexed: 09/27/2024] Open
Abstract
The global prevalence of obesity is rising year by year, which has become a public health problem worldwide. Many animal and clinical studies have shown that Lactiplantibacillus plantarum is considered an ideal probiotic and potential supplement for the treatment of obesity. In this study, we aimed to complete the genome sequence of L. plantarum HOM2217, which was isolated from human milk, and study its physiological characteristics and anti-obesity effects in 3T3-L1 cells and rats fed a high-fat diet (HFD) to determine its potential as a starter for functional food products. Whole-genome analysis demonstrated that HOM2217 contained a single circular chromosome of 3,267,529 bp with a GC content of 44.5% and one plasmid (62,350 bp) with a GC content of 38.5%. Compared to the reference strains, HOM2217 demonstrated superior tolerance to gastrointestinal conditions, higher adhesion to intestinal epithelial cell lines, potent antimicrobial activity against Enterobacter cloacae ATCC 13047, and effective cholesterol removal ability in vitro. Treatment with heat-killed HOM2217 significantly reduced lipid accumulation and intracellular triglyceride production in 3T3-L1 adipocytes. Daily treatment of HFD-fed rats with HOM2217 for 7 weeks decreased body weight, body weight gain, and body fat without changes in food intake. HOM2217 also significantly increased the serum high-density lipoprotein cholesterol (HDL-C) level, decreased the serum tumor necrosis factor (TNF-α) and increased short-chain fatty acid (SCFA) (formic acid, acetic acid, and butyric acid) levels in the cecum. Thus, HOM2217 could potentially prevent obesity in rats by inhibiting inflammatory responses and regulating lipid metabolism and SCFAs expression. Therefore, HOM2217 has potential as an alternative treatment for obesity.
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Affiliation(s)
- Tingting Wang
- Research Center, Beijing Hanmi Pharmaceutical Co., Ltd., Beijing, China
| | - Xiao Zhang
- Research Center, Beijing Hanmi Pharmaceutical Co., Ltd., Beijing, China
| | - Linlin Fan
- Research Center, Beijing Hanmi Pharmaceutical Co., Ltd., Beijing, China
| | - Ying Zhao
- Research Center, Beijing Hanmi Pharmaceutical Co., Ltd., Beijing, China
| | - Zhengwen Zhang
- Research Center, Beijing Hanmi Pharmaceutical Co., Ltd., Beijing, China
| | - Zhonghua Cao
- Research Center, Beijing Hanmi Pharmaceutical Co., Ltd., Beijing, China
| | - Ying Xu
- Food & Biotech R&D Center, Coree Beijing Co., Ltd., Beijing, China
| | - Suwon Lee
- Food & Biotech R&D Center, Coree Beijing Co., Ltd., Beijing, China
| | - Chongyoon Lim
- Food & Biotech R&D Center, Coree Beijing Co., Ltd., Beijing, China
| | - Shiqi Zhang
- Food & Biotech R&D Center, Coree Beijing Co., Ltd., Beijing, China
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30
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Arnone AA, Wilson AS, Soto-Pantoja DR, Cook KL. Diet Modulates the Gut Microbiome, Metabolism, and Mammary Gland Inflammation to Influence Breast Cancer Risk. Cancer Prev Res (Phila) 2024; 17:415-428. [PMID: 38701438 PMCID: PMC11372361 DOI: 10.1158/1940-6207.capr-24-0055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Revised: 04/03/2024] [Accepted: 04/26/2024] [Indexed: 05/05/2024]
Abstract
Several studies indicate a strong link between obesity and the risk of breast cancer. Obesity decreases gut microbial biodiversity and modulates Bacteroidetes-to-Firmicutes phyla proportional abundance, suggesting that increased energy-harvesting capacity from indigestible dietary fibers and elevated lipopolysaccharide bioavailability may promote inflammation. To address the limited evidence linking diet-mediated changes in gut microbiota to breast cancer risk, we aimed to determine how diet affects the microbiome and breast cancer risk. For ten weeks, female 3-week-old BALB/c mice were fed six different diets (control, high-sugar, lard, coconut oil, lard + flaxseed oil, and lard + safflower oil). Fecal 16S sequencing was performed for each group. Diet shifted fecal microbiome populations and modulated mammary gland macrophage infiltration. Fecal-conditioned media shifted macrophage polarity and inflammation. In our DMBA-induced breast cancer model, diet differentially modulated tumor and mammary gland metabolism. We demonstrated how dietary patterns change metabolic outcomes and the gut microbiota, possibly contributing to breast tumor risk. Furthermore, we showed the influence of diet on metabolism, inflammation, and macrophage polarity. This study suggests that dietary-microbiome interactions are key mediators of breast cancer risk. Prevention Relevance: Our study demonstrates the impact of diet on breast cancer risk, focusing on the interplay between diet, the gut microbiome, and mammary gland inflammation.
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Affiliation(s)
- Alana A Arnone
- Department of Surgery, Wake Forest University School of Medicine, Winston-Salem, North Carolina
| | - Adam S Wilson
- Department of Surgery, Wake Forest University School of Medicine, Winston-Salem, North Carolina
| | - David R Soto-Pantoja
- Department of Surgery, Wake Forest University School of Medicine, Winston-Salem, North Carolina
- Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, North Carolina
- Atrium Health Wake Forest Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina
| | - Katherine L Cook
- Department of Surgery, Wake Forest University School of Medicine, Winston-Salem, North Carolina
- Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, North Carolina
- Atrium Health Wake Forest Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina
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31
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Chowdhury B, Sharma A, Akshit FNU, Mohan MS, Salunke P, Anand S. A review of oleogels applications in dairy foods. Crit Rev Food Sci Nutr 2024; 64:9691-9709. [PMID: 37229559 DOI: 10.1080/10408398.2023.2215871] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/27/2023]
Abstract
The characteristics of dairy products, such as texture, color, flavor, and nutritional profile, are significantly influenced by the presence of milk fat. However, saturated fatty acids account for 65% of total milk fat. With increased health awareness and regulatory recommendations, consumer preferences have evolved toward low/no saturated fat food products. Reducing the saturated fat content of dairy products to meet market demands is an urgent yet challenging task, as it may compromise product quality and increase production costs. In this regard, oleogels have emerged as a viable milk fat replacement in dairy foods. This review focuses on recent advances in oleogel systems and explores their potential for incorporation into dairy products as a milk fat substitute. Overall, it can be concluded that oleogel can be a potential alternative to replace milk fat fully or partially in the product matrix to improve nutritional profile by mimicking similar rheological and textural product characteristics as milk fat. Furthermore, the impact of consuming oleogel-based dairy foods on digestibility and gut health is also discussed. A thorough comprehension of the application of oleogels in dairy products will provide an opportunity for the dairy sector to develop applications that will appeal to the changing consumer needs.
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Affiliation(s)
- Bhaswati Chowdhury
- Department of Dairy and Food Science, South Dakota State University, Brookings, South Dakota, USA
| | - Aditya Sharma
- Department of Dairy and Food Science, South Dakota State University, Brookings, South Dakota, USA
| | - F N U Akshit
- Department of Dairy and Food Science, South Dakota State University, Brookings, South Dakota, USA
| | - Maneesha S Mohan
- Department of Dairy and Food Science, South Dakota State University, Brookings, South Dakota, USA
| | - Prafulla Salunke
- Department of Dairy and Food Science, South Dakota State University, Brookings, South Dakota, USA
| | - Sanjeev Anand
- Department of Dairy and Food Science, South Dakota State University, Brookings, South Dakota, USA
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Schleicher WE, Hoag B, De Dominici M, DeGregori J, Pietras EM. CHIP: a clonal odyssey of the bone marrow niche. J Clin Invest 2024; 134:e180068. [PMID: 39087468 PMCID: PMC11290965 DOI: 10.1172/jci180068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/02/2024] Open
Abstract
Clonal hematopoiesis of indeterminate potential (CHIP) is characterized by the selective expansion of hematopoietic stem and progenitor cells (HSPCs) carrying somatic mutations. While CHIP is typically asymptomatic, it has garnered substantial attention due to its association with the pathogenesis of multiple disease conditions, including cardiovascular disease (CVD) and hematological malignancies. In this Review, we will discuss seminal and recent studies that have advanced our understanding of mechanisms that drive selection for mutant HSPCs in the BM niche. Next, we will address recent studies evaluating potential relationships between the clonal dynamics of CHIP and hematopoietic development across the lifespan. Next, we will examine the roles of systemic factors that can influence hematopoietic stem cell (HSC) fitness, including inflammation, and exposures to cytotoxic agents in driving selection for CHIP clones. Furthermore, we will consider how - through their impact on the BM niche - lifestyle factors, including diet, exercise, and psychosocial stressors, might contribute to the process of somatic evolution in the BM that culminates in CHIP. Finally, we will review the role of old age as a major driver of selection in CHIP.
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Affiliation(s)
| | - Bridget Hoag
- Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Marco De Dominici
- Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - James DeGregori
- Division of Hematology, Department of Medicine, and
- Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
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Ma Y, Nenkov M, Chen Y, Gaßler N. The Role of Adipocytes Recruited as Part of Tumor Microenvironment in Promoting Colorectal Cancer Metastases. Int J Mol Sci 2024; 25:8352. [PMID: 39125923 PMCID: PMC11313311 DOI: 10.3390/ijms25158352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Revised: 07/15/2024] [Accepted: 07/29/2024] [Indexed: 08/12/2024] Open
Abstract
Adipose tissue dysfunction, which is associated with an increased risk of colorectal cancer (CRC), is a significant factor in the pathophysiology of obesity. Obesity-related inflammation and extracellular matrix (ECM) remodeling promote colorectal cancer metastasis (CRCM) by shaping the tumor microenvironment (TME). When CRC occurs, the metabolic symbiosis of tumor cells recruits adjacent adipocytes into the TME to supply energy. Meanwhile, abundant immune cells, from adipose tissue and blood, are recruited into the TME, which is stimulated by pro-inflammatory factors and triggers a chronic local pro-inflammatory TME. Dysregulated ECM proteins and cell surface adhesion molecules enhance ECM remodeling and further increase contractibility between tumor and stromal cells, which promotes epithelial-mesenchymal transition (EMT). EMT increases tumor migration and invasion into surrounding tissues or vessels and accelerates CRCM. Colorectal symbiotic microbiota also plays an important role in the promotion of CRCM. In this review, we provide adipose tissue and its contributions to CRC, with a special emphasis on the role of adipocytes, macrophages, neutrophils, T cells, ECM, and symbiotic gut microbiota in the progression of CRC and their contributions to the CRC microenvironment. We highlight the interactions between adipocytes and tumor cells, and potential therapeutic approaches to target these interactions.
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Affiliation(s)
| | | | | | - Nikolaus Gaßler
- Section Pathology of the Institute of Forensic Medicine, Jena University Hospital, Friedrich Schiller University Jena, Am Klinikum 1, 07747 Jena, Germany (M.N.)
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Zhang Y, Wang W. Probiotics in reducing obesity by reconfiguring the gut microbiota. ZHONG NAN DA XUE XUE BAO. YI XUE BAN = JOURNAL OF CENTRAL SOUTH UNIVERSITY. MEDICAL SCIENCES 2024; 49:1042-1051. [PMID: 39788492 PMCID: PMC11495983 DOI: 10.11817/j.issn.1672-7347.2024.240361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Indexed: 01/05/2025]
Abstract
Obesity, as a global health crisis, is increasingly linked to intestinal microecology. Probiotics colonise the body, effectively regulating the balance of intestinal flora, while strengthening the intestinal barrier, activating the immune response, releasing beneficial substances, and maintaining micro-ecological balance. This process not only enhances the defence against pathogens, but also reduces the production of inflammatory factors and lowers the level of chronic inflammation. However, the specific process and mechanism by which probiotics influence the intestinal microecology through the immune response, improve metabolic disorders caused by obesity, and participate in weight management are not clear. Through multiple neural pathways including the 'gut-brain axis' and their direct interaction with the intestine, probiotics increase the number of beneficial bacteria in the intestine and inhibit the growth of harmful bacteria, thus effectively restructuring the balance of the intestinal flora. This restructuring of the balance can optimise the intestinal environment and enhance the efficiency of food digestion and nutrient absorption. Probiotics show positive effects on obesity management by regulating the metabolic process and reducing fat accumulation, providing individuals with a new way to control body weight and prevent obesity. Therefore, the application of probiotics is of great significance in promoting gut health and weight management.
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Affiliation(s)
- Yunuo Zhang
- Department of Endocrinology, First Affiliated Hospital of Baotou Medical College, Baotou Inner Mongolia Autonomous Region 014010, China.
| | - Wei Wang
- Department of Endocrinology, First Affiliated Hospital of Baotou Medical College, Baotou Inner Mongolia Autonomous Region 014010, China.
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35
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Jamka JR, Gulbransen BD. Mechanisms of enteric neuropathy in diverse contexts of gastrointestinal dysfunction. Neurogastroenterol Motil 2024:e14870. [PMID: 39038157 DOI: 10.1111/nmo.14870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 06/11/2024] [Accepted: 07/10/2024] [Indexed: 07/24/2024]
Abstract
The enteric nervous system (ENS) commands moment-to-moment gut functions through integrative neurocircuitry housed in the gut wall. The functional continuity of ENS networks is disrupted in enteric neuropathies and contributes to major disturbances in normal gut activities including abnormal gut motility, secretions, pain, immune dysregulation, and disrupted signaling along the gut-brain axis. The conditions under which enteric neuropathy occurs are diverse and the mechanistic underpinnings are incompletely understood. The purpose of this brief review is to summarize the current understanding of the cell types involved, the conditions in which neuropathy occurs, and the mechanisms implicated in enteric neuropathy such as oxidative stress, toll like receptor signaling, purines, and pre-programmed cell death.
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Affiliation(s)
- Julia R Jamka
- Department of Physiology, Michigan State University, East Lansing, Michigan, USA
| | - Brian D Gulbransen
- Department of Physiology, Michigan State University, East Lansing, Michigan, USA
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Mpakosi A, Sokou R, Theodoraki M, Kaliouli-Antonopoulou C. Neonatal Gut Mycobiome: Immunity, Diversity of Fungal Strains, and Individual and Non-Individual Factors. Life (Basel) 2024; 14:902. [PMID: 39063655 PMCID: PMC11278438 DOI: 10.3390/life14070902] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Revised: 07/11/2024] [Accepted: 07/18/2024] [Indexed: 07/28/2024] Open
Abstract
The human gastrointestinal ecosystem, or microbiome (comprising the total bacterial genome in an environment), plays a crucial role in influencing host physiology, immune function, metabolism, and the gut-brain axis. While bacteria, fungi, viruses, and archaea are all present in the gastrointestinal ecosystem, research on the human microbiome has predominantly focused on the bacterial component. The colonization of the human intestine by microbes during the first two years of life significantly impacts subsequent composition and diversity, influencing immune system development and long-term health. Early-life exposure to pathogens is crucial for establishing immunological memory and acquired immunity. Factors such as maternal health habits, delivery mode, and breastfeeding duration contribute to gut dysbiosis. Despite fungi's critical role in health, particularly for vulnerable newborns, research on the gut mycobiome in infants and children remains limited. Understanding early-life factors shaping the gut mycobiome and its interactions with other microbial communities is a significant research challenge. This review explores potential factors influencing the gut mycobiome, microbial kingdom interactions, and their connections to health outcomes from childhood to adulthood. We identify gaps in current knowledge and propose future research directions in this complex field.
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Affiliation(s)
- Alexandra Mpakosi
- Department of Microbiology, General Hospital of Nikaia “Agios Panteleimon”, 18454 Piraeus, Greece
| | - Rozeta Sokou
- Neonatal Intensive Care Unit, General Hospital of Nikaia “Agios Panteleimon”, 18454 Piraeus, Greece;
- Neonatal Department, National and Kapodistrian University of Athens, Aretaieio Hospital, 11528 Athens, Greece
| | - Martha Theodoraki
- Neonatal Intensive Care Unit, General Hospital of Nikaia “Agios Panteleimon”, 18454 Piraeus, Greece;
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Harvei S, Skogen V, Egelandsdal B, Birkeland S, Paulsen JE, Carlsen H. Chronic oral LPS administration does not increase inflammation or induce metabolic dysregulation in mice fed a western-style diet. Front Nutr 2024; 11:1376493. [PMID: 39077160 PMCID: PMC11284168 DOI: 10.3389/fnut.2024.1376493] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Accepted: 06/25/2024] [Indexed: 07/31/2024] Open
Abstract
Introduction Lipopolysaccharides (LPS) present in the intestine are suggested to enter the bloodstream after consumption of high-fat diets and cause systemic inflammation and metabolic dysregulation through a process named "metabolic endotoxemia." This study aimed to determine the role of orally administered LPS to mice in the early stage of chronic low-grade inflammation induced by diet. Methods We supplemented the drinking water with E. coli derived LPS to mice fed either high-fat Western-style diet (WSD) or standard chow (SC) for 7 weeks (n = 16-17). Body weight was recorded weekly. Systemic inflammatory status was assessed by in vivo imaging of NF-κB activity at different time points, and glucose dysregulation was assessed by insulin sensitivity test and glucose tolerance test near the end of the study. Systemic LPS exposure was estimated indirectly via quantification of LPS-binding protein (LBP) and antibodies against LPS in plasma, and directly using an LPS-sensitive cell reporter assay. Results and discussion Our results demonstrate that weight development and glucose regulation are not affected by LPS. We observed a transient LPS dependent upregulation of NF-κB activity in the liver region in both diet groups, a response that disappeared within the first week of LPS administration and remained low during the rest of the study. However, WSD fed mice had overall a higher NF-κB activity compared to SC fed mice at all time points independent of LPS administration. Our findings indicate that orally administered LPS has limited to no impact on systemic inflammation and metabolic dysregulation in mice fed a high-fat western diet and we question the capability of intestinally derived LPS to initiate systemic inflammation through a healthy and uncompromised intestine, even when exposed to a high-fat diet.
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Affiliation(s)
- Silje Harvei
- Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, As, Norway
| | - Vemund Skogen
- Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, As, Norway
| | - Bjørg Egelandsdal
- Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, As, Norway
| | - Signe Birkeland
- Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, As, Norway
| | - Jan Erik Paulsen
- Faculty of Veterinary Medicine, Norwegian University of Life Sciences, As, Norway
| | - Harald Carlsen
- Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, As, Norway
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38
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Kim JY, Jang S, Song HJ, Lee S, Cheon S, Seo EJ, Choi YH, Kim SH. Sargassum horneri extract fermented by Lactiplantibacillus pentosus SH803 mediates adipocyte metabolism in 3T3-L1 preadipocytes by regulating oxidative damage and inflammation. Sci Rep 2024; 14:15064. [PMID: 38956395 PMCID: PMC11220060 DOI: 10.1038/s41598-024-65956-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2024] [Accepted: 06/25/2024] [Indexed: 07/04/2024] Open
Abstract
Sargassum horneri (S. horneri), a brown seaweed excessively proliferating along Asian coastlines, are damaging marine ecosystems. Thus, this study aimed to enhance nutritional value of S. horneri through lactic acid bacteria fermentation to increase S. horneri utilization as a functional food supplement, and consequently resolve coastal S. horneri accumulation. S. horneri supplemented fermentation was most effective with Lactiplantibacillus pentosus SH803, thus this product (F-SHWE) was used for further in vitro studies. F-SHWE normalized expressions of oxidative stress related genes NF-κB, p53, BAX, cytochrome C, caspase 9, and caspase 3, while non-fermented S. horneri (SHWE) did not, in a H2O2-induced HT-29 cell model. Moreover, in an LPS-induced HT-29 cell model, F-SHWE repaired expressions of inflammation marker genes ZO1, IL1β, IFNγ more effectively than SHWE. For further functional assessment, F-SHWE was also treated in 3T3-L1 adipocytes. As a result, F-SHWE decreased lipid accumulation, along with gene expression of adipogenesis markers PPARγ, C/EBPα, C/EBPβ, aP2, and Lpl; lipogenesis markers Lep, Akt, SREBP1, Acc, Fas; inflammation markers IFN-γ and NF-κB. Notably, gene expression of C/EBPβ, IFN-γ and NF-κB were suppressed only by F-SHWE, suggesting the enhancing effect of fermentation on obesity-related properties. Compositional analysis attributed the protective effects of F-SHWE to acetate, an organic acid significantly higher in F-SHWE than SHWE. Therefore, F-SHWE is a novel potential anti-obesity agent, providing a strategy to reduce excess S. horneri populations along marine ecosystems.
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Affiliation(s)
- Jae-Young Kim
- College of Life Science and Biotechnology East Building, Korea University, 145, Anam-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea
- Institute of Life Science and Natural Resources, Korea University, Seoul, 02841, Republic of Korea
| | - Sejin Jang
- College of Life Science and Biotechnology East Building, Korea University, 145, Anam-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea
| | - Hyun Ji Song
- College of Life Science and Biotechnology East Building, Korea University, 145, Anam-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea
| | - SangHoon Lee
- College of Life Science and Biotechnology East Building, Korea University, 145, Anam-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea
| | - Sejin Cheon
- College of Life Science and Biotechnology East Building, Korea University, 145, Anam-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea
| | - Eun Jin Seo
- College of Life Science and Biotechnology East Building, Korea University, 145, Anam-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea
| | - Yi Hyun Choi
- College of Life Science and Biotechnology East Building, Korea University, 145, Anam-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea
| | - Sae Hun Kim
- College of Life Science and Biotechnology East Building, Korea University, 145, Anam-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea.
- Institute of Life Science and Natural Resources, Korea University, Seoul, 02841, Republic of Korea.
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39
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Baek JS, Lee DY, Han SW, Kim DH. A probiotic NVP1704 alleviates stress-induced sleeplessness/depression-like symptoms in mice by upregulating serotonergic and GABAergic systems and downregulating NF-κB activation. Lett Appl Microbiol 2024; 77:ovae065. [PMID: 38977897 DOI: 10.1093/lambio/ovae065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 06/30/2024] [Accepted: 07/04/2024] [Indexed: 07/10/2024]
Abstract
Sleeplessness (insomnia) is a potential symptom of depression. A probiotic NVP1704 alleviates depression-like behavior and neuroinflammation in mice. Therefore, to understand whether NVP1704 could be effective against sleeplessness in vivo, we exposed immobilization stress (IS) in mice, then orally administered NVP1704 for 5 days, and assayed depression/anxiety-like behavior in the open field, elevated plus maze, and tail suspension tests, sleeping latency time, and sleep duration, euthanized then by exposure to CO2, and analyzed their related biomarkers. Oral administration of NVP1704 decreased IS-induced depression/anxiety-like behavior and sleeping latency time and increased IS-suppressed sleeping duration. NVP1704 increased IS-suppressed expression of γ-aminobutyric acid (GABA), GABAA receptor α1 (GABAARα1) and α2 subunits (GABAARα2), serotonin, 5-HT receptors (5-HT1AR and 5-HT1BR), and melatonin receptors (MT1R and MT2R) in the prefrontal cortex and thalamus. NVP1704 also increased the IS-suppressed GABAARα1-positive cell population in the prefrontal cortex and decreased IS-induced corticosterone, TNF-α, and IL-6 expression and the NF-κB+Iba1+ cell population in the brain and myeloperoxidase, TNF-α, and IL-6 expression and the NF-κB+CD11c+ cell population in the colon. Based on these findings, NVP1704 may alleviate depression/anxiety/sleeplessness-like behaviors through the upregulation of serotonergic and GABAergic systems and downregulation of NF-κB activation.
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Affiliation(s)
- Ji-Su Baek
- Neurobiota Research Center, College of Pharmacy, Kyung Hee University, Dongdaemun-gu, Seoul 02447, Korea
| | - Dong-Yun Lee
- Neurobiota Research Center, College of Pharmacy, Kyung Hee University, Dongdaemun-gu, Seoul 02447, Korea
| | - Seung-Won Han
- PB Department, NVP Healthcare, Inc., Suwon 16209, Korea
| | - Dong-Hyun Kim
- Neurobiota Research Center, College of Pharmacy, Kyung Hee University, Dongdaemun-gu, Seoul 02447, Korea
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Jain H, Kumar A, Almousa S, Mishra S, Langsten KL, Kim S, Sharma M, Su Y, Singh S, Kerr BA, Deep G. Characterisation of LPS+ bacterial extracellular vesicles along the gut-hepatic portal vein-liver axis. J Extracell Vesicles 2024; 13:e12474. [PMID: 39001704 PMCID: PMC11245684 DOI: 10.1002/jev2.12474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2024] [Accepted: 06/10/2024] [Indexed: 07/15/2024] Open
Abstract
Gut microbiome dysbiosis is a major contributing factor to several pathological conditions. However, the mechanistic understanding of the communication between gut microbiota and extra-intestinal organs remains largely elusive. Extracellular vesicles (EVs), secreted by almost every form of life, including bacteria, could play a critical role in this inter-kingdom crosstalk and are the focus of present study. Here, we present a novel approach for isolating lipopolysaccharide (LPS)+ bacterial extracellular vesicles (bEVLPS) from complex biological samples, including faeces, plasma and the liver from lean and diet-induced obese (DIO) mice. bEVLPS were extensively characterised using nanoparticle tracking analyses, immunogold labelling coupled with transmission electron microscopy, flow cytometry, super-resolution microscopy and 16S sequencing. In liver tissues, the protein expressions of TLR4 and a few macrophage-specific biomarkers were assessed by immunohistochemistry, and the gene expressions of inflammation-related cytokines and their receptors (n = 89 genes) were measured using a PCR array. Faecal samples from DIO mice revealed a remarkably lower concentration of total EVs but a significantly higher percentage of LPS+ EVs. Interestingly, DIO faecal bEVLPS showed a higher abundance of Proteobacteria by 16S sequencing. Importantly, in DIO mice, a higher number of total EVs and bEVLPS consistently entered the hepatic portal vein and subsequently reached the liver, associated with increased expression of TLR4, macrophage markers (F4/80, CD86 and CD206), cytokines and receptors (Il1rn, Ccr1, Cxcl10, Il2rg and Ccr2). Furthermore, a portion of bEVLPS escaped liver and entered the peripheral circulation. In conclusion, bEV could be the key mediator orchestrating various well-established biological effects induced by gut bacteria on distant organs.
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Affiliation(s)
- Heetanshi Jain
- Department of Cancer BiologyWake Forest University School of MedicineWinston‐SalemNorth CarolinaUSA
| | - Ashish Kumar
- Department of Cancer BiologyWake Forest University School of MedicineWinston‐SalemNorth CarolinaUSA
| | - Sameh Almousa
- Department of Cancer BiologyWake Forest University School of MedicineWinston‐SalemNorth CarolinaUSA
| | - Shalini Mishra
- Department of Cancer BiologyWake Forest University School of MedicineWinston‐SalemNorth CarolinaUSA
| | - Kendall L. Langsten
- Department of Cancer BiologyWake Forest University School of MedicineWinston‐SalemNorth CarolinaUSA
| | - Susy Kim
- Department of Cancer BiologyWake Forest University School of MedicineWinston‐SalemNorth CarolinaUSA
| | - Mitu Sharma
- Department of Cancer BiologyWake Forest University School of MedicineWinston‐SalemNorth CarolinaUSA
| | - Yixin Su
- Department of Cancer BiologyWake Forest University School of MedicineWinston‐SalemNorth CarolinaUSA
| | - Sangeeta Singh
- Department of Cancer BiologyWake Forest University School of MedicineWinston‐SalemNorth CarolinaUSA
| | - Bethany A. Kerr
- Department of Cancer BiologyWake Forest University School of MedicineWinston‐SalemNorth CarolinaUSA
- Atrium Health Wake Forest Baptist Comprehensive Cancer CenterWinston‐SalemNorth CarolinaUSA
| | - Gagan Deep
- Department of Cancer BiologyWake Forest University School of MedicineWinston‐SalemNorth CarolinaUSA
- Atrium Health Wake Forest Baptist Comprehensive Cancer CenterWinston‐SalemNorth CarolinaUSA
- Department of Internal Medicine‐Gerontology and Geriatric MedicineWake Forest University School of MedicineWinston‐SalemNorth CarolinaUSA
- Sticht Center for Healthy Aging and Alzheimer's PreventionWake Forest University School of MedicineWinston‐SalemNorth CarolinaUSA
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41
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Shantaram D, Hoyd R, Blaszczak AM, Antwi L, Jalilvand A, Wright VP, Liu J, Smith AJ, Bradley D, Lafuse W, Liu Y, Williams NF, Snyder O, Wheeler C, Needleman B, Brethauer S, Noria S, Renton D, Perry KA, Nagareddy P, Wozniak D, Mahajan S, Rana PSJB, Pietrzak M, Schlesinger LS, Spakowicz DJ, Hsueh WA. Obesity-associated microbiomes instigate visceral adipose tissue inflammation by recruitment of distinct neutrophils. Nat Commun 2024; 15:5434. [PMID: 38937454 PMCID: PMC11211470 DOI: 10.1038/s41467-024-48935-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 05/17/2024] [Indexed: 06/29/2024] Open
Abstract
Neutrophils are increasingly implicated in chronic inflammation and metabolic disorders. Here, we show that visceral adipose tissue (VAT) from individuals with obesity contains more neutrophils than in those without obesity and is associated with a distinct bacterial community. Exploring the mechanism, we gavaged microbiome-depleted mice with stool from patients with and without obesity during high-fat or normal diet administration. Only mice receiving high-fat diet and stool from subjects with obesity show enrichment of VAT neutrophils, suggesting donor microbiome and recipient diet determine VAT neutrophilia. A rise in pro-inflammatory CD4+ Th1 cells and a drop in immunoregulatory T cells in VAT only follows if there is a transient spike in neutrophils. Human VAT neutrophils exhibit a distinct gene expression pattern that is found in different human tissues, including tumors. VAT neutrophils and bacteria may be a novel therapeutic target for treating inflammatory-driven complications of obesity, including insulin resistance and colon cancer.
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Affiliation(s)
- Dharti Shantaram
- Diabetes and Metabolism Research Center, Division of Endocrinology, Diabetes & Metabolism, Department of Internal Medicine, Wexner Medical Center at The Ohio State University, Columbus, OH, 43210, USA
| | - Rebecca Hoyd
- Pelotonia Institute for Immuno-Oncology at The Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH, 43210, USA
| | - Alecia M Blaszczak
- Diabetes and Metabolism Research Center, Division of Endocrinology, Diabetes & Metabolism, Department of Internal Medicine, Wexner Medical Center at The Ohio State University, Columbus, OH, 43210, USA
| | - Linda Antwi
- Pelotonia Institute for Immuno-Oncology at The Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH, 43210, USA
| | - Anahita Jalilvand
- Diabetes and Metabolism Research Center, Division of Endocrinology, Diabetes & Metabolism, Department of Internal Medicine, Wexner Medical Center at The Ohio State University, Columbus, OH, 43210, USA
| | - Valerie P Wright
- Diabetes and Metabolism Research Center, Division of Endocrinology, Diabetes & Metabolism, Department of Internal Medicine, Wexner Medical Center at The Ohio State University, Columbus, OH, 43210, USA
| | - Joey Liu
- Diabetes and Metabolism Research Center, Division of Endocrinology, Diabetes & Metabolism, Department of Internal Medicine, Wexner Medical Center at The Ohio State University, Columbus, OH, 43210, USA
| | - Alan J Smith
- Diabetes and Metabolism Research Center, Division of Endocrinology, Diabetes & Metabolism, Department of Internal Medicine, Wexner Medical Center at The Ohio State University, Columbus, OH, 43210, USA
| | - David Bradley
- Diabetes and Metabolism Research Center, Division of Endocrinology, Diabetes & Metabolism, Department of Internal Medicine, Wexner Medical Center at The Ohio State University, Columbus, OH, 43210, USA
| | - William Lafuse
- Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, 43210, USA
| | - YunZhou Liu
- Pelotonia Institute for Immuno-Oncology at The Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH, 43210, USA
| | - Nyelia F Williams
- Pelotonia Institute for Immuno-Oncology at The Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH, 43210, USA
| | - Owen Snyder
- Pelotonia Institute for Immuno-Oncology at The Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH, 43210, USA
| | - Caroline Wheeler
- Pelotonia Institute for Immuno-Oncology at The Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH, 43210, USA
| | - Bradley Needleman
- Center for Minimally Invasive Surgery, Department of General Surgery, The Ohio State University, Columbus, OH, 43210, USA
| | - Stacy Brethauer
- Center for Minimally Invasive Surgery, Department of General Surgery, The Ohio State University, Columbus, OH, 43210, USA
| | - Sabrena Noria
- Center for Minimally Invasive Surgery, Department of General Surgery, The Ohio State University, Columbus, OH, 43210, USA
| | - David Renton
- Center for Minimally Invasive Surgery, Department of General Surgery, The Ohio State University, Columbus, OH, 43210, USA
| | - Kyle A Perry
- Center for Minimally Invasive Surgery, Department of General Surgery, The Ohio State University, Columbus, OH, 43210, USA
| | - Prabha Nagareddy
- Department of Internal Medicine, Cardiovascular Section University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, OK, 73117, USA
| | - Daniel Wozniak
- Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, 43210, USA
| | - Sahil Mahajan
- Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, 43210, USA
| | - Pranav S J B Rana
- Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, 43210, USA
| | - Maciej Pietrzak
- Department of Biomedical Informatics, The Ohio State University, Columbus, OH, 43210, USA
| | - Larry S Schlesinger
- Host Pathogen Interactions Program, Texas Biomedical Research Institute, San Antonio, TX, 78227, USA
| | - Daniel J Spakowicz
- Pelotonia Institute for Immuno-Oncology at The Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH, 43210, USA.
| | - Willa A Hsueh
- Diabetes and Metabolism Research Center, Division of Endocrinology, Diabetes & Metabolism, Department of Internal Medicine, Wexner Medical Center at The Ohio State University, Columbus, OH, 43210, USA.
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Manzo R, Gallardo-Becerra L, Díaz de León-Guerrero S, Villaseñor T, Cornejo-Granados F, Salazar-León J, Ochoa-Leyva A, Pedraza-Alva G, Pérez-Martínez L. Environmental Enrichment Prevents Gut Dysbiosis Progression and Enhances Glucose Metabolism in High-Fat Diet-Induced Obese Mice. Int J Mol Sci 2024; 25:6904. [PMID: 39000013 PMCID: PMC11241766 DOI: 10.3390/ijms25136904] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Revised: 06/01/2024] [Accepted: 06/10/2024] [Indexed: 07/14/2024] Open
Abstract
Obesity is a global health concern implicated in numerous chronic degenerative diseases, including type 2 diabetes, dyslipidemia, and neurodegenerative disorders. It is characterized by chronic low-grade inflammation, gut microbiota dysbiosis, insulin resistance, glucose intolerance, and lipid metabolism disturbances. Here, we investigated the therapeutic potential of environmental enrichment (EE) to prevent the progression of gut dysbiosis in mice with high-fat diet (HFD)-induced metabolic syndrome. C57BL/6 male mice with obesity and metabolic syndrome, continuously fed with an HFD, were exposed to EE. We analyzed the gut microbiota of the mice by sequencing the 16s rRNA gene at different intervals, including on day 0 and 12 and 24 weeks after EE exposure. Fasting glucose levels, glucose tolerance, insulin resistance, food intake, weight gain, lipid profile, hepatic steatosis, and inflammatory mediators were evaluated in serum, adipose tissue, and the colon. We demonstrate that EE intervention prevents the progression of HFD-induced dysbiosis, reducing taxa associated with metabolic syndrome (Tepidimicrobium, Acidaminobacteraceae, and Fusibacter) while promoting those linked to healthy physiology (Syntrophococcus sucrumutans, Dehalobacterium, Prevotella, and Butyricimonas). Furthermore, EE enhances intestinal barrier integrity, increases mucin-producing goblet cell population, and upregulates Muc2 expression in the colon. These alterations correlate with reduced systemic lipopolysaccharide levels and attenuated colon inflammation, resulting in normalized glucose metabolism, diminished adipose tissue inflammation, reduced liver steatosis, improved lipid profiles, and a significant reduction in body weight gain despite mice's continued HFD consumption. Our findings highlight EE as a promising anti-inflammatory strategy for managing obesity-related metabolic dysregulation and suggest its potential in developing probiotics targeting EE-modulated microbial taxa.
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Affiliation(s)
- Rubiceli Manzo
- Laboratorio de Neuroinmunobiología, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca 62210, Morelos, Mexico
| | - Luigui Gallardo-Becerra
- Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca 62210, Morelos, Mexico
| | - Sol Díaz de León-Guerrero
- Laboratorio de Neuroinmunobiología, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca 62210, Morelos, Mexico
| | - Tomas Villaseñor
- Laboratorio de Neuroinmunobiología, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca 62210, Morelos, Mexico
| | - Fernanda Cornejo-Granados
- Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca 62210, Morelos, Mexico
| | - Jonathan Salazar-León
- Laboratorio de Neuroinmunobiología, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca 62210, Morelos, Mexico
| | - Adrian Ochoa-Leyva
- Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca 62210, Morelos, Mexico
| | - Gustavo Pedraza-Alva
- Laboratorio de Neuroinmunobiología, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca 62210, Morelos, Mexico
| | - Leonor Pérez-Martínez
- Laboratorio de Neuroinmunobiología, Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca 62210, Morelos, Mexico
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Averina OV, Poluektova EU, Zorkina YA, Kovtun AS, Danilenko VN. Human Gut Microbiota for Diagnosis and Treatment of Depression. Int J Mol Sci 2024; 25:5782. [PMID: 38891970 PMCID: PMC11171505 DOI: 10.3390/ijms25115782] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Revised: 05/21/2024] [Accepted: 05/23/2024] [Indexed: 06/21/2024] Open
Abstract
Nowadays, depressive disorder is spreading rapidly all over the world. Therefore, attention to the studies of the pathogenesis of the disease in order to find novel ways of early diagnosis and treatment is increasing among the scientific and medical communities. Special attention is drawn to a biomarker and therapeutic strategy through the microbiota-gut-brain axis. It is known that the symbiotic interactions between the gut microbes and the host can affect mental health. The review analyzes the mechanisms and ways of action of the gut microbiota on the pathophysiology of depression. The possibility of using knowledge about the taxonomic composition and metabolic profile of the microbiota of patients with depression to select gene compositions (metagenomic signature) as biomarkers of the disease is evaluated. The use of in silico technologies (machine learning) for the diagnosis of depression based on the biomarkers of the gut microbiota is given. Alternative approaches to the treatment of depression are being considered by balancing the microbial composition through dietary modifications and the use of additives, namely probiotics, postbiotics (including vesicles) and prebiotics as psychobiotics, and fecal transplantation. The bacterium Faecalibacterium prausnitzii is under consideration as a promising new-generation probiotic and auxiliary diagnostic biomarker of depression. The analysis conducted in this review may be useful for clinical practice and pharmacology.
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Affiliation(s)
- Olga V. Averina
- Vavilov Institute of General Genetics, Russian Academy of Sciences (RAS), 119333 Moscow, Russia; (E.U.P.); (Y.A.Z.); (A.S.K.); (V.N.D.)
| | - Elena U. Poluektova
- Vavilov Institute of General Genetics, Russian Academy of Sciences (RAS), 119333 Moscow, Russia; (E.U.P.); (Y.A.Z.); (A.S.K.); (V.N.D.)
| | - Yana A. Zorkina
- Vavilov Institute of General Genetics, Russian Academy of Sciences (RAS), 119333 Moscow, Russia; (E.U.P.); (Y.A.Z.); (A.S.K.); (V.N.D.)
- V. Serbsky National Medical Research Centre of Psychiatry and Narcology, Kropotkinsky per. 23, 119034 Moscow, Russia
- Mental-Health Clinic No. 1 Named after N.A. Alekseev, Zagorodnoe Highway 2, 115191 Moscow, Russia
| | - Alexey S. Kovtun
- Vavilov Institute of General Genetics, Russian Academy of Sciences (RAS), 119333 Moscow, Russia; (E.U.P.); (Y.A.Z.); (A.S.K.); (V.N.D.)
| | - Valery N. Danilenko
- Vavilov Institute of General Genetics, Russian Academy of Sciences (RAS), 119333 Moscow, Russia; (E.U.P.); (Y.A.Z.); (A.S.K.); (V.N.D.)
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Qiu Y, Song B, Xie M, Tao Y, Yin Z, Wang M, Ma C, Chen Z, Wang Z. Causal links between gut microbiomes, cytokines and risk of different subtypes of epilepsy: a Mendelian randomization study. Front Neurosci 2024; 18:1397430. [PMID: 38855442 PMCID: PMC11157073 DOI: 10.3389/fnins.2024.1397430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Accepted: 05/13/2024] [Indexed: 06/11/2024] Open
Abstract
Objective Recent research suggests a potential link between the gut microbiome (GM) and epilepsy. We undertook a Mendelian randomization (MR) study to determine the possible causal influence of GM on epilepsy and its various subtypes, and explore whether cytokines act as mediators. Methods We utilized Genome-Wide Association Study (GWAS) summary statistics to examine the causal relationships between GM, cytokines, and four epilepsy subtypes. Furthermore, we assessed whether cytokines mediate the relationship between GM and epilepsy. Significant GMs were further investigated using transcriptomic MR analysis with genes mapped from the FUMA GWAS. Sensitivity analyses and reverse MR were conducted for validation, and false discovery rate (FDR) correction was applied for multiple comparisons. Results We pinpointed causal relationships between 30 GMs and various epilepsy subtypes. Notably, the Family Veillonellaceae (OR:1.03, 95%CI:1.02-1.05, p = 0.0003) consistently showed a strong positive association with child absence epilepsy, and this causal association endured even after FDR correction (p-FDR < 0.05). Seven cytokines were significantly associated with epilepsy and its subtypes. A mediating role for cytokines has not been demonstrated. Sensitivity tests validated the primary MR analysis outcomes. Additionally, no reverse causality was detected between significant GMs and epilepsy. Of the mapped genes of notable GMs, genes like BLK, FDFT1, DOK2, FAM167A, ZSCAN9, RNGTT, RBM47, DNAJC21, SUMF1, TCF20, GLO1, TMTC1, VAV2, and RNF14 exhibited a profound correlation with the risk factors of epilepsy subtypes. Conclusion Our research validates the causal role of GMs and cytokines in various epilepsy subtypes, and there has been no evidence that cytokines play a mediating role between GM and epilepsy. This could provide fresh perspectives for the prevention and treatment of epilepsy.
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Affiliation(s)
- Youjia Qiu
- Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Bingyi Song
- Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Minjia Xie
- Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Yuchen Tao
- Suzhou Medical College of Soochow University, Suzhou, China
| | - Ziqian Yin
- Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Menghan Wang
- Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Chao Ma
- Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Zhouqing Chen
- Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Zhong Wang
- Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, China
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Kropp DR, Rainville JR, Glover ME, Tsyglakova M, Samanta R, Hage TR, Carlson AE, Clinton SM, Hodes GE. Chronic variable stress leads to sex specific gut microbiome alterations in mice. Brain Behav Immun Health 2024; 37:100755. [PMID: 38618010 PMCID: PMC11010943 DOI: 10.1016/j.bbih.2024.100755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 03/17/2024] [Indexed: 04/16/2024] Open
Abstract
Stress has been implicated in the incidence and severity of psychiatric and gastrointestinal disorders. The immune system is capable of modulating the activity and composition of the gut following stress and vice versa. In this study we sought to examine the sequential relationship between immune signaling and microbiome composition occurring in male and female mice over time using a variable stress paradigm. Tissue was collected prior to, during, and after the stress paradigm from the same mice. Cytokines from plasma and brain were quantified using a multiplexed cytokine assay. Fecal samples were collected at the same timepoints and 16S rRNA amplicon sequencing was performed to determine the relative abundance of microbiota residing in the guts of stressed and control mice. We found sex differences in the response of the gut microbiota to stress following 28 days of chronic variable stress but not 6 days of sub-chronic variable stress. Immune activation was quantified in the nucleus accumbens immediately following Sub-chronic variable when alterations of gut composition had not yet occurred. In both sexes, 28 days of stress induced significant changes in the proportion of Erysipelotrichaceae and Lactobacillaceae, but in opposite directions for male and female mice. Alterations to the gut microbiome in both sexes were associated with changes in cytokines related to eosinophilic immune activity. Our use of an animal stress model reveals the immune mechanisms that may underly changes in gut microbiome composition during and after stress. This study reveals potential drug targets and microbiota of interest for the intervention of stress related conditions.
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Affiliation(s)
- Dawson R. Kropp
- School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA
| | - Jennifer R. Rainville
- School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA
| | - Matthew E. Glover
- School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA
| | - Mariya Tsyglakova
- School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA
| | - Rupabali Samanta
- School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA
| | - Tamer R. Hage
- School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA
| | - Audrey E. Carlson
- School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA
| | - Sarah M. Clinton
- School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA
| | - Georgia E. Hodes
- School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA
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Fromm E, Zinger L, Pellerin F, Di Gesu L, Jacob S, Winandy L, Aguilée R, Parthuisot N, Iribar A, White J, Bestion E, Cote J. Warming effects on lizard gut microbiome depend on habitat connectivity. Proc Biol Sci 2024; 291:20240220. [PMID: 38654642 PMCID: PMC11040258 DOI: 10.1098/rspb.2024.0220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Accepted: 03/21/2024] [Indexed: 04/26/2024] Open
Abstract
Climate warming and landscape fragmentation are both factors well known to threaten biodiversity and to generate species responses and adaptation. However, the impact of warming and fragmentation interplay on organismal responses remains largely under-explored, especially when it comes to gut symbionts, which may play a key role in essential host functions and traits by extending its functional and genetic repertoire. Here, we experimentally examined the combined effects of climate warming and habitat connectivity on the gut bacterial communities of the common lizard (Zootoca vivipara) over three years. While the strength of effects varied over the years, we found that a 2°C warmer climate decreases lizard gut microbiome diversity in isolated habitats. However, enabling connectivity among habitats with warmer and cooler climates offset or even reversed warming effects. The warming effects and the association between host dispersal behaviour and microbiome diversity appear to be a potential driver of this interplay. This study suggests that preserving habitat connectivity will play a key role in mitigating climate change impacts, including the diversity of the gut microbiome, and calls for more studies combining multiple anthropogenic stressors when predicting the persistence of species and communities through global changes.
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Affiliation(s)
- Emma Fromm
- Centre de Recherche sur la Biodiversité et l'Environnement (CRBE), Université de Toulouse, CNRS, IRD, Toulouse INP, Université Toulouse 3 – Paul Sabatier (UT3), Toulouse, France
| | - Lucie Zinger
- Institut de Biologie de l'ENS (IBENS), Département de biologie, École normale supérieure, CNRS, INSERM, Université PSL, Paris, France
- Instituto Tecnológico Vale, Rua Boaventura da Silva 955, 66055-090, Belém, Pará, Brazil
| | - Félix Pellerin
- Centre de Recherche sur la Biodiversité et l'Environnement (CRBE), Université de Toulouse, CNRS, IRD, Toulouse INP, Université Toulouse 3 – Paul Sabatier (UT3), Toulouse, France
| | - Lucie Di Gesu
- Station d'Écologie Théorique et Expérimentale (SETE), UAR2029, CNRS, Moulis, France
| | - Staffan Jacob
- Station d'Écologie Théorique et Expérimentale (SETE), UAR2029, CNRS, Moulis, France
| | - Laurane Winandy
- Centre de Recherche sur la Biodiversité et l'Environnement (CRBE), Université de Toulouse, CNRS, IRD, Toulouse INP, Université Toulouse 3 – Paul Sabatier (UT3), Toulouse, France
- High Fens Scientific Station, Freshwater and Oceanic Science Unit of Research (FOCUS), University of Liege, Liege, Belgium
| | - Robin Aguilée
- Centre de Recherche sur la Biodiversité et l'Environnement (CRBE), Université de Toulouse, CNRS, IRD, Toulouse INP, Université Toulouse 3 – Paul Sabatier (UT3), Toulouse, France
| | - Nathalie Parthuisot
- Centre de Recherche sur la Biodiversité et l'Environnement (CRBE), Université de Toulouse, CNRS, IRD, Toulouse INP, Université Toulouse 3 – Paul Sabatier (UT3), Toulouse, France
| | - Amaia Iribar
- Centre de Recherche sur la Biodiversité et l'Environnement (CRBE), Université de Toulouse, CNRS, IRD, Toulouse INP, Université Toulouse 3 – Paul Sabatier (UT3), Toulouse, France
| | - Joël White
- Centre de Recherche sur la Biodiversité et l'Environnement (CRBE), Université de Toulouse, CNRS, IRD, Toulouse INP, Université Toulouse 3 – Paul Sabatier (UT3), Toulouse, France
- École Nationale Supérieure de Formation de l'Enseignement Agricole, 2 Route de Narbonne, 31320 Castanet-Tolosan, France
| | - Elvire Bestion
- Station d'Écologie Théorique et Expérimentale (SETE), UAR2029, CNRS, Moulis, France
| | - Julien Cote
- Centre de Recherche sur la Biodiversité et l'Environnement (CRBE), Université de Toulouse, CNRS, IRD, Toulouse INP, Université Toulouse 3 – Paul Sabatier (UT3), Toulouse, France
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Choi SI, Kim N, Choi Y, Nam RH, Jang JY, Cho SY. The Effect of Clostridium butyricum on Gut Microbial Changes and Functional Profiles of Metabolism in High-fat Diet-fed Rats Depending on Age and Sex. J Neurogastroenterol Motil 2024; 30:236-250. [PMID: 38576373 PMCID: PMC10999835 DOI: 10.5056/jnm23096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 10/24/2023] [Accepted: 11/16/2023] [Indexed: 04/06/2024] Open
Abstract
Background/Aims A high-fat diet (HFD) causes dysbiosis and promotes inflammatory responses in the colon. This study aims to evaluate the effects of Clostridium butyricum on HFD-induced gut microbial changes in rats. Methods Six-week-old Fischer-344 rats with both sexes were given a control or HFD during 8 weeks, and 1-to-100-fold diluted Clostridium butyricum were administered by gavage. Fecal microbiota analyses were conducted using 16S ribosomal RNA metagenomic sequencing and predictive functional profiling of microbial communities in metabolism. Results A significant increase in Ruminococcaceae and Lachnospiraceae, which are butyric acid-producing bacterial families, was observed in the probiotics groups depending on sex. In contrast, Akkermansia muciniphila, which increased through a HFD regardless of sex, and decreased in the probiotics groups. A. muciniphila positively correlated with Claudin-1 expression in males (P < 0.001) and negatively correlated with the expression of Claudin-2 (P = 0.042), IL-1β (P = 0.037), and IL-6 (P = 0.044) in females. In terms of functional analyses, a HFD decreased the relative abundances of M00131 (carbohydrate metabolism module), M00579, and M00608 (energy metabolism), and increased those of M00307 (carbohydrate metabolism), regardless of sex. However, these changes recovered especially in male C. butyricum groups. Furthermore, M00131, M00579, and M00608 showed a positive correlation and M00307 showed a negative correlation with the relative abundance of A. muciniphila (P < 0.001). Conclusion The beneficial effects of C. butyricum on HFD-induced gut dysbiosis in young male rats originate from the functional profiles of carbohydrate and energy metabolism.
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Affiliation(s)
- Soo In Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Yonghoon Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea
| | - Ryoung Hee Nam
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea
| | - Jae Young Jang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea
- Department of Medical Device Development, Seoul National University College of Medicine, Seoul, Korea
| | - Sung-Yup Cho
- Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea
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48
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Wang J, Gu J, Yi J, Li J, Li W, Zhai Z. High-fat diets induce inflammatory IMD/NFκB signaling via gut microbiota remodeling in Drosophila. Front Cell Infect Microbiol 2024; 14:1347716. [PMID: 38716198 PMCID: PMC11074423 DOI: 10.3389/fcimb.2024.1347716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Accepted: 04/02/2024] [Indexed: 06/05/2024] Open
Abstract
High-fat diets (HFDs), a prevailing daily dietary style worldwide, induce chronic low-grade inflammation in the central nervous system and peripheral tissues, promoting a variety of diseases including pathologies associated with neuroinflammation. However, the mechanisms linking HFDs to inflammation are not entirely clear. Here, using a Drosophila HFD model, we explored the mechanism of HFD-induced inflammation in remote tissues. We found that HFDs activated the IMD/NFκB immune pathway in the head through remodeling of the commensal gut bacteria. Removal of gut microbiota abolished such HFD-induced remote inflammatory response. Further experiments revealed that HFDs significantly increased the abundance of Acetobacter malorum in the gut, and the re-association of this bacterium was sufficient to elicit inflammatory response in remote tissues. Mechanistically, Acetobacter malorum produced a greater amount of peptidoglycan (PGN), a well-defined microbial molecular pattern that enters the circulation and remotely activates an inflammatory response. Our results thus show that HFDs trigger inflammation mediated by a bacterial molecular pattern that elicits host immune response.
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Affiliation(s)
| | | | | | | | | | - Zongzhao Zhai
- Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, College of Life Sciences, Hunan Normal University, Changsha, China
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Luo J, Luo M, Kaminga AC, Wei J, Dai W, Peng Y, Zhao K, Duan Y, Xiao X, Ouyang S, Yao Z, Liu Y, Pan X. Integrative metabolomics highlights gut microbiota metabolites as novel NAFLD-related candidate biomarkers in children. Microbiol Spectr 2024; 12:e0523022. [PMID: 38445874 PMCID: PMC10986516 DOI: 10.1128/spectrum.05230-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Accepted: 12/29/2023] [Indexed: 03/07/2024] Open
Abstract
Altered gut microbiota and metabolites are important for non-alcoholic fatty liver disease (NAFLD) in children. We aimed to comprehensively examine the effects of gut metabolites on NAFLD progression. We performed integrative metabolomics (untargeted discovery and targeted validation) analysis of non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), and obesity in children. Fecal samples were collected from 75 subjects in the discovery cohort (25 NAFL, 25 NASH, and 25 obese control children) and 145 subjects in an independent validation cohort (53 NAFL, 39 NASH, and 53 obese control children). Among 2,491 metabolites, untargeted metabolomics revealed a complete NAFLD metabolic map containing 318 increased and 123 decreased metabolites. Then, machine learning selected 65 important metabolites that can distinguish the severity of the NAFLD. Furthermore, precision-targeted metabolomics selected 5 novel gut metabolites from 20 typical metabolites. The functionality of candidate metabolites was validated in hepatocyte cell lines. In the end, this study annotated two novel elevated pathogenic metabolites (dodecanoic acid and creatinine) and a relationship between depleted protective gut microbiota (Butyricicoccus and Alistipes), increased inflammation (IL-1β), lipid metabolism (TG), and liver function (ALT and AST). This study demonstrates the role of novel gut metabolites (dodecanoic acid and creatinine), as the fatty acid metabolism regulator contributing to NAFLD development through its influence on inflammation and liver function. IMPORTANCE Altered gut microbiota and metabolites are a major cause of non-alcoholic fatty liver disease (NAFLD) in children. This study demonstrated a complete gut metabolic map of children with NAFLD, containing 318 increased and 123 decreased metabolites by untargeted metabolomic. Multiple validation approaches (machine learning and targeted metabolomic) selected five novel gut metabolites for targeted metabolomics, which can distinguish NAFLD status and severity. The gut microbiota (Butyricicoccus and Alistipes) and metabolites (creatinine and dodecanoic acid) were novel biomarkers associated with impaired liver function and inflammation and validated by experiments of hepatocyte cell lines. The data provide a better understanding of the importance of gut microbiota and metabolite alterations in NAFLD, which implies that the altered gut microbiota and metabolites may represent a potential target to prevent NAFLD development.
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Affiliation(s)
- Jiayou Luo
- Pediatrics Research Institute of Hunan Province, Hunan Children’s Hospital, Changsha, China
- Department of Maternal and Child Health, Xiangya School of Public Health, Central South University, Changsha, China
| | - Miyang Luo
- Department of Maternal and Child Health, Xiangya School of Public Health, Central South University, Changsha, China
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China
- Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
| | | | - Jia Wei
- Department of Maternal and Child Health, Xiangya School of Public Health, Central South University, Changsha, China
| | - Wen Dai
- Department of Maternal and Child Health, Xiangya School of Public Health, Central South University, Changsha, China
| | - Yunlong Peng
- Department of Epidemiology and Health Statistics, Medical College of Soochow University, Suzhou, China
| | - Kunyan Zhao
- School of Public Health, University of South China, Hengyang, China
| | - Yamei Duan
- Department of Maternal and Child Health, Xiangya School of Public Health, Central South University, Changsha, China
| | - Xiang Xiao
- Department of Maternal and Child Health, Xiangya School of Public Health, Central South University, Changsha, China
| | - SiSi Ouyang
- Department of Maternal and Child Health, Xiangya School of Public Health, Central South University, Changsha, China
| | - Zhenzhen Yao
- Department of Maternal and Child Health, Xiangya School of Public Health, Central South University, Changsha, China
| | - Yixu Liu
- Department of Maternal and Child Health, Xiangya School of Public Health, Central South University, Changsha, China
| | - Xiongfeng Pan
- Pediatrics Research Institute of Hunan Province, Hunan Children’s Hospital, Changsha, China
- Department of Maternal and Child Health, Xiangya School of Public Health, Central South University, Changsha, China
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Beckers KF, Flanagan JP, Sones JL. Microbiome and pregnancy: focus on microbial dysbiosis coupled with maternal obesity. Int J Obes (Lond) 2024; 48:439-448. [PMID: 38145995 PMCID: PMC10978494 DOI: 10.1038/s41366-023-01438-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Revised: 11/22/2023] [Accepted: 12/01/2023] [Indexed: 12/27/2023]
Abstract
Obesity is becoming a worldwide pandemic with over one billion people affected. Of women in the United States, who are of childbearing age, two-thirds of them are considered overweight/obese. Offspring of women with obesity have a greater likelihood of developing cardiometabolic disease later in life, therefore making obesity a transgenerational issue. Emerging topics such as maternal microbial dysbiosis with altered levels of bacterial phyla and maternal obesity programming offspring cardiometabolic disease are a novel area of research discussed in this review. In the authors' opinion, beneficial therapeutics will be developed from knowledge of bacterial-host interactions at the most specific level possible. Although there is an abundance of obesity-related microbiome research, it is not concise, readily available, nor easy to interpret at this time. This review details the current knowledge regarding the relationship between obesity and the gut microbiome, with an emphasis on maternal obesity.
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Affiliation(s)
- Kalie F Beckers
- Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA
| | - Juliet P Flanagan
- Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA
| | - Jenny L Sones
- Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA.
- Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA.
- Clinical Sciences, Colorado State University College of Veterinary Medicine and Biomedical Sciences, Fort Collins, CO, USA.
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