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Wang N, Xu Y, Yang G, Chen H, Wang X, Fu J, Li L, Pan X. The Impact of Proton Pump Inhibitors on the Efficacy of Immune Checkpoint Inhibitor Combinations in Patients with HBV-Associated Advanced Hepatocellular Carcinoma. J Hepatocell Carcinoma 2024; 11:1311-1321. [PMID: 38979082 PMCID: PMC11230117 DOI: 10.2147/jhc.s464033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Accepted: 06/19/2024] [Indexed: 07/10/2024] Open
Abstract
Purpose There is limited research on whether Proton Pump Inhibitors (PPIs) will affect the efficacy of immune checkpoint inhibitors (ICIs) in treating hepatocellular carcinoma (HCC).This study aimed to determine whether PPIs affect the survival outcomes of patients with HBV-associated advanced HCC receiving combination therapy based on ICIs. Methods We retrospectively analyzed patients with hepatitis B virus (HBV)-associated advanced HCC who underwent ICIs combination therapy from January 1, 2020, to December 30, 2022. Patients were stratified into PPI and non-PPI groups based on whether they received PPI treatment within 30 days before or after ICIs therapy. Patients' survival and the risk of PPI-associated mortality was assessed. Adverse events were also evaluated. Results A total of 183 patients with HBV-associated HCC treated with ICI combination therapy were included. The median survival time (12.5 months vs 13.7 months, P = 0.285) and incidence of adverse events (P = 0.729) did not significantly differ between the PPI and non-PPI groups. Even after propensity score matching, the difference in median overall survival (OS) between the two groups was not significant (10.7 months vs 11.4 months; P = 0.596) and the patient's OS is not significantly related to the dosage of PPI application (P > 0.05).However, according to our subgroup analysis, among HCC patients with a serum HBV DNA concentration ≥ 200 IU/mL, the use of PPIs significantly increased the risk of mortality in patients receiving ICI combination therapy (P = 0.024). Conclusion PPIs do not notably influence the survival prognosis of patients receiving ICI combination therapy for HBV-associated advanced HCC. However, among patients with high levels of HBV DNA, PPIs increase the risk of mortality. Therefore, antiviral therapy should be intensified in the patients with HBVDNA > 200 IU/mL. Additionally, PPIs do not impact the incidence of adverse reactions in these patients.
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Affiliation(s)
- Ningning Wang
- Department of Infectious Disease, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, People's Republic of China
| | - Yuanyuan Xu
- Department of Infectious Disease, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, People's Republic of China
| | - Guangde Yang
- Department of Infectious Disease, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, People's Republic of China
| | - He Chen
- Department of Infectious Disease, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, People's Republic of China
| | - Xia Wang
- Department of Infectious Disease, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, People's Republic of China
| | - Juanjuan Fu
- Department of Infectious Disease, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, People's Republic of China
| | - Li Li
- Department of Infectious Disease, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, People's Republic of China
| | - Xiucheng Pan
- Department of Infectious Disease, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, People's Republic of China
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Qian J, Zheng W, Fang J, Cheng S, Zhang Y, Zhuang X, Song C. Causal relationships of gut microbiota, plasma metabolites, and metabolite ratios with diffuse large B-cell lymphoma: a Mendelian randomization study. Front Microbiol 2024; 15:1356437. [PMID: 38860219 PMCID: PMC11163048 DOI: 10.3389/fmicb.2024.1356437] [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: 12/15/2023] [Accepted: 05/08/2024] [Indexed: 06/12/2024] Open
Abstract
Background Recent studies have revealed changes in microbiota constitution and metabolites associated with tumor progression, however, no causal relation between microbiota or metabolites and diffuse large B-cell lymphoma (DLBCL) has yet been reported. Methods We download a microbiota dataset from the MiBioGen study, a metabolites dataset from the Canadian Longitudinal Study on Aging (CLSA) study, and a DLBCL dataset from Integrative Epidemiology Unit Open genome-wide association study (GWAS) project. Mendelian randomization (MR) analysis was conducted using the R packages, TwoSampleMR and MR-PRESSO. Five MR methods were used: MR-Egger, inverse variance weighting (IVW), weighted median, simple mode, and weighted mode. Reverse MR analyses were also conducted to explore the causal effects of DLBCL on the microbiome, metabolites, and metabolite ratios. Pleiotropy was evaluated by MR Egger regression and MR-PRESSO global analyses, heterogeneity was assessed by Cochran's Q-test, and stability analyzed using the leave-one-out method. Results 119 microorganisms, 1,091 plasma metabolite, and 309 metabolite ratios were analyzed. According to IVW analysis, five microorganisms were associated with risk of DLBCL. The genera Terrisporobacter (OR: 3.431, p = 0.049) andgenera Oscillibacter (OR: 2.406, p = 0.029) were associated with higher risk of DLBCL. Further, 27 plasma metabolites were identified as having a significant causal relationships with DLBCL, among which citrate levels had the most significant protective causal effect against DLBCL (p = 0.006), while glycosyl-N-tricosanoyl-sphingadienine levels was related to higher risk of DLBCL (p = 0.003). In addition, we identified 19 metabolite ratios with significant causal relationships to DLBCL, of which taurine/glutamate ratio had the most significant protective causal effect (p = 0.005), while the phosphoethanolamine/choline ratio was related to higher risk of DLBCL (p = 0.009). Reverse MR analysis did not reveal any significant causal influence of DLBCL on the above microbiota, metabolites, and metabolite ratios (p > 0.05). Sensitivity analyses revealed no significant heterogeneity or pleiotropy (p > 0.05). Conclusion We present the first elucidation of the causal influence of microbiota and metabolites on DLBCL using MR methods, providing novel insights for potential targeting of specific microbiota or metabolites to prevent, assist in diagnosis, and treat DLBCL.
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Affiliation(s)
- Jingrong Qian
- Department of Clinical Laboratory, Shandong Provincial Third Hospital, Shandong University, Jinan, Shandong, China
| | - Wen Zheng
- Department of Clinical Laboratory, Shandong Provincial Third Hospital, Shandong University, Jinan, Shandong, China
| | - Jun Fang
- Department of Medical Engineering, Shandong Provincial Third Hospital, Shandong University, Jinan, Shandong, China
| | - Shiliang Cheng
- Department of Clinical Laboratory, Shandong Provincial Third Hospital, Shandong University, Jinan, Shandong, China
| | - Yanli Zhang
- Department of Clinical Laboratory, Shandong Provincial Third Hospital, Shandong University, Jinan, Shandong, China
| | - Xuewei Zhuang
- Department of Clinical Laboratory, Shandong Provincial Third Hospital, Shandong University, Jinan, Shandong, China
| | - Chao Song
- Department of Administration, Shandong Provincial Third Hospital, Shandong University, Jinan, Shandong, China
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Yu Q, Zhang Y, Zeng W, Sun Y, Zhang X, Guo L, Zhang Y, Yu B, Guo M, Wang Y, Li H, Suo Y, Jiang X, Song L. Buyang Huanwu Decoction Alleviates Atherosclerosis by Regulating gut Microbiome and Metabolites in Apolipoprotein E-deficient Mice fed with High-fat Diet. JOURNAL OF PHYSIOLOGICAL INVESTIGATION 2024; 67:88-102. [PMID: 38780293 DOI: 10.4103/ejpi.ejpi-d-23-00031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Accepted: 01/25/2024] [Indexed: 05/25/2024]
Abstract
ABSTRACT The traditional Chinese herbal prescription Buyang Huanwu decoction (BHD), effectively treats atherosclerosis. However, the mechanism of BHD in atherosclerosis remains unclear. We aimed to determine whether BHD could alleviate atherosclerosis by altering the microbiome-associated metabolic changes in atherosclerotic mice. An atherosclerotic model was established in apolipoprotein E-deficient mice fed high-fat diet, and BHD was administered through gavage for 12 weeks at 8.4 g/kg/d and 16.8 g/kg/d. The atherosclerotic plaque size, composition, serum lipid profile, and inflammatory cytokines, were assessed. Mechanistically, metabolomic and microbiota profiles were analyzed by liquid chromatography-mass spectrometry and 16S rRNA gene sequencing, respectively. Furthermore, intestinal microbiota and atherosclerosis-related metabolic parameters were correlated using Spearman analysis. Atherosclerotic mice treated with BHD exhibited reduced plaque area, aortic lumen occlusion, and lipid accumulation in the aortic root. Nine perturbed serum metabolites were significantly restored along with the relative abundance of microbiota at the family and genus levels but not at the phylum level. Gut microbiome improvement was strongly negatively correlated with improved metabolite levels. BHD treatment effectively slows the progression of atherosclerosis by regulating altered intestinal microbiota and perturbed metabolites.
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Affiliation(s)
- Qun Yu
- School of Preclinical Medicine, Zunyi Medical University, Zunyi, Guizhou Province, China
| | - Yilin Zhang
- School of Integrated Chinese and Western Medicine, Tianjin University of Traditional Chinese Medicine, Jinghai, Tianjin, China
| | - Wenyun Zeng
- Oncology, Ganzhou People's Hospital, Ganzhou, China
| | - Yingxin Sun
- School of Faculty of Health and Exercise Science, Tianjin University of Sport, Tianjin, China
| | - Xiaolu Zhang
- School of Integrated Chinese and Western Medicine, Tianjin University of Traditional Chinese Medicine, Jinghai, Tianjin, China
| | - Lin Guo
- School of Integrated Chinese and Western Medicine, Tianjin University of Traditional Chinese Medicine, Jinghai, Tianjin, China
| | - Yue Zhang
- School of Integrated Chinese and Western Medicine, Tianjin University of Traditional Chinese Medicine, Jinghai, Tianjin, China
| | - Bin Yu
- School of Integrated Chinese and Western Medicine, Tianjin University of Traditional Chinese Medicine, Jinghai, Tianjin, China
| | - Maojuan Guo
- School of Integrated Chinese and Western Medicine, Tianjin University of Traditional Chinese Medicine, Jinghai, Tianjin, China
| | - Yu Wang
- School of Integrated Chinese and Western Medicine, Tianjin University of Traditional Chinese Medicine, Jinghai, Tianjin, China
| | - Huhu Li
- School of Integrated Chinese and Western Medicine, Tianjin University of Traditional Chinese Medicine, Jinghai, Tianjin, China
| | - Yanrong Suo
- Oncology, Ganzhou People's Hospital, Ganzhou, China
| | - Xijuan Jiang
- School of Integrated Chinese and Western Medicine, Tianjin University of Traditional Chinese Medicine, Jinghai, Tianjin, China
| | - Lili Song
- School of Integrated Chinese and Western Medicine, Tianjin University of Traditional Chinese Medicine, Jinghai, Tianjin, China
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Huang P, Gao J, Du J, Nie Z, Li Q, Sun Y, Xu G, Cao L. Prometryn exposure disrupts the intestinal health of Eriocheir sinensis: Physiological responses and underlying mechanism. Comp Biochem Physiol C Toxicol Pharmacol 2024; 277:109820. [PMID: 38145793 DOI: 10.1016/j.cbpc.2023.109820] [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: 10/02/2023] [Revised: 11/26/2023] [Accepted: 12/14/2023] [Indexed: 12/27/2023]
Abstract
Most toxicity studies of prometryn in non-target aquatic animals have focused on hepatotoxicity, cardiotoxicity, embryonic developmental and growth toxicity, while studies on the molecular mechanisms of intestinal toxicity of prometryn are still unknown. In the current study, the intestinal tissues of the Chinese mitten crab (Eriocheir sinensis) were used to uncover the underlying molecular mechanisms of stress by 96-h acute in vivo exposure to prometryn. The results showed that prometryn activated the Nrf2-Keap1 pathway and up-regulated the expression of downstream antioxidant genes. Prometryn induced the expression of genes associated with non-specific immunity and autophagy, and induced apoptosis through the MAPK pathway. Interestingly, the significant up-or down-regulation of the above genes mainly occurred at 12 h- 24 h after exposure. Intestinal flora sequencing revealed that prometryn disrupted the intestinal normal barrier function mainly by reducing beneficial bacteria abundance, which further weakened the intestinal resistance to exogenous toxicants and caused an inflammatory response. Correlation analyses found that differential flora at the genus level had potential associations with gut stress-related genes. In conclusion, our study contributes to understanding the molecular mechanisms behind the intestinal stress caused by herbicides on aquatic crustaceans.
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Affiliation(s)
- Peng Huang
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi 214081, China
| | - Jiancao Gao
- Key Laboratory of Integrated Rice-Fish Farming Ecology, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China
| | - Jinliang Du
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi 214081, China; Key Laboratory of Integrated Rice-Fish Farming Ecology, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China
| | - Zhijuan Nie
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi 214081, China; Key Laboratory of Integrated Rice-Fish Farming Ecology, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China
| | - Quanjie Li
- Key Laboratory of Integrated Rice-Fish Farming Ecology, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China
| | - Yi Sun
- Key Laboratory of Integrated Rice-Fish Farming Ecology, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China
| | - Gangchun Xu
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi 214081, China; Key Laboratory of Integrated Rice-Fish Farming Ecology, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China.
| | - Liping Cao
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi 214081, China; Key Laboratory of Integrated Rice-Fish Farming Ecology, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China.
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Kim HN, Cheong HS, Kim B, Sohn W, Cho YK, Kwon MJ, Kim J, Song Y, Joo EJ. Human gut microbiota from hepatitis B virus-infected individuals is associated with reduced triglyceride level in mice: faecal transplantation study. Microbes Infect 2024; 26:105281. [PMID: 38128750 DOI: 10.1016/j.micinf.2023.105281] [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: 03/12/2023] [Revised: 12/09/2023] [Accepted: 12/18/2023] [Indexed: 12/23/2023]
Abstract
BACKGROUND AND AIMS Chronic hepatitis B virus (HBV) infection is associated with a reduced risk of dyslipidaemia. Using a human faecal microbiota transplantation (FMT), we compared changes in gut microbiota and lipid profiles in mice transplanted with human faeces from HBV-infected and non-infected individuals. APPROACH AND RESULTS A total of 19 mice received human FMT from four HBV-infected individuals and were categorised into the HBV-positive mice group, while 20 mice received FMT from four HBV-non-infected individuals into the HBV-negative one. In the analysis of gut microbiota in FMT mice, we observed a robust increase in alpha diversity and abundance of Akkermansia muciniphila in HBV-positive mice, compared to that in HBV-negative. Functional inference analysis revealed that the pathways involved in glycerolipid metabolism were more enriched in HBV-positive mice. At 5 weeks of FMT, the reduced triglyceride (TG) level was predominantly observed in HBV-positive mice. CONCLUSIONS Altered gut microbiota accompanied by HBV infection was associated with a robust increase in alpha diversity and butyrate producers, which resulted in a reduced level of TG at 5 weeks post-FMT. This indicates that the reduced risk of dyslipidaemia in chronic HBV infection may be due to the altered gut microbiota accompanied by HBV infection.
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Affiliation(s)
- Han-Na Kim
- Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, 115 Irwon-ro, Gangnam-gu, Seoul 06355, Republic of Korea; Biomedical Statistics Center, Research Institute for Future Medicine, Samsung Medical Center, Gangnam-gu, Seoul 06351, Republic of Korea
| | - Hae Suk Cheong
- Division of Infectious Diseases, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul 03181, Republic of Korea
| | - Bomi Kim
- Division of Infectious Diseases, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul 03181, Republic of Korea
| | - Won Sohn
- Division of Gastroenterology and Hepatology, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul 03181, Republic of Korea
| | - Yong Kyun Cho
- Division of Gastroenterology and Hepatology, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul 03181, Republic of Korea
| | - Min-Jung Kwon
- Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul 03181, Republic of Korea
| | - Juhee Kim
- Medical Research Institute, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul 03181, Republic of Korea
| | - Youngmi Song
- Medical Research Institute, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul 03181, Republic of Korea.
| | - Eun-Jeong Joo
- Division of Infectious Diseases, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul 03181, Republic of Korea.
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Kouroumalis E, Tsomidis I, Voumvouraki A. Viral Liver Disease and Intestinal Gut–Liver Axis. GASTROINTESTINAL DISORDERS 2024; 6:64-93. [DOI: 10.3390/gidisord6010005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
The intestinal microbiota is closely related to liver diseases via the intestinal barrier and bile secretion to the gut. Impairment of the barrier can translocate microbes or their components to the liver where they can contribute to liver damage and fibrosis. The components of the barrier are discussed in this review along with the other elements of the so-called gut–liver axis. This bidirectional relation has been widely studied in alcoholic and non-alcoholic liver disease. However, the involvement of microbiota in the pathogenesis and treatment of viral liver diseases have not been extensively studied, and controversial data have been published. Therefore, we reviewed data regarding the integrity and function of the intestinal barrier and the changes of the intestinal microbioma that contribute to progression of Hepatitis B (HBV) and Hepatitis C (HCV) infection. Their consequences, such as cirrhosis and hepatic encephalopathy, were also discussed in connection with therapeutic interventions such as the effects of antiviral eradication and the use of probiotics that may influence the outcome of liver disease. Profound alterations of the microbioma with significant reduction in microbial diversity and changes in the abundance of both beneficial and pathogenic bacteria were found.
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Affiliation(s)
- Elias Kouroumalis
- Department of Gastroenterology, Medical School, University of Crete, 71500 Heraklion, Greece
| | - Ioannis Tsomidis
- Department of Gastroenterology, Medical School, University of Crete, 71500 Heraklion, Greece
| | - Argyro Voumvouraki
- 1st Department of Internal Medicine, AHEPA University Hospital, 54621 Thessaloniki, Greece
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Magdy Wasfy R, Mbaye B, Borentain P, Tidjani Alou M, Murillo Ruiz ML, Caputo A, Andrieu C, Armstrong N, Million M, Gerolami R. Ethanol-Producing Enterocloster bolteae Is Enriched in Chronic Hepatitis B-Associated Gut Dysbiosis: A Case-Control Culturomics Study. Microorganisms 2023; 11:2437. [PMID: 37894093 PMCID: PMC10608849 DOI: 10.3390/microorganisms11102437] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2023] [Revised: 09/25/2023] [Accepted: 09/26/2023] [Indexed: 10/29/2023] Open
Abstract
BACKGROUND Hepatitis B virus (HBV) infection is a global health epidemic that causes fatal complications, leading to liver cirrhosis and hepatocellular carcinoma. The link between HBV-related dysbiosis and specific bacterial taxa is still under investigation. Enterocloster is emerging as a new genus (formerly Clostridium), including Enterocloster bolteae, a gut pathogen previously associated with dysbiosis and human diseases such as autism, multiple sclerosis, and inflammatory bowel diseases. Its role in liver diseases, especially HBV infection, is not reported. METHODS The fecal samples of eight patients with chronic HBV infection and ten healthy individuals were analyzed using the high-throughput culturomics approach and compared to 16S rRNA sequencing. Quantification of ethanol, known for its damaging effect on the liver, produced from bacterial strains enriched in chronic HBV was carried out by gas chromatography-mass spectrometry. RESULTS Using culturomics, 29,120 isolated colonies were analyzed by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-TOF); 340 species were identified (240 species in chronic HBV samples, 254 species in control samples) belonging to 169 genera and 6 phyla. In the chronic HBV group, 65 species were already known in the literature; 48 were associated with humans but had not been previously found in the gut, and 17 had never been associated with humans previously. Six species were newly isolated in our study. By comparing bacterial species frequency, three bacterial genera were serendipitously found with significantly enriched bacterial diversity in patients with chronic HBV: Enterocloster, Clostridium, and Streptococcus (p = 0.0016, p = 0.041, p = 0.053, respectively). However, metagenomics could not identify this enrichment, possibly concerning its insufficient taxonomical resolution (equivocal assignment of operational taxonomic units). At the species level, the significantly enriched species in the chronic HBV group almost all belonged to class Clostridia, such as Clostridium perfringens, Clostridium sporogenes, Enterocloster aldenensis, Enterocloster bolteae, Enterocloster clostridioformis, and Clostridium innocuum. Two E. bolteae strains, isolated from two patients with chronic HBV infection, showed high ethanol production (27 and 200 mM). CONCLUSIONS Culturomics allowed us to identify Enterocloster species, specifically, E. bolteae, enriched in the gut microbiota of patients with chronic HBV. These species had never been isolated in chronic HBV infection before. Moreover, ethanol production by E. bolteae strains isolated from the chronic HBV group could contribute to liver disease progression. Additionally, culturomics might be critical for better elucidating the relationship between dysbiosis and chronic HBV infection in the future.
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Affiliation(s)
- Reham Magdy Wasfy
- IHU Méditerranée Infection, 13005 Marseille, France (M.T.A.); (C.A.)
- MEPHI, IRD, Aix-Marseille Université, 13005 Marseille, France
| | - Babacar Mbaye
- IHU Méditerranée Infection, 13005 Marseille, France (M.T.A.); (C.A.)
- MEPHI, IRD, Aix-Marseille Université, 13005 Marseille, France
| | - Patrick Borentain
- Unité Hépatologie, Hôpital de la Timone, APHM, 13005 Marseille, France;
- Assistance Publique-Hôpitaux de Marseille (APHM), 13005 Marseille, France
| | - Maryam Tidjani Alou
- IHU Méditerranée Infection, 13005 Marseille, France (M.T.A.); (C.A.)
- MEPHI, IRD, Aix-Marseille Université, 13005 Marseille, France
| | - Maria Leticia Murillo Ruiz
- IHU Méditerranée Infection, 13005 Marseille, France (M.T.A.); (C.A.)
- MEPHI, IRD, Aix-Marseille Université, 13005 Marseille, France
| | - Aurelia Caputo
- IHU Méditerranée Infection, 13005 Marseille, France (M.T.A.); (C.A.)
- Assistance Publique-Hôpitaux de Marseille (APHM), 13005 Marseille, France
| | - Claudia Andrieu
- IHU Méditerranée Infection, 13005 Marseille, France (M.T.A.); (C.A.)
- Assistance Publique-Hôpitaux de Marseille (APHM), 13005 Marseille, France
| | - Nicholas Armstrong
- IHU Méditerranée Infection, 13005 Marseille, France (M.T.A.); (C.A.)
- Assistance Publique-Hôpitaux de Marseille (APHM), 13005 Marseille, France
| | - Matthieu Million
- IHU Méditerranée Infection, 13005 Marseille, France (M.T.A.); (C.A.)
- MEPHI, IRD, Aix-Marseille Université, 13005 Marseille, France
- Assistance Publique-Hôpitaux de Marseille (APHM), 13005 Marseille, France
| | - Rene Gerolami
- IHU Méditerranée Infection, 13005 Marseille, France (M.T.A.); (C.A.)
- MEPHI, IRD, Aix-Marseille Université, 13005 Marseille, France
- Unité Hépatologie, Hôpital de la Timone, APHM, 13005 Marseille, France;
- Assistance Publique-Hôpitaux de Marseille (APHM), 13005 Marseille, France
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Zhang Q, Zhou J, Zhang X, Mao R, Zhang C. Mendelian randomization supports causality between gut microbiota and chronic hepatitis B. Front Microbiol 2023; 14:1243811. [PMID: 37655340 PMCID: PMC10467284 DOI: 10.3389/fmicb.2023.1243811] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Accepted: 08/01/2023] [Indexed: 09/02/2023] Open
Abstract
Background Observational studies have provided evidence of a close association between gut microbiota and the progression of chronic hepatitis B (CHB). However, establishing a causal relationship between gut microbiota and CHB remains a subject of investigation. Methods Genome-wide association study (GWAS) summary data of gut microbiota came from the MiBioGen consortium, while the GWAS summary data of CHB came from the Medical Research Council Integrative Epidemiology Unit (IEU) Open GWAS project. Based on the maximum likelihood (ML), Mendelian randomization (MR)-Egger regression, inverse variance weighted (IVW), MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and weighted-mode and weighted-median methods, we conducted a bidirectional, two-sample, MR analysis to explore the causal relationship between the gut microbiota and CHB. Additionally, we evaluated the genetic associations between individual gut microbes and CHB using the Linkage disequilibrium score regression (LDSC) program. Results According to the IVW method estimates, genetically predicted class Alphaproteobacteria (odds ratio [OR] = 0.57; 95% confidence interval [CI], 0.34-0.96; false discovery rate [FDR] = 0.046), genus Family XIII AD3011 group (OR = 0.60; 95% CI, 0.39-0.91; FDR = 0.026), genus Prevotella 7 (OR = 0.73; 95% CI, 0.56-0.94; FDR = 0.022) exhibited a protective effect against CHB. On the other hand, family Family XIII (OR = 1.79; 95% CI, 1.03-3.12; FDR = 0.061), genus Eggerthella group (OR = 1.34; 95% CI, 1.04-1.74; FDR = 0.043), genus Eubacterium ventriosum group (OR = 1.59; 95% CI, 1.01-2.51; FDR = 0.056), genus Holdemania (OR = 1.35; 95% CI, 1.00-1.82; FDR = 0.049), and genus Ruminococcus gauvreauii group (OR = 1.69; 95% CI, 1.10-2.61; FDR = 0.076) were associated with an increased risk of CHB. The results from LDSC also indicated a significant genetic correlation between most of the aforementioned gut microbiota and CHB. Our reverse MR analysis demonstrated no causal relationship between genetically predicted CHB and gut microbiota, and we observed no significant horizontal pleiotropy or heterogeneity of instrumental variables (IVs). Conclusion In this study, we identified three types of gut microbiota with a protective effect on CHB and five types with an adverse impact on CHB. We postulate that this information will facilitate the clinical prevention and treatment of CHB through fecal microbiota transplantation.
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Affiliation(s)
- Quanzheng Zhang
- Department of Critical Care Medicine, The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan, China
| | - Jinhua Zhou
- Department of Critical Care Medicine, The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan, China
| | - Xiaoxiao Zhang
- West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Rui Mao
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China
| | - Chuan Zhang
- Department of Critical Care Medicine, The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan, China
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Yang X, Mai H, Zhou J, Li Z, Wang Q, Lan L, Lu F, Yang X, Guo B, Ye L, Cui P, Liang H, Huang J. Alterations of the gut microbiota associated with the occurrence and progression of viral hepatitis. Front Cell Infect Microbiol 2023; 13:1119875. [PMID: 37342245 PMCID: PMC10277638 DOI: 10.3389/fcimb.2023.1119875] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Accepted: 05/22/2023] [Indexed: 06/22/2023] Open
Abstract
Background Gut microbiota is the largest population of microorganisms and is closely related to health. Many studies have explored changes in gut microbiota in viral hepatitis. However, the correlation between gut microbiota and the occurrence and progression of viral hepatitis has not been fully clarified. Methods PubMed and BioProject databases were searched for studies about viral hepatitis disease and 16S rRNA gene sequencing of gut microbiota up to January 2023. With bioinformatics analyses, we explored changes in microbial diversity of viral hepatitis, screened out crucial bacteria and microbial functions related to viral hepatitis, and identified the potential microbial markers for predicting risks for the occurrence and progression of viral hepatitis based on ROC analysis. Results Of the 1389 records identified, 13 studies met the inclusion criteria, with 950 individuals including 656 patient samples (HBV, n = 546; HCV, n = 86; HEV, n = 24) and 294 healthy controls. Gut microbial diversity is significantly decreased as the infection and progression of viral hepatitis. Alpha diversity and microbiota including Butyricimonas, Escherichia-Shigella, Lactobacillus, and Veillonella were identified as the potential microbial markers for predicting the risk of development of viral hepatitis (AUC>0.7). Microbial functions including tryptophan metabolism, fatty acid biosynthesis, lipopolysaccharide biosynthesis, and lipid metabolism related to the microbial community increased significantly as the development of viral hepatitis. Conclusions This study demonstrated comprehensively the gut microbiota characteristics in viral hepatitis, screened out crucial microbial functions related to viral hepatitis, and identified the potential microbial markers for predicting the risk of viral hepatitis.
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Affiliation(s)
- Xing Yang
- School of Public Health, Guangxi Medical University, Nanning, China
- Guangxi Key Laboratory of AIDS Prevention and Treatment, Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, Guangxi Medical University, Nanning, China
| | - Huanzhuo Mai
- School of Public Health, Guangxi Medical University, Nanning, China
- Guangxi Key Laboratory of AIDS Prevention and Treatment, Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, Guangxi Medical University, Nanning, China
| | - Jie Zhou
- School of Public Health, Guangxi Medical University, Nanning, China
- Guangxi Key Laboratory of AIDS Prevention and Treatment, Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, Guangxi Medical University, Nanning, China
| | - Zhuoxin Li
- School of Public Health, Guangxi Medical University, Nanning, China
- Guangxi Key Laboratory of AIDS Prevention and Treatment, Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, Guangxi Medical University, Nanning, China
| | - Qing Wang
- School of Public Health, Guangxi Medical University, Nanning, China
- Guangxi Key Laboratory of AIDS Prevention and Treatment, Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, Guangxi Medical University, Nanning, China
| | - Liuyan Lan
- School of Public Health, Guangxi Medical University, Nanning, China
- Guangxi Key Laboratory of AIDS Prevention and Treatment, Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, Guangxi Medical University, Nanning, China
| | - Fang Lu
- School of Public Health, Guangxi Medical University, Nanning, China
- Guangxi Key Laboratory of AIDS Prevention and Treatment, Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, Guangxi Medical University, Nanning, China
| | - Xiping Yang
- School of Public Health, Guangxi Medical University, Nanning, China
- Guangxi Key Laboratory of AIDS Prevention and Treatment, Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, Guangxi Medical University, Nanning, China
| | - Baodong Guo
- School of Public Health, Guangxi Medical University, Nanning, China
- Guangxi Key Laboratory of AIDS Prevention and Treatment, Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, Guangxi Medical University, Nanning, China
| | - Li Ye
- School of Public Health, Guangxi Medical University, Nanning, China
- Guangxi Key Laboratory of AIDS Prevention and Treatment, Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, Guangxi Medical University, Nanning, China
| | - Ping Cui
- Guangxi Key Laboratory of AIDS Prevention and Treatment, Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, Guangxi Medical University, Nanning, China
- Life Science Institute, Guangxi Medical University, Nanning, China
- Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry, Guangxi Medical University, Nanning, China
| | - Hao Liang
- School of Public Health, Guangxi Medical University, Nanning, China
- Guangxi Key Laboratory of AIDS Prevention and Treatment, Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, Guangxi Medical University, Nanning, China
- Life Science Institute, Guangxi Medical University, Nanning, China
- Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry, Guangxi Medical University, Nanning, China
| | - Jiegang Huang
- School of Public Health, Guangxi Medical University, Nanning, China
- Guangxi Key Laboratory of AIDS Prevention and Treatment, Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, Guangxi Medical University, Nanning, China
- Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, China
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10
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Bu Y, Zhao K, Xu Z, Zheng Y, Hua R, Wu C, Zhu C, Xia Y, Cheng X. Antibiotic-induced gut bacteria depletion has no effect on HBV replication in HBV immune tolerance mouse model. Virol Sin 2023:S1995-820X(23)00048-2. [PMID: 37141990 DOI: 10.1016/j.virs.2023.04.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Accepted: 04/26/2023] [Indexed: 05/06/2023] Open
Abstract
Commensal microbiota is closely related to Hepatitis B virus (HBV) infection. Gut bacteria maturation accelerates HBV immune clearance in hydrodynamic injection (HDI) HBV mouse model. However, the effect of gut bacteria on HBV replication in recombinant adeno-associated virus (AAV)-HBV mouse model with immune tolerance remains obscure. We aim to investigate its role on HBV replication in AAV-HBV mouse model. C57BL/6 mice were administrated with broad-spectrum antibiotic mixtures (ABX) to deplete gut bacteria and intravenously injected with AAV-HBV to establish persistent HBV replication. Gut microbiota community was analyzed by fecal qPCR assay and 16S ribosomal RNA (rRNA) gene sequencing. HBV replication markers in blood and liver were determined by ELISA, qPCR assay and Western blot at indicated time points. Immune response in AAV-HBV mouse model was activated through HDI of HBV plasmid or poly(I:C) and then detected by quantifying the percentage of IFN-γ+/CD8+ T cells in the spleen via flow cytometry as well as the splenic IFN-γ mRNA level via qPCR assay. We found that antibiotic exposure remarkably decreased gut bacteria abundance and diversity. Antibiotic treatment failed to alter the levels of serological HBV antigens, intrahepatic HBV RNA transcripts and HBc protein in AAV-HBV mouse model, but contributed to HBsAg increase after breaking of immune tolerance. Overall, our data uncovered that antibiotic-induced gut bacteria depletion has no effect on HBV replication in immune tolerant AAV-HBV mouse model, providing new thoughts for elucidating the correlation between gut bacteria dysbiosis by antibiotic abuse and clinical chronic HBV infection.
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Affiliation(s)
- Yanan Bu
- State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy and Immunology, Hubei Jiangxia Laboratory, Institute of Medical Virology, TaiKang Center for Life and Medical Sciences, TaiKang Medical School, Wuhan University, Wuhan, 430071, China
| | - Kaitao Zhao
- State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy and Immunology, Hubei Jiangxia Laboratory, Institute of Medical Virology, TaiKang Center for Life and Medical Sciences, TaiKang Medical School, Wuhan University, Wuhan, 430071, China
| | - Zaichao Xu
- State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy and Immunology, Hubei Jiangxia Laboratory, Institute of Medical Virology, TaiKang Center for Life and Medical Sciences, TaiKang Medical School, Wuhan University, Wuhan, 430071, China
| | - Yingcheng Zheng
- State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy and Immunology, Hubei Jiangxia Laboratory, Institute of Medical Virology, TaiKang Center for Life and Medical Sciences, TaiKang Medical School, Wuhan University, Wuhan, 430071, China
| | - Rong Hua
- State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy and Immunology, Hubei Jiangxia Laboratory, Institute of Medical Virology, TaiKang Center for Life and Medical Sciences, TaiKang Medical School, Wuhan University, Wuhan, 430071, China
| | - Chuanjian Wu
- State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy and Immunology, Hubei Jiangxia Laboratory, Institute of Medical Virology, TaiKang Center for Life and Medical Sciences, TaiKang Medical School, Wuhan University, Wuhan, 430071, China
| | - Chengliang Zhu
- Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, 430060; China
| | - Yuchen Xia
- State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy and Immunology, Hubei Jiangxia Laboratory, Institute of Medical Virology, TaiKang Center for Life and Medical Sciences, TaiKang Medical School, Wuhan University, Wuhan, 430071, China.
| | - Xiaoming Cheng
- Department of Pathology, Center for Pathology and Molecular Diagnostics, Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Zhongnan Hospital of Wuhan University, TaiKang Medical School, Wuhan University, Wuhan, 430071, China.
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11
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Liu Y, Wu Y, Jiang X, Chen B, Lu J, Cai Z, Fu B, Zheng W, Wu R, Chen G, Tian S, Ren J. Apolipoprotein H induces sex-specific steatohepatitis and gut dysbiosis during chronic hepatitis B infection. iScience 2023; 26:106100. [PMID: 36852272 PMCID: PMC9958358 DOI: 10.1016/j.isci.2023.106100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Revised: 12/07/2022] [Accepted: 01/25/2023] [Indexed: 02/04/2023] Open
Abstract
Apolipoprotein H (APOH) is involved in lipid metabolism and functions as an acute-phase protein during hepatitis B virus (HBV) infection. Herein, we explored whether APOH acts on the development of fatty liver upon chronic HBV infection. Serum APOH level was significantly lower in cirrhosis patients than in healthy controls or patients with chronic infection. It showed sex bias, with elevated levels in female patients with chronic infection. Also, serum APOH levels were negatively correlated with HBV surface antigen (HBsAg) but positively correlated with albumin and triglyceride levels. In In vitro HBV infection model, HBV upregulated APOH expression in a non-temporal manner, and HBsAg levels were elevated by silencing APOH. RNA sequencing (RNA-seq) demonstrated bidirectional expression of APOH, which impacted the immunoregulation upon infection or the metabolic regulation in HepG2.2.15 cells. Then, ApoH -/- mice with persistent HBV replication displayed steatohepatitis and gut microbiota dysbiosis with synergistic sex differences. Our study deciphers the roles of APOH in chronic liver diseases.
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Affiliation(s)
- Yaming Liu
- Department of Gastroenterology and Hepatology, Xiamen University Zhongshan Hospital, Xiamen, Fujian Province 361001, China,Department of Digestive Diseases, School of Medicine, Xiamen University, Xiamen, Fujian Province 361001, China
| | - Yangtao Wu
- Department of Digestive Diseases, School of Medicine, Xiamen University, Xiamen, Fujian Province 361001, China,National Institute of Diagnostic and Vaccine Development in Infectious Disease, Xiamen University, Xiamen, Fujian Province 361001, China
| | - Xiaoming Jiang
- Department of Hepatology, The First Hospital of Jilin University, Changchun, Jilin Province 132001, China
| | - Bo Chen
- Department of Hepatobiliary Surgery, The first affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, China
| | - Jing Lu
- Department of Digestive Diseases, School of Medicine, Xiamen University, Xiamen, Fujian Province 361001, China
| | - Zexin Cai
- Department of Digestive Diseases, School of Medicine, Xiamen University, Xiamen, Fujian Province 361001, China
| | - Baorong Fu
- Department of Digestive Diseases, School of Medicine, Xiamen University, Xiamen, Fujian Province 361001, China,National Institute of Diagnostic and Vaccine Development in Infectious Disease, Xiamen University, Xiamen, Fujian Province 361001, China
| | - Wei Zheng
- Department of Digestive Diseases, School of Medicine, Xiamen University, Xiamen, Fujian Province 361001, China,Department of Pathology, Xiamen University Zhongshan Hospital, Xiamen, Fujian Province 361001, China
| | - Ruihong Wu
- Department of Hepatology, The First Hospital of Jilin University, Changchun, Jilin Province 132001, China
| | - Gang Chen
- Department of Hepatobiliary Surgery, The first affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, China
| | - Shulan Tian
- Division of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA
| | - Jianlin Ren
- Department of Gastroenterology and Hepatology, Xiamen University Zhongshan Hospital, Xiamen, Fujian Province 361001, China,Department of Digestive Diseases, School of Medicine, Xiamen University, Xiamen, Fujian Province 361001, China,Corresponding author
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12
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Many Ways to Communicate-Crosstalk between the HBV-Infected Cell and Its Environment. Pathogens 2022; 12:pathogens12010029. [PMID: 36678377 PMCID: PMC9866324 DOI: 10.3390/pathogens12010029] [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: 11/17/2022] [Revised: 12/19/2022] [Accepted: 12/22/2022] [Indexed: 12/28/2022] Open
Abstract
Chronic infection with the hepatitis B virus (HBV) affects an estimated 257 million people worldwide and can lead to liver diseases such as cirrhosis and liver cancer. Viral replication is generally considered not to be cytopathic, and although some HBV proteins may have direct carcinogenic effects, the majority of HBV infection-related disease is related to chronic inflammation resulting from disrupted antiviral responses and aberrant innate immune reactions. Like all cells, healthy and HBV-infected cells communicate with each other, as well as with other cell types, such as innate and adaptive immune cells. They do so by both interacting directly and by secreting factors into their environment. Such factors may be small molecules, such as metabolites, single viral proteins or host proteins, but can also be more complex, such as virions, protein complexes, and extracellular vesicles. The latter are small, membrane-enclosed vesicles that are exchanged between cells, and have recently gained a lot of attention for their potential to mediate complex communication and their potential for therapeutic repurposing. Here, we review how HBV infection affects the communication between HBV-infected cells and cells in their environment. We discuss the impact of these interactions on viral persistence in chronic infection, as well as their relation to HBV infection-related pathology.
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13
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Li YG, Yu ZJ, Li A, Ren ZG. Gut microbiota alteration and modulation in hepatitis B virus-related fibrosis and complications: Molecular mechanisms and therapeutic inventions. World J Gastroenterol 2022; 28:3555-3572. [PMID: 36161048 PMCID: PMC9372803 DOI: 10.3748/wjg.v28.i28.3555] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 06/06/2022] [Accepted: 06/24/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) has posed a threat to public health, mainly resulting in liver damage. With long-term accumulation of extracellular matrix, patients with chronic hepatitis B are at high risk of developing into liver fibrosis and cirrhosis and even life-threatening hepatic carcinoma. The occurrence of complications such as spontaneous bacterial peritonitis and hepatic encephalopathy greatly increases disability and mortality. With deeper understanding of the bidirectional interaction between the liver and the gut (gut-liver axis), there is a growing consensus that the human health closely relates to the gut microbiota. Supported by animal and human studies, the gut microbiota alters as the HBV-related liver fibrosis initials and progresses, characterized as the decrease of the ratio between “good” and “potentially pathogenic” microbes. When the primary disease is controlled via antiviral treatment, the gut microbiota dysfunction tends to be improved. Conversely, the recovery of gut microbiota can promote the regression of liver fibrosis. Therapeutic strategies targeted on gut microbiota (rifaximin, probiotics, engineered probiotics and fecal microbiota transplantation) have been applied to animal models and patients, obtaining satisfactory results.
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Affiliation(s)
- Yao-Guang Li
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
- Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Zu-Jiang Yu
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
- Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Ang Li
- Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Zhi-Gang Ren
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
- Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250000, Shandong Province, China
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14
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Wang T, Rong X, Zhao C. Circadian Rhythms Coordinated With Gut Microbiota Partially Account for Individual Differences in Hepatitis B-Related Cirrhosis. Front Cell Infect Microbiol 2022; 12:936815. [PMID: 35846774 PMCID: PMC9283756 DOI: 10.3389/fcimb.2022.936815] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 06/09/2022] [Indexed: 12/12/2022] Open
Abstract
Cirrhosis is the end stage of chronic liver diseases like chronic hepatitis B. In China, hepatitis B accounts for around 60% of cases of cirrhosis. So far, clinical and laboratory indexes for the early diagnosis of cirrhosis are far from satisfactory. Nevertheless, there haven’t been specific drugs for cirrhosis. Thus, it is quite necessary to uncover more specific factors which play their roles in cirrhosis and figure out the possible therapeutic targets. Among emerging factors taking part in the initiation and progression of cirrhosis, gut microbiota might be a pivot of systemic factors like metabolism and immune and different organs like gut and liver. Discovery of detailed molecular mechanism in gut microbiota and gut liver axis leads to a more promising prospect of developing new drugs intervening in these pathways. Time-based medication regimen has been proofed to be helpful in hormonotherapy, especially in the use of glucocorticoid. Thus, circadian rhythms, though haven’t been strongly linked to hepatitis B and its complications, are still pivotal to various pathophysiological progresses. Gut microbiota as a potential effective factor of circadian rhythms has also received increasing attentions. Here, our work, restricting cirrhosis to the post-hepatitis B one, is aimed to summarize how circadian rhythms and hepatitis B-related cirrhosis can intersect via gut microbiota, and to throw new insights on the development of new and time-based therapies for hepatitis B-related cirrhosis and other cirrhosis.
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Affiliation(s)
- Tongyao Wang
- Ministry of Education (MOE)/National Health Commission (NHC)/Chinese Academy of Medical Science (CAMS) Key Lab of Medical Molecular Virology, School of Basic Medical Sciences & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xingyu Rong
- Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Chao Zhao
- Ministry of Education (MOE)/National Health Commission (NHC)/Chinese Academy of Medical Science (CAMS) Key Lab of Medical Molecular Virology, School of Basic Medical Sciences & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Shanghai, China
- *Correspondence: Chao Zhao,
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15
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Mizutani T, Ishizaka A, Koga M, Tsutsumi T, Yotsuyanagi H. Role of Microbiota in Viral Infections and Pathological Progression. Viruses 2022; 14:950. [PMID: 35632692 PMCID: PMC9144409 DOI: 10.3390/v14050950] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 04/29/2022] [Accepted: 04/29/2022] [Indexed: 02/04/2023] Open
Abstract
Viral infections are influenced by various microorganisms in the environment surrounding the target tissue, and the correlation between the type and balance of commensal microbiota is the key to establishment of the infection and pathogenicity. Some commensal microorganisms are known to resist or promote viral infection, while others are involved in pathogenicity. It is also becoming evident that the profile of the commensal microbiota under normal conditions influences the progression of viral diseases. Thus, to understand the pathogenesis underlying viral infections, it is important to elucidate the interactions among viruses, target tissues, and the surrounding environment, including the commensal microbiota, which should have different relationships with each virus. In this review, we outline the role of microorganisms in viral infections. Particularly, we focus on gaining an in-depth understanding of the correlations among viral infections, target tissues, and the surrounding environment, including the commensal microbiota and the gut virome, and discussing the impact of changes in the microbiota (dysbiosis) on the pathological progression of viral infections.
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Affiliation(s)
- Taketoshi Mizutani
- Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-8562, Japan
- Division of Infectious Diseases, Advanced Clinical Research Center, the Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; (A.I.); (M.K.); (T.T.); (H.Y.)
| | - Aya Ishizaka
- Division of Infectious Diseases, Advanced Clinical Research Center, the Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; (A.I.); (M.K.); (T.T.); (H.Y.)
| | - Michiko Koga
- Division of Infectious Diseases, Advanced Clinical Research Center, the Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; (A.I.); (M.K.); (T.T.); (H.Y.)
| | - Takeya Tsutsumi
- Division of Infectious Diseases, Advanced Clinical Research Center, the Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; (A.I.); (M.K.); (T.T.); (H.Y.)
| | - Hiroshi Yotsuyanagi
- Division of Infectious Diseases, Advanced Clinical Research Center, the Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; (A.I.); (M.K.); (T.T.); (H.Y.)
- Department of Infectious Diseases and Applied Immunology, IMSUT Hospital of Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
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16
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Hartmann P. Editorial: The Microbiome in Hepatobiliary and Intestinal Disease. Front Physiol 2022; 13:893074. [PMID: 35492588 PMCID: PMC9044070 DOI: 10.3389/fphys.2022.893074] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Accepted: 03/11/2022] [Indexed: 12/12/2022] Open
Affiliation(s)
- Phillipp Hartmann
- Department of Pediatrics, University of California, San Diego, San Diego, CA, United States
- Division of Gastroenterology, Hepatology and Nutrition, Rady Children’s Hospital San Diego, San Diego, CA, United States
- *Correspondence: Phillipp Hartmann,
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