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Schwenger KJP, Copeland JK, Ghorbani Y, Chen L, Comelli EM, Guttman DS, Fischer SE, Jackson TD, Okrainec A, Allard JP. Characterization of liver, adipose, and fecal microbiome in obese patients with MASLD: links with disease severity and metabolic dysfunction parameters. MICROBIOME 2025; 13:9. [PMID: 39810228 PMCID: PMC11730849 DOI: 10.1186/s40168-024-02004-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Accepted: 12/10/2024] [Indexed: 01/16/2025]
Abstract
BACKGROUND Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a range of histological findings from the generally benign simple steatosis to steatohepatitis (MASH) which can progress to fibrosis and cirrhosis. Several factors, including the microbiome, may contribute to disease progression. RESULTS Here, we demonstrate links between the presence and abundance of specific bacteria in the adipose and liver tissues, inflammatory genes, immune cell responses, and disease severity. Overall, in MASLD patients, we observed a generalized obesity-induced translocation of gut bacteria to hepatic and adipose tissues. We identified microbial patterns unique to more severely diseased tissues. Specifically, Enterococcus, Granulicatella, and Morganellaceae abundance is positively correlated with immune cell counts and inflammatory gene expression levels, and both genera are significantly enriched in MASH patients. Brevibacterium is enriched in adipose tissues of patients with liver fibrosis. CONCLUSION Together, these results provide further insight into the microbial factors that may be driving disease severity. Video Abstract.
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Affiliation(s)
| | - Julia K Copeland
- Centre for the Analysis of Genome Evolution & Function, University of Toronto, Toronto, Canada
| | - Yasaman Ghorbani
- Toronto General Hospital, University Health Network, Toronto, Canada
| | - Lina Chen
- Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada
| | - Elena M Comelli
- Department of Nutritional Sciences, University of Toronto, Toronto, Canada
| | - David S Guttman
- Centre for the Analysis of Genome Evolution & Function, University of Toronto, Toronto, Canada
| | - Sandra E Fischer
- Toronto General Hospital, University Health Network, Toronto, Canada
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada
| | - Timothy D Jackson
- Division of General Surgery, University of Toronto, Toronto, Canada
- Division of General Surgery, Toronto Western Hospital, University Health Network, Toronto, Canada
| | - Allan Okrainec
- Division of General Surgery, University of Toronto, Toronto, Canada
- Division of General Surgery, Toronto Western Hospital, University Health Network, Toronto, Canada
| | - Johane P Allard
- Toronto General Hospital, University Health Network, Toronto, Canada.
- Department of Nutritional Sciences, University of Toronto, Toronto, Canada.
- Division of Gastroenterology, Department of Medicine, Toronto General Hospital, 585 University Avenue, 9N-973, Toronto, ON, M5G 2N2, Canada.
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2
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Ezhilarasan D, Langeswaran K. Hepatocellular Interactions of Potential Nutraceuticals in the Management of Inflammatory NAFLD. Cell Biochem Funct 2024; 42:e4112. [PMID: 39238138 DOI: 10.1002/cbf.4112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Revised: 07/17/2024] [Accepted: 08/09/2024] [Indexed: 09/07/2024]
Abstract
Numerous studies highlight the potential of natural antioxidants, such as those found in foods and plants, to prevent or treat nonalcoholic fatty liver disease (NAFLD). Inflammation is a key factor in the progression from high-fat diet-induced NAFLD to nonalcoholic steatohepatitis (NASH). Injured liver cells and immune cells release inflammatory cytokines, activating hepatic stellate cells. These cells acquire a profibrogenic phenotype, leading to extracellular matrix accumulation and fibrosis. Persistent fibrosis can progress to cirrhosis. Fatty infiltration, oxidative stress, and inflammation exacerbate fatty liver diseases. Thus, many plant-derived antioxidants, like silymarin, silibinin, curcumin, resveratrol, berberine, and quercetin, have been extensively studied in experimental models and clinical patients with NAFLD. Experimentally, these compounds have shown beneficial effects in reducing lipid accumulation, oxidative stress, and inflammatory markers by modulating the ERK, NF-κB, AMPKα, and PPARγ pathways. They also help decrease metabolic endotoxemia, intestinal permeability, and gut inflammation. Clinically, silymarin and silibinin have been found to reduce transaminase levels, while resveratrol and curcumin help alleviate inflammation in NAFLD patients. However, these phytocompounds exhibit poor water solubility, leading to low oral bioavailability and hindering their biological efficacy. Additionally, inconclusive clinical results highlight the need for further trials with larger populations, longer durations, and standardized protocols.
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Affiliation(s)
- Devaraj Ezhilarasan
- Hepatology and Molecular Medicine Lab, Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai, Tamil Nadu, India
| | - Kulanthaivel Langeswaran
- Department of Biomedical Science, Science Campus, Alagappa University, Karaikudi, Tamil Nadu, India
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3
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Chen Y, Gan Y, Zhong H, Liu Y, Huang J, Wang W, Geng J. Gut microbe and hepatic macrophage polarization in non-alcoholic fatty liver disease. Front Microbiol 2023; 14:1285473. [PMID: 38125578 PMCID: PMC10731260 DOI: 10.3389/fmicb.2023.1285473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Accepted: 11/21/2023] [Indexed: 12/23/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a common chronic hepatic disorder with the potential to progress to hepatic fibrosis, hepatic cirrhosis, and even hepatocellular carcinoma. Activation of hepatic macrophages, important innate immune cells predominantly composed of Kupffer cells, plays a pivotal role in NAFLD initiation and progression. Recent findings have underscored the regulatory role of microbes in both local and distal immune responses, including in the liver, emphasizing their contribution to NAFLD initiation and progression. Key studies have further revealed that gut microbes can penetrate the intestinal mucosa and translocate to the liver, thereby directly influencing hepatic macrophage polarization and NAFLD progression. In this review, we discuss recent evidence regarding the translocation of intestinal microbes into the liver, as well as their impact on hepatic macrophage polarization and associated cellular and molecular signaling pathways. Additionally, we summarize the potential mechanisms by which translocated microbes may activate hepatic macrophages and accelerate NAFLD progression.
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Affiliation(s)
- Yao Chen
- Department of Infectious Disease and Hepatic Disease, First People’s Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China
- School of Medicine, Kunming University of Science and Technology, Kunming, Yunnan, China
| | - Yumeng Gan
- Department of Infectious Disease and Hepatic Disease, First People’s Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China
- School of Medicine, Kunming University of Science and Technology, Kunming, Yunnan, China
| | - Huijie Zhong
- Department of Infectious Disease and Hepatic Disease, First People’s Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China
- School of Medicine, Kunming University of Science and Technology, Kunming, Yunnan, China
| | - Yincong Liu
- Department of Infectious Disease and Hepatic Disease, First People’s Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China
- School of Medicine, Kunming University of Science and Technology, Kunming, Yunnan, China
| | - Jingdi Huang
- Department of Infectious Disease and Hepatic Disease, First People’s Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China
| | - Wenxue Wang
- Department of Infectious Disease and Hepatic Disease, First People’s Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China
- School of Medicine, Kunming University of Science and Technology, Kunming, Yunnan, China
- School of Basic Medicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, China
| | - Jiawei Geng
- Department of Infectious Disease and Hepatic Disease, First People’s Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China
- School of Medicine, Kunming University of Science and Technology, Kunming, Yunnan, China
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan, China
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4
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Li Y, Johnson JP, Yang Y, Yu D, Kubo H, Berretta RM, Wang T, Zhang X, Foster M, Yu J, Tilley DG, Houser SR, Chen X. Effects of maternal hypothyroidism on postnatal cardiomyocyte proliferation and cardiac disease responses of the progeny. Am J Physiol Heart Circ Physiol 2023; 325:H702-H719. [PMID: 37539452 PMCID: PMC10659327 DOI: 10.1152/ajpheart.00320.2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 07/31/2023] [Accepted: 08/01/2023] [Indexed: 08/05/2023]
Abstract
Maternal hypothyroidism (MH) could adversely affect the cardiac disease responses of the progeny. This study tested the hypothesis that MH reduces early postnatal cardiomyocyte (CM) proliferation so that the adult heart of MH progeny has a smaller number of larger cardiac myocytes, which imparts adverse cardiac disease responses following injury. Thyroidectomy (TX) was used to establish MH. The progeny from mice that underwent sham or TX surgery were termed Ctrl (control) or MH (maternal hypothyroidism) progeny, respectively. MH progeny had similar heart weight (HW) to body weight (BW) ratios and larger CM size consistent with fewer CMs at postnatal day 60 (P60) compared with Ctrl (control) progeny. MH progeny had lower numbers of EdU+, Ki67+, and phosphorylated histone H3 (PH3)+ CMs, which suggests they had a decreased CM proliferation in the postnatal timeframe. RNA-seq data showed that genes related to DNA replication were downregulated in P5 MH hearts, including bone morphogenetic protein 10 (Bmp10). Both in vivo and in vitro studies showed Bmp10 treatment increased CM proliferation. After transverse aortic constriction (TAC), the MH progeny had more severe cardiac pathological remodeling compared with the Ctrl progeny. Thyroid hormone (T4) treatment for MH mothers preserved their progeny's postnatal CM proliferation capacity and prevented excessive pathological remodeling after TAC. Our results suggest that CM proliferation during early postnatal development was significantly reduced in MH progeny, resulting in fewer CMs with hypertrophy in adulthood. These changes were associated with more severe cardiac disease responses after pressure overload.NEW & NOTEWORTHY Our study shows that compared with Ctrl (control) progeny, the adult progeny of mothers who have MH (MH progeny) had fewer CMs. This reduction of CM numbers was associated with decreased postnatal CM proliferation. Gene expression studies showed a reduced expression of Bmp10 in MH progeny. Bmp10 has been linked to myocyte proliferation. In vivo and in vitro studies showed that Bmp10 treatment of MH progeny and their myocytes could increase CM proliferation. Differences in CM number and size in adult hearts of MH progeny were linked to more severe cardiac structural and functional remodeling after pressure overload. T4 (synthetic thyroxine) treatment of MH mothers during their pregnancy, prevented the reduction in CM number in their progeny and the adverse response to disease stress.
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Affiliation(s)
- Yijia Li
- Cardiovascular Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, United States
| | - Jaslyn P Johnson
- Cardiovascular Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, United States
| | - Yijun Yang
- Cardiovascular Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, United States
| | - Daohai Yu
- Department of Biomedical Education and Data Science, Center for Biostatistics and Epidemiology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, United States
| | - Hajime Kubo
- Cardiovascular Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, United States
| | - Remus M Berretta
- Cardiovascular Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, United States
| | - Tao Wang
- Cardiovascular Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, United States
| | - Xiaoying Zhang
- Department of Cardiovascular Sciences, Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, Cardiovascular Research Center, Philadelphia, Pennsylvania, United States
| | - Michael Foster
- Cardiovascular Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, United States
| | - Jun Yu
- Department of Cardiovascular Sciences, Center for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Cardiovascular Research Center, Philadelphia, Pennsylvania, United States
| | - Douglas G Tilley
- Department of Cardiovascular Sciences, Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, Cardiovascular Research Center, Philadelphia, Pennsylvania, United States
| | - Steven R Houser
- Cardiovascular Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, United States
| | - Xiongwen Chen
- Cardiovascular Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, United States
- Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, People's Republic of China
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5
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Xu GX, Wei S, Yu C, Zhao SQ, Yang WJ, Feng YH, Pan C, Yang KX, Ma Y. Activation of Kupffer cells in NAFLD and NASH: mechanisms and therapeutic interventions. Front Cell Dev Biol 2023; 11:1199519. [PMID: 37261074 PMCID: PMC10228659 DOI: 10.3389/fcell.2023.1199519] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 05/05/2023] [Indexed: 06/02/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are emerging as the leading causes of liver disease worldwide. These conditions can lead to cirrhosis, liver cancer, liver failure, and other related ailments. At present, liver transplantation remains the sole treatment option for end-stage NASH, leading to a rapidly growing socioeconomic burden. Kupffer cells (KCs) are a dominant population of macrophages that reside in the liver, playing a crucial role in innate immunity. Their primary function includes phagocytosing exogenous substances, presenting antigens, and triggering immune responses. Moreover, they interact with other liver cells during the pathogenesis of NAFLD, and this crosstalk may either delay or exacerbate disease progression. Stimulation by endogenous signals triggers the activation of KCs, resulting in the expression of various inflammatory factors and chemokines, such as NLRP3, TNF-α, IL-1B, and IL-6, and contributing to the inflammatory cascade. In the past 5 years, significant advances have been made in understanding the biological properties and immune functions of KCs in NAFLD, including their interactions with tissue molecules, underlying molecular mechanisms, signaling pathways, and relevant therapeutic interventions. Having a comprehensive understanding of these mechanisms and characteristics can have enormous potential in guiding future strategies for the prevention and treatment of NAFLD.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Yong Ma
- *Correspondence: Kun-Xing Yang, ; Yong Ma,
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6
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Tourkochristou E, Assimakopoulos SF, Thomopoulos K, Marangos M, Triantos C. NAFLD and HBV interplay - related mechanisms underlying liver disease progression. Front Immunol 2022; 13:965548. [PMID: 36544761 PMCID: PMC9760931 DOI: 10.3389/fimmu.2022.965548] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Accepted: 11/15/2022] [Indexed: 12/08/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) and Hepatitis B virus infection (HBV) constitute common chronic liver diseases with worldwide distribution. NAFLD burden is expected to grow in the coming decade, especially in western countries, considering the increased incidence of diabetes and obesity. Despite the organized HBV vaccinations and use of anti-viral therapies globally, HBV infection remains endemic and challenging public health issue. As both NAFLD and HBV have been associated with the development of progressive fibrosis, cirrhosis and hepatocellular carcinoma (HCC), the co-occurrence of both diseases has gained great research and clinical interest. The causative relationship between NAFLD and HBV infection has not been elucidated so far. Dysregulated fatty acid metabolism and lipotoxicity in NAFLD disease seems to initiate activation of signaling pathways that enhance pro-inflammatory responses and disrupt hepatocyte cell homeostasis, promoting progression of NAFLD disease to NASH, fibrosis and HCC and can affect HBV replication and immune encountering of HBV virus, which may further have impact on liver disease progression. Chronic HBV infection is suggested to have an influence on metabolic changes, which could lead to NAFLD development and the HBV-induced inflammatory responses and molecular pathways may constitute an aggravating factor in hepatic steatosis development. The observed altered immune homeostasis in both HBV infection and NAFLD could be associated with progression to HCC development. Elucidation of the possible mechanisms beyond HBV chronic infection and NAFLD diseases, which could lead to advanced liver disease or increase the risk for severe complications, in the case of HBV-NAFLD co-existence is of high clinical significance in the context of designing effective therapeutic targets.
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Affiliation(s)
- Evanthia Tourkochristou
- Division of Gastroenterology, Department of Internal Medicine, Medical School, University of Patras, Patras, Greece
| | - Stelios F. Assimakopoulos
- Division of Infectious Diseases, Department of Internal Medicine, Medical School, University of Patras, Patras, Greece
| | - Konstantinos Thomopoulos
- Division of Gastroenterology, Department of Internal Medicine, Medical School, University of Patras, Patras, Greece
| | - Markos Marangos
- Division of Infectious Diseases, Department of Internal Medicine, Medical School, University of Patras, Patras, Greece
| | - Christos Triantos
- Division of Gastroenterology, Department of Internal Medicine, Medical School, University of Patras, Patras, Greece
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7
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Zhou Z, Pan X, Li L. Crosstalk between liver macrophages and gut microbiota: An important component of inflammation-associated liver diseases. Front Cell Dev Biol 2022; 10:1070208. [PMID: 36483677 PMCID: PMC9723159 DOI: 10.3389/fcell.2022.1070208] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Accepted: 11/10/2022] [Indexed: 08/30/2023] Open
Abstract
Hepatic macrophages have been recognized as primary sensors and responders in liver inflammation. By processing host or exogenous biochemical signals, including microbial components and metabolites, through the gut-liver axis, hepatic macrophages can both trigger or regulate inflammatory responses. Crosstalk between hepatic macrophages and gut microbiota is an important component of liver inflammation and related liver diseases, such as acute liver injury (ALI), alcoholic liver disease (ALD), and nonalcoholic fatty liver disease (NAFLD). This review summarizes recent advances in knowledge related to the crosstalk between hepatic macrophages and gut microbiota, including the therapeutic potential of targeting hepatic macrophages as a component of gut microecology in inflammation-associated liver diseases.
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Affiliation(s)
| | | | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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8
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Wei J, Zhang X, Yang F, Shi X, Wang X, Chen R, Du F, Shi M, Jiang W. Gut microbiome changes in anti-N-methyl-D-aspartate receptor encephalitis patients. BMC Neurol 2022; 22:276. [PMID: 35879681 PMCID: PMC9310403 DOI: 10.1186/s12883-022-02804-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Accepted: 07/14/2022] [Indexed: 11/18/2022] Open
Abstract
Background Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a type of autoimmune encephalitis. The underlying mechanism(s) remain largely unknown. Recent evidence has indicated that the gut microbiome may be involved in neurological immune diseases via the "gut-brain axis". This study aimed to explore the possible relationship between anti-NMDAR encephalitis and the gut microbiome. Methods Fecal specimens were collected from 10 patients with anti-NMDAR encephalitis and 10 healthy volunteers. The microbiome analysis was based on Illumina sequencing of the V3-V4 hypervariable region of the 16S rRNA gene. The alpha, beta, and taxonomic diversity analyses were mainly based on the QIIME2 pipeline. Results There were no statistical differences in epidemiology, medication, and clinical characteristics (except for those related to anti-NMDAR encephalitis) between the two groups. ASV analysis showed that Prevotella was significantly increased, while Bacteroides was reduced in the gut microbiota of the patients, compared with the controls. Alpha diversity results showed a decrease in diversity in the patients compared with the healthy controls, analyzed by the Shannon diversity, Simpson diversity, and Pielou_E uniformity based on the Kruskal–Wallis test (P = 0.0342, 0.0040, and 0.0002, respectively). Beta diversity analysis showed that the abundance and composition of the gut microbiota was significantly different between the two groups, analyzed by weighted and unweighted UniFrac distance (P = 0.005 and 0.001, respectively). Conclusions The abundance and evenness of bacterial distribution were significantly lower and jeopardized in patients with anti-NMDAR encephalitis than in healthy controls. Thus, our findings suggest that gut microbiome composition changes might be associated with the anti-NMDAR encephalitis. It could be a causal agent, or a consequence.
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Affiliation(s)
- Jingya Wei
- Department of Neurology, Xijing Hospital, Fourth Military Medical University, No. 15 Changle West Street, Xi'an, 710032, Shaanxi province, China
| | - Xiao Zhang
- Department of Neurology, Xijing Hospital, Fourth Military Medical University, No. 15 Changle West Street, Xi'an, 710032, Shaanxi province, China
| | - Fang Yang
- Department of Neurology, Xijing Hospital, Fourth Military Medical University, No. 15 Changle West Street, Xi'an, 710032, Shaanxi province, China
| | - Xiaodan Shi
- Department of Neurology, Xijing Hospital, Fourth Military Medical University, No. 15 Changle West Street, Xi'an, 710032, Shaanxi province, China
| | - Xuan Wang
- Department of Neurology, Xijing Hospital, Fourth Military Medical University, No. 15 Changle West Street, Xi'an, 710032, Shaanxi province, China
| | - Rong Chen
- Department of Neurology, Xijing Hospital, Fourth Military Medical University, No. 15 Changle West Street, Xi'an, 710032, Shaanxi province, China
| | - Fang Du
- Department of Neurology, Xijing Hospital, Fourth Military Medical University, No. 15 Changle West Street, Xi'an, 710032, Shaanxi province, China
| | - Ming Shi
- Department of Neurology, Xijing Hospital, Fourth Military Medical University, No. 15 Changle West Street, Xi'an, 710032, Shaanxi province, China.
| | - Wen Jiang
- Department of Neurology, Xijing Hospital, Fourth Military Medical University, No. 15 Changle West Street, Xi'an, 710032, Shaanxi province, China.
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9
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Gaddam RR, Dhuri K, Kim YR, Jacobs JS, Kumar V, Li Q, Irani K, Bahal R, Vikram A. γ Peptide Nucleic Acid-Based miR-122 Inhibition Rescues Vascular Endothelial Dysfunction in Mice Fed a High-Fat Diet. J Med Chem 2022; 65:3332-3342. [PMID: 35133835 PMCID: PMC8883473 DOI: 10.1021/acs.jmedchem.1c01831] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
![]()
The blood levels
of microRNA-122 (miR-122) is associated with the
severity of cardiovascular disorders, and targeting it with efficient
and safer miR inhibitors could be a promising approach. Here, we report
the generation of a γ-peptide nucleic acid (γPNA)-based
miR-122 inhibitor (γP-122-I) that rescues vascular endothelial
dysfunction in mice fed a high-fat diet. We synthesized diethylene
glycol-containing γP-122-I and found that its systemic administration
counteracted high-fat diet (HFD)-feeding-associated increase in blood
and aortic miR-122 levels, impaired endothelial function, and reduced
glycemic control. A comprehensive safety analysis established that
γP-122-I affects neither the complete blood count nor biochemical
tests of liver and kidney functions during acute exposure. In addition,
long-term exposure to γP-122-I did not change the overall adiposity,
or histology of the kidney, liver, and heart. Thus, γP-122-I
rescues endothelial dysfunction without any evidence of toxicity in vivo and demonstrates the suitability of γPNA technology
in generating efficient and safer miR inhibitors.
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Affiliation(s)
- Ravinder Reddy Gaddam
- Department of Internal Medicine, Carver College of Medicine University of Iowa, Iowa City, Iowa 52242, United States
| | - Karishma Dhuri
- Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut 06269, United States
| | - Young-Rae Kim
- Department of Internal Medicine, Carver College of Medicine University of Iowa, Iowa City, Iowa 52242, United States
| | - Julia S Jacobs
- Department of Internal Medicine, Carver College of Medicine University of Iowa, Iowa City, Iowa 52242, United States
| | - Vikas Kumar
- Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut 06269, United States
| | - Qiuxia Li
- Department of Internal Medicine, Carver College of Medicine University of Iowa, Iowa City, Iowa 52242, United States
| | - Kaikobad Irani
- Department of Internal Medicine, Carver College of Medicine University of Iowa, Iowa City, Iowa 52242, United States
| | - Raman Bahal
- Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut 06269, United States
| | - Ajit Vikram
- Department of Internal Medicine, Carver College of Medicine University of Iowa, Iowa City, Iowa 52242, United States
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10
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Marti-Aguado D, Fernández-Patón M, Alfaro-Cervello C, Mestre-Alagarda C, Bauza M, Gallen-Peris A, Merino V, Benlloch S, Pérez-Rojas J, Ferrández A, Puglia V, Gimeno-Torres M, Aguilera V, Monton C, Escudero-García D, Alberich-Bayarri Á, Serra MA, Marti-Bonmati L. Digital Pathology Enables Automated and Quantitative Assessment of Inflammatory Activity in Patients with Chronic Liver Disease. Biomolecules 2021; 11:1808. [PMID: 34944452 PMCID: PMC8699191 DOI: 10.3390/biom11121808] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 11/22/2021] [Accepted: 11/29/2021] [Indexed: 12/12/2022] Open
Abstract
Traditional histological evaluation for grading liver disease severity is based on subjective and semi-quantitative scores. We examined the relationship between digital pathology analysis and corresponding scoring systems for the assessment of hepatic necroinflammatory activity. A prospective, multicenter study including 156 patients with chronic liver disease (74% nonalcoholic fatty liver disease-NAFLD, 26% chronic hepatitis-CH etiologies) was performed. Inflammation was graded according to the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network system and METAVIR score. Whole-slide digital image analysis based on quantitative (I-score: inflammation ratio) and morphometric (C-score: proportionate area of staining intensities clusters) measurements were independently performed. Our data show that I-scores and C-scores increase with inflammation grades (p < 0.001). High correlation was seen for CH (ρ = 0.85-0.88), but only moderate for NAFLD (ρ = 0.5-0.53). I-score (p = 0.008) and C-score (p = 0.002) were higher for CH than NAFLD. Our MATLAB algorithm performed better than QuPath software for the diagnosis of low-moderate inflammation (p < 0.05). C-score AUC for classifying NASH was 0.75 (95%CI, 0.65-0.84) and for moderate/severe CH was 0.99 (95%CI, 0.97-1.00). Digital pathology measurements increased with fibrosis stages (p < 0.001). In conclusion, quantitative and morphometric metrics of inflammatory burden obtained by digital pathology correlate well with pathologists' scores, showing a higher accuracy for the evaluation of CH than NAFLD.
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Affiliation(s)
- David Marti-Aguado
- Digestive Disease Department, Clinic University Hospital, INCLIVA Health Research Institute, 46010 Valencia, Spain; (V.M.); (C.M.); (D.E.-G.)
- Biomedical Imaging Research Group (GIBI230), La Fe Health Research Institute, 46026 Valencia, Spain; (M.F.-P.); (Á.A.-B.); (L.M.-B.)
| | - Matías Fernández-Patón
- Biomedical Imaging Research Group (GIBI230), La Fe Health Research Institute, 46026 Valencia, Spain; (M.F.-P.); (Á.A.-B.); (L.M.-B.)
| | - Clara Alfaro-Cervello
- Pathology Department, Clinic University Hospital, INCLIVA Health Research Institute, 46010 Valencia, Spain; (C.A.-C.); (C.M.-A.); (A.F.)
- Faculty of Medicine, University of Valencia, 46010 Valencia, Spain;
| | - Claudia Mestre-Alagarda
- Pathology Department, Clinic University Hospital, INCLIVA Health Research Institute, 46010 Valencia, Spain; (C.A.-C.); (C.M.-A.); (A.F.)
| | - Mónica Bauza
- Pathology Department, La Fe University and Polytechnic Hospital, 46026 Valencia, Spain; (M.B.); (J.P.-R.)
| | - Ana Gallen-Peris
- Digestive Disease Department, Hospital Arnau de Vilanova, 46015 Valencia, Spain; (A.G.-P.); (S.B.)
| | - Víctor Merino
- Digestive Disease Department, Clinic University Hospital, INCLIVA Health Research Institute, 46010 Valencia, Spain; (V.M.); (C.M.); (D.E.-G.)
| | - Salvador Benlloch
- Digestive Disease Department, Hospital Arnau de Vilanova, 46015 Valencia, Spain; (A.G.-P.); (S.B.)
- CIBERehd, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, 28029 Madrid, Spain;
| | - Judith Pérez-Rojas
- Pathology Department, La Fe University and Polytechnic Hospital, 46026 Valencia, Spain; (M.B.); (J.P.-R.)
| | - Antonio Ferrández
- Pathology Department, Clinic University Hospital, INCLIVA Health Research Institute, 46010 Valencia, Spain; (C.A.-C.); (C.M.-A.); (A.F.)
- Faculty of Medicine, University of Valencia, 46010 Valencia, Spain;
| | - Víctor Puglia
- Pathology Department, Hospital Arnau de Vilanova, 46015 Valencia, Spain;
| | - Marta Gimeno-Torres
- Hepatology and Liver Transplantation Unit, La Fe University and Polytechnic Hospital, 46026 Valencia, Spain;
| | - Victoria Aguilera
- CIBERehd, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, 28029 Madrid, Spain;
- Hepatology and Liver Transplantation Unit, La Fe University and Polytechnic Hospital, 46026 Valencia, Spain;
| | - Cristina Monton
- Digestive Disease Department, Clinic University Hospital, INCLIVA Health Research Institute, 46010 Valencia, Spain; (V.M.); (C.M.); (D.E.-G.)
| | - Desamparados Escudero-García
- Digestive Disease Department, Clinic University Hospital, INCLIVA Health Research Institute, 46010 Valencia, Spain; (V.M.); (C.M.); (D.E.-G.)
- Faculty of Medicine, University of Valencia, 46010 Valencia, Spain;
| | - Ángel Alberich-Bayarri
- Biomedical Imaging Research Group (GIBI230), La Fe Health Research Institute, 46026 Valencia, Spain; (M.F.-P.); (Á.A.-B.); (L.M.-B.)
- Quantitative Imaging Biomarkers in Medicine, QUIBIM SL, 46021 Valencia, Spain
| | - Miguel A. Serra
- Faculty of Medicine, University of Valencia, 46010 Valencia, Spain;
| | - Luis Marti-Bonmati
- Biomedical Imaging Research Group (GIBI230), La Fe Health Research Institute, 46026 Valencia, Spain; (M.F.-P.); (Á.A.-B.); (L.M.-B.)
- Radiology Department, La Fe University and Polytechnic Hospital, 46026 Valencia, Spain
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11
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Wong SK, Chin KY, Ima-Nirwana S. A review on the molecular basis underlying the protective effects of Andrographis paniculata and andrographolide against myocardial injury. Drug Des Devel Ther 2021; 15:4615-4632. [PMID: 34785890 PMCID: PMC8591231 DOI: 10.2147/dddt.s331027] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Accepted: 11/02/2021] [Indexed: 12/23/2022] Open
Abstract
Andrographolide is the major compound found in the medicinal plant, Andrographis paniculata (Burm.f.) Nees, which accounts for its medicinal properties. Both the plant extract and compound have been reported to exhibit potential cardiovascular activities. This review summarises related studies describing the biological activities and target mechanisms of A. paniculata and andrographolide in vivo and in vitro. The current evidence unambiguously indicated the protective effects provided by A. paniculata and andrographolide administration against myocardial injury. The intervention ameliorates the symptoms of myocardial injury by interfering with the inductive phase of a) inflammatory response mediated by nuclear factor-kappa B (NF-κB), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) signalling molecules; b) oxidative stress via activation of nuclear factor erythroid 2-related factor (Nrf-2) and reduction of enzymes responsible for generating reactive oxygen and nitrogen species; c) intrinsic and extrinsic mechanisms in apoptosis regulated by upstream insulin-like growth factor-1 receptor (IGF-1R) and peroxisome proliferator-activated receptor-alpha (PPAR-α); d) profibrotic growth factors thus reducing cardiac fibrosis, improving endothelial function and fibrinolytic function. In conclusion, A. paniculata and andrographolide possess therapeutic potential in the management of myocardial injury, which requires further validation in human clinical trials.
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Affiliation(s)
- Sok Kuan Wong
- Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, 56000, Malaysia
| | - Kok-Yong Chin
- Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, 56000, Malaysia
| | - Soelaiman Ima-Nirwana
- Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, 56000, Malaysia
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12
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Patel AM, Liu YS, Davies SP, Brown RM, Kelly DA, Scheel-Toellner D, Reynolds GM, Stamataki Z. The Role of B Cells in Adult and Paediatric Liver Injury. Front Immunol 2021; 12:729143. [PMID: 34630404 PMCID: PMC8495195 DOI: 10.3389/fimmu.2021.729143] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 08/16/2021] [Indexed: 12/16/2022] Open
Abstract
B lymphocytes are multitasking cells that direct the immune response by producing pro- or anti-inflammatory cytokines, by presenting processed antigen for T cell activation and co-stimulation, and by turning into antibody-secreting cells. These functions are important to control infection in the liver but can also exacerbate tissue damage and fibrosis as part of persistent inflammation that can lead to end stage disease requiring a transplant. In transplantation, immunosuppression increases the incidence of lymphoma and often this is of B cell origin. In this review we bring together information on liver B cell biology from different liver diseases, including alcohol-related and metabolic fatty liver disease, autoimmune hepatitis, primary biliary and primary sclerosing cholangitis, viral hepatitis and, in infants, biliary atresia. We also discuss the impact of B cell depletion therapy in the liver setting. Taken together, our analysis shows that B cells are important in the pathogenesis of liver diseases and that further research is necessary to fully characterise the human liver B cell compartment.
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Affiliation(s)
- Arzoo M. Patel
- Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
| | - Yuxin S. Liu
- Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
- Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom
| | - Scott P. Davies
- Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
| | - Rachel M. Brown
- Department of Histopathology, Queen Elizabeth Hospital, Birmingham Women’s and Children’s National Health Service (NHS) Foundation Trust, Birmingham, United Kingdom
| | - Deirdre A. Kelly
- The Liver Unit, Birmingham Women’s and Children’s Hospital and the University of Birmingham, Birmingham, United Kingdom
| | - Dagmar Scheel-Toellner
- Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom
| | - Gary M. Reynolds
- Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
- The Liver Unit, Birmingham Women’s and Children’s Hospital and the University of Birmingham, Birmingham, United Kingdom
| | - Zania Stamataki
- Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
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13
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Milosevic I, Russo E, Vujovic A, Barac A, Stevanovic O, Gitto S, Amedei A. Microbiota and viral hepatitis: State of the art of a complex matter. World J Gastroenterol 2021; 27:5488-5501. [PMID: 34588747 PMCID: PMC8433613 DOI: 10.3748/wjg.v27.i33.5488] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 03/26/2021] [Accepted: 07/21/2021] [Indexed: 02/06/2023] Open
Abstract
Changes in gut microbiota influence both the gut and liver, which are strictly connected by the so-called "gut-liver axis". The gut microbiota acts as a major determinant of this relationship in the onset and clinical course of liver diseases. According to the results of several studies, gut dysbiosis is linked to viral hepatitis, mainly hepatitis C virus and hepatitis B virus infection. Gut bacteria-derived metabolites and cellular components are key molecules that affect liver function and modulate the pathology of viral hepatitis. Recent studies showed that the gut microbiota produces various molecules, such as peptidoglycans, lipopolysaccharides, DNA, lipoteichoic acid, indole-derivatives, bile acids, and trimethylamine, which are translocated to the liver and interact with liver immune cells causing pathological effects. Therefore, the existence of crosstalk between the gut microbiota and the liver and its implications on host health and pathologic status are essential factors impacting the etiology and therapeutic approach. Concrete mechanisms behind the pathogenic role of gut-derived components on the pathogenesis of viral hepatitis remain unclear and not understood. In this review, we discuss the current findings of research on the bidirectional relationship of the components of gut microbiota and the progression of liver diseases and viral hepatitis and vice versa. Moreover, this paper highlights the current therapeutic and preventive strategies, such as fecal transplantation, used to restore the gut microbiota composition and so improve host health.
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Affiliation(s)
- Ivana Milosevic
- Clinic for Infectious and Tropical Diseases, Clinical Centre of Serbia Faculty of Medicine, University of Belgrade, Belgrade 101801, Serbia
| | - Edda Russo
- Department of Experimental and Clinical Medicine, University of Florence, Firenze 50100, Italy
| | - Ankica Vujovic
- Clinic for Infectious and Tropical Diseases, Clinical Centre of Serbia Faculty of Medicine, University of Belgrade, Belgrade 101801, Serbia
| | - Aleksandra Barac
- Clinic for Infectious and Tropical Diseases, Clinical Centre of Serbia Faculty of Medicine, University of Belgrade, Belgrade 101801, Serbia
| | - Olja Stevanovic
- Clinic for Infectious and Tropical Diseases, Clinical Centre of Serbia Faculty of Medicine, University of Belgrade, Belgrade 101801, Serbia
| | - Stefano Gitto
- Department of Experimental and Clinical Medicine, University of Florence, Firenze 50100, Italy
| | - Amedeo Amedei
- Department of Experimental and Clinical Medicine, University of Florence, Firenze 50100, Italy
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14
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Kang K, Sun Y, Pan D, Sang LX, Sun MJ, Li YL, Chang B. Distinctive gut microbial dysbiosis between chronic alcoholic fatty liver disease and metabolic-associated fatty liver disease in mice. Exp Ther Med 2021; 21:418. [PMID: 33777186 PMCID: PMC7967804 DOI: 10.3892/etm.2021.9862] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Accepted: 01/18/2021] [Indexed: 02/06/2023] Open
Abstract
The gut microbiota, which may affect normal physiological and biochemical functions, has an important role in the development of human liver diseases. The aim of the present study was to investigate differences in the gut microbiota between chronic alcoholic fatty liver disease (AFLD) and metabolic-associated fatty liver disease (MAFLD). AFLD was induced by chronic alcohol administration and MAFLD was induced by a Western-style diet in C57BL/6 mice. After 8 weeks, the levels of plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (TC), lipopolysaccharide (LPS), tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β and IL-10 were assessed and H&E staining of mouse liver tissue was performed. High-throughput sequencing of 16S ribosomal DNA from the intestinal contents was used to analyze the different effects of AFLD and MAFLD on the gut microbiota. Differences in the gut microbiota composition were assessed by the t-test. The results revealed increases in LPS, ALT, AST, TG, IL-1β and TNF-α in the AFLD group. Compared with those in the MAFLD control group, the MAFLD group exhibited increased plasma ALT, TG, TC, IL-6, IL-1β and TNF-α levels and decreased plasma IL-10 levels. In addition, the α- and β-diversities revealed that the AFLD and MAFLD groups exhibited obvious changes in the gut structure (with an increase in abundance in the AFLD group and a decrease in abundance in the MAFLD group). In comparison to the AFLD control group, Enterococcaceae were the most abundant bacteria at the family level and Enterococcus and Streptococcus were the most abundant bacteria at the genus level in the AFLD group. However, in the MAFLD group, Lachnospiraceae was the most abundant at the family level, with increases in Erysipelatoclostridium, Gordonibacter and Streptococcus at the genus level and a decrease in the genus Bifidobacterium. In conclusion, the present study confirmed that the AFLD and MAFLD groups harbored differences in the gut microbiota. The marked differences in the gut microbiota at the family and genus levels may contribute to the development process of FLD.
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Affiliation(s)
- Kai Kang
- Department of Gastroenterology, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, P.R. China
| | - Yue Sun
- Department of Gastroenterology, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, P.R. China
| | - Dan Pan
- Department of Geriatrics, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, P.R. China
| | - Li-Xuan Sang
- Department of Geriatrics, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, P.R. China
| | - Ming-Jun Sun
- Department of Gastroenterology, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, P.R. China
| | - Yi-Ling Li
- Department of Gastroenterology, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, P.R. China
| | - Bing Chang
- Department of Gastroenterology, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, P.R. China
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15
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Jia W, Rajani C, Xu H, Zheng X. Gut microbiota alterations are distinct for primary colorectal cancer and hepatocellular carcinoma. Protein Cell 2020; 12:374-393. [PMID: 32797354 PMCID: PMC8106555 DOI: 10.1007/s13238-020-00748-0] [Citation(s) in RCA: 56] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Accepted: 06/15/2020] [Indexed: 12/12/2022] Open
Abstract
Colorectal cancer (CRC) and hepatocellular carcinoma (HCC) are the second and third most common causes of death by cancer, respectively. The etiologies of the two cancers are either infectious insult or due to chronic use of alcohol, smoking, diet, obesity and diabetes. Pathological changes in the composition of the gut microbiota that lead to intestinal inflammation are a common factor for both HCC and CRC. However, the gut microbiota of the cancer patient evolves with disease pathogenesis in unique ways that are affected by etiologies and environmental factors. In this review, we examine the changes that occur in the composition of the gut microbiota across the stages of the HCC and CRC. Based on the idea that the gut microbiota are an additional "lifeline" and contribute to the tumor microenvironment, we can observe from previously published literature how the microbiota can cause a shift in the balance from normal → inflammation → diminished inflammation from early to later disease stages. This pattern leads to the hypothesis that tumor survival depends on a less pro-inflammatory tumor microenvironment. The differences observed in the gut microbiota composition between different disease etiologies as well as between HCC and CRC suggest that the tumor microenvironment is unique for each case.
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Affiliation(s)
- Wei Jia
- Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China. .,Hong Kong Tranditional Chinese Medicine Phenome Research Center, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, 999077, Hong Kong, China.
| | - Cynthia Rajani
- University of Hawaii Cancer Center, Honolulu, HI, 96813, USA
| | - Hongxi Xu
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Xiaojiao Zheng
- Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
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16
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Schwenger KJ, Clermont-Dejean N, Allard JP. The role of the gut microbiome in chronic liver disease: the clinical evidence revised. JHEP Rep 2019; 1:214-226. [PMID: 32039372 PMCID: PMC7001555 DOI: 10.1016/j.jhepr.2019.04.004] [Citation(s) in RCA: 95] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Revised: 04/08/2019] [Accepted: 04/27/2019] [Indexed: 02/07/2023] Open
Abstract
Recent research has suggested a role for the intestinal microbiota in the pathogenesis and potential treatment of a wide range of liver diseases. The intestinal microbiota and bacterial products may contribute to the development of liver diseases through multiple mechanisms including increased intestinal permeability, chronic systemic inflammation, production of short-chain fatty acids and changes in metabolism. This suggests a potential role for pre-, pro- and synbiotic products in the prevention or treatment of some liver diseases. In addition, there is emerging evidence on the effects of faecal microbial transplant. Herein, we discuss the relationship between the intestinal microbiota and liver diseases, as well as reviewing intestinal microbiota-based treatment options that are currently being investigated.
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Affiliation(s)
- Katherine Jp Schwenger
- Toronto General Hospital, University Health Network, Toronto, Canada.,Department of Medicine, University of Toronto, Toronto, Canada
| | | | - Johane P Allard
- Toronto General Hospital, University Health Network, Toronto, Canada.,Department of Medicine, University of Toronto, Toronto, Canada.,Department of Nutritional Sciences, University of Toronto, Toronto, Canada
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