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Brulin L, Sanchez MP, Cai Z, Ducrocq S, Even G, Martel S, Merlin S, Audebert C, Estellé J, Sahana G, Croiseau P. Sequence-based genome-wide association study reveals host genomic regions and candidate genes influencing the fecal microbiota of Holstein cows. J Dairy Sci 2025:S0022-0302(25)00361-3. [PMID: 40383381 DOI: 10.3168/jds.2024-26203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Accepted: 04/29/2025] [Indexed: 05/20/2025]
Abstract
In recent decades, the digestive tract microbiota of livestock has been extensively studied, revealing associations with host phenotypes, including production- and health-related traits. The effect of host genetics on gut microbes has been documented in several species; however, in dairy cattle, the specific genomic regions that influence microbial communities remain relatively unexplored. This study aimed to conduct a sequence-based GWAS and a gene-based association study to identify the genomic regions and candidate genes affecting fecal microbiota diversity and composition in a population of 1,875 commercial Holstein cows. From the sequence-based GWAS conducted on 116 fecal microbiota taxonomic levels, 6 QTL were significantly associated with the abundances of Paeniclostridium, an unclassified genus from the Paludibacteraceae family, Sutterella, Turicibacter, and Akkermansia genera, as well as the associated family Akkermansiaceae. These QTL explained between 2.0% and 25.5% of the phenotypic variances of the taxa abundances. Conversely, no genomic variants were found significant for either the α- or the β-diversity of the fecal microbiota. A gene-based association study subsequently conducted on the sequence-based GWAS results revealed significant effects of 90 genes across the bovine genome, effecting the relative abundances of some fecal taxa. Many of these genes were located within the major histocompatibility complex and enriched in immune response pathways. By combining GWAS with gene-based association studies, we specifically identified an association between the ABO gene and the fecal abundance of Akkermansia and Akkermansiaceae. The study represents a significant step forward in understanding the genetic determinism of the complex interactions between the fecal microbiota and their host. It provides new insights into the biological mechanisms underlying host-microbiota interaction in dairy cattle and unveils strong associations between host genomic regions and fecal microbiota in a commercial population. This study holds promise for large-scale breeding strategies to shape the fecal microbiota in Holstein cows and benefit from the host-microbiota interactions.
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Affiliation(s)
- L Brulin
- GD Biotech - Gènes Diffusion, Lille, 59000, France; Université Paris-Saclay, INRAE, AgroParisTech, GABI, Jouy-en-Josas, 78350, France.
| | - M-P Sanchez
- Université Paris-Saclay, INRAE, AgroParisTech, GABI, Jouy-en-Josas, 78350, France
| | - Z Cai
- Center for Quantitative Genetics and Genomics, Aarhus University, Aarhus, 8000, Denmark
| | - S Ducrocq
- GD Biotech - Gènes Diffusion, Lille, 59000, France; PEGASE-Biosciences, Institut Pasteur de Lille, Lille, 59019, France
| | - G Even
- GD Biotech - Gènes Diffusion, Lille, 59000, France; PEGASE-Biosciences, Institut Pasteur de Lille, Lille, 59019, France
| | - S Martel
- GD Biotech - Gènes Diffusion, Lille, 59000, France; PEGASE-Biosciences, Institut Pasteur de Lille, Lille, 59019, France
| | - S Merlin
- GD Biotech - Gènes Diffusion, Lille, 59000, France; PEGASE-Biosciences, Institut Pasteur de Lille, Lille, 59019, France
| | - C Audebert
- GD Biotech - Gènes Diffusion, Lille, 59000, France; PEGASE-Biosciences, Institut Pasteur de Lille, Lille, 59019, France
| | - J Estellé
- Université Paris-Saclay, INRAE, AgroParisTech, GABI, Jouy-en-Josas, 78350, France
| | - G Sahana
- Center for Quantitative Genetics and Genomics, Aarhus University, Aarhus, 8000, Denmark
| | - P Croiseau
- Université Paris-Saclay, INRAE, AgroParisTech, GABI, Jouy-en-Josas, 78350, France
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2
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Chen S, Dan L, Xiang L, He Q, Hu D, Gao Y. The role of gut flora-driven Th cell responses in preclinical rheumatoid arthritis. J Autoimmun 2025; 154:103426. [PMID: 40300482 DOI: 10.1016/j.jaut.2025.103426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Revised: 03/24/2025] [Accepted: 04/22/2025] [Indexed: 05/01/2025]
Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder with an immune pathogenesis that evolves over decades. Preclinical RA (PreRA) represents a dynamic immune phase preceding clinical RA, marked by the loss of autoimmune tolerance, the appearance of tissue-invasive effector T cells, and the production of autoantibodies (such as antibodies against citrullinated proteins and rheumatoid factors). Extensive research has demonstrated that gut microbiota influence mucosal T-cell responses, driving the progression of PreRA through multiple mechanisms, including altered intestinal permeability, gene-environment interactions, bacterial antigenic specificity, molecular mimicry, and metabolite production. Environmental risk factors such as smoking, hormonal changes, and high-sodium (Na) diets, may contribute to RA pathogenesis via the gut microbiome. The next challenge in RA research lies in developing therapeutic strategies to intervene during the asymptomatic autoimmune phase, where dietary adjustments, natural compounds, probiotics, and other approaches could effectively modulate gut flora to prevent or delay RA onset.
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Affiliation(s)
- Shuanglan Chen
- Department of Rheumatology and Immunology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China
| | - Lijuan Dan
- Department of Infection, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China
| | - Li Xiang
- Department of Rheumatology and Immunology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China
| | - Qingman He
- Department of Rheumatology and Immunology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China
| | - Dongsen Hu
- Sichuan Jinxin Xi'nan Women's and Children's Hospital Co., Ltd, Chengdu, 610023, China
| | - Yongxiang Gao
- Department of Rheumatology and Immunology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China.
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Mao X, Huang H, Zhao L, Li F, Wang Z, Yuan X, Lau HC, Hsueh CY, Zhang M. Complex of intratumoral mycobiome and bacteriome predicts the recurrence of laryngeal squamous cell carcinoma. Appl Environ Microbiol 2025; 91:e0195424. [PMID: 39982111 PMCID: PMC11921384 DOI: 10.1128/aem.01954-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Accepted: 01/10/2025] [Indexed: 02/22/2025] Open
Abstract
Dysbiosis of intratumoral fungal and bacterial communities is associated with poor prognosis in various cancers. However, the mycobiome characteristics in laryngeal squamous cell carcinoma (LSCC) and its correlation with recurrence have not yet been investigated. The mycobiome in 80 LSCC samples was characterized using internal transcribed spacer sequencing, encompassing both tumor tissues and their matched para-cancerous tissues. The intratumoral bacteriome was further identified using 16S rRNA sequencing. These two microbial communities were analyzed using bioinformatics and statistical methods to determine its potential correlation with LSCC recurrence. The fungal alpha diversity in tumors was higher compared with that in para-cancerous tissues (P < 0.001). A significant difference in the overall fungal community patterns between tumor tissues and para-cancerous tissues was observed based on Bray-Curtis dissimilarity (P < 0.001). The presence of Alloprevotella, Porphyromonas, Candida, and Fusarium in tumors exhibited a correlation with alcohol consumption. The relative abundance of Penicillium, Exophiala, and Aspergillus in the mycobiome, as well as that of Alloprevotella, Porphyromonas, and Peptostreptococcus in the bacteriome significantly increased the risk of LSCC recurrence (P < 0.05). These six microorganisms can combine to form a microbial complex, which may independently contribute to recurrence risk in patients with LSCC when enriched within the tumor (hazard ratio = 6.844, P < 0.01). Intratumoral fungi and bacteria can be valuable indicators for assessing recurrence in patients with LSCC, indicating their potential as valuable targets for therapeutic intervention. IMPORTANCE Our results revealed that dysbiosis of intratumoral microbiota, including increased fungal community diversity and overgrowth of several fungal or bacterial organisms, is substantially linked to the recurrence of LSCC. Drinking habits might alter the laryngeal microbiota to influence the recurrence of LSCC. We also explored a method to potentially predict the recurrence of LSCC from a novel perspective. These findings could offer insights into the etiology of LSCC and pave way to prevent and treat LSCC.
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Affiliation(s)
- Xinhui Mao
- ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, China
| | - Huiying Huang
- ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, China
| | - Limin Zhao
- Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Feiran Li
- ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, China
| | - Zhenwei Wang
- ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, China
| | - Xiaohui Yuan
- ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, China
| | - Hui-Ching Lau
- ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, China
| | - Chi-Yao Hsueh
- ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, China
| | - Ming Zhang
- ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, China
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Lee JY, Kim Y, Kim J, Kim JK. Fecal Microbiota Transplantation: Indications, Methods, and Challenges. J Microbiol 2024; 62:1057-1074. [PMID: 39557804 DOI: 10.1007/s12275-024-00184-3] [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: 07/09/2024] [Revised: 09/25/2024] [Accepted: 10/16/2024] [Indexed: 11/20/2024]
Abstract
Over the past two decades, as the importance of gut microbiota to human health has become widely known, attempts have been made to treat diseases by correcting dysbiosis of gut microbiota through fecal microbiota transplantation (FMT). Apart from current knowledge of gut microbiota, FMT to treat disease has a long history, from the treatment of food poisoning in the fourth century to the treatment of Clostridioides difficile infections in the twentieth century. In 2013, FMT was recognized as a standard treatment for recurrent C. difficile because it consistently showed high efficacy. Though recurrent C. difficile is the only disease internationally recognized for FMT efficacy, FMT has been tested for other diseases and shown some promising preliminary results. Different FMT methods have been developed using various formulations and administration routes. Despite advances in FMT, some issues remain to be resolved, such as donor screening, manufacturing protocols, and unknown components in the fecal microbiota. In this review, we discuss the mechanisms, clinical indications, methods, and challenges of current FMT. We also discuss the development of alternative therapies to overcome the challenges of FMT.
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Affiliation(s)
- Jee Young Lee
- Department of Microbiology, Kosin University College of Medicine, Busan, 49267, Republic of Korea
| | - Yehwon Kim
- Department of Medicine, Kosin University College of Medicine, Busan, 49267, Republic of Korea
| | - Jiyoun Kim
- Department of Medicine, Kosin University College of Medicine, Busan, 49267, Republic of Korea
| | - Jiyeun Kate Kim
- Department of Microbiology, Kosin University College of Medicine, Busan, 49267, Republic of Korea.
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Khalil M, Di Ciaula A, Mahdi L, Jaber N, Di Palo DM, Graziani A, Baffy G, Portincasa P. Unraveling the Role of the Human Gut Microbiome in Health and Diseases. Microorganisms 2024; 12:2333. [PMID: 39597722 PMCID: PMC11596745 DOI: 10.3390/microorganisms12112333] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 11/12/2024] [Accepted: 11/14/2024] [Indexed: 11/29/2024] Open
Abstract
The human gut is a complex ecosystem that supports billions of living species, including bacteria, viruses, archaea, phages, fungi, and unicellular eukaryotes. Bacteria give genes and enzymes for microbial and host-produced compounds, establishing a symbiotic link between the external environment and the host at both the gut and systemic levels. The gut microbiome, which is primarily made up of commensal bacteria, is critical for maintaining the healthy host's immune system, aiding digestion, synthesizing essential nutrients, and protecting against pathogenic bacteria, as well as influencing endocrine, neural, humoral, and immunological functions and metabolic pathways. Qualitative, quantitative, and/or topographic shifts can alter the gut microbiome, resulting in dysbiosis and microbial dysfunction, which can contribute to a variety of noncommunicable illnesses, including hypertension, cardiovascular disease, obesity, diabetes, inflammatory bowel disease, cancer, and irritable bowel syndrome. While most evidence to date is observational and does not establish direct causation, ongoing clinical trials and advanced genomic techniques are steadily enhancing our understanding of these intricate interactions. This review will explore key aspects of the relationship between gut microbiota, eubiosis, and dysbiosis in human health and disease, highlighting emerging strategies for microbiome engineering as potential therapeutic approaches for various conditions.
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Affiliation(s)
- Mohamad Khalil
- Clinica Medica “A. Murri”, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), Medical School, University of Bari Aldo Moro, 70124 Bari, Italy; (M.K.); (A.D.C.); (L.M.); (N.J.)
| | - Agostino Di Ciaula
- Clinica Medica “A. Murri”, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), Medical School, University of Bari Aldo Moro, 70124 Bari, Italy; (M.K.); (A.D.C.); (L.M.); (N.J.)
| | - Laura Mahdi
- Clinica Medica “A. Murri”, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), Medical School, University of Bari Aldo Moro, 70124 Bari, Italy; (M.K.); (A.D.C.); (L.M.); (N.J.)
| | - Nour Jaber
- Clinica Medica “A. Murri”, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), Medical School, University of Bari Aldo Moro, 70124 Bari, Italy; (M.K.); (A.D.C.); (L.M.); (N.J.)
| | - Domenica Maria Di Palo
- Division of Hygiene, Department of Interdisciplinary Medicine, University of Bari Aldo Moro, Piazza Giulio Cesare 11, 70124 Bari, Italy;
| | - Annarita Graziani
- Institut AllergoSan Pharmazeutische Produkte Forschungs- und Vertriebs GmbH, 8055 Graz, Austria;
| | - Gyorgy Baffy
- Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02130, USA;
- Section of Gastroenterology, Department of Medicine, VA Boston Healthcare System, Boston, MA 02130, USA
| | - Piero Portincasa
- Clinica Medica “A. Murri”, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), Medical School, University of Bari Aldo Moro, 70124 Bari, Italy; (M.K.); (A.D.C.); (L.M.); (N.J.)
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6
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Zhou D, He B, Huang Q, Li S, Nan W, Chen Q, Yu Q. Relationship between dietary live microbe intake and the prevalence of COPD in adults: a cross-sectional study of NHANES 2013-2018. BMC Pulm Med 2024; 24:225. [PMID: 38724980 PMCID: PMC11084018 DOI: 10.1186/s12890-024-03045-2] [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: 02/29/2024] [Accepted: 05/03/2024] [Indexed: 05/12/2024] Open
Abstract
OBJECTIVE To explore the potential association between dietary live microbes and the prevalence of Chronic Obstructive Pulmonary Diseases (COPD). METHODS In this cross-sectional study, data of 9791 participants aged 20 years or older in this study were collected from the National Health and Nutrition Examination Survey (NHANES) between 2013 and 2018. Participants in this study were classified into three groups according to the Sanders' dietary live microbe classification system: low, medium, and high dietary live microbe groups. COPD was defined by a combination of self-reported physician diagnoses and standardized medical status questionnaires. Logistic regression and subgroup analysis were used to assess whether dietary live microbes were associated with the risk of COPD. RESULTS Through full adjustment for confounders, participants in the high dietary live microbe group had a low prevalence of COPD in contrast to those in low dietary live microbe group (OR: 0.614, 95% CI: 0.474-0.795, and p < 0.001), but no significant association with COPD was detected in the medium and the low dietary live microbe groups. This inverse relationship between dietary live microbe intake and COPD prevalence was more inclined to occur in smokers, females, participants aged from 40 to 59 years old and non-obese participants. CONCLUSION A high dietary live microbe intake was associated with a low prevalence of COPD, and this negative correlation was detected especially in smokers, females, participants aged from 40 to 59 years old and non-obese participants.
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Affiliation(s)
- Dongbo Zhou
- Department of Geriatric Respiratory and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Baimei He
- Department of Geriatric Respiratory and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Qiong Huang
- Department of Geriatric Respiratory and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Siqi Li
- Department of Geriatric Respiratory and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Wenbin Nan
- Department of Emergency Medicine, Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Qiong Chen
- Department of Geriatric Respiratory and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Qiao Yu
- Department of Geriatric Respiratory and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China.
- Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China.
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Xie W, Zhong YS, Li XJ, Kang YK, Peng QY, Ying HZ. Postbiotics in colorectal cancer: intervention mechanisms and perspectives. Front Microbiol 2024; 15:1360225. [PMID: 38450163 PMCID: PMC10914944 DOI: 10.3389/fmicb.2024.1360225] [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: 12/22/2023] [Accepted: 02/06/2024] [Indexed: 03/08/2024] Open
Abstract
Colorectal cancer (CRC) is a common malignancy affecting the gastrointestinal tract worldwide. The etiology and progression of CRC are related to factors such as environmental influences, dietary structure, and genetic susceptibility. Intestinal microbiota can influence the integrity of the intestinal mucosal barrier and modulate intestinal immunity by secreting various metabolites. Dysbiosis of the intestinal microbiota can affect the metabolites of the microbial, leading to the accumulation of toxic metabolites, which can trigger chronic inflammation or DNA damage and ultimately lead to cellular carcinogenesis and the development of CRC. Postbiotics are preparations of inanimate microorganisms or their components that are beneficial to the health of the host, with the main components including bacterial components (e.g., exopolysaccharides, teichoic acids, surface layer protein) and metabolites (e.g., short-chain fatty acids, tryptophan metabolite, bile acids, vitamins and enzymes). Compared with traditional probiotics, it has a more stable chemical structure and higher safety. In recent years, it has been demonstrated that postbiotics are involved in regulating intestinal microecology and improving the progression of CRC, which provides new ideas for the prevention and diagnosis of CRC. In this article, we review the changes in intestinal microbiota in different states of the gut and the mechanisms of anti-tumor activity of postbiotic-related components, and discuss the potential significance of postbiotics in the diagnosis and treatment of CRC. This reviews the changes and pathogenesis of intestinal microbiota in the development of CRC, and summarizes the relevant mechanisms of postbiotics in resisting the development of CRC in recent years, as well as the advantages and limitations of postbiotics in the treatment process of CRC.
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Affiliation(s)
| | | | | | | | | | - Hua-Zhong Ying
- Key Laboratory of Experimental Animal and Safety Evaluation, Hangzhou Medical College, Hangzhou, China
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8
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Li S, Wang T, Ren Y, Liu Z, Gao J, Guo Z. Prognostic impact of oral microbiome on survival of malignancies: a systematic review and meta-analysis. Syst Rev 2024; 13:41. [PMID: 38273347 PMCID: PMC10809532 DOI: 10.1186/s13643-023-02419-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Accepted: 12/05/2023] [Indexed: 01/27/2024] Open
Abstract
BACKGROUND Recent studies have shown that there exists a significant correlation between oral microbiome and the occurrence of malignancies. However, the prognostic significance of oral microbiome for cancer patients remains unclear. The purpose of this meta-analysis is to evaluate the impact of oral microbiome on the survival of patients with malignant neoplasms. METHODS We conducted a thorough literature search of PubMed, Embase, and Cochrane Library databases until September 2022. The hazard ratio (HR) with a corresponding 95% confidence interval (CI) was analyzed using Review Manager 5.4 software for survival outcomes, including overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS), and disease-free survival (DFS). RESULTS A total of 15 studies, covering 5191 samples with various types of cancers, were selected based on specified inclusion and exclusion criteria. In both univariate and multivariate analysis, patients with low diversity of the oral microbiome, or those with Fusobacterium-high/positive, or P. gingivalis positive in cancer tissue displayed poorer OS (univariate HR = 1.74; 95% CI 1.15-2.62; P = 0.009; multivariate HR = 1.56; 95% CI 1.07-2.27; P = 0.02), DSS (univariate HR = 2.06; 95% CI 1.50-2.84; P < 0.00001; multivariate HR = 1.80; 95% CI 1.48-2.20; P < 0.00001), and PFS/DFS (univariate HR = 2.00; 95% CI 1.12-3.58; P = 0.002; multivariate HR = 1.78; 95% CI 1.05-3.02; P = 0.003). Subgroup analysis revealed that Fusobacterium positive or high abundance in cancer tissues was associated with poor OS in multivariate analysis but had no statistical differences in PFS or DFS in univariate and multivariate analysis. Additionally, P. gingivalis positive in cancer tissue was also associated with worse OS. CONCLUSIONS Our meta-analysis suggests that the composition of the oral microbiome may play a significant role in predicting survival outcomes for cancer patients.
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Affiliation(s)
- Shuluan Li
- Department of Nutrition, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
| | - Tianyu Wang
- Department of Breast Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, People's Republic of China
| | - Ya Ren
- Department of Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, People's Republic of China
| | - Zhou Liu
- Department of Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, People's Republic of China.
| | - Jidong Gao
- Department of Breast Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, People's Republic of China.
| | - Zhi Guo
- Department of Hematology, Huazhong University of Science and Technology Union Shenzhen Hospital, Guangdong, 518000, People's Republic of China.
- Institute of Infection, Immunology and Tumor Microenvironent, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Medical School, Wuhan University of Science and Technology, Wuhan, People's Republic of China.
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9
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Ma L, Ge Y, Brown J, Choi SC, Elshikha A, Kanda N, Terrell M, Six N, Garcia A, Mohamadzadeh M, Silverman G, Morel L. Dietary tryptophan and genetic susceptibility expand gut microbiota that promote systemic autoimmune activation. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.01.16.575942. [PMID: 38293097 PMCID: PMC10827173 DOI: 10.1101/2024.01.16.575942] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/01/2024]
Abstract
Tryptophan modulates disease activity and the composition of microbiota in the B6.Sle1.Sle2.Sle3 (TC) mouse model of lupus. To directly test the effect of tryptophan on the gut microbiome, we transplanted fecal samples from TC and B6 control mice into germ-free or antibiotic-treated non-autoimmune B6 mice that were fed with a high or low tryptophan diet. The recipient mice with TC microbiota and high tryptophan diet had higher levels of immune activation, autoantibody production and intestinal inflammation. A bloom of Ruminococcus gnavus (Rg), a bacterium associated with disease flares in lupus patients, only emerged in the recipients of TC microbiota fed with high tryptophan. Rg depletion in TC mice decreased autoantibody production and increased the frequency of regulatory T cells. Conversely, TC mice colonized with Rg showed higher autoimmune activation. Overall, these results suggest that the interplay of genetic and tryptophan can influence the pathogenesis of lupus through the gut microbiota.
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Affiliation(s)
- Longhuan Ma
- Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health San Antonio, San Antonio, TX
| | - Yong Ge
- Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health San Antonio, San Antonio, TX
| | - Josephine Brown
- Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL
| | - Seung-Chul Choi
- Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health San Antonio, San Antonio, TX
| | - Ahmed Elshikha
- Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL
| | - Nathalie Kanda
- Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL
| | - Morgan Terrell
- Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL
| | - Natalie Six
- Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health San Antonio, San Antonio, TX
| | - Abigail Garcia
- Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health San Antonio, San Antonio, TX
| | - Mansour Mohamadzadeh
- Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health San Antonio, San Antonio, TX
| | | | - Laurence Morel
- Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health San Antonio, San Antonio, TX
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Yang Q, Liu H, Jafari H, Liu B, Wang Z, Su J, Wang F, Yang G, Sun M, Cheng J, Dong B, Li M, Gen M, Yu J. Metabolic changes before and after weaning in Dezhou donkey foals in relation to gut microbiota. Front Microbiol 2024; 14:1306039. [PMID: 38282742 PMCID: PMC10812615 DOI: 10.3389/fmicb.2023.1306039] [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: 10/03/2023] [Accepted: 12/22/2023] [Indexed: 01/30/2024] Open
Abstract
Weaning is undoubtedly one of the most crucial stages in the growth and development of all mammalian animals, including donkey foals. Weaning is a dynamic and coordinated process of the body, which is closely associated with the health, nutrition, and metabolism of the host. Many studies have shown that the intestinal microbiota and serum metabolites of mammals exhibit different changes during lactation, weaning, and postweaning. However, the alterations in serum metabolites in donkey foals before and postweaning and the correlation between serum metabolites and intestinal microbiota are largely unknown. This study is based on the fecal 16S rRNA and serum metabolomes of Dezhou donkey foals. In total, 10 samples (fecal and serum) were collected during the following three stages: before weaning (F.M.1), during weaning (F.M.3), and postweaning (F.M.6). To study the alterations in intestinal microflora, serum metabolites, and their correlation before and postweaning. We found that with the growth and weaning progress of donkey foals, the intestinal microbiota of donkey foals underwent obvious changes, and the diversity of fecal bacteria increased (Chao1 and Shannon indexes). The main intestinal microbial flora of donkey foals include Bacteroides and Firmicutes. We found many microbiota that are associated with immunity and digestion in the postweaning group, such as Verrucomicrobiales, Clostridia, Oscillospiraceae, Akkermansia, and Rikenellaceae, which can be considered microbial markers for the transition from liquid milk to solid pellet feed. Clostridia and Oscillospiraceae can produce organic acids, including butyric acid and acetic acid, which are crucial for regulating the intestinal microecological balance of donkeys. Furthermore, the metabolome showed that the serum metabolites enriched before and postweaning were mainly related to arachidonic acid metabolism and riboflavin metabolism. Riboflavin was associated with the development of the small intestine and affected the absorption of the small intestine. We also found that the changes in the gut microbiome of the foals were significantly correlated with changes in serum metabolites, including lysophosphatidylcholine (LPC; 12,0) and positively correlated with Lachnoclostridium and Roseburia. To summarize, this study provides theoretical data for the changes in the intestinal microbiome and serum metabolism during the entire weaning period of donkey foals.
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Affiliation(s)
- Qiwen Yang
- National Engineering Research Center for Gelatin-Based Traditional Chinese Medicine, Dong-E-E-Jiao Co. Ltd., Dong'e County, Shandong, China
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Xianyang, Shaanxi, China
| | - Haibing Liu
- National Engineering Research Center for Gelatin-Based Traditional Chinese Medicine, Dong-E-E-Jiao Co. Ltd., Dong'e County, Shandong, China
| | - Halima Jafari
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Xianyang, Shaanxi, China
| | - Bing Liu
- National Engineering Research Center for Gelatin-Based Traditional Chinese Medicine, Dong-E-E-Jiao Co. Ltd., Dong'e County, Shandong, China
| | - Zhaofei Wang
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Xianyang, Shaanxi, China
| | - Jiangtian Su
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Xianyang, Shaanxi, China
| | - Fuwen Wang
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Xianyang, Shaanxi, China
| | - Ge Yang
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Xianyang, Shaanxi, China
| | - Minhao Sun
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Xianyang, Shaanxi, China
| | - Jie Cheng
- National Engineering Research Center for Gelatin-Based Traditional Chinese Medicine, Dong-E-E-Jiao Co. Ltd., Dong'e County, Shandong, China
| | - Boying Dong
- National Engineering Research Center for Gelatin-Based Traditional Chinese Medicine, Dong-E-E-Jiao Co. Ltd., Dong'e County, Shandong, China
| | - Min Li
- National Engineering Research Center for Gelatin-Based Traditional Chinese Medicine, Dong-E-E-Jiao Co. Ltd., Dong'e County, Shandong, China
| | - Mingjian Gen
- National Engineering Research Center for Gelatin-Based Traditional Chinese Medicine, Dong-E-E-Jiao Co. Ltd., Dong'e County, Shandong, China
| | - Jie Yu
- National Engineering Research Center for Gelatin-Based Traditional Chinese Medicine, Dong-E-E-Jiao Co. Ltd., Dong'e County, Shandong, China
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11
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Li Z, Wang Q, Huang X, Wu Y, Shan D. Microbiome's role in musculoskeletal health through the gut-bone axis insights. Gut Microbes 2024; 16:2410478. [PMID: 39387683 PMCID: PMC11469435 DOI: 10.1080/19490976.2024.2410478] [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: 03/27/2024] [Revised: 08/06/2024] [Accepted: 09/24/2024] [Indexed: 10/15/2024] Open
Abstract
The interplay between the human microbiome and the musculoskeletal system represents a burgeoning field of research with profound implications for understanding and treating musculoskeletal disorders. This review articulates the pivotal role of the microbiome in modulating bone health, highlighting the gut-bone axis as a critical nexus for potential therapeutic intervention. Through a meticulous analysis of recent clinical research, we underscore the microbiome's influence on osteoporosis, sarcopenia, osteoarthritis, and rheumatoid arthritis, delineating both the direct and indirect mechanisms by which microbiota could impact musculoskeletal integrity and function. Our investigation reveals novel insights into the microbiota's contribution to bone density regulation, hormone production, immune modulation, and nutrient absorption, laying the groundwork for innovative microbiome-based strategies in musculoskeletal disease management. Significantly, we identify the challenges hindering the translation of research into clinical practice, including the limitations of current microbial sequencing techniques and the need for standardized methodologies in microbiome studies. Furthermore, we highlight promising directions for future research, particularly in the realm of personalized medicine, where the microbiome's variability offers unique opportunities for tailored treatment approaches. This review sets a new agenda for leveraging gut microbiota in the diagnosis, prevention, and treatment of musculoskeletal conditions, marking a pivotal step toward integrating microbiome science into clinical musculoskeletal care.
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Affiliation(s)
- Zhengrui Li
- School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Qi Wang
- Jiangsu University, Zhenjiang, China
| | - Xufeng Huang
- Faculty of Dentistry, University of Debrecen, Debrecen, Hungary
| | - Yinteng Wu
- Department of Orthopedic and Trauma Surgery, The First Affiliated Hospital, Guangxi Medical University, Nanning, China
| | - Dan Shan
- Faculty of Health and Medicine, Lancaster University, Lancaster, UK
- Department of Biobehavioral Sciences, Columbia University, New York, NY, USA
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12
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Wei L, Chen Z, Lv Q. Mucosal-associated invariant T cells display both pathogenic and protective roles in patients with inflammatory bowel diseases. Amino Acids 2023; 55:1819-1827. [PMID: 37819474 DOI: 10.1007/s00726-023-03344-8] [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: 08/21/2023] [Accepted: 09/26/2023] [Indexed: 10/13/2023]
Abstract
An important subtype of the innate-like T lymphocytes is mucosal-associated invariant T (MAIT) cells expressing a semi-invariant T cell receptor α (TCR-α) chain. MAIT cells could be activated mainly by TCR engagement or cytokines. They have been found to have essential roles in various immune mediated. There have been growing preclinical and clinical findings that show an association between MAIT cells and the physiopathology of inflammatory bowel diseases (IBD). Of note, published reports demonstrate contradictory findings regarding the role of MAIT cells in IBD patients. A number of reports suggests a protective effect, whereas others show a pathogenic impact. The present review article aimed to explore and discuss the findings of experimental and clinical investigations evaluating the effects of MAIT cells in IBD subjects and animal models. Findings indicate that MAIT cells could exert opposite effects in the course of IBD, including an anti-inflammatory protective effect of blood circulating MAIT cells and an effector pathogenic effect of colonic MAIT cells. Another important finding is that blood levels of MAIT cells can be considered as a potential biomarker in IBD patients.
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Affiliation(s)
- Lei Wei
- Department of General Surgery, Pudong New District Gongli Hospital of Shanghai, Shanghai, 200120, China
| | - Zhigang Chen
- Department of General Surgery, Pudong New District Gongli Hospital of Shanghai, Shanghai, 200120, China
| | - Qiang Lv
- Department of General Surgery, Pudong New District Gongli Hospital of Shanghai, Shanghai, 200120, China.
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13
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Chen Y, Li W, Chang ET, Debelius JW, Manoharan L, Zheng Y, Li Y, Huang G, Adami HO, Knight R, Cai Y, Zhang Z, Ye W. Oral fungal profiling and risk of nasopharyngeal carcinoma: a population-based case-control study. EBioMedicine 2023; 96:104813. [PMID: 37776725 PMCID: PMC10550808 DOI: 10.1016/j.ebiom.2023.104813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 08/06/2023] [Accepted: 09/15/2023] [Indexed: 10/02/2023] Open
Abstract
BACKGROUND Dysbiosis of the oral mycobiome has been linked to some diseases, including cancers. However, the role of oral fungal communities in nasopharyngeal carcinoma (NPC) carcinogenesis has not previously been investigated. METHODS We characterized the oral salivary fungal mycobiome in 476 untreated incident NPC patients and 537 population-based controls using fungal internal transcribed spacer (ITS)-2 sequencing. The relationship between oral fungal mycobiome and the risk of NPC was assessed through bioinformatic and biostatistical analyses. FINDINGS We found that lower fungal alpha diversity was associated with an increased odds of NPC [lower vs. higher: observed features (adjusted odds ratio [OR] = 5.81, 95% confidence interval [CI] = 3.60-9.38); Simpson diversity (1.53, 1.03-2.29); Shannon diversity (2.03, 1.35-3.04)]. We also observed a significant difference in global fungal community patterns between cases and controls based on Bray-Curtis dissimilarity (P < 0.001). Carriage of oral fungal species, specifically, Saccharomyces cerevisiae, Candida tropicalis, Lodderomyces elongisporus, Candida albicans, and Fusarium poae, was associated with significantly higher odds of NPC, with ORs ranging from 1.56 to 4.66. Individuals with both low fungal and low bacterial alpha diversity had a profoundly elevated risk of NPC. INTERPRETATION Our results suggest that dysbiosis in the oral mycobiome, characterized by a loss of fungal community diversity and overgrowth of several fungal organisms, is associated with a substantially increased risk of NPC. FUNDING This work was funded by the US National Institutes of Health, the Swedish Research Council, the High-level Talents Research Start-up Project of Fujian Medical University, and the China Scholarship Council.
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Affiliation(s)
- Yufeng Chen
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, 17177, Sweden
| | - Wanxin Li
- Department of Epidemiology and Health Statistics & Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350000, China
| | - Ellen T Chang
- Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, 94143, USA
| | - Justine W Debelius
- Center for Translational Microbiome Research, Department of Microbiology, Tumor and Cancer Biology, Karolinska Institutet, Stockholm, 17177, Sweden; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA
| | - Lokeshwaran Manoharan
- National Bioinformatics Infrastructure Sweden (NBIS), Lund University, Lund, 22100, Sweden
| | - Yuming Zheng
- Guangxi Health Commission Key Laboratory of Molecular Epidemiology of Nasopharyngeal Carcinoma, Wuzhou Red Cross Hospital, Wuzhou, 543002, China; Department of Preventive Medicine, Wuzhou Cancer Center, Wuzhou, 543002, China
| | - Yancheng Li
- Guangxi Health Commission Key Laboratory of Molecular Epidemiology of Nasopharyngeal Carcinoma, Wuzhou Red Cross Hospital, Wuzhou, 543002, China; Cangwu Institute for Nasopharyngeal Carcinoma Control and Prevention, Wuzhou, 543002, China
| | - Guangwu Huang
- Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China; Key Laboratory of High-Incidence-Tumor Prevention & Treatment (Guangxi Medical University), Ministry of Education, Nanning, 530021, China
| | - Hans-Olov Adami
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, 17177, Sweden; Clinical Effectiveness Group, Institute of Health and Society, University of Oslo, Oslo, NO-0316, Norway
| | - Rob Knight
- Department of Pediatrics, University of California San Diego, CA, 92093, USA
| | - Yonglin Cai
- Guangxi Health Commission Key Laboratory of Molecular Epidemiology of Nasopharyngeal Carcinoma, Wuzhou Red Cross Hospital, Wuzhou, 543002, China; Department of Preventive Medicine, Wuzhou Cancer Center, Wuzhou, 543002, China.
| | - Zhe Zhang
- Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China; Key Laboratory of High-Incidence-Tumor Prevention & Treatment (Guangxi Medical University), Ministry of Education, Nanning, 530021, China.
| | - Weimin Ye
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, 17177, Sweden; Department of Epidemiology and Health Statistics & Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350000, China.
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14
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Benameur T, Porro C, Twfieg ME, Benameur N, Panaro MA, Filannino FM, Hasan A. Emerging Paradigms in Inflammatory Disease Management: Exploring Bioactive Compounds and the Gut Microbiota. Brain Sci 2023; 13:1226. [PMID: 37626582 PMCID: PMC10452544 DOI: 10.3390/brainsci13081226] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 08/06/2023] [Accepted: 08/14/2023] [Indexed: 08/27/2023] Open
Abstract
The human gut microbiota is a complex ecosystem of mutualistic microorganisms that play a critical role in maintaining human health through their individual interactions and with the host. The normal gastrointestinal microbiota plays a specific physiological function in host immunomodulation, nutrient metabolism, vitamin synthesis, xenobiotic and drug metabolism, maintenance of structural and functional integrity of the gut mucosal barrier, and protection against various pathogens. Inflammation is the innate immune response of living tissues to injury and damage caused by infections, physical and chemical trauma, immunological factors, and genetic derangements. Most diseases are associated with an underlying inflammatory process, with inflammation mediated through the contribution of active immune cells. Current strategies to control inflammatory pathways include pharmaceutical drugs, lifestyle, and dietary changes. However, this remains insufficient. Bioactive compounds (BCs) are nutritional constituents found in small quantities in food and plant extracts that provide numerous health benefits beyond their nutritional value. BCs are known for their antioxidant, antimicrobial, anticarcinogenic, anti-metabolic syndrome, and anti-inflammatory properties. Bioactive compounds have been shown to reduce the destructive effect of inflammation on tissues by inhibiting or modulating the effects of inflammatory mediators, offering hope for patients suffering from chronic inflammatory disorders like atherosclerosis, arthritis, inflammatory bowel diseases, and neurodegenerative diseases. The aim of the present review is to summarise the role of natural bioactive compounds in modulating inflammation and protecting human health, for their safety to preserve gut microbiota and improve their physiology and behaviour.
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Affiliation(s)
- Tarek Benameur
- Department of Biomedical Sciences, College of Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia
| | - Chiara Porro
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
| | - Mohammed-Elfatih Twfieg
- Department of Biomedical Sciences, College of Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia
| | - Nassima Benameur
- Faculty of Exact Sciences and Sciences of Nature and Life, Research Laboratory of Civil Engineering, Hydraulics, Sustainable Development and Environment (LARGHYDE), Mohamed Khider University, Biskra 07000, Algeria
| | - Maria Antonietta Panaro
- Department of Biosciences, Biotechnologies and Environment, University of Bari, 70125 Bari, Italy
| | | | - Abeir Hasan
- Department of Biomedical Sciences, College of Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia
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15
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Tsetseri MN, Silman AJ, Keene DJ, Dakin SG. The role of the microbiome in rheumatoid arthritis: a review. Rheumatol Adv Pract 2023; 7:rkad034. [PMID: 38606003 PMCID: PMC11007908 DOI: 10.1093/rap/rkad034] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Accepted: 03/26/2023] [Indexed: 04/13/2024] Open
Abstract
The close bidirectional relationship between the microbiome and the immune system is well supported, and a role of gut dysbiosis has been implied in many systemic autoimmune diseases. This review aims to provide a critical summary and appraisal of 6 murine studies and 16 clinical studies. The findings of the literature review suggest that gut dysbiosis precedes arthritis and that local intestinal inflammation leads to systemic inflammation in genetically predisposed individuals. However, the exact mechanism by which microorganisms provoke immune responses at distal sites remains to be elucidated. Although a characteristic RA microbiome was not identified, there were some common findings among studies: overabundance of Prevotella copri in early RA patients, and proliferation of the genus Collinsela and some Lactobacillus species. Three mechanisms by which microbiota might contribute to RA pathogenesis were proposed: inflammatory responses (P. copri and Lactobacillus), molecular mimicry (P. copri) and loss of intestinal barrier integrity (Collinsella). Larger longitudinal studies are required in order to shed light on the mechanisms involved and unravel the therapeutic potential of the microbiome, and clinical trials are needed to evaluate the safety and efficacy of the implied therapeutic interventions.
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Affiliation(s)
- Maria-Nefeli Tsetseri
- Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - Alan J Silman
- Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - David J Keene
- Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
- Faculty of Health and Life Sciences, University of Exeter, Exeter, UK
| | - Stephanie G Dakin
- Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
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16
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Elvevi A, Laffusa A, Gallo C, Invernizzi P, Massironi S. Any Role for Microbiota in Cholangiocarcinoma? A Comprehensive Review. Cells 2023; 12:370. [PMID: 36766711 PMCID: PMC9913249 DOI: 10.3390/cells12030370] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 01/09/2023] [Accepted: 01/10/2023] [Indexed: 01/20/2023] Open
Abstract
Alterations in the human microbiota have been linked to carcinogenesis in several cancers. To date, few studies have addressed the role of the microbiota in cholangiocarcinoma (CCA). Our work aims to update the knowledge about the role of the microbiota in the CCA microenvironment, and to highlight possible novel insights for the development of new diagnostic, prognostic, or even therapeutic strategies. We thus conducted a review of the literature. In recent years, great progress has been made in understanding the pathogenesis, the clinical and histological behavior, and the molecular profile of CCA. Much evidence suggests that the bile microbiota plays an essential role in biliary diseases, including CCA. Some studies have demonstrated that alterations in the qualitative and quantitative composition of the intestinal commensal bacteria lead to overall cancer susceptibility through various pathways. Other studies suggest that the gut microbiota plays a role in the pathogenesis and/or progression of CCA. The clinical implications are far-reaching, and the role of the microbiota in the CCA microenvironment may lead to considering the exciting implications of implementing therapeutic strategies that target the microbiota-immune system axis.
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Affiliation(s)
- Alessandra Elvevi
- Gastroenterology Unit, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy
| | - Alice Laffusa
- Gastroenterology Unit, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy
- Dipartimento di Medicina e Chirurgia, Università degli Studi Milano-Bicocca, 20900 Monza, Italy
| | - Camilla Gallo
- Gastroenterology Unit, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy
- Dipartimento di Medicina e Chirurgia, Università degli Studi Milano-Bicocca, 20900 Monza, Italy
| | - Pietro Invernizzi
- Gastroenterology Unit, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy
- Dipartimento di Medicina e Chirurgia, Università degli Studi Milano-Bicocca, 20900 Monza, Italy
| | - Sara Massironi
- Gastroenterology Unit, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy
- Dipartimento di Medicina e Chirurgia, Università degli Studi Milano-Bicocca, 20900 Monza, Italy
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17
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The microbiome, IgGs and schizophrenia. A R20+ adult-only story. Brain Behav Immun 2023; 107:397-398. [PMID: 36400333 DOI: 10.1016/j.bbi.2022.11.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Accepted: 11/12/2022] [Indexed: 11/16/2022] Open
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18
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S A, K G, A AM. Intermodulation of gut-lung axis microbiome and the implications of biotics to combat COVID-19. J Biomol Struct Dyn 2022; 40:14262-14278. [PMID: 34699326 DOI: 10.1080/07391102.2021.1994875] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The novel coronavirus disease pandemic caused by the COVID-19 virus has infected millions of people around the world with a surge in transmission and mortality rates. Although it is a respiratory viral infection that affects airway epithelial cells, a diverse set of complications, including cytokine storm, gastrointestinal disorders, neurological distress, and hyperactive immune responses have been reported. However, growing evidence indicates that the bidirectional crosstalk of the gut-lung axis can decipher the complexity of the disease. Though not much research has been focused on the gut-lung axis microbiome, there is a translocation of COVID-19 infection from the lung to the gut through the lymphatic system resulting in disruption of gut permeability and its integrity. It is believed that detailed elucidation of the gut-lung axis crosstalk and the role of microbiota can unravel the most significant insights on the discovery of diagnosis using microbiome-based-therapeutics for COVID-19. This review calls attention to relate the influence of dysbiosis caused by COVID-19 and the involvement of the gut-lung axis. It presents first of its kind details that concentrate on the momentousness of biotics in disease progression and restoration. Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Aishwarya S
- Department of Bioinformatics, Stella Maris College, Chennai, India.,Centre for Advanced Studies in Crystallography and Biophysics, University of Madras, Chennai, India
| | - Gunasekaran K
- Centre for Advanced Studies in Crystallography and Biophysics, University of Madras, Chennai, India
| | - Anita Margret A
- Department of Biotechnology and Bioinformatics, Bishop Heber College, Tiruchirappalli, Tamil Nadu, India
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19
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Afzaal M, Saeed F, Shah YA, Hussain M, Rabail R, Socol CT, Hassoun A, Pateiro M, Lorenzo JM, Rusu AV, Aadil RM. Human gut microbiota in health and disease: Unveiling the relationship. Front Microbiol 2022; 13:999001. [PMID: 36225386 PMCID: PMC9549250 DOI: 10.3389/fmicb.2022.999001] [Citation(s) in RCA: 228] [Impact Index Per Article: 76.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Accepted: 08/31/2022] [Indexed: 12/04/2022] Open
Abstract
The human gut possesses millions of microbes that define a complex microbial community. The gut microbiota has been characterized as a vital organ forming its multidirectional connecting axis with other organs. This gut microbiota axis is responsible for host-microbe interactions and works by communicating with the neural, endocrinal, humoral, immunological, and metabolic pathways. The human gut microorganisms (mostly non-pathogenic) have symbiotic host relationships and are usually associated with the host’s immunity to defend against pathogenic invasion. The dysbiosis of the gut microbiota is therefore linked to various human diseases, such as anxiety, depression, hypertension, cardiovascular diseases, obesity, diabetes, inflammatory bowel disease, and cancer. The mechanism leading to the disease development has a crucial correlation with gut microbiota, metabolic products, and host immune response in humans. The understanding of mechanisms over gut microbiota exerts its positive or harmful impacts remains largely undefined. However, many recent clinical studies conducted worldwide are demonstrating the relation of specific microbial species and eubiosis in health and disease. A comprehensive understanding of gut microbiota interactions, its role in health and disease, and recent updates on the subject are the striking topics of the current review. We have also addressed the daunting challenges that must be brought under control to maintain health and treat diseases.
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Affiliation(s)
- Muhammad Afzaal
- Department of Food Science, Government College University Faisalabad, Faisalabad, Pakistan
- *Correspondence: Muhammad Afzaal,
| | - Farhan Saeed
- Department of Food Science, Government College University Faisalabad, Faisalabad, Pakistan
| | - Yasir Abbas Shah
- Department of Food Science, Government College University Faisalabad, Faisalabad, Pakistan
| | - Muzzamal Hussain
- Department of Food Science, Government College University Faisalabad, Faisalabad, Pakistan
| | - Roshina Rabail
- National Institute of Food Science and Technology, University of Agriculture, Faisalabad, Pakistan
| | | | - Abdo Hassoun
- Sustainable AgriFoodtech Innovation & Research (SAFIR), Arras, France
- Syrian Academic Expertise (SAE), Gaziantep, Turkey
| | - Mirian Pateiro
- Centro Tecnológico de la Carne de Galicia, Ourense, Spain
| | - José M. Lorenzo
- Centro Tecnológico de la Carne de Galicia, Ourense, Spain
- Área de Tecnoloxía dos Alimentos, Faculdade de Ciências de Ourense, Universidade de Vigo, Ourense, Spain
| | - Alexandru Vasile Rusu
- Life Science Institute, University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca, Cluj-Napoca, Romania
- Faculty of Animal Science and Biotechnology, University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca, Cluj-Napoca, Romania
| | - Rana Muhammad Aadil
- National Institute of Food Science and Technology, University of Agriculture, Faisalabad, Pakistan
- Rana Muhammad Aadil,
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20
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Valentino MS, Esposito C, Colosimo S, Caprio AM, Puzone S, Guarino S, Marzuillo P, Miraglia del Giudice E, Di Sessa A. Gut microbiota and COVID-19: An intriguing pediatric perspective. World J Clin Cases 2022; 10:8076-8087. [PMID: 36159525 PMCID: PMC9403663 DOI: 10.12998/wjcc.v10.i23.8076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2022] [Revised: 06/14/2022] [Accepted: 07/11/2022] [Indexed: 02/06/2023] Open
Abstract
Gastrointestinal (GI) involvement has been reported in approximately 50% of patients with coronavirus disease 2019 (COVID-19), which is due to the pathogenic role of inflammation and the intestinal function of the angiotensin-converting enzyme 2 and its receptor. Accumulating adult data has pointed out that gut dysbiosis might occur in these patients with a potential impact on the severity of the disease, however the role of gut microbiota in susceptibility and severity of COVID-19 disease in children is still poorly known. During the last decades, the crosstalk between gut and lung has been largely recognized resulting in the concept of "gut-lung axis" as a central player in modulating the development of several diseases. Both organs are involved in the common mucosal immune system (including bronchus-associated and gut-associated lymphoid tissues) and their homeostasis is crucial for human health. In this framework, it has been found that the role of GI dysbiosis is affecting the homeostasis of the gut-liver axis. Of note, a gut microbiome imbalance has been linked to COVID-19 severity in adult subjects, but it remains to be clarified. Based on the increased risk of inflammatory diseases in children with COVID-19, the potential correlation between gut microbiota dysfunction and COVID-19 needs to be studied in this population. We aimed to summarize the most recent evidence on this striking aspect of COVID-19 in childhood.
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Affiliation(s)
- Maria Sole Valentino
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Claudia Esposito
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Simone Colosimo
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Angela Maria Caprio
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Simona Puzone
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Stefano Guarino
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Pierluigi Marzuillo
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Emanuele Miraglia del Giudice
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Anna Di Sessa
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
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21
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Charoensappakit A, Sae-Khow K, Leelahavanichkul A. Gut Barrier Damage and Gut Translocation of Pathogen Molecules in Lupus, an Impact of Innate Immunity (Macrophages and Neutrophils) in Autoimmune Disease. Int J Mol Sci 2022; 23:ijms23158223. [PMID: 35897790 PMCID: PMC9367802 DOI: 10.3390/ijms23158223] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Revised: 07/25/2022] [Accepted: 07/25/2022] [Indexed: 02/08/2023] Open
Abstract
The gut barrier is a single cell layer that separates gut micro-organisms from the host, and gut permeability defects result in the translocation of microbial molecules from the gut into the blood. Despite the silent clinical manifestation, gut translocation of microbial molecules can induce systemic inflammation that might be an endogenous exacerbating factor of systemic lupus erythematosus. In contrast, circulatory immune-complex deposition and the effect of medications on the gut, an organ with an extremely large surface area, of patients with active lupus might cause gut translocation of microbial molecules, which worsens lupus severity. Likewise, the imbalance of gut microbiota may initiate lupus and/or interfere with gut integrity which results in microbial translocation and lupus exacerbation. Moreover, immune hyper-responsiveness of innate immune cells (macrophages and neutrophils) is demonstrated in a lupus model from the loss of inhibitory Fc gamma receptor IIb (FcgRIIb), which induces prominent responses through the cross-link between activating-FcgRs and innate immune receptors. The immune hyper-responsiveness can cause cell death, especially apoptosis and neutrophil extracellular traps (NETosis), which possibly exacerbates lupus, partly through the enhanced exposure of the self-antigens. Leaky gut monitoring and treatments (such as probiotics) might be beneficial in lupus. Here, we discuss the current information on leaky gut in lupus.
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Affiliation(s)
- Awirut Charoensappakit
- Center of Excellence in Translational Research in Inflammation and Immunology (CETRII), Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | - Kritsanawan Sae-Khow
- Center of Excellence in Translational Research in Inflammation and Immunology (CETRII), Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | - Asada Leelahavanichkul
- Center of Excellence in Translational Research in Inflammation and Immunology (CETRII), Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
- Nephrology Unit, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
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22
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Sharma T, Gupta A, Chauhan R, Bhat AA, Nisar S, Hashem S, Akhtar S, Ahmad A, Haris M, Singh M, Uddin S. Cross-talk between the microbiome and chronic inflammation in esophageal cancer: potential driver of oncogenesis. Cancer Metastasis Rev 2022; 41:281-299. [PMID: 35511379 PMCID: PMC9363391 DOI: 10.1007/s10555-022-10026-6] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Accepted: 03/12/2022] [Indexed: 12/11/2022]
Abstract
Esophageal cancer (EC) is frequently considered a lethal malignancy and is often identified at a later stage. It is one of the major causes of cancer-related deaths globally. The conventional treatment methods like chemotherapy, radiotherapy, and surgery offer limited efficacy and poor clinical outcome with a less than 25% 5-year survival rate. The poor prognosis of EC persists despite the growth in the development of diagnostic and therapeutic modalities to treat EC. This underlines the need to elucidate the complex molecular mechanisms that drive esophageal oncogenesis. Apart from the role of the tumor microenvironment and its structural and cellular components in tumorigenesis, mounting evidence points towards the involvement of the esophageal microbiome, inflammation, and their cross-talk in promoting esophageal cancer. The current review summarizes recent research that delineates the underlying molecular mechanisms by which the microbiota and inflammation promote the pathophysiology of esophageal cancer, thus unraveling targets for potential therapeutic intervention.
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Affiliation(s)
- Tarang Sharma
- Department of Medical Oncology (Lab), All India Institute of Medical Sciences, New Delhi, India
| | - Ashna Gupta
- Department of Medical Oncology (Lab), All India Institute of Medical Sciences, New Delhi, India
| | - Ravi Chauhan
- Department of Medical Oncology (Lab), All India Institute of Medical Sciences, New Delhi, India
| | - Ajaz A Bhat
- Laboratory of Molecular and Metabolic Imaging, Cancer Research Department, Sidra Medicine, Doha, Qatar
| | - Sabah Nisar
- Laboratory of Molecular and Metabolic Imaging, Cancer Research Department, Sidra Medicine, Doha, Qatar
| | - Sheema Hashem
- Laboratory of Molecular and Metabolic Imaging, Cancer Research Department, Sidra Medicine, Doha, Qatar
| | - Sabah Akhtar
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
| | - Aamir Ahmad
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
- Dermatology Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
| | - Mohammad Haris
- Laboratory of Molecular and Metabolic Imaging, Cancer Research Department, Sidra Medicine, Doha, Qatar
- Center for Advanced Metabolic Imaging in Precision Medicine, Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, PA, Philadelphia, USA
- Laboratory Animal Research Center, Qatar University, Doha, Qatar
| | - Mayank Singh
- Department of Medical Oncology (Lab), All India Institute of Medical Sciences, New Delhi, India.
| | - Shahab Uddin
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar.
- Dermatology Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar.
- Laboratory Animal Research Center, Qatar University, Doha, Qatar.
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23
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Liu H, Bai C, Xian F, Liu S, Long C, Hu L, Liu T, Gu X. A high-calorie diet aggravates LPS-induced pneumonia by disturbing the gut microbiota and Th17/Treg balance. J Leukoc Biol 2022; 112:127-141. [PMID: 35638590 DOI: 10.1002/jlb.3ma0322-458rr] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 03/29/2022] [Accepted: 05/09/2022] [Indexed: 12/17/2022] Open
Abstract
The intestinal flora plays an important role in the inflammatory response to the systemic or local infections in the host. A high-calorie diet has been shown to aggravate pneumonia and delay recovery, especially in children. However, the underlying mechanisms remain unclear. Our previous studies demonstrated that a high-calorie diet and LPS atomization synergistically promoted lung inflammation injury in juvenile rats. In this study, specific pathogen-free juvenile rats were placed in a routine environment, and subjected to a high-calorie diet or LPS atomization in isolation as well as combination. Our data revealed that LPS nebulization combined with a high-calorie diet resulted in significant changes in rats, such as slow weight gain, increased lung index, and aggravated lung inflammatory damage. Meanwhile, we found that the aggravation of LPS-induced pneumonia by a high-calorie diet disturbs the balance of Th17/Treg cells. Furthermore, high-throughput sequencing of intestinal contents revealed that a high-calorie diet changed the gut microbiome composition, decreased microbial diversity, and particularly reduced the abundance of the intestinal microbiota associated with the production of short-chain fatty acids (SCFAs) in rats. Consequently, the levels of SCFAs, especially acetate, propionate, and butyrate, were significantly decreased following the intervention of a high-calorie diet. More critically, the effects of a high-calorie diet were shown to be transmissible among pneumonia rats through cohousing microbiota transplantation. Taken together, we provide evidence to support that a high-calorie diet can potentially reset the gut microbiome and metabolites, disrupt Th17/Treg cell balance and immune homeostasis, and aggravate LPS-induced lung inflammatory damage, which may provide a new perspective on the pathogenesis of lung inflammation injury, and suggest a novel microbiota-targeting therapy for inflammatory lung diseases.
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Affiliation(s)
- Hui Liu
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No.11, Bei San Huan East Road, Beijing, China
| | - Chen Bai
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No.11, Bei San Huan East Road, Beijing, China
| | - Fuyang Xian
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No.11, Bei San Huan East Road, Beijing, China
| | - Shaoyang Liu
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No.11, Bei San Huan East Road, Beijing, China
| | - Chaojun Long
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No.11, Bei San Huan East Road, Beijing, China
| | - Li Hu
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No.11, Bei San Huan East Road, Beijing, China
| | - Tiegang Liu
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No.11, Bei San Huan East Road, Beijing, China
| | - Xiaohong Gu
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No.11, Bei San Huan East Road, Beijing, China
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24
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Du Y, Feng R, Chang ET, Debelius JW, Yin L, Xu M, Huang T, Zhou X, Xiao X, Li Y, Liao J, Zheng Y, Huang G, Adami HO, Zhang Z, Cai Y, Ye W. Influence of Pre-treatment Saliva Microbial Diversity and Composition on Nasopharyngeal Carcinoma Prognosis. Front Cell Infect Microbiol 2022; 12:831409. [PMID: 35392614 PMCID: PMC8981580 DOI: 10.3389/fcimb.2022.831409] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Accepted: 02/21/2022] [Indexed: 11/13/2022] Open
Abstract
Background The human microbiome has been reported to mediate the response to anticancer therapies. However, research about the influence of the oral microbiome on nasopharyngeal carcinoma (NPC) survival is lacking. We aimed to explore the effect of oral microbiota on NPC prognosis. Methods Four hundred eighty-two population-based NPC cases in southern China between 2010 and 2013 were followed for survival, and their saliva samples were profiled using 16s rRNA sequencing. We analyzed associations of the oral microbiome diversity with mortality from all causes and NPC. Results Within- and between-community diversities of saliva were associated with mortality with an average of 5.29 years follow-up. Lower Faith’s phylogenetic diversity was related to higher all-cause mortality [adjusted hazard ratio (aHR), 1.52 (95% confidence interval (CI), 1.06–2.17)] and NPC-specific mortality [aHR, 1.57 (95% CI, 1.07–2.29)], compared with medium diversity, but higher phylogenetic diversity was not protective. The third principal coordinate (PC3) identified from principal coordinates analysis (PCoA) on Bray–Curtis distance was marginally associated with reduced all-cause mortality [aHR, 0.85 (95% CI, 0.73–1.00)], as was the first principal coordinate (PC1) from PCoA on weighted UniFrac [aHR, 0.86 (95% CI, 0.74–1.00)], but neither was associated with NPC-specific mortality. PC3 from robust principal components analysis was associated with lower all-cause and NPC-specific mortalities, with HRs of 0.72 (95% CI, 0.61–0.85) and 0.71 (95% CI, 0.60–0.85), respectively. Conclusions Oral microbiome may be an explanatory factor for NPC prognosis. Lower within-community diversity was associated with higher mortality, and certain measures of between-community diversity were related to mortality. Specifically, candidate bacteria were not related to mortality, suggesting that observed associations may be due to global patterns rather than particular pathogens.
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Affiliation(s)
- Yun Du
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Ruimei Feng
- Department of Epidemiology and Health Statistics and Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Ellen T. Chang
- Exponent, Inc., Center for Health Sciences, Menlo Park, CA, United States
| | - Justine W. Debelius
- Centre for Translational Microbiome Research, Department of Microbiology, Tumor, and Cell Biology, Karolinska Institutet, Solna, Sweden
- Karolinska Institutet, Science for Life Laboratory, Solna, Sweden
| | - Li Yin
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Miao Xu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Tingting Huang
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
- Radiation Oncology Clinical Medical Research of Guangxi Medical University, Nanning, China
| | - Xiaoying Zhou
- Life Science Institute, Guangxi Medical University, Nanning, China
- Key Laboratory of High-Incidence-Tumor Prevention & Treatment (Guangxi Medical University), Ministry of Education, Nanning, China
| | - Xue Xiao
- Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Yancheng Li
- Guangxi Health Commission Key Laboratory of Molecular Epidemiology of Nasopharyngeal Carcinoma, Wuzhou Red Cross Hospital, Wuzhou, China
| | - Jian Liao
- Cangwu Institute for Nasopharyngeal Carcinoma Control and Prevention, Wuzhou, China
| | - Yuming Zheng
- Guangxi Health Commission Key Laboratory of Molecular Epidemiology of Nasopharyngeal Carcinoma, Wuzhou Red Cross Hospital, Wuzhou, China
| | - Guangwu Huang
- Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Hans-Olov Adami
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Clinical Effectiveness Research Group, Institute of Health, University of Oslo, Oslo, Norway
- Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, United States
| | - Zhe Zhang
- Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Yonglin Cai
- Guangxi Health Commission Key Laboratory of Molecular Epidemiology of Nasopharyngeal Carcinoma, Wuzhou Red Cross Hospital, Wuzhou, China
| | - Weimin Ye
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- *Correspondence: Weimin Ye,
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25
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Cardinale S, Kadarmideen HN. Host Genome-Metagenome Analyses Using Combinatorial Network Methods Reveal Key Metagenomic and Host Genetic Features for Methane Emission and Feed Efficiency in Cattle. Front Genet 2022; 13:795717. [PMID: 35281842 PMCID: PMC8905538 DOI: 10.3389/fgene.2022.795717] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Accepted: 01/10/2022] [Indexed: 12/22/2022] Open
Abstract
Cattle production is one of the key contributors to global warming due to methane emission, which is a by-product of converting feed stuff into milk and meat for human consumption. Rumen hosts numerous microbial communities that are involved in the digestive process, leading to notable amounts of methane emission. The key factors underlying differences in methane emission between individual animals are due to, among other factors, both specific enrichments of certain microbial communities and host genetic factors that influence the microbial abundances. The detection of such factors involves various biostatistical and bioinformatics methods. In this study, our main objective was to reanalyze a publicly available data set using our proprietary Synomics Insights platform that is based on novel combinatorial network and machine learning methods to detect key metagenomic and host genetic features for methane emission and residual feed intake (RFI) in dairy cattle. The other objective was to compare the results with publicly available standard tools, such as those found in the microbiome bioinformatics platform QIIME2 and classic GWAS analysis. The data set used was publicly available and comprised 1,016 dairy cows with 16S short read sequencing data from two dairy cow breeds: Holstein and Nordic Reds. Host genomic data consisted of both 50 k and 150 k SNP arrays. Although several traits were analyzed by the original authors, here, we considered only methane emission as key phenotype for associating microbial communities and host genetic factors. The Synomics Insights platform is based on combinatorial methods that can identify taxa that are differentially abundant between animals showing high or low methane emission or RFI. Focusing exclusively on enriched taxa, for methane emission, the study identified 26 order-level taxa that combinatorial networks reported as significantly enriched either in high or low emitters. Additionally, a Z-test on proportions found 21/26 (81%) of these taxa were differentially enriched between high and low emitters (p value <.05). In particular, the phylum of Proteobacteria and the order Desulfovibrionales were found enriched in high emitters while the order Veillonellales was found to be more abundant in low emitters as previously reported for cattle (Wallace et al., 2015). In comparison, using the publicly available tool ANCOM only the order Methanosarcinales could be identified as differentially abundant between the two groups. We also investigated a link between host genome and rumen microbiome by applying our Synomics Insights platform and comparing it with an industry standard GWAS method. This resulted in the identification of genetic determinants in cows that are associated with changes in heritable components of the rumen microbiome. Only four key SNPs were found by both our platform and GWAS, whereas the Synomics Insights platform identified 1,290 significant SNPs that were not found by GWAS. Gene Ontology (GO) analysis found transcription factor as the dominant biological function. We estimated heritability of a core 73 taxa from the original set of 150 core order-level taxonomies and showed that some species are medium to highly heritable (0.25–0.62), paving the way for selective breeding of animals with desirable core microbiome characteristics. We identified a set of 113 key SNPs associated with >90% of these core heritable taxonomies. Finally, we have characterized a small set (<10) of SNPs strongly associated with key heritable bacterial orders with known role in methanogenesis, such as Desulfobacterales and Methanobacteriales.
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Affiliation(s)
- Stefano Cardinale
- Synomics Ltd, Hanborough Business Park, Long Hanborough, United Kingdom
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26
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Poonacha KNT, Villa TG, Notario V. The Interplay among Radiation Therapy, Antibiotics and the Microbiota: Impact on Cancer Treatment Outcomes. Antibiotics (Basel) 2022; 11:331. [PMID: 35326794 PMCID: PMC8944497 DOI: 10.3390/antibiotics11030331] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 02/27/2022] [Accepted: 02/28/2022] [Indexed: 12/01/2022] Open
Abstract
Radiation therapy has been used for more than a century, either alone or in combination with other therapeutic modalities, to treat most types of cancer. On average, radiation therapy is included in the treatment plans for over 50% of all cancer patients, and it is estimated to contribute to about 40% of curative protocols, a success rate that may reach 90%, or higher, for certain tumor types, particularly on patients diagnosed at early disease stages. A growing body of research provides solid support for the existence of bidirectional interaction between radiation exposure and the human microbiota. Radiation treatment causes quantitative and qualitative changes in the gut microbiota composition, often leading to an increased abundance of potentially hazardous or pathogenic microbes and a concomitant decrease in commensal bacteria. In turn, the resulting dysbiotic microbiota becomes an important contributor to worsen the adverse events caused in patients by the inflammatory process triggered by the radiation treatment and a significant determinant of the radiation therapy anti-tumor effectiveness. Antibiotics, which are frequently included as prophylactic agents in cancer treatment protocols to prevent patient infections, may affect the radiation/microbiota interaction through mechanisms involving both their antimicrobial activity, as a mediator of microbiota imbalances, and their dual capacity to act as pro- or anti-tumorigenic effectors and, consequently, as critical determinants of radiation therapy outcomes. In this scenario, it becomes important to introduce the use of probiotics and/or other agents that may stabilize the healthy microbiota before patients are exposed to radiation. Ultimately, newly developed methodologies may facilitate performing personalized microbiota screenings on patients before radiation therapy as an accurate way to identify which antibiotics may be used, if needed, and to inform the overall treatment planning. This review examines currently available data on these issues from the perspective of improving radiation therapy outcomes.
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Affiliation(s)
| | - Tomás G. Villa
- Department of Microbiology, Faculty of Pharmacy, University of Santiago de Compostela, Santiago de Compostela, 15705 La Coruña, Spain;
| | - Vicente Notario
- Department of Radiation Medicine, Georgetown University Medical Center, Washington, DC 20057, USA
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27
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Lee D, Goh TW, Kang MG, Choi HJ, Yeo SY, Yang J, Huh CS, Kim YY, Kim Y. Perspectives and Advances in Probiotics and the Gut Microbiome in
Companion Animals. JOURNAL OF ANIMAL SCIENCE AND TECHNOLOGY 2022; 64:197-217. [PMID: 35530406 PMCID: PMC9039956 DOI: 10.5187/jast.2022.e8] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 01/14/2022] [Accepted: 01/17/2022] [Indexed: 11/30/2022]
Abstract
As the number of households that raise dogs and cats is increasing, there is
growing interest in animal health. The gut plays an important role in animal
health. In particular, the microbiome in the gut is known to affect both the
absorption and metabolism of nutrients and the protective functions of the host.
Using probiotics on pets has beneficial effects, such as modulating the immune
system, helping to reduce stress, protecting against pathogenic bacteria and
developing growth performance. The goals of this review are to summarize the
relationship between probiotics/the gut microbiome and animal health, to feature
technology used for identifying the diversity of microbiota composition of
canine and feline microbiota, and to discuss recent reports on probiotics in
canines and felines and the safety issues associated with probiotics and the gut
microbiome in companion animals.
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Affiliation(s)
- Daniel Lee
- Department of Agricultural Biotechnology
and Research Institute of Agriculture and Life Science, Seoul National
University, Seoul 08826, Korea
| | - Tae Wook Goh
- Department of Agricultural Biotechnology
and Research Institute of Agriculture and Life Science, Seoul National
University, Seoul 08826, Korea
| | - Min Geun Kang
- Department of Agricultural Biotechnology
and Research Institute of Agriculture and Life Science, Seoul National
University, Seoul 08826, Korea
| | - Hye Jin Choi
- Department of Agricultural Biotechnology
and Research Institute of Agriculture and Life Science, Seoul National
University, Seoul 08826, Korea
| | - So Young Yeo
- Department of Agricultural Biotechnology
and Research Institute of Agriculture and Life Science, Seoul National
University, Seoul 08826, Korea
| | | | - Chul Sung Huh
- Research Institute of Eco-Friendly
Livestock Science, Institute of Green-Bio Science and Technology, Seoul
National University, Pyeongchang 25354, Korea
- Graduate School of International
Agricultural Technology, Seoul National University,
Pyeongchang 25354, Korea
| | - Yoo Yong Kim
- Department of Agricultural Biotechnology
and Research Institute of Agriculture and Life Science, Seoul National
University, Seoul 08826, Korea
| | - Younghoon Kim
- Department of Agricultural Biotechnology
and Research Institute of Agriculture and Life Science, Seoul National
University, Seoul 08826, Korea
- Corresponding author: Younghoon Kim, Department of
Agricultural Biotechnology and Research Institute of Agriculture and Life
Science, Seoul National University, Seoul 08826, Korea. Tel: +82-2-880-4808,
E-mail:
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28
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The Study of Microbe–Host Two-Way Communication. Microorganisms 2022; 10:microorganisms10020408. [PMID: 35208862 PMCID: PMC8875206 DOI: 10.3390/microorganisms10020408] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 02/02/2022] [Accepted: 02/07/2022] [Indexed: 12/22/2022] Open
Abstract
Back-and-forth intercommunication in host–pathogen interactions has long been recognized to play an important role in commensalism and microbial pathogenesis. For centuries, we have studied these microbes in our surroundings, yet many questions about the evolutionary cross-talk between host and microbe remain unanswered. With the recent surge in research interest in the commensal microbiome, basic immunological questions have returned to the fore, such as, how are vast numbers of microbes capable of coexisting within animals and humans while also maintaining a healthy functional immune system? How is the evasion and subversion of the immune system achieved by some microbes but not others? The intricate and important-to-remember two-way interaction and coevolution of host and microbe is the communication network we must tap into as researchers to answer these questions.
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Muninathan C, Guruchandran S, Viswanath Kalyan AJ, Ganesan ND. Microbial exopolysaccharides: role in functional food engineering and gut‐health management. Int J Food Sci Technol 2022. [DOI: 10.1111/ijfs.15334] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
| | | | | | - Nandhini Devi Ganesan
- Centre for Food Technology Department of Biotechnology Anna University Chennai 600025 India
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30
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Zhou J, Sun S, Luan S, Xiao X, Yang Y, Mao C, Chen L, Zeng X, Zhang Y, Yuan Y. Gut Microbiota for Esophageal Cancer: Role in Carcinogenesis and Clinical Implications. Front Oncol 2021; 11:717242. [PMID: 34733778 PMCID: PMC8558403 DOI: 10.3389/fonc.2021.717242] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Accepted: 09/24/2021] [Indexed: 02/05/2023] Open
Abstract
Esophageal cancer (EC) is a common malignant tumor of the upper digestive tract. The microbiota in the digestive tract epithelium comprises a large number of microorganisms that adapt to the immune defense and interact with the host to form symbiotic networks, which affect many physiological processes such as metabolism, tissue development, and immune response. Reports indicate that there are microbial compositional changes in patients with EC, which provides an important opportunity to advance clinical applications based on findings on the gut microbiota. For example, microbiota detection can be used as a biomarker for screening and prognosis, and microorganism levels can be adjusted to treat cancer and decrease the adverse effects of treatment. This review aims to provide an outline of the gut microbiota in esophageal neoplasia, including the mechanisms involved in microbiota-related carcinogenesis and the prospect of utilizing the microbiota as EC biomarkers and treatment targets. These findings have important implications for translating the use of gut microbiota in clinical applications.
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Affiliation(s)
- Jianfeng Zhou
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Shangwei Sun
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Siyuan Luan
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Xin Xiao
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Yushang Yang
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Chengyi Mao
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Longqi Chen
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaoxi Zeng
- West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China
| | - Yonggang Zhang
- Department of Periodical Press, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.,Nursing Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
| | - Yong Yuan
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
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Bu Y, Chan YK, Wong HL, Poon SHL, Lo ACY, Shih KC, Tong L. A Review of the Impact of Alterations in Gut Microbiome on the Immunopathogenesis of Ocular Diseases. J Clin Med 2021; 10:jcm10204694. [PMID: 34682816 PMCID: PMC8541376 DOI: 10.3390/jcm10204694] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 10/01/2021] [Accepted: 10/09/2021] [Indexed: 12/11/2022] Open
Abstract
Recent studies have highlighted the association between ocular diseases and microbiota profiles of the host intestinal tract and oral cavity. There is mounting evidence supporting the existence of a 'gut-eye axis', whereby changes in gut microbiome alter host immunity, with consequential implications for ocular health and disease. In this review, we examined recent published findings on the association between gut microbiome and ocular morbidity, based on 25 original articles published between 2011 to 2020. The review included both clinical and in vivo animal studies, with particular focus on the influence of the microbiome on host immunity and metabolism. Significant associations between altered intestinal microbiome and specific ocular diseases and pathological processes, including Behçet's syndrome, autoimmune uveitis, age-related macular degeneration, choroidal neovascularization, bacterial keratitis, and Sjögren-like lacrimal keratoconjunctivitis have been demonstrated. Furthermore, alterations in the gut microbiome resulted in quantifiable changes in the host immune response, suggesting immunopathogenesis as the basis for the link between intestinal dysbiosis and ocular disease. We also examined and compared different techniques used in the identification and quantification of gut microorganisms. With our enhanced understanding of the potential role of gut commensals in ophthalmic disease, the stage is set for further studies on the underlying mechanisms linking the gut microbiome, the host immune response, and the pathogenesis of ophthalmic disease.
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Affiliation(s)
- Yashan Bu
- Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; (Y.B.); (Y.-K.C.); (H.-L.W.); (S.H.-L.P.); (A.C.-Y.L.)
| | - Yau-Kei Chan
- Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; (Y.B.); (Y.-K.C.); (H.-L.W.); (S.H.-L.P.); (A.C.-Y.L.)
| | - Ho-Lam Wong
- Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; (Y.B.); (Y.-K.C.); (H.-L.W.); (S.H.-L.P.); (A.C.-Y.L.)
| | - Stephanie Hiu-Ling Poon
- Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; (Y.B.); (Y.-K.C.); (H.-L.W.); (S.H.-L.P.); (A.C.-Y.L.)
| | - Amy Cheuk-Yin Lo
- Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; (Y.B.); (Y.-K.C.); (H.-L.W.); (S.H.-L.P.); (A.C.-Y.L.)
| | - Kendrick Co Shih
- Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; (Y.B.); (Y.-K.C.); (H.-L.W.); (S.H.-L.P.); (A.C.-Y.L.)
- Correspondence:
| | - Louis Tong
- Cornea and External Eye Disease Service, Singapore National Eye Centre, Singapore 168751, Singapore;
- Ocular Surface Research Group, Singapore Eye Research Institute, Singapore 169856, Singapore
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Zhang J, Xia Y, Sun J. Breast and gut microbiome in health and cancer. Genes Dis 2021; 8:581-589. [PMID: 34291130 PMCID: PMC8278537 DOI: 10.1016/j.gendis.2020.08.002] [Citation(s) in RCA: 59] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 07/19/2020] [Accepted: 08/14/2020] [Indexed: 02/06/2023] Open
Abstract
The microbiota plays essential roles in health and disease, in both the intestine and the extra-intestine. Dysbiosis of the gut microbiota causes dysfunction in the intestine, which leads to inflammatory, immune, and infectious diseases. Dysbiosis is also associated with diseases beyond the intestine via microbial translocation or metabolisms. The in situ breast microbiome, which may be sourced from the gut through lactation and sexual contact, could be altered and cause breast diseases. In this review, we summarize the recent progress in understanding the interactions among the gut microbiome, breast microbiome, and breast diseases. We discuss the intestinal microbiota, microbial metabolites, and roles of microbiota in immune system. We emphasize the novel roles and mechanisms of the microbiome (both in situ and gastrointestinal sourced) and bacterial products in the development and progression of breast cancer. The intestinal microbial translocation suggests that the gut microbiome is translocated to the skin and subsequently to the breast tissue. The gut bacterial translocation is also due to the increased intestinal permeability. The breast and intestinal microbiota are important factors in maintaining healthy breasts. Micronutrition queuine (Q) is derived from a de novo synthesized metabolite in bacteria. All human cells use queuine and incorporate it into the wobble anticodon position of specific transfer RNAs. We have demonstrated that Q modification regulates genes critical in tight junctions and migration in human breast cancer cells and a breast tumor model. We further discuss the challenges and future perspectives that can move the field forward for prevention, diagnosis, and treatment of breast diseases.
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Affiliation(s)
- Jilei Zhang
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, IL 60607, USA
| | - Yinglin Xia
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, IL 60607, USA
| | - Jun Sun
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, IL 60607, USA
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Faraj J, Takanti V, Tavakoli HR. The Gut-Brain Axis: Literature Overview and Psychiatric Applications. Fed Pract 2021; 38:356-362. [PMID: 34733087 PMCID: PMC8560095 DOI: 10.12788/fp.0159] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
IMPORTANCE Literature exploring the relationship between the intestinal microbiome and its effects on general health and well-being has grown significantly in recent years, and our knowledge of this subject continues to grow. Mounting evidence indicates that the intestinal microbiome is a potential target for therapeutic intervention in psychiatric illness and in neurodegenerative disorders such as Alzheimer disease. It is reasonable to consider modulating not just a patient's neurochemistry, behavior, or cognitive habits, but also their intestinal microbiome in an effort to improve psychiatric symptoms. OBSERVATIONS In this review paper, we show that intestinal microbiota possess the ability to directly influence both physical and mental well-being; therefore, should be included in future discussions regarding psychiatric treatment. CONCLUSIONS Clinicians are encouraged to consider patients' gut health when evaluating and treating psychiatric conditions, such as anxiety and depression. Optimization and diversification of gut flora through the use of psychobiotics-probiotics that confer mental health benefits-may soon become standard practice in conjunction with traditional psychiatric treatment modalities such as pharmacotherapy and psychotherapy.
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Affiliation(s)
- Janine Faraj
- is a General Medical Officer at Naval Surface Forces Atlantic, Medical Readiness Division, Norfolk, Virginia. is a Resident Physician in the Department of Anesthesiology at Rush University Hospital in Chicago, Illinois. is the head of Psychiatry Consultation-Liaison Services at the Naval Medical Center, Portsmouth, Virginia
| | - Varun Takanti
- is a General Medical Officer at Naval Surface Forces Atlantic, Medical Readiness Division, Norfolk, Virginia. is a Resident Physician in the Department of Anesthesiology at Rush University Hospital in Chicago, Illinois. is the head of Psychiatry Consultation-Liaison Services at the Naval Medical Center, Portsmouth, Virginia
| | - Hamid R Tavakoli
- is a General Medical Officer at Naval Surface Forces Atlantic, Medical Readiness Division, Norfolk, Virginia. is a Resident Physician in the Department of Anesthesiology at Rush University Hospital in Chicago, Illinois. is the head of Psychiatry Consultation-Liaison Services at the Naval Medical Center, Portsmouth, Virginia
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Miller MO, Kashyap PC, Becker SL, Thomas RM, Hodin RA, Miller G, Hundeyin M, Pushalkar S, Cohen D, Saxena D, Shogan BD, Morris-Stiff GJ. SSAT State-of-the-Art Conference: Advancements in the Microbiome. J Gastrointest Surg 2021; 25:1885-1895. [PMID: 32989690 DOI: 10.1007/s11605-020-04551-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The microbiome plays a major role in human physiology by influencing obesity, inducing inflammation, and impacting cancer therapies. During the 60th Annual Meeting of the Society of the Alimentary Tract (SSAT) at the State-of-the-Art Conference, experts in the field discussed the influence of the microbiome. This paper is a summary of the influence of the microbiome on obesity, inflammatory bowel disease, pancreatic cancer, cancer therapies, and gastrointestinal optimization. This review shows how the microbiome plays an important role in the development of diseases and surgical complications. Future studies are needed in targeting the gut microbiome to develop individualized therapies.
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Affiliation(s)
- Miquell O Miller
- Department of General Surgery, Stanford University, 300 Pasteur Dr, Stanford, CA, 94305, USA.
| | - Purna C Kashyap
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, 55905, USA
| | - Sarah L Becker
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, 55905, USA
| | - Ryan M Thomas
- Departments of Surgery, Molecular Genetics and Microbiology, University of Florida, Gainesville, FL, 32610, USA
| | - Richard A Hodin
- Department of Surgery, Massachusetts General Hospital, Boston, MA, 02114, USA
| | - George Miller
- Departments of Surgery and Cell Biology, New York University School of Medicine, New York, NY, 10016, USA
| | - Mautin Hundeyin
- Departments of Surgery and Cell Biology, New York University School of Medicine, New York, NY, 10016, USA
| | - Smruti Pushalkar
- Department of Medicine, New York University School of Medicine, New York, NY, 10016, USA
| | - Deirdre Cohen
- Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, NY, 10010, USA
| | - Deepak Saxena
- Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, NY, 10010, USA
| | - Benjamin D Shogan
- Department of Surgery, University of Chicago, Chicago, IL, 60637, USA
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Candelli M, Franza L, Pignataro G, Ojetti V, Covino M, Piccioni A, Gasbarrini A, Franceschi F. Interaction between Lipopolysaccharide and Gut Microbiota in Inflammatory Bowel Diseases. Int J Mol Sci 2021; 22:6242. [PMID: 34200555 PMCID: PMC8226948 DOI: 10.3390/ijms22126242] [Citation(s) in RCA: 179] [Impact Index Per Article: 44.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 05/22/2021] [Accepted: 06/08/2021] [Indexed: 02/06/2023] Open
Abstract
Lipopolysaccharides (LPSs) are bacterial surface glycolipids, produced by Gram-negative bacteria. LPS is known to determine acute inflammatory reactions, particularly in the context of sepsis. However, LPS can also trigger chronic inflammation. In this case, the source of LPS is not an external infection, but rather an increase in endogenous production, which is usually sustained by gut microbiota (GM), and LPS contained in food. The first site in which LPS can exert its inflammatory action is the gut: both GM and gut-associated lymphoid tissue (GALT) are influenced by LPS and shift towards an inflammatory pattern. The changes in GM and GALT induced by LPS are quite similar to the ones seen in IBD: GM loses diversity, while GALT T regulatory (Tregs) lymphocytes are reduced in number, with an increase in Th17 and Th1 lymphocytes. Additionally, the innate immune system is triggered, through the activation of toll-like receptor (TLR)-4, while the epithelium is directly damaged, further triggering inflammation. In this review, we will discuss the importance of the crosstalk between LPS, GM, and GALT, and discuss the possible implications.
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Affiliation(s)
- Marcello Candelli
- Emergency Medicine Department, Fondazione Policlinico Universitario Agostino Gemelli—IRCCS, Università Cattolica del Sacro Cuore di Roma, Largo A. Gemelli 8, 00168 Rome, Italy; (L.F.); (G.P.); (V.O.); (M.C.); (A.P.); (F.F.)
| | - Laura Franza
- Emergency Medicine Department, Fondazione Policlinico Universitario Agostino Gemelli—IRCCS, Università Cattolica del Sacro Cuore di Roma, Largo A. Gemelli 8, 00168 Rome, Italy; (L.F.); (G.P.); (V.O.); (M.C.); (A.P.); (F.F.)
| | - Giulia Pignataro
- Emergency Medicine Department, Fondazione Policlinico Universitario Agostino Gemelli—IRCCS, Università Cattolica del Sacro Cuore di Roma, Largo A. Gemelli 8, 00168 Rome, Italy; (L.F.); (G.P.); (V.O.); (M.C.); (A.P.); (F.F.)
| | - Veronica Ojetti
- Emergency Medicine Department, Fondazione Policlinico Universitario Agostino Gemelli—IRCCS, Università Cattolica del Sacro Cuore di Roma, Largo A. Gemelli 8, 00168 Rome, Italy; (L.F.); (G.P.); (V.O.); (M.C.); (A.P.); (F.F.)
| | - Marcello Covino
- Emergency Medicine Department, Fondazione Policlinico Universitario Agostino Gemelli—IRCCS, Università Cattolica del Sacro Cuore di Roma, Largo A. Gemelli 8, 00168 Rome, Italy; (L.F.); (G.P.); (V.O.); (M.C.); (A.P.); (F.F.)
| | - Andrea Piccioni
- Emergency Medicine Department, Fondazione Policlinico Universitario Agostino Gemelli—IRCCS, Università Cattolica del Sacro Cuore di Roma, Largo A. Gemelli 8, 00168 Rome, Italy; (L.F.); (G.P.); (V.O.); (M.C.); (A.P.); (F.F.)
| | - Antonio Gasbarrini
- Medical and Surgical Science Department, Fondazione Policlinico Universitario Agostino Gemelli—IRCCS, Università Cattolica del Sacro Cuore di Roma, Largo A. Gemelli 8, 00168 Rome, Italy;
| | - Francesco Franceschi
- Emergency Medicine Department, Fondazione Policlinico Universitario Agostino Gemelli—IRCCS, Università Cattolica del Sacro Cuore di Roma, Largo A. Gemelli 8, 00168 Rome, Italy; (L.F.); (G.P.); (V.O.); (M.C.); (A.P.); (F.F.)
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Boeri L, Perottoni S, Izzo L, Giordano C, Albani D. Microbiota-Host Immunity Communication in Neurodegenerative Disorders: Bioengineering Challenges for In Vitro Modeling. Adv Healthc Mater 2021; 10:e2002043. [PMID: 33661580 PMCID: PMC11468246 DOI: 10.1002/adhm.202002043] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Revised: 02/01/2021] [Indexed: 12/12/2022]
Abstract
Human microbiota communicates with its host by secreting signaling metabolites, enzymes, or structural components. Its homeostasis strongly influences the modulation of human tissue barriers and immune system. Dysbiosis-induced peripheral immunity response can propagate bacterial and pro-inflammatory signals to the whole body, including the brain. This immune-mediated communication may contribute to several neurodegenerative disorders, as Alzheimer's disease. In fact, neurodegeneration is associated with dysbiosis and neuroinflammation. The interplay between the microbial communities and the brain is complex and bidirectional, and a great deal of interest is emerging to define the exact mechanisms. This review focuses on microbiota-immunity-central nervous system (CNS) communication and shows how gut and oral microbiota populations trigger immune cells, propagating inflammation from the periphery to the cerebral parenchyma, thus contributing to the onset and progression of neurodegeneration. Moreover, an overview of the technological challenges with in vitro modeling of the microbiota-immunity-CNS axis, offering interesting technological hints about the most advanced solutions and current technologies is provided.
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Affiliation(s)
- Lucia Boeri
- Department of Chemistry, Materials and Chemical Engineering “Giulio Natta”Politecnico di MilanoPiazza Leonardo da Vinci 32Milan20133Italy
| | - Simone Perottoni
- Department of Chemistry, Materials and Chemical Engineering “Giulio Natta”Politecnico di MilanoPiazza Leonardo da Vinci 32Milan20133Italy
| | - Luca Izzo
- Department of Chemistry, Materials and Chemical Engineering “Giulio Natta”Politecnico di MilanoPiazza Leonardo da Vinci 32Milan20133Italy
| | - Carmen Giordano
- Department of Chemistry, Materials and Chemical Engineering “Giulio Natta”Politecnico di MilanoPiazza Leonardo da Vinci 32Milan20133Italy
| | - Diego Albani
- Department of NeuroscienceIstituto di Ricerche Farmacologiche Mario Negri IRCCSvia Mario Negri 2Milan20156Italy
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Volovat SR, Negru S, Stolniceanu CR, Volovat C, Lungulescu C, Scripcariu D, Cobzeanu BM, Stefanescu C, Grigorescu C, Augustin I, Lupascu Ursulescu C, Volovat CC. Nanomedicine to modulate immunotherapy in cutaneous melanoma (Review). Exp Ther Med 2021; 21:535. [PMID: 33815608 PMCID: PMC8014970 DOI: 10.3892/etm.2021.9967] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Accepted: 01/05/2021] [Indexed: 02/07/2023] Open
Abstract
Cancer immunotherapy has shifted the paradigm in cancer treatment in recent years. Immune checkpoint blockage (ICB), the active cancer vaccination and chimeric antigen receptor (CAR) for T-cell-based adoptive cell transfer represent the main developments, achieving a surprising increased survival in patients included in clinical trials. In spite of these results, the current state-of-the-art immunotherapy has its limitations in efficacy. The existence of an interdisciplinary interface involving current knowledge in biology, immunology, bioengineering and materials science represents important progress in increasing the effectiveness of immunotherapy in cancer. Cutaneous melanoma remains a difficult cancer to treat, in which immunotherapy is a major therapeutic option. In fact, enhancing immunotherapy is possible using sophisticated biomedical nanotechnology platforms of organic or inorganic materials or engineering various immune cells to enhance the immune system. In addition, biological devices have developed, changing the approach to and treatment results in melanoma. In this review, we present different modalities to modulate the immune system, as well as opportunities and challenges in melanoma treatment.
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Affiliation(s)
- Simona Ruxandra Volovat
- Department of Medicine III-Medical Oncology-Radiotherapy, 'Grigore T. Popa' University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Serban Negru
- Department of Medical Oncology, 'Victor Babes' University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Cati Raluca Stolniceanu
- Department of Biophysics and Medical Physics-Nuclear Medicine, 'Grigore T. Popa' University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Constantin Volovat
- Department of Medicine III-Medical Oncology-Radiotherapy, 'Grigore T. Popa' University of Medicine and Pharmacy, 700115 Iasi, Romania.,Department of Medical Oncology, 'Euroclinic' Center of Oncology, 70010 Iasi, Romania
| | - Cristian Lungulescu
- Department of Medical Oncology, University of Medicine and Pharmacy, 200349 Craiova, Romania
| | - Dragos Scripcariu
- Department of Surgery, 'Grigore T. Popa' University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Bogdan Mihail Cobzeanu
- Department of Surgery, 'Grigore T. Popa' University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Cipriana Stefanescu
- Department of Biophysics and Medical Physics-Nuclear Medicine, 'Grigore T. Popa' University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Cristina Grigorescu
- Department of Surgery, 'Grigore T. Popa' University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Iolanda Augustin
- Department of Medical Oncology, 'Euroclinic' Center of Oncology, 70010 Iasi, Romania
| | - Corina Lupascu Ursulescu
- Department of Radiology, 'Grigore T. Popa' University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Cristian Constantin Volovat
- Department of Radiology, 'Grigore T. Popa' University of Medicine and Pharmacy, 700115 Iasi, Romania.,Department of Radiology, 'Sf. Spiridon' Emergency Clinic Hospital, 700111 Iasi, Romania
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Dietary Fucose Affects Macrophage Polarization and Reproductive Performance in Mice. Nutrients 2021; 13:nu13030855. [PMID: 33807914 PMCID: PMC8001062 DOI: 10.3390/nu13030855] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 03/02/2021] [Indexed: 12/30/2022] Open
Abstract
Intestinal mucus protects epithelial and immune cells from the gut resident microorganisms, and provides growth-promoting factors as mucus-derived O-glycans for beneficial bacteria. A lack of intestinal protective mucus results in changes in the commensal microflora composition, mucosal immune system reprogramming, and inflammation. Previous work has shown that fucose, the terminal glycan chain component of the intestinal glycoprotein Mucin2, and fucoidan polysaccharides have an anti-inflammatory effect in some mouse models of colitis. This study evaluates the effect of fucose on reproductive performance in heterozygous mutant Muc2 female mice. We found that even though Muc2+/− females are physiologically indistinguishable from C57Bl/6 mice, they have a significantly reduced reproductive performance upon dietary fucose supplementation. Metagenomic analysis reveals that the otherwise healthy wild-type siblings of Muc2−/− animals have reduced numbers of some of the intestinal commensal bacterial species, compared to C57BL/6 mice. We propose that the changes in beneficial microflora affect the immune status in Muc2+/− mice, which causes implantation impairment. In accordance with this hypothesis, we find that macrophage polarization during pregnancy is impaired in Muc2+/− females upon addition of fucose. Metabolic profiling of peritoneal macrophages from Muc2+/− females reveals their predisposition towards anaerobic glycolysis in favor of oxidative phosphorylation, compared to C57BL/6-derived cells. In vitro experiments on phagocytosis activity and mitochondrial respiration suggest that fucose affects oxidative phosphorylation in a genotype-specific manner, which might interfere with implantation depending on the initial status of macrophages. This hypothesis is further confirmed in BALB/c female mice, where fucose caused pregnancy loss and opposed implantation-associated M2 macrophage polarization. Taken together, these data suggest that intestinal microflora affects host immunity and pregnancy outcome. At the same time, dietary fucose might act as a differential regulator of macrophage polarization during implantation, depending on the immune status of the host.
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Host genetics exerts lifelong effects upon hindgut microbiota and its association with bovine growth and immunity. ISME JOURNAL 2021; 15:2306-2321. [PMID: 33649551 PMCID: PMC8319427 DOI: 10.1038/s41396-021-00925-x] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Revised: 01/26/2021] [Accepted: 02/03/2021] [Indexed: 12/22/2022]
Abstract
The gut microbiota is a complex ecological community that plays multiple critical roles within a host. Known intrinsic and extrinsic factors affect gut microbiota structure, but the influence of host genetics is understudied. To investigate the role of host genetics upon the gut microbiota structure, we performed a longitudinal study in which we evaluated the hindgut microbiota and its association with animal growth and immunity across life. We evaluated three different growth stages in an Angus-Brahman multibreed population with a graduated spectrum of genetic variation, raised under variable environmental conditions and diets. We found the gut microbiota structure was changed significantly during growth when preweaning, and fattening calves experienced large variations in diet and environmental changes. However, regardless of the growth stage, we found gut microbiota is significantly influenced by breed composition throughout life. Host genetics explained the relative abundances of 52.2%, 40.0%, and 37.3% of core bacterial taxa at the genus level in preweaning, postweaning, and fattening calves, respectively. Sutterella, Oscillospira, and Roseburia were consistently associated with breed composition at these three growth stages. Especially, butyrate-producing bacteria, Roseburia and Oscillospira, were associated with nine single-nucleotide polymorphisms (SNPs) located in genes involved in the regulation of host immunity and metabolism in the hindgut. Furthermore, minor allele frequency analysis found breed-associated SNPs in the short-chain fatty acids (SCFAs) receptor genes that promote anti-inflammation and enhance intestinal epithelial barrier functions. Our findings provide evidence of dynamic and lifelong host genetic effects upon gut microbiota, regardless of growth stages. We propose that diet, environmental changes, and genetic components may explain observed variation in critical hindgut microbiota throughout life.
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Lee LH, Wong SH, Chin SF, Singh V, Ab Mutalib NS. Editorial: Human Microbiome: Symbiosis to Pathogenesis. Front Microbiol 2021; 12:605783. [PMID: 33679632 PMCID: PMC7928290 DOI: 10.3389/fmicb.2021.605783] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2020] [Accepted: 01/26/2021] [Indexed: 12/15/2022] Open
Affiliation(s)
- Learn-Han Lee
- Novel Bacteria and Drug Discovery (NBDD) Research Group, Microbiome and Bioresource Research Strength (MBRS), Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Subang Jaya, Malaysia
| | - Sunny Hei Wong
- Li Ka Shing Institute of Health Sciences, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Siok-Fong Chin
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Vishal Singh
- Department of Nutritional Sciences, The Pennsylvania State University, State College, PA, United States
| | - Nurul-Syakima Ab Mutalib
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
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Ketpueak T, Thiennimitr P, Apaijai N, Chattipakorn SC, Chattipakorn N. Association of Chronic Opisthorchis Infestation and Microbiota Alteration on Tumorigenesis in Cholangiocarcinoma. Clin Transl Gastroenterol 2020; 12:e00292. [PMID: 33464733 PMCID: PMC8345922 DOI: 10.14309/ctg.0000000000000292] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Accepted: 11/10/2020] [Indexed: 12/24/2022] Open
Abstract
Cholangiocarcinoma (CCA) is a common hepatobiliary cancer in East and Southeast Asia. The data of microbiota contribution in CCA are still unclear. Current available reports have demonstrated that an Opisthorchis viverrini (OV) infection leads to dysbiosis in the bile duct. An increase in the commensal bacteria Helicobacter spp. in OV-infected CCA patients is associated with bile duct inflammation, severity of bile duct fibrosis, and cholangiocyte proliferation. In addition, secondary bile acids, major microbial metabolites, can mediate cholangiocyte inflammation and proliferation in the liver. A range of samples from CCA patients (stool, bile, and tumor) showed different degrees of dysbiosis. The evidence from these samples suggests that OV infection is associated with alterations in microbiota and could potentially have a role in CCA. In this comprehensive review, reports from in vitro, in vivo, and clinical studies that demonstrate possible links between OV infection, microbiota, and CCA pathogenesis are summarized and discussed. Understanding these associations may pave ways for novel potential adjunct intervention in gut microbiota in CCA patients.
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Affiliation(s)
- Thanika Ketpueak
- Division of Oncology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Parameth Thiennimitr
- Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
- Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand
| | - Nattayaporn Apaijai
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
- Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand
| | - Siriporn C. Chattipakorn
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
- Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand
| | - Nipon Chattipakorn
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
- Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand
- Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
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42
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Cianci R, Franza L, Massaro MG, Borriello R, De Vito F, Gambassi G. The Interplay between Immunosenescence and Microbiota in the Efficacy of Vaccines. Vaccines (Basel) 2020; 8:vaccines8040636. [PMID: 33147686 PMCID: PMC7712068 DOI: 10.3390/vaccines8040636] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Revised: 10/24/2020] [Accepted: 10/28/2020] [Indexed: 12/20/2022] Open
Abstract
Vaccinations are among the most effective medical procedures and have had an incredible impact on almost everyone’s life. One of the populations that can benefit the most from them are elderly people. Unfortunately, in this group, vaccines are less effective than in other groups, due to immunosenescence. The immune system ages like the whole body and becomes less effective in responding to infections and vaccinations. At the same time, immunosenescence also favors an inflammatory microenvironment, which is linked to many conditions typical of the geriatrics population. The microbiota is one of the key actors in modulating the immune response and, in this review, we discuss the current evidence on the role of microbiota in regulating the immune response to vaccines, particularly in elderly people.
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Affiliation(s)
- Rossella Cianci
- General Medicine, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Roma, Italy; (M.G.M.); (R.B.); (F.D.V.); (G.G.)
- Correspondence: ; Tel.: +39-06-3015-7597; Fax: +39-06-3550-2775
| | - Laura Franza
- Emergency Medicine, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Roma, Italy;
| | - Maria Grazia Massaro
- General Medicine, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Roma, Italy; (M.G.M.); (R.B.); (F.D.V.); (G.G.)
| | - Raffaele Borriello
- General Medicine, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Roma, Italy; (M.G.M.); (R.B.); (F.D.V.); (G.G.)
| | - Francesco De Vito
- General Medicine, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Roma, Italy; (M.G.M.); (R.B.); (F.D.V.); (G.G.)
| | - Giovanni Gambassi
- General Medicine, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Roma, Italy; (M.G.M.); (R.B.); (F.D.V.); (G.G.)
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Hernández-Granados MJ, Franco-Robles E. Postbiotics in human health: Possible new functional ingredients? Food Res Int 2020; 137:109660. [DOI: 10.1016/j.foodres.2020.109660] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Revised: 08/25/2020] [Accepted: 08/31/2020] [Indexed: 02/06/2023]
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Buonsenso D, Sali M, Pata D, De Rose C, Sanguinetti M, Valentini P, Delogu G. Children and COVID-19: Microbiological and immunological insights. Pediatr Pulmonol 2020; 55:2547-2555. [PMID: 32710652 DOI: 10.1002/ppul.24978] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Accepted: 07/21/2020] [Indexed: 12/12/2022]
Abstract
Since its first description in China, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide being declared a pandemic by the World Health Organization. More than 10.3 million people have been infected and more than 506 000 people died. However, SARS-CoV-2 had a lower impact on the pediatric population. Only about 1% to 2% of infected people are children and few deaths under the age of 14 are described so far. In this article, we discuss microbiological and immunological characteristics of SARS-CoV-2 infection in children highlighting the main differences from adult SARS-CoV-2 infection.
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Affiliation(s)
- Danilo Buonsenso
- Istituto di Microbiologia, Università Cattolica del Sacro Cuore, Rome, Italy.,Dipartimento Scienze della salute della donna, del bambino e di sanità pubblica, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Michela Sali
- Istituto di Microbiologia, Università Cattolica del Sacro Cuore, Rome, Italy.,Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario Agostino Gemelli IRCSS, Rome, Italy
| | - Davide Pata
- Istituto di Pediatria, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Cristina De Rose
- Istituto di Pediatria, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Maurizio Sanguinetti
- Istituto di Microbiologia, Università Cattolica del Sacro Cuore, Rome, Italy.,Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario Agostino Gemelli IRCSS, Rome, Italy
| | - Piero Valentini
- Dipartimento Scienze della salute della donna, del bambino e di sanità pubblica, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.,Istituto di Pediatria, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Giovanni Delogu
- Istituto di Microbiologia, Università Cattolica del Sacro Cuore, Rome, Italy.,Mater Olbia Hospital, Olbia, Italy
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Effects of Vigiis 101-LAB on a healthy population's gut microflora, peristalsis, immunity, and anti-oxidative capacity: A randomized, double-blind, placebo-controlled clinical study. Heliyon 2020; 6:e04979. [PMID: 32995642 PMCID: PMC7511805 DOI: 10.1016/j.heliyon.2020.e04979] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 07/07/2020] [Accepted: 09/16/2020] [Indexed: 01/01/2023] Open
Abstract
Vigiis 101-LAB capsules are produced from the fermentation of Lactobacillus paracasei subsp. paracasei NTU 101. We tested effects of Vigiis 101-LAB capsules I or II (5 or 10 billion CFU/day, respectively) on gut microflora in clinical trial I, and on peristalsis, immunity, and anti-oxidative capacity in clinical trial II, during a 4-week randomized, double-blind, placebo-controlled, adaptive-design study. In trial I, 36 subjects were divided into capsule I and placebo groups. After 4 weeks, Bifidobacterium spp. and Lactobacillus spp. counts were significantly higher in the feces of treatment subjects, with increases of 4.01- and 4.25-fold, respectively. In trial II, 52 subjects were divided into capsule II and placebo groups. After 4 weeks, the treatment group was found to have improved motility, decreased food transit time, and significantly increased immunoglobulin G, immunoglobulin M, and antioxidant activity. Thus, daily administration of Vigiis 101 capsule II can improve peristalsis, immunity, and anti-oxidative capacity.
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Microbiota Modulates the Immunomodulatory Effects of Filifolinone on Atlantic Salmon. Microorganisms 2020; 8:microorganisms8091320. [PMID: 32872599 PMCID: PMC7564783 DOI: 10.3390/microorganisms8091320] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Revised: 08/21/2020] [Accepted: 08/26/2020] [Indexed: 02/06/2023] Open
Abstract
Filifolinone is an aromatic geranyl derivative, a natural compound isolated from Heliotropum sclerocarpum, which has immunomodulatory effects on Atlantic salmon, upregulating cytokines involved in Th1-type responses through a mechanism that remains unknown. In this work, we determined whether the immunomodulatory effects of filifolinone depend on the host microbiotic composition. We evaluated the effect of filifolinone on immune genes and intestinal microbiotic composition of normal fish and fish previously treated with bacitracin/neomycin. Filifolinone induced the early expression of IFN-α1 and TGF-β, followed by the induction of TNF-α, IL-1β, and IFN-γ. A pre-treatment with antibiotics modified this effect, mainly changing the expression of IL-1β and IFN-γ. The evaluation of microbial diversity shows that filifolinone modifies the composition of intestinal microbiota, increasing the abundance of immunostimulating organisms like yeast and firmicutes. We identified 69 operational taxonomic units (OTUs) associated with filifolinone-induced IFN-γ. Our results indicate that filifolinone stimulates the immune system in two ways, one dependent on fish microbiota and the other not. To our knowledge, this is the first report of microbiota-dependent immunostimulation in Salmonids.
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Troublesome friends within us: the role of gut microbiota on rheumatoid arthritis etiopathogenesis and its clinical and therapeutic relevance. Clin Exp Med 2020; 21:1-13. [PMID: 32712721 DOI: 10.1007/s10238-020-00647-y] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Accepted: 07/13/2020] [Indexed: 12/14/2022]
Abstract
The role of gut microbiota on immune regulation and the development of autoimmune diseases such as rheumatoid arthritis (RA) is an emerging research topic. Multiple studies have demonstrated alterations on gut microbiota composition and/or function (referred to as dysbiosis) both in early and established RA patients. Still, research delineating the molecular mechanisms by which gut microorganisms induce the loss of immune tolerance or contribute to disease progression is scarce. Available data indicate that gut microbiota alterations are involved in RA autoimmune response by several mechanisms including the post-translational modification of host proteins, molecular mimicry between bacterial and host epitopes, activation of immune system and polarization toward inflammatory phenotypes, as well as induction of intestinal permeability. Therefore, in this review we analyze recent clinical and molecular evidence linking gut microbiota with the etiopathogenesis of RA. The potential of the gut microbiota as a diagnostic or severity biomarker is discussed, as well as the opportunity areas for the development of complementary therapeutic strategies based on the modulation of gut microbiota in the rheumatic patient.
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Jang YO, Lee SH, Choi JJ, Kim DH, Choi JM, Kang MJ, Oh YM, Park YJ, Shin Y, Lee SW. Fecal microbial transplantation and a high fiber diet attenuates emphysema development by suppressing inflammation and apoptosis. Exp Mol Med 2020; 52:1128-1139. [PMID: 32681029 PMCID: PMC8080776 DOI: 10.1038/s12276-020-0469-y] [Citation(s) in RCA: 71] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2020] [Revised: 05/24/2020] [Accepted: 06/08/2020] [Indexed: 12/12/2022] Open
Abstract
Recent work has suggested a microbial dysbiosis association between the lung and gut in respiratory diseases. Here, we demonstrated that gut microbiome modulation attenuated emphysema development. To modulate the gut microbiome, fecal microbiota transplantation (FMT) and diet modification were adopted in mice exposed to smoking and poly I:C for the emphysema model. We analyzed the severity of emphysema by the mean linear intercept (MLI) and apoptosis by the fluorescent TUNEL assay. Microbiome analysis was also performed in feces and fecal extracellular vesicles (EVs). The MLI was significantly increased with smoking exposure. FMT or a high-fiber diet (HFD) attenuated the increase. Weight loss, combined with smoking exposure, was not noted in mice with FMT. HFD significantly decreased macrophages and lymphocytes in bronchoalveolar lavage fluid. Furthermore, IL-6 and IFN-γ were decreased in the bronchoalveolar lavage fluid and serum. The TUNEL score was significantly lower in mice with FMT or HFD, suggesting decreased cell apoptosis. In the microbiome analysis, Bacteroidaceae and Lachnospiraceae, which are alleged to metabolize fiber into short-chain fatty acids (SCFAs), increased at the family level with FMT and HFD. FMT and HFD attenuated emphysema development via local and systemic inhibition of inflammation and changes in gut microbiota composition, which could provide a new paradigm in COPD treatment.
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Affiliation(s)
- Yoon Ok Jang
- Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea
- Department of Convergence Medicine, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea
| | - Se Hee Lee
- Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea
- Department of Pulmonology, Allergy and Critical Care Medicine, CHA Bundang Medical Center, CHA University, Seongnam-si, 13496, Republic of Korea
| | - Jong Jin Choi
- Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea
| | - Do-Hyun Kim
- Department of Life Science, College of Natural Sciences, Research Institute for Natural Sciences, Research Institute for Convergence of Basic Sciences, Hanyang University, Seoul, 04763, Republic of Korea
| | - Je-Min Choi
- Department of Life Science, College of Natural Sciences, Research Institute for Natural Sciences, Research Institute for Convergence of Basic Sciences, Hanyang University, Seoul, 04763, Republic of Korea
| | - Min-Jong Kang
- Section of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, 06520-8057, Connecticut, USA
| | - Yeon-Mok Oh
- Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea
| | - Young-Jun Park
- Environmental Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea
| | - Yong Shin
- Department of Convergence Medicine, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea.
| | - Sei Won Lee
- Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea.
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Zhang X, Pan Z. Influence of microbiota on immunity and immunotherapy for gastric and esophageal cancers. Gastroenterol Rep (Oxf) 2020; 8:206-214. [PMID: 32665852 PMCID: PMC7333930 DOI: 10.1093/gastro/goaa014] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2020] [Revised: 03/05/2020] [Accepted: 03/11/2020] [Indexed: 12/13/2022] Open
Abstract
Gastric and esophageal cancers are multifactorial and multistage-involved malignancy. While the impact of gut microbiota on overall human health and diseases has been well documented, the influence of gastric and esophageal microbiota on gastric and esophageal cancers remains unclear. This review will discuss the reported alteration in the composition of gastric and esophageal microbiota in normal and disease conditions, and the potential role of dysbiosis in carcinogenesis and tumorigenesis. This review will also discuss how dysbiosis stimulates local and systemic immunity, which may impact on the immunotherapy for cancer.
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Affiliation(s)
- Xiaoli Zhang
- Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA
| | - Zui Pan
- College of Nursing and Health Innovation, The University of Texas at Arlington, Arlington, TX, USA
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50
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Kechida M. Update on Autoimmune Diseases Pathogenesis. Curr Pharm Des 2020; 25:2947-2952. [PMID: 31686634 DOI: 10.2174/1381612825666190709205421] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2019] [Accepted: 06/30/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Autoimmune diseases result from the interplay of cellular effectors like T and B cells, regulatory cells in addition to molecular factors like cytokines and regulatory molecules. METHODS Different electronic databases were searched in a non-systematic way to find out the literature of interest. RESULTS Pathogenesis of autoimmune diseases involves typical factors such as genetic background including HLA and non HLA system genes, environmental factors such as infectious agents and inflammatory cells mainly T and B lymphocytes abnormally activated leading to immune dysfunction. Other recently reported less typical factors such as micro-RNAs, circular RNAs, myeloperoxidase, vimentine and microbiome dysbiosis seem to be potential target therapies. CONCLUSION We aimed in this manuscript to review common factors in the pathogenesis of autoimmune diseases.
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Affiliation(s)
- Melek Kechida
- Internal Medicine and Endocrinology Department of Fattouma Bourguiba University Hospital, University of Monastir, BP 56 Avenue Taher Haddad, Monastir 5000, Tunisia
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