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Li H, He B, Ma N, Liu C, Cai K, Zhang X, Ma X. Quorum sensing of Bifidobacteria: Research and progress. Microbiol Res 2025; 294:128102. [PMID: 39965277 DOI: 10.1016/j.micres.2025.128102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 01/17/2025] [Accepted: 02/12/2025] [Indexed: 02/20/2025]
Abstract
Quorum sensing (QS) is a common method of communication among bacteria. While previous studies have discovered the mechanisms of QS in a variety of pathogenic bacteria, relatively little research has focused on probiotics, such as Bifidobacteria. Recent studies have detected QS signalling molecules in Bifidobacteria, but it remains unclear whether the probiotic properties of Bifidobacteria are mediated by QS. This review aims to provide an overview of the QS system in Bifidobacteria and its role in promoting the secretion of metabolites such as extracellular vesicles and biofilms. The review further examines the inhibition of virulence gene expression by Bifidobacteria QS through the luxS/AI-2 system, as well as its role in promoting host-microbial interactions. Understanding the QS mechanisms of Bifidobacteria can reveal beneficial interactions with hosts, which may facilitate the control of bacterial infections, including therapeutic strategies for intestinal diseases. This knowledge can also help improve gut health, thereby addressing the opportunities and challenges of enhancing the body's nutritional status.
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Affiliation(s)
- Huahui Li
- College of Public Health, North China University of Science and Technology, Tangshan, Hebei 063210, China
| | - Bin He
- College of Public Health, North China University of Science and Technology, Tangshan, Hebei 063210, China
| | - Ning Ma
- College of Animal Science and Technology, China Agricultural University, Haidian, Beijing 100193, China
| | - Chunchen Liu
- College of Public Health, North China University of Science and Technology, Tangshan, Hebei 063210, China
| | - Kun Cai
- College of Animal Science and Technology, China Agricultural University, Haidian, Beijing 100193, China
| | - Xiujun Zhang
- College of Public Health, North China University of Science and Technology, Tangshan, Hebei 063210, China.
| | - Xi Ma
- College of Public Health, North China University of Science and Technology, Tangshan, Hebei 063210, China; College of Animal Science and Technology, China Agricultural University, Haidian, Beijing 100193, China.
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2
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Lee S, Jung SY, Yoo D, Go D, Park JY, Lee JM, Um W. Alternatives of mesenchymal stem cell-derived exosomes as potential therapeutic platforms. Front Bioeng Biotechnol 2024; 12:1478517. [PMID: 39315312 PMCID: PMC11417005 DOI: 10.3389/fbioe.2024.1478517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Accepted: 08/26/2024] [Indexed: 09/25/2024] Open
Abstract
With outstanding therapeutic potential in the tissue regeneration and anti-inflammation, mesenchymal stem cell-derived exosomes (MSC-EXOs) have emerged as a prominent therapeutic in recent. However, poor production yield and reproducibility have remained as significant challenges of their practical applications. To surmount these challenges, various alternative materials with stem cell-like functions, have been recently investigated, however, there has been no comprehensive analysis in these alternatives so far. Here, we discuss the recent progress of alternatives of MSC-EXOs, including exosomes and exosome-like nanovesicles from various biological sources such as plants, milk, microbes, and body fluids. Moreover, we extensively compare each alternative by summarizing their unique functions and mode of actions to suggest the expected therapeutic target and future directions for developing alternatives for MSC-EXOs.
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Affiliation(s)
| | | | | | | | | | - Jong Min Lee
- Department of Biotechnology, College of Fisheries Science, Pukyong National University, Busan, Republic of Korea
| | - Wooram Um
- Department of Biotechnology, College of Fisheries Science, Pukyong National University, Busan, Republic of Korea
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3
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Li S, Liu Z, Zhang Q, Su D, Wang P, Li Y, Shi W, Zhang Q. The Antidiabetic Potential of Probiotics: A Review. Nutrients 2024; 16:2494. [PMID: 39125375 PMCID: PMC11313988 DOI: 10.3390/nu16152494] [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: 06/28/2024] [Revised: 07/26/2024] [Accepted: 07/26/2024] [Indexed: 08/12/2024] Open
Abstract
Diabetes has become one of the most prevalent global epidemics, significantly impacting both the economy and the health of individuals. Diabetes is associated with numerous complications, such as obesity; hyperglycemia; hypercholesterolemia; dyslipidemia; metabolic endotoxemia; intestinal barrier damage; insulin-secretion defects; increased oxidative stress; and low-grade, systemic, and chronic inflammation. Diabetes cannot be completely cured; therefore, current research has focused on developing various methods to control diabetes. A promising strategy is the use of probiotics for diabetes intervention. Probiotics are a class of live, non-toxic microorganisms that can colonize the human intestine and help improve the balance of intestinal microbiota. In this review, we summarize the current clinical studies on using probiotics to control diabetes in humans, along with mechanistic studies conducted in animal models. The primary mechanism by which probiotics regulate diabetes is improved intestinal barrier integrity, alleviated oxidative stress, enhanced immune response, increased short-chain fatty acid production, etc. Therefore, probiotic supplementation holds great potential for the prevention and management of diabetes.
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Affiliation(s)
- Shiming Li
- Department of Nutrition and Health, China Agricultural University, Beijing 100193, China; (S.L.); (Z.L.); (Q.Z.); (P.W.); (Y.L.)
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100193, China
| | - Zichao Liu
- Department of Nutrition and Health, China Agricultural University, Beijing 100193, China; (S.L.); (Z.L.); (Q.Z.); (P.W.); (Y.L.)
| | - Qi Zhang
- Department of Nutrition and Health, China Agricultural University, Beijing 100193, China; (S.L.); (Z.L.); (Q.Z.); (P.W.); (Y.L.)
| | - Dan Su
- Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14850, USA;
| | - Pengjie Wang
- Department of Nutrition and Health, China Agricultural University, Beijing 100193, China; (S.L.); (Z.L.); (Q.Z.); (P.W.); (Y.L.)
| | - Yixuan Li
- Department of Nutrition and Health, China Agricultural University, Beijing 100193, China; (S.L.); (Z.L.); (Q.Z.); (P.W.); (Y.L.)
| | - Wenbiao Shi
- Department of Nutrition and Health, China Agricultural University, Beijing 100193, China; (S.L.); (Z.L.); (Q.Z.); (P.W.); (Y.L.)
| | - Qian Zhang
- Department of Nutrition and Health, China Agricultural University, Beijing 100193, China; (S.L.); (Z.L.); (Q.Z.); (P.W.); (Y.L.)
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Helmy YA, Taha-Abdelaziz K, Hawwas HAEH, Ghosh S, AlKafaas SS, Moawad MMM, Saied EM, Kassem II, Mawad AMM. Antimicrobial Resistance and Recent Alternatives to Antibiotics for the Control of Bacterial Pathogens with an Emphasis on Foodborne Pathogens. Antibiotics (Basel) 2023; 12:274. [PMID: 36830185 PMCID: PMC9952301 DOI: 10.3390/antibiotics12020274] [Citation(s) in RCA: 42] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2023] [Revised: 01/21/2023] [Accepted: 01/27/2023] [Indexed: 01/31/2023] Open
Abstract
Antimicrobial resistance (AMR) is one of the most important global public health problems. The imprudent use of antibiotics in humans and animals has resulted in the emergence of antibiotic-resistant bacteria. The dissemination of these strains and their resistant determinants could endanger antibiotic efficacy. Therefore, there is an urgent need to identify and develop novel strategies to combat antibiotic resistance. This review provides insights into the evolution and the mechanisms of AMR. Additionally, it discusses alternative approaches that might be used to control AMR, including probiotics, prebiotics, antimicrobial peptides, small molecules, organic acids, essential oils, bacteriophage, fecal transplants, and nanoparticles.
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Affiliation(s)
- Yosra A. Helmy
- Department of Veterinary Science, College of Agriculture, Food and Environment, University of Kentucky, Lexington, KY 40546, USA
- Department of Zoonoses, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt
| | - Khaled Taha-Abdelaziz
- Department of Animal and Veterinary Sciences, Clemson University, Clemson, SC 29634, USA
| | - Hanan Abd El-Halim Hawwas
- Department of Zoonoses, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt
| | - Soumya Ghosh
- Department of Genetics, Faculty of Natural and Agricultural Sciences, University of the Free State, Bloemfontein 9301, South Africa
| | - Samar Sami AlKafaas
- Molecular Cell Biology Unit, Division of Biochemistry, Department of Chemistry, Faculty of Science, Tanta University, Tanta 31511, Egypt
| | | | - Essa M. Saied
- Chemistry Department, Faculty of Science, Suez Canal University, Ismailia 41522, Egypt
- Institute for Chemistry, Humboldt Universität zu Berlin, Brook-Taylor-Str. 2, 12489 Berlin, Germany
| | - Issmat I. Kassem
- Centre for Food Safety, Department of Food Science and Technology, University of Georgia, Griffin, GA 30609, USA
| | - Asmaa M. M. Mawad
- Department of Biology, College of Science, Taibah University, Madinah 42317, Saudi Arabia
- Botany and Microbiology Department, Faculty of Science, Assiut University, Assiut 71516, Egypt
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5
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Chen J, Chen X, Ho CL. Recent Development of Probiotic Bifidobacteria for Treating Human Diseases. Front Bioeng Biotechnol 2022; 9:770248. [PMID: 35004640 PMCID: PMC8727868 DOI: 10.3389/fbioe.2021.770248] [Citation(s) in RCA: 79] [Impact Index Per Article: 26.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Accepted: 12/08/2021] [Indexed: 12/12/2022] Open
Abstract
Bifidobacterium is a non-spore-forming, Gram-positive, anaerobic probiotic actinobacterium and commonly found in the gut of infants and the uterine region of pregnant mothers. Like all probiotics, Bifidobacteria confer health benefits on the host when administered in adequate amounts, showing multifaceted probiotic effects. Examples include B. bifidum, B. breve, and B. longum, common Bifidobacterium strains employed to prevent and treat gastrointestinal disorders, including intestinal infections and cancers. Herein, we review the latest development in probiotic Bifidobacteria research, including studies on the therapeutic impact of Bifidobacterial species on human health and recent efforts in engineering Bifidobacterium. This review article would provide readers with a wholesome understanding of Bifidobacteria and its potentials to improve human health.
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Affiliation(s)
- Jun Chen
- Department of Biomedical Engineering, Southern University of Science and Technology (SUSTech), Shenzhen, China
| | - Xinyi Chen
- Department of Biomedical Engineering, Southern University of Science and Technology (SUSTech), Shenzhen, China
| | - Chun Loong Ho
- Department of Biomedical Engineering, Southern University of Science and Technology (SUSTech), Shenzhen, China
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6
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Jimenez-Trigos E, Toquet M, Barba M, Gómez-Martín Á, Quereda JJ, Bataller E. Search of antimicrobial lactic acid bacteria from Salmonella-negative dogs. BMC Vet Res 2022; 18:12. [PMID: 35042502 PMCID: PMC8767738 DOI: 10.1186/s12917-021-03070-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Accepted: 10/30/2021] [Indexed: 01/05/2023] Open
Abstract
Background Salmonellosis is one of the most important food-borne zoonotic disease affecting both animals and humans. The objective of the present study was to identify gastrointestinal (GI) lactic acid bacteria (LAB) of canine-origin from Salmonella-negative dogs’ faeces able to inhibit monophasic Salmonella Typhimurium previously isolated from dogs’ faeces, in order to be used as a potential probiotic in pet nutrition. Results Accordingly, 37 LAB were isolated from Salmonella-negative dogs’ faeces and tested against monophasic S. Typhimurium using the spot on lawn method out of which 7 strains showed an inhibition halo higher than 2.5 cm. These 7 strains were also tested with the co-culture method and one showed the greatest inhibition value (p < 0.05). Subsequently, the isolate was identified through 16S rRNA sequencing and sequence homology and designated as Ligilactobacillus salivarius (L. salivarius). LAB from Salmonella-positive dogs were also identified and none was the selected strain. Finally, to identify the mechanism of inhibition of L. salivarius, the supernatant was analyzed, and a dose response effect was observed. Conclusions It is concluded that the canine-origin L. salivarius, could possess some in vitro functional attributes of a candidate probiotic and could prevent monophasic S. Typhimurium colonization or inhibit its activity if the infection occurs. Supplementary Information The online version contains supplementary material available at 10.1186/s12917-021-03070-x.
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7
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Intestinal microbiota and their metabolic contribution to type 2 diabetes and obesity. J Diabetes Metab Disord 2021; 20:1855-1870. [PMID: 34900829 PMCID: PMC8630233 DOI: 10.1007/s40200-021-00858-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Accepted: 07/14/2021] [Indexed: 02/06/2023]
Abstract
Obesity and type 2 diabetes mellitus (T2DM) are common, chronic metabolic disorders with associated significant long-term health problems at global epidemic levels. It is recognised that gut microbiota play a central role in maintaining host homeostasis and through technological advances in both animal and human models it is becoming clear that gut microbiota are heavily involved in key pathophysiological roles in the aetiology and progression of both conditions. This review will focus on current knowledge regarding microbiota interactions with short chain fatty acids, the host inflammatory response, signaling pathways, integrity of the intestinal barrier, the interaction of the gut-brain axis and the subsequent impact on the metabolic health of the host.
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8
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Awany D, Allali I, Chimusa ER. Dissecting genome-wide studies for microbiome-related metabolic diseases. Hum Mol Genet 2021; 29:R73-R80. [PMID: 32478833 DOI: 10.1093/hmg/ddaa105] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Revised: 05/14/2020] [Accepted: 05/29/2020] [Indexed: 12/14/2022] Open
Abstract
Despite the meteoric rise in genome-wide association studies for metabolic diseases (MetD) over the last few years, our understanding of the pathogenesis of these diseases is still far from complete. Recent developments have established that MetD arises from complex interactions between host genetics, the gut microbiome and the environment. However, our knowledge of the genetic and microbiome components involved and the underlying molecular mechanisms remains limited. Here, we review and summarize recent studies investigating the genetic and microbiome basis of MetD. Then, given the critical importance of study-individual's ancestry in these studies, we leverage 4932 whole-genome sequence samples from 18 worldwide ethnic groups to examine genetic diversity in currently reported variants associated with MetD. The analyses show marked differences in gene-specific proportion of pathogenic single-nucleotide polymorphisms (SNPs) and gene-specific SNPs MAFs across ethnic groups, highlighting the importance of population- and ethnic-specific investigations in pinpointing the causative factors for MetD. We conclude with a discussion of research areas where further investigation on interactions between host genetics, microbiome and the environment is needed.
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Affiliation(s)
- Denis Awany
- Division of Human Genetics, Department of Pathology, University of Cape Town, Observatory 7925, Cape Town, South Africa
| | - Imane Allali
- Laboratory of Human Pathologies Biology, Department of Biology, Faculty of Sciences, and Genomic Center of Human Pathologies, Faculty of Medicine and Pharmacy, Mohammed V University, Agdal Rabat, B.P, 8007 N.U, Morocco
| | - Emile R Chimusa
- Division of Human Genetics, Department of Pathology, University of Cape Town, Observatory 7925, Cape Town, South Africa.,Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Observatory 7925, Cape Town, South Africa
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9
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Cunningham AL, Stephens JW, Harris DA. Gut microbiota influence in type 2 diabetes mellitus (T2DM). Gut Pathog 2021; 13:50. [PMID: 34362432 PMCID: PMC8343927 DOI: 10.1186/s13099-021-00446-0] [Citation(s) in RCA: 114] [Impact Index Per Article: 28.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Accepted: 07/25/2021] [Indexed: 12/12/2022] Open
Abstract
A strong and expanding evidence base supports the influence of gut microbiota in human metabolism. Altered glucose homeostasis is associated with altered gut microbiota, and is clearly associated with the development of type 2 diabetes mellitus (T2DM) and associated complications. Understanding the causal association between gut microbiota and metabolic risk has the potential role of identifying susceptible individuals to allow early targeted intervention.
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Affiliation(s)
- A L Cunningham
- Department of Surgery, Swansea Bay University Health Board, Singleton Hospital, Swansea, SA2 8QA, Wales. .,School of Medicine, Swansea University Medical School, Institute of Life Science 2, Swansea, SA2 8QA, Wales.
| | - J W Stephens
- Department of Surgery, Swansea Bay University Health Board, Singleton Hospital, Swansea, SA2 8QA, Wales.,School of Medicine, Swansea University Medical School, Institute of Life Science 2, Swansea, SA2 8QA, Wales
| | - D A Harris
- Department of Surgery, Swansea Bay University Health Board, Singleton Hospital, Swansea, SA2 8QA, Wales.,School of Medicine, Swansea University Medical School, Institute of Life Science 2, Swansea, SA2 8QA, Wales
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10
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Dissecting the Evolutionary Development of the Species Bifidobacterium animalis through Comparative Genomics Analyses. Appl Environ Microbiol 2019; 85:AEM.02806-18. [PMID: 30709821 DOI: 10.1128/aem.02806-18] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2018] [Accepted: 01/28/2019] [Indexed: 12/20/2022] Open
Abstract
Bifidobacteria are members of the gut microbiota of animals, including mammals, birds, and social insects. In this study, we analyzed and determined the pangenome of Bifidobacterium animalis species, encompassing B. animalis subsp. animalis and the B. animalis subsp. lactis taxon, which is one of the most intensely exploited probiotic bifidobacterial species. In order to reveal differences within the B. animalis species, detailed comparative genomics and phylogenomics analyses were performed, indicating that these two subspecies recently arose through divergent evolutionary events. A subspecies-specific core genome was identified for both B. animalis subspecies, revealing the existence of subspecies-defining genes involved in carbohydrate metabolism. Notably, these in silico analyses coupled with carbohydrate profiling assays suggest genetic adaptations toward a distinct glycan milieu for each member of the B. animalis subspecies, resulting in a divergent evolutionary development of the two subspecies.IMPORTANCE The majority of characterized B. animalis strains have been isolated from human fecal samples. In order to explore genome variability within this species, we isolated 15 novel strains from the gastrointestinal tracts of different animals, including mammals and birds. The present study allowed us to reconstruct the pangenome of this taxon, including the genome contents of 56 B. animalis strains. Through careful assessment of subspecies-specific core genes of the B. animalis subsp. animalis/lactis taxon, we identified genes encoding enzymes involved in carbohydrate transport and metabolism, while unveiling specific gene acquisition and loss events that caused the evolutionary emergence of these two subspecies.
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11
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Arenas‐Padilla M, Duarte‐Gutiérrez J, Mata‐Haro V. Bifidobacterium animalis ssp. lactis Bb12 induces IL-10 through cell membrane-associated components via TLR2 in swine. J Appl Microbiol 2018; 125:1881-1889. [PMID: 30106205 PMCID: PMC7166459 DOI: 10.1111/jam.14069] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Revised: 05/06/2018] [Accepted: 08/09/2018] [Indexed: 01/22/2023]
Abstract
AIM To investigate the role of Toll-like receptor 2 (TLR2) in interleukin-10 (IL-10) production induced by Bifidobacterium animalis ssp. lactis Bb12 (Bb12) in swine immune cells. METHODS AND RESULTS Blood-monocytes and cells from mesenteric lymph nodes were obtained from pigs and cultured with live Bb12 for 4 and 12 h. Transcript levels of IL-10 and TLR2 were analysed. Furthermore, TLR2 was blocked to determine its participation in IL-10 production. TLR2 blockade was achieved with neutralizing antibodies, followed by stimulation with Bb12. Bifidobacteria induced IL-10 production in both swine monocytes and mesenteric cells. Monocytes with TLR2 blockade had a decrease in IL-10 transcripts, while mesenteric cells did not. Bacterial cell wall components were responsible for Bb12-induced IL-10 production since no IL-10 was detected in the culture supernatant. CONCLUSIONS We demonstrated that IL-10 production is largely mediated through the recognition of Bb12 structures by TLR2, as bacterial metabolites in the culture supernatant failed to induce IL-10 expression. SIGNIFICANCE AND IMPACT OF THE STUDY The present study provides evidence for the potential use of Bb12 in the swine industry; these bacteria can also be used as additional method to treat intestinal inflammation and enhance intestinal health in pigs.
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Affiliation(s)
- M. Arenas‐Padilla
- Department of Food Science, Microbiology and ImmunologyCentro de Investigación en Alimentación y Desarrollo, A. C.HermosilloMéxico
| | - J.L. Duarte‐Gutiérrez
- Department of Food Science, Microbiology and ImmunologyCentro de Investigación en Alimentación y Desarrollo, A. C.HermosilloMéxico
| | - V. Mata‐Haro
- Department of Food Science, Microbiology and ImmunologyCentro de Investigación en Alimentación y Desarrollo, A. C.HermosilloMéxico
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12
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Bogner J. [Probiotics - is there evidence for use against antibiotic induced diarrhea, CDAD and travellers diarrhea?]. MMW Fortschr Med 2017; 159:49-52. [PMID: 28265914 DOI: 10.1007/s15006-017-9339-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Affiliation(s)
- Johannes Bogner
- Med. Klinik und Poliklinik IV, Sektion Klinische Infektiologie, Klinikum der Univ., Campus Innenstadt, Pettenkoferstr. 8a, D-80336, München, Deutschland.
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13
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Anaerobic Probiotics: The Key Microbes for Human Health. ADVANCES IN BIOCHEMICAL ENGINEERING/BIOTECHNOLOGY 2017; 156:397-431. [PMID: 26907552 DOI: 10.1007/10_2015_5008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Human gastrointestinal microbiota (HGIM) incorporate a large number of microbes from different species. Anaerobic bacteria are the dominant organisms in this microbial consortium and play a crucial role in human health. In addition to their functional role as the main source of many essential metabolites for human health, they are considered as biotherapeutic agents in the regulation of different human metabolites. They are also important in the prevention and in the treatment of different physical and mental diseases. Bifidobacteria are the dominant anaerobic bacteria in HGIM and are widely used in the development of probiotic products for infants, children and adults. To develop bifidobacteria-based bioproducts, therefore, it is necessary to develop a large-scale biomass production platform based on a good understanding of the ideal medium and bioprocessing parameters for their growth and viability. In addition, high cell viability should be maintained during downstream processing and storage of probiotic cell powder or the final formulated product. In this work we review the latest information about the biology, therapeutic activities, cultivation and industrial production of bifidobacteria.
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14
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Galley JD, Parry NM, Ahmer BMM, Fox JG, Bailey MT. The commensal microbiota exacerbate infectious colitis in stressor-exposed mice. Brain Behav Immun 2017; 60:44-50. [PMID: 27633986 PMCID: PMC5214661 DOI: 10.1016/j.bbi.2016.09.010] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2016] [Revised: 09/06/2016] [Accepted: 09/11/2016] [Indexed: 12/12/2022] Open
Abstract
Exposure to a prolonged restraint stressor disrupts the colonic microbiota community composition, and is associated with an elevated inflammatory response to colonic pathogen challenge. Since the stability of the microbiota has been implicated in the development and modulation of mucosal immune responses, we hypothesized that the disruptive effect of the stressor upon the microbiota composition directly contributed to the stressor-induced exacerbation of pathogen-induced colitis. In order to establish a causative role for stressor-induced changes in the microbiota, conventional mice were exposed to prolonged restraint to change the microbiota. Germfree mice were then colonized by microbiota from either stressor-exposed or non-stressed control mice. One day after colonization, mice were infected with the colonic pathogen, Citrobacter rodentium. At six days post-infection, mice that received microbiota from stressor-exposed animals had significant increases in colonic pathology and pro-inflammatory cytokine (e.g. IL-1β) and chemokine (e.g. CCL2) levels after C. rodentium infection in comparison with mice that received microbiota from non-stressed mice. 16S rRNA gene sequencing revealed that microbial communities from stressed mice did not have any detectable Bifidobacterium present, a stark contrast with the microbial communities from non-stressed mice, suggesting that stressor-induced alterations in commensal, immunomodulatory Bifidobacterium levels may predispose to an increased inflammatory response to pathogen challenge. This study demonstrates that the commensal microbiota directly contribute to excessive inflammatory responses to C. rodentium during stressor exposure, and may help to explain why gastrointestinal disorders are worsened during stressful experiences.
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Affiliation(s)
- Jeffrey D. Galley
- Institute for Behavioral Medicine Research, The Ohio State University, Columbus, OH 43210,Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030
| | - Nicola M. Parry
- Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, 02139
| | - Brian M. M. Ahmer
- Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH 43210,Center for Microbial Interface Biology, The Ohio State University, Columbus, OH 43210
| | - James G. Fox
- Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, 02139
| | - Michael T. Bailey
- Institute for Behavioral Medicine Research, The Ohio State University, Columbus, OH 43210,Center for Microbial Interface Biology, The Ohio State University, Columbus, OH 43210,Center for Microbial Pathogenesis, The Research Institute at Nationwide Children’s Hospital, Columbus, OH, 43205,Department of Pediatrics, The Ohio State University Wexner Medical Center, Columbus, OH 43210
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15
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Acute ileitis facilitates infection with multidrug resistant Pseudomonas aeruginosa in human microbiota-associated mice. Gut Pathog 2017; 9:4. [PMID: 28115993 PMCID: PMC5241993 DOI: 10.1186/s13099-017-0154-4] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2016] [Accepted: 01/10/2017] [Indexed: 01/26/2023] Open
Abstract
Background The rising incidence of multidrug resistant (MDR) Gram-negative bacteria including Pseudomonas aeruginosa has become a serious issue in prevention of its spread particularly among hospitalized patients. It is, however, unclear whether distinct conditions such as acute intestinal inflammation facilitate P. aeruginosa infection of vertebrate hosts. Methods and results To address this, we analysed P. aeruginosa infection in human microbiota-associated (hma) mice with acute ileitis induced by peroral Toxoplasma gondii challenge. When perorally infected with P. aeruginosa at day 3 post ileitis induction, hma mice displayed higher intestinal P. aeruginosa loads as compared to hma mice without ileitis. However, the overall intestinal microbiota composition was not disturbed by P. aeruginosa (except for lowered bifidobacterial populations), and the infection did not further enhance ileal immune cell responses. Pro-inflammatory cytokines including IFN-γ and IL-12p70 were similarly increased in ileum and mesenteric lymph nodes of P. aeruginosa infected and uninfected hma mice with ileitis. The anti-inflammatory cytokine IL-10 increased multifold upon ileitis induction, but interestingly more distinctly in P. aeruginosa infected as compared to uninfected controls. Immune responses were not restricted to the intestines as indicated by elevated pro-inflammatory cytokine levels in liver and kidney upon ileitis induction. However, except for hepatic TNF-α levels, P. aeruginosa infection did not result in more distinct pro-inflammatory cytokine secretion in liver and kidney of hma mice with ileitis. Whereas viable intestinal bacteria were more frequently detected in systemic compartments such as spleen and cardiac blood of P. aeruginosa infected than uninfected mice at day 7 following ileitis induction, P. aeruginosa infection did not exacerbate systemic pro-inflammatory sequelae, but resulted in lower IL-10 serum levels. Conclusion Acute intestinal inflammation facilitates infection of the vertebrate host with MDR bacteria including P. aeruginosa and might also pose particularly hospitalized patients at risk for acquisition. Since acute T. gondii induced inflammation might mask immunopathology caused by P. aeruginosa, a subacute or chronic inflammation model might be better suited to investigate the potential role of P. aeruginosa infection in the aggravation of intestinal disease. Electronic supplementary material The online version of this article (doi:10.1186/s13099-017-0154-4) contains supplementary material, which is available to authorized users.
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Scheithauer TP, Dallinga-Thie GM, de Vos WM, Nieuwdorp M, van Raalte DH. Causality of small and large intestinal microbiota in weight regulation and insulin resistance. Mol Metab 2016; 5:759-70. [PMID: 27617199 PMCID: PMC5004227 DOI: 10.1016/j.molmet.2016.06.002] [Citation(s) in RCA: 131] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2016] [Revised: 06/01/2016] [Accepted: 06/06/2016] [Indexed: 02/08/2023] Open
Abstract
OBJECTIVE The twin pandemics of obesity and Type 2 diabetes (T2D) are a global challenge for health care systems. Changes in the environment, behavior, diet, and lifestyle during the last decades are considered the major causes. A Western diet, which is rich in saturated fat and simple sugars, may lead to changes in gut microbial composition and physiology, which have recently been linked to the development of metabolic diseases. METHODS We will discuss evidence that demonstrates the influence of the small and large intestinal microbiota on weight regulation and the development of insulin resistance, based on literature search. RESULTS Altered large intestinal microbial composition may promote obesity by increasing energy harvest through specialized gut microbes. In both large and small intestine, microbial alterations may increase gut permeability that facilitates the translocation of whole bacteria or endotoxic bacterial components into metabolic active tissues. Moreover, changed microbial communities may affect the production of satiety-inducing signals. Finally, bacterial metabolic products, such as short chain fatty acids (SCFAs) and their relative ratios, may be causal in disturbed immune and metabolic signaling, notably in the small intestine where the surface is large. The function of these organs (adipose tissue, brain, liver, muscle, pancreas) may be disturbed by the induction of low-grade inflammation, contributing to insulin resistance. CONCLUSIONS Interventions aimed to restoring gut microbial homeostasis, such as ingestion of specific fibers or therapeutic microbes, are promising strategies to reduce insulin resistance and the related metabolic abnormalities in obesity, metabolic syndrome, and type 2 diabetes. This article is part of a special issue on microbiota.
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Key Words
- 16s rRNA, 16S ribosomal RNA (30S small subunit of prokaryotic ribosomes)
- AMP, adenosine monophosphate
- AMPK, AMP-activated protein kinase
- AS160, Akt substrate of 160 kDa
- Angptl4, Angiopoietin-like 4
- CB1R, cannabinoid receptor type 1
- CCL2, Chemokine (C–C motif) ligand 2
- DIO, diet-induced obesity
- Diabetes
- GF, germ-free
- GLP, glucagon-like peptide
- Gpr, G-protein coupled receptor
- Gut microbiota
- HFD, high fat diet
- IL, interleukin
- IRS-1, insulin receptor substrate 1
- Insulin resistance
- JNK, C-Jun N-terminal kinase
- LBP, LPS-binding protein
- LPL, lipoprotein lipase
- LPS, lipopolysaccharide
- MCP-1, monocyte chemotactic protein 1
- NOD1, nucleotide-binding oligomerization domain-containing protein 1
- Obesity
- PKB, protein kinase B (also known as Akt)
- PYY, peptide YY (for tyrosine–tyrosine)
- RYGB, Roux-en-Y gastric bypass
- SCFA, short-chain fatty acid
- T2D, Type 2 diabetes mellitus
- TLR, toll-like receptor
- TNF-α, tumor necrosis factor alpha
- VLDL, very low density lipoprotein
- WHO, World Health Organization
- Weight regulation
- ZO, zonula occludens
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Affiliation(s)
- Torsten P.M. Scheithauer
- Department of Vascular Medicine, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands
- Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands
- Institute for Cardiovascular Research (ICaR), VU University Medical Center, Amsterdam, The Netherlands
| | - Geesje M. Dallinga-Thie
- Department of Vascular Medicine, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands
| | - Willem M. de Vos
- WU Agrotechnology and Food Sciences, Wagening University, Wageningen, The Netherlands
| | - Max Nieuwdorp
- Department of Vascular Medicine, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands
- Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands
- Institute for Cardiovascular Research (ICaR), VU University Medical Center, Amsterdam, The Netherlands
| | - Daniël H. van Raalte
- Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands
- Institute for Cardiovascular Research (ICaR), VU University Medical Center, Amsterdam, The Netherlands
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Villena J, Aso H, Kitazawa H. Regulation of toll-like receptors-mediated inflammation by immunobiotics in bovine intestinal epitheliocytes: role of signaling pathways and negative regulators. Front Immunol 2014; 5:421. [PMID: 25228903 PMCID: PMC4151153 DOI: 10.3389/fimmu.2014.00421] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2014] [Accepted: 08/19/2014] [Indexed: 12/13/2022] Open
Abstract
Intestinal epithelial cells (IECs) detect bacterial and viral associated molecular patterns via germline-encoded pattern-recognition receptors (PRRs) and are responsible for maintaining immune tolerance to the communities of resident commensal bacteria while being also capable to mount immune responses against pathogens. Toll-like receptors (TLRs) are a major class of PRRs expressed on IECs and immune cells, which are involved in the induction of both tolerance and inflammation. In the last decade, experimental and clinical evidence was generated to support the application of probiotics with immunoregulatory capacities (immunobiotics) for the prevention and treatment of several gastrointestinal inflammatory disorders in which TLRs exert a significant role. The majority of these studies were performed in mouse and human cell lines, and despite the growing interest in the bovine immune system due to the economic importance of cattle as livestock, only few studies have been conducted on cattle. In this regard, our group has established a bovine intestinal epithelial (BIE) cell line originally derived from fetal bovine intestinal epitheliocytes and used this cell line to evaluate the impact of immunobiotics in TLR-mediated inflammation. This review aims to summarize the current knowledge of the beneficial effects of immunobiotics in the regulation of intestinal inflammation/infection in cattle. Especially, we discuss the role of TLRs and their negative regulators in both the inflammatory response and the beneficial effects of immunobiotics in bovine IECs. This review article emphasizes the cellular and molecular interactions of immunobiotics with BIE cells through TLRs and gives the scientific basis for the development of immunomodulatory feed for bovine healthy development.
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Affiliation(s)
- Julio Villena
- Immunobiotics Research Group , Tucuman , Argentina ; Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET) , Tucuman , Argentina
| | - Hisashi Aso
- Cell Biology Laboratory, Graduate School of Agricultural Science, Tohoku University , Sendai , Japan
| | - Haruki Kitazawa
- Food and Feed Immunology Group, Laboratory of Animal Products Chemistry, Graduate School of Agricultural Science, Tohoku University , Sendai , Japan
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Cruz-Mora J, Martínez-Hernández NE, Martín del Campo-López F, Viramontes-Hörner D, Vizmanos-Lamotte B, Muñoz-Valle JF, García-García G, Parra-Rojas I, Castro-Alarcón N. Effects of a Symbiotic on Gut Microbiota in Mexican Patients With End-Stage Renal Disease. J Ren Nutr 2014; 24:330-5. [DOI: 10.1053/j.jrn.2014.05.006] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2014] [Revised: 04/07/2014] [Accepted: 05/19/2014] [Indexed: 01/28/2023] Open
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Heimesaat MM, Dunay IR, Alutis M, Fischer A, Möhle L, Göbel UB, Kühl AA, Bereswill S. Nucleotide-oligomerization-domain-2 affects commensal gut microbiota composition and intracerebral immunopathology in acute Toxoplasma gondii induced murine ileitis. PLoS One 2014; 9:e105120. [PMID: 25141224 PMCID: PMC4139296 DOI: 10.1371/journal.pone.0105120] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2014] [Accepted: 07/18/2014] [Indexed: 01/01/2023] Open
Abstract
Background Within one week following peroral high dose infection with Toxoplasma (T.) gondii, susceptible mice develop non-selflimiting acute ileitis due to an underlying Th1-type immunopathology. The role of the innate immune receptor nucleotide-oligomerization-domain-2 (NOD2) in mediating potential extra-intestinal inflammatory sequelae including the brain, however, has not been investigated so far. Methodology/Principal Findings Following peroral infection with 100 cysts of T. gondii strain ME49, NOD2-/- mice displayed more severe ileitis and higher small intestinal parasitic loads as compared to wildtype (WT) mice. However, systemic (i.e. splenic) levels of pro-inflammatory cytokines such as TNF-α and IFN-γ were lower in NOD2-/- mice versus WT controls at day 7 p.i. Given that the immunopathological outcome might be influenced by the intestinal microbiota composition, which is shaped by NOD2, we performed a quantitative survey of main intestinal bacterial groups by 16S rRNA analysis. Interestingly, Bifidobacteria were virtually absent in NOD2-/- but not WT mice, whereas differences in remaining bacterial species were rather subtle. Interestingly, more distinct intestinal inflammation was accompanied by higher bacterial translocation rates to extra-intestinal tissue sites such as liver, spleen, and kidneys in T. gondii infected NOD2-/- mice. Strikingly, intracerebral inflammatory foci could be observed as early as seven days following T. gondii infection irrespective of the genotype of animals, whereas NOD2-/- mice exhibited higher intracerebral parasitic loads, higher F4/80 positive macrophage and microglia numbers as well as higher IFN-γ mRNA expression levels as compared to WT control animals. Conclusion/Significance NOD2 signaling is involved in protection of mice from T. gondii induced acute ileitis. The parasite-induced Th1-type immunopathology at intestinal as well as extra-intestinal sites including the brain is modulated in a NOD2-dependent manner.
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Affiliation(s)
- Markus M. Heimesaat
- Department of Microbiology and Hygiene, Charité - University Medicine Berlin, Berlin, Germany
- * E-mail:
| | - Ildiko R. Dunay
- Department of Microbiology and Hygiene, University of Magdeburg, Magdeburg, Germany
| | - Marie Alutis
- Department of Microbiology and Hygiene, Charité - University Medicine Berlin, Berlin, Germany
| | - André Fischer
- Department of Microbiology and Hygiene, Charité - University Medicine Berlin, Berlin, Germany
| | - Luisa Möhle
- Department of Microbiology and Hygiene, University of Magdeburg, Magdeburg, Germany
| | - Ulf B. Göbel
- Department of Microbiology and Hygiene, Charité - University Medicine Berlin, Berlin, Germany
| | - Anja A. Kühl
- Department of Internal Medicine, Rheumatology and Clinical Immunology/Research Center ImmunoSciences (RCIS), Charité - University Medicine Berlin, Berlin, Germany
| | - Stefan Bereswill
- Department of Microbiology and Hygiene, Charité - University Medicine Berlin, Berlin, Germany
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Gomes AC, Bueno AA, de Souza RGM, Mota JF. Gut microbiota, probiotics and diabetes. Nutr J 2014; 13:60. [PMID: 24939063 PMCID: PMC4078018 DOI: 10.1186/1475-2891-13-60] [Citation(s) in RCA: 217] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2013] [Accepted: 06/12/2014] [Indexed: 02/07/2023] Open
Abstract
Diabetes is a condition of multifactorial origin, involving several molecular mechanisms related to the intestinal microbiota for its development. In type 2 diabetes, receptor activation and recognition by microorganisms from the intestinal lumen may trigger inflammatory responses, inducing the phosphorylation of serine residues in insulin receptor substrate-1, reducing insulin sensitivity. In type 1 diabetes, the lowered expression of adhesion proteins within the intestinal epithelium favours a greater immune response that may result in destruction of pancreatic β cells by CD8+ T-lymphocytes, and increased expression of interleukin-17, related to autoimmunity. Research in animal models and humans has hypothesized whether the administration of probiotics may improve the prognosis of diabetes through modulation of gut microbiota. We have shown in this review that a large body of evidence suggests probiotics reduce the inflammatory response and oxidative stress, as well as increase the expression of adhesion proteins within the intestinal epithelium, reducing intestinal permeability. Such effects increase insulin sensitivity and reduce autoimmune response. However, further investigations are required to clarify whether the administration of probiotics can be efficiently used for the prevention and management of diabetes.
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Affiliation(s)
- Aline Corado Gomes
- Laboratório de Investigação em Nutrição Clínica e Esportiva (Labince). Faculdade de Nutrição, Universidade Federal de Goiás, Rua 227 Qd. 68s/nº - Setor Leste Universitário, Goiânia, Goiás, Brazil
| | - Allain Amador Bueno
- Institute of Science and the Environment, University of Worcester, Henwick Grove, Worcester WR2 6AJ, UK
| | - Rávila Graziany Machado de Souza
- Laboratório de Investigação em Nutrição Clínica e Esportiva (Labince). Faculdade de Nutrição, Universidade Federal de Goiás, Rua 227 Qd. 68s/nº - Setor Leste Universitário, Goiânia, Goiás, Brazil
| | - João Felipe Mota
- Laboratório de Investigação em Nutrição Clínica e Esportiva (Labince). Faculdade de Nutrição, Universidade Federal de Goiás, Rua 227 Qd. 68s/nº - Setor Leste Universitário, Goiânia, Goiás, Brazil
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21
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Bereswill S, Kühl AA, Alutis M, Fischer A, Möhle L, Struck D, Liesenfeld O, Göbel UB, Dunay IR, Heimesaat MM. The impact of Toll-like-receptor-9 on intestinal microbiota composition and extra-intestinal sequelae in experimental Toxoplasma gondii induced ileitis. Gut Pathog 2014; 6:19. [PMID: 24932221 PMCID: PMC4057803 DOI: 10.1186/1757-4749-6-19] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2014] [Accepted: 05/26/2014] [Indexed: 01/01/2023] Open
Abstract
Background Following peroral Toxoplasma (T.) gondii infection, susceptible mice develop acute ileitis due to a microbiota-dependent Th1 type immunopathology. Toll-like-receptor (TLR)-9 is known to recognize bacterial DNA and mediates intestinal inflammation, but its impact on intestinal microbiota composition and extra-intestinal sequelae following T. gondii infection has not yet been elucidated. Methods and results Seven days following peroral infection (p.i.) with 100 cysts of T. gondii ME49 strain, TLR-9-/- and wildtype (WT) mice suffered from comparable ileitis, whereas ileal parasitic loads as well as IFN-γ and nitric oxide levels were higher in TLR-9-/- compared to WT mice. Locally, TLR-9-/- mice exhibited increased ileal CD3+, but not FOXP3+ cell numbers at day 7 p.i.; in mesenteric lymph nodes IFN-γ-producing CD4+ cell numbers and TNF-α and IFN-γ concentrations were also increased in TLR-9-/- compared to WT mice. T. gondii DNA levels, however, did not differ in mice of either genotype. Differences in intestinal microbiota were rather subtle except for bifidobacteria that were virtually absent in both, naïve and T. gondii infected TLR-9-/-, but not WT mice. Extra-intestinally, TLR-9-/- mice displayed less distinct systemic immune responses as indicated by lower serum IL-6, and splenic TNF-α and IFN-γ levels as compared to WT mice despite higher translocation rates of intestinal bacteria to extra-intestinal compartments such as liver, spleen, kidney, and cardiac blood. Most importantly, brains were also affected in this inflammatory scenario as early as day 7 p.i. Remarkably, TLR-9-/- mice exhibited more pronounced inflammatory infiltrates with higher numbers of F4/80+ macrophages and microglia in the cortex and meninges as compared to WT mice, whereas T. gondii DNA levels did not differ. Conclusion We here show that TLR-9 is not required for the development of T. gondii induced ileitis but mediates distinct inflammatory changes in intestinal and extra-intestinal compartments including the brain.
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Affiliation(s)
- Stefan Bereswill
- Department of Microbiology and Hygiene, Charité - University Medicine Berlin, Centrum 5, Campus Benjamin Franklin, Hindenburgdamm 27, D-12203 Berlin, Germany
| | - Anja A Kühl
- Department of Internal Medicine, Rheumatology and Clinical Immunology/Research Center ImmunoSciences (RCIS), Charité - University Medicine Berlin, Berlin, Germany
| | - Marie Alutis
- Department of Microbiology and Hygiene, Charité - University Medicine Berlin, Centrum 5, Campus Benjamin Franklin, Hindenburgdamm 27, D-12203 Berlin, Germany
| | - André Fischer
- Department of Microbiology and Hygiene, Charité - University Medicine Berlin, Centrum 5, Campus Benjamin Franklin, Hindenburgdamm 27, D-12203 Berlin, Germany
| | - Luisa Möhle
- Department of Microbiology and Hygiene, University of Magdeburg, Magdeburg, Germany
| | - Daniela Struck
- Department of Microbiology and Hygiene, Charité - University Medicine Berlin, Centrum 5, Campus Benjamin Franklin, Hindenburgdamm 27, D-12203 Berlin, Germany
| | - Oliver Liesenfeld
- Department of Microbiology and Hygiene, Charité - University Medicine Berlin, Centrum 5, Campus Benjamin Franklin, Hindenburgdamm 27, D-12203 Berlin, Germany
| | - Ulf B Göbel
- Department of Microbiology and Hygiene, Charité - University Medicine Berlin, Centrum 5, Campus Benjamin Franklin, Hindenburgdamm 27, D-12203 Berlin, Germany
| | - Ildikò R Dunay
- Department of Microbiology and Hygiene, University of Magdeburg, Magdeburg, Germany
| | - Markus M Heimesaat
- Department of Microbiology and Hygiene, Charité - University Medicine Berlin, Centrum 5, Campus Benjamin Franklin, Hindenburgdamm 27, D-12203 Berlin, Germany
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Immune modulating capability of two exopolysaccharide-producing Bifidobacterium strains in a Wistar rat model. BIOMED RESEARCH INTERNATIONAL 2014; 2014:106290. [PMID: 24971309 PMCID: PMC4058098 DOI: 10.1155/2014/106290] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/11/2014] [Accepted: 04/28/2014] [Indexed: 12/14/2022]
Abstract
Fermented dairy products are the usual carriers for the delivery of probiotics to humans, Bifidobacterium and Lactobacillus being the most frequently used bacteria. In this work, the strains Bifidobacterium animalis subsp. lactis IPLA R1 and Bifidobacterium longum IPLA E44 were tested for their capability to modulate immune response and the insulin-dependent glucose homeostasis using male Wistar rats fed with a standard diet. Three intervention groups were fed daily for 24 days with 10% skimmed milk, or with 109 cfu of the corresponding strain suspended in the same vehicle. A significant increase of the suppressor-regulatory TGF-β cytokine occurred with both strains in comparison with a control (no intervention) group of rats; the highest levels were reached in rats fed IPLA R1. This strain presented an immune protective profile, as it was able to reduce the production of the proinflammatory IL-6. Moreover, phosphorylated Akt kinase decreased in gastroctemius muscle of rats fed the strain IPLA R1, without affecting the glucose, insulin, and HOMA index in blood, or levels of Glut-4 located in the membrane of muscle and adipose tissue cells. Therefore, the strain B. animalis subsp. lactis IPLA R1 is a probiotic candidate to be tested in mild grade inflammation animal models.
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Dostal A, Gagnon M, Chassard C, Zimmermann MB, O'Mahony L, Lacroix C. Salmonella adhesion, invasion and cellular immune responses are differentially affected by iron concentrations in a combined in vitro gut fermentation-cell model. PLoS One 2014; 9:e93549. [PMID: 24676135 PMCID: PMC3968171 DOI: 10.1371/journal.pone.0093549] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2013] [Accepted: 03/06/2014] [Indexed: 12/20/2022] Open
Abstract
In regions with a high infectious disease burden, concerns have been raised about the safety of iron supplementation because higher iron concentrations in the gut lumen may increase risk of enteropathogen infection. The aim of this study was to investigate interactions of the enteropathogen Salmonella enterica ssp. enterica Typhimurium with intestinal cells under different iron concentrations encountered in the gut lumen during iron deficiency and supplementation using an in vitro colonic fermentation system inoculated with immobilized child gut microbiota combined with Caco-2/HT29-MTX co-culture monolayers. Colonic fermentation effluents obtained during normal, low (chelation by 2,2'-dipyridyl) and high iron (26.5 mg iron/L) fermentation conditions containing Salmonella or pure Salmonella cultures with similar iron conditions were applied to cellular monolayers. Salmonella adhesion and invasion capacity, cellular integrity and immune response were assessed. Under high iron conditions in pure culture, Salmonella adhesion was 8-fold increased compared to normal iron conditions while invasion was not affected leading to decreased invasion efficiency (-86%). Moreover, cellular cytokines IL-1β, IL-6, IL-8 and TNF-α secretion as well as NF-κB activation in THP-1 cells were attenuated under high iron conditions. Low iron conditions in pure culture increased Salmonella invasion correlating with an increase in IL-8 release. In fermentation effluents, Salmonella adhesion was 12-fold and invasion was 428-fold reduced compared to pure culture. Salmonella in high iron fermentation effluents had decreased invasion efficiency (-77.1%) and cellular TNF-α release compared to normal iron effluent. The presence of commensal microbiota and bacterial metabolites in fermentation effluents reduced adhesion and invasion of Salmonella compared to pure culture highlighting the importance of the gut microbiota as a barrier during pathogen invasion. High iron concentrations as encountered in the gut lumen during iron supplementation attenuated Salmonella invasion efficiency and cellular immune response suggesting that high iron concentrations alone may not lead to an increased Salmonella invasion.
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Affiliation(s)
- Alexandra Dostal
- Laboratory of Food Biotechnology, Institute of Food, Nutrition and Health, ETH Zurich, Zurich, Switzerland
| | - Mélanie Gagnon
- Laboratory of Food Biotechnology, Institute of Food, Nutrition and Health, ETH Zurich, Zurich, Switzerland
| | - Christophe Chassard
- Laboratory of Food Biotechnology, Institute of Food, Nutrition and Health, ETH Zurich, Zurich, Switzerland
| | - Michael Bruce Zimmermann
- Laboratory of Human Nutrition, Institute of Food, Nutrition and Health, ETH Zurich, Zurich, Switzerland
| | - Liam O'Mahony
- Swiss Institute of Allergy and Asthma Research, University of Zurich, Davos, Switzerland
| | - Christophe Lacroix
- Laboratory of Food Biotechnology, Institute of Food, Nutrition and Health, ETH Zurich, Zurich, Switzerland
- * E-mail:
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Murata K, Tomosada Y, Villena J, Chiba E, Shimazu T, Aso H, Iwabuchi N, Xiao JZ, Saito T, Kitazawa H. Bifidobacterium breve MCC-117 Induces Tolerance in Porcine Intestinal Epithelial Cells: Study of the Mechanisms Involved in the Immunoregulatory Effect. BIOSCIENCE OF MICROBIOTA FOOD AND HEALTH 2014; 33:1-10. [PMID: 24936377 PMCID: PMC4034327 DOI: 10.12938/bmfh.33.1] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/10/2013] [Accepted: 07/22/2013] [Indexed: 12/17/2022]
Abstract
Bifidobacterium breve MCC-117 is able to significantly reduce the expression of inflammatory cytokines in porcine intestinal epithelial (PIE) cells and to improve IL-10 levels in CD4(+)CD25(high) Foxp3(+) lymphocytes in response to heat-stable enterotoxigenic Escherichia coli (ETEC) pathogen-associated molecular patterns (PAMPs), while the immunoregulatory effect of B. adolescentis ATCC15705 was significantly lower than that observed for the MCC-117 strain. Considering the different capacities of the two bifidobacterium strains to activate toll-like receptor (TLR)-2 and their differential immunoregulatory activities in PIE and immune cells, we hypothesized that comparative studies with both strains could provide important information regarding the molecular mechanism(s) involved in the anti-inflammatory activity of bifidobacteria. In this work, we demonstrated that the anti-inflammatory effect of B. breve MCC-117 was achieved by a complex interaction of multiple negative regulators of TLRs as well as inhibition of multiple signaling pathways. We showed that B. breve MCC-117 reduced heat-stable ETEC PAMP-induced NF-κB, p38 MAPK and PI3 K activation and expression of pro-inflammatory cytokines in PIE cells. In addition, we demonstrated that B. breve MCC-117 may activate TLR2 synergistically and cooperatively with one or more other pattern recognition receptors (PRRs), and that interactions may result in a coordinated sum of signals that induce the upregulation of A20, Bcl-3, Tollip and SIGIRR. Upregulation of these negative regulators could have an important physiological impact on maintaining or reestablishing homeostatic TLR signals in PIE cells. Therefore, in the present study, we gained insight into the molecular mechanisms involved in the immunoregulatory effect of B. breve MCC-117.
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Affiliation(s)
- Kozue Murata
- Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan
| | - Yohsuke Tomosada
- Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan
| | - Julio Villena
- Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan ; Laboratory of Clinical and Experimental Biochemistry, Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman, Argentina
| | - Eriko Chiba
- Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan
| | - Tomoyuki Shimazu
- Laboratory of Animal Breeding and Genetics, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan
| | - Hisashi Aso
- Cell Biology Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan
| | - Noriyuki Iwabuchi
- Food Science and Technology Institute, Morinaga Milk Industry Co., Ltd., Zama, Kanagawa, 252-8583, Japan
| | - Jin-Zhong Xiao
- Food Science and Technology Institute, Morinaga Milk Industry Co., Ltd., Zama, Kanagawa, 252-8583, Japan
| | - Tadao Saito
- Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan
| | - Haruki Kitazawa
- Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan
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Fitzpatrick LR. Probiotics for the treatment of Clostridium difficile associated disease. World J Gastrointest Pathophysiol 2013; 4:47-52. [PMID: 23946887 PMCID: PMC3740259 DOI: 10.4291/wjgp.v4.i3.47] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2013] [Revised: 05/15/2013] [Accepted: 06/04/2013] [Indexed: 02/06/2023] Open
Abstract
The purpose of this review paper is to update the current and potential future role of probiotics for Clostridium difficile-associated disease (CDAD). Included in this review, is an update on the testing of newer probiotics (e.g., Bacillus coagulans GBI-30, 6086) in animal models of CDAD. There is a focus on the modulation of signal transduction pathways (i.e., transcription factors like cAMP response element-binding, activator protein 1, and nuclear factor kappa B), as well as the inhibition of certain kinases (e.g., p38 mitogen activated protein kinases) by probiotics. Inhibition of signal transduction by probiotics, such as Saccharomyces boulardii, result in multiple effects on intestinal fluid secretion, neutrophil influx into the colon, inflammation, and colonocyte apoptosis that may positively impact CDAD. Recent clinical approaches with probiotics, for the prevention of primary and recurrent CDAD, are also summarized in this review paper. Future directions for the treatment of CDAD by probiotics are also mentioned in this review. In particular, the use of multi-strain probiotic formulations such as Ecologic® AAD and VSL #3® may represent a rationale pharmacological approach, particularly as adjunctive therapies for CDAD. Understanding the mechanistic basis of CDAD, and how probiotics interfere at ceratin steps in the pathogenic process, may also present the opportunity to design other multi-strain probiotics that could have a future impact on CDAD.
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Diabetes, obesity and gut microbiota. Best Pract Res Clin Gastroenterol 2013; 27:73-83. [PMID: 23768554 DOI: 10.1016/j.bpg.2013.03.007] [Citation(s) in RCA: 373] [Impact Index Per Article: 31.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2012] [Revised: 02/28/2013] [Accepted: 03/14/2013] [Indexed: 01/31/2023]
Abstract
The gut microbiota composition has been associated with several hallmarks of metabolic syndrome (e.g., obesity, type 2 diabetes, cardiovascular diseases, and non-alcoholic steatohepatitis). Growing evidence suggests that gut microbes contribute to the onset of the low-grade inflammation characterising these metabolic disorders via mechanisms associated with gut barrier dysfunctions. Recently, enteroendocrine cells and the endocannabinoid system have been shown to control gut permeability and metabolic endotoxaemia. Moreover, targeted nutritional interventions using non-digestible carbohydrates with prebiotic properties have shown promising results in pre-clinical studies in this context, although human intervention studies warrant further investigations. Thus, in this review, we discuss putative mechanisms linking gut microbiota and type 2 diabetes. These data underline the advantage of investigating and changing the gut microbiota as a therapeutic target in the context of obesity and type 2 diabetes.
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Murata K, Villena J, Tomosada Y, Hara R, Chiba E, Shimazu T, Aso H, Suda Y, Iwabuchi N, Xiao JZ, Saito T, Kitazawa H. Bifidobacteria Upregulate Expression of Toll-Like Receptor Negative Regulators Counteracting Enterotoxigenic <i>Escherichia coli</i> Mediated Inflammation in Bovine Intestinal Epitheliocytes. ACTA ACUST UNITED AC 2013. [DOI: 10.4236/ojvm.2013.32023] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Characterisation of the bacterial community in expressed prostatic secretions from patients with chronic prostatitis/chronic pelvic pain syndrome and infertile men: a preliminary investigation. Asian J Androl 2012; 14:566-73. [PMID: 22635162 DOI: 10.1038/aja.2012.30] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
The expressed prostatic secretions (EPSs) of men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), infertile men and normal men were subjected to microbiological study. EPSs were collected from the subjects, which included 26 normal men, 11 infertile patients and 51 CP/CPPS patients. DNA was extracted from each specimen, and the V3 regions of the 16S rRNA genes were amplified using universal bacterial primers. The results showed that the EPS 16S rRNA gene-positive rate in the CP/CPPS and infertile patients was much higher than in the normal men, but without any difference among the three patient groups. The denaturing gradient gel electrophoresis (DGGE) method was used to characterize the EPS bacterial community structure of the prostate fluid from patients with CP/CPPS or infertility issues. Principal component analysis (PCA) and partial least squares (PLS) analyses of PCR-DGGE profiles revealed that the EPS bacterial community structure differed among the three groups. Three bands were identified as the key factors responsible for the discrepancy between CP/CPPS patients and infertile patients (P<0.05). Two bands were identified as priority factors in the discrepancy of category IIIA and category IIIB prostatitis patients (P<0.05). According to this research, the ecological balance of the prostate and low urethra tract, when considered as a microenvironment, might play an important role in the maintenance of a healthy male reproductive tract.
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López P, González-Rodríguez I, Gueimonde M, Margolles A, Suárez A. Immune response to Bifidobacterium bifidum strains support Treg/Th17 plasticity. PLoS One 2011; 6:e24776. [PMID: 21966367 PMCID: PMC3178565 DOI: 10.1371/journal.pone.0024776] [Citation(s) in RCA: 102] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2011] [Accepted: 08/17/2011] [Indexed: 12/20/2022] Open
Abstract
In this work we analyzed the immune activation properties of different Bifidobacterium strains in order to establish their ability as inductors of specific effector (Th) or regulatory (Treg) responses. First, we determined the cytokine pattern induced by 21 Bifidobacterium strains in peripheral blood mononuclear cells (PBMCs). Results showed that four Bifidobacterium bifidum strains showed the highest production of IL-17 as well as a poor secretion of IFNγ and TNFα, suggesting a Th17 profile whereas other Bifidobacterium strains exhibited a Th1-suggestive profile. Given the key role of Th17 subsets in mucosal defence, strains suggestive of Th17 responses and the putative Th1 Bifidobacterium breve BM12/11 were selected to stimulate dendritic cells (DC) to further determine their capability to induce the differentiation of naïve CD4+ lymphocytes toward different Th or Treg cells. All selected strains were able to induce phenotypic DC maturation, but showed differences in cytokine stimulation, DC treated with the putative Th17 strains displaying high IL-1β/IL-12 and low IL-12/IL-10 index, whereas BM12/11-DC exhibited the highest IL-12/IL-10 ratio. Differentiation of naïve lymphocytes confirmed Th1 polarization by BM12/11. Unexpectedly, any B. bifidum strain showed significant capability for Th17 generation, and they were able to generate functional Treg, thus suggesting differences between in vivo and vitro responses. In fact, activation of memory lymphocytes present in PBMCS with these bacteria, point out the presence in vivo of specific Th17 cells, supporting the plasticity of Treg/Th17 populations and the key role of commensal bacteria in mucosal tolerance and T cell reprogramming when needed.
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Affiliation(s)
- Patricia López
- Immunology Area, Department of Functional Biology, University of Oviedo, Oviedo, Asturias, Spain
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA), Consejo Superior de Investigaciones Científicas (CSIC), Villaviciosa, Asturias, Spain
| | - Irene González-Rodríguez
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA), Consejo Superior de Investigaciones Científicas (CSIC), Villaviciosa, Asturias, Spain
| | - Miguel Gueimonde
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA), Consejo Superior de Investigaciones Científicas (CSIC), Villaviciosa, Asturias, Spain
| | - Abelardo Margolles
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA), Consejo Superior de Investigaciones Científicas (CSIC), Villaviciosa, Asturias, Spain
- * E-mail:
| | - Ana Suárez
- Immunology Area, Department of Functional Biology, University of Oviedo, Oviedo, Asturias, Spain
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Abstract
Several reviews recently explored how the gut microbiota was able to control host energy metabolism, and thereby the development of adiposity. In this review, we focused on the state of the art that supports a link between the gut microbiota composition and activity, and the management of glycemia associated with overweight and diabetes. Several microbial-derived compounds are related to disturbances of glucose homeostasis including the gram-negative-derived lipopolysaccharides. Some nutrients with prebiotic properties, which escape the digestion in the upper part of the gut, modify the composition of the gut microbiota in favor of bacteria that could play a beneficial role on glucose homeostasis, namely by modulating the endocrine function of the gut, and by reinforcing the gut barrier. Adequate intervention studies in diabetic patients are required to assess the relevance of those experimental data for human health.
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Affiliation(s)
- Nathalie M Delzenne
- Louvain Drug Research Institute, Metabolism and Nutrition Research Group, Université Catholique de Louvain, Brussels, Belgium.
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