|
1
|
Fang ZX, Kuang XY, Li YH, Yu RX, Wang F, Luo SW. Comparative Analysis of the Probiotic Features of Lysinibacillus and Enterobacter Strains Isolated from Gut Tract of Triploid Cyprinid Fish. Curr Microbiol 2025; 82:91. [PMID: 39825897 DOI: 10.1007/s00284-025-04074-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2024] [Accepted: 01/04/2025] [Indexed: 01/20/2025]
Abstract
Gut mucosal immunity of teleost is mainly governed by mucosa-associated lymphoid tissues (MALT) and indigenous microbiota on mucosal surfaces of gut tract, which can confer protection against pathogenic invasion. However, the probiotic features of bacterial isolates from gut tract of triploid cyprinid fish (TCF) were largely unclear. In this study, Lysinibacillus and Enterobacter strains were isolated for probiotic identification. Whole genome sequencing (WGS) analysis indicated that Lysinibacillus and Enterobacter isolates possessed a variety of functional genes associated with probiotic features. Biofilm-forming activity (BFA) were one of the most important probiotic features, which can enable probiotic strains to communicate with indigenous microbiota by forming sessile community and then confer protection against stressors and invading pathogens. In this study, Lysinibacillus and Enterobacter isolates displayed high levels of BFA, hydrophobicity as well as aggregating potentials. Moreover, supernatants of probiotic isolates not only decreased pathogenic BFA and growth activity, but also showed high decomposing activity to macronutrients. These results indicated that probiotic isolates from gut tract of TCFs may pose protective roles in health of farmed fish.
Collapse
Affiliation(s)
- Zi-Xuan Fang
- State Key Laboratory of Developmental Biology of Freshwater Fish, Engineering Research Center of Polyploidy Fish Reproduction and Breeding of the State Education Ministry, College of Life Science, Hunan Normal University, Changsha, 410081, People's Republic of China
| | - Xu-Ying Kuang
- State Key Laboratory of Developmental Biology of Freshwater Fish, Engineering Research Center of Polyploidy Fish Reproduction and Breeding of the State Education Ministry, College of Life Science, Hunan Normal University, Changsha, 410081, People's Republic of China
| | - Yao-Hui Li
- State Key Laboratory of Developmental Biology of Freshwater Fish, Engineering Research Center of Polyploidy Fish Reproduction and Breeding of the State Education Ministry, College of Life Science, Hunan Normal University, Changsha, 410081, People's Republic of China
| | - Ruo-Xing Yu
- State Key Laboratory of Developmental Biology of Freshwater Fish, Engineering Research Center of Polyploidy Fish Reproduction and Breeding of the State Education Ministry, College of Life Science, Hunan Normal University, Changsha, 410081, People's Republic of China
| | - Fei Wang
- State Key Laboratory of Developmental Biology of Freshwater Fish, Engineering Research Center of Polyploidy Fish Reproduction and Breeding of the State Education Ministry, College of Life Science, Hunan Normal University, Changsha, 410081, People's Republic of China
| | - Sheng-Wei Luo
- State Key Laboratory of Developmental Biology of Freshwater Fish, Engineering Research Center of Polyploidy Fish Reproduction and Breeding of the State Education Ministry, College of Life Science, Hunan Normal University, Changsha, 410081, People's Republic of China.
| |
Collapse
|
|
2
|
Zuo M, Du J, Liu Y, Chen M, Liu B, Li G, Li M, Huang S, Yu G. Deletion of the gsk-3β (Glycogen synthase kinase-3β) in zebrafish results in decreased susceptibility to Aeromonas hydrophila. Microb Pathog 2025; 198:107129. [PMID: 39557225 DOI: 10.1016/j.micpath.2024.107129] [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: 08/13/2024] [Revised: 11/15/2024] [Accepted: 11/15/2024] [Indexed: 11/20/2024]
Abstract
Aeromonas hydrophila is a significant pathogen in the field of fish farming, resulting in substantial financial losses for the aquaculture industry. As the pathogen's resistance to commercially available antibiotics continues to rise, the identification of novel antimicrobial strategies becomes increasingly crucial. This study aims to explore the modulatory impact of gsk-3β (Glycogen synthase kinase-3β) on the intrinsic immunity against Aeromonas hydrophila in zebrafish, with the objective of uncovering a new avenue for enhancing fish antimicrobial activity through gene editing. Our investigation involved an analysis of the evolutionary patterns and protein sequence of gsk-3β, elucidating its conserved characteristics in zebrafish and fish species of economic importance. In this research, CRISPR-Cas9 technology was employed to generate a zebrafish model with a knockout of gsk-3β, resulting in a decreased resistance of zebrafish to Aeromonas hydrophila (ATCC 7966) infection. Furthermore, we conducted preliminary investigations into the potential mechanisms through which gsk-3β governs antimicrobial immunity. Our findings revealed that knockout of gsk-3β resulted in diminished activation of innate immunity, antioxidant capacity, and autophagy. Hence, the findings of this study are highly significant in improving the economic benefits of aquaculture and in effectively preventing and controlling infection caused by Aeromonas hydrophila.
Collapse
Affiliation(s)
- Mingzhong Zuo
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou, 450046, People's Republic of China
| | - Juan Du
- Institute of Maternal and Child Health, Wuhan Children' s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430016, Hubei, People's Republic of China
| | - Yuqing Liu
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou, 450046, People's Republic of China
| | - Mengjuan Chen
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou, 450046, People's Republic of China
| | - Bianzhi Liu
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou, 450046, People's Republic of China
| | - Guoxi Li
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou, 450046, People's Republic of China
| | - Ming Li
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou, 450046, People's Republic of China
| | - Shucheng Huang
- College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, 450046, People's Republic of China.
| | - Guangqing Yu
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou, 450046, People's Republic of China.
| |
Collapse
|
|
3
|
Huang W, Hu W, Fang M, Zhang Q, Zhang Y, Wang H. Impacts of prenatal environmental exposures on fetal-placental-maternal bile acid homeostasis and long-term health in offspring. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2024; 283:116929. [PMID: 39213751 DOI: 10.1016/j.ecoenv.2024.116929] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Revised: 08/06/2024] [Accepted: 08/21/2024] [Indexed: 09/04/2024]
Abstract
During pregnancy, the maternal body undergoes a series of adaptative physiological changes, leading to a slight increase in serum bile acid (BA) levels. Although the fetal liver can synthesize BAs since the first trimester through the alternative pathway, the BA metabolic system is immature in the fetus. Compared to adults, the fetus has a distinct composition of BA pool and limited expression of BA synthesis enzymes and transporters. Besides, the "enterohepatic circulation" of BAs is absent in fetus. Thus, fetal BAs need to be transported to the mother through the placenta for further metabolism and excretion, and maternal BAs can also be transported to the fetus. That is what we call the "fetal-placental-maternal BA circulation". Various BA transporters and nuclear receptors are essential for maintaining the balance of this BA circulation to ensure normal fetal development. However, prenatal adverse environments can alter fetal BA metabolism, resulting in intrauterine developmental abnormalities and susceptibility to a variety of adult chronic diseases. This review summarizes the current understanding of the fetal-placental-maternal BA circulation and discusses the effects of prenatal adverse environments on this particular BA circulation, aiming to provide a theoretical basis for exploring early prevention and treatment strategies for BA metabolism-associated adverse pregnancy outcomes and long-term impairments.
Collapse
Affiliation(s)
- Wen Huang
- Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China; Department of Obstetrics and Gynaecology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
| | - Wen Hu
- Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China; Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan 430071, China
| | - Man Fang
- Department of Obstetrics and Gynaecology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
| | - Qi Zhang
- Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China
| | - Yuanzhen Zhang
- Department of Obstetrics and Gynaecology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan 430071, China
| | - Hui Wang
- Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China; Department of Obstetrics and Gynaecology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan 430071, China.
| |
Collapse
|
|
4
|
Hossain A, Gnanagobal H, Cao T, Chakraborty S, Chukwu-Osazuwa J, Soto-Dávila M, Vasquez I, Santander J. Role of cold shock proteins B and D in Aeromonas salmonicida subsp. salmonicida physiology and virulence in lumpfish ( Cyclopterus lumpus). Infect Immun 2024; 92:e0001124. [PMID: 38920386 PMCID: PMC11320987 DOI: 10.1128/iai.00011-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Accepted: 06/05/2024] [Indexed: 06/27/2024] Open
Abstract
Cold shock proteins (Csp) are pivotal nucleic acid binding proteins known for their crucial roles in the physiology and virulence of various bacterial pathogens affecting plant, insect, and mammalian hosts. However, their significance in bacterial pathogens of teleost fish remains unexplored. Aeromonas salmonicida subsp. salmonicida (hereafter A. salmonicida) is a psychrotrophic pathogen and the causative agent of furunculosis in marine and freshwater fish. Four csp genes (cspB, cspD, cspA, and cspC) have been identified in the genome of A. salmonicida J223 (wild type). Here, we evaluated the role of DNA binding proteins, CspB and CspD, in A. salmonicida physiology and virulence in lumpfish (Cyclopterus lumpus). A. salmonicida ΔcspB, ΔcspD, and the double ΔcspBΔcspD mutants were constructed and characterized. A. salmonicida ΔcspB and ΔcspBΔcspD mutants showed a faster growth at 28°C, and reduced virulence in lumpfish. A. salmonicida ΔcspD showed a slower growth at 28°C, biofilm formation, lower survival in low temperatures and freezing conditions (-20°C, 0°C, and 4°C), deficient in lipopolysaccharide synthesis, and low virulence in lumpfish. Additionally, ΔcspBΔcspD mutants showed less survival in the presence of bile compared to the wild type. Transcriptome analysis revealed that 200, 37, and 921 genes were differentially expressed in ΔcspB, ΔcspD, and ΔcspBΔcspD, respectively. In ΔcspB and ΔcspBΔcspD virulence genes in the chromosome and virulence plasmid were downregulated. Our analysis indicates that CspB and CspD mostly act as a transcriptional activator, influencing cell division (e.g., treB), virulence factors (e.g., aexT), and ultimately virulence.
Collapse
Affiliation(s)
- Ahmed Hossain
- Marine Microbial Pathogenesis and Vaccinology Laboratory, Department of Ocean Sciences, Memorial University of Newfoundland, Ocean Science Center, St. John's, Newfoundland, Canada
| | - Hajarooba Gnanagobal
- Marine Microbial Pathogenesis and Vaccinology Laboratory, Department of Ocean Sciences, Memorial University of Newfoundland, Ocean Science Center, St. John's, Newfoundland, Canada
| | - Trung Cao
- Marine Microbial Pathogenesis and Vaccinology Laboratory, Department of Ocean Sciences, Memorial University of Newfoundland, Ocean Science Center, St. John's, Newfoundland, Canada
| | - Setu Chakraborty
- Marine Microbial Pathogenesis and Vaccinology Laboratory, Department of Ocean Sciences, Memorial University of Newfoundland, Ocean Science Center, St. John's, Newfoundland, Canada
| | - Joy Chukwu-Osazuwa
- Marine Microbial Pathogenesis and Vaccinology Laboratory, Department of Ocean Sciences, Memorial University of Newfoundland, Ocean Science Center, St. John's, Newfoundland, Canada
| | - Manuel Soto-Dávila
- Marine Microbial Pathogenesis and Vaccinology Laboratory, Department of Ocean Sciences, Memorial University of Newfoundland, Ocean Science Center, St. John's, Newfoundland, Canada
| | - Ignacio Vasquez
- Marine Microbial Pathogenesis and Vaccinology Laboratory, Department of Ocean Sciences, Memorial University of Newfoundland, Ocean Science Center, St. John's, Newfoundland, Canada
| | - Javier Santander
- Marine Microbial Pathogenesis and Vaccinology Laboratory, Department of Ocean Sciences, Memorial University of Newfoundland, Ocean Science Center, St. John's, Newfoundland, Canada
| |
Collapse
|
|
5
|
Niu YR, Yu HN, Yan ZH, Yan XH. Multiomics Analysis Reveals Leucine Deprivation Promotes Bile Acid Synthesis by Upregulating Hepatic CYP7A1 and Intestinal Turicibacter sanguinis in Mice. J Nutr 2024; 154:1970-1984. [PMID: 38692354 DOI: 10.1016/j.tjnut.2024.04.033] [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: 01/07/2024] [Revised: 03/19/2024] [Accepted: 04/26/2024] [Indexed: 05/03/2024] Open
Abstract
BACKGROUND Leucine, a branched-chain amino acid, participates in the regulation of lipid metabolism and the composition of the intestinal microbiota. However, the related mechanism remains unclear. OBJECTIVES Here, we aimed to reveal the potential mechanisms by which hepatic CYP7A1 (a rate-limiting enzyme for bile acid [BA] synthesis) and gut microbiota coregulate BA synthesis under leucine deprivation. METHODS To this end, 8-wk-old C57BL/6J mice were fed with either regular diets or leucine-free diets for 1 wk. Then, we investigated whether secondary BAs were synthesized by Turicibacter sanguinis in 7-wk-old C57BL/6J germ-free mice gavaged with T. sanguinis for 2 wk by determining BA concentrations in the plasma, liver, and cecum contents using liquid chromatography-tandem mass spectrometry. RESULTS The results showed that leucine deprivation resulted in a significant increase in total BA concentration in the plasma and an increase in the liver, but no difference in total BA was observed in the cecum contents before and after leucine deprivation. Furthermore, leucine deprivation significantly altered BA profiles such as taurocholic acid and ω-muricholic acid in the plasma, liver, and cecum contents. CYP7A1 expression was significantly upregulated in the liver under leucine deprivation. Leucine deprivation also regulated the composition of the gut microbiota; specifically, it significantly upregulated the relative abundance of T. sanguinis, thus enhancing the conversion of primary BAs into secondary BAs by intestinal T. sanguinis in mice. CONCLUSIONS Overall, leucine deprivation regulated BA profiles in enterohepatic circulation by upregulating hepatic CYP7A1 expression and increasing intestinal T. sanguinis abundance. Our findings reveal the contribution of gut microbiota to BA metabolism under dietary leucine deprivation.
Collapse
Affiliation(s)
- Yao-Rong Niu
- National Key Laboratory of Agricultural Microbiology, Frontiers Science Center for Animal Breeding and Sustainable Production, Hubei Hongshan Laboratory, College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, Hubei, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, Hubei, China; Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, Hubei, China
| | - Hao-Nan Yu
- National Key Laboratory of Agricultural Microbiology, Frontiers Science Center for Animal Breeding and Sustainable Production, Hubei Hongshan Laboratory, College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, Hubei, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, Hubei, China; Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, Hubei, China
| | - Zhen-Hong Yan
- National Key Laboratory of Agricultural Microbiology, Frontiers Science Center for Animal Breeding and Sustainable Production, Hubei Hongshan Laboratory, College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, Hubei, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, Hubei, China; Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, Hubei, China
| | - Xiang-Hua Yan
- National Key Laboratory of Agricultural Microbiology, Frontiers Science Center for Animal Breeding and Sustainable Production, Hubei Hongshan Laboratory, College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, Hubei, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, Hubei, China; Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology, Wuhan, Hubei, China.
| |
Collapse
|
|
6
|
Sun L, Wang H, Fan Y, Yang F, Li M, Sun X, Sun E, Jin Y, Zhao L. The adsorption of 2-amino-1-methyl-6-phenyl-imidazolium [4, 5-B] pyridine (PhIP) by lactic acid bacteria 37X-15 and its peptidoglycan. Food Chem 2024; 440:138193. [PMID: 38128427 DOI: 10.1016/j.foodchem.2023.138193] [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: 08/08/2023] [Revised: 12/06/2023] [Accepted: 12/10/2023] [Indexed: 12/23/2023]
Abstract
The heterocyclic amine 2-amino-1-methyl-6-phenyl-imidazolium [4, 5-B] pyridine (PhIP), commonly found in roasted meat products, is considered a potential carcinogen. This study is to explore the underlying mechanisms involved in the adsorption of PhIP by lactic acid bacteria 37X-15 and its peptidoglycan. The scanning electron microscope results suggested that the strain's adsorption on PhIP occurs on the cell wall, primarily composed of peptidoglycan. The fourier-transformed infrared spectroscopy results indicated that PhIP adsorption by both lactic acid bacteria 37X-15 and its peptidoglycan primarily involved OH and NH binding groups. Different adsorption conditions affected the adsorption rate of PhIP by peptidoglycan. The optimal values for each adsorption condition were 2 h, 37 °C, and pH 6 when the maximum adsorption rate reached. This study provides a new direction for the application of lactic acid bacteria and its peptidoglycan in food safety.
Collapse
Affiliation(s)
- Lina Sun
- College of Food Science and Engineering, Inner Mongolia Agricultural University, Hohhot 010018, China; Integrative Research Base of Beef and Lamb Processing Technology, Ministry of Agriculture and Rural Affairs of the People's Republic of China, Hohhot 010018, China
| | - Huiting Wang
- College of Food Science and Engineering, Inner Mongolia Agricultural University, Hohhot 010018, China; Integrative Research Base of Beef and Lamb Processing Technology, Ministry of Agriculture and Rural Affairs of the People's Republic of China, Hohhot 010018, China
| | - Yande Fan
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China
| | - Fan Yang
- Ordos Ecological Environment Vocational College, Ordos 017010, China
| | - Meijun Li
- Market Supervision and Administration of Hohhot Xincheng District, Hohhot 010010, China
| | - Xueying Sun
- College of Food Science and Engineering, Inner Mongolia Agricultural University, Hohhot 010018, China; Integrative Research Base of Beef and Lamb Processing Technology, Ministry of Agriculture and Rural Affairs of the People's Republic of China, Hohhot 010018, China
| | - Erke Sun
- College of Food Science and Engineering, Inner Mongolia Agricultural University, Hohhot 010018, China; Integrative Research Base of Beef and Lamb Processing Technology, Ministry of Agriculture and Rural Affairs of the People's Republic of China, Hohhot 010018, China
| | - Ye Jin
- College of Food Science and Engineering, Inner Mongolia Agricultural University, Hohhot 010018, China; Integrative Research Base of Beef and Lamb Processing Technology, Ministry of Agriculture and Rural Affairs of the People's Republic of China, Hohhot 010018, China
| | - Lihua Zhao
- College of Food Science and Engineering, Inner Mongolia Agricultural University, Hohhot 010018, China; Integrative Research Base of Beef and Lamb Processing Technology, Ministry of Agriculture and Rural Affairs of the People's Republic of China, Hohhot 010018, China.
| |
Collapse
|
|
7
|
Niciura SCM, Cardoso TF, Ibelli AMG, Okino CH, Andrade BG, Benavides MV, Chagas ACDS, Esteves SN, Minho AP, Regitano LCDA, Gondro C. Multi-omics data elucidate parasite-host-microbiota interactions and resistance to Haemonchus contortus in sheep. Parasit Vectors 2024; 17:102. [PMID: 38429820 PMCID: PMC10908167 DOI: 10.1186/s13071-024-06205-9] [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: 12/27/2023] [Accepted: 02/18/2024] [Indexed: 03/03/2024] Open
Abstract
BACKGROUND The integration of molecular data from hosts, parasites, and microbiota can enhance our understanding of the complex biological interactions underlying the resistance of hosts to parasites. Haemonchus contortus, the predominant sheep gastrointestinal parasite species in the tropics, causes significant production and economic losses, which are further compounded by the diminishing efficiency of chemical control owing to anthelmintic resistance. Knowledge of how the host responds to infection and how the parasite, in combination with microbiota, modulates host immunity can guide selection decisions to breed animals with improved parasite resistance. This understanding will help refine management practices and advance the development of new therapeutics for long-term helminth control. METHODS Eggs per gram (EPG) of feces were obtained from Morada Nova sheep subjected to two artificial infections with H. contortus and used as a proxy to select animals with high resistance or susceptibility for transcriptome sequencing (RNA-seq) of the abomasum and 50 K single-nucleotide genotyping. Additionally, RNA-seq data for H. contortus were generated, and amplicon sequence variants (ASV) were obtained using polymerase chain reaction amplification and sequencing of bacterial and archaeal 16S ribosomal RNA genes from sheep feces and rumen content. RESULTS The heritability estimate for EPG was 0.12. GAST, GNLY, IL13, MGRN1, FGF14, and RORC genes and transcripts were differentially expressed between resistant and susceptible animals. A genome-wide association study identified regions on chromosomes 2 and 11 that harbor candidate genes for resistance, immune response, body weight, and adaptation. Trans-expression quantitative trait loci were found between significant variants and differentially expressed transcripts. Functional co-expression modules based on sheep genes and ASVs correlated with resistance to H. contortus, showing enrichment in pathways of response to bacteria, immune and inflammatory responses, and hub features of the Christensenellaceae, Bacteroides, and Methanobrevibacter genera; Prevotellaceae family; and Verrucomicrobiota phylum. In H. contortus, some mitochondrial, collagen-, and cuticle-related genes were expressed only in parasites isolated from susceptible sheep. CONCLUSIONS The present study identified chromosome regions, genes, transcripts, and pathways involved in the elaborate interactions between the sheep host, its gastrointestinal microbiota, and the H. contortus parasite. These findings will assist in the development of animal selection strategies for parasite resistance and interdisciplinary approaches to control H. contortus infection in sheep.
Collapse
|
|
8
|
Petito-da-Silva TI, Villardi FM, Penna-de-Carvalho A, Mandarim-de-Lacerda CA, Souza-Mello V, Barbosa-da-Silva S. An Intestinal FXR Agonist Mitigates Dysbiosis, Intestinal Tight Junctions, and Inflammation in High-Fat Diet-Fed Mice. Mol Nutr Food Res 2024; 68:e2300148. [PMID: 38085111 DOI: 10.1002/mnfr.202300148] [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: 03/15/2023] [Revised: 10/23/2023] [Indexed: 03/01/2024]
Abstract
SCOPE To analyze the effects of fexaramine (FEX), as an intestinal FXR agonist, on the modulation of the intestinal microbiota and ileum of mice fed a high-fat (HF) diet. METHODS AND RESULTS Three-month-old C57Bl/6 male mice are divided into two groups and received a control (C, 10% of energy from lipids) or HF (50% of energy from lipids) diet for 12 weeks. They are subdivided into the C, C + FEX, HF, and HF + FEX groups. FEX is administered (FEX-5 mg kg-1 ) via orogastric gavage for three weeks. Body mass (BM), glucose metabolism, qPCR 16S rRNA gene expression, and ileum gene expression, bile acids (BAs), tight junctions (TJs), and incretin are analyzed. FEX reduces BM and glucose intolerance, reduces plasma lipid concentrations and the Firmicutes/Bacteroidetes ratio, increases the Lactobacillus sp. and Prevotella sp. abundance, and reduces the Escherichia coli abundance. Consequently, the ileal gene expression of Fxr-Fgf15, Tgr5-Glp1, and Cldn-Ocldn-Zo1 is increased, and Tlr4-Il6-Il1beta is decreased. CONCLUSION FEX stimulates intestinal FXR and improves dysbiosis, intestinal TJs, and the release of incretins, mitigating glucose intolerance and BM increases induced by an HF diet. However, FEX results in glucose intolerance, insulin resistance, and reduces intestinal TJs in a control group, thus demonstrating limitations to this dietary model.
Collapse
Affiliation(s)
- Tamiris Ingrid Petito-da-Silva
- Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Felipe Missiba Villardi
- Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Aline Penna-de-Carvalho
- Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Carlos Alberto Mandarim-de-Lacerda
- Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Vanessa Souza-Mello
- Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Sandra Barbosa-da-Silva
- Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| |
Collapse
|
|
9
|
Bourayou E, Perchet T, Meunier S, Bouvier H, Mailhe MP, Melanitou E, Cumano A, Golub R. Bone marrow monocytes sustain NK cell-poiesis during non-alcoholic steatohepatitis. Cell Rep 2024; 43:113676. [PMID: 38217855 DOI: 10.1016/j.celrep.2024.113676] [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: 07/14/2023] [Revised: 11/22/2023] [Accepted: 01/02/2024] [Indexed: 01/15/2024] Open
Abstract
Natural killer (NK) cells are the predominant lymphocyte population in the liver. At the onset of non-alcoholic steatohepatitis (NASH), an accumulation of activated NK cells is observed in the liver in parallel with inflammatory monocyte recruitment and an increased systemic inflammation. Using in vivo and in vitro experiments, we unveil a specific stimulation of NK cell-poiesis during NASH by medullary monocytes that trans-present interleukin-15 (IL-15) and secrete osteopontin, a biomarker for patients with NASH. This cellular dialogue leads to increased survival and maturation of NK precursors that are recruited to the liver, where they dampen the inflammatory monocyte infiltration. The increase in the production of both osteopontin and the IL-15/IL-15Rα complex by bone marrow monocytes is induced by endotoxemia. We propose a tripartite gut-liver-bone marrow axis regulating the immune population dynamics and effector functions during liver inflammation.
Collapse
Affiliation(s)
- Elsa Bourayou
- Institut Pasteur, Université Paris Cité, INSERM U1223, Lymphocyte and Immunity Unit, 75015 Paris, France
| | - Thibaut Perchet
- Institut Pasteur, Université Paris Cité, INSERM U1223, Lymphocyte and Immunity Unit, 75015 Paris, France
| | - Sylvain Meunier
- Institut Pasteur, Université Paris Cité, INSERM U1223, Lymphocyte and Immunity Unit, 75015 Paris, France; Institut Mondor de Recherche Biomédicale (IMRB), INSERM U955, 94000 Créteil, France
| | - Hugo Bouvier
- Institut Pasteur, Université Paris Cité, INSERM U1223, Lymphocyte and Immunity Unit, 75015 Paris, France
| | - Marie-Pierre Mailhe
- Institut Pasteur, Université Paris Cité, INSERM U1223, Lymphocyte and Immunity Unit, 75015 Paris, France
| | - Evie Melanitou
- Institut Pasteur, Université Paris Cité, Department of Parasites and Insect Vectors, 75015 Paris, France
| | - Ana Cumano
- Institut Pasteur, Université Paris Cité, INSERM U1223, Lymphocyte and Immunity Unit, 75015 Paris, France
| | - Rachel Golub
- Institut Pasteur, Université Paris Cité, INSERM U1223, Lymphocyte and Immunity Unit, 75015 Paris, France.
| |
Collapse
|
|
10
|
Chen Z, Chen H, Huang W, Guo X, Yu L, Shan J, Deng X, Liu J, Li W, Shen W, Fan H. Bacteroides fragilis alleviates necrotizing enterocolitis through restoring bile acid metabolism balance using bile salt hydrolase and inhibiting FXR-NLRP3 signaling pathway. Gut Microbes 2024; 16:2379566. [PMID: 39013030 PMCID: PMC11253882 DOI: 10.1080/19490976.2024.2379566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Accepted: 07/09/2024] [Indexed: 07/18/2024] Open
Abstract
Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in premature infants with no specific treatments available. We aimed to identify the molecular mechanisms underlying NEC and investigate the therapeutic effects of Bacteroides fragilis on NEC. Clinical samples of infant feces, bile acid-targeted metabolomics, pathological staining, bioinformatics analysis, NEC rat model, and co-immunoprecipitation were used to explore the pathogenesis of NEC. Taxonomic characterization of the bile salt hydrolase (bsh) gene, enzyme activity assays, 16S rRNA sequencing, and organoids were used to explore the therapeutic effects of B. fragilis on NEC-related intestinal damage. Clinical samples, NEC rat models, and in vitro experiments revealed that total bile acid increased in the blood but decreased in feces. Moreover, the levels of FXR and other bile acid metabolism-related genes were abnormal, resulting in disordered bile acid metabolism in NEC. Taurochenodeoxycholic acid accelerated NEC pathogenesis and taurodeoxycholate alleviated NEC. B. fragilis displayed bsh genes and enzyme activity and alleviated intestinal damage by restoring gut microbiota dysbiosis and bile acid metabolism abnormalities by inhibiting the FXR-NLRP3 signaling pathway. Our results provide valuable insights into the therapeutic role of B. fragilis in NEC. Administering B. fragilis may substantially alleviate intestinal damage in NEC.
Collapse
MESH Headings
- Enterocolitis, Necrotizing/metabolism
- Enterocolitis, Necrotizing/microbiology
- Enterocolitis, Necrotizing/drug therapy
- Animals
- NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
- NLR Family, Pyrin Domain-Containing 3 Protein/genetics
- Bacteroides fragilis/metabolism
- Bacteroides fragilis/genetics
- Signal Transduction/drug effects
- Bile Acids and Salts/metabolism
- Rats
- Receptors, Cytoplasmic and Nuclear/metabolism
- Receptors, Cytoplasmic and Nuclear/genetics
- Gastrointestinal Microbiome/drug effects
- Amidohydrolases/metabolism
- Amidohydrolases/genetics
- Humans
- Rats, Sprague-Dawley
- Infant, Newborn
- Disease Models, Animal
- Male
- Female
- Probiotics/administration & dosage
- Probiotics/pharmacology
- Infant, Premature
- Dysbiosis/microbiology
Collapse
Affiliation(s)
- Zhenhui Chen
- Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China
| | - Huijuan Chen
- Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China
| | - Wanwen Huang
- Experimental Teaching Center of Preventive Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China
| | - Xiaotong Guo
- Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China
| | - Lu Yu
- Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Jiamin Shan
- Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China
| | - Xiaoshi Deng
- Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China
| | - Jiaxin Liu
- Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China
| | - Wendan Li
- Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China
| | - Wei Shen
- Department of Neonatology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Hongying Fan
- Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China
| |
Collapse
|
|
11
|
Chattaraj B, Nandi A, Lin WY. Role of the gallbladder in our metabolism and immune system. GALLSTONE FORMATION, DIAGNOSIS, TREATMENT AND PREVENTION 2024:23-38. [DOI: 10.1016/b978-0-443-16098-1.00008-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
12
|
Han C, Li Z, Liu R, Zhao Z, Wang Y, Zuo X, Zhang Y, Geng Z, Huang H, Pan X, Li W. Lonicerae flos polysaccharides improve nonalcoholic fatty liver disease by activating the adenosine 5'-monophosphate-activated protein kinase pathway and reshaping gut microbiota. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2023; 103:7721-7738. [PMID: 37439182 DOI: 10.1002/jsfa.12854] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Revised: 07/09/2023] [Accepted: 07/13/2023] [Indexed: 07/14/2023]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver cirrhosis and cancer. Lonicerae flos polysaccharides (LPs) have been shown to be effective in treating metabolic diseases; however, the therapeutic effects and underlying molecular mechanisms of LPs in NAFLD remain unclear. PURPOSE The objective of this study was to investigate the morphological characterization of Lonicerae flos polysaccharides (LPs) and the mechanism of LPs in relieving NAFLD. METHODS The morphology of LPs was observed using atomic force microscopy (AFM), X-ray diffraction (XRD), thermal weight (TG), and thermal weight derivative (DTG); NAFLD mice were treated with LPs at the same time as they were induced with a Western diet, and then the indexes related to glycolipid metabolism, fibrosis, inflammation, and autophagy in the serum and liver of the mice were detected. RESULTS The atomic force microscope analysis results indicated that the LPs displayed sugar-chain aggregates, exhibited an amorphous structure, and were relatively stable in thermal cracking at 150 °C. It was also found that LPs exerted therapeutic effects in NAFLD. The LPs prevented high-fat and -cholesterol diet-induced NAFLD progression by regulating glucose metabolism dysregulation, insulin resistance, lipid accumulation, inflammation, fibrosis, and autophagy. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) inhibitor compound C abrogated LP-induced hepatoprotection in mice with NAFLD. The LPs further treated NAFLD by reshaping the structure of the gut microbiota, in which Desulfovibrio bacteria plays a key roles. CONCLUSION Lonicerae flos polysaccharides exert protective effects against NAFLD in mice by improving the structure of the intestinal flora and activating the AMPK signaling pathway. © 2023 Society of Chemical Industry.
Collapse
Affiliation(s)
- Chao Han
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Zongshuo Li
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Ruiying Liu
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Zihan Zhao
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Yu Wang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Xuli Zuo
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Yushi Zhang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Zeyu Geng
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Houyu Huang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Xiuzhen Pan
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Weidong Li
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| |
Collapse
|
|
13
|
Zhang W, Dong XY, Huang R. Gut Microbiota in Ischemic Stroke: Role of Gut Bacteria-Derived Metabolites. Transl Stroke Res 2023; 14:811-828. [PMID: 36279071 DOI: 10.1007/s12975-022-01096-3] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 09/05/2022] [Accepted: 10/07/2022] [Indexed: 11/30/2022]
Abstract
Ischemic stroke (IS) remains a leading cause of death and long-term disability globally. Several mechanisms including glutamate excitotoxicity, calcium overload, neuroinflammation, oxidative stress, mitochondrial damage, and apoptosis are known to be involved in the pathogenesis of IS, but the underlying pathophysiology mechanisms of IS are not fully clarified. During the past decade, gut microbiota were recognized as a key regulator to affect the health of the host either directly or via their metabolites. Recent studies indicate that gut bacterial dysbiosis is closely related to hypertension, diabetes, obesity, dyslipidemia, and metabolic syndrome, which are the main risk factors for cardiovascular diseases. Increasing evidence indicates that IS can lead to perturbation in gut microbiota and increased permeability of the gut mucosa, known as "leaky gut," resulting in endotoxemia and bacterial translocation. In turn, gut dysbiosis and impaired intestinal permeability can alter gut bacterial metabolite signaling profile from the gut to the brain. Microbiota-derived products and metabolites, such as short-chain fatty acids (SCFAs), bile acids (BAs), trimethylamine N-oxide (TMAO), lipopolysaccharides (LPS), and phenylacetylglutamine (PAGln) can exert beneficial or detrimental effects on various extraintestinal organs, including the brain, liver, and heart. These metabolites have been increasingly acknowledged as biomarkers and mediators of IS. However, the specific role of the gut bacterial metabolites in the context of stroke remains incompletely understood. In-depth studies on these products and metabolites may provide new insight for the development of novel therapeutics for IS.
Collapse
Affiliation(s)
- Wei Zhang
- Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xiao Yu Dong
- Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Rui Huang
- Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, China.
| |
Collapse
|
|
14
|
Yang M, Liu S, Cai J, Sun X, Li C, Tan M, He B. Bile acids ameliorates lipopolysaccharide-induced endometritis in mice by inhibiting NLRP3 inflammasome activation. Life Sci 2023; 331:122062. [PMID: 37666389 DOI: 10.1016/j.lfs.2023.122062] [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: 05/09/2023] [Revised: 08/23/2023] [Accepted: 08/28/2023] [Indexed: 09/06/2023]
Abstract
AIMS Endometritis is a common inflammatory disorder affecting the reproductive health in both humans and livestock. The NLR family pyrin domain containing 3 (NLRP3) inflammasome has recently been identified as a possible therapeutic target for several inflammatory disorders. Bile acids (BAs) have been shown to possess anti-inflammatory properties by inhibiting the activation of the NLRP3 inflammasome. However, whether BAs ameliorate endometritis by targeting NLRP3 inflammasome remain poorly understood. MAIN METHODS Female NLRP3+/+ and NLRP3-/- mice were subjected to uterine perfusion with lipopolysaccharide (LPS) to establish the endometritis model. For BAs pre-treatment, wild-type mice were administered oral gavage of BAs for seven days followed by uterine perfusion with LPS. All mice were euthanized and the uterine tissues were collected for analysis. KEY FINDINGS The abundances of NLRP3 and interleukin-1 beta (IL-1β) were significantly upregulated in the uterine tissues of endometritis mice. NLRP3 deficiency led to a reduction in the inflammatory response, neutrophil infiltration, and myeloperoxidase (MPO) activity in the uterus, as well as an inhibition of IL-1β secretion. Moreover, BAs pre-treatment successfully decreased LPS-induced upregulation of NLRP3, ASC, and Caspase1, lessened histopathological alteration in the uterus, and notably reduced MPO activity and secretion of IL-1β. SIGNIFICANCE NLRP3 inflammasome is a promising target for endometritis treatment and BAs exhibit anti-inflammatory properties by repressing NLRP3 inflammasome activation, making them a possible novel therapeutic strategy for endometritis.
Collapse
Affiliation(s)
- Miaoxin Yang
- Key Laboratory of Animal Physiology & Biochemistry, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China
| | - Suyuan Liu
- Key Laboratory of Animal Physiology & Biochemistry, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China
| | - Jiangxue Cai
- Key Laboratory of Animal Physiology & Biochemistry, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China
| | - Xiaoxiao Sun
- Key Laboratory of Animal Physiology & Biochemistry, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China
| | - Chenxuan Li
- Key Laboratory of Animal Physiology & Biochemistry, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China
| | - Meiling Tan
- Key Laboratory of Animal Physiology & Biochemistry, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China
| | - Bin He
- Key Laboratory of Animal Physiology & Biochemistry, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China; MOE Joint International Research Laboratory of Animal Health & Food Safety, Nanjing Agricultural University, Nanjing 210095, PR China.
| |
Collapse
|
|
15
|
Stojanović NM, Randjelović PJ, Maslovarić A, Kostić M, Raičević V, Sakač M, Bjedov S. How do different bile acid derivatives affect rat macrophage function - Friends or foes? Chem Biol Interact 2023; 383:110688. [PMID: 37648052 DOI: 10.1016/j.cbi.2023.110688] [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: 07/20/2023] [Revised: 08/13/2023] [Accepted: 08/26/2023] [Indexed: 09/01/2023]
Abstract
Due to an increased need for new immunomodulatory agents, many previously known molecules have been structurally modified in order to obtain new drugs, preserving at the same time some of the benevolent characteristics of the parent molecule. This study aimed to evaluate the immunomodulatory potential of a selected library of bile acid derivatives (BAD) using a broad spectrum of assays, evaluating rat peritoneal macrophages viability, cell membrane damage, lysosomal and adhesion function, and nitric oxide and cytokine production as a response to lipopolysaccharide stimulation. Also, in silico studies on two bile acid-activated receptors were conducted and the results were related to the observed in vitro effects. All tested BAD exerted significant toxicity in concentrations higher than 10 μM, which was determined based on mitochondria and cell membrane damage in a panel of assays. On the other hand, at lower concentrations, the tested BAD proved to be immunomodulatory since they affected lysosomal function, cell adhesion capacities and the ability to produce inflammatory cytokines in response to a stimulus. One of the compounds proved to exhibit significant toxicity toward macrophages, but also caused a concentration-dependent decrease in nitric oxide levels and was identified as a potential farnesoid X receptor agonist.
Collapse
Affiliation(s)
- Nikola M Stojanović
- Department of Physiology, Faculty of Medicine, University of Niš, 18000, Niš, Serbia.
| | - Pavle J Randjelović
- Department of Physiology, Faculty of Medicine, University of Niš, 18000, Niš, Serbia
| | | | - Miloš Kostić
- Department of Immunology, Faculty of Medicine, University of Niš, 18000, Niš, Serbia
| | - Vidak Raičević
- Department of Chemistry, Biochemistry, and Environmental Protection, Faculty of Sciences, University of Novi Sad, 21000, Novi Sad, Serbia
| | - Marija Sakač
- Department of Chemistry, Biochemistry, and Environmental Protection, Faculty of Sciences, University of Novi Sad, 21000, Novi Sad, Serbia
| | - Srđan Bjedov
- Department of Chemistry, Biochemistry, and Environmental Protection, Faculty of Sciences, University of Novi Sad, 21000, Novi Sad, Serbia
| |
Collapse
|
|
16
|
Pathare NN, Fayet-Moore F, Fogarty JA, Jacka FN, Strandwitz P, Strangman GE, Donoviel DB. Nourishing the brain on deep space missions: nutritional psychiatry in promoting resilience. Front Neural Circuits 2023; 17:1170395. [PMID: 37663891 PMCID: PMC10469890 DOI: 10.3389/fncir.2023.1170395] [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: 02/20/2023] [Accepted: 07/31/2023] [Indexed: 09/05/2023] Open
Abstract
The grueling psychological demands of a journey into deep space coupled with ever-increasing distances away from home pose a unique problem: how can we best take advantage of the benefits of fresh foods in a place that has none? Here, we consider the biggest challenges associated with our current spaceflight food system, highlight the importance of supporting optimal brain health on missions into deep space, and discuss evidence about food components that impact brain health. We propose a future food system that leverages the gut microbiota that can be individually tailored to best support the brain and mental health of crews on deep space long-duration missions. Working toward this goal, we will also be making investments in sustainable means to nourish the crew that remains here on spaceship Earth.
Collapse
Affiliation(s)
- Nihar N. Pathare
- Center for Space Medicine, Baylor College of Medicine, Houston, TX, United States
| | | | - Jennifer A. Fogarty
- Center for Space Medicine, Baylor College of Medicine, Houston, TX, United States
- Department of Medicine, Baylor College of Medicine, Houston, TX, United States
- Translational Research Institute for Space Health (TRISH), Houston, TX, United States
| | - Felice N. Jacka
- Food and Mood Centre, Institute for Mental and Physical Health and Clinical Translation (IMPACT) Strategic Research Centre, Deakin University, Geelong, VIC, Australia
- Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia
| | | | - Gary E. Strangman
- Neural Systems Group, Division of Health Sciences and Technology, Massachusetts General Hospital, Harvard Medical School and Harvard-MIT, Charlestown, MA, United States
- Department of Psychology, Harvard University, Cambridge, MA, United States
| | - Dorit B. Donoviel
- Center for Space Medicine, Baylor College of Medicine, Houston, TX, United States
- Translational Research Institute for Space Health (TRISH), Houston, TX, United States
- Department of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, TX, United States
| |
Collapse
|
|
17
|
Karmaus W, Kheirkhah Rahimabad P, Pham N, Mukherjee N, Chen S, Anthony TM, Arshad HS, Rathod A, Sultana N, Jones AD. Association of Metabolites, Nutrients, and Toxins in Maternal and Cord Serum with Asthma, IgE, SPT, FeNO, and Lung Function in Offspring. Metabolites 2023; 13:737. [PMID: 37367895 DOI: 10.3390/metabo13060737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 06/01/2023] [Accepted: 06/05/2023] [Indexed: 06/28/2023] Open
Abstract
The role of metabolites, nutrients, and toxins (MNTs) in sera at the end of pregnancy and of their association with offspring respiratory and allergic disorders is underexplored. Untargeted approaches detecting a variety of compounds, known and unknown, are limited. In this cohort study, we first aimed at discovering associations of MNTs in grandmaternal (F0) serum with asthma, immunoglobulin E, skin prick tests, exhaled nitric oxide, and lung function parameters in their parental (F1) offspring. Second, for replication, we tested the identified associations of MNTs with disorders in their grandchildren (F2-offspring) based on F2 cord serum. The statistical analyses were sex-stratified. Using liquid chromatography/high-resolution mass spectrometry in F0, we detected signals for 2286 negative-ion lipids, 59 positive-ion lipids, and 6331 polar MNTs. Nine MNTs (one unknown MNT) discovered in F0-F1 and replicated in F2 showed higher risks of respiratory/allergic outcomes. Twelve MNTs (four unknowns) constituted a potential protection in F1 and F2. We recognized MNTs not yet considered candidates for respiratory/allergic outcomes: a phthalate plasticizer, an antihistamine, a bile acid metabolite, tryptophan metabolites, a hemiterpenoid glycoside, triacylglycerols, hypoxanthine, and polyphenol syringic acid. The findings suggest that MNTs are aspirants for clinical trials to prevent adverse respiratory/allergic outcomes.
Collapse
Affiliation(s)
- Wilfried Karmaus
- Division of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, University of Memphis, Memphis, TN 38152, USA
| | - Parnian Kheirkhah Rahimabad
- Division of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, University of Memphis, Memphis, TN 38152, USA
| | - Ngan Pham
- Division of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, University of Memphis, Memphis, TN 38152, USA
| | - Nandini Mukherjee
- Department of Epidemiology, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
| | - Su Chen
- Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE 68198-4375, USA
| | - Thilani M Anthony
- Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, MI 48824, USA
| | - Hasan S Arshad
- Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO17 1BJ, UK
- David Hide Asthma and Allergy Research Centre, Isle of Wight PO30 5TG, UK
| | - Aniruddha Rathod
- Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Nahid Sultana
- Division of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, University of Memphis, Memphis, TN 38152, USA
| | - A Daniel Jones
- Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, MI 48824, USA
| |
Collapse
|
|
18
|
Cramer T. Impact of dietary carbohydrate restriction on the pathobiology of Hepatocellular Carcinoma: The gut-liver axis and beyond. Semin Immunol 2023; 66:101736. [PMID: 36857893 DOI: 10.1016/j.smim.2023.101736] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 02/02/2023] [Accepted: 02/09/2023] [Indexed: 03/01/2023]
Abstract
Despite decades of fiercely competitive research and colossal financial investments, the majority of patients with advanced solid cancers cannot be treated with curative intent. To improve this situation, conceptually novel treatment approaches are urgently needed. Cancer is increasingly appreciated as a systemic disease and numerous organismal factors are functionally linked to neoplastic growth, e.g. systemic metabolic dysregulation, chronic inflammation, intestinal dysbiosis and disrupted circadian rhythms. It is tempting to hypothesize that interventions targeting these processes could be of significant account for cancer patients. One important driver of tumor-supporting systemic derangements is inordinate consumption of simple and highly processed carbohydrates. This dietary pattern is causally linked to hyperinsulinemia, insulin resistance, chronic inflammation and intestinal dysbiosis, begging the pertinent question whether the adoption of dietary carbohydrate restriction can be beneficial for patients with cancer. This review summarizes the published data on the role of dietary carbohydrate restriction in the pathogenesis of Hepatocellular Carcinoma (HCC), the most frequent type of primary liver cancer. In addition to outlining the functional interplay between diet, the intestinal microbiome and immunity, the review underscores the importance of bile acids as interconnectors between the intestinal microbiota and immune cells.
Collapse
Affiliation(s)
- Thorsten Cramer
- Department of General, Visceral and Transplantation Surgery, RWTH University Hospital, 52074 Aachen, Germany; Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands; NUTRIM - School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.
| |
Collapse
|
|
19
|
Ji J, Wu L, Wei J, Wu J, Guo C. The Gut Microbiome and Ferroptosis in MAFLD. J Clin Transl Hepatol 2023; 11:174-187. [PMID: 36406312 PMCID: PMC9647110 DOI: 10.14218/jcth.2022.00136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 05/22/2022] [Accepted: 06/12/2022] [Indexed: 12/04/2022] Open
Abstract
Metabolic-associated fatty liver disease (MAFLD) is a new disease definition, and is proposed to replace the previous name, nonalcoholic fatty liver disease (NAFLD). Globally, MAFLD/NAFLD is the most common liver disease, with an incidence rate ranging from 6% to 35% in adult populations. The pathogenesis of MAFLD/NAFLD is closely related to insulin resistance (IR), and the genetic susceptibility to acquired metabolic stress-associated liver injury. Similarly, the gut microbiota in MAFLD/NAFLD is being revaluated by scientists, as the gut and liver influence each other via the gut-liver axis. Ferroptosis is a novel form of programmed cell death caused by iron-dependent lipid peroxidation. Emerging evidence suggests that ferroptosis has a key role in the pathological progression of MAFLD/NAFLD, and inhibition of ferroptosis may become a novel therapeutic strategy for the treatment of NAFLD. This review focuses on the main mechanisms behind the promotion of MAFLD/NAFLD occurrence and development by the intestinal microbiota and ferroptosis. It outlines new strategies to target the intestinal microbiota and ferroptosis to facilitate future MAFLD/NAFLD therapies.
Collapse
Affiliation(s)
- Jie Ji
- Department of Gastroenterology, Putuo People’s Hospital, Tongji University, Shanghai, China
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
| | - Liwei Wu
- Department of Gastroenterology, Putuo People’s Hospital, Tongji University, Shanghai, China
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
| | - Jue Wei
- Department of Gastroenterology Shanghai Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jianye Wu
- Department of Gastroenterology, Putuo People’s Hospital, Tongji University, Shanghai, China
- Correspondence to: Chuanyong Guo, Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, NO. 301, Middle Yanchang Road, Jing’an District, Shanghai 200072, China. ORCID: https://orcid.org/0000-0002-6527-4673. E-mail: ; Jianye Wu: Department of Gastroenterology, Putuo People’s Hospital, NO. 1291, Jiangning road, Putuo, Shanghai 200060, China. ORCID: https://orcid.org/0000-0003-2675-4241. E-mail:
| | - Chuanyong Guo
- Department of Gastroenterology, Putuo People’s Hospital, Tongji University, Shanghai, China
- Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
- Correspondence to: Chuanyong Guo, Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, NO. 301, Middle Yanchang Road, Jing’an District, Shanghai 200072, China. ORCID: https://orcid.org/0000-0002-6527-4673. E-mail: ; Jianye Wu: Department of Gastroenterology, Putuo People’s Hospital, NO. 1291, Jiangning road, Putuo, Shanghai 200060, China. ORCID: https://orcid.org/0000-0003-2675-4241. E-mail:
| |
Collapse
|
|
20
|
Akahoshi DT, Natwick DE, Yuan W, Lu W, Collins SR, Bevins CL. Flagella-driven motility is a target of human Paneth cell defensin activity. PLoS Pathog 2023; 19:e1011200. [PMID: 36821624 PMCID: PMC9990921 DOI: 10.1371/journal.ppat.1011200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 03/07/2023] [Accepted: 02/10/2023] [Indexed: 02/24/2023] Open
Abstract
In the mammalian intestine, flagellar motility can provide microbes competitive advantage, but also threatens the spatial segregation established by the host at the epithelial surface. Unlike microbicidal defensins, previous studies indicated that the protective activities of human α-defensin 6 (HD6), a peptide secreted by Paneth cells of the small intestine, resides in its remarkable ability to bind microbial surface proteins and self-assemble into protective fibers and nets. Given its ability to bind flagellin, we proposed that HD6 might be an effective inhibitor of bacterial motility. Here, we utilized advanced automated live cell fluorescence imaging to assess the effects of HD6 on actively swimming Salmonella enterica in real time. We found that HD6 was able to effectively restrict flagellar motility of individual bacteria. Flagellin-specific antibody, a classic inhibitor of flagellar motility that utilizes a mechanism of agglutination, lost its activity at low bacterial densities, whereas HD6 activity was not diminished. A single amino acid variant of HD6 that was able to bind flagellin, but not self-assemble, lost ability to inhibit flagellar motility. Together, these results suggest a specialized role of HD6 self-assembly into polymers in targeting and restricting flagellar motility.
Collapse
Affiliation(s)
- Douglas T. Akahoshi
- Department of Microbiology and Immunology, School of Medicine, University of California Davis, Davis, California, United States of America
| | - Dean E. Natwick
- Department of Microbiology and Molecular Genetics, University of California Davis, Davis, California, United States of America
| | - Weirong Yuan
- Institute of Human Virology and Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America
| | - Wuyuan Lu
- Institute of Human Virology and Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America
| | - Sean R. Collins
- Department of Microbiology and Molecular Genetics, University of California Davis, Davis, California, United States of America
| | - Charles L. Bevins
- Department of Microbiology and Immunology, School of Medicine, University of California Davis, Davis, California, United States of America
| |
Collapse
|
|
21
|
Lai Z, Zhan X, Lin L, Zhang J, Qi W, Yang H, Mao S, Jin W. High-grain diet feeding alters ileal microbiota and disrupts bile acid metabolism in lactating dairy cows. J Anim Sci 2023; 101:skad278. [PMID: 37606090 PMCID: PMC10494876 DOI: 10.1093/jas/skad278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 08/18/2023] [Indexed: 08/23/2023] Open
Abstract
Bile acids (BAs) play an important role in the regulation of lipid metabolic homeostasis, but little is known about their metabolism in dairy cows fed a high-grain (HG) diet. In the present study, we examined the bacterial community, BA profile, and the FXR/FGF19 signaling pathway in the ileum and liver to investigate the gut microbe-BA metabolism interactions response to HG diet and the changes in the subsequent enterohepatic circulation of dairy cows. The results showed that the ileal bacterial community was altered, with an increase of Paraclostridium, Anaerobutyricum, Shuttleworthia, and Stomatobaculum in the relative abundance in the HG group. Moreover, real-time polymerase chain reaction (PCR) showed that the abundance of total bacteria and bacterial bile-salt hydrolase (BSH) genes was increased in the ileal digesta in the HG group. Meanwhile, HG feeding also decreased the total BA content in the digesta of jejunum and ileum and in feces. HG feeding altered the BA profile in the ileal digesta by increasing unconjugated BAs and decreasing conjugated BAs. In addition, the intestinal FXR/FGF19 signaling pathway was activated. The expression of CYP7A1 (cholesterol 7α-hydroxylase) was depressed, which inhibited BAs synthesis in the liver of cows fed HG. Overall, HG feeding altered the ileal bacterial community and BA profile, and activated FXR/FGF19 signaling pathway, resulting in a decrease of BA level in the ileal digesta via the inhibition of hepatic BA synthesis. The findings provided novel insights into understanding the relationship between gut microbiota and the homeostasis of BAs in dairy cows fed a HG diet.
Collapse
Affiliation(s)
- Zheng Lai
- Ruminant Nutrition and Feed Engineering Technology Research Center, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, the National Center for International Research on Animal Gut Nutrition, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
| | - Xiaoxiu Zhan
- Ruminant Nutrition and Feed Engineering Technology Research Center, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, the National Center for International Research on Animal Gut Nutrition, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
| | - Limei Lin
- Ruminant Nutrition and Feed Engineering Technology Research Center, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, the National Center for International Research on Animal Gut Nutrition, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
| | - Jiyou Zhang
- Ruminant Nutrition and Feed Engineering Technology Research Center, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, the National Center for International Research on Animal Gut Nutrition, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
| | - Weibiao Qi
- Ruminant Nutrition and Feed Engineering Technology Research Center, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, the National Center for International Research on Animal Gut Nutrition, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
| | - Huisheng Yang
- Ruminant Nutrition and Feed Engineering Technology Research Center, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, the National Center for International Research on Animal Gut Nutrition, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
| | - Shengyong Mao
- Ruminant Nutrition and Feed Engineering Technology Research Center, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, the National Center for International Research on Animal Gut Nutrition, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
| | - Wei Jin
- Ruminant Nutrition and Feed Engineering Technology Research Center, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, the National Center for International Research on Animal Gut Nutrition, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
- Anhui Provincial Key Laboratory of Livestock and Poultry Product Safety Engineering, Anhui Academy of Agricultural Sciences, Hefei 230041, China
| |
Collapse
|
|
22
|
Ruiz A, Andree KB, Furones D, Holhorea PG, Calduch-Giner JÀ, Viñas M, Pérez-Sánchez J, Gisbert E. Modulation of gut microbiota and intestinal immune response in gilthead seabream ( Sparus aurata) by dietary bile salt supplementation. Front Microbiol 2023; 14:1123716. [PMID: 37168118 PMCID: PMC10166234 DOI: 10.3389/fmicb.2023.1123716] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Accepted: 04/04/2023] [Indexed: 05/13/2023] Open
Abstract
Given their role in lipid digestion, feed supplementation with bile salts could be an economic and sustainable solution to alterations in adiposity and intestinal inflammation generated by some strategies currently used in aquaculture. An important part of the metabolism of bile salts takes place in the intestine, where the microbiota transforms them into more toxic forms. Consequently, we aimed to evaluate the gut immune response and microbial populations in gilthead seabream (Sparus aurata) fed a diet supplemented with a blend of bile salts with proven background as a regulator of lipid metabolism and fat content. After the 90-day feeding trial, a differential modulation of the microbiota between the anterior and posterior intestine was observed. While in the anterior intestine the relative abundance of Desulfobacterota doubled, in the posterior intestine, the levels of Firmicutes increased and Proteobacteria, Actinobacteriota, and Campylobacterota were reduced when supplementing the diet with bile salts. Even so, only in the anterior intestine, there was a decrease in estimated richness (Chao1 and ACE indices) in presence of dietary bile salts. No significant differences were displayed in alpha (Shannon and Simpson indices) nor beta-diversity, showing that bile sales did not have a great impact on the intestinal microbiota. Regarding the gene expression profile in 2 h postprandial-fish, several changes were observed in the analyzed biomarkers of epithelial integrity, nutrient transport, mucus production, interleukins, cell markers, immunoglobulin production and pathogen recognition receptors. These results may indicate the development of an intestinal immune-protective status to tackle future threats. This work also suggests that this immune response is not only regulated by the presence of the dietary bile salts in the intestine, but also by the microbial populations that are in turn modulated by bile salts. After a fasting period of 2 days, the overall gene expression profile was stabilized with respect to fish fed the unsupplemented diet, indicating that the effect of bile salts was transient after short periods of fasting. On the balance, bile salts can be used as a dietary supplement to enhance S. aurata farming and production without compromising their intestinal health.
Collapse
Affiliation(s)
- Alberto Ruiz
- Aquaculture Program, Institut de Recerca i Tecnologia Agroalimentàries (IRTA), Centre de La Ràpita, La Ràpita, Spain
- Ph.D. Program in Aquaculture, Universitat de Barcelona, Barcelona, Spain
- *Correspondence: Alberto Ruiz,
| | - Karl B. Andree
- Aquaculture Program, Institut de Recerca i Tecnologia Agroalimentàries (IRTA), Centre de La Ràpita, La Ràpita, Spain
| | - Dolors Furones
- Aquaculture Program, Institut de Recerca i Tecnologia Agroalimentàries (IRTA), Centre de La Ràpita, La Ràpita, Spain
| | - Paul G. Holhorea
- Nutrigenomics and Fish Growth Endocrinology Group, Institute of Aquaculture Torre de la Sal, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Castellón, Spain
| | - Josep À. Calduch-Giner
- Nutrigenomics and Fish Growth Endocrinology Group, Institute of Aquaculture Torre de la Sal, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Castellón, Spain
| | - Marc Viñas
- Sustainability in Biosystems, Institut de Recerca i Tecnologia Agroalimentàries (IRTA) Torre Marimon, Barcelona, Spain
| | - Jaume Pérez-Sánchez
- Nutrigenomics and Fish Growth Endocrinology Group, Institute of Aquaculture Torre de la Sal, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Castellón, Spain
| | - Enric Gisbert
- Aquaculture Program, Institut de Recerca i Tecnologia Agroalimentàries (IRTA), Centre de La Ràpita, La Ràpita, Spain
| |
Collapse
|
|
23
|
Li Q, Liu W, Zhang H, Chen C, Liu R, Hou H, Luo Q, Yu Q, Ouyang H, Feng Y, Zhu W. α-D-1,3-glucan from Radix Puerariae thomsonii improves NAFLD by regulating the intestinal flora and metabolites. Carbohydr Polym 2023; 299:120197. [PMID: 36876767 DOI: 10.1016/j.carbpol.2022.120197] [Citation(s) in RCA: 56] [Impact Index Per Article: 28.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 10/01/2022] [Accepted: 10/04/2022] [Indexed: 11/06/2022]
Abstract
Radix Puerariae thomsonii, the root of the botanical family Fabaceae species Pueraria montana var. thomsonii (Benth.) MR Almeida, can be used as food or medicine. Polysaccharides are important active constituents of this root. A low molecular weight polysaccharide, RPP-2 having α-D-1,3-glucan as the main chain, was isolated and purified. RPP-2 could promote the growth of probiotics in-vitro. Therefore, the effects of RPP-2 on a high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) C57/BL6J mouse models were investigated. RPP-2 could reduce HFD-induced liver injury by reducing inflammation, glucose metabolism, and steatosis, thereby improving NAFLD. RPP-2 regulated the abundances of intestinal floral genera Flintibacter, Butyricicoccus, and Oscillibacter, and their metabolites Lipopolysaccharide (LPS), bile acids, and short-chain fatty acids (SCFAs), thereby improving inflammation, lipid metabolism, and energy metabolism signaling pathways. These results confirmed that RPP-2 play a prebiotic role by regulating intestinal flora and microbial metabolites, playing a multi-pathway and multi-target role in improving NAFLD.
Collapse
Affiliation(s)
- Qiong Li
- Jiangxi University of Chinese Medicine, No. 818 Yunwan Road, Nanchang 330002, PR China
| | - Wenjun Liu
- Research and Development Department, Jiangzhong Pharmaceutical Co., Ltd., No. 1899 Meiling Road, Nanchang 330103, PR China
| | - Hua Zhang
- Jiangxi University of Chinese Medicine, No. 818 Yunwan Road, Nanchang 330002, PR China
| | - Chong Chen
- Research and Development Department, Jiangzhong Pharmaceutical Co., Ltd., No. 1899 Meiling Road, Nanchang 330103, PR China
| | - Ronghua Liu
- Jiangxi University of Chinese Medicine, No. 818 Yunwan Road, Nanchang 330002, PR China
| | - Hengwei Hou
- Jiangxi University of Chinese Medicine, No. 818 Yunwan Road, Nanchang 330002, PR China
| | - Quan Luo
- Jiangxi University of Chinese Medicine, No. 818 Yunwan Road, Nanchang 330002, PR China
| | - Qinqin Yu
- Jiangxi University of Chinese Medicine, No. 818 Yunwan Road, Nanchang 330002, PR China
| | - Hui Ouyang
- Jiangxi University of Chinese Medicine, No. 818 Yunwan Road, Nanchang 330002, PR China; State Key Laboratory of Innovative Drug and Efficient Energy-Saving Pharmaceutical Equipment, No. 56 Yangming Road, Nanchang 330006, PR China.
| | - Yulin Feng
- State Key Laboratory of Innovative Drug and Efficient Energy-Saving Pharmaceutical Equipment, No. 56 Yangming Road, Nanchang 330006, PR China.
| | - Weifeng Zhu
- Jiangxi University of Chinese Medicine, No. 818 Yunwan Road, Nanchang 330002, PR China; Key Laboratory of Modern Preparation of Chinese Medicine of Jiangxi University of Chinese Medicine, No. 818 Yunwan Road, Nanchang 330002, PR China.
| |
Collapse
|
|
24
|
Xu Z, Jiang N, Xiao Y, Yuan K, Wang Z. The role of gut microbiota in liver regeneration. Front Immunol 2022; 13:1003376. [PMID: 36389782 PMCID: PMC9647006 DOI: 10.3389/fimmu.2022.1003376] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 10/12/2022] [Indexed: 12/02/2022] Open
Abstract
The liver has unique regeneration potential, which ensures the continuous dependence of the human body on hepatic functions. As the composition and function of gut microbiota has been gradually elucidated, the vital role of gut microbiota in liver regeneration through gut-liver axis has recently been accepted. In the process of liver regeneration, gut microbiota composition is changed. Moreover, gut microbiota can contribute to the regulation of the liver immune microenvironment, thereby modulating the release of inflammatory factors including IL-6, TNF-α, HGF, IFN-γ and TGF-β, which involve in different phases of liver regeneration. And previous research have demonstrated that through enterohepatic circulation, bile acids (BAs), lipopolysaccharide, short-chain fatty acids and other metabolites of gut microbiota associate with liver and may promote liver regeneration through various pathways. In this perspective, by summarizing gut microbiota-derived signaling pathways that promote liver regeneration, we unveil the role of gut microbiota in liver regeneration and provide feasible strategies to promote liver regeneration by altering gut microbiota composition.
Collapse
Affiliation(s)
- Zhe Xu
- Department of Liver Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
- Laboratory of Liver Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Nan Jiang
- Department of Liver Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
- Laboratory of Liver Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Yuanyuan Xiao
- Department of Obstetrics and Gynecology, West China Second Hospital of Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China
- *Correspondence: Zhen Wang, ; Kefei Yuan, ; Yuanyuan Xiao,
| | - Kefei Yuan
- Department of Liver Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
- Laboratory of Liver Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
- *Correspondence: Zhen Wang, ; Kefei Yuan, ; Yuanyuan Xiao,
| | - Zhen Wang
- Department of Liver Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
- Laboratory of Liver Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
- *Correspondence: Zhen Wang, ; Kefei Yuan, ; Yuanyuan Xiao,
| |
Collapse
|
|
25
|
Luo W, Guo S, Zhou Y, Zhu J, Zhao J, Wang M, Sang L, Wang B, Chang B. Hepatocellular carcinoma: Novel understandings and therapeutic strategies based on bile acids (Review). Int J Oncol 2022; 61:117. [PMID: 35929515 PMCID: PMC9450808 DOI: 10.3892/ijo.2022.5407] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Accepted: 07/26/2022] [Indexed: 11/06/2022] Open
Abstract
Bile acids (BAs) are the major components of bile and products of cholesterol metabolism. Cholesterol is catalyzed by a variety of enzymes in the liver to form primary BAs, which are excreted into the intestine with bile, and secondary BAs are formed under the modification of the gut microbiota. Most of the BAs return to the liver via the portal vein, completing the process of enterohepatic circulation. BAs have an important role in the development of hepatocellular carcinoma (HCC), which may participate in the progression of HCC by recognizing receptors such as farnesoid X receptor (FXR) and mediating multiple downstream pathways. Certain BAs, such as ursodeoxycholic acid and obeticholic acid, were indicated to be able to delay liver injury and HCC progression. In the present review, the structure and function of BAs were introduced and the metabolism of BAs and the process of enterohepatic circulation were outlined. Furthermore, the mechanisms by which BAs participate in the development of HCC were summarized and possible strategies for targeting BAs and key sites of their metabolic processes to treat HCC were suggested.
Collapse
Affiliation(s)
- Wenyu Luo
- Department of Gastroenterology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110122, P.R. China
| | - Shiqi Guo
- 104K class 87, The Second Clinical College, China Medical University, Shenyang, Liaoning 110122, P.R. China
| | - Yang Zhou
- 104K class 87, The Second Clinical College, China Medical University, Shenyang, Liaoning 110122, P.R. China
| | - Junfeng Zhu
- Department of Clinical Laboratory, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541001, P.R. China
| | - Jingwen Zhao
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
| | - Mengyao Wang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
| | - Lixuan Sang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
| | - Bingyuan Wang
- Department of Geriatric Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110122, P.R. China
| | - Bing Chang
- Department of Gastroenterology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110122, P.R. China
| |
Collapse
|
|
26
|
Massa M, Compari C, Fisicaro E. On the mechanism of the cholesterol lowering ability of soluble dietary fibers: Interaction of some bile salts with pectin, alginate, and chitosan studied by isothermal titration calorimetry. Front Nutr 2022; 9:968847. [PMID: 36245485 PMCID: PMC9558102 DOI: 10.3389/fnut.2022.968847] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 09/15/2022] [Indexed: 11/29/2022] Open
Abstract
Reducing high blood cholesterol is an important strategy to decrease the chances of a cardiovascular disease occurrence, the main cause of mortality in western developed countries. Therefore, the search for an alternative therapeutic or preventive approach being natural, biocompatible, and not toxic is still more relevant than ever. This need is particularly felt in Pediatrics for treating childhood hypercholesterolemia, due to statins interference in the production of steroid hormones in prepuberal children. Notwithstanding the general acceptance of the healthy role of the fibers in the diet, the mechanism underlying the cholesterol-lowering ability of soluble fibers is still under discussion. Therefore, we started a systematic study of the binding ability of some soluble dietary fibers (SDF) originated from different natural sources toward selected bile salts (BS) by isothermal titration calorimetry (ITC). Here we report the results of our ITC studies on the interaction of alginate, pectin and chitosan with sodium cholate (NaC), sodium deoxycholate (NaDC), sodium taurocholate (NaTC) and sodium taurodeoxycholate (NaTDC). Thermodynamic data on the micelle formation process of the above bile salts, as a premise to the study of their binding ability to the SDF, are also reported. Alginate does not show specific binding interaction with BS, while pectin shows a strong exothermic bond with NaDC in monomeric form. Chitosan, positively charged and soluble only at low pH, shows strong exothermic interactions with NaTC and NaTDC (soluble at pH = 3 in acetate buffer) with precipitate formation. For NaTC, the exothermic peak starts at about 5 mM. At this concentration NaTC bound on the fiber reaches locally the cmc value and micelles start forming on the fiber inducing its conformational change. For NaTDC the same process occurs at much lower concentrations, due to lower cmc, and with a greater quantity of heat involved. The first set of results here presented shows that for some SDF the binding of BS could be an important mechanism in cholesterol lowering but not the only one. The information here presented could be a starting point for the design of optimized functional foods with high cholesterol lowering ability.
Collapse
Affiliation(s)
- Michele Massa
- Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, Rome, Italy
| | | | - Emilia Fisicaro
- Department of Food and Drug, University of Parma, Parma, Italy
- *Correspondence: Emilia Fisicaro,
| |
Collapse
|
|
27
|
Lanthier N, Delzenne N. Targeting the Gut Microbiome to Treat Metabolic Dysfunction-Associated Fatty Liver Disease: Ready for Prime Time? Cells 2022; 11:2718. [PMID: 36078124 PMCID: PMC9454620 DOI: 10.3390/cells11172718] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 08/23/2022] [Accepted: 08/26/2022] [Indexed: 11/17/2022] Open
Abstract
Numerous studies show a modification of the gut microbiota in patients with obesity or diabetes. Animal studies have also shown a causal role of gut microbiota in liver metabolic disorders including steatosis whereas the human situation is less clear. Patients with metabolic dysfunction associated fatty liver disease (MAFLD) also have a modification in their gut microbiota composition but the changes are not fully characterized. The absence of consensus on a precise signature is probably due to disease heterogeneity, possible concomitant medications and different selection or evaluation criteria. The most consistent changes were increased relative abundance of Proteobacteria, Enterobacteriaceae and Escherichia species and decreased abundance of Coprococcus and Eubacterium. Possible mechanisms linking the microbiota and MAFLD are increased intestinal permeability with translocation of microbial products into the portal circulation, but also changes in the bile acids and production of microbial metabolites such as ethanol, short chain fatty acids and amino acid derivatives able to modulate liver metabolism and inflammation. Several interventional studies exist that attempt to modulate liver disease by administering antibiotics, probiotics, prebiotics, synbiotics, postbiotics or fecal transplantation. In conclusion, there are both gaps and hopes concerning the interest of gut microbiome evaluation for diagnosis purposes of MAFLD and for new therapeutic developments that are often tested on small size cohorts.
Collapse
Affiliation(s)
- Nicolas Lanthier
- Service d’Hépato-Gastroentérologie, Cliniques Universitaires Saint-Luc, UCLouvain, 1200 Brussels, Belgium
- Laboratory of Gastroenterology and Hepatology, Institut de Recherche Expérimentale et Clinique, UCLouvain, 1200 Brussels, Belgium
| | - Nathalie Delzenne
- Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, 1200 Brussels, Belgium
| |
Collapse
|
|
28
|
Santopaolo F, Coppola G, Giuli L, Gasbarrini A, Ponziani FR. Influence of Gut–Liver Axis on Portal Hypertension in Advanced Chronic Liver Disease: The Gut Microbiome as a New Protagonist in Therapeutic Management. MICROBIOLOGY RESEARCH 2022; 13:539-555. [DOI: 10.3390/microbiolres13030038] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025] Open
Abstract
Clinically significant portal hypertension is associated with most complications of advanced chronic liver disease (ACLD), including variceal bleeding, ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, and hepatic encephalopathy. Gut dysbiosis is a hallmark of ACLD with portal hypertension and consists of the overgrowth of potentially pathogenic bacteria and a decrease in autochthonous bacteria; additionally, congestion makes the intestinal barrier more permeable to bacteria and their products, which contributes to the development of complications through inflammatory mechanisms. This review summarizes current knowledge on the role of the gut–liver axis in the pathogenesis of portal hypertension, with a focus on therapies targeting portal hypertension and the gut microbiota. The modulation of the gut microbiota on several levels represents a major challenge in the upcoming years; in-depth characterization of the molecular and microbiological mechanisms linking the gut–liver axis to portal hypertension in a bidirectional relationship could pave the way to the identification of new therapeutic targets for innovative therapies in the management of ACLD.
Collapse
Affiliation(s)
- Francesco Santopaolo
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Gaetano Coppola
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Lucia Giuli
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Francesca Romana Ponziani
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| |
Collapse
|
|
29
|
Riaz F, Wei P, Pan F. Fine-tuning of regulatory T cells is indispensable for the metabolic steatosis-related hepatocellular carcinoma: A review. Front Cell Dev Biol 2022; 10:949603. [PMID: 35912096 PMCID: PMC9337771 DOI: 10.3389/fcell.2022.949603] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2022] [Accepted: 06/28/2022] [Indexed: 12/12/2022] Open
Abstract
The majority of chronic hepatic diseases are caused by nutritional imbalance. These nutritional inequities include excessive intake of alcohol and fat, which causes alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD), respectively. The pathogenesis of hepatic diseases is mainly dependent on oxidative stress, autophagy, DNA damage, and gut microbiota and their metabolites. These factors influence the normal physiology of the liver and impact the hepatic microenvironment. The hepatic microenvironment contains several immune cells and inflammatory cytokines which interact with each other and contribute to the progression of chronic hepatic diseases. Among these immune cells, Foxp3+ CD4+ regulatory T cells (Tregs) are the crucial subset of CD4+ T cells that create an immunosuppressive environment. This review emphasizes the function of Tregs in the pathogenesis of ALD and NAFLD and their role in the progression of NAFLD-associated hepatocellular carcinoma (HCC). Briefly, Tregs establish an immunosuppressive landscape in the liver by interacting with the innate immune cells and gut microbiota and their metabolites. Meanwhile, with the advancement of steatosis, these Tregs inhibit the proliferation, activation and functions of other cytotoxic T cells and support the progression of simple steatosis to HCC. Briefly, it can be suggested that targeting Tregs can act as a favourable prognostic indicator by modulating steatosis and insulin resistance during the pathogenesis of hepatic steatosis and NAFLD-associated HCC.
Collapse
Affiliation(s)
- Farooq Riaz
- Center for Cancer Immunology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
| | - Ping Wei
- Center for Cancer Immunology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
- Chongqing Key Laboratory of Pediatrics, Department of otolaryngology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
| | - Fan Pan
- Center for Cancer Immunology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
- *Correspondence: Fan Pan,
| |
Collapse
|
|
30
|
Kean IRL, Wagner J, Wijeyesekera A, De Goffau M, Thurston S, Clark JA, White DK, Ridout J, Agrawal S, Kayani R, O'Donnell R, Ramnarayan P, Peters MJ, Klein N, Holmes E, Parkhill J, Baker S, Pathan N. Profiling gut microbiota and bile acid metabolism in critically ill children. Sci Rep 2022; 12:10432. [PMID: 35729169 PMCID: PMC9213539 DOI: 10.1038/s41598-022-13640-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Accepted: 05/26/2022] [Indexed: 11/08/2022] Open
Abstract
Broad-spectrum antimicrobial use during the treatment of critical illness influences gastrointestinal fermentation endpoints, host immune response and metabolic activity including the conversion of primary to secondary bile acids. We previously observed reduced fermentation capacity in the faecal microbiota of critically ill children upon hospital admission. Here, we further explore the timecourse of the relationship between the microbiome and bile acid profile in faecal samples collected from critically ill children. The microbiome was assayed by sequencing of the 16S rRNA gene, and faecal water bile acids were measured by liquid chromatography mass spectrometry. In comparison to admission faecal samples, members of the Lachnospiraceae recovered during the late-acute phase (days 8-10) of hospitalisation. Patients with infections had a lower proportion of Lachnospiraceae in their gut microbiota than controls and patients with primary admitting diagnoses. Keystone species linked to ecological recovery were observed to decline with the length of PICU admission. These species were further suppressed in patients with systemic infection, respiratory failure, and undergoing surgery. Bile acid composition recovers quickly after intervention for critical illness which may be aided by the compositional shift in Lachnospiraceae. Our findings suggest gut microbiota recovery can be readily assessed via measurement of faecal bile acids.
Collapse
Affiliation(s)
| | - Joseph Wagner
- The Peter Doherty Institute for Infection and Immunity, Melbourne Health, Melbourne, Australia
- Wellcome Sanger Institute, Cambridge, United Kingdom
| | - Anisha Wijeyesekera
- Department of Food and Nutritional Sciences, University of Reading, Reading, United Kingdom
| | - Marcus De Goffau
- Wellcome Sanger Institute, Cambridge, United Kingdom
- Department of Experimental Vascular Medicine, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands
- Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom
| | - Sarah Thurston
- Department of Paediatrics, University of Cambridge, Cambridge, United Kingdom
- Department of Haematology, University of Cambridge, Cambridge, United Kingdom
| | - John A Clark
- Department of Paediatrics, University of Cambridge, Cambridge, United Kingdom
| | - Deborah K White
- Department of Paediatrics, University of Cambridge, Cambridge, United Kingdom
| | - Jenna Ridout
- Department of Paediatrics, University of Cambridge, Cambridge, United Kingdom
- EACH, Milton, Cambridge, United Kingdom
| | - Shruti Agrawal
- Department of Paediatrics, University of Cambridge, Cambridge, United Kingdom
- Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, United Kingdom
| | - Riaz Kayani
- Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, United Kingdom
| | - Roddy O'Donnell
- Department of Paediatrics, University of Cambridge, Cambridge, United Kingdom
- Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, United Kingdom
| | - Padmanabhan Ramnarayan
- Paediatric Intensive Care Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom
- St Mary's Hospital, London, United Kingdom
| | - Mark J Peters
- Paediatric Intensive Care Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom
- UCL Great Ormond Street Institute of Child Health, London, United Kingdom
| | - Nigel Klein
- Paediatric Intensive Care Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom
- UCL Great Ormond Street Institute of Child Health, London, United Kingdom
| | - Elaine Holmes
- Section of Biomolecular Medicine, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom
| | - Julian Parkhill
- Wellcome Sanger Institute, Cambridge, United Kingdom
- Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom
| | - Stephen Baker
- Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, United Kingdom
- Department of Medicine, University of Cambridge, Cambridge, United Kingdom
| | - Nazima Pathan
- Department of Paediatrics, University of Cambridge, Cambridge, United Kingdom
- Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, United Kingdom
| |
Collapse
|
|
31
|
Luo W, Guo S, Zhou Y, Zhao J, Wang M, Sang L, Chang B, Wang B. Hepatocellular Carcinoma: How the Gut Microbiota Contributes to Pathogenesis, Diagnosis, and Therapy. Front Microbiol 2022; 13:873160. [PMID: 35572649 PMCID: PMC9092458 DOI: 10.3389/fmicb.2022.873160] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 04/05/2022] [Indexed: 12/12/2022] Open
Abstract
The gut microbiota is gaining increasing attention, and the concept of the "gut-liver axis" is gradually being recognized. Leaky gut resulting from injury and/or inflammation can cause the translocation of flora to the liver. Microbiota-associated metabolites and components mediate the activation of a series of signalling pathways, thereby playing an important role in the development of hepatocellular carcinoma (HCC). For this reason, targeting the gut microbiota in the diagnosis, prevention, and treatment of HCC holds great promise. In this review, we summarize the gut microbiota and the mechanisms by which it mediates HCC development, and the characteristic alterations in the gut microbiota during HCC pathogenesis. Furthermore, we propose several strategies to target the gut microbiota for the prevention and treatment of HCC, including antibiotics, probiotics, faecal microbiota transplantation, and immunotherapy.
Collapse
Affiliation(s)
- Wenyu Luo
- Department of Gastroenterology, The First Affiliated Hospital of China Medical University, Shenyang, China
- The Second Clinical College, China Medical University, Shenyang, China
| | - Shiqi Guo
- The Second Clinical College, China Medical University, Shenyang, China
| | - Yang Zhou
- The Second Clinical College, China Medical University, Shenyang, China
| | - Jingwen Zhao
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Mengyao Wang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Lixuan Sang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Bing Chang
- Department of Gastroenterology, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Bingyuan Wang
- Department of Geriatric Medicine, The First Affiliated Hospital of China Medical University, Shenyang, China
| |
Collapse
|
|
32
|
Suau R, Pardina E, Domènech E, Lorén V, Manyé J. The Complex Relationship Between Microbiota, Immune Response and Creeping Fat in Crohn's Disease. J Crohns Colitis 2022; 16:472-489. [PMID: 34528668 DOI: 10.1093/ecco-jcc/jjab159] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
In the last decade, there has been growing interest in the pathological involvement of hypertrophic mesenteric fat attached to the serosa of the inflamed intestinal segments involved in Crohn's disease [CD], known as creeping fat. In spite of its protective nature, creeping fat harbours an aberrant inflammatory activity which, in an already inflamed intestine, may explain why creeping fat is associated with a greater severity of CD. The transmural inflammation of CD facilitates the interaction of mesenteric fat with translocated intestinal microorganisms, contributing to activation of the immune response. This may be not the only way in which microorganisms alter the homeostasis of this fatty tissue: intestinal dysbiosis may also impair xenobiotic metabolism. All these CD-related alterations have a functional impact on nuclear receptors such as the farnesoid X receptor or the peroxisome proliferator-activated receptor γ, which are implicated in regulation of the immune response, adipogenesis and the maintenance of barrier function, as well as on creeping fat production of inflammatory-associated cells such as adipokines. The dysfunction of creeping fat worsens the inflammatory course of CD and may favour intestinal fibrosis and fistulizing complications. However, our current knowledge of the pathophysiology and pathogenic role of creeping fat is controversial and a better understanding might provide new therapeutic targets for CD. Here we aim to review and update the key cellular and molecular alterations involved in this inflammatory process that link the pathological components of CD with the development of creeping fat.
Collapse
Affiliation(s)
- Roger Suau
- IBD Research Group, 'Germans Trias i Pujol' Research Institute (IGTP), Badalona (Catalonia), Spain.,Centro de Investigación Biomédica en Red (CIBER), Madrid, Spain
| | - Eva Pardina
- Biochemistry and Molecular Biomedicine Department, University of Barcelona, Barcelona (Catalonia), Spain
| | - Eugeni Domènech
- IBD Research Group, 'Germans Trias i Pujol' Research Institute (IGTP), Badalona (Catalonia), Spain.,Centro de Investigación Biomédica en Red (CIBER), Madrid, Spain.,Gastroenterology Department, 'Germans Trias i Pujol' University Hospital, Badalona (Catalonia), Spain
| | - Violeta Lorén
- IBD Research Group, 'Germans Trias i Pujol' Research Institute (IGTP), Badalona (Catalonia), Spain.,Centro de Investigación Biomédica en Red (CIBER), Madrid, Spain
| | - Josep Manyé
- IBD Research Group, 'Germans Trias i Pujol' Research Institute (IGTP), Badalona (Catalonia), Spain.,Centro de Investigación Biomédica en Red (CIBER), Madrid, Spain
| |
Collapse
|
|
33
|
Sun Q, Xin X, An Z, Hu Y, Feng Q. Therapeutic Potential of Natural Plants Against Non-Alcoholic Fatty Liver Disease: Targeting the Interplay Between Gut Microbiota and Bile Acids. Front Cell Infect Microbiol 2022; 12:854879. [PMID: 35356532 PMCID: PMC8959594 DOI: 10.3389/fcimb.2022.854879] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Accepted: 02/16/2022] [Indexed: 12/12/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) remains a common disease with a significant health and economic burden worldwide. The gut microbiota (GM) and bile acids (BAs), which play important roles in the gut-liver axis, have been confirmed to jointly participate in the development of NAFLD. GM not only regulate bile acids’ synthesis, transport, and reabsorption by regulating other metabolites (such as trimetlyl amine oxide, butyrate), but also regulate dehydrogenation, dehydroxylation and desulfurization of bile acids. Meanwhile, disordered bile acids influence the gut microbiota mainly through promoting the bacterial death and lowering the microbial diversity. Although weight loss and lifestyle changes are effective in the treatment of NAFLD, the acceptability and compliance of patients are poor. Recently, increasing natural plants and their active ingredients have been proved to alleviate NAFLD by modulating the joint action of gut microbiota and bile acids, and considered to be promising potential candidates. In this review, we discuss the efficacy of natural plants in treating NAFLD in the context of their regulation of the complex interplay between the gut microbiota and bile acids, the crosstalk of which has been shown to significantly promote the progression of NAFLD. Herein, we summarize the prior work on this topic and further suggest future research directions in the field.
Collapse
Affiliation(s)
- QinMei Sun
- Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xin Xin
- Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - ZiMing An
- Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - YiYang Hu
- Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, China
- Key Laboratory of Liver and Kidney Diseases, Shanghai University of Traditional Chinese Medicine, Ministry of Education, Shanghai, China
- *Correspondence: YiYang Hu, ; Qin Feng,
| | - Qin Feng
- Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, China
- Key Laboratory of Liver and Kidney Diseases, Shanghai University of Traditional Chinese Medicine, Ministry of Education, Shanghai, China
- *Correspondence: YiYang Hu, ; Qin Feng,
| |
Collapse
|
|
34
|
The New Therapeutic Approaches in the Treatment of Non-Alcoholic Fatty Liver Disease. Int J Mol Sci 2021; 22:ijms222413219. [PMID: 34948020 PMCID: PMC8704688 DOI: 10.3390/ijms222413219] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Revised: 11/25/2021] [Accepted: 12/02/2021] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease which is characterized by extremely complex pathogenetic mechanisms and multifactorial etiology. Some of the many pathophysiological mechanisms involved in the development of NAFLD include oxidative stress, impaired mitochondrial metabolism, inflammation, gut microbiota, and interaction between the brain-liver-axis and the regulation of hepatic lipid metabolism. The new therapeutic approaches in the treatment of NAFLD are targeting some of these milestones along the pathophysiological pathway and include drugs like agonists of peroxisome proliferator-activated receptors (PPARs), glucagon-like peptide-1 (GLP-1) agonists, sodium/glucose transport protein 2 (SGLT2) inhibitors, farnesoid X receptor (FXR) agonists, probiotics, and symbiotics. Further efforts in biomedical sciences should focus on the investigation of the relationship between the microbiome, liver metabolism, and response to inflammation, systemic consequences of metabolic syndrome.
Collapse
|
|
35
|
González-Silvera D, Cuesta A, Esteban MÁ. Immune defence mechanisms presented in liver homogenates and bile of gilthead seabream (Sparus aurata). JOURNAL OF FISH BIOLOGY 2021; 99:1958-1967. [PMID: 34486119 DOI: 10.1111/jfb.14901] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/04/2021] [Revised: 08/23/2021] [Accepted: 08/31/2021] [Indexed: 06/13/2023]
Abstract
Because the role of the liver of fishes in providing possible immunity remains largely unknown, the aim of this work was to identify and characterize different humoral defence mechanisms in the liver homogenates and bile of gilthead seabream (Sparus aurata) for the first time. Total protein levels and several immune parameters (complement activity, lysozyme and immunoglobulin M level) were studied. Furthermore, the activity of some lytic (proteases, antiproteases, esterase, alkaline phosphatase) and antioxidant (superoxide dismutase, catalase and peroxidase) enzymes was determined. Finally, bacteriostatic activity on three opportunist fish pathogens (Vibrio harveyi, Vibrio angillarum and Photobacterium damselae) was measured. Lysozyme and antiprotease activity were undetected in liver and bile, while natural haemolytic complement activity was only detected in bile, and immunoglobulin M was detected in both samples. The levels of proteases, esterase and antioxidant enzymes were greater in bile than in liver homogenates, while the level of alkaline phosphatase was very low in both samples. In addition, while no bacteriostatic activity was detected on liver homogenates, the bile revealed a very potent bacteriostatic activity against all the tested pathogenic bacteria. These results corroborate that fish liver - especially fish bile - contains many factors involved in innate immunity that could be useful for better understanding the role of the liver as an organ involved in fish immune functions as well as the possible contribution of bile to gut mucosal immunity.
Collapse
Affiliation(s)
- Daniel González-Silvera
- Immunobiology for Aquaculture Group, Department of Cell Biology and Histology, Faculty of Biology, University of Murcia, Murcia, Spain
| | - Alberto Cuesta
- Immunobiology for Aquaculture Group, Department of Cell Biology and Histology, Faculty of Biology, University of Murcia, Murcia, Spain
| | - Maria Ángeles Esteban
- Immunobiology for Aquaculture Group, Department of Cell Biology and Histology, Faculty of Biology, University of Murcia, Murcia, Spain
| |
Collapse
|
|
36
|
Raheem A, Wang M, Zhang J, Liang L, Liang R, Yin Y, Zhu Y, Yang W, Wang L, Lv X, Jia Y, Qin T, Zhang G. The probiotic potential of Lactobacillus plantarum strain RW1 isolated from canine faeces. J Appl Microbiol 2021; 132:2306-2322. [PMID: 34709709 DOI: 10.1111/jam.15341] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 08/05/2021] [Accepted: 09/04/2021] [Indexed: 12/11/2022]
Abstract
AIM To evaluation the probiotic potential of Lactobacillus plantarum strain RW1 isolated from healthy dogs for its further utilization as a dietary supplement for dogs. METHODS AND RESULTS This study aimed to evaluate the probiotic potential of L. plantarum strain RW1 isolated from canine faeces. After confirming by conventional and then by 16S rRNA sequencing, the identified strain RW1 was in vitro screened for its survivability in simulated gastrointestinal conditions, low pH, bile salts and adhesion to gut epithelial tissues, growth inhibitory effects on common pathogens and anti-inflammatory potential by measuring the mRNA expression level of IL-6, IL-8, IL-1ꞵ in Salmonella-infected MODE-K cells. Furthermore, the effects on epithelial barrier function and host defensin peptide (beta-defensin 3) was studied by measuring the mRNA expression level of tight junction protein (occludin) and beta-defensin 3 in MODE-K cells. The strain RW1 showed a considerable potential to survive in simulated gastrointestinal environmental conditions, low pH and high bile salt concentrations along with good adhesion to MODE-K cell line. Pathogenic bacterial growth and their adhesion to MODE-K cell line were significantly inhibited by the strain RW1. Real-time PCR analyses demonstrated that the strain RW1 inhibited Salmonella-induced pro-inflammatory cytokines (IL-6, IL-8 and IL-1ꞵ) production and reinforced the expression of tight junction protein (occludin). The strain RW1 did not induce mRNA expression of beta-defensin 3. CONCLUSION Based on in vitro results, the strain RW1 has the potential to be used as a probiotic supplement in dogs. However, further study involving in vivo health effects is needed. SIGNIFICANCE AND IMPACT OF THE STUDY Antibiotics have many side effects and nowadays the probiotics are considered as a potential alternative to antibiotics. This study evaluates the probiotic potential of dog isolated L. plantarum strain RW1 to use it as a dietary supplement in dogs feeding to control infectious diseases.
Collapse
Affiliation(s)
- Abdul Raheem
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.,Scientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Technology of Beijing, Ministry of Agriculture, Beijing, China
| | - Mingyan Wang
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.,Scientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Technology of Beijing, Ministry of Agriculture, Beijing, China
| | - Jianwei Zhang
- Beijing General Station of Animal Husbandry, Beijing, China
| | - Lin Liang
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.,Scientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Technology of Beijing, Ministry of Agriculture, Beijing, China
| | - Ruiying Liang
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.,Scientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Technology of Beijing, Ministry of Agriculture, Beijing, China
| | - Yajie Yin
- College of Veterinary Medicine, Hebei Agricultural University, Hebei, China
| | - Yali Zhu
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.,Scientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Technology of Beijing, Ministry of Agriculture, Beijing, China
| | - Weifang Yang
- Beijing General Station of Animal Husbandry, Beijing, China
| | - Liang Wang
- Beijing General Station of Animal Husbandry, Beijing, China
| | - Xueze Lv
- Beijing General Station of Animal Husbandry, Beijing, China
| | - Yaxiong Jia
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.,Scientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Technology of Beijing, Ministry of Agriculture, Beijing, China
| | - Tong Qin
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.,Scientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Technology of Beijing, Ministry of Agriculture, Beijing, China
| | - Guangzhi Zhang
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.,Scientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Technology of Beijing, Ministry of Agriculture, Beijing, China
| |
Collapse
|
|
37
|
Ali MS, Lee EB, Lee SJ, Lee SP, Boby N, Suk K, Birhanu BT, Park SC. Aronia melanocarpa Extract Fermented by Lactobacillus plantarum EJ2014 Modulates Immune Response in Mice. Antioxidants (Basel) 2021; 10:antiox10081276. [PMID: 34439524 PMCID: PMC8389331 DOI: 10.3390/antiox10081276] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2021] [Revised: 08/06/2021] [Accepted: 08/07/2021] [Indexed: 12/14/2022] Open
Abstract
The present study aimed to assess the immunomodulatory effects of fermented Aronia melanocarpa extract (FAME) on RAW 264.7 cells and BALB/c mice. Aronia melanocarpa fruit was fermented with Lactobacillus plantarum EJ2014 by adding yeast extract and monosodium glutamate for 9 days at 30 °C to produce γ-aminobutyric acid (GABA). After fermentation, significant GABA production was noted, along with minerals, polyphenols, and flavonoids (p < 0.05). The polyphenol content was confirmed by liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis. RAW 264.7 cells were stimulated with lipopolysaccharide (LPS, 1 μg/mL) in the presence or absence of FAME, and proinflammatory cytokine contents were measured by qPCR. In the in vivo experiment, female BALB/c mice were administered 125, 250, and 500 mg/kg of FAME for 21 days. FAME treatment increased neutrophil migration and phagocytosis (p < 0.05). It also increased splenocyte proliferation, CD4+ and CD8+ T-cell expression, and lymphocyte proliferation. Furthermore, it increased IFN-γ, IL-2, and IL-4 cytokine levels in a dose-dependent manner (p < 0.05). However, it decreased TNF-α and IL-6 levels (p < 0.05). These results indicate that FAME fortified with GABA including bioactive compounds exerts anti-inflammatory effects by inhibiting proinflammatory cytokines in RAW 264.7 cells and modulates immune response in mice. Thus, FAME could be a potential therapeutic agent for inflammatory disorders.
Collapse
Affiliation(s)
- Md. Sekendar Ali
- Department of Biomedical Science and Department of Pharmacology, School of Medicine, Brain Science and Engineering Institute, Kyungpook National University, Daegu 41944, Korea; (M.S.A.); (K.S.)
- Laboratory of Veterinary Pharmacokinetics and Pharmacodynamics, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Korea; (E.-B.L.); (N.B.)
- Department of Pharmacy, International Islamic University Chittagong, Kumira, Chittagong 4318, Bangladesh
| | - Eon-Bee Lee
- Laboratory of Veterinary Pharmacokinetics and Pharmacodynamics, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Korea; (E.-B.L.); (N.B.)
| | - Seung-Jin Lee
- Development and Reproductive Toxicology Research Group, Korea Institute of Toxicology, Daejeon 34114, Korea;
| | - Sam-Pin Lee
- Department of Food Science and Technology, Keimyung University, Daegu 42601, Korea;
| | - Naila Boby
- Laboratory of Veterinary Pharmacokinetics and Pharmacodynamics, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Korea; (E.-B.L.); (N.B.)
| | - Kyoungho Suk
- Department of Biomedical Science and Department of Pharmacology, School of Medicine, Brain Science and Engineering Institute, Kyungpook National University, Daegu 41944, Korea; (M.S.A.); (K.S.)
| | - Biruk Tesfaye Birhanu
- Laboratory of Veterinary Pharmacokinetics and Pharmacodynamics, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Korea; (E.-B.L.); (N.B.)
- Correspondence: (B.T.B.); (S.-C.P.); Tel.: +82-10-5105-5545 (B.T.B.); +82-53-950-5964 (S.-C.P.)
| | - Seung-Chun Park
- Laboratory of Veterinary Pharmacokinetics and Pharmacodynamics, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Korea; (E.-B.L.); (N.B.)
- Correspondence: (B.T.B.); (S.-C.P.); Tel.: +82-10-5105-5545 (B.T.B.); +82-53-950-5964 (S.-C.P.)
| |
Collapse
|
|
38
|
Schaffner SH, Lee AV, Pham MTN, Kassaye BB, Li H, Tallada S, Lis C, Lang M, Liu Y, Ahmed N, Galbraith LG, Moore JP, Bischof KM, Menke CC, Slonczewski JL. Extreme Acid Modulates Fitness Trade-Offs of Multidrug Efflux Pumps MdtEF-TolC and AcrAB-TolC in Escherichia coli K-12. Appl Environ Microbiol 2021; 87:e0072421. [PMID: 34085861 PMCID: PMC8315180 DOI: 10.1128/aem.00724-21] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Accepted: 05/29/2021] [Indexed: 12/26/2022] Open
Abstract
Bacterial genomes encode various multidrug efflux pumps (MDR) whose specific conditions for fitness advantage are unknown. We show that the efflux pump MdtEF-TolC, in Escherichia coli, confers a fitness advantage during exposure to extreme acid (pH 2). Our flow cytometry method revealed pH-dependent fitness trade-offs between bile acids (a major pump substrate) and salicylic acid, a membrane-permeant aromatic acid that induces a drug resistance regulon but depletes proton motive force (PMF). The PMF drives MdtEF-TolC and related pumps such as AcrAB-TolC. Deletion of mdtE (with loss of the pump MdtEF-TolC) increased the strain's relative fitness during growth with or without salicylate or bile acids. However, when the growth cycle included a 2-h incubation at pH 2 (below the pH growth range), MdtEF-TolC conferred a fitness advantage. The fitness advantage required bile salts but was decreased by the presence of salicylate, whose uptake is amplified by acid. For comparison, AcrAB-TolC, the primary efflux pump for bile acids, conferred a PMF-dependent fitness advantage with or without acid exposure in the growth cycle. A different MDR pump, EmrAB-TolC, conferred no selective benefit during growth in the presence of bile acids. Without bile acids, all three MDR pumps incurred a large fitness cost with salicylate when exposed at pH 2. These results are consistent with the increased uptake of salicylate at low pH. Overall, we showed that MdtEF-TolC is an MDR pump adapted for transient extreme-acid exposure and that low pH amplifies the salicylate-dependent fitness cost for drug pumps. IMPORTANCE Antibiotics and other drugs that reach the gut must pass through stomach acid. However, little is known of how extreme acid modulates the effect of drugs on gut bacteria. We find that extreme-acid exposure leads to a fitness advantage for a multidrug pump that otherwise incurs a fitness cost. At the same time, extreme acid amplifies the effect of salicylate selection against multidrug pumps. Thus, organic acids and stomach acid could play important roles in regulating multidrug resistance in the gut microbiome. Our flow cytometry assay provides a way to measure the fitness effects of extreme-acid exposure to various membrane-soluble organic acids, including plant-derived nutrients and pharmaceutical agents. Therapeutic acids might be devised to control the prevalence of multidrug pumps in environmental and host-associated habitats.
Collapse
Affiliation(s)
| | - Abigail V. Lee
- Department of Biology, Kenyon College, Gambier, Ohio, USA
| | | | | | - Haofan Li
- Department of Biology, Kenyon College, Gambier, Ohio, USA
| | | | - Cassandra Lis
- Department of Biology, Kenyon College, Gambier, Ohio, USA
| | - Mark Lang
- Department of Biology, Kenyon College, Gambier, Ohio, USA
| | - Yangyang Liu
- Department of Biology, Kenyon College, Gambier, Ohio, USA
| | - Nafeez Ahmed
- Department of Biology, Kenyon College, Gambier, Ohio, USA
| | | | | | | | | | | |
Collapse
|
|
39
|
Hu Y, He J, Zheng P, Mao X, Huang Z, Yan H, Luo Y, Yu J, Luo J, Yu B, Chen D. Prebiotic inulin as a treatment of obesity related nonalcoholic fatty liver disease through gut microbiota: a critical review. Crit Rev Food Sci Nutr 2021; 63:862-872. [PMID: 34292103 DOI: 10.1080/10408398.2021.1955654] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
The microbial-derived products, including short chain fatty acids, lipopolysaccharide and secondary bile acids, have been shown to participate in the regulation of hepatic lipid metabolism. Previous studies have demonstrated that prebiotics, such as oligosaccharide and inulin, have abilities to change the concentration of microbial-derived products through modulating the microbial community structure, thus controlling body weight and alleviating hepatic fat accumulation. However, recent evidence indicates that there are individual differences in host response upon inulin treatment due to the differences in host microbial composition before dietary intervention. Probably it is because of the multiple relationships among bacterial species (e.g., competition and mutualism), which play key roles in the degradation of inulin and the regulation of microbial structure. Thereby, analyzing the composition and function of initial gut microbiota is essential for improving the efficacy of prebiotics supplementation. Furthermore, considering that different structures of polysaccharides can be used by different microorganisms, the chemical structure of processed inulin should be tested before using prebiotic inulin to treat obesity related nonalcoholic fatty liver disease.
Collapse
Affiliation(s)
- Yaolian Hu
- Key laboratory of Animal Disease-resistant Nutrition, Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Yaan, People's Republic of China
| | - Jun He
- Key laboratory of Animal Disease-resistant Nutrition, Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Yaan, People's Republic of China
| | - Ping Zheng
- Key laboratory of Animal Disease-resistant Nutrition, Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Yaan, People's Republic of China
| | - Xiangbing Mao
- Key laboratory of Animal Disease-resistant Nutrition, Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Yaan, People's Republic of China
| | - Zhiqing Huang
- Key laboratory of Animal Disease-resistant Nutrition, Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Yaan, People's Republic of China
| | - Hui Yan
- Key laboratory of Animal Disease-resistant Nutrition, Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Yaan, People's Republic of China
| | - Yuheng Luo
- Key laboratory of Animal Disease-resistant Nutrition, Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Yaan, People's Republic of China
| | - Jie Yu
- Key laboratory of Animal Disease-resistant Nutrition, Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Yaan, People's Republic of China
| | - Junqiu Luo
- Key laboratory of Animal Disease-resistant Nutrition, Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Yaan, People's Republic of China
| | - Bing Yu
- Key laboratory of Animal Disease-resistant Nutrition, Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Yaan, People's Republic of China
| | - Daiwen Chen
- Key laboratory of Animal Disease-resistant Nutrition, Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Yaan, People's Republic of China
| |
Collapse
|
|
40
|
Abstract
Bile acids and their signaling pathways are increasingly recognized as potential therapeutic targets for cholestatic and metabolic liver diseases. This review summarizes new insights in bile acid physiology, focusing on regulatory roles of bile acids in the control of immune regulation and on effects of pharmacological modulators of bile acid signaling pathways in human liver disease. Recent mouse studies have highlighted the importance of the interactions between bile acids and gut microbiome. Interfering with microbiome composition may be beneficial for cholestatic and metabolic liver diseases by modulating formation of secondary bile acids, as different bile acid species have different signaling functions. Bile acid receptors such as FXR, VDR, and TGR5 are expressed in a variety of cells involved in innate as well as adaptive immunity, and specific microbial bile acid metabolites positively modulate immune responses of the host. Identification of Cyp2c70 as the enzyme responsible for the generation of hydrophilic mouse/rat-specific muricholic acids has allowed the generation of murine models with a human-like bile acid composition. These novel mouse models will aid to accelerate translational research on the (patho)physiological roles of bile acids in human liver diseases .
Collapse
|
|
41
|
Ji XG, Chang KL, Chen M, Zhu LL, Osman A, Yin H, Zhao LM. In vitro fermentation of chitooligosaccharides and their effects on human fecal microbial community structure and metabolites. Lebensm Wiss Technol 2021. [DOI: 10.1016/j.lwt.2021.111224] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
|
|
42
|
Zhang CH, Sheng JQ, Xie WH, Luo XQ, Xue YN, Xu GL, Chen C. Mechanism and Basis of Traditional Chinese Medicine Against Obesity: Prevention and Treatment Strategies. Front Pharmacol 2021; 12:615895. [PMID: 33762940 PMCID: PMC7982543 DOI: 10.3389/fphar.2021.615895] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Accepted: 01/26/2021] [Indexed: 12/13/2022] Open
Abstract
In the last few decades, the incidences of obesity and related metabolic disorders worldwide have increased dramatically. Major pathophysiology of obesity is termed "lipotoxicity" in modern western medicine (MWM) or "dampness-heat" in traditional Chinese medicine (TCM). "Dampness-heat" is a very common and critically important syndrome to guild clinical treatment in TCM. However, the pathogenesis of obesity in TCM is not fully clarified, especially by MWM theories compared to TCM. In this review, the mechanism underlying the action of TCM in the treatment of obesity and related metabolic disorders was thoroughly discussed, and prevention and treatment strategies were proposed accordingly. Hypoxia and inflammation caused by lipotoxicity exist in obesity and are key pathophysiological characteristics of "dampness-heat" syndrome in TCM. "Dampness-heat" is prevalent in chronic low-grade systemic inflammation, prone to insulin resistance (IR), and causes variant metabolic disorders. In particular, the MWM theories of hypoxia and inflammation were applied to explain the "dampness-heat" syndrome of TCM, and we summarized and proposed the pathological path of obesity: lipotoxicity, hypoxia or chronic low-grade inflammation, IR, and metabolic disorders. This provides significant enrichment to the scientific connotation of TCM theories and promotes the modernization of TCM.
Collapse
Affiliation(s)
- Chang-Hua Zhang
- College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, China
| | - Jun-Qing Sheng
- College of Life Science, Nanchang University, Nanchang, China
| | - Wei-Hua Xie
- College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, China
| | - Xiao-Quan Luo
- Experimental Animal Science and Technology Center of TCM, Jiangxi University of Traditional Chinese Medicine, Nanchang, China
| | - Ya-Nan Xue
- College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, China
| | - Guo-Liang Xu
- Research Center for Differentiation and Development of Basic Theory of TCM, Jiangxi University of Traditional Chinese Medicine, Nanchang, China
| | - Chen Chen
- School of Biomedical Sciences, University of Queensland, Brisbane, QLD, Australia
| |
Collapse
|
|
43
|
Fiorucci S, Distrutti E, Carino A, Zampella A, Biagioli M. Bile acids and their receptors in metabolic disorders. Prog Lipid Res 2021; 82:101094. [PMID: 33636214 DOI: 10.1016/j.plipres.2021.101094] [Citation(s) in RCA: 153] [Impact Index Per Article: 38.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Revised: 02/03/2021] [Accepted: 02/12/2021] [Indexed: 02/08/2023]
Abstract
Bile acids are a large family of atypical steroids which exert their functions by binding to a family of ubiquitous cell membrane and nuclear receptors. There are two main bile acid activated receptors, FXR and GPBAR1, that are exclusively activated by bile acids, while other receptors CAR, LXRs, PXR, RORγT, S1PR2and VDR are activated by bile acids in addition to other more selective endogenous ligands. In the intestine, activation of FXR and GPBAR1 promotes the release of FGF15/19 and GLP1 which integrate their signaling with direct effects exerted by theother receptors in target tissues. This network is tuned in a time ordered manner by circadian rhythm and is critical for the regulation of metabolic process including autophagy, fast-to-feed transition, lipid and glucose metabolism, energy balance and immune responses. In the last decade FXR ligands have entered clinical trials but development of systemic FXR agonists has been proven challenging because their side effects including increased levels of cholesterol and Low Density Lipoproteins cholesterol (LDL-c) and reduced High-Density Lipoprotein cholesterol (HDL-c). In addition, pruritus has emerged as a common, dose related, side effect of FXR ligands. Intestinal-restricted FXR and GPBAR1 agonists and dual FXR/GPBAR1 agonists have been developed. Here we review the last decade in bile acids physiology and pharmacology.
Collapse
Affiliation(s)
- Stefano Fiorucci
- Dipartimento di Medicina e Chirurgia, Università di Perugia, Perugia, Italy.
| | - Eleonora Distrutti
- SC di Gastroenterologia ed Epatologia, Azienda Ospedaliera di Perugia, Perugia, Italy
| | - Adriana Carino
- Dipartimento di Medicina e Chirurgia, Università di Perugia, Perugia, Italy
| | - Angela Zampella
- Department of Pharmacy, University of Napoli, Federico II, Napoli, Italy
| | - Michele Biagioli
- Dipartimento di Medicina e Chirurgia, Università di Perugia, Perugia, Italy
| |
Collapse
|
|
44
|
Liang H, Jiang F, Cheng R, Luo Y, Wang J, Luo Z, Li M, Shen X, He F. A high-fat diet and high-fat and high-cholesterol diet may affect glucose and lipid metabolism differentially through gut microbiota in mice. Exp Anim 2021; 70:73-83. [PMID: 32999215 PMCID: PMC7887617 DOI: 10.1538/expanim.20-0094] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Accepted: 08/30/2020] [Indexed: 12/16/2022] Open
Abstract
This study was conducted to investigate the effects of a high-fat diet (HFD) and high-fat and high-cholesterol diet (HFHCD) on glucose and lipid metabolism and on the intestinal microbiota of the host animal. A total of 30 four-week-old female C57BL/6 mice were randomly divided into three groups (n=10) and fed with a normal diet (ND), HFD, or HFHCD for 12 weeks, respectively. The HFD significantly increased body weight and visceral adipose accumulation and partly lowered oral glucose tolerance compared with the ND and HFHCD. The HFHCD increased liver weight, liver fat infiltration, liver triglycerides, and liver total cholesterol compared with the ND and HFD. Moreover, it increased serum high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total cholesterol compared with the ND and HFD and upregulated alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase significantly. The HFHCD also significantly decreased the α-diversity of the fecal bacteria of the mice, to a greater extent than the HFD. The composition of fecal bacteria among the three groups was apparently different. Compared with the HFHCD-fed mice, the HFD-fed mice had more Oscillospira, Odoribacter, Bacteroides, and [Prevotella], but less [Ruminococcus] and Akkermansia. Cecal short-chain fatty acids were significantly decreased after the mice were fed the HFD or HFHCD for 12 weeks. Our findings indicate that an HFD and HFHCD can alter the glucose and lipid metabolism of the host animal differentially; modifications of intestinal microbiota and their metabolites may be an important underlying mechanism.
Collapse
Affiliation(s)
- Huijing Liang
- Department of Nutrition, Food Hygiene and Toxicology, West China School of Public Health and West China Fourth Hospital, Sichuan University, No.16, 3rd section, South Renmin Road, 610041 Chengdu, Sichuan, China
| | - Fengling Jiang
- Department of Nutrition, Food Hygiene and Toxicology, West China School of Public Health and West China Fourth Hospital, Sichuan University, No.16, 3rd section, South Renmin Road, 610041 Chengdu, Sichuan, China
| | - Ruyue Cheng
- Department of Nutrition, Food Hygiene and Toxicology, West China School of Public Health and West China Fourth Hospital, Sichuan University, No.16, 3rd section, South Renmin Road, 610041 Chengdu, Sichuan, China
| | - Yating Luo
- Department of Nutrition, Food Hygiene and Toxicology, West China School of Public Health and West China Fourth Hospital, Sichuan University, No.16, 3rd section, South Renmin Road, 610041 Chengdu, Sichuan, China
| | - Jiani Wang
- Department of Nutrition, Food Hygiene and Toxicology, West China School of Public Health and West China Fourth Hospital, Sichuan University, No.16, 3rd section, South Renmin Road, 610041 Chengdu, Sichuan, China
| | - Zihao Luo
- Department of Nutrition, Food Hygiene and Toxicology, West China School of Public Health and West China Fourth Hospital, Sichuan University, No.16, 3rd section, South Renmin Road, 610041 Chengdu, Sichuan, China
| | - Ming Li
- Department of Nutrition, Food Hygiene and Toxicology, West China School of Public Health and West China Fourth Hospital, Sichuan University, No.16, 3rd section, South Renmin Road, 610041 Chengdu, Sichuan, China
| | - Xi Shen
- Department of Nutrition, Food Hygiene and Toxicology, West China School of Public Health and West China Fourth Hospital, Sichuan University, No.16, 3rd section, South Renmin Road, 610041 Chengdu, Sichuan, China
| | - Fang He
- Department of Nutrition, Food Hygiene and Toxicology, West China School of Public Health and West China Fourth Hospital, Sichuan University, No.16, 3rd section, South Renmin Road, 610041 Chengdu, Sichuan, China
| |
Collapse
|
|
45
|
Hu Q, Zhang W, Wu Z, Tian X, Xiang J, Li L, Li Z, Peng X, Wei S, Ma X, Zhao Y. Baicalin and the liver-gut system: Pharmacological bases explaining its therapeutic effects. Pharmacol Res 2021; 165:105444. [PMID: 33493657 DOI: 10.1016/j.phrs.2021.105444] [Citation(s) in RCA: 122] [Impact Index Per Article: 30.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Revised: 01/03/2021] [Accepted: 01/11/2021] [Indexed: 02/06/2023]
Abstract
With the development of high-throughput screening and bioinformatics technology, natural products with a range of pharmacological targets in multiple diseases have become important sources of new drug discovery. These compounds are derived from various plants, including the dried root of Scutellaria baicalensis Georgi, which is often used as a traditional Chinese herb named Huangqin, a popular medication used for thousands of years in China. Many studies have shown that baicalin, an extract from Scutellaria baicalensis Georgi, exerts various protective effects on liver and gut diseases. Baicalin plays a therapeutic role mainly by mediating downstream apoptosis and immune response pathways induced by upstream oxidative stress and inflammation. During oxidative stress regulation, PI3K/Akt/NRF2, Keap-1, NF-κB and HO-1 are key factors associated with the healing effects of baicalin on NAFLD/NASH, ulcerative colitis and cholestasis. In the inflammatory response, IL-6, IL-1β, TNF-α, MIP-2 and MIP-1α are involved in the alleviation of NAFLD/NASH, cholestasis and liver fibrosis by baicalin, as are TGF-β1/Smads, STAT3 and NF-κB. Regarding the apoptosis pathway, Bax, Bcl-2, Caspase-3 and Caspase-9 are key factors related to the suppression of hepatocellular carcinoma and attenuation of liver injury and colorectal cancer. In addition to immune regulation, PD-1/PDL-1 and TLR4-NF-κB are correlated with the alleviation of hepatocellular carcinoma, ulcerative colitis and colorectal cancer by baicalin. Moreover, baicalin regulates intestinal flora by promoting the production of SCFAs. Furthermore, BA is involved in the interactions of the liver-gut axis by regulating TGR5, FXR, bile acids and the microbiota. In general, a comprehensive analysis of this natural compound was conducted to determine the mechanism by which it regulates bile acid metabolism, the intestinal flora and related signaling pathways, providing new insights into the pharmacological effects of baicalin. The mechanism linking the liver and gut systems needs to be elucidated to draw attention to its great clinical importance.
Collapse
Affiliation(s)
- Qichao Hu
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Wenwen Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Zhao Wu
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Xin Tian
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Junbao Xiang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Longxuan Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Zhihao Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Xi Peng
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Shizhang Wei
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China; Department of Pharmacy, Fifth Medical Center of PLA General Hospital, Beijing, 100039, China
| | - Xiao Ma
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
| | - Yanling Zhao
- Department of Pharmacy, Fifth Medical Center of PLA General Hospital, Beijing, 100039, China.
| |
Collapse
|
|
46
|
Micó-Carnero M, Rojano-Alfonso C, Álvarez-Mercado AI, Gracia-Sancho J, Casillas-Ramírez A, Peralta C. Effects of Gut Metabolites and Microbiota in Healthy and Marginal Livers Submitted to Surgery. Int J Mol Sci 2020; 22:44. [PMID: 33375200 PMCID: PMC7793124 DOI: 10.3390/ijms22010044] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 12/18/2020] [Accepted: 12/20/2020] [Indexed: 12/12/2022] Open
Abstract
Microbiota is defined as the collection of microorganisms within the gastrointestinal ecosystem. These microbes are strongly implicated in the stimulation of immune responses. An unbalanced microbiota, termed dysbiosis, is related to the development of several liver diseases. The bidirectional relationship between the gut, its microbiota and the liver is referred to as the gut-liver axis. The translocation of bacterial products from the intestine to the liver induces inflammation in different cell types such as Kupffer cells, and a fibrotic response in hepatic stellate cells, resulting in deleterious effects on hepatocytes. Moreover, ischemia-reperfusion injury, a consequence of liver surgery, alters the microbiota profile, affecting inflammation, the immune response and even liver regeneration. Microbiota also seems to play an important role in post-operative outcomes (i.e., liver transplantation or liver resection). Nonetheless, studies to determine changes in the gut microbial populations produced during and after surgery, and affecting liver function and regeneration are scarce. In the present review we analyze and discuss the preclinical and clinical studies reported in the literature focused on the evaluation of alterations in microbiota and its products as well as their effects on post-operative outcomes in hepatic surgery.
Collapse
Affiliation(s)
- Marc Micó-Carnero
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain; (M.M.-C.); (C.R.-A.)
| | - Carlos Rojano-Alfonso
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain; (M.M.-C.); (C.R.-A.)
| | - Ana Isabel Álvarez-Mercado
- Departamento de Bioquímica y Biología Molecular II, Escuela de Farmacia, Universidad de Granada, 18071 Granada, Spain;
- Institut of Nutrition and Food Technology “José Mataix”, Center of Biomedical Research, University of Granada, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria ibs, GRANADA, Complejo Hospitalario Universitario de Granada, 18014 Granada, Spain
| | - Jordi Gracia-Sancho
- Liver Vascular Biology Research Group, Barcelona Hepatic Hemodynamic Laboratory IDIBAPS, 03036 Barcelona, Spain;
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 08036 Barcelona, Spain
| | - Araní Casillas-Ramírez
- Hospital Regional de Alta Especialidad de Ciudad Victoria “Bicentenario 2010”, Ciudad Victoria 87087, Mexico;
- Facultad de Medicina e Ingeniería en Sistemas Computacionales de Matamoros, Universidad Autónoma de Tamaulipas, Matamoros 87300, Mexico
| | - Carmen Peralta
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain; (M.M.-C.); (C.R.-A.)
| |
Collapse
|
|
47
|
Immunomodulatory effects of fermented fig (Ficus carica L.) fruit extracts on cyclophosphamide-treated mice. J Funct Foods 2020. [DOI: 10.1016/j.jff.2020.104219] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
|
|
48
|
Wu YN, Zhang L, Chen T, Li X, He LH, Liu GX. Granulocyte-macrophage colony-stimulating factor protects mice against hepatocellular carcinoma by ameliorating intestinal dysbiosis and attenuating inflammation. World J Gastroenterol 2020; 26:5420-5436. [PMID: 33024394 PMCID: PMC7520605 DOI: 10.3748/wjg.v26.i36.5420] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 06/11/2020] [Accepted: 08/25/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. The gut microbiota can help maintain healthy metabolism and immunity. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a critical factor in promoting health and homeostasis; it promotes intestinal immunity, stimulates bone marrow precursors to generate macrophage colonies, and enhances the antibacterial and antitumor activity of circulating monocytes. As such, GM-CSF may protect against HCC development by regulating immunity as well as intestinal microecology.
AIM To investigate the impact of GM-CSF on the gut microbiome and metabolic characteristics of HCC.
METHODS Thirty-six male BALB/c nude mice were divided into three groups: Control (n = 10), HCC (n = 13), and HCC + GM-CSF (GM-CSF overexpression, n = 13). We utilized HCC cells to establish orthotopic transplantation tumor models of HCC with normal and over-expressing GM-CSF. Liver injury, immune inflammatory function and intestinal barrier function were evaluated. The fecal microbiome and metabolome were studied using 16S rRNA absolute quantification sequencing and gas chromatography-mass spectrometry.
RESULTS GM-CSF overexpression significantly affected the gut microbiome of mice with HCC and resulted in a high abundance of organisms of the genera Roseburia, Blautia and Butyricimonass, along with a significant reduction in Prevotella, Parabacteroides, Anaerotruncus, Streptococcus, Clostridium, and Mucispirillum. Likewise, GM-CSF overexpression resulted in a substantial increase in fecal biotin and oleic acid levels, along with a prominent decrease in the fecal succinic acid, adenosine, fumaric acid, lipoic acid, and maleic acid levels. Correlation analysis revealed that the intestinal microbiota and fecal metabolites induced by GM-CSF were primarily involved in pathways related to reducing the inflammatory response, biotin metabolism, and intestinal barrier dysfunction.
CONCLUSION GM-CSF can protect against HCC development by regulating immunity and modulating the abundance of specific intestinal microorganisms and their metabolites. This study provides new insights into the therapeutic approaches for HCC.
Collapse
Affiliation(s)
- Yong-Na Wu
- Key Laboratory of Desert and Desertification, Northwest Institute of Eco-Environment and Resources, Chinese Academy of Sciences, Lanzhou 730000, Gansu Province, China
- Key Laboratory of Extreme Environmental Microbial Resources and Engineering of Gansu Province, Lanzhou 730000, Gansu Province, China
- University of Chinese Academy of Sciences, Beijing 100049, China
- The First Hospital of Lanzhou University, Lanzhou University, Lanzhou 730000, Gansu Province, China
- Key Laboratory of Biological Therapy and Regenerative Medicine Transformation Gansu Province, Lanzhou 730000, Gansu Province, China
| | - Lei Zhang
- The First Hospital of Lanzhou University, Lanzhou University, Lanzhou 730000, Gansu Province, China
- Key Laboratory of Biological Therapy and Regenerative Medicine Transformation Gansu Province, Lanzhou 730000, Gansu Province, China
| | - Tuo Chen
- Key Laboratory of Desert and Desertification, Northwest Institute of Eco-Environment and Resources, Chinese Academy of Sciences, Lanzhou 730000, Gansu Province, China
- Key Laboratory of Extreme Environmental Microbial Resources and Engineering of Gansu Province, Lanzhou 730000, Gansu Province, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Xun Li
- The First Hospital of Lanzhou University, Lanzhou University, Lanzhou 730000, Gansu Province, China
- Key Laboratory of Biological Therapy and Regenerative Medicine Transformation Gansu Province, Lanzhou 730000, Gansu Province, China
| | - Li-Hong He
- The First Hospital of Lanzhou University, Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Guang-Xiu Liu
- Key Laboratory of Desert and Desertification, Northwest Institute of Eco-Environment and Resources, Chinese Academy of Sciences, Lanzhou 730000, Gansu Province, China
- Key Laboratory of Extreme Environmental Microbial Resources and Engineering of Gansu Province, Lanzhou 730000, Gansu Province, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| |
Collapse
|
|
49
|
Zhu Y, Zhang JY, Wei YL, Hao JY, Lei YQ, Zhao WB, Xiao YH, Sun AD. The polyphenol-rich extract from chokeberry ( Aronia melanocarpa L .) modulates gut microbiota and improves lipid metabolism in diet-induced obese rats. Nutr Metab (Lond) 2020; 17:54. [PMID: 32655675 PMCID: PMC7339576 DOI: 10.1186/s12986-020-00473-9] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Accepted: 06/24/2020] [Indexed: 12/15/2022] Open
Abstract
The gut microbiota plays a critical role in obesity and lipid metabolism disorder. Chokeberry (Aronia melanocarpa L.) are rich in polyphenols with various physiological and pharmacological activities. We determined serum physiological parameters and fecal microbial components by using related kits, liquid chromatography-mass spectrometry (LC-MS) and 16S rRNA gene sequencing every 10 days. Real-time PCR analysis was used to measure gene expression of bile acids (BAs) and lipid metabolism in liver and adipose tissues. We analyzed the effects of different Chokeberry polyphenol (CBPs) treatment time on obesity and lipid metabolism in high fat diet (HFD)-fed rats. The results indicated that CBPs treatment prevents obesity, liver steatosis and improves dyslipidemia in HFD-fed rats. CBPs modulated the composition of the gut microbiota with the extended treatment time, reducing the Firmicutes/Bacteroidetes ratio (F/B ratio) and increasing the relative abundance of Bacteroides, Prevotella, Akkermansia and other bacterial species associated with anti-obesity properties. We found that CBPs treatment gradually decreased the total BAs pool and particularly reduced the relative content of cholic acid (CA), deoxycholic acid (DCA) and enhanced the relative content of chenodeoxycholic acid (CDCA). These changes were positively correlated Bacteroides, Prevotella and negatively correlated with Clostridium, Eubacterium, Ruminococcaceae. In liver and white adipose tissues, the gene expression of lipogenesis, lipolysis and BAs metabolism were regulated after CBPs treatment in HFD-fed rats, which was most likely mediated through FXR and TGR-5 signaling pathway to improve lipid metabolism. In addition, the mRNA expression of PPARγ, UCP1 and PGC-1α were upregulated markedly in interscapular brown adipose tissue (iBAT) after CBPs treatment. We confirmed that CBPs could reduce the body weight of HFD-fed rats by accelerating energy homeostasis and thermogenesis in iBAT. Finally, the fecal microbiota transplantation (FMT) experiment results demonstrated that FMT from CBPs-treated rats failed to reduce the weight of HFD-fed rats. However, FMT from CBPs-treated rats improved dyslipidemia and reshaped gut microbiota in HFD-fed rats. In conclusion, CBPs treatment improved obesity and complications by regulating gut microbiota in HFD-fed rats. The gut microbiota plays an important role in BAs metabolism after CBPs treatment, and BAs have therefore emerged as major effectors in microbe-host signaling events that influence host lipid metabolism, energy metabolism and thermogenesis.
Collapse
Affiliation(s)
- Yue Zhu
- College of Biological Sciences and Technology, Beijing Forestry University, Beijing, 100083 China
| | - Jia-ying Zhang
- College of Biological Sciences and Technology, Beijing Forestry University, Beijing, 100083 China
| | - Yu-long Wei
- College of Biological Sciences and Technology, Beijing Forestry University, Beijing, 100083 China
| | - Jing-yi Hao
- College of Biological Sciences and Technology, Beijing Forestry University, Beijing, 100083 China
| | - Yu-qing Lei
- College of Biological Sciences and Technology, Beijing Forestry University, Beijing, 100083 China
| | - Wan-bin Zhao
- College of Biological Sciences and Technology, Beijing Forestry University, Beijing, 100083 China
| | - Yu-hang Xiao
- College of Biological Sciences and Technology, Beijing Forestry University, Beijing, 100083 China
| | - Ai-dong Sun
- College of Biological Sciences and Technology, Beijing Forestry University, Beijing, 100083 China
| |
Collapse
|
|
50
|
Sipe LM, Chaib M, Pingili AK, Pierre JF, Makowski L. Microbiome, bile acids, and obesity: How microbially modified metabolites shape anti-tumor immunity. Immunol Rev 2020; 295:220-239. [PMID: 32320071 PMCID: PMC7841960 DOI: 10.1111/imr.12856] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Accepted: 03/02/2020] [Indexed: 02/06/2023]
Abstract
Bile acids (BAs) are known facilitators of nutrient absorption but recent paradigm shifts now recognize BAs as signaling molecules regulating both innate and adaptive immunity. Bile acids are synthesized from cholesterol in the liver with subsequent microbial modification and fermentation adding complexity to pool composition. Bile acids act on several receptors such as Farnesoid X Receptor and the G protein-coupled BA receptor 1 (TGR5). Interestingly, BA receptors (BARs) are expressed on immune cells and activation either by BAs or BAR agonists modulates innate and adaptive immune cell populations skewing their polarization toward a more tolerogenic anti-inflammatory phenotype. Intriguingly, recent evidence also suggests that BAs promote anti-tumor immune response through activation and recruitment of tumoricidal immune cells such as natural killer T cells. These exciting findings have redefined BA signaling in health and disease wherein they may suppress inflammation on the one hand, yet promote anti-tumor immunity on the other hand. In this review, we provide our readers with the most recent understanding of the interaction of BAs with the host microbiome, their effect on innate and adaptive immunity in health and disease with a special focus on obesity, bariatric surgery-induced weight loss, and immune checkpoint blockade in cancer.
Collapse
Affiliation(s)
- Laura M. Sipe
- Division of Hematology and Oncology, Department of Medicine, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Mehdi Chaib
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Ajeeth K. Pingili
- Division of Hematology and Oncology, Department of Medicine, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Joseph F. Pierre
- Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Liza Makowski
- Division of Hematology and Oncology, Department of Medicine, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, USA
- Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN, USA
| |
Collapse
|