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Zugman M, Wong M, Jaime-Casas S, Pal SK. The gut microbiome and dietary metabolites in the treatment of renal cell carcinoma. Urol Oncol 2025; 43:244-253. [PMID: 39095306 DOI: 10.1016/j.urolonc.2024.07.003] [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: 04/10/2024] [Revised: 06/13/2024] [Accepted: 07/02/2024] [Indexed: 08/04/2024]
Abstract
The gut microbiome is interlinked with renal cell carcinoma (RCC) and its response to systemic treatment. Mounting data suggests that certain elements of the gut microbiome may correlate with improved outcomes. New generation sequencing techniques and advanced bioinformatic data curation are accelerating the investigation of specific markers and metabolites that could predict treatment response. A variety of new therapeutic strategies, such as fecal microbiota transplantation, probiotic supplements, and dietary interventions, are currently being developed to modify the gut microbiome and improve anticancer therapies in patients with RCC. This review discusses the preliminary evidence indicating the role of the microbiome in cancer treatment, the techniques and tools necessary for its proper study and some of the current forms with which the microbiome can be modulated to improve patient outcomes.
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Affiliation(s)
- Miguel Zugman
- Department of Medical Oncology and Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA; Centro de Oncologia e Hematologia Família Dayan-Daycoval Einstein, Hospital Israelita Albert, São Paulo, São Paulo, Brazil
| | - Megan Wong
- Department of Medical Oncology and Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA
| | - Salvador Jaime-Casas
- Department of Medical Oncology and Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA
| | - Sumanta K Pal
- Department of Medical Oncology and Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA.
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2
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Misselwitz B, Haller D. [The intestinal microbiota in inflammatory bowel diseases]. INNERE MEDIZIN (HEIDELBERG, GERMANY) 2025; 66:146-155. [PMID: 39870907 DOI: 10.1007/s00108-024-01845-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 12/18/2024] [Indexed: 01/29/2025]
Abstract
BACKGROUND The intestinal microbiota comprises all living microorganisms in the gastrointestinal tract and is crucial for its function. Clinical observations and laboratory findings confirm a central role of the microbiota in chronic inflammatory bowel diseases (IBD). However, many mechanistic details remain unclear. OBJECTIVES Changes in the microbiota and the causal relationship with the pathogenesis of IBD are described and current and future diagnostic and therapeutic options are discussed. MATERIALS AND METHODS Narrative review. RESULTS The intestinal microbiota is altered in composition, diversity, and function in IBD patients, but specific (universal) IBD-defining bacteria have not been identified. The healthy microbiota has numerous anti-inflammatory functions such as the production of short-chain fatty acids or competition with pathogens. In contrast, the IBD microbiota promotes inflammation through the destruction of the intestinal barrier and direct interaction with the immune system. The balance between pro- and anti-inflammatory effects of the microbiota appears to be crucial for the development of intestinal inflammation. Microbiota-based IBD diagnostics show promise but are not yet ready for clinical use. Probiotics and fecal microbiota transplantation have clinical effects, especially in ulcerative colitis, but the potential of microbiota-based therapies is far from being fully realized. CONCLUSION IBD dysbiosis remains undefined so far. It is unclear how the many parallel pro- and anti-inflammatory mechanisms contribute to IBD pathogenesis. An inadequate mechanistic understanding hinders the development of microbiota-based diagnostics and therapies.
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Affiliation(s)
- Benjamin Misselwitz
- Medizinische Klinik und Poliklinik II, Ludwig-Maximilians-Universität München, Marchioninistraße 15, 83477, München, Deutschland.
| | - Dirk Haller
- Lehrstuhl für Ernährung und Immunologie, School of Life Sciences, Technische Universität München, Gregor-Mendel-Straße 2, 85354, Freising, Deutschland.
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3
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Liu C, Zeng H, Ouyang J, Wen S, Zhou F, Jiang R, Zhang X, Wang Z, Huang J, Liu Z. Eurotium-Cristatum fermented black tea alleviates ulcerative colitis through the PPARγ-NF-κB signaling axis. Food Res Int 2025; 200:115436. [PMID: 39779091 DOI: 10.1016/j.foodres.2024.115436] [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: 07/09/2024] [Revised: 10/29/2024] [Accepted: 11/26/2024] [Indexed: 01/11/2025]
Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel condition that significantly impairs patient quality of life and remains incurable. Effective dietary management is crucial for both prevention and treatment. This study investigates the effects and mechanisms of Eurotium cristatum-fermented black tea (FBT) in a dextran sulfate sodium (DSS)-induced UC mouse model using transcriptome sequencing, immunofluorescence, and flow cytometry. Our results demonstrate that FBT significantly protects intestinal integrity by suppressing NF-κB-dependent inflammatory genes through the activation of peroxisome proliferator-activated receptor gamma (PPARγ) and modulation of the NF-κB signaling pathway. FBT enhances intestinal barrier integrity by limiting microbial penetration and metabolite translocation into systemic circulation, thereby reducing systemic inflammation risk. Additionally, FBT promotes intestinal mucosa repair and maintains microecological homeostasis by regulating intestinal flora and enhancing the biosynthesis of short-chain fatty acids and amino acids. These findings suggest that FBT has promising prophylactic potential for preventing and alleviating UC by modulating multiple biological pathways, including reducing inflammation, mitigating oxidative stress, and strengthening intestinal barrier integrity. This study lays the groundwork for future research on dietary interventions for UC prevention and management.
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Affiliation(s)
- Changwei Liu
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China; School of Life and Health Sciences, Hunan University of Science and Technology, Xiangtan 411201, China
| | - Hongzhe Zeng
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China
| | - Jian Ouyang
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China
| | - Shuai Wen
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China
| | - Fang Zhou
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China
| | - Ronggang Jiang
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China
| | - Xinyi Zhang
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China
| | - Zhong Wang
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China
| | - Jianan Huang
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China; Co-Innovation Center of Education Ministry for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, China; National Research Center of Engineering and Technology for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, China.
| | - Zhonghua Liu
- Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha 410128, China; Co-Innovation Center of Education Ministry for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, China; National Research Center of Engineering and Technology for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha 410128, China.
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Yang C, Chen J, Zhao Y, Wu J, Xu Y, Xu J, Chen F, Chen Y, Chen N. Salivary exosomes exacerbate colitis by bridging the oral cavity and intestine. iScience 2024; 27:111061. [PMID: 39759079 PMCID: PMC11700645 DOI: 10.1016/j.isci.2024.111061] [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: 05/24/2024] [Revised: 07/18/2024] [Accepted: 09/24/2024] [Indexed: 01/07/2025] Open
Abstract
Inflammatory bowel disease (IBD) presents a range of extraintestinal manifestations, notably including oral cavity involvement. The mechanisms underlying oral-gut crosstalk in IBD are not fully understood. Exosomes, found in various body fluids such as saliva, play an unclear role in IBD that requires further exploration. In the dextran sulfate sodium (DSS) mouse model, salivary exosomes from patients with active IBD (active IBD-Sexos) exacerbated colitis, while those from IBD patients in remission (remission IBD-Sexos) did not. Possible reasons may include the regulation of macrophage polarization, disruption of intestinal epithelial function, and alteration of the intestinal flora. During co-culture with active IBD-Sexos, THP-1 cells exhibited inflammatory responses, while Caco-2 cells showed reduced tight junction protein expression. Additionally, 35 differentially expressed miRNAs were identified in active IBD-Sexos. In brief, our findings substantiate an intriguing phenomenon whereby active IBD-Sexos exacerbate colitis by bridging the oral cavity and intestine.
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Affiliation(s)
- Congyi Yang
- Department of Gastroenterology, Peking University People’s Hospital, Beijing 100044, China
| | - Jingyi Chen
- Department of Gastroenterology, Peking University People’s Hospital, Beijing 100044, China
| | - Yuzheng Zhao
- Department of Gastroenterology, Peking University People’s Hospital, Beijing 100044, China
| | - Jushan Wu
- Department of Gastroenterology, Peking University People’s Hospital, Beijing 100044, China
| | - Yalan Xu
- Department of Gastroenterology, Peking University People’s Hospital, Beijing 100044, China
| | - Jun Xu
- Department of Gastroenterology, Peking University People’s Hospital, Beijing 100044, China
| | - Feng Chen
- Central Laboratory, Peking University School of Stomatology, Beijing 100081, China
| | - Yang Chen
- Center for Precision Medicine Multi-Omics Research, Institute of Advanced Clinical Medicine, Peking University, Beijing 100191, China
| | - Ning Chen
- Department of Gastroenterology, Peking University People’s Hospital, Beijing 100044, China
- Clinical Center of Immune-Mediated Digestive Diseases, Peking University People’s Hospital, Beijing 100044, China
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5
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Kwoji ID, Aiyegoro OA, Okpeku M, Adeleke MA. Elucidating the Mechanisms of Cell-to-Cell Crosstalk in Probiotics Co-culture: A Proteomics Study of Limosilactobacillus reuteri ZJ625 and Ligilactobacillus salivarius ZJ614. Probiotics Antimicrob Proteins 2024; 16:1817-1835. [PMID: 37581751 PMCID: PMC11445297 DOI: 10.1007/s12602-023-10133-y] [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: 07/31/2023] [Indexed: 08/16/2023]
Abstract
Limosilactobacillus reuteri ZJ625 and Ligilactobacillus salivarius ZJ614 are potential probiotic bacteria with improved benefits when administered to the host as a multi-strain preparation. To elucidate the mechanisms of cell-to-cell crosstalk between these two strains, we studied their intracellular and extracellular proteomes in co-culture by liquid-chromatography mass-spectrometry (LC-MS) using Dionex Nano-RSLC and fusion mass spectrometer. The experiment consisted of five biological replicates, and samples were collected during the mid-exponential growth phase. The quantitative proteomic profiles revealed several differentially expressed proteins (DEPs), which are down- or up-regulated between and within groups for both the intracellular and extracellular proteomes. These DEPs include proteins synthesising autoinducer-2, a sensor compound for cell-to-cell bacterial crosstalk during quorum sensing in mixed culture. Other important DEPs identified include enolase, phosphoglycerate kinase, and l-lactate dehydrogenase, which play roles in carbohydrate metabolism. Proteins associated with transcription, ATP production and transport across the membrane, DNA repair, and those with the potential to bind to the host epithelium were also identified. The post-translational modifications associated with the proteins include oxidation, deamidation, and ammonia loss. Importantly, this study revealed a significant expression of S-ribosylhomocysteine lyase (luxS) involved in synthesising autoinducer-2 that plays important roles in quorum sensing, aiding bacterial cell-to-cell crosstalk in co-cultures. The proteome of L. salivarius ZJ614 was most affected when co-cultured with L. reuteri ZJ625. In contrast, omitting some medium components from the defined medium exerted more effects on L. reuteri ZJ625 than L. salivarius ZJ614.
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Affiliation(s)
- Iliya Dauda Kwoji
- Discipline of Genetics, School of Life Sciences, College of Agriculture, Engineering and Sciences, University of KwaZulu-Natal, Westville Campus, Durban, 4000, South Africa
| | - Olayinka Ayobami Aiyegoro
- Unit for Environmental Sciences and Management, North-West University, Potchefstroom, Northwest, South Africa
| | - Moses Okpeku
- Discipline of Genetics, School of Life Sciences, College of Agriculture, Engineering and Sciences, University of KwaZulu-Natal, Westville Campus, Durban, 4000, South Africa
| | - Matthew Adekunle Adeleke
- Discipline of Genetics, School of Life Sciences, College of Agriculture, Engineering and Sciences, University of KwaZulu-Natal, Westville Campus, Durban, 4000, South Africa.
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6
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Che S, Qin B, Wu K, Zhu M, Hu H, Peng C, Wang Z, Yin Y, Xia Y, Wu M. EGCG drives gut microbial remodeling-induced epithelial GPR43 activation to lessen Th1 polarization in colitis. Redox Biol 2024; 75:103291. [PMID: 39116526 PMCID: PMC11363845 DOI: 10.1016/j.redox.2024.103291] [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: 07/05/2024] [Revised: 07/25/2024] [Accepted: 07/27/2024] [Indexed: 08/10/2024] Open
Abstract
Modulation of immune microenvironment is critical for inflammatory bowel disease (IBD) intervention. Epigallocatechin gallate (EGCG), as a natural low toxicity product, has shown promise in treating IBD. However, whether and how EGCG regulates the intestinal microenvironment is not fully understood. Here we report that EGCG lessens colitis by orchestrating Th1 polarization and self-amplification in a novel manner that required multilevel-regulated intestinal microecosystem. Mechanistically, EGCG activates GPR43 on IEC to inhibit Th1 polarization dependently of short chain fatty acid (SCFA)-producing gut microbiota. Inhibition of GPR43 activity weakens the protective effects of EGCG on colitis development. Moreover, we confirm that fecal SCFAs and/or intestinal GPR43 are limited in patients with colitis and are correlated with Th1 cell number. Taken together, our study reveals an intestinal microenvironment-dependent immunoregulatory effects of EGCG in treating IBD and provides insight into mechanisms of EGCG-based novel immunotherapeutic strategies for IBD.
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Affiliation(s)
- Siyan Che
- Hunan Provincial Key Laboratory for the Products Quality Regulation of Livestock and Poultry, College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan, 410128, China
| | - Beibei Qin
- Hunan Provincial Key Laboratory for the Products Quality Regulation of Livestock and Poultry, College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan, 410128, China
| | - Kunfu Wu
- Hunan Provincial Key Laboratory for the Products Quality Regulation of Livestock and Poultry, College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan, 410128, China
| | - Mingzhi Zhu
- Key Laboratory of Tea Science of Ministry of Education, National Research Center of Engineering Technology for Utilization of Functional Ingredients from Botanicals, Hunan Agricultural University, Changsha, 410128, China
| | - Han Hu
- Institute of Apicultural Research/State Key Laboratory of Resource Insects, Chinese Academy of Agricultural Sciences, Beijing, 100093, China
| | - Can Peng
- Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, 410125, China
| | - Zi Wang
- Department of Hematology, The Second Xiangya Hospital of Central South University; Molecular Biology Research Center, Center for Medical Genetics, School of Life Sciences; Hunan Province Key Laboratory of Basic and Applied Hematology, Central South University, Changsha 410011, China.
| | - Yulong Yin
- Hunan Provincial Key Laboratory for the Products Quality Regulation of Livestock and Poultry, College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan, 410128, China; Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, 410125, China
| | - Yaoyao Xia
- College of Animal Science and Technology, Southwest University, Chongqing, 400715, China.
| | - Miaomiao Wu
- Hunan Provincial Key Laboratory for the Products Quality Regulation of Livestock and Poultry, College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan, 410128, China.
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7
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Han D, Guan X, Zhu F, Yang Q, Su D. Oral aged garlic ( Allium sativum) alleviates ulcerative colitis in mice by improving gut homeostasis. Food Funct 2024; 15:8935-8951. [PMID: 39145619 DOI: 10.1039/d4fo03105a] [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: 08/16/2024]
Abstract
Aged garlic, obtained by heating raw garlic (Allium sativum) under high temperature and controlled humidity for a period, possesses a wide range of bioactivities, but its role in ulcerative colitis and its mechanism are not fully elucidated. We investigated the bioactive constituents in aged garlic (AG) and explored the effect of oral AG delivery on DSS-induced murine colitis. The results revealed that the aging process up-regulated anti-oxidative, anti-inflammatory and anti-microbial compounds such as dihydrocaffeic acid, 5-acetylsalicylic acid, verticine, S-allyl-L-cysteine and D-fucose. Oral AG obviously alleviated colitis, reducing colon damage and enhancing anti-oxidative and anti-inflammatory effects. Escherichia coli and Streptococcus equinus dramatically were enriched in the colon of mice with colitis that were strongly associated with Parkinson's disease, bacterial invasion of epithelial cells, aerobactin biosynthesis, and heme biosynthesis, but a distinct AG-mediated alteration in the colon due to increasing abundance of Akkermansia muciniphila, Lactobacillus sp. L-YJ, Bifidobacterium breve, Blautia wexlerae, Desulfomicrobium sp. P100A, and Lentilactobacillus hilgardii was observed. Next, we demonstrated that colonic microbiome reconstruction by oral AG significantly increased the production of short-chain fatty acids such as acetic acid, propionic acid, isobutyric acid, and isovaleric acid. This study provides the first data indicating that oral AG ameliorates colonic inflammation in a gut microbiota-dependent manner. Our findings provide novel insights into the AG-mediated remission of colitis and AG as a functional food for modulating the gut microbiota to prevent and treat colitis.
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Affiliation(s)
- Deping Han
- Peking University Institute of Advanced Agricultural Sciences, Shandong Laboratory of Advanced Agricultural Sciences in Weifang, Shandong 261325, China.
| | - Xuke Guan
- College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China
| | - Fengxia Zhu
- Peking University Institute of Advanced Agricultural Sciences, Shandong Laboratory of Advanced Agricultural Sciences in Weifang, Shandong 261325, China.
- College of Food Science and Nutritional Engineering, Shandong Agricultural University, Taian 271018, China
| | - Qing Yang
- College of Food Science and Nutritional Engineering, Shandong Agricultural University, Taian 271018, China
| | - Dingding Su
- Peking University Institute of Advanced Agricultural Sciences, Shandong Laboratory of Advanced Agricultural Sciences in Weifang, Shandong 261325, China.
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Han Z, Sun J, Jiang B, Chen K, Ge L, Sun Z, Wang A. Fecal microbiota transplantation accelerates restoration of florfenicol-disturbed intestinal microbiota in a fish model. Commun Biol 2024; 7:1006. [PMID: 39152200 PMCID: PMC11329668 DOI: 10.1038/s42003-024-06727-z] [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: 05/01/2022] [Accepted: 08/13/2024] [Indexed: 08/19/2024] Open
Abstract
Antibiotic-induced dysbiosis in the fish gut causes significant adverse effects. We use fecal microbiota transplantation (FMT) to accelerate the restoration of florfenicol-perturbed intestinal microbiota in koi carp, identifying key bacterial populations and metabolites involved in the recovery process through microbiome and metabolome analyses. We demonstrate that florfenicol disrupts intestinal microbiota, reducing beneficial genera such as Lactobacillus, Bifidobacterium, Bacteroides, Romboutsia, and Faecalibacterium, and causing mucosal injuries. Key metabolites, including aromatic amino acids and glutathione-related compounds, are diminished. We show that FMT effectively restores microbial populations, repairs intestinal damage, and normalizes critical metabolites, while natural recovery is less effective. Spearman correlation analyses reveal strong associations between the identified bacterial genera and the levels of aromatic amino acids and glutathione-related metabolites. This study underscores the potential of FMT to counteract antibiotic-induced dysbiosis and maintain fish intestinal health. The restored microbiota and normalized metabolites provide a basis for developing personalized probiotic therapies for fish.
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Affiliation(s)
- Zhuoran Han
- Key Laboratory of Smart Breeding (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Tianjin Agricultural University, Tianjin, China
- Tianjin Key Laboratory of Aqua-ecology and Aquaculture, Fisheries College, Tianjin Agricultural University, Tianjin, China
- College of Life Science, South China Normal University, Guangzhou, Guangdong, China
| | - Jingfeng Sun
- Key Laboratory of Smart Breeding (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Tianjin Agricultural University, Tianjin, China.
- Tianjin Key Laboratory of Aqua-ecology and Aquaculture, Fisheries College, Tianjin Agricultural University, Tianjin, China.
| | - Boyun Jiang
- Tianjin Key Laboratory of Aqua-ecology and Aquaculture, Fisheries College, Tianjin Agricultural University, Tianjin, China
| | - Kun Chen
- Tianjin Key Laboratory of Aqua-ecology and Aquaculture, Fisheries College, Tianjin Agricultural University, Tianjin, China
| | - Lunhua Ge
- Tianjin Key Laboratory of Aqua-ecology and Aquaculture, Fisheries College, Tianjin Agricultural University, Tianjin, China
| | - Zhongshi Sun
- Tianjin Key Laboratory of Aqua-ecology and Aquaculture, Fisheries College, Tianjin Agricultural University, Tianjin, China
| | - Anli Wang
- College of Life Science, South China Normal University, Guangzhou, Guangdong, China
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Li A, Liu A, Wang J, Song H, Luo P, Zhan M, Zhou X, Chen L, Zhang L. The prophylaxis functions of Lactobacillus fermentum GLF-217 and Lactobacillus plantarum FLP-215 on ulcerative colitis via modulating gut microbiota of mice. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2024; 104:5816-5825. [PMID: 38406876 DOI: 10.1002/jsfa.13410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Revised: 12/09/2023] [Accepted: 02/18/2024] [Indexed: 02/27/2024]
Abstract
BACKGROUND The strong connection between gut microbes and human health has been confirmed by an increasing number of studies. Although probiotics have been found to relieve ulcerative colitis, the mechanism varies by the species involved. In this study, the physiological, immune and pathological factors of mice were measured and shotgun metagenomic sequencing was conducted to investigate the potential mechanisms in preventing ulcerative colitis. RESULTS The results demonstrated that ingestion of Lactobacillus fermentum GLF-217 and Lactobacillus plantarum FLP-215 significantly alleviated ulcerative colitis induced by dextran sulfate sodium (DSS), as evidenced by the increase in body weight, food intake, water intake and colon length as well as the decrease in disease activity index, histopathological score and inflammatory factor. Both strains not only improved intestinal mucosa by increasing mucin-2 and zonula occludens-1, but also improved the immune system response by elevating interleukin-10 levels and decreasing the levels of interleukin-1β, interleukin-6, tumor necrosis factor-α and interferon-γ. Moreover, L. fermentum GLF-217 and L. plantarum FLP-215 play a role in preventing DSS-induced colitis by regulating the structure of gut microbiota and promoting the formation of short-chain fatty acids. CONCLUSIONS This study may provide a reference for the prevention strategy of ulcerative colitis. © 2024 Society of Chemical Industry.
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Affiliation(s)
- Ao Li
- Key Laboratory of Food Nutrition and Functional Food of Hainan Province, School of Food Science and Engineering, Hainan University, Haikou, China
| | | | - Jun Wang
- Key Laboratory of Food Nutrition and Functional Food of Hainan Province, School of Food Science and Engineering, Hainan University, Haikou, China
| | - Hainan Song
- Key Laboratory of Food Nutrition and Functional Food of Hainan Province, School of Food Science and Engineering, Hainan University, Haikou, China
| | | | | | | | | | - Lin Zhang
- Key Laboratory of Food Nutrition and Functional Food of Hainan Province, School of Food Science and Engineering, Hainan University, Haikou, China
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10
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Ordinola-Zapata R, Costalonga M, Dietz M, Lima BP, Staley C. The root canal microbiome diversity and function. A whole-metagenome shotgun analysis. Int Endod J 2024; 57:872-884. [PMID: 36861850 DOI: 10.1111/iej.13911] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 02/23/2023] [Accepted: 02/25/2023] [Indexed: 03/03/2023]
Abstract
AIM To evaluate the root canal microbiome composition and bacterial functional capability in cases of primary and secondary apical periodontitis utilizing whole-metagenome shotgun sequencing. METHODOLOGY Twenty-two samples from patients with primary root canal infections, and 18 samples obtained from previously treated teeth currently diagnosed with apical periodontitis were analysed with whole-metagenome shotgun sequencing at a depth of 20 M reads. Taxonomic and functional gene annotations were made using MetaPhlAn3 and HUMAnN3 software. The Shannon and Chao1 indices were utilized to measure alpha diversity. Differences in community composition were evaluated utilizing analysis of similarity (ANOSIM) using Bray-Curtis dissimilarities. The Wilcoxon rank sum test was used to compare differences in taxa and functional genes. RESULTS Microbial community variations within a community were significantly lower in secondary relative to primary infections (alpha diversity p = .001). Community composition was significantly different in primary versus secondary infection (R = .11, p = .005). The predominant taxa observed among samples (>2.5%) were Pseudopropionibacterium propionicum, Prevotella oris, Eubacterium infirmum, Tannerella forsythia, Atopobium rimae, Peptostreptococcus stomatis, Bacteroidetes bacterium oral taxon 272, Parvimonas micra, Olsenella profusa, Streptococcus anginosus, Lactobacillus rhamnosus, Porphyromonas endodontalis, Pseudoramibacter alactolyticus, Fusobacterium nucleatum, Eubacterium brachy and Solobacterium moorei. The Wilcoxon rank test revealed no significant differences in relative abundances of functional genes in both groups. Genes with greater relative abundances (top 25) were associated with genetic, signalling and cellular processes including the iron and peptide/nickel transport system. Numerous genes encoding toxins were identified: exfoliative toxin, haemolysins, thiol-activated cytolysin, phospholipase C, cAMP factor, sialidase, and hyaluronic glucosaminidase. CONCLUSIONS Despite taxonomic differences between primary and secondary apical periodontitis, the functional capability of the microbiomes was similar.
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Affiliation(s)
- Ronald Ordinola-Zapata
- Division of Endodontics, Department of Restorative Sciences, School of Dentistry, University of Minnesota, Minneapolis, Minnesota, USA
| | - Massimo Costalonga
- Division of Basic Sciences, Department of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota, Minneapolis, Minnesota, USA
| | - Matthew Dietz
- Division of Basic & Translational Research, Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA
| | - Bruno P Lima
- Division of Basic Sciences, Department of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota, Minneapolis, Minnesota, USA
| | - Christopher Staley
- Division of Basic & Translational Research, Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA
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11
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Rio P, Gasbarrini A, Gambassi G, Cianci R. Pollutants, microbiota and immune system: frenemies within the gut. Front Public Health 2024; 12:1285186. [PMID: 38799688 PMCID: PMC11116734 DOI: 10.3389/fpubh.2024.1285186] [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: 10/11/2023] [Accepted: 04/24/2024] [Indexed: 05/29/2024] Open
Abstract
Pollution is a critical concern of modern society for its heterogeneous effects on human health, despite a widespread lack of awareness. Environmental pollutants promote several pathologies through different molecular mechanisms. Pollutants can affect the immune system and related pathways, perturbing its regulation and triggering pro-inflammatory responses. The exposure to several pollutants also leads to alterations in gut microbiota with a decreasing abundance of beneficial microbes, such as short-chain fatty acid-producing bacteria, and an overgrowth of pro-inflammatory species. The subsequent intestinal barrier dysfunction, together with oxidative stress and increased inflammatory responses, plays a role in the pathogenesis of gastrointestinal inflammatory diseases. Moreover, pollutants encourage the inflammation-dysplasia-carcinoma sequence through various mechanisms, such as oxidative stress, dysregulation of cellular signalling pathways, cell cycle impairment and genomic instability. In this narrative review, we will describe the interplay between pollutants, gut microbiota, and the immune system, focusing on their relationship with inflammatory bowel diseases and colorectal cancer. Understanding the biological mechanisms underlying the health-to-disease transition may allow the design of public health policies aimed at reducing the burden of disease related to pollutants.
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Affiliation(s)
| | | | | | - Rossella Cianci
- Department of Translational Medicine and Surgery, Catholic University of Sacred Heart, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
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Sgro M, Kodila ZN, Li C, Carmichael I, Warren S, Reichelt AC, Yamakawa GR, Mychasiuk R. Microbiome depletion prior to repeat mild TBI differentially alters social deficits and prefrontal cortex plasticity in adolescent and adult rats. iScience 2024; 27:109395. [PMID: 38510122 PMCID: PMC10952042 DOI: 10.1016/j.isci.2024.109395] [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: 10/02/2023] [Revised: 11/21/2023] [Accepted: 02/28/2024] [Indexed: 03/22/2024] Open
Abstract
Although aging, repeat mild traumatic brain injury (RmTBI), and microbiome modifications independently change social behavior, there has been no investigation into their cumulative effects on social behavior and neuroplasticity within the prefrontal cortex. Therefore, we examined how microbiome depletion prior to RmTBI affected social behavior and neuroplasticity in adolescent and adult rats. Play, temperament analysis, elevated plus maze, and the hot/cold plate assessed socio-emotional function. Analyses of perineuronal nets (PNNs) and parvalbumin (PV) interneurons was completed. Social-emotional deficits were more pronounced in adults, with microbiome depletion attenuating social behavior deficits associated with RmTBI in both age groups. Microbiome depletion increased branch length and PNN arborization within the PFC but decreased the overall number of PNNs. Adults and males were more vulnerable to RmTBI. Interestingly, microbiome depletion may have attenuated the changes to neuroplasticity and subsequent social deficits, suggesting that the microbiome is a viable, but age-specific, target for RmTBI therapeutics.
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Affiliation(s)
- Marissa Sgro
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia
| | - Zoe N. Kodila
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia
| | - Crystal Li
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia
| | - Irena Carmichael
- Monash Micro Imaging, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia
| | - Samantha Warren
- Monash Micro Imaging, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia
| | - Amy C. Reichelt
- School of Biomedicine, University of Adelaide, Adelaide, SA 5005, Australia
| | - Glenn R. Yamakawa
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia
| | - Richelle Mychasiuk
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia
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13
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Reis SK, Socca EAR, de Souza BR, Genaro SC, Durán N, Fávaro WJ. Effects of probiotic supplementation on chronic inflammatory process modulation in colorectal carcinogenesis. Tissue Cell 2024; 87:102293. [PMID: 38244400 DOI: 10.1016/j.tice.2023.102293] [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: 09/17/2023] [Revised: 12/17/2023] [Accepted: 12/20/2023] [Indexed: 01/22/2024]
Abstract
The current study investigated the potential effects of probiotic supplementation on colorectal carcinogenesis chemically induced with 1,2-dimethylhydrazine (DMH) and treated with 5-fluorouracil (5FU)-based chemotherapy in mice. Animals were randomly allocated in five different groups: Control: which not receive any treatment throughout the experimental course; Colitis model group (DMH): treated with DMH; DMH+ 5FU: animals received I.P. (intraperitoneal) dose of chemotherapy on a weekly basis; DMH+PROB: animals received daily administrations (via gavage) of probiotics (Lactobacillus: acidophilus and paracasei, Bifidobacterium lactis and bifidum); and DMH+ PROB+ 5FU: animals received the same treatment as the previous groups. After ten-week treatment, mice's large intestine was collected and subjected to colon length, histopathological, periodic acid-schiff (PAS) staining and immunohistochemistry (TLR2, MyD88, NF-κB, IL-6, TLR4, TRIF, IRF-3, IFN-γ, Ki-67, KRAS, p53, IL-10, and TGF-β) analyzes. Variance (ANOVA) and Kruskal-Wallis tests were used for statistical analysis, at significance level p 0.05. Probiotics' supplementation has increased the production of Ki-67 cell-proliferation marker, reduced body weight, and colon shortening, as well as modulated the chronic inflammatory process in colorectal carcinogenesis by inhibiting NF-κB expression and mitigating mucin depletion. Thus, these findings lay a basis for guide future studies focused on probiotics' action mechanisms in tumor microenvironment which might have implications in clinical practice.
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Affiliation(s)
- Sabrina Karen Reis
- Faculty Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil; Laboratory of Urogenital Carcinogenesis and Immunotherapy, Department of Structural and Functional Biology, State University of Campinas (UNICAMP), Campinas, SP, Brazil.
| | - Eduardo Augusto Rabelo Socca
- Laboratory of Urogenital Carcinogenesis and Immunotherapy, Department of Structural and Functional Biology, State University of Campinas (UNICAMP), Campinas, SP, Brazil
| | - Bianca Ribeiro de Souza
- British Columbia's Gynecological Cancer Research (OVCARE) Program and Department of Obstetrics and Gynecology, University of British Columbia, Vancouver General Hospital, Vancouver, BC, Canada.
| | | | - Nelson Durán
- Laboratory of Urogenital Carcinogenesis and Immunotherapy, Department of Structural and Functional Biology, State University of Campinas (UNICAMP), Campinas, SP, Brazil; Nanomedicine Research Unit (Nanomed), Federal University of ABC (UFABC), Santo André, SP, Brazil
| | - Wagner José Fávaro
- Faculty Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil; Laboratory of Urogenital Carcinogenesis and Immunotherapy, Department of Structural and Functional Biology, State University of Campinas (UNICAMP), Campinas, SP, Brazil
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14
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Hou JJ, Ding L, Yang T, Yang YF, Jin YP, Zhang XP, Ma AH, Qin YH. The proteolytic activity in inflammatory bowel disease: insight from gut microbiota. Microb Pathog 2024; 188:106560. [PMID: 38272327 DOI: 10.1016/j.micpath.2024.106560] [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: 08/02/2023] [Revised: 01/20/2024] [Accepted: 01/22/2024] [Indexed: 01/27/2024]
Abstract
Inflammatory bowel disease (IBD) is a chronic, recurrent inflammatory disease caused by the destruction of the intestinal mucosal epithelium that affects a growing number of people worldwide. Although the etiology of IBD is complex and still elucidated, the role of dysbiosis and dysregulated proteolysis is well recognized. Various studies observed altered composition and diversity of gut microbiota, as well as increased proteolytic activity (PA) in serum, plasma, colonic mucosa, and fecal supernatant of IBD compared to healthy individuals. The imbalance of intestinal microecology and intestinal protein hydrolysis were gradually considered to be closely related to IBD. Notably, the pivotal role of intestinal microbiota in maintaining proteolytic balance received increasing attention. In summary, we have speculated a mesmerizing story, regarding the hidden role of PA and microbiota-derived PA hidden in IBD. Most importantly, we provided the diagnosis and therapeutic targets for IBD as well as the formulation of new treatment strategies for other digestive diseases and protease-related diseases.
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Affiliation(s)
- Jun-Jie Hou
- Department of Gastroenterology, Shaoxing People's Hospital, Shaoxing, PR China
| | - Liang Ding
- Department of Gastroenterology, Shaoxing People's Hospital, Shaoxing, PR China
| | - Tao Yang
- Department of Gastroenterology, Shaoxing People's Hospital, Shaoxing, PR China
| | - Yan-Fei Yang
- Department of Gastroenterology, Shaoxing People's Hospital, Shaoxing, PR China
| | - Yue-Ping Jin
- Department of Gastroenterology, Shaoxing People's Hospital, Shaoxing, PR China
| | - Xiao-Ping Zhang
- Department of Gastroenterology, Shaoxing People's Hospital, Shaoxing, PR China
| | - A-Huo Ma
- Department of Gastroenterology, Shaoxing People's Hospital, Shaoxing, PR China
| | - Yue-Hua Qin
- Department of Gastroenterology, Shaoxing People's Hospital, Shaoxing, PR China.
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15
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Skoufou M, Tsigalou C, Vradelis S, Bezirtzoglou E. The Networked Interaction between Probiotics and Intestine in Health and Disease: A Promising Success Story. Microorganisms 2024; 12:194. [PMID: 38258020 PMCID: PMC10818559 DOI: 10.3390/microorganisms12010194] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 01/14/2024] [Accepted: 01/15/2024] [Indexed: 01/24/2024] Open
Abstract
Probiotics are known to promote human health either precautionary in healthy individuals or therapeutically in patients suffering from certain ailments. Although this knowledge was empirical in past tomes, modern science has already verified it and expanded it to new limits. These microorganisms can be found in nature in various foods such as dairy products or in supplements formulated for clinical or preventive use. The current review examines the different mechanisms of action of the probiotic strains and how they interact with the organism of the host. Emphasis is put on the clinical therapeutic use of these beneficial microorganisms in various clinical conditions of the human gastrointestinal tract. Diseases of the gastrointestinal tract and particularly any malfunction and inflammation of the intestines seriously compromise the health of the whole organism. The interaction between the probiotic strains and the host's microbiota can alleviate the clinical signs and symptoms while in some cases, in due course, it can intervene in the underlying pathology. Various safety issues of the use of probiotics are also discussed.
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Affiliation(s)
- Maria Skoufou
- Master Program in “Food, Nutrition and Microbiome”, Department of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (C.T.); (S.V.)
- Proctology Department, Paris Saint Joseph Hospital Paris, 75014 Paris, France
| | - Christina Tsigalou
- Master Program in “Food, Nutrition and Microbiome”, Department of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (C.T.); (S.V.)
- Laboratory of Hygiene and Environmental Protection, Faculty of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece
| | - Stergios Vradelis
- Master Program in “Food, Nutrition and Microbiome”, Department of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (C.T.); (S.V.)
- Department of Gastrenterology, Faculty of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece
| | - Eugenia Bezirtzoglou
- Master Program in “Food, Nutrition and Microbiome”, Department of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (C.T.); (S.V.)
- Laboratory of Hygiene and Environmental Protection, Faculty of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece
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16
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Amin U, Jiang R, Raza SM, Fan M, Liang L, Feng N, Li X, Yang Y, Guo F. Gut-joint axis: Oral Probiotic ameliorates Osteoarthritis. J Tradit Complement Med 2024; 14:26-39. [PMID: 38223812 PMCID: PMC10785157 DOI: 10.1016/j.jtcme.2023.06.002] [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: 12/30/2022] [Revised: 03/10/2023] [Accepted: 06/13/2023] [Indexed: 01/16/2024] Open
Abstract
Osteoarthritis (OA) etiology is multifactorial, and its prevalence is growing globally. The Gut microbiota shapes our immune system and impacts all aspects of health and disease. The idea of utilizing probiotics to treat different conditions prevails. Concerning musculoskeletal illness and health, current data lack the link to understand the interactions between the host and microbiome. We report that S. thermophilus, L. pentosus (as probiotics), and γ-aminobutyric acid (GABA) harbour against osteoarthritis in vivo and alleviate IL-1β induced changes in chondrocytes in vitro. We examined the increased GABA concentration in mice's serum and small intestine content followed by bacterial treatment. The treatment inhibited the catabolism of cartilage and rescued mice joints from degradation. Furthermore, the anabolic markers upregulated and decreased inflammatory markers in mice knee joints and chondrocytes. This study is the first to represent GABA's chondrogenic and chondroprotective effects on joints and human chondrocytes. This data provides a foundation for future studies to elucidate the role of GABA in regulating chondrocyte cell proliferation. These findings opened future horizons to understanding the gut-joint axis and OA treatment. Thus, probiotic/GABA therapy shields OA joints in mice and could at least serve as adjuvant therapy to treat osteoarthritis.
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Affiliation(s)
- Uzma Amin
- Laboratory of Developmental Biology, Department of Cell Biology and Genetics, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, China
- Department of Microbiology, Government College University, Faisalabad, 38000, Punjab, Pakistan
| | - Rong Jiang
- Laboratory of Stem Cells and Tissue Engineering, Chongqing Medical University, Chongqing, 400016, China
| | - Shahid Masood Raza
- School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
- Department of Microbiology, Government College University, Faisalabad, 38000, Punjab, Pakistan
| | - Mengtian Fan
- Laboratory of Developmental Biology, Department of Cell Biology and Genetics, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, China
| | - Li Liang
- Laboratory of Developmental Biology, Department of Cell Biology and Genetics, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, China
| | - Naibo Feng
- Laboratory of Developmental Biology, Department of Cell Biology and Genetics, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, China
| | - Xiaoli Li
- Laboratory of Developmental Biology, Department of Cell Biology and Genetics, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, China
| | - Yuyou Yang
- Laboratory of Developmental Biology, Department of Cell Biology and Genetics, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, China
| | - Fengjin Guo
- Laboratory of Developmental Biology, Department of Cell Biology and Genetics, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, China
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17
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Giannì ML, Morniroli D, Mosca F, Rescigno M. Can Postbiotics Represent a New Strategy for NEC? ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1449:43-57. [PMID: 39060730 DOI: 10.1007/978-3-031-58572-2_3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/28/2024]
Abstract
Intestinal bacteria, also known as gut microbiota, are a rich ecology of microorganisms found in the human digestive tract. Extensive study has highlighted their critical relevance in preserving human health. New research has revealed that bacterial viability is not invariably necessary to induce health benefits. Postbiotics (defined soluble substances produced as a byproduct of the metabolic processes of living microbes) have thus emerged as an important topic of research. They contribute to shaping the gut microbiota, exert immune-modulation activity, and improve the integrity of the gut barrier.Alterations in preterm gut colonization associated with intestinal barrier immaturity and the increased reactivity of the intestinal mucosa to colonizing bacteria have been implicated in the pathogenesis of necrotizing enterocolitis. Postbiotics have shown promising outcomes in reducing the risk of developing NEC, lowering inflammation, encouraging the development of good bacteria, and strengthening the intestinal barrier. This is an important advancement in newborn care and highlights the potential of postbiotics to avoid severe intestinal disorders.
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Affiliation(s)
- Maria Lorella Giannì
- Fondazione I.R.C.C.S. Ca' Granda Ospedale Maggiore Policlinico, Neonatal Intensive Care Unit, Milan, Italy
- Department of Clinical Science and Community Health, University of Milan, Milan, Italy
| | - Daniela Morniroli
- Fondazione I.R.C.C.S. Ca' Granda Ospedale Maggiore Policlinico, Neonatal Intensive Care Unit, Milan, Italy
- Department of Clinical Science and Community Health, University of Milan, Milan, Italy
| | - Fabio Mosca
- Fondazione I.R.C.C.S. Ca' Granda Ospedale Maggiore Policlinico, Neonatal Intensive Care Unit, Milan, Italy.
- Department of Clinical Science and Community Health, University of Milan, Milan, Italy.
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18
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Salimi A, Sepehr A, Hejazifar N, Talebi M, Rohani M, Pourshafie MR. The Anti-Inflammatory Effect of a Probiotic Cocktail in Human Feces Induced-Mouse Model. Inflammation 2023; 46:2178-2192. [PMID: 37599322 DOI: 10.1007/s10753-023-01870-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Revised: 06/18/2023] [Accepted: 07/03/2023] [Indexed: 08/22/2023]
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract due to altered interaction between the immune system and the gut microbiota. The aim of this study was to investigate the role of a probiotic cocktail in modulating immune dysregulation induced in mice. Mice were divided into 5 groups (n = 5/group), and inflammation was induced in two separate groups by fecal microbiota transplantation (FMT) from the stool of human with IBD and dextran sulfate sodium (DSS). In the other two groups, the cocktail of Lactobacillus spp. and Bifidobacterium spp. (108CFU/kg/day) was administered daily for a total of 28days in addition to inducing inflammation. A group as a contcxsrol group received only water and food. The alteration of the selected genera of gut microbiota and the expression of some genes involved in the regulation of the inflammatory response were studied in the probiotic-treated and untreated groups by quantitative real-time PCR. The selected genera of gut microbiota of the FMT and DSS groups showed similar patterns on day 28 after each treatment. In the probiotic-treated groups, the population of the selected genera of gut microbiota normalized and the abundance of Firmicutes and Actinobacteria increased compared to the DSS and FMT groups. The expression of genes related to immune response and tight junctions was positively affected by the probiotic. Changes in the gut microbiota could influence the inflammatory status in the gut, and probiotics as a preventive or complementary treatment could improve the well-being of patients with inflammatory bowel disease symptoms.
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Affiliation(s)
- Afsaneh Salimi
- Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran
| | - Amin Sepehr
- Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran
| | - Niloofar Hejazifar
- Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy
| | - Maliheh Talebi
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mahdi Rohani
- Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran.
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Chathuranga K, Shin Y, Uddin MB, Paek J, Chathuranga WAG, Seong Y, Bai L, Kim H, Shin JH, Chang YH, Lee JS. The novel immunobiotic Clostridium butyricum S-45-5 displays broad-spectrum antiviral activity in vitro and in vivo by inducing immune modulation. Front Immunol 2023; 14:1242183. [PMID: 37881429 PMCID: PMC10595006 DOI: 10.3389/fimmu.2023.1242183] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2023] [Accepted: 09/20/2023] [Indexed: 10/27/2023] Open
Abstract
Clostridium butyricum is known as a probiotic butyric acid bacterium that can improve the intestinal environment. In this study, we isolated a new strain of C. butyricum from infant feces and evaluated its physiological characteristics and antiviral efficacy by modulating the innate immune responses in vitro and in vivo. The isolated C. butyricum S-45-5 showed typical characteristics of C. butyricum including bile acid resistance, antibacterial ability, and growth promotion of various lactic acid bacteria. As an antiviral effect, C. butyricum S-45-5 markedly reduced the replication of influenza A virus (PR8), Newcastle Disease Virus (NDV), and Herpes Simplex Virus (HSV) in RAW264.7 cells in vitro. This suppression can be explained by the induction of antiviral state in cells by the induction of antiviral, IFN-related genes and secretion of IFNs and pro-inflammatory cytokines. In vivo, oral administration of C. butyricum S-45-5 exhibited prophylactic effects on BALB/c mice against fatal doses of highly pathogenic mouse-adapted influenza A subtypes (H1N1, H3N2, and H9N2). Before challenge with influenza virus, C. butyricum S-45-5-treated BALB/c mice showed increased levels of IFN-β, IFN-γ, IL-6, and IL-12 in serum, the small intestine, and bronchoalveolar lavage fluid (BALF), which correlated with observed prophylactic effects. Interestingly, after challenge with influenza virus, C. butyricum S-45-5-treated BALB/c mice showed reduced levels of pro-inflammatory cytokines and relatively higher levels of anti-inflammatory cytokines at day 7 post-infection. Taken together, these findings suggest that C. butyricum S-45-5 plays an antiviral role in vitro and in vivo by inducing an antiviral state and affects immune modulation to alleviate local and systemic inflammatory responses caused by influenza virus infection. Our study provides the beneficial effects of the new C. butyricum S-45-5 with antiviral effects as a probiotic.
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Affiliation(s)
- Kiramage Chathuranga
- College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea
| | - Yeseul Shin
- Access to Genetic Resources and Benefit-Sharing (ABS) Research Support Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea
| | - Md Bashir Uddin
- College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea
- Department of Medicine, Sylhet Agricultural University, Sylhet, Bangladesh
- Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, United States
| | - Jayoung Paek
- Access to Genetic Resources and Benefit-Sharing (ABS) Research Support Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea
| | | | - Yebin Seong
- College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea
| | - Lu Bai
- Access to Genetic Resources and Benefit-Sharing (ABS) Research Support Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea
| | - Hongik Kim
- Research and Development Division, Vitabio, Inc., Daejeon, Republic of Korea
| | - Jeong Hwan Shin
- Department of Laboratory Medicine, Inje University College of Medicine, Busan, Republic of Korea
| | - Young-Hyo Chang
- Access to Genetic Resources and Benefit-Sharing (ABS) Research Support Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea
| | - Jong-Soo Lee
- College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea
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Li C, Peng K, Xiao S, Long Y, Yu Q. The role of Lactobacillus in inflammatory bowel disease: from actualities to prospects. Cell Death Discov 2023; 9:361. [PMID: 37773196 PMCID: PMC10541886 DOI: 10.1038/s41420-023-01666-w] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Revised: 09/18/2023] [Accepted: 09/22/2023] [Indexed: 10/01/2023] Open
Abstract
Inflammatory Bowel Disease (IBD), a chronic nonspecific intestinal inflammatory disease, is comprised of Ulcerative Colitis (UC) and Crohn's Disease (CD). IBD is closely related to a systemic inflammatory reaction and affects the progression of many intestinal and extraintestinal diseases. As one of the representative bacteria for probiotic-assisted therapy in IBD, multiple strains of Lactobacillus have been proven to alleviate intestinal damage and strengthen the intestinal immunological barrier, epithelial cell barrier, and mucus barrier. Lactobacillus also spares no effort in the alleviation of IBD-related diseases such as Colitis-associated Colorectal cancer (CAC), Alzheimer's Disease (AD), Depression, Anxiety, Autoimmune Hepatitis (AIH), and so on via gut-brain axis and gut-liver axis. This article aims to discuss the role of Lactobacillus in IBD and IBD-related diseases, including its underlying mechanisms and related curative strategies from the present to the future.
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Affiliation(s)
- Congxin Li
- Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China
- Institute of Liver and Gastrointestinal Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China
| | - Kaixin Peng
- Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China
- Institute of Liver and Gastrointestinal Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China
| | - Siqi Xiao
- Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China
- Institute of Liver and Gastrointestinal Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China
| | - Yuanyuan Long
- Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China
- Institute of Liver and Gastrointestinal Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China
| | - Qin Yu
- Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China.
- Institute of Liver and Gastrointestinal Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China.
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Wen X, Xie R, Wang HG, Zhang MN, He L, Zhang MH, Yang XZ. Fecal microbiota transplantation alleviates experimental colitis through the Toll-like receptor 4 signaling pathway. World J Gastroenterol 2023; 29:4657-4670. [PMID: 37662857 PMCID: PMC10472902 DOI: 10.3748/wjg.v29.i30.4657] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 07/03/2023] [Accepted: 07/11/2023] [Indexed: 08/10/2023] Open
Abstract
BACKGROUND Fecal microbiota transplantation (FMT) has shown promising therapeutic effects on mice with experimental colitis and patients with ulcerative colitis (UC). FMT modulates the Toll-like receptor 4 (TLR4) signaling pathway to treat some other diseases. However, it remains unknown whether this modulation is also involved in the treatment of UC. AIM To clarify the necessity of TLR4 signaling pathway in FMT on dextran sodium sulphate (DSS)-induced mice and explain the mechanism of FMT on UC, through association analysis of gut microbiota with colon transcriptome in mice. METHODS A mouse colitis model was constructed with wild-type (WT) and TLR4-knockout (KO) mice. Fecal microbiota was transplanted by gavage. Colon inflammation severity was measured by disease activity index (DAI) scoring and hematoxylin and eosin staining. Gut microbiota structure was analyzed through 16S ribosomal RNA sequencing. Gene expression in the mouse colon was obtained by transcriptome sequencing. RESULTS The KO (DSS + Water) and KO (DSS + FMT) groups displayed indistinguishable body weight loss, colon length, DAI score, and histology score, which showed that FMT could not inhibit the disease in KO mice. In mice treated with FMT, the relative abundance of Akkermansia decreased, and Lactobacillus became dominant. In particular, compared with those in WT mice, the scores of DAI and colon histology were clearly decreased in the KO-DSS group. Microbiota structure showed a significant difference between KO and WT mice. Akkermansia were the dominant genus in healthy KO mice. The ineffectiveness of FMT in KO mice was related to the decreased abundance of Akkermansia. Gene Ontology enrichment analysis showed that differentially expressed genes between each group were mainly involved in cytoplasmic translation and cellular response to DNA damage stimulus. The top nine genes correlating with Akkermansia included Aqp4, Clca4a, Dpm3, Fau, Mcrip1, Meis3, Nupr1 L, Pank3, and Rps13 (|R| > 0.9, P < 0.01). CONCLUSION FMT may ameliorate DSS-induced colitis by regulating the TLR4 signaling pathway. TLR4 modulates the composition of gut microbiota and the expression of related genes to ameliorate colitis and maintain the stability of the intestinal environment. Akkermansia bear great therapeutic potential for colitis.
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Affiliation(s)
- Xin Wen
- Department of Gastroenterology, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huai’an 223300, Jiangsu Province, China
| | - Rui Xie
- Department of Gastroenterology, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huai’an 223300, Jiangsu Province, China
| | - Hong-Gang Wang
- Department of Gastroenterology, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huai’an 223300, Jiangsu Province, China
| | - Min-Na Zhang
- Department of Gastroenterology, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huai’an 223300, Jiangsu Province, China
| | - Le He
- Department of Gastroenterology, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huai’an 223300, Jiangsu Province, China
| | - Meng-Hui Zhang
- Department of Gastroenterology, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huai’an 223300, Jiangsu Province, China
| | - Xiao-Zhong Yang
- Department of Gastroenterology, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huai’an 223300, Jiangsu Province, China
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22
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Liu J, Cai J, Fan P, Dong X, Zhang N, Tai J, Cao Y. Salidroside alleviates dextran sulfate sodium-induced colitis in mice by modulating the gut microbiota. Food Funct 2023; 14:7506-7519. [PMID: 37504971 DOI: 10.1039/d3fo01929b] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/29/2023]
Abstract
Dysbiosis causes continuous progress of inflammatory bowel disease (IBD). Herein, we aim to explore whether Salidroside (Sal), which is a major glycoside extracted from Rhodiola rosea L., could ameliorate dextran sulfate sodium (DSS)-induced colitis by modulating the microbiota. Results showed that oral treatment with 15 mg kg-1 of Sal inhibited DSS-induced colitis in mice as evidenced by colon length, histological analysis, disease activity index (DAI) score, and the proportion and number of macrophages in the intestine. The gut microbiota of colitic mice was also partly restored by Sal. A fecal microbiota transplantation (FMT) study was designed to verify the causality. Compared with DSS-treated mice, FM from the Sal-treated donor mice significantly mitigated the symptoms of colitic mice, including reducing the DAI score, alleviating tissue damage, boosting the expression of mucin protein (mucin-2) and tight junction (TJ) proteins (occludin and zonula occludens-1 (ZO-1), and decreasing M1 macrophages in the gut. It was found that both Sal and FMT affected the structure and abundance of the gut microbiota as reflected by the decreased relative abundance of Turicibacter, Alistipes, Romboutsia and the increased relative abundance of Lactobacillus at the genus level. Moreover, the anti-inflammatory effect of Sal disappeared when the gut microbiota was depleted by antibiotics, demonstrating that Sal alleviated the intestinal inflammation in a gut microbiota-dependent manner. Thus, Sal could be a remarkable candidate as a functional food for colitis.
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Affiliation(s)
- Jiuxi Liu
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, 130062 Changchun, People's Republic of China.
- CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, 510530 Guangzhou, People's Republic of China
| | - Jiapei Cai
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, 130062 Changchun, People's Republic of China.
| | - Peng Fan
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, 130062 Changchun, People's Republic of China.
| | - Xue Dong
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, 130062 Changchun, People's Republic of China.
| | - Naisheng Zhang
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, 130062 Changchun, People's Republic of China.
| | - Jiandong Tai
- Department of Colorectal & Anal Surgery, General Surgery Center, The First Hospital of Jilin University, 130021 Changchun, People's Republic of China.
| | - Yongguo Cao
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, 130062 Changchun, People's Republic of China.
- Key Laboratory for Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, 130062 Changchun, People's Republic of China
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23
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Ding X, Jiang W, Li M, Xiong S, Wei W, Liu M, Xin H, Luo Z, Zhao Y. An ROS/DAMP dual-scavenging nanomedicine for normalizing macrophage polarization and microbiome in colitis. NANO TODAY 2023; 51:101924. [DOI: 10.1016/j.nantod.2023.101924] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2025]
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24
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Li X, Wu J, Wu Y, Duan Z, Luo M, Li L, Li S, Jia Y. Imbalance of Vaginal Microbiota and Immunity: Two Main Accomplices of Cervical Cancer in Chinese Women. Int J Womens Health 2023; 15:987-1002. [PMID: 37424699 PMCID: PMC10329453 DOI: 10.2147/ijwh.s406596] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Accepted: 06/27/2023] [Indexed: 07/11/2023] Open
Abstract
Objective To explore the correlation of female vaginal microbiota and immune factors with cervical cancer. Methods The distribution pattern difference of vaginal microbiota of four groups of women (cervical cancer, HPV-positive CIN, HPV-positive non-CIN, and HPV-negative groups) were compared by microbial 16S rDNA sequencing. The protein chip was used to detect the composition and changes of the immune factors in the four groups. Results Alpha diversity analysis demonstrated that the diversity of the vaginal microbiota was increased as the disease develops. Among those bacteria abundant in the vaginal microbiota, Lactobacillus, Prevotella, and Gardnerella dominate at the genus level of vaginal flora. Compared with the HPV-negative group, the differentially dominant bacteria, such as Prevotella, Ralstonia, Gardnerella and Sneathia, are enriched in the cervical cancer group. Likewise, Gardnerella, Prevotella, and Sneathia are more in the HPV-positive CIN group, while Gardnerella and Prevotella in the HPV-positive non-CIN group, respectively. In contrast, Lactobacillus and Atopobium are dominant in the HPV-negative group (LDA>4log10). The concentration of inflammatory immune factors IP-10 and VEGF-A were increased in the cervical cancer group (P < 0.05), compared with other groups. Conclusion The occurrence of cervical cancer is related to an increase of vaginal microbiota diversity and up-regulation of inflammatory immune factor proteins. The abundance of Lactobacillus was decreased while the one of Prevotella and Gardnerella were increased in the cervical cancer group, compared with other three groups. Moreover, the IP-10 and VEGF-A were also increased in the cervical cancer group. Thus, evaluation of changes in the vaginal microbiota and these two immune factor levels might be a potential non-invasive and simple method to predict cervical cancer. Furthermore, it is significant to adjust and restore the balance of vaginal microbiota and maintain normal immune function in preventing and treating cervical cancer.
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Affiliation(s)
- Xiaoge Li
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China
| | - Jin Wu
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China
| | - Yutong Wu
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China
| | - Zhaoning Duan
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China
| | - Ming Luo
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China
| | - Ling Li
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China
| | - Sijing Li
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China
| | - Ying Jia
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China
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Ozen M, Piloquet H, Schaubeck M. Limosilactobacillus fermentum CECT5716: Clinical Potential of a Probiotic Strain Isolated from Human Milk. Nutrients 2023; 15:2207. [PMID: 37432320 PMCID: PMC10181152 DOI: 10.3390/nu15092207] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 04/28/2023] [Accepted: 05/02/2023] [Indexed: 07/12/2023] Open
Abstract
Breastfeeding provides the ideal nutrition for infants. Human milk contains a plethora of functional ingredients which foster the development of the immune system. The human milk microbiota predominantly contributes to this protective effect. This is mediated by various mechanisms, such as an antimicrobial effect, pathogen exclusion and barrier integrity, beneficial effects on the gastrointestinal microbiota, vitamin synthesis, immunity enhancement, secreted probiotic factors, and postbiotic mechanisms. Therefore, human milk is a good source for isolating probiotics for infants who cannot be exclusively breastfed. One such probiotic which was isolated from human milk is Limosilactobacillus fermentum CECT5716. In this review, we give an overview of available interventional studies using Limosilactobacillus fermentum CECT5716 and summarise preclinical trials in several animal models of different pathologies, which have given first insights into its mechanisms of action. We present several randomised clinical studies, which have been conducted to investigate the clinical efficacy of the Limosilactobacillus fermentum CECT5716 strain in supporting the host's health.
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Affiliation(s)
- Metehan Ozen
- School of Medicine, Acibadem Mehmet Ali Aydinlar University, 34752 Istanbul, Türkiye;
| | - Hugues Piloquet
- Department of Paediatric Chronic Diseases, Nantes University Hospital, 44000 Nantes, France;
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26
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Hu Y, Guan X, He Z, Xie Y, Niu Z, Zhang W, Wang A, Zhang J, Si C, Li F, Hu W. Apigenin-7-O-glucoside alleviates DSS-induced colitis by improving intestinal barrier function and modulating gut microbiota. J Funct Foods 2023. [DOI: 10.1016/j.jff.2023.105499] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/28/2023] Open
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27
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Pal R, Athamneh AI, Deshpande R, Ramirez JAR, Adu KT, Muthuirulan P, Pawar S, Biazzo M, Apidianakis Y, Sundekilde UK, de la Fuente-Nunez C, Martens MG, Tegos GP, Seleem MN. Probiotics: insights and new opportunities for Clostridioides difficile intervention. Crit Rev Microbiol 2023; 49:414-434. [PMID: 35574602 PMCID: PMC9743071 DOI: 10.1080/1040841x.2022.2072705] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 04/17/2022] [Accepted: 04/28/2022] [Indexed: 02/08/2023]
Abstract
Clostridioides difficile infection (CDI) is a life-threatening disease caused by the Gram-positive, opportunistic intestinal pathogen C. difficile. Despite the availability of antimicrobial drugs to treat CDI, such as vancomycin, metronidazole, and fidaxomicin, recurrence of infection remains a significant clinical challenge. The use of live commensal microorganisms, or probiotics, is one of the most investigated non-antibiotic therapeutic options to balance gastrointestinal (GI) microbiota and subsequently tackle dysbiosis. In this review, we will discuss major commensal probiotic strains that have the potential to prevent and/or treat CDI and its recurrence, reassess the efficacy of probiotics supplementation as a CDI intervention, delve into lessons learned from probiotic modulation of the immune system, explore avenues like genome-scale metabolic network reconstructions, genome sequencing, and multi-omics to identify novel strains and understand their functionality, and discuss the current regulatory framework, challenges, and future directions.
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Affiliation(s)
- Rusha Pal
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, 24061, USA
| | - Ahmad I.M. Athamneh
- Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA
| | | | - Jose A. R Ramirez
- ProbioWorld Consulting Group, James Cook University, 4811, Queensland, Australia
| | - Kayode T. Adu
- ProbioWorld Consulting Group, James Cook University, 4811, Queensland, Australia
- Cann Group, Walter and Eliza Hall Institute, La Trobe University, Victoria 3083, Australia
| | | | - Shrikant Pawar
- The Anlyan Center Yale Center for Genomic Analysis, Yale School of Medicine, New Haven CT USA
| | - Manuele Biazzo
- The Bioarte Ltd Laboratories at Life Science Park, San Gwann, Malta
| | | | | | - Cesar de la Fuente-Nunez
- Machine Biology Group, Departments of Psychiatry and Microbiology, Institute for Biomedical Informatics, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
- Departments of Bioengineering and Chemical and Biomolecular Engineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
- Penn Institute for Computational Science, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
| | - Mark G. Martens
- Reading Hospital, Tower Health, West Reading, PA 19611, USA
- Drexel University College of Medicine, Philadelphia, PA, 19129, USA
| | - George P. Tegos
- Drexel University College of Medicine, Philadelphia, PA, 19129, USA
| | - Mohamed N. Seleem
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, 24061, USA
- Center for Emerging, Zoonotic and Arthropod-borne Pathogens, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA
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28
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Řezáč M, Řezáčová V, Gloríková N, Némethová E, Heneberg P. Food provisioning to Pardosa spiders decreases the levels of tissue-resident endosymbiotic bacteria. Sci Rep 2023; 13:6943. [PMID: 37117271 PMCID: PMC10147729 DOI: 10.1038/s41598-023-34229-1] [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: 12/12/2022] [Accepted: 04/26/2023] [Indexed: 04/30/2023] Open
Abstract
The diversity, host specificity, and physiological effects of endosymbiotic bacteria in spiders (Araneae) are poorly characterized. We used 16S rDNA sequencing to evaluate endosymbionts in the cephalothorax and legs of a wolf spider Pardosa agrestis. We tested the effects of feeding once or twice daily with fruit flies, aphids, or starved and compared them to those of syntopically occurring Pardosa palustris. The feeding increased traveled distance up to five times in some of the groups provisioned with food relative to the starved control. The Shannon diversity t-test revealed significant differences between these component communities of the two spider species. The increased frequency of feeding with fruit flies, but not aphids, increased the dominance and decreased the alpha diversity of OTUs. The obligate or facultative endosymbionts were present in all analyzed spider individuals and were represented mostly by Rickettsiella, Rhabdochlamydia, Spiroplasma, and the facultative intracellular parasite Legionella. Vertically transmitted endosymbionts were less common, represented by Wolbachia pipientis and Rickettsia sp. H820. The relative abundance of Mycoplasma spp. was negatively correlated with provisioned or killed aphids. In conclusion, the tissues of Pardosa spiders host tremendously diverse assemblages of bacteria, including obligate or facultative endosymbionts, with yet unknown phenotypic effects.
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Affiliation(s)
- Milan Řezáč
- Crop Research Institute, Drnovská 507, 160 00, Prague, Czech Republic
| | - Veronika Řezáčová
- Crop Research Institute, Drnovská 507, 160 00, Prague, Czech Republic.
| | - Nela Gloríková
- Crop Research Institute, Drnovská 507, 160 00, Prague, Czech Republic
| | - Ema Némethová
- Crop Research Institute, Drnovská 507, 160 00, Prague, Czech Republic
| | - Petr Heneberg
- Crop Research Institute, Drnovská 507, 160 00, Prague, Czech Republic.
- Charles University, Third Faculty of Medicine, Ruská 87, 100 00, Prague, Czech Republic.
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Jach ME, Serefko A, Szopa A, Sajnaga E, Golczyk H, Santos LS, Borowicz-Reutt K, Sieniawska E. The Role of Probiotics and Their Metabolites in the Treatment of Depression. Molecules 2023; 28:molecules28073213. [PMID: 37049975 PMCID: PMC10096791 DOI: 10.3390/molecules28073213] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 03/31/2023] [Accepted: 04/02/2023] [Indexed: 04/08/2023] Open
Abstract
Depression is a common and complex mental and emotional disorder that causes disability, morbidity, and quite often mortality around the world. Depression is closely related to several physical and metabolic conditions causing metabolic depression. Studies have indicated that there is a relationship between the intestinal microbiota and the brain, known as the gut–brain axis. While this microbiota–gut–brain connection is disturbed, dysfunctions of the brain, immune system, endocrine system, and gastrointestinal tract occur. Numerous studies show that intestinal dysbiosis characterized by abnormal microbiota and dysfunction of the microbiota–gut–brain axis could be a direct cause of mental and emotional disorders. Traditional treatment of depression includes psychotherapy and pharmacotherapy, and it mainly targets the brain. However, restoration of the intestinal microbiota and functions of the gut–brain axis via using probiotics, their metabolites, prebiotics, and healthy diet may alleviate depressive symptoms. Administration of probiotics labeled as psychobiotics and their metabolites as metabiotics, especially as an adjuvant to antidepressants, improves mental disorders. It is a new approach to the prevention, management, and treatment of mental and emotional illnesses, particularly major depressive disorder and metabolic depression. For the effectiveness of antidepressant therapy, psychobiotics should be administered at a dose higher than 1 billion CFU/day for at least 8 weeks.
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Affiliation(s)
- Monika Elżbieta Jach
- Department of Molecular Biology, The John Paul II Catholic University of Lublin, Konstantynów Street 1I, 20-708 Lublin, Poland
| | - Anna Serefko
- Department of Clinical Pharmacy and Pharmaceutical Care, Medical University of Lublin, Chodźki Street 1, 20-093 Lublin, Poland
| | - Aleksandra Szopa
- Department of Clinical Pharmacy and Pharmaceutical Care, Medical University of Lublin, Chodźki Street 1, 20-093 Lublin, Poland
| | - Ewa Sajnaga
- Department of Biomedicine and Environmental Research, The John Paul II Catholic University of Lublin, Konstantynów Street 1J, 20-708 Lublin, Poland
| | - Hieronim Golczyk
- Department of Molecular Biology, The John Paul II Catholic University of Lublin, Konstantynów Street 1I, 20-708 Lublin, Poland
| | - Leandro Soares Santos
- Department of Animal and Rural Technology, State University of Southwest Bahia, Itapetinga 45700-000, BA, Brazil
| | - Kinga Borowicz-Reutt
- Independent Unit of Experimental Neuropathophysiology, Department of Toxicology, Medical University of Lublin, Jaczewskiego 8b, 20-090 Lublin, Poland
| | - Elwira Sieniawska
- Department of Natural Products Chemistry, Medical University of Lublin, Chodźki Street 1, 20-093 Lublin, Poland
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30
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Mazziotta C, Tognon M, Martini F, Torreggiani E, Rotondo JC. Probiotics Mechanism of Action on Immune Cells and Beneficial Effects on Human Health. Cells 2023; 12:cells12010184. [PMID: 36611977 PMCID: PMC9818925 DOI: 10.3390/cells12010184] [Citation(s) in RCA: 221] [Impact Index Per Article: 110.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 12/12/2022] [Accepted: 12/29/2022] [Indexed: 01/03/2023] Open
Abstract
Immune cells and commensal microbes in the human intestine constantly communicate with and react to each other in a stable environment in order to maintain healthy immune activities. Immune system-microbiota cross-talk relies on a complex network of pathways that sustain the balance between immune tolerance and immunogenicity. Probiotic bacteria can interact and stimulate intestinal immune cells and commensal microflora to modulate specific immune functions and immune homeostasis. Growing evidence shows that probiotic bacteria present important health-promoting and immunomodulatory properties. Thus, the use of probiotics might represent a promising approach for improving immune system activities. So far, few studies have been reported on the beneficial immune modulatory effect of probiotics. However, many others, which are mainly focused on their metabolic/nutritional properties, have been published. Therefore, the mechanisms behind the interaction between host immune cells and probiotics have only been partially described. The present review aims to collect and summarize the most recent scientific results and the resulting implications of how probiotic bacteria and immune cells interact to improve immune functions. Hence, a description of the currently known immunomodulatory mechanisms of probiotic bacteria in improving the host immune system is provided.
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Affiliation(s)
- Chiara Mazziotta
- Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy
- Center for Studies on Gender Medicine, Department of Medical Sciences, University of Ferrara, 64/b, Fossato di Mortara Street, 44121 Ferrara, Italy
| | - Mauro Tognon
- Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy
| | - Fernanda Martini
- Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy
- Center for Studies on Gender Medicine, Department of Medical Sciences, University of Ferrara, 64/b, Fossato di Mortara Street, 44121 Ferrara, Italy
- Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, 44121 Ferrara, Italy
| | - Elena Torreggiani
- Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy
- Correspondence: (E.T.); (J.C.R.); Tel.: +39-053-2455-557 (E.T.); +39-053-245-5536 (J.C.R.)
| | - John Charles Rotondo
- Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy
- Center for Studies on Gender Medicine, Department of Medical Sciences, University of Ferrara, 64/b, Fossato di Mortara Street, 44121 Ferrara, Italy
- Correspondence: (E.T.); (J.C.R.); Tel.: +39-053-2455-557 (E.T.); +39-053-245-5536 (J.C.R.)
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31
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Caballero V, Estévez M, Tomás-Barberán FA, Morcuende D, Martín I, Delgado J. Biodegradation of Punicalagin into Ellagic Acid by Selected Probiotic Bacteria: A Study of the Underlying Mechanisms by MS-Based Proteomics. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2022; 70:16273-16285. [PMID: 36519204 PMCID: PMC9801417 DOI: 10.1021/acs.jafc.2c06585] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 12/02/2022] [Accepted: 12/05/2022] [Indexed: 05/31/2023]
Abstract
Pomegranate (Punica granatum L.) is a well-known source of bioactive phenolic compounds such as ellagitannins, anthocyanins, and flavanols. Punicalagin, one of the main constituents of pomegranate, needs to be biodegraded by bacteria to yield metabolites of medicinal interest. In this work, we tested 30 lactic acid bacteria (LAB) and their capacity to transform punicalagin from a punicalagin-rich pomegranate extract into smaller bioactive molecules, namely, ellagic acid and urolithins. These were identified and quantified by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS2). Further, we evaluated the molecular mechanism governing this transformation through label-free comparative MS-based proteomics. All tested LAB strains were capable of transforming punicalagin into ellagic acid, while the biosynthesis of urolithins was not observed. Proteomic analysis revealed an increase of generic transglycosylases that might have a hydrolytic role in the target phenolic molecule, coupled with an increase in the quantity of ATP-binding cassette (ABC) transporters, which might play a relevant role in transporting the resulting byproducts in and out of the cell.
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Affiliation(s)
- Víctor Caballero
- Food
Technology, IPROCAR Research Institute, Universidad de Extremadura, 10003Cáceres, Spain
- Food
Hygiene and Safety, IPROCAR Research Institute, Universidad de Extremadura, 10003Cáceres, Spain
| | - Mario Estévez
- Food
Technology, IPROCAR Research Institute, Universidad de Extremadura, 10003Cáceres, Spain
| | | | - David Morcuende
- Food
Technology, IPROCAR Research Institute, Universidad de Extremadura, 10003Cáceres, Spain
| | - Irene Martín
- Food
Hygiene and Safety, IPROCAR Research Institute, Universidad de Extremadura, 10003Cáceres, Spain
| | - Josué Delgado
- Food
Hygiene and Safety, IPROCAR Research Institute, Universidad de Extremadura, 10003Cáceres, Spain
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32
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Changes in resident microbiota associated with mice susceptibility or resistance to the intestinal trematode Echinostoma caproni. Parasitology 2022; 149:1781-1793. [PMID: 36176223 PMCID: PMC10090781 DOI: 10.1017/s0031182022001366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Echinostoma caproni (Trematoda: Echinostomatidae) is an intestinal trematode with no tissue phases in the definitive host that has been extensively used as an experimental model to study the factors that determine resistance against intestinal helminths. In E. caproni infections in mice, interleukin-25 (IL-25) plays a critical role and it is required for the resistance to infection. However, little is known on the factors that determine its production. Primary E. caproni infection in mice is characterized by the development of chronic infections and elevated worm recovery, in relation to a local Th1 response with elevated production of interferon-γ. However, partial resistance against secondary E. caproni infections in ICR (Institute of Cancer Research) mice is developed after the chemotherapeutic cure of a primary infection and the innately produced IL-25 after pharmacological treatment. In this paper, we analyse the potential role of intestinal microbiota in the production of IL-25, and the subsequent resistance to infection. For this purpose, we analysed the production of IL-25 under conditions of experimental dysbiosis and also the changes in the resident microbiota in primary infections, pharmacological curation and secondary infections. The results obtained showed that resident microbiota play a major role in the production of IL-25 and the appearance of members of the phylum Verrucomicrobia as a consequence of the curation of the primary infection could be related to the partial resistance to secondary infection.
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Liang X, Dai N, Sheng K, Lu H, Wang J, Chen L, Wang Y. Gut bacterial extracellular vesicles: important players in regulating intestinal microenvironment. Gut Microbes 2022; 14:2134689. [PMID: 36242585 PMCID: PMC9578468 DOI: 10.1080/19490976.2022.2134689] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Intestinal microenvironment dysbiosis is one of the major causes of diseases, such as obesity, diabetes, inflammatory bowel disease, and colon cancer. Microbiota-based strategies have excellent clinical potential in the treatment of repetitive and refractory diseases; however, the underlying regulatory mechanisms remain elusive. Identification of the internal regulatory mechanism of the gut microbiome and the interaction mechanisms involving bacteria-host is essential to achieve precise control of the gut microbiome and obtain effective clinical data. Gut bacteria-derived extracellular vesicles (GBEVs) are lipid bilayer nanoparticles secreted by the gut microbiota and are considered key players in bacteria-bacteria and bacteria-host communication. This review focusses on the role of GBEVs in gut microbiota interactions and bacteria-host communication, and the potential clinical applications of GBEVs.
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Affiliation(s)
- Xiao Liang
- School of Life Sciences, Anhui University, Hefei, China,Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, China,Anhui Key Laboratory of Modern Biomanufacturing, Anhui University, Hefei, China
| | - Nini Dai
- School of Life Sciences, Anhui University, Hefei, China,Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, China,Anhui Key Laboratory of Modern Biomanufacturing, Anhui University, Hefei, China
| | - Kangliang Sheng
- School of Life Sciences, Anhui University, Hefei, China,Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, China,Anhui Key Laboratory of Modern Biomanufacturing, Anhui University, Hefei, China
| | - Hengqian Lu
- School of Life Sciences, Anhui University, Hefei, China,Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, China,Anhui Key Laboratory of Modern Biomanufacturing, Anhui University, Hefei, China
| | - Jingmin Wang
- School of Life Sciences, Anhui University, Hefei, China,Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, China,Anhui Key Laboratory of Modern Biomanufacturing, Anhui University, Hefei, China
| | - Liping Chen
- School of Life Sciences, Anhui University, Hefei, China,Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, China,Anhui Key Laboratory of Modern Biomanufacturing, Anhui University, Hefei, China
| | - Yongzhong Wang
- School of Life Sciences, Anhui University, Hefei, China,Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, China,Anhui Key Laboratory of Modern Biomanufacturing, Anhui University, Hefei, China,Institute of Physical Science and Information Technology, Anhui University, Hefei, China,CONTACT Yongzhong Wang School of Life Sciences, Anhui University, Hefei, China
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Delgadinho M, Ginete C, Santos B, Fernandes C, Silva C, Miranda A, de Vasconcelos JN, Brito M. How Hydroxyurea Alters the Gut Microbiome: A Longitudinal Study Involving Angolan Children with Sickle Cell Anemia. Int J Mol Sci 2022; 23:9061. [PMID: 36012325 PMCID: PMC9409137 DOI: 10.3390/ijms23169061] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 08/08/2022] [Accepted: 08/11/2022] [Indexed: 11/16/2022] Open
Abstract
Sickle cell anemia (SCA) is an inherited hematological disorder and a serious global health problem, especially in Sub-Saharan Africa. Although hydroxyurea (HU) is the leading treatment for patients with SCA, its effects on the gut microbiome have not yet been explored. In this context, the aim of this study was to investigate this association by characterizing the gut microbiome of an Angolan SCA pediatric population before and after 6 months of HU treatment. A total of 66 stool samples were obtained and sequenced for the 16S rRNA gene (V3-V4 regions). Significant associations were observed in alpha and beta-diversity, with higher values of species richness for the children naïve for HU. We also noticed that children after HU had higher proportions of several beneficial bacteria, mostly short-chain fatty acids (SCFAs) producing species, such as Blautia luti, Roseburia inulinivorans, Eubacterium halli, Faecalibacterium, Ruminococcus, Lactobacillus rogosae, among others. In addition, before HU there was a higher abundance of Clostridium_g24, which includes C. bolteae and C. clostridioforme, both considered pathogenic. This study provides the first evidence of the HU effect on the gut microbiome and unravels several microorganisms that could be considered candidate biomarkers for disease severity and HU efficacy.
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Affiliation(s)
- Mariana Delgadinho
- H&TRC-Health & Technology Research Center, ESTeSL-Escola Superior de Tecnologia da Saúde, Instituto Politécnico de Lisboa, 1990-096 Lisbon, Portugal
| | - Catarina Ginete
- H&TRC-Health & Technology Research Center, ESTeSL-Escola Superior de Tecnologia da Saúde, Instituto Politécnico de Lisboa, 1990-096 Lisbon, Portugal
| | - Brígida Santos
- Centro de Investigação em Saúde de Angola (CISA), Hospital Geral do Bengo, Bengo 9999, Angola
- Hospital Pediátrico David Bernardino (HPDB), Luanda 3067, Angola
| | - Carolina Fernandes
- H&TRC-Health & Technology Research Center, ESTeSL-Escola Superior de Tecnologia da Saúde, Instituto Politécnico de Lisboa, 1990-096 Lisbon, Portugal
| | - Carina Silva
- H&TRC-Health & Technology Research Center, ESTeSL-Escola Superior de Tecnologia da Saúde, Instituto Politécnico de Lisboa, 1990-096 Lisbon, Portugal
- Centro de Estatística e Aplicações, Universidade de Lisboa, 1749-016 Lisbon, Portugal
| | - Armandina Miranda
- Instituto Nacional de Saúde Doutor Ricardo Jorge (INSA), 1649-016 Lisbon, Portugal
| | | | - Miguel Brito
- H&TRC-Health & Technology Research Center, ESTeSL-Escola Superior de Tecnologia da Saúde, Instituto Politécnico de Lisboa, 1990-096 Lisbon, Portugal
- Centro de Investigação em Saúde de Angola (CISA), Hospital Geral do Bengo, Bengo 9999, Angola
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Hamamoto H, Ogasawara AA, Iwasa M, Sekimizu K. Establishment of a polymerase chain reaction-based method for strain-level management of Enterococcus faecalis EF-2001 using species-specific sequences identified by whole genome sequences. Front Microbiol 2022; 13:959063. [PMID: 36033901 PMCID: PMC9411961 DOI: 10.3389/fmicb.2022.959063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Accepted: 07/21/2022] [Indexed: 11/16/2022] Open
Abstract
In the development and manufacture of fermented foods, it is crucial to control and manage the bacterial species used in the products. We previously reported a complete genome sequence analysis of the Enterococcus faecalis EF-2001 strain that was used for supplements. By comparing this sequence to the publicly available complete genome sequence of E. faecalis strains, we were able to identify specific sequences of the EF-2001 strain. We designed primer sets to amplify these specific regions and performed a polymerase chain reaction (PCR). We confirmed that the DNA fragments were specifically amplified in the genome of the EF-2001 strain, but not those of other lactic acid bacteria (LABs) or strains of the same genus. Furthermore, these primers amplified DNA fragments even in genomic DNA extracted from heat-treated bacteria at 121°C and foods containing the EF-2001 strain. These results suggest that this method allows for simple and highly accurate identification of specific fermentation strains, such as LABs at the strain level, which will be useful for controlling the quality of fermented foods.
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Affiliation(s)
- Hiroshi Hamamoto
- Teikyo University Institute of Medical Mycology, Hachio-ji shi, Tokyo, Japan
| | | | | | - Kazuhisa Sekimizu
- Drug Discoveries by Silkworm Models, Faculty of Pharma-Science, Teikyo University, Hachio-ji shi, Tokyo, Japan
- Genome Pharmaceuticals Institute, Ltd., Bunkyo-ku, Tokyo, Japan
- *Correspondence: Kazuhisa Sekimizu,
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Bilal M, Ashraf S, Zhao X. Dietary Component-Induced Inflammation and Its Amelioration by Prebiotics, Probiotics, and Synbiotics. Front Nutr 2022; 9:931458. [PMID: 35938108 PMCID: PMC9354043 DOI: 10.3389/fnut.2022.931458] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Accepted: 06/20/2022] [Indexed: 12/12/2022] Open
Abstract
A balanced diet with many dietary components maintains immune homeostasis directly by interacting with innate and adaptive immune components or indirectly through gut microbiota and their metabolites. Dietary components may inhibit pro-inflammatory mediators and promote anti-inflammatory functions or vice versa. Western diets with imbalanced dietary components skew the immune balance toward pro-inflammation and induce intestinal inflammation, consequently leading to many intestinal and systemic inflammatory diseases like ulcerative colitis, Crohn's disease, irritable bowel syndrome, cardiovascular problems, obesity, and diabetes. The dietary component-induced inflammation is usually chronic in nature and frequently caused or accompanied by alterations in gut microbiota. Therefore, microbiome-targeted therapies such as probiotics, prebiotics and synbiotics hold great potentials to amend immune dysregulation and gut dysbiosis, preventing and treating intestinal and systemic inflammatory diseases. Probiotics, prebiotics and synbioitcs are progressively being added to foods and beverages, with claims of health benefits. However, the underlining mechanisms of these interventions for preventing and treating dietary component-induced inflammation are still not very clear. In addition, possibly ineffective or negative consequences of some probiotics, prebiotics and synbiotics call for stringent testing and regulation. Here, we will first briefly review inflammation, in terms of its types and the relationship between different dietary components and immune responses. Then, we focus on current knowledge about the direct and indirect effects of probiotics, prebiotics and synbiotics on intestinal and systemic inflammation. Understanding how probiotics, prebiotics and synbiotics modulate the immune system and gut microbiota will improve our strategies for preventing and treating dietary component-induced intestinal inflammation and inflammatory diseases.
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Hamilton AM, Sampson TR. Traumatic spinal cord injury and the contributions of the post-injury microbiome. INTERNATIONAL REVIEW OF NEUROBIOLOGY 2022; 167:251-290. [PMID: 36427958 DOI: 10.1016/bs.irn.2022.06.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Spinal cord injuries are an enormous burden on injured individuals and their caregivers. The pathophysiological effects of injury are not limited to the spine and limb function, but affect numerous body systems. Growing observations in human studies and experimental models suggest that the gut microbiome is altered following spinal cord injury. Given the importance of signals derived from the gut microbiome for host physiology, it is possible that injury-triggered dysbiosis subsequently affects aspects of recovery. Here, we review emerging literature on the role of the microbiome following spinal cord injury. Specifically, we highlight findings from both human and experimental studies that correlate taxonomic changes to aspects of injury recovery. Examination of both observational and emerging interventional studies supports the notion that future therapeutic avenues for spinal cord injury pathologies may lie at the interface of the host and indigenous microbes.
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Affiliation(s)
- Adam M Hamilton
- Department of Cell Biology, Emory University School of Medicine, Atlanta, GA, United States
| | - Timothy R Sampson
- Department of Cell Biology, Emory University School of Medicine, Atlanta, GA, United States.
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Tetragenococcus halophilus Alleviates Intestinal Inflammation in Mice by Altering Gut Microbiota and Regulating Dendritic Cell Activation via CD83. Cells 2022; 11:cells11121903. [PMID: 35741032 PMCID: PMC9221263 DOI: 10.3390/cells11121903] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 06/08/2022] [Accepted: 06/09/2022] [Indexed: 01/27/2023] Open
Abstract
Ulcerative colitis (UC) is one of the major subtypes of inflammatory bowel disease with unknown etiology. Probiotics have recently been introduced as a treatment for UC. Tetragenococcus halophilus (T. halophilus) is a lactic acid-producing bacterium that survives in environments with high salt concentrations, though little is known about its immunomodulatory function as a probiotic. The purpose of this study is to determine whether T. halophilus exerts an anti-inflammatory effect on intestinal inflammation in mice. Colitis was induced in C57BL/6J mice by feeding 4% DSS in drinking water for 7 days. T. halophilus was orally administered with DSS. Anti-inflammatory functions were subsequently evaluated by flow cytometry, qRT-PCT, and ELISA. Gut microbial composition was analyzed by 16S rRNA metagenomic analysis. DSS-induced colitis mice treated with T. halophilus showed less weight loss and significantly suppressed colonic shortening compared to DSS-induced colitis mice. T. halophilus significantly reduced the frequency of the dendritic cell activation molecule CD83 in peripheral blood leukocytes and intestinal epithelial lymphocytes. Frequencies of CD8+NK1.1+ cells decreased in mice with colitis after T. halophilus treatment and IL-1β levels were also reduced. Alteration of gut microbiota was observed in mice with colitis after administration of T. halophilus. These results suggest T. halophilus is effective in alleviating DSS-induced colitis in mice by altering immune regulation and gut microbiome compositions.
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Hitch TCA, Hall LJ, Walsh SK, Leventhal GE, Slack E, de Wouters T, Walter J, Clavel T. Microbiome-based interventions to modulate gut ecology and the immune system. Mucosal Immunol 2022; 15:1095-1113. [PMID: 36180583 PMCID: PMC9705255 DOI: 10.1038/s41385-022-00564-1] [Citation(s) in RCA: 65] [Impact Index Per Article: 21.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 08/12/2022] [Accepted: 08/22/2022] [Indexed: 02/04/2023]
Abstract
The gut microbiome lies at the intersection between the environment and the host, with the ability to modify host responses to disease-relevant exposures and stimuli. This is evident in how enteric microbes interact with the immune system, e.g., supporting immune maturation in early life, affecting drug efficacy via modulation of immune responses, or influencing development of immune cell populations and their mediators. Many factors modulate gut ecosystem dynamics during daily life and we are just beginning to realise the therapeutic and prophylactic potential of microbiome-based interventions. These approaches vary in application, goal, and mechanisms of action. Some modify the entire community, such as nutritional approaches or faecal microbiota transplantation, while others, such as phage therapy, probiotics, and prebiotics, target specific taxa or strains. In this review, we assessed the experimental evidence for microbiome-based interventions, with a particular focus on their clinical relevance, ecological effects, and modulation of the immune system.
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Affiliation(s)
- Thomas C A Hitch
- Functional Microbiome Research Group, Institute of Medical Microbiology, University Hospital of RWTH Aachen, Aachen, Germany
| | - Lindsay J Hall
- Gut Microbes & Health, Quadram Institute Biosciences, Norwich, UK
- Intestinal Microbiome, School of Life Sciences, ZIEL-Institute for Food & Health, Technical University of Munich, Freising, Germany
- Norwich Medical School, University of East Anglia, Norwich, UK
| | - Sarah Kate Walsh
- School of Food and Nutritional Sciences, University College Cork, Cork, Ireland
- APC Microbiome Ireland, School of Microbiology and Department of Medicine, University College Cork, Cork, Ireland
| | | | - Emma Slack
- Institute of Food, Nutrition and Health, Department of Health Sciences and Technology, ETH Zürich, Zürich, Switzerland
| | | | - Jens Walter
- APC Microbiome Ireland, School of Microbiology and Department of Medicine, University College Cork, Cork, Ireland
| | - Thomas Clavel
- Functional Microbiome Research Group, Institute of Medical Microbiology, University Hospital of RWTH Aachen, Aachen, Germany.
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Methamphetamine induces intestinal injury by altering gut microbiota and promoting inflammation in mice. Toxicol Appl Pharmacol 2022; 443:116011. [PMID: 35390362 DOI: 10.1016/j.taap.2022.116011] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2021] [Revised: 03/27/2022] [Accepted: 03/31/2022] [Indexed: 02/06/2023]
Abstract
Methamphetamine (METH) is a psychostimulant abused worldwide. Its abuse induces intestinal toxicity. Moreover, the gut microbiota is altered by drugs, which induces intestinal injury. Whether gut microbiota mediates METH-induced intestinal toxicity remains to be validated. In the present study, wild-type and TLR4-/- mice were treated with METH. Gut microbiota was determined using 16S rRNA gene sequencing. Transcriptomics of the intestinal mucosa was performed by RNA-Sequencing. Blood levels of pro-inflammatory cytokines and lipopolysaccharide (LPS), the intestinal barrier, and inflammation were also assessed. METH treatment weakened the intestinal barrier and increased pro-inflammatory cytokines and LPS levels in the blood. Moreover, METH treatment significantly decreased the diversity of probiotics but increased the abundance of pathogenic gut microbiota, contributing to the over-production of LPS and disruption of intestinal barrier. Inflammatory pathways were enriched in the intestinal mucosa of METH-treated mice by KEGG analysis. Consistently, activation of the TLR4 pathway was determined in METH-treated mice, which confirmed intestinal inflammation. However, pretreatment with antibiotics or Tlr4 silencing significantly alleviated METH-induced gut microbiota dysbiosis, LPS over-production, intestinal inflammation, and disruption of the intestinal barrier. These findings suggested that the gut microbiota and LPS-mediated inflammation took an important role in METH-induced intestinal injury. Taken together, these findings suggest that METH-induced intestinal injury is mediated by gut microbiota dysbiosis and LPS-associated inflammation.
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Musazadeh V, Zarezadeh M, Faghfouri AH, Keramati M, Jamilian P, Jamilian P, Mohagheghi A, Farnam A. Probiotics as an effective therapeutic approach in alleviating depression symptoms: an umbrella meta-analysis. Crit Rev Food Sci Nutr 2022; 63:8292-8300. [PMID: 35348020 DOI: 10.1080/10408398.2022.2051164] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Growing evidence has suggested that the consumption of probiotics can decrease depressive symptoms. However, even the results of meta-analyses are conflicting. In this regard, we performed an umbrella meta-analysis and proposed the decisive impacts of probiotics on depressive symptoms. The following international databases were searched up to July 2021: PubMed/Medline, Web of Science, Scopus, EMBASE, and Google Scholar. Meta-analyses investigating the impact of supplementation of probiotics on depression symptoms in adults were included. According to the studies, random-effects model was used to perform the analysis. Subgroup analysis was performed by dosage of probiotics, duration of supplementation and total sample size. Publication bias was assessed using Egger's, Begg's and visual inspection of funnel plot. Ten meta-analyses (n = 8886 participants) were included in study. The pooled data indicated that probiotic supplementation significantly reduced depression symptoms (ES= -1.41; 95% CI: -2.53, -0.30, p = 0.016; I2 = 99.4, p = <0.001). Subgroup analysis of studies with intervention duration >8 weeks and dosage >10 × 109 CFU demonstrated a more robust effect of probiotics on decreasing depression symptoms. There was also significant between-study heterogeneity in which dosage was identified as source of it. The results of present umbrella meta-analysis suggest administration of probiotics for relieving depression symptoms for >8 weeks with dosage of >10 × 109 CFU.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2022.2051164.
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Affiliation(s)
- Vali Musazadeh
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Community Nutrition, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Meysam Zarezadeh
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
- Nutrition Research Center, Department of Clinical Nutrition, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amir Hossein Faghfouri
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Community Nutrition, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Majid Keramati
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Community Nutrition, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Parmida Jamilian
- School of Pharmacy and Bio Engineering, Keele University, Staffordshire, UK
| | - Parsa Jamilian
- Keele University School of Medicine, Keele University, Staffordshire, UK
| | - Arash Mohagheghi
- Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Alireza Farnam
- Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
- Research Center of Psychiatry and Behavioral Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
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Evangelista AG, Danielski GM, Corrêa JAF, Cavalari CMDA, Souza IR, Luciano FB, Macedo REFD. Carnobacterium as a bioprotective and potential probiotic culture to improve food quality, food safety, and human health - a scoping review. Crit Rev Food Sci Nutr 2022; 63:6946-6959. [PMID: 35156482 DOI: 10.1080/10408398.2022.2038079] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
It is well-known that some bacteria can promote human and animal health. Bacteria of the genus Carnobacterium, while underexplored, have demonstrated significant probiotic and bioprotective potential. In this review, the recent scientific advances in this area are discussed. There are several requirements for a strain to be considered a probiotic or bioprotective agent, including the absence of antimicrobial resistance and the ability to colonize the gastrointestinal tract. Several researchers have reported such features in Carnobacterium bacteria, especially with regard to the production of antimicrobial substances. Research into animal production has advanced, especially in the aquaculture field, wherein inhibitory activity has been demonstrated against several important pathogens (for example Vibrio), and improvement in zootechnical indexes is evident. With respect to human health-related applications, research is still in the early stages. However, excellent in vitro results against pathogens, such as Candida albicans and Pseudomonas aeruginosa, have been reported. Carnobacterium bacteria have been assessed for a variety of applications in food, including direct application to the matrix and application to smart packaging, with proven effectiveness against Listeria monocytogenes. However, there is a lack of in vivo studies on Carnobacterium applications, which hinders its applications in various industries despite its high potential.
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Affiliation(s)
| | - Gabriela Maia Danielski
- Graduate Program in Animal Science, Pontifícia Universidade Católica do Paraná, Curitiba, Paraná, Brazil
- Undergraduate Program in Agronomy, Universidade Federal do Paraná, Curitiba, Paraná, Brazil
| | | | | | - Isabelle Ramos Souza
- Undergraduate Program in Veterinary Medicine, Pontifícia Universidade Católica do Paraná, Curitiba, Paraná, Brazil
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Probiotic Molecules That Inhibit Inflammatory Diseases. APPLIED SCIENCES-BASEL 2022. [DOI: 10.3390/app12031147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Consumption of probiotics for health purposes has increased vastly in the past few decades, and yet the scientific evidence to support health benefits from probiotics is only beginning to emerge. As more probiotics are studied, we are beginning to understand the mechanisms of action by which they benefit human health, as well as to identify the bacterial molecules responsible for these benefits. A new era of therapeutics is on the horizon in which purified molecules from probiotics will be used to prevent and treat diseases. In this review, we summarize the active molecules from probiotic bacteria that have been shown to affect innate and adaptive immunity and have health benefits in experimental settings. We focus particularly on the cellular and molecular mechanisms of the probiotic Bacillus subtilis and its active molecule, exopolysaccharide (ESPBs).
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Solieri L, Sola L, Vaccalluzzo A, Randazzo CL, Martini S, Tagliazucchi D. Characterization of Cell-Envelope Proteinases from Two Lacticaseibacillus casei Strains Isolated from Parmigiano Reggiano Cheese. BIOLOGY 2022; 11:biology11010139. [PMID: 35053137 PMCID: PMC8773131 DOI: 10.3390/biology11010139] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 01/12/2022] [Accepted: 01/12/2022] [Indexed: 04/25/2023]
Abstract
In the present work, two cell-envelope proteinases (CEPs) from Lacticaseibacillus casei strains PRA205 and 2006 were characterized at both the biochemical and genetic levels. The genomes of both L. casei strains included two putative CEPs genes prtP2 and prtR1, but only prtR1 was transcribed. The extracted PrtR1 proteinases were serine proteinases with optimal activity at 40 °C and pH 7.5, and were activated by Ca2+ ions. Interestingly, PrtR1 from L. casei PRA205 exhibited high residual activity at pH 4 and at 5 °C, suggesting its possible exploitation for fermented food production. The caseinolytic activity against αS1- and β-casein indicated that both PrtR1s belonged to the PI/PIII type. These PrtR1s cleaved β-casein peptide bonds preferentially when amino acid M or N was present at the P1 subsite and amino acids A and D were at the P1' subsite. Several bioactive peptides were found to be released from PrtR1 after αs1- and β-casein hydrolysis.
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Affiliation(s)
- Lisa Solieri
- Department of Life Sciences, University of Modena and Reggio Emilia, via Amendola, 2—Pad. Besta, 42100 Reggio Emilia, Italy; (L.S.); (L.S.); (S.M.)
| | - Laura Sola
- Department of Life Sciences, University of Modena and Reggio Emilia, via Amendola, 2—Pad. Besta, 42100 Reggio Emilia, Italy; (L.S.); (L.S.); (S.M.)
| | - Amanda Vaccalluzzo
- Department of Agriculture, Food and Environment, University of Catania, via Santa Sofia, 100, 95123 Catania, Italy; (A.V.); (C.L.R.)
| | - Cinzia Lucia Randazzo
- Department of Agriculture, Food and Environment, University of Catania, via Santa Sofia, 100, 95123 Catania, Italy; (A.V.); (C.L.R.)
- ProBioEtna srl, Spin off University of Catania, via Santa Sofia, 100, 95123 Catania, Italy
| | - Serena Martini
- Department of Life Sciences, University of Modena and Reggio Emilia, via Amendola, 2—Pad. Besta, 42100 Reggio Emilia, Italy; (L.S.); (L.S.); (S.M.)
| | - Davide Tagliazucchi
- Department of Life Sciences, University of Modena and Reggio Emilia, via Amendola, 2—Pad. Besta, 42100 Reggio Emilia, Italy; (L.S.); (L.S.); (S.M.)
- Correspondence: ; Tel.: +39-0522-522060
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Harnessing murine models of Crohn's disease ileitis to advance concepts of pathophysiology and treatment. Mucosal Immunol 2022; 15:10-26. [PMID: 34316007 DOI: 10.1038/s41385-021-00433-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 07/09/2021] [Accepted: 07/12/2021] [Indexed: 02/04/2023]
Abstract
Crohn's disease (CD) and ulcerative colitis (UC) are both characterized by chronic inflammation and severe dysfunction of the gastrointestinal tract. These two forms of inflammatory bowel disease (IBD) represent distinct clinical disorders with diverse driving mechanisms; however, this divergence is not reflected in currently approved therapeutics that commonly target general proinflammatory pathways. A compelling need therefore remains to understand factors that differentiate the topology and the distinct clinical manifestations of CD versus UC, in order to develop more effective and specialized therapies. Animal models provide valuable platforms for studying IBD heterogeneity and deciphering disease-specific mechanisms. Both the established and the newly developed ileitis mouse models are characterized by various disease initiating mechanisms and diverse phenotypic outcomes that reflect the complexity of human CD-ileitis. Microbial dysbiosis, destruction of epithelial barrier integrity, immune cell deregulation, as well as the recently described genome instability and stromal cell activation have all been proposed as the triggering factors for the development of ileitis-associated pathology. In this review, we aim to critically evaluate the mechanistic underpinnings of murine models of CD-ileitis, discuss their phenotypic similarities to human disease, and envisage their further exploitation for the development of novel targeted and personalized therapeutics.
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Yang X, Jiang W, Cheng J, Hao J, Han F, Zhang Y, Xu J, Shan C, Wang J, Yang Y, Yang J, Chang B. Reductions in Intestinal Taurine-Conjugated Bile Acids and Short-Chain Fatty Acid-Producing Bacteria Might be Novel Mechanisms of Type 2 Diabetes Mellitus in Otsuka Long-Evans Tokushima Fatty Rats. Exp Clin Endocrinol Diabetes 2021; 130:237-247. [PMID: 34929746 DOI: 10.1055/a-1643-1689] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
BACKGROUND The pathogenesis of spontaneously diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats, among the best models for human type 2 diabetes mellitus (T2DM), remains poorly defined. Therefore, we investigated the dynamic changes in taurine-conjugated bile acids (T-BAs) and intestinal microbiota during T2DM development in OLETF rats. METHODS OLETF rats and corresponding diabetes-resistant Long Evans Tokushima Otsuka (LETO) rats were fed a normal baseline diet. The progress of T2DM was divided into four phases, including normal glycemia-normal insulinemia (baseline), normal glycemia-hyperinsulinemia, impaired glucose tolerance, and DM. Body weight, liver function, blood lipids, fasting plasma glucose, fasting plasma insulin, fasting plasma glucagon-like peptide (GLP)-1 and GLP-2, serum and fecal T-BAs, and gut microbiota were analyzed during the entire course of T2DM development. RESULTS There were reductions in fecal T-BAs and short-chain fatty acids (SCFAs)-producing bacteria including Phascolarctobacterium and Lactobacillus in OLETF rats compared with those in LETO rats at baseline, and low levels of fecal T-BAs and SCFAs-producing bacteria were maintained throughout the whole course of the development of T2DM among OLETF rats compared with those in corresponding age-matched LETO rats. Fecal taurine-conjugated chenodeoxycholic acid correlated positively with Phascolarctobacterium. Fecal taurine-conjugated deoxycholic acid correlated positively with Lactobacillus and fasting plasma GLP-1 and inversely with fasting plasma glucose. CONCLUSION The fecal BAs profiles and microbiota structure among OLETF rats were different from those of LETO rats during the entire course of T2DM development, indicating that reductions in intestinal T-BAs and specific SCFA-producing bacteria may be potential mechanisms of T2DM in OLETF rats.
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Affiliation(s)
- Xiaoyun Yang
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.,Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China
| | - Wenhui Jiang
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.,Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine of Hebei Province, Hebei Province, China
| | - Jingli Cheng
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
| | - Jintong Hao
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
| | - Fei Han
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
| | - Yi Zhang
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
| | - Jie Xu
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
| | - Chunyan Shan
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
| | - Jingyu Wang
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
| | - Yanhui Yang
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
| | - Juhong Yang
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
| | - Baocheng Chang
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
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Jastrząb R, Graczyk D, Siedlecki P. Molecular and Cellular Mechanisms Influenced by Postbiotics. Int J Mol Sci 2021; 22:ijms222413475. [PMID: 34948270 PMCID: PMC8707144 DOI: 10.3390/ijms222413475] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Revised: 11/29/2021] [Accepted: 12/07/2021] [Indexed: 12/12/2022] Open
Abstract
In recent years, commensal bacteria colonizing the human body have been recognized as important determinants of health and multiple pathologic conditions. Among the most extensively studied commensal bacteria are the gut microbiota, which perform a plethora of functions, including the synthesis of bioactive products, metabolism of dietary compounds, and immunomodulation, both through attenuation and immunostimulation. An imbalance in the microbiota population, i.e., dysbiosis, has been linked to many human pathologies, including various cancer types and neurodegenerative diseases. Targeting gut microbiota and microbiome-host interactions resulting from probiotics, prebiotics, and postbiotics is a growing opportunity for the effective treatment of various diseases. As more research is being conducted, the microbiome field is shifting from simple descriptive analysis of commensal compositions to more molecular, cellular, and functional studies. Insight into these mechanisms is of paramount importance for understanding and modulating the effects that microbiota, probiotics, and their derivatives exert on host health.
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An BC, Yoon YS, Park HJ, Park S, Kim TY, Ahn JY, Kwon D, Choi O, Heo JY, Ryu Y, Kim JH, Eom H, Chung MJ. Toxicological Evaluation of a Probiotic-Based Delivery System for P8 Protein as an Anti-Colorectal Cancer Drug. Drug Des Devel Ther 2021; 15:4761-4793. [PMID: 34866901 PMCID: PMC8637785 DOI: 10.2147/dddt.s319930] [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: 07/06/2021] [Accepted: 10/23/2021] [Indexed: 11/24/2022] Open
Abstract
Purpose This study aimed to toxicological evaluate a probiotics-based delivery system for p8 protein as an anti-colorectal cancer drug. Introduction Lactic acid bacteria (LAB) have been widely ingested for many years and are regarded as very safe. Recently, a Pediococcus pentosaceus SL4 (PP) strain that secretes the probiotic-derived anti-cancer protein P8 (PP-P8) has been developed as an anti-colorectal cancer (CRC) biologic by Cell Biotech. We initially identified a Lactobacillus rhamnosus (LR)-derived anti-cancer protein, P8, that suppresses CRC growth. We also showed that P8 penetrates specifically into CRC cells (DLD-1 cells) through endocytosis. We then confirmed the efficacy of PP-P8, showing that oral administration of this agent significantly decreased tumor mass (~42%) relative to controls in a mouse CRC xenograft model. In terms of molecular mechanism, PP-P8 induces cell-cycle arrest in G2 phase through down-regulation of Cyclin B1 and Cdk1. In this study, we performed in vivo toxicology profiling to obtain evidence that PP-P8 is safe, with the goal of receiving approval for an investigational new drug application (IND). Methods Based on gene therapy guidelines of the Ministry of Food and Drug Safety (MFDS) of Korea, the potential undesirable effects of PP-P8 had to be investigated in intact small rodent or marmoset models prior to first-in-human (FIH) administration. The estimated doses of PP-P8 for FIH are 1.0×1010 – 1.0×1011 CFU/person (60 kg). Therefore, to perform toxicological investigations in non-clinical animal models, we orally administered PP-P8 at doses of 3.375 × 1011, 6.75 × 1011, and 13.5×1011 CFU/kg/day; thus the maximum dose was 800–8000-fold higher than the estimated dose for FIH. Results In our animal models, we observed no adverse effects of PP-P8 on clinicopathologic findings, relative organ weight, or tissue pathology. In addition, we observed no inflammation or ulceration during pathological necropsy. Conclusion These non-clinical toxicology studies could be used to furnish valuable data for the safety certification of PP-P8.
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Affiliation(s)
- Byung Chull An
- R&D Center, Cell Biotech, Co., Ltd., Gimpo-si, Gyeonggi-do, Korea
| | - Yeo-Sang Yoon
- R&D Center, Cell Biotech, Co., Ltd., Gimpo-si, Gyeonggi-do, Korea
| | - Ho Jin Park
- R&D Center, Cell Biotech, Co., Ltd., Gimpo-si, Gyeonggi-do, Korea
| | - Sangkyun Park
- R&D Center, Cell Biotech, Co., Ltd., Gimpo-si, Gyeonggi-do, Korea
| | - Tai Yeub Kim
- R&D Center, Cell Biotech, Co., Ltd., Gimpo-si, Gyeonggi-do, Korea
| | - Jun Young Ahn
- R&D Center, Cell Biotech, Co., Ltd., Gimpo-si, Gyeonggi-do, Korea
| | - Daebeom Kwon
- R&D Center, Cell Biotech, Co., Ltd., Gimpo-si, Gyeonggi-do, Korea
| | - Oksik Choi
- R&D Center, Cell Biotech, Co., Ltd., Gimpo-si, Gyeonggi-do, Korea
| | - Jin Young Heo
- R&D Center, Cell Biotech, Co., Ltd., Gimpo-si, Gyeonggi-do, Korea
| | - Yongku Ryu
- R&D Center, Cell Biotech, Co., Ltd., Gimpo-si, Gyeonggi-do, Korea
| | - Joong-Hyun Kim
- Laboratory Animal Center, Osong Medical Innovation Foundation, Chungbuk, Cheongju, 28160, Korea
| | - Heejong Eom
- Laboratory Animal Center, Osong Medical Innovation Foundation, Chungbuk, Cheongju, 28160, Korea
| | - Myung Jun Chung
- R&D Center, Cell Biotech, Co., Ltd., Gimpo-si, Gyeonggi-do, Korea
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Ali MQ, Kohler TP, Schulig L, Burchhardt G, Hammerschmidt S. Pneumococcal Extracellular Serine Proteases: Molecular Analysis and Impact on Colonization and Disease. Front Cell Infect Microbiol 2021; 11:763152. [PMID: 34790590 PMCID: PMC8592123 DOI: 10.3389/fcimb.2021.763152] [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: 08/23/2021] [Accepted: 10/08/2021] [Indexed: 11/24/2022] Open
Abstract
The pathobiont Streptococcus pneumoniae causes life-threatening diseases, including pneumonia, sepsis, meningitis, or non-invasive infections such as otitis media. Serine proteases are enzymes that have been emerged during evolution as one of the most abundant and functionally diverse group of proteins in eukaryotic and prokaryotic organisms. S. pneumoniae expresses up to four extracellular serine proteases belonging to the category of trypsin-like or subtilisin-like family proteins: HtrA, SFP, PrtA, and CbpG. These serine proteases have recently received increasing attention because of their immunogenicity and pivotal role in the interaction with host proteins. This review is summarizing and focusing on the molecular and functional analysis of pneumococcal serine proteases, thereby discussing their contribution to pathogenesis.
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Affiliation(s)
- Murtadha Q Ali
- Department of Molecular Genetics and Infection Biology, Interfaculty Institute of Genetics and Functional Genomics, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany
| | - Thomas P Kohler
- Department of Molecular Genetics and Infection Biology, Interfaculty Institute of Genetics and Functional Genomics, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany
| | - Lukas Schulig
- Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, University of Greifswald, Greifswald, Germany
| | - Gerhard Burchhardt
- Department of Molecular Genetics and Infection Biology, Interfaculty Institute of Genetics and Functional Genomics, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany
| | - Sven Hammerschmidt
- Department of Molecular Genetics and Infection Biology, Interfaculty Institute of Genetics and Functional Genomics, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany
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Kameli N, Becker HEF, Welbers T, Jonkers DMAE, Penders J, Savelkoul P, Stassen FR. Metagenomic Profiling of Fecal-Derived Bacterial Membrane Vesicles in Crohn's Disease Patients. Cells 2021; 10:cells10102795. [PMID: 34685776 PMCID: PMC8535131 DOI: 10.3390/cells10102795] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Revised: 10/14/2021] [Accepted: 10/14/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND In the past, many studies suggested a crucial role for dysbiosis of the gut microbiota in the etiology of Crohn's disease (CD). However, despite being important players in host-bacteria interaction, the role of bacterial membrane vesicles (MV) has been largely overlooked in the pathogenesis of CD. In this study, we addressed the composition of the bacterial and MV composition in fecal samples of CD patients and compared this to the composition in healthy individuals. METHODS Fecal samples from six healthy subjects (HC) in addition to twelve CD patients (six active, six remission) were analyzed in this study. Fecal bacterial membrane vesicles (fMVs) were isolated by a combination of ultrafiltration and size exclusion chromatography. DNA was obtained from the fMV fraction, the pellet of dissolved feces as bacterial DNA (bDNA), or directly from feces as fecal DNA (fDNA). The fMVs were characterized by nanoparticle tracking analysis and cryo-electron microscopy. Amplicon sequencing of 16s rRNA V4 hypervariable gene regions was conducted to assess microbial composition of all fractions. RESULTS Beta-diversity analysis showed that the microbial community structure of the fMVs was significantly different from the microbial profiles of the fDNA and bDNA. However, no differences were observed in microbial composition between fDNA and bDNA. The microbial richness of fMVs was significantly decreased in CD patients compared to HC, and even lower in active patients. Profiling of fDNA and bDNA demonstrated that Firmicutes was the most dominant phylum in these fractions, while in fMVs Bacteroidetes was dominant. In fMV, several families and genera belonging to Firmicutes and Proteobacteria were significantly altered in CD patients when compared to HC. CONCLUSION The microbial alterations of MVs in CD patients particularly in Firmicutes and Proteobacteria suggest a possible role of MVs in host-microbe symbiosis and induction or progression of inflammation in CD pathogenesis. Yet, the exact role for these fMV in the pathogenesis of the disease needs to be elucidated in future studies.
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Affiliation(s)
- Nader Kameli
- Department of Medical Microbiology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center+, 6229 ER Maastricht, The Netherlands; (H.E.F.B.); (T.W.); (J.P.); (P.S.)
- Department of Medical Microbiology, Faculty of Applied Medical Sciences, Jazan University, Jazan 45142, Saudi Arabia
- Correspondence: (N.K.); (F.R.S.)
| | - Heike E. F. Becker
- Department of Medical Microbiology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center+, 6229 ER Maastricht, The Netherlands; (H.E.F.B.); (T.W.); (J.P.); (P.S.)
- Department of Internal Medicine, Division of Gastroenterology/Hepatology, NUTRIM school of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, 6200 MD Maastricht, The Netherlands;
| | - Tessa Welbers
- Department of Medical Microbiology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center+, 6229 ER Maastricht, The Netherlands; (H.E.F.B.); (T.W.); (J.P.); (P.S.)
| | - Daisy M. A. E. Jonkers
- Department of Internal Medicine, Division of Gastroenterology/Hepatology, NUTRIM school of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, 6200 MD Maastricht, The Netherlands;
| | - John Penders
- Department of Medical Microbiology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center+, 6229 ER Maastricht, The Netherlands; (H.E.F.B.); (T.W.); (J.P.); (P.S.)
- Department of Medical Microbiology, Caphri School for Public Health and Primary Care, Maastricht University Medical Centre+, 6229 ER Maastricht, The Netherlands
| | - Paul Savelkoul
- Department of Medical Microbiology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center+, 6229 ER Maastricht, The Netherlands; (H.E.F.B.); (T.W.); (J.P.); (P.S.)
- Department of Medical Microbiology and Infection Control, VU University Medical Center, 1081 HV Amsterdam, The Netherlands
| | - Frank R. Stassen
- Department of Medical Microbiology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center+, 6229 ER Maastricht, The Netherlands; (H.E.F.B.); (T.W.); (J.P.); (P.S.)
- Correspondence: (N.K.); (F.R.S.)
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