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1
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Ke HY, Chen MH, Tsao CM, Hii HP, Kuo CW, Ka SM, Wu CC, Shih CC. Therapeutic potential of butyrate against heat Stress-Induced intestinal damage, systemic inflammation, and multiple organ Dysfunction: Insights from in vitro and in vivo experiments. Eur J Pharmacol 2025; 999:177710. [PMID: 40348323 DOI: 10.1016/j.ejphar.2025.177710] [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: 01/07/2025] [Revised: 05/04/2025] [Accepted: 05/06/2025] [Indexed: 05/14/2025]
Abstract
Global warming is a major risk factor for life-threatening heat stroke (HS). Systemic inflammation plays a key role in the pathophysiology of HS, substantially affecting clinical outcomes. Reduced intestinal blood flow during HS causes ischemia-reperfusion injury, compromising the intestinal barrier and triggering systemic inflammation and organ damage. Butyrate, a short-chain fatty acid, plays a multifaceted role in maintaining intestinal health, inhibiting inflammation, and alleviating oxidative stress. Therefore, this study aimed to evaluate butyrate's therapeutic potential against HS and explored the mechanisms underlying its protective effects. Male Wistar rats were divided into 4 groups: control, control + butyrate, HS, and HS + butyrate. Hemodynamic changes, biochemical parameters, coagulation markers, cytokine levels, polymorphonuclear neutrophil infiltration, and survival rates were analyzed. Additionally, ileal samples (from rats) and LS174T cells were used to investigate the effect of butyrate on intestinal function. Heat stress induced cytotoxicity; reduced transepithelial resistance in intestinal goblet cells; and triggered intestinal inflammation, oxidative stress, and apoptosis in HS rats. These rats exhibited systemic inflammation, hypotension, tachycardia, coagulopathy, multiple organ dysfunction, and mortality. Butyrate treatment reduced cytotoxicity and improved transepithelial resistance in LS174T cells. Butyrate also reduced intestinal heat stress, inflammation, oxidative stress, and apoptosis, as well as systemic inflammation in HS rats. Furthermore, butyrate ameliorated hypotension, tachycardia, coagulopathy, and multiple organ dysfunction and increased survival in HS rats. These findings indicate that butyrate is a promising intervention for mitigating heat stress-induced intestinal damage, systemic inflammation, and multiple organ dysfunction.
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Affiliation(s)
- Hung-Yen Ke
- Division of Cardiovascular Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Ming-Hua Chen
- Department of Internal Medicine, Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan
| | - Cheng-Ming Tsao
- Department of Anesthesiology, Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan
| | - Hiong-Ping Hii
- Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan
| | - Chia-Wen Kuo
- Department of Nephrology, Taichung Armed Forces General Hospital, Taichung, Taiwan
| | - Shuk-Man Ka
- Graduate Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei, Taiwan
| | - Chin-Chen Wu
- Department and Graduate Institute of Pharmacology, National Defense Medical Center, Taipei, Taiwan
| | - Chih-Chin Shih
- Department and Graduate Institute of Pharmacology, National Defense Medical Center, Taipei, Taiwan.
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2
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Guan Y, Cheng H, Zhang N, Cai Y, Zhang Q, Jiang X, Wang A, Zeng H, Jia B. The role of the esophageal and intestinal microbiome in gastroesophageal reflux disease: past, present, and future. Front Immunol 2025; 16:1558414. [PMID: 40061946 PMCID: PMC11885504 DOI: 10.3389/fimmu.2025.1558414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Accepted: 02/04/2025] [Indexed: 05/13/2025] Open
Abstract
Gastroesophageal reflux disease (GERD) is one of the common diseases of the digestive system, and its incidence is increasing year by year, in addition to its typical symptoms of acid reflux and heartburn affecting the quality of patients' survival. The pathogenesis of GERD has not yet been clarified. With the development of detection technology, microbiome have been studied in depth. Normal microbiome are symbiotic with the host and can assist the host to fulfill the roles of digestion and absorption, and promote the development of the host. Dysbiosis of the microbiome forms a new internal environment, under which it may affect the development of GERD from the perspectives of molecular mechanisms: microbial activation of Toll-like receptors, microbial stimulation of cyclooxygenase-2 expression, microbial stimulation of inducible nitrous oxide synthase, and activation of the NLRP3 inflammatory vesicle; immune mechanisms; and impact on the dynamics of the lower gastrointestinal tract. This review will explore the esophageal microbiome and intestinal microbiome characteristics of GERD and the mechanisms by which dysbiotic microbiome induces GERD.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Boyi Jia
- Department of Spleen and Stomach Diseases, Fangshan Traditional Medical Hospital of Beijing, Beijing, China
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3
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Itoh T, Miyazono D, Sugata H, Mori C, Takahata M. Anti-inflammatory effects of heat-killed Lactiplantibacillus argentoratensis BBLB001 on a gut inflammation co-culture cell model and dextran sulfate sodium-induced colitis mouse model. Int Immunopharmacol 2024; 143:113408. [PMID: 39461236 DOI: 10.1016/j.intimp.2024.113408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Revised: 09/16/2024] [Accepted: 10/11/2024] [Indexed: 10/29/2024]
Abstract
Dysbiosis caused by dietary changes can alter the intestinal bacterial species and is closely associated with inflammatory bowel disease (IBD). Among the possible treatment options, postbiotics, which act to balance the constituent intestinal microflora, have gained substantial attention. Herein, we investigated the anti-inflammatory effects of heat-killed Lactiplantibacillus argentoratensis (hk-LA) BBLB001 isolated from a marine environment using both cell (Caco2/RAW264.7 cell co-culture) and animal (dextran sodium sulfate [DSS]-induced colitis in mice) models. hk-LA BBLB001 markedly reduced IL-8 secretion in Caco-2 cell culture medium after lipopolysaccharide-mediated stimulation of RAW264.7 cells by enhancing the expression of cell adhesion factors.The body weight loss, reduced inflammatory cytokine levels in the serum and colon tissues, colon shortening, and myeloperoxidase activation caused by DSS in mice were alleviated by hk-LA BBLB001. Similar to that in the intestinal cell model, the gene and protein expressions of cell adhesion molecules in the colon tissue were increased upon hk-LA BBLB001 treatment in DSS-induced colitis mice. We observed increased mucin expression and secretory IgA concentration in colon tissues, suggesting that hk-LA BBLB001 intake may benefit pathogen defense and the regulation of intestinal commensal bacteria. Thus, hk-LA BBLB001 may serve as an instrumental postbiotic material in IBD treatment.
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Affiliation(s)
- Tomohiro Itoh
- Laboratory for Molecular Chemistry of Aquatic Materials, Department of Life Sciences, Graduate School of Bioresources, Mie University, 1577 Kurimamachiya, Tsu, Mie 514-8507, Japan.
| | - Daiki Miyazono
- Laboratory for Molecular Chemistry of Aquatic Materials, Department of Life Sciences, Graduate School of Bioresources, Mie University, 1577 Kurimamachiya, Tsu, Mie 514-8507, Japan
| | - Hayato Sugata
- BIOBANK Co., Ltd., 388-1 Hirata, Kita, Okayama 700-0952, Japan
| | - Chizuru Mori
- BIOBANK Co., Ltd., 388-1 Hirata, Kita, Okayama 700-0952, Japan
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Guamán LP, Carrera-Pacheco SE, Zúñiga-Miranda J, Teran E, Erazo C, Barba-Ostria C. The Impact of Bioactive Molecules from Probiotics on Child Health: A Comprehensive Review. Nutrients 2024; 16:3706. [PMID: 39519539 PMCID: PMC11547800 DOI: 10.3390/nu16213706] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Revised: 10/04/2024] [Accepted: 10/08/2024] [Indexed: 11/16/2024] Open
Abstract
Background: This review investigates the impact of bioactive molecules produced by probiotics on child health, focusing on their roles in modulating gut microbiota, enhancing immune function, and supporting overall development. Key metabolites, including short-chain fatty acids (SCFAs), bacteriocins, exopolysaccharides (EPSs), vitamins, and gamma-aminobutyric acid (GABA), are highlighted for their ability to maintain gut health, regulate inflammation, and support neurodevelopment. Objectives: The aim of this review is to examine the mechanisms of action and clinical evidence supporting the use of probiotics and postbiotics in pediatric healthcare, with a focus on promoting optimal growth, development, and overall health in children. Methods: The review synthesizes findings from clinical studies that investigate the effects of probiotics and their metabolites on pediatric health. The focus is on specific probiotics and their ability to influence gut health, immune responses, and developmental outcomes. Results: Clinical studies demonstrate that specific probiotics and their metabolites can reduce gastrointestinal disorders, enhance immune responses, and decrease the incidence of allergies and respiratory infections in pediatric populations. Additionally, postbiotics-bioactive compounds from probiotic fermentation-offer promising benefits, such as improved gut barrier function, reduced inflammation, and enhanced nutrient absorption, while presenting fewer safety concerns compared to live probiotics. Conclusions: By examining the mechanisms of action and clinical evidence, this review underscores the potential of integrating probiotics and postbiotics into pediatric healthcare strategies to promote optimal growth, development, and overall health in children.
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Affiliation(s)
- Linda P. Guamán
- Centro de Investigación Biomédica (CENBIO), Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Quito 170527, Ecuador; (S.E.C.-P.); (J.Z.-M.)
| | - Saskya E. Carrera-Pacheco
- Centro de Investigación Biomédica (CENBIO), Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Quito 170527, Ecuador; (S.E.C.-P.); (J.Z.-M.)
| | - Johana Zúñiga-Miranda
- Centro de Investigación Biomédica (CENBIO), Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Quito 170527, Ecuador; (S.E.C.-P.); (J.Z.-M.)
| | - Enrique Teran
- Colegio de Ciencias de la Salud, Universidad San Francisco de Quito USFQ, Quito 170901, Ecuador; (E.T.); (C.E.)
| | - Cesar Erazo
- Colegio de Ciencias de la Salud, Universidad San Francisco de Quito USFQ, Quito 170901, Ecuador; (E.T.); (C.E.)
| | - Carlos Barba-Ostria
- Colegio de Ciencias de la Salud, Universidad San Francisco de Quito USFQ, Quito 170901, Ecuador; (E.T.); (C.E.)
- Instituto de Microbiología, Universidad San Francisco de Quito USFQ, Quito 170901, Ecuador
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5
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Hou M, Yu QQ, Yang L, Zhao H, Jiang P, Qin L, Zhang Q. The role of short-chain fatty acid metabolism in the pathogenesis, diagnosis and treatment of cancer. Front Oncol 2024; 14:1451045. [PMID: 39435279 PMCID: PMC11491288 DOI: 10.3389/fonc.2024.1451045] [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: 06/19/2024] [Accepted: 09/19/2024] [Indexed: 10/23/2024] Open
Abstract
Short-chain fatty acids (SCFAs), which are saturated fatty acids consisting of six or fewer carbon atoms, have been found to be closely associated with the biological behavior of malignant tumors. This manuscript provides a comprehensive review on the role of SCFAs in regulating cell cycle, apoptosis, tumor angiogenesis, epithelial-mesenchymal transition, protein regulatory pathways, and histone regulation in promoting the development of malignant tumors. Furthermore, we discuss the potential therapeutic strategies targeting SCFAs for treating malignant tumors. This review offers a theoretical foundation for investigating the mechanisms by which SCFAs impact malignant tumors and provides insights into developing novel treatment targets.
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Affiliation(s)
- Maolin Hou
- Department of Internal Medicine, Siziwangqi People’s Hospital, Wulancabu, China
| | - Qing-Qing Yu
- Translational Pharmaceutical Laboratory, Jining NO.1 People’s Hospital, Jining, China
| | - Le Yang
- Department of Gastrointestinal Surgery, Jining NO.1 People’s Hospital, Jining, China
| | - Haibo Zhao
- Department of Oncology, Jining No.1 People’s Hospital, Jining, China
| | - Pei Jiang
- Translational Pharmaceutical Laboratory, Jining NO.1 People’s Hospital, Jining, China
| | - Lei Qin
- Department of Gastrointestinal Surgery, Jining NO.1 People’s Hospital, Jining, China
| | - Qiujie Zhang
- Department of Oncology, Jining No.1 People’s Hospital, Jining, China
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6
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Sharma R, Raza GS, Sodum N, Walkowiak J, Herzig KH. Effect of hypoxia on GLP-1 secretion - an in vitro study using enteroendocrine STC-1 -cells as a model. Pflugers Arch 2024; 476:1613-1621. [PMID: 39075239 PMCID: PMC11381484 DOI: 10.1007/s00424-024-02996-z] [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: 05/22/2024] [Revised: 07/16/2024] [Accepted: 07/17/2024] [Indexed: 07/31/2024]
Abstract
Glucagon-like peptide (GLP)-1 is a hormone released by enteroendocrine L-cells after food ingestion. L-cells express various receptors for nutrient sensing including G protein-coupled receptors (GPRs). Intestinal epithelial cells near the lumen have a lower O2 tension than at the base of the crypts, which leads to hypoxia in L-cells. We hypothesized that hypoxia affects nutrient-stimulated GLP-1 secretion from the enteroendocrine cell line STC-1, the most commonly used model. In this study, we investigated the effect of hypoxia (1% O2) on alpha-linolenic acid (αLA) stimulated GLP-1 secretion and their receptor expressions. STC-1 cells were incubated for 12 h under hypoxia (1% O2) and treated with αLA to stimulate GLP-1 secretion. 12 h of hypoxia did not change basal GLP-1 secretion, but significantly reduced nutrient (αLA) stimulated GLP-1 secretion. In normoxia, αLA (12.5 μM) significantly stimulated (~ 5 times) GLP-1 secretion compared to control, but under hypoxia, GLP-1 secretion was reduced by 45% compared to normoxia. αLA upregulated GPR120, also termed free fatty acid receptor 4 (FFAR4), expressions under normoxia as well as hypoxia. Hypoxia downregulated GPR120 and GPR40 expression by 50% and 60%, respectively, compared to normoxia. These findings demonstrate that hypoxia does not affect the basal GLP-1 secretion but decreases nutrient-stimulated GLP-1 secretion. The decrease in nutrient-stimulated GLP-1 secretion was due to decreased GPR120 and GPR40 receptors expression. Changes in the gut environment and inflammation might contribute to the hypoxia of the epithelial and L-cells.
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Affiliation(s)
- Ravikant Sharma
- Research Unit of Biomedicine and Internal Medicine, Biocenter of Oulu, Medical Research Center, University of Oulu, Aapistie 5, 90220, Oulu, Finland
| | - Ghulam Shere Raza
- Research Unit of Biomedicine and Internal Medicine, Biocenter of Oulu, Medical Research Center, University of Oulu, Aapistie 5, 90220, Oulu, Finland
| | - Nalini Sodum
- Research Unit of Biomedicine and Internal Medicine, Biocenter of Oulu, Medical Research Center, University of Oulu, Aapistie 5, 90220, Oulu, Finland
| | - Jaroslaw Walkowiak
- Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences, 60572, Poznań, Poland
| | - Karl-Heinz Herzig
- Research Unit of Biomedicine and Internal Medicine, Biocenter of Oulu, Medical Research Center, University of Oulu, Aapistie 5, 90220, Oulu, Finland.
- Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences, 60572, Poznań, Poland.
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7
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Ikegami M, Narabayashi H, Nakata K, Yamashita M, Sugi Y, Fuji Y, Matsufuji H, Harata G, Yoda K, Miyazawa K, Nakanishi Y, Takahashi K. Intervention in gut microbiota increases intestinal γ-aminobutyric acid and alleviates anxiety behavior: a possible mechanism via the action on intestinal epithelial cells. Front Cell Infect Microbiol 2024; 14:1421791. [PMID: 39301289 PMCID: PMC11410766 DOI: 10.3389/fcimb.2024.1421791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Accepted: 08/14/2024] [Indexed: 09/22/2024] Open
Abstract
The role of the gut microbiota in the gut-brain axis has attracted attention in recent years. Some gut microbiota produces γ-aminobutyric acid (GABA), a major inhibitory neurotransmitter in mammals, in vitro, but the correlation between gut microbiota composition and intestinal GABA concentration, as well as the action of intestinal GABA in vivo, are poorly understood. Herein, we found that the intestinal GABA concentration was increased in mice by the intervention of the gut microbiota with neomycin or Bifidobacterium bifidum TMC3115 (TMC3115). Administration of TMC3115 reduced anxiety without affecting serum levels of serotonin, corticosterone, or GABA. We further found that intestinal epithelial cells expressed GABA receptor subunits and mediated mitogen-activated protein kinase signaling upon GABA stimulation. In addition, administration of TMC3115 induced mitogen-activated protein kinase signaling in colonic epithelial cells but not in small intestinal epithelial cells in mice. These results indicate that GABA produced by the gut microbiota, mainly in the colon, may affect host behavioral characteristics via GABA receptors expressed in intestinal epithelial cells without being transferred to the blood. This study suggests a novel mechanism by which intestinal GABA exerts physiological effects, even in the presence of the blood-brain barrier.
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Affiliation(s)
- Mion Ikegami
- Nihon University Graduate School of Bioresource Sciences, Fujisawa, Kanagawa, Japan
| | - Hikari Narabayashi
- Nihon University Graduate School of Bioresource Sciences, Fujisawa, Kanagawa, Japan
| | - Kazuaki Nakata
- Nihon University Graduate School of Bioresource Sciences, Fujisawa, Kanagawa, Japan
| | - Miyu Yamashita
- Nihon University Graduate School of Bioresource Sciences, Fujisawa, Kanagawa, Japan
| | - Yutaka Sugi
- College of Bioresource Sciences, Nihon University, Fujisawa, Kanagawa, Japan
| | - Yushiro Fuji
- Nihon University Graduate School of Bioresource Sciences, Fujisawa, Kanagawa, Japan
| | - Hiroshi Matsufuji
- Nihon University Graduate School of Bioresource Sciences, Fujisawa, Kanagawa, Japan
- College of Bioresource Sciences, Nihon University, Fujisawa, Kanagawa, Japan
| | - Gaku Harata
- Technical Research Laboratory, Takanashi Milk Products Co., Ltd, Yokohama, Kanagawa, Japan
| | - Kazutoyo Yoda
- Technical Research Laboratory, Takanashi Milk Products Co., Ltd, Yokohama, Kanagawa, Japan
| | - Kenji Miyazawa
- Technical Research Laboratory, Takanashi Milk Products Co., Ltd, Yokohama, Kanagawa, Japan
| | - Yusuke Nakanishi
- Nihon University Graduate School of Bioresource Sciences, Fujisawa, Kanagawa, Japan
- College of Bioresource Sciences, Nihon University, Fujisawa, Kanagawa, Japan
| | - Kyoko Takahashi
- Nihon University Graduate School of Bioresource Sciences, Fujisawa, Kanagawa, Japan
- College of Bioresource Sciences, Nihon University, Fujisawa, Kanagawa, Japan
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8
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Intarajak T, Udomchaiprasertkul W, Khoiri AN, Sutheeworapong S, Kusonmano K, Kittichotirat W, Thammarongtham C, Cheevadhanarak S. Distinct gut microbiomes in Thai patients with colorectal polyps. World J Gastroenterol 2024; 30:3336-3355. [PMID: 39086748 PMCID: PMC11287419 DOI: 10.3748/wjg.v30.i27.3336] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 04/30/2024] [Accepted: 05/31/2024] [Indexed: 07/11/2024] Open
Abstract
BACKGROUND Colorectal polyps that develop via the conventional adenoma-carcinoma sequence [e.g., tubular adenoma (TA)] often progress to malignancy and are closely associated with changes in the composition of the gut microbiome. There is limited research concerning the microbial functions and gut microbiomes associated with colorectal polyps that arise through the serrated polyp pathway, such as hyperplastic polyps (HP). Exploration of microbiome alterations associated with HP and TA would improve the understanding of mechanisms by which specific microbes and their metabolic pathways contribute to colorectal carcinogenesis. AIM To investigate gut microbiome signatures, microbial associations, and microbial functions in HP and TA patients. METHODS Full-length 16S rRNA sequencing was used to characterize the gut microbiome in stool samples from control participants without polyps [control group (CT), n = 40], patients with HP (n = 52), and patients with TA (n = 60). Significant differences in gut microbiome composition and functional mechanisms were identified between the CT group and patients with HP or TA. Analytical techniques in this study included differential abundance analysis, co-occurrence network analysis, and differential pathway analysis. RESULTS Colorectal cancer (CRC)-associated bacteria, including Streptococcus gallolyticus (S. gallolyticus), Bacteroides fragilis, and Clostridium symbiosum, were identified as characteristic microbial species in TA patients. Mediterraneibacter gnavus, associated with dysbiosis and gastrointestinal diseases, was significantly differentially abundant in the HP and TA groups. Functional pathway analysis revealed that HP patients exhibited enrichment in the sulfur oxidation pathway exclusively, whereas TA patients showed dominance in pathways related to secondary metabolite biosynthesis (e.g., mevalonate); S. gallolyticus was a major contributor. Co-occurrence network and dynamic network analyses revealed co-occurrence of dysbiosis-associated bacteria in HP patients, whereas TA patients exhibited co-occurrence of CRC-associated bacteria. Furthermore, the co-occurrence of SCFA-producing bacteria was lower in TA patients than HP patients. CONCLUSION This study revealed distinct gut microbiome signatures associated with pathways of colorectal polyp development, providing insights concerning the roles of microbial species, functional pathways, and microbial interactions in colorectal carcinogenesis.
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Affiliation(s)
- Thoranin Intarajak
- Bioinformatics Unit, Chulabhorn Royal Academy, Lak Si 10210, Bangkok, Thailand
- Bioinformatics and Systems Biology Program, School of Bioresources and Technology, and School of Information Technology, King Mongkut’s University of Technology Thonburi, Bang Khun Thian 10150, Bangkok, Thailand
- Systems Biology and Bioinformatics Unit, Pilot Plant Development and Training Institute, King Mongkut’s University of Technology Thonburi, Bang Khun Thian 10150, Bangkok, Thailand
| | | | - Ahmad Nuruddin Khoiri
- Bioinformatics and Systems Biology Program, School of Bioresources and Technology, and School of Information Technology, King Mongkut’s University of Technology Thonburi, Bang Khun Thian 10150, Bangkok, Thailand
| | - Sawannee Sutheeworapong
- Systems Biology and Bioinformatics Unit, Pilot Plant Development and Training Institute, King Mongkut’s University of Technology Thonburi, Bang Khun Thian 10150, Bangkok, Thailand
| | - Kanthida Kusonmano
- Bioinformatics and Systems Biology Program, School of Bioresources and Technology, and School of Information Technology, King Mongkut’s University of Technology Thonburi, Bang Khun Thian 10150, Bangkok, Thailand
- Systems Biology and Bioinformatics Unit, Pilot Plant Development and Training Institute, King Mongkut’s University of Technology Thonburi, Bang Khun Thian 10150, Bangkok, Thailand
| | - Weerayuth Kittichotirat
- Bioinformatics and Systems Biology Program, School of Bioresources and Technology, and School of Information Technology, King Mongkut’s University of Technology Thonburi, Bang Khun Thian 10150, Bangkok, Thailand
- Systems Biology and Bioinformatics Unit, Pilot Plant Development and Training Institute, King Mongkut’s University of Technology Thonburi, Bang Khun Thian 10150, Bangkok, Thailand
| | - Chinae Thammarongtham
- National Center for Genetic Engineering and Biotechnology, King Mongkut's University of Technology Thonburi, Bang Khun Thian 10150, Bangkok, Thailand
| | - Supapon Cheevadhanarak
- Systems Biology and Bioinformatics Unit, Pilot Plant Development and Training Institute, King Mongkut’s University of Technology Thonburi, Bang Khun Thian 10150, Bangkok, Thailand
- School of Bioresources and Technology, King Mongkut’s University of Technology Thonburi, Bank Khun Thian 10150, Bangkok, Thailand
- Fungal Biotechnology Unit, Pilot Plant Development and Training Institute, King Mongkut’s University of Technology Thonburi, Bang Khun Thian 10150, Bangkok, Thailand
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9
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Binienda A, Fichna J. Current understanding of free fatty acids and their receptors in colorectal cancer treatment. Nutr Res 2024; 127:133-143. [PMID: 38943731 DOI: 10.1016/j.nutres.2024.05.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Revised: 05/29/2024] [Accepted: 05/29/2024] [Indexed: 07/01/2024]
Abstract
Colorectal cancer (CRC) is one of the leading causes of cancer-related death. Currently, dietary factors are being emphasized in the pathogenesis of CRC. There is strong evidence that fatty acids (FAs) and free FA receptors (FFARs) are involved in CRC. This comprehensive review discusses the role of FAs and their receptors in CRC pathophysiology, development, and treatment. In particular, butyrate and n-3 polyunsaturated fatty acids have been found to exert anticancer properties by, among others, inhibiting proliferation and metastasis and inducing apoptosis in tumor cells. Consequently, they are used in conjunction with conventional therapies. Furthermore, FFAR gene expression is down-regulated in CRC, suggesting their suppressive character. Recent studies showed that the FFAR4 agonist, GW9508, can inhibit tumor growth. In conclusion, natural as well as synthetic FFAR ligands are considered promising candidates for CRC therapy.
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Affiliation(s)
- Agata Binienda
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
| | - Jakub Fichna
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
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10
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Wu J, Fu K, Hou C, Wang Y, Ji C, Xue F, Ren J, Dai J, Barr JJ, Tang F. Bacteriophage defends murine gut from Escherichia coli invasion via mucosal adherence. Nat Commun 2024; 15:4764. [PMID: 38834561 DOI: 10.1038/s41467-024-48560-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Accepted: 05/07/2024] [Indexed: 06/06/2024] Open
Abstract
Bacteriophage are sophisticated cellular parasites that can not only parasitize bacteria but are increasingly recognized for their direct interactions with mammalian hosts. Phage adherence to mucus is known to mediate enhanced antimicrobial effects in vitro. However, little is known about the therapeutic efficacy of mucus-adherent phages in vivo. Here, using a combination of in vitro gastrointestinal cell lines, a gut-on-a-chip microfluidic model, and an in vivo murine gut model, we demonstrated that a E. coli phage, øPNJ-6, provided enhanced gastrointestinal persistence and antimicrobial effects. øPNJ-6 bound fucose residues, of the gut secreted glycoprotein MUC2, through domain 1 of its Hoc protein, which led to increased intestinal mucus production that was suggestive of a positive feedback loop mediated by the mucus-adherent phage. These findings extend the Bacteriophage Adherence to Mucus model into phage therapy, demonstrating that øPNJ-6 displays enhanced persistence within the murine gut, leading to targeted depletion of intestinal pathogenic bacteria.
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Affiliation(s)
- Jiaoling Wu
- College of Veterinary Medicine, Nanjing Agricultural University; Key Laboratory of Animal Bacteriology, Ministry of Agriculture, Nanjing, China
| | - Kailai Fu
- College of Veterinary Medicine, Nanjing Agricultural University; Key Laboratory of Animal Bacteriology, Ministry of Agriculture, Nanjing, China
| | - Chenglin Hou
- College of Veterinary Medicine, Nanjing Agricultural University; Key Laboratory of Animal Bacteriology, Ministry of Agriculture, Nanjing, China
| | - Yuxin Wang
- College of Veterinary Medicine, Nanjing Agricultural University; Key Laboratory of Animal Bacteriology, Ministry of Agriculture, Nanjing, China
| | - Chengyuan Ji
- College of Veterinary Medicine, Nanjing Agricultural University; Key Laboratory of Animal Bacteriology, Ministry of Agriculture, Nanjing, China
| | - Feng Xue
- College of Veterinary Medicine, Nanjing Agricultural University; Key Laboratory of Animal Bacteriology, Ministry of Agriculture, Nanjing, China
| | - Jianluan Ren
- College of Veterinary Medicine, Nanjing Agricultural University; Key Laboratory of Animal Bacteriology, Ministry of Agriculture, Nanjing, China
| | - Jianjun Dai
- College of Veterinary Medicine, Nanjing Agricultural University; Key Laboratory of Animal Bacteriology, Ministry of Agriculture, Nanjing, China.
- School of Pharmacy, China Pharmaceutical University; Engineering Research Center for Anti-infective Drug Discovery, Ministry of Education (ERCADD), Nanjing, China.
| | - Jeremy J Barr
- School of Biological Sciences, Monash University, Victoria, Australia.
| | - Fang Tang
- College of Veterinary Medicine, Nanjing Agricultural University; Key Laboratory of Animal Bacteriology, Ministry of Agriculture, Nanjing, China.
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11
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Facchin S, Bertin L, Bonazzi E, Lorenzon G, De Barba C, Barberio B, Zingone F, Maniero D, Scarpa M, Ruffolo C, Angriman I, Savarino EV. Short-Chain Fatty Acids and Human Health: From Metabolic Pathways to Current Therapeutic Implications. Life (Basel) 2024; 14:559. [PMID: 38792581 PMCID: PMC11122327 DOI: 10.3390/life14050559] [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: 03/25/2024] [Revised: 04/24/2024] [Accepted: 04/25/2024] [Indexed: 05/26/2024] Open
Abstract
The gastrointestinal tract is home to trillions of diverse microorganisms collectively known as the gut microbiota, which play a pivotal role in breaking down undigested foods, such as dietary fibers. Through the fermentation of these food components, short-chain fatty acids (SCFAs) such as acetate, propionate, and butyrate are produced, offering numerous health benefits to the host. The production and absorption of these SCFAs occur through various mechanisms within the human intestine, contingent upon the types of dietary fibers reaching the gut and the specific microorganisms engaged in fermentation. Medical literature extensively documents the supplementation of SCFAs, particularly butyrate, in the treatment of gastrointestinal, metabolic, cardiovascular, and gut-brain-related disorders. This review seeks to provide an overview of the dynamics involved in the production and absorption of acetate, propionate, and butyrate within the human gut. Additionally, it will focus on the pivotal roles these SCFAs play in promoting gastrointestinal and metabolic health, as well as their current therapeutic implications.
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Affiliation(s)
- Sonia Facchin
- Department of Surgery, Oncology and Gastroenterology (DISCOG), University Hospital of Padua, 35128 Padua, Italy (L.B.); (B.B.)
| | - Luisa Bertin
- Department of Surgery, Oncology and Gastroenterology (DISCOG), University Hospital of Padua, 35128 Padua, Italy (L.B.); (B.B.)
| | - Erica Bonazzi
- Department of Surgery, Oncology and Gastroenterology (DISCOG), University Hospital of Padua, 35128 Padua, Italy (L.B.); (B.B.)
| | - Greta Lorenzon
- Department of Surgery, Oncology and Gastroenterology (DISCOG), University Hospital of Padua, 35128 Padua, Italy (L.B.); (B.B.)
| | - Caterina De Barba
- Department of Surgery, Oncology and Gastroenterology (DISCOG), University Hospital of Padua, 35128 Padua, Italy (L.B.); (B.B.)
| | - Brigida Barberio
- Department of Surgery, Oncology and Gastroenterology (DISCOG), University Hospital of Padua, 35128 Padua, Italy (L.B.); (B.B.)
| | - Fabiana Zingone
- Department of Surgery, Oncology and Gastroenterology (DISCOG), University Hospital of Padua, 35128 Padua, Italy (L.B.); (B.B.)
| | - Daria Maniero
- Department of Surgery, Oncology and Gastroenterology (DISCOG), University Hospital of Padua, 35128 Padua, Italy (L.B.); (B.B.)
| | - Marco Scarpa
- General Surgery Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35138 Padua, Italy (C.R.); (I.A.)
| | - Cesare Ruffolo
- General Surgery Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35138 Padua, Italy (C.R.); (I.A.)
| | - Imerio Angriman
- General Surgery Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35138 Padua, Italy (C.R.); (I.A.)
| | - Edoardo Vincenzo Savarino
- Department of Surgery, Oncology and Gastroenterology (DISCOG), University Hospital of Padua, 35128 Padua, Italy (L.B.); (B.B.)
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12
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Holmberg SM, Feeney RH, Prasoodanan P K V, Puértolas-Balint F, Singh DK, Wongkuna S, Zandbergen L, Hauner H, Brandl B, Nieminen AI, Skurk T, Schroeder BO. The gut commensal Blautia maintains colonic mucus function under low-fiber consumption through secretion of short-chain fatty acids. Nat Commun 2024; 15:3502. [PMID: 38664378 PMCID: PMC11045866 DOI: 10.1038/s41467-024-47594-w] [Citation(s) in RCA: 39] [Impact Index Per Article: 39.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Accepted: 04/03/2024] [Indexed: 04/28/2024] Open
Abstract
Beneficial gut bacteria are indispensable for developing colonic mucus and fully establishing its protective function against intestinal microorganisms. Low-fiber diet consumption alters the gut bacterial configuration and disturbs this microbe-mucus interaction, but the specific bacteria and microbial metabolites responsible for maintaining mucus function remain poorly understood. By using human-to-mouse microbiota transplantation and ex vivo analysis of colonic mucus function, we here show as a proof-of-concept that individuals who increase their daily dietary fiber intake can improve the capacity of their gut microbiota to prevent diet-mediated mucus defects. Mucus growth, a critical feature of intact colonic mucus, correlated with the abundance of the gut commensal Blautia, and supplementation of Blautia coccoides to mice confirmed its mucus-stimulating capacity. Mechanistically, B. coccoides stimulated mucus growth through the production of the short-chain fatty acids propionate and acetate via activation of the short-chain fatty acid receptor Ffar2, which could serve as a new target to restore mucus growth during mucus-associated lifestyle diseases.
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Affiliation(s)
- Sandra M Holmberg
- Department of Molecular Biology, Umeå University, Umeå, Sweden
- Laboratory for Molecular Infection Medicine Sweden (MIMS) and Umeå Center for Microbial Research (UCMR), Umeå University, Umeå, Sweden
| | - Rachel H Feeney
- Department of Molecular Biology, Umeå University, Umeå, Sweden
- Laboratory for Molecular Infection Medicine Sweden (MIMS) and Umeå Center for Microbial Research (UCMR), Umeå University, Umeå, Sweden
| | - Vishnu Prasoodanan P K
- Department of Molecular Biology, Umeå University, Umeå, Sweden
- Laboratory for Molecular Infection Medicine Sweden (MIMS) and Umeå Center for Microbial Research (UCMR), Umeå University, Umeå, Sweden
| | - Fabiola Puértolas-Balint
- Department of Molecular Biology, Umeå University, Umeå, Sweden
- Laboratory for Molecular Infection Medicine Sweden (MIMS) and Umeå Center for Microbial Research (UCMR), Umeå University, Umeå, Sweden
| | - Dhirendra K Singh
- Department of Molecular Biology, Umeå University, Umeå, Sweden
- Laboratory for Molecular Infection Medicine Sweden (MIMS) and Umeå Center for Microbial Research (UCMR), Umeå University, Umeå, Sweden
| | - Supapit Wongkuna
- Department of Molecular Biology, Umeå University, Umeå, Sweden
- Laboratory for Molecular Infection Medicine Sweden (MIMS) and Umeå Center for Microbial Research (UCMR), Umeå University, Umeå, Sweden
| | - Lotte Zandbergen
- Department of Molecular Biology, Umeå University, Umeå, Sweden
- Laboratory for Molecular Infection Medicine Sweden (MIMS) and Umeå Center for Microbial Research (UCMR), Umeå University, Umeå, Sweden
| | - Hans Hauner
- Institute in Nutritional Medicine, TU Munich, Munich, Germany
- TU Munich, School of Medicine, Munich, Germany
| | - Beate Brandl
- ZIEL Institute for Food and Health, TU Munich, Munich, Germany
| | - Anni I Nieminen
- Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland
| | - Thomas Skurk
- ZIEL Institute for Food and Health, TU Munich, Munich, Germany
| | - Bjoern O Schroeder
- Department of Molecular Biology, Umeå University, Umeå, Sweden.
- Laboratory for Molecular Infection Medicine Sweden (MIMS) and Umeå Center for Microbial Research (UCMR), Umeå University, Umeå, Sweden.
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13
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Tanigaki T, Ogawa T, Nomura S, Ito K, Kurata Y, Matsukida A, Ishihara M, Yoshino A, Kawana A, Kimizuka Y. Severe Atelectasis due to Aspirated Valproic Acid Tablet. Case Rep Pulmonol 2024; 2024:6650141. [PMID: 38529055 PMCID: PMC10963110 DOI: 10.1155/2024/6650141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Revised: 02/20/2024] [Accepted: 03/09/2024] [Indexed: 03/27/2024] Open
Abstract
A 60-year-old man treated with valproic acid (VPA) for epilepsy developed atelectasis and respiratory failure after an accidentally aspirated VPA tablet-induced mucus hypersecretion. Following bronchoscopic removal of the aspirated tablet, his respiratory status improved and massive sputum production did not recur. We hypothesized that the aspirated VPA tablet increased the expression of mucin-related genes, thereby increasing mucus production. Our in vitro experiments using a human respiratory epithelial cell line revealed that VPA directly upregulates the airway mucin-related genes. We believe that this is the first case report of aspirated VPA-induced severe atelectasis and respiratory failure, which were successfully treated with the bronchoscopic removal of the VPA tablet.
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Affiliation(s)
- Tomomi Tanigaki
- Division of Infectious Diseases and Respiratory Medicine, Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan
| | - Takunori Ogawa
- Division of Infectious Diseases and Respiratory Medicine, Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan
| | - Sakika Nomura
- Division of Infectious Diseases and Respiratory Medicine, Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan
| | - Koki Ito
- Division of Infectious Diseases and Respiratory Medicine, Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan
| | - Yuhei Kurata
- Division of Infectious Diseases and Respiratory Medicine, Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan
| | - Akira Matsukida
- Division of Infectious Diseases and Respiratory Medicine, Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan
| | - Morio Ishihara
- Division of Psychiatry, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan
| | - Aihide Yoshino
- Division of Psychiatry, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan
| | - Akihiko Kawana
- Division of Infectious Diseases and Respiratory Medicine, Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan
| | - Yoshifumi Kimizuka
- Division of Infectious Diseases and Respiratory Medicine, Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan
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Zha X, Su S, Wu D, Zhang P, Wei Y, Fan S, Huang Q, Peng X. The impact of gut microbiota changes on the intestinal mucus barrier in burned mice: a study using 16S rRNA and metagenomic sequencing. BURNS & TRAUMA 2023; 11:tkad056. [PMID: 38130728 PMCID: PMC10734567 DOI: 10.1093/burnst/tkad056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 10/29/2023] [Accepted: 11/06/2023] [Indexed: 12/23/2023]
Abstract
Background The gut microbiota is a complex ecosystem that plays a critical role in human health and disease. However, the relationship between gut microbiota and intestinal damage caused by burns is not well understood. The intestinal mucus layer is crucial for maintaining intestinal homeostasis and providing a physiological barrier against bacterial invasion. This study aims to investigate the impact of gut microbiota on the synthesis and degradation of intestinal mucus after burns and explore potential therapeutic targets for burn injury. Methods A modified histopathological grading system was employed to investigate the effects of burn injury on colon tissue and the intestinal mucus barrier in mice. Subsequently, 16S ribosomal RNA sequencing was used to analyze alterations in the gut microbiota at days 1-10 post-burn. Based on this, metagenomic sequencing was conducted on samples collected at days 1, 5 and 10 to investigate changes in mucus-related microbiota and explore potential underlying mechanisms. Results Our findings showed that the mucus barrier was disrupted and that bacterial translocation occurred on day 3 following burn injury in mice. Moreover, the gut microbiota in mice was significantly disrupted from days 1 to 3 following burn injury, but gradually recovered to normal as the disease progressed. Specifically, there was a marked increase in the abundance of symbiotic and pathogenic bacteria associated with mucin degradation on day 1 after burns, but the abundance returned to normal on day 5. Conversely, the abundance of probiotic bacteria associated with mucin synthesis changed in the opposite direction. Further analysis revealed that after a burn injury, bacteria capable of degrading mucus may utilize glycoside hydrolases, flagella and internalins to break down the mucus layer, while bacteria that synthesize mucus may help restore the mucus layer by promoting the production of short-chain fatty acids. Conclusions Burn injury leads to disruption of colonic mucus barrier and dysbiosis of gut microbiota. Some commensal and pathogenic bacteria may participate in mucin degradation via glycoside hydrolases, flagella, internalins, etc. Probiotics may provide short-chain fatty acids (particularly butyrate) as an energy source for stressed intestinal epithelial cells, promote mucin synthesis and accelerate repair of mucus layer.
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Affiliation(s)
- Xule Zha
- Clinical Medical Research Center, Southwest Hospital, Third Military Medical University (Army Medical University), Gaotanyan Street, Shapingba District, Chongqing, 400038, China
| | - Sen Su
- Clinical Medical Research Center, Southwest Hospital, Third Military Medical University (Army Medical University), Gaotanyan Street, Shapingba District, Chongqing, 400038, China
| | - Dan Wu
- Clinical Medical Research Center, Southwest Hospital, Third Military Medical University (Army Medical University), Gaotanyan Street, Shapingba District, Chongqing, 400038, China
| | - Panyang Zhang
- Clinical Medical Research Center, Southwest Hospital, Third Military Medical University (Army Medical University), Gaotanyan Street, Shapingba District, Chongqing, 400038, China
| | - Yan Wei
- Clinical Medical Research Center, Southwest Hospital, Third Military Medical University (Army Medical University), Gaotanyan Street, Shapingba District, Chongqing, 400038, China
| | - Shijun Fan
- Clinical Medical Research Center, Southwest Hospital, Third Military Medical University (Army Medical University), Gaotanyan Street, Shapingba District, Chongqing, 400038, China
| | - Qianying Huang
- Clinical Medical Research Center, Southwest Hospital, Third Military Medical University (Army Medical University), Gaotanyan Street, Shapingba District, Chongqing, 400038, China
| | - Xi Peng
- Clinical Medical Research Center, Southwest Hospital, Third Military Medical University (Army Medical University), Gaotanyan Street, Shapingba District, Chongqing, 400038, China
- State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China
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15
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Gomez D, Toribio R, Caddey B, Costa M, Vijan S, Dembek K. Longitudinal effects of oral administration of antimicrobial drugs on fecal microbiota of horses. J Vet Intern Med 2023; 37:2562-2572. [PMID: 37681574 PMCID: PMC10658497 DOI: 10.1111/jvim.16853] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Accepted: 08/23/2023] [Indexed: 09/09/2023] Open
Abstract
BACKGROUND Antimicrobial drug-associated diarrhea (AAD) is the most common adverse effect in horses receiving antimicrobials. Little information on how oral administration of antimicrobials alters intestinal microbiota in horses is available. OBJECTIVE Investigate changes of the fecal microbiota in response to oral administration of antimicrobials. ANIMALS Twenty healthy horses. METHODS Prospective, longitudinal study. Horses were randomly assigned to 4 groups comprising 4 horses each: group 1 (metronidazole); group 2 (erythromycin); group 3 (doxycycline); group 4 (sulfadiazine/trimethoprim, SMZ-TMP); and group 5 (control). Antimicrobials were administered for 5 days. Fecal samples were obtained before (day 0) and at 1, 2, 3, 4, 5, 6, and 30 days of the study period. Fecal microbiota was characterized by high throughput sequencing of the V4 region of the 16S rRNA. RESULTS Horses remained healthy throughout the study. Richness and diversity in doxycycline, erythromycin, and metronidazole, but not SMZ-TMP groups, was significantly lower (P < .05) at multiple time points after administration of antimicrobials compared with samples from day 0. Main changes in the microbiota were observed during the time of antimicrobial administration (day 2-5; weighted and unweighted UniFrac PERMANOVA P < .05). Administration of erythromycin, doxycycline and, to a lesser extent, metronidazole produced a pronounced alteration in the microbiota compared with day 0 samples by decreasing the abundance of Treponema, Fibrobacter, and Lachnospiraceae and increasing Fusobacterium and Escherichia-Shigella. CONCLUSIONS AND CLINICAL IMPORTANCE Oral administration of antimicrobials alters the intestinal microbiota of healthy horses resembling horses with dysbiosis, potentially resulting in intestinal inflammation and predisposition to diarrhea.
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Affiliation(s)
- Diego Gomez
- Department of Clinical Studies, Ontario Veterinary CollegeUniversity of GuelphGuelphOntarioCanada
| | - Ramiro Toribio
- Department of Clinical SciencesThe Ohio State University, College of Veterinary MedicineColumbusOhioUSA
| | - Benjamin Caddey
- Faculty of Veterinary MedicineUniversity of CalgaryCalgaryAlbertaCanada
| | - Marcio Costa
- Faculté de Médecine Vétérinaire – Département de Biomédecine VétérinaireUniversity of MontrealSaint‐HyacintheQuebecCanada
| | - Stephanie Vijan
- Department of Clinical SciencesThe Ohio State University, College of Veterinary MedicineColumbusOhioUSA
| | - Katarzyna Dembek
- Department of Clinical Sciences, College of Veterinary MedicineNorth Carolina State UniversityRaleighNorth CarolinaUSA
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16
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Stolfi C, Pacifico T, Monteleone G, Laudisi F. Impact of Western Diet and Ultra-Processed Food on the Intestinal Mucus Barrier. Biomedicines 2023; 11:2015. [PMID: 37509654 PMCID: PMC10377275 DOI: 10.3390/biomedicines11072015] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Revised: 06/19/2023] [Accepted: 07/15/2023] [Indexed: 07/30/2023] Open
Abstract
The intestinal epithelial barrier plays a key role in the absorption of nutrients and water, in the regulation of the interactions between luminal contents and the underlying immune cells, and in the defense against enteric pathogens. Additionally, the intestinal mucus layer provides further protection due to mucin secretion and maturation by goblet cells, thus representing a crucial player in maintaining intestinal homeostasis. However, environmental factors, such as dietary products, can disrupt this equilibrium, leading to the development of inflammatory intestinal disorders. In particular, ultra-processed food, which is broadly present in the Western diet and includes dietary components containing food additives and/or undergoing multiple industrial processes (such as dry heating cooking), was shown to negatively impact intestinal health. In this review, we summarize and discuss current knowledge on the impact of a Western diet and, in particular, ultra-processed food on the mucus barrier and goblet cell function, as well as potential therapeutic approaches to maintain and restore the mucus layer under pathological conditions.
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Affiliation(s)
- Carmine Stolfi
- Department of Systems Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy
| | - Teresa Pacifico
- Department of Systems Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy
| | - Giovanni Monteleone
- Department of Systems Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy
- Gastroenterology Unit, Policlinico Universitario Tor Vergata, 00133 Rome, Italy
| | - Federica Laudisi
- Department of Systems Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy
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17
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Wang T, Zhou N, He J, Hao Z, Zhou C, Du Y, Du Z, Su X, Zhang M. Xylanase improves the intestinal barrier function of Nile tilapia (Oreochromis niloticus) fed with soybean (Glycine max) meal. J Anim Sci Biotechnol 2023; 14:86. [PMID: 37415202 DOI: 10.1186/s40104-023-00883-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Accepted: 04/10/2023] [Indexed: 07/08/2023] Open
Abstract
BACKGROUND Soybean (Glycine max) meal is one of the important protein sources for fish, but the non-starch polysaccharides (NSP) in soybean meal impair the intestinal barrier function. Here we aimed to investigate whether xylanase can alleviate the adverse effects on the gut barrier induced by soybean meal in Nile tilapia and to explore the possible mechanism. RESULTS Nile tilapia (Oreochromis niloticus) (4.09 ± 0.02 g) were fed with two diets including SM (soybean meal) and SMC (soybean meal + 3,000 U/kg xylanase) for 8 weeks. We characterized the effects of xylanase on the gut barrier, and the transcriptome analysis was performed to investigate the underlying mechanism. Dietary xylanase improved intestinal morphology and decreased the concentration of lipopolysaccharide (LPS) in serum. The results of transcriptome and Western blotting showed that dietary xylanase up-regulated the expression level of mucin2 (MUC2) which may be related to the inhibition of protein kinase RNA-like endoplasmic reticulum kinase (perk)/activating transcription factor 4 (atf4) signaling pathways. Microbiome analysis showed that addition of xylanase in soybean meal altered the intestinal microbiota composition and increased the concentration of butyric acid in the gut. Notably, dietary sodium butyrate was supplemented into the soybean meal diet to feed Nile tilapia, and the data verified that sodium butyrate mirrored the beneficial effects of xylanase. CONCLUSIONS Collectively, supplementation of xylanase in soybean meal altered the intestinal microbiota composition and increased the content of butyric acid which can repress the perk/atf4 signaling pathway and increase the expression of muc2 to enhance the gut barrier function of Nile tilapia. The present study reveals the mechanism by which xylanase improves the intestinal barrier, and it also provides a theoretical basis for the application of xylanase in aquaculture.
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Affiliation(s)
- Tong Wang
- Laboratory of Aquaculture Nutrition and Environmental Health (LANEH), School of Life Sciences, East China Normal University, Shanghai, 200241, China
| | - Nannan Zhou
- Laboratory of Aquaculture Nutrition and Environmental Health (LANEH), School of Life Sciences, East China Normal University, Shanghai, 200241, China
| | - Junyi He
- Laboratory of Aquaculture Nutrition and Environmental Health (LANEH), School of Life Sciences, East China Normal University, Shanghai, 200241, China
| | - Zhenzhen Hao
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
| | - Chentao Zhou
- Laboratory of Aquaculture Nutrition and Environmental Health (LANEH), School of Life Sciences, East China Normal University, Shanghai, 200241, China
| | - Yidi Du
- Laboratory of Aquaculture Nutrition and Environmental Health (LANEH), School of Life Sciences, East China Normal University, Shanghai, 200241, China
| | - Zhenyu Du
- Laboratory of Aquaculture Nutrition and Environmental Health (LANEH), School of Life Sciences, East China Normal University, Shanghai, 200241, China
| | - Xiaoyun Su
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
| | - Meiling Zhang
- Laboratory of Aquaculture Nutrition and Environmental Health (LANEH), School of Life Sciences, East China Normal University, Shanghai, 200241, China.
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Jeong JJ, Ganesan R, Jin YJ, Park HJ, Min BH, Jeong MK, Yoon SJ, Choi MR, Choi J, Moon JH, Min U, Lim JH, Lee DY, Han SH, Ham YL, Kim BY, Suk KT. Multi-strain probiotics alleviate loperamide-induced constipation by adjusting the microbiome, serotonin, and short-chain fatty acids in rats. Front Microbiol 2023; 14:1174968. [PMID: 37333632 PMCID: PMC10272585 DOI: 10.3389/fmicb.2023.1174968] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Accepted: 05/15/2023] [Indexed: 06/20/2023] Open
Abstract
Constipation is one of the most common gastrointestinal (GI) disorders worldwide. The use of probiotics to improve constipation is well known. In this study, the effect on loperamide-induced constipation by intragastric administration of probiotics Consti-Biome mixed with SynBalance® SmilinGut (Lactobacillus plantarum PBS067, Lactobacillus rhamnosus LRH020, Bifidobacterium animalis subsp. lactis BL050; Roelmi HPC), L. plantarum UALp-05 (Chr. Hansen), Lactobacillus acidophilus DDS-1 (Chr. Hansen), and Streptococcus thermophilus CKDB027 (Chong Kun Dang Bio) to rats was evaluated. To induce constipation, 5 mg/kg loperamide was intraperitoneally administered twice a day for 7 days to all groups except the normal control group. After inducing constipation, Dulcolax-S tablets and multi-strain probiotics Consti-Biome were orally administered once a day for 14 days. The probiotics were administered 0.5 mL at concentrations of 2 × 108 CFU/mL (G1), 2 × 109 CFU/mL (G2), and 2 × 1010 CFU/mL (G3). Compared to the loperamide administration group (LOP), the multi-strain probiotics not only significantly increased the number of fecal pellets but also improved the GI transit rate. The mRNA expression levels of serotonin- and mucin-related genes in the colons that were treated with the probiotics were also significantly increased compared to levels in the LOP group. In addition, an increase in serotonin was observed in the colon. The cecum metabolites showed a different pattern between the probiotics-treated groups and the LOP group, and an increase in short-chain fatty acids was observed in the probiotic-treated groups. The abundances of the phylum Verrucomicrobia, the family Erysipelotrichaceae and the genus Akkermansia were increased in fecal samples of the probiotic-treated groups. Therefore, the multi-strain probiotics used in this experiment were thought to help alleviate LOP-induced constipation by altering the levels of short-chain fatty acids, serotonin, and mucin through improvement in the intestinal microflora.
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Affiliation(s)
- Jin-Ju Jeong
- Institute for Liver and Digestive Disease, Hallym University, Chuncheon, Republic of Korea
| | - Raja Ganesan
- Institute for Liver and Digestive Disease, Hallym University, Chuncheon, Republic of Korea
| | - Yoo-Jeong Jin
- R&D Center, Chong Kun Dang Healthcare, Seoul, Republic of Korea
| | - Hee Jin Park
- Institute for Liver and Digestive Disease, Hallym University, Chuncheon, Republic of Korea
| | - Byeong Hyun Min
- Institute for Liver and Digestive Disease, Hallym University, Chuncheon, Republic of Korea
| | - Min Kyo Jeong
- Institute for Liver and Digestive Disease, Hallym University, Chuncheon, Republic of Korea
| | - Sang Jun Yoon
- Institute for Liver and Digestive Disease, Hallym University, Chuncheon, Republic of Korea
| | - Mi Ran Choi
- Institute for Liver and Digestive Disease, Hallym University, Chuncheon, Republic of Korea
| | - Jieun Choi
- Department of Agricultural Biotechnology, Center for Food and Bioconvergence, Research Institute of Agricultural and Life Sciences, Seoul National University, Seoul, Republic of Korea
| | - Ji Hyun Moon
- Department of Agricultural Biotechnology, Center for Food and Bioconvergence, Research Institute of Agricultural and Life Sciences, Seoul National University, Seoul, Republic of Korea
| | - Uigi Min
- R&D Center, Chong Kun Dang Healthcare, Seoul, Republic of Korea
| | - Jong-Hyun Lim
- R&D Center, Chong Kun Dang Healthcare, Seoul, Republic of Korea
| | - Do Yup Lee
- Department of Agricultural Biotechnology, Center for Food and Bioconvergence, Research Institute of Agricultural and Life Sciences, Seoul National University, Seoul, Republic of Korea
| | - Sang Hak Han
- Department of Pathology, Hallym University College of Medicine, Chuncheon, Republic of Korea
| | - Young Lim Ham
- Department of Nursing, Daewon University College, Jecheon, Republic of Korea
| | - Byung-Yong Kim
- R&D Center, Chong Kun Dang Healthcare, Seoul, Republic of Korea
| | - Ki Tae Suk
- Institute for Liver and Digestive Disease, Hallym University, Chuncheon, Republic of Korea
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19
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Dang Y, Ma C, Chen K, Chen Y, Jiang M, Hu K, Li L, Zeng Z, Zhang H. The Effects of a High-Fat Diet on Inflammatory Bowel Disease. Biomolecules 2023; 13:905. [PMID: 37371485 PMCID: PMC10296751 DOI: 10.3390/biom13060905] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2023] [Revised: 05/26/2023] [Accepted: 05/26/2023] [Indexed: 06/29/2023] Open
Abstract
The interactions among diet, intestinal immunity, and microbiota are complex and play contradictory roles in inflammatory bowel disease (IBD). An increasing number of studies has shed light on this field. The intestinal immune balance is disrupted by a high-fat diet (HFD) in several ways, such as impairing the intestinal barrier, influencing immune cells, and altering the gut microbiota. In contrast, a rational diet is thought to maintain intestinal immunity by regulating gut microbiota. In this review, we emphasize the crucial contributions made by an HFD to the gut immune system and microbiota.
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Affiliation(s)
- Yuan Dang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, China
- Centre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu 610041, China
- Laboratory of Inflammatory Bowel Disease, Institute of Immunology and Inflammation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Chunxiang Ma
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, China
- Centre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu 610041, China
- Laboratory of Inflammatory Bowel Disease, Institute of Immunology and Inflammation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Kexin Chen
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, China
- Centre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu 610041, China
- Laboratory of Inflammatory Bowel Disease, Institute of Immunology and Inflammation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yiding Chen
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Mingshan Jiang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, China
- Centre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu 610041, China
- Laboratory of Inflammatory Bowel Disease, Institute of Immunology and Inflammation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Kehan Hu
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, China
- Centre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu 610041, China
- Laboratory of Inflammatory Bowel Disease, Institute of Immunology and Inflammation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Lili Li
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, China
- Centre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu 610041, China
- Laboratory of Inflammatory Bowel Disease, Institute of Immunology and Inflammation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Zhen Zeng
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, China
- Centre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu 610041, China
- Laboratory of Inflammatory Bowel Disease, Institute of Immunology and Inflammation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Hu Zhang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, China
- Centre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu 610041, China
- Laboratory of Inflammatory Bowel Disease, Institute of Immunology and Inflammation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China
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20
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Duncan SH, Conti E, Ricci L, Walker AW. Links between Diet, Intestinal Anaerobes, Microbial Metabolites and Health. Biomedicines 2023; 11:biomedicines11051338. [PMID: 37239009 DOI: 10.3390/biomedicines11051338] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 04/23/2023] [Accepted: 04/26/2023] [Indexed: 05/28/2023] Open
Abstract
A dense microbial community resides in the human colon, with considerable inter-individual variability in composition, although some species are relatively dominant and widespread in healthy individuals. In disease conditions, there is often a reduction in microbial diversity and perturbations in the composition of the microbiota. Dietary complex carbohydrates that reach the large intestine are important modulators of the composition of the microbiota and their primary metabolic outputs. Specialist gut bacteria may also transform plant phenolics to form a spectrum of products possessing antioxidant and anti-inflammatory activities. Consumption of diets high in animal protein and fat may lead to the formation of potentially deleterious microbial products, including nitroso compounds, hydrogen sulphide, and trimethylamine. Gut anaerobes also form a range of secondary metabolites, including polyketides that may possess antimicrobial activity and thus contribute to microbe-microbe interactions within the colon. The overall metabolic outputs of colonic microbes are derived from an intricate network of microbial metabolic pathways and interactions; however, much still needs to be learnt about the subtleties of these complex networks. In this review we consider the multi-faceted relationships between inter-individual microbiota variation, diet, and health.
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Affiliation(s)
- Sylvia H Duncan
- Rowett Institute, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK
| | - Elena Conti
- Rowett Institute, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK
| | - Liviana Ricci
- Rowett Institute, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK
| | - Alan W Walker
- Rowett Institute, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK
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21
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Chen T, Chen Y, Li K, Chen Z, Zhao Q, Fan Y, Liu Y, Zhang S, Hao Z. Ginkgo biloba Extract Preventively Intervenes in Citrobacter Rodentium-Induced Colitis in Mice. Nutrients 2023; 15:2008. [PMID: 37111225 PMCID: PMC10145670 DOI: 10.3390/nu15082008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 04/15/2023] [Accepted: 04/18/2023] [Indexed: 04/29/2023] Open
Abstract
Inflammatory bowel disease (IBD) represents a highly recurrent gastrointestinal disorder and global public health issue. However, it lacks effective and safe strategies for its control. Although Ginkgo biloba extract (GBE) has been suggested to exhibit preventive and therapeutic activity for the control of IBD, whether its activity is associated with its ability to modulate intestinal microbiota remains to be addressed. To investigate the effect of GBE on controlling IBD, a Citrobacter Rodentium (CR)-induced mouse colitis model was used, and then histopathological examinations, biochemical assays, immunohistochemistry, and immunoblotting were performed to detect histological changes, cytokines, and tight junction (TJ) proteins in the intestine samples. We also studied 16s rRNA to detect changes in intestinal microbiota and used GC-MS to determine the microbiota-related metabolites short chain fatty acids (SCFAs). The results of our studies revealed that pre-treatment with GBE was sufficient for protecting the animals from CR-induced colitis. As a mechanism for GBE activity, GBE treatment was able to modulate the intestinal microbiota and increase the SCFAs capable of decreasing the pro-inflammatory factors and up-regulating the anti-inflammatory factors while elevating the intestinal-barrier-associated proteins to maintain the integrity of the intestines. Accordingly, our results led to a strong suggestion that GBE should be seriously considered in the preventive control of CR-induced colitis and in the development of effective and safe therapeutic strategies for controlling IBD.
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Affiliation(s)
- Tingting Chen
- College of Veterinary Medicine, China Agricultural University, Beijing 100193, China
- Key Biology Laboratory of Chinese Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Beijing 100193, China
- National Center of Technology Innovation for Medicinal Function of Food, National Food and Strategic Reserves Administration, Beijing 100193, China
| | - Yiqiang Chen
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Kaiyuan Li
- College of Veterinary Medicine, China Agricultural University, Beijing 100193, China
- Key Biology Laboratory of Chinese Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Beijing 100193, China
- National Center of Technology Innovation for Medicinal Function of Food, National Food and Strategic Reserves Administration, Beijing 100193, China
| | - Zhuo Chen
- College of Veterinary Medicine, China Agricultural University, Beijing 100193, China
- Key Biology Laboratory of Chinese Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Beijing 100193, China
- National Center of Technology Innovation for Medicinal Function of Food, National Food and Strategic Reserves Administration, Beijing 100193, China
| | - Qingyu Zhao
- College of Veterinary Medicine, China Agricultural University, Beijing 100193, China
- Key Biology Laboratory of Chinese Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Beijing 100193, China
- National Center of Technology Innovation for Medicinal Function of Food, National Food and Strategic Reserves Administration, Beijing 100193, China
| | - Yimeng Fan
- College of Veterinary Medicine, China Agricultural University, Beijing 100193, China
- Key Biology Laboratory of Chinese Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Beijing 100193, China
- National Center of Technology Innovation for Medicinal Function of Food, National Food and Strategic Reserves Administration, Beijing 100193, China
| | - Ying Liu
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Suxia Zhang
- College of Veterinary Medicine, China Agricultural University, Beijing 100193, China
| | - Zhihui Hao
- College of Veterinary Medicine, China Agricultural University, Beijing 100193, China
- Key Biology Laboratory of Chinese Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Beijing 100193, China
- National Center of Technology Innovation for Medicinal Function of Food, National Food and Strategic Reserves Administration, Beijing 100193, China
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Butyrate Differentiates Permissiveness to Clostridioides difficile Infection and Influences Growth of Diverse C. difficile Isolates. Infect Immun 2023; 91:e0057022. [PMID: 36692308 PMCID: PMC9933713 DOI: 10.1128/iai.00570-22] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
A disrupted "dysbiotic" gut microbiome engenders susceptibility to the diarrheal pathogen Clostridioides difficile by impacting the metabolic milieu of the gut. Diet, in particular the microbiota-accessible carbohydrates (MACs) found in dietary fiber, is one of the most powerful ways to affect the composition and metabolic output of the gut microbiome. As such, diet is a powerful tool for understanding the biology of C. difficile and for developing alternative approaches for coping with this pathogen. One prominent class of metabolites produced by the gut microbiome is short-chain fatty acids (SCFAs), the major metabolic end products of MAC metabolism. SCFAs are known to decrease the fitness of C. difficile in vitro, and high intestinal SCFA concentrations are associated with reduced fitness of C. difficile in animal models of C. difficile infection (CDI). Here, we use controlled dietary conditions (8 diets that differ only by MAC composition) to show that C. difficile fitness is most consistently impacted by butyrate, rather than the other two prominent SCFAs (acetate and propionate), during murine model CDI. We similarly show that butyrate concentrations are lower in fecal samples from humans with CDI than in those from healthy controls. Finally, we demonstrate that butyrate impacts growth in diverse C. difficile isolates. These findings provide a foundation for future work which will dissect how butyrate directly impacts C. difficile fitness and will lead to the development of diverse approaches distinct from antibiotics or fecal transplant, such as dietary interventions, for mitigating CDI in at-risk human populations. IMPORTANCE Clostridioides difficile is a leading cause of infectious diarrhea in humans, and it imposes a tremendous burden on the health care system. Current treatments for C. difficile infection (CDI) include antibiotics and fecal microbiota transplant, which contribute to recurrent CDIs and face major regulatory hurdles, respectively. Therefore, there is an ongoing need to develop new ways to cope with CDI. Notably, a disrupted "dysbiotic" gut microbiota is the primary risk factor for CDI, but we incompletely understand how a healthy microbiota resists CDI. Here, we show that a specific molecule produced by the gut microbiota, butyrate, is negatively associated with C. difficile burdens in humans and in a mouse model of CDI and that butyrate impedes the growth of diverse C. difficile strains in pure culture. These findings help to build a foundation for designing alternative, possibly diet-based, strategies for mitigating CDI in humans.
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Hodgkinson K, El Abbar F, Dobranowski P, Manoogian J, Butcher J, Figeys D, Mack D, Stintzi A. Butyrate's role in human health and the current progress towards its clinical application to treat gastrointestinal disease. Clin Nutr 2023; 42:61-75. [PMID: 36502573 DOI: 10.1016/j.clnu.2022.10.024] [Citation(s) in RCA: 112] [Impact Index Per Article: 56.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 10/17/2022] [Accepted: 10/29/2022] [Indexed: 11/06/2022]
Abstract
Butyrate is a key energy source for colonocytes and is produced by the gut microbiota through fermentation of dietary fiber. Butyrate is a histone deacetylase inhibitor and also signals through three G-protein coupled receptors. It is clear that butyrate has an important role in gastrointestinal health and that butyrate levels can impact both host and microbial functions that are intimately coupled with each other. Maintaining optimal butyrate levels improves gastrointestinal health in animal models by supporting colonocyte function, decreasing inflammation, maintaining the gut barrier, and promoting a healthy microbiome. Butyrate has also shown protective actions in the context of intestinal diseases such as inflammatory bowel disease, graft-versus-host disease of the gastrointestinal tract, and colon cancer, whereas lower levels of butyrate and/or the microbes which are responsible for producing this metabolite are associated with disease and poorer health outcomes. However, clinical efforts to increase butyrate levels in humans and reverse these negative outcomes have generated mixed results. This article discusses our current understanding of the molecular mechanisms of butyrate action with a focus on the gastrointestinal system, the links between host and microbial factors, and the efforts that are currently underway to apply the knowledge gained from the bench to bedside.
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Affiliation(s)
- Kendra Hodgkinson
- Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
| | - Faiha El Abbar
- Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
| | - Peter Dobranowski
- Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
| | - Juliana Manoogian
- Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
| | - James Butcher
- Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
| | - Daniel Figeys
- Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada; School of Pharmaceutical Sciences, University of Ottawa, Ottawa, ON K1H 8M5, Canada
| | - David Mack
- Department of Paediatrics, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8L1, Canada; Children's Hospital of Eastern Ontario Inflammatory Bowel Disease Centre and Research Institute, Ottawa, ON K1H 8L1, Canada
| | - Alain Stintzi
- Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
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24
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Zhao C, Sun C, Yuan J, Tsopmejio ISN, Li Y, Jiang Y, Song H. Hericium caput-medusae (Bull.:Fr.) Pers. fermentation concentrate polysaccharides improves intestinal bacteria by activating chloride channels and mucus secretion. JOURNAL OF ETHNOPHARMACOLOGY 2023; 300:115721. [PMID: 36115601 DOI: 10.1016/j.jep.2022.115721] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 09/02/2022] [Accepted: 09/09/2022] [Indexed: 06/15/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE As a traditional edible fungus in China and many other Asian countries, Hericium caput-medusae (Bull. Fr.) Pers. is widely used to improve the health of the gastrointestinal tract. For example, the drug "Weilexin Granules" is mainly composed of H. caput-medusae (Bull. Fr.) Pers. fermentation concentrate. However, the mechanism of action remains to be elucidated. AIMS OF THE STUDY The purpose of this study was to assess whether polysaccharides from H. caput-medusae (Bull. Fr.) Pers. fermentation concentrate (HFP) exerts a gut protective effect and a regulatory effect on the intestinal microbiota through the chloride channels and mucus secretion. MATERIALS AND METHODS HFP was extracted, characterized and different concentrations of HFP (100, 200, 400 mg/kg) were administered to mice for 14 days. The changes in gut microbiota were observed via 16S high throughput sequencing. Short-chain fatty acids (SCFAs) was detected by GC-MS. AB-PAS staining was used to observe the secretion of mucus. The chloride channel activity and protein expression were verified by short-circuit current measurement and Western blot. RESULTS HFP regulated the abundance of gut microbiota in mice, with increased levels of Ruminococcaceae and Lachnospiraceae and reduced proportions of Staphylococcus and Enterobacter. HFP enhanced mucus volume as well as increased intestinal fluid secretion by activating the chloride channels. In addition, short-circuit current experiments also proved that HFP activates Cl⁻ currents targeting cystic fibrosis transmembrane conductance regulator (CFTR) and Anoamin1 (ANO1). CONCLUSION In conclusion, HFP might increase intestinal fluid secretion by promoting Cl⁻ secretion, which in turn advanced mucus hydration as well as regulated gut microbiota to improve intestinal health. Therefore, H. caput-medusae (Bull. Fr.) Pers. could be potentially used in the regulation of intestinal secretion and microbes.
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Affiliation(s)
- Cong Zhao
- College of Life Science, Jilin Agricultural University, 130118, Changchun, China
| | - Chang Sun
- College of Life Science, Jilin Agricultural University, 130118, Changchun, China
| | - Jing Yuan
- College of Life Science, Jilin Agricultural University, 130118, Changchun, China
| | | | - Yuting Li
- College of Life Science, Jilin Agricultural University, 130118, Changchun, China
| | - Yu Jiang
- College of Life Science, Jilin Agricultural University, 130118, Changchun, China.
| | - Hui Song
- College of Life Science, Jilin Agricultural University, 130118, Changchun, China; Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, 130118, Changchun, China.
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25
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Microbial and host factors contribute to bloodstream infection in a pediatric acute lymphocytic leukemia mouse model. Heliyon 2022; 8:e11340. [PMID: 36345525 PMCID: PMC9636473 DOI: 10.1016/j.heliyon.2022.e11340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 06/15/2022] [Accepted: 10/25/2022] [Indexed: 11/09/2022] Open
Abstract
Background Hematological malignancies are the most common cancers in the pediatric population, and T-cell acute lymphocytic leukemia (T-ALL) is the most common hematological malignancy in children. Bloodstream infection (BSI) is a commonly occurring complication in leukemia due to underlying conditions and therapy-induced neutropenia. Several studies identified the gut microbiome as a major source of BSI due to bacterial translocation. This study aimed to investigate changes in the intestinal and fecal microbiome, and their roles in the pathophysiology of BSI in a pediatric T-ALL mouse model using high-throughput shotgun metagenomics sequencing, and metabolomics. Results Our results show that BSI in ALL is characterized by an increase of a mucin degrading bacterium (Akkermansia muciniphila) and a decrease of butyrate producer Clostridia spp., along with a decrease in short-chain fatty acid (SCFA) concentrations and differential expression of tight junction proteins in the small intestine. Functional analysis of the small intestinal microbiome indicated a reduced capability of SCFA synthesis, while SCFA supplementation ameliorated the development of BSI in ALL. Conclusions Our data indicates that changes in the microbiome, and the resulting changes in levels of SCFAs contribute significantly to the pathogenesis of bloodstream infection in ALL. Our study provides tailored preventive or therapeutic approaches to reduce BSI-associated mortality in ALL.
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26
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Jiang W, Wu J, Zhu S, Xin L, Yu C, Shen Z. The Role of Short Chain Fatty Acids in Irritable Bowel Syndrome. J Neurogastroenterol Motil 2022; 28:540-548. [PMID: 36250361 PMCID: PMC9577580 DOI: 10.5056/jnm22093] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2022] [Accepted: 10/07/2022] [Indexed: 11/20/2022] Open
Abstract
Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that is characterized by abdominal pain and disordered bowel habits. The etiology of IBS is multifactorial, including abnormal gut-brain interactions, visceral hypersensitivity, altered colon motility, and psychological factors. Recent studies have shown that the intestinal microbiota and its metabolites short chain fatty acids (SCFAs) may be involved in the pathogenesis of IBS. SCFAs play an important role in the pathophysiology of IBS. We discuss the underlying mechanisms of action of SCFAs in intestinal inflammation and immunity, intestinal barrier integrity, motility, and the microbiota-gut-brain axis. Limited to previous studies, further studies are required to investigate the mechanisms of action of SCFAs in IBS and provide more precise therapeutic strategies for IBS.
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Affiliation(s)
- Wenxi Jiang
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Jiali Wu
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Shefeng Zhu
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Linying Xin
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Chaohui Yu
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Zhe Shen
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
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27
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van Deuren T, Blaak EE, Canfora EE. Butyrate to combat obesity and obesity-associated metabolic disorders: Current status and future implications for therapeutic use. Obes Rev 2022; 23:e13498. [PMID: 35856338 PMCID: PMC9541926 DOI: 10.1111/obr.13498] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 06/04/2022] [Accepted: 06/28/2022] [Indexed: 12/17/2022]
Abstract
Evidence is increasing that disturbances in the gut microbiome may play a significant role in the etiology of obesity and type 2 diabetes. The short chain fatty acid butyrate, a major end product of the bacterial fermentation of indigestible carbohydrates, is reputed to have anti-inflammatory properties and positive effects on body weight control and insulin sensitivity. However, whether butyrate has therapeutic potential for the treatment and prevention of obesity and obesity-related complications remains to be elucidated. Overall, animal studies strongly indicate that butyrate administered via various routes (e.g., orally) positively affects adipose tissue metabolism and functioning, energy and substrate metabolism, systemic and tissue-specific inflammation, and insulin sensitivity and body weight control. A limited number of human studies demonstrated interindividual differences in clinical effectiveness suggesting that outcomes may depend on the metabolic, microbial, and lifestyle-related characteristics of the target population. Hence, despite abundant evidence from animal data, support of human data is urgently required for the implementation of evidence-based oral and gut-derived butyrate interventions. To increase the efficacy of butyrate-focused interventions, future research should investigate which factors impact treatment outcomes including baseline gut microbial activity and functionality, thereby optimizing targeted-interventions and identifying individuals that merit most from such interventions.
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Affiliation(s)
- Thirza van Deuren
- Department of Human Biology, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center+, Maastricht, The Netherlands
| | - Ellen E Blaak
- Department of Human Biology, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center+, Maastricht, The Netherlands
| | - Emanuel E Canfora
- Department of Human Biology, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center+, Maastricht, The Netherlands
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28
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Mineral-Enriched Postbiotics: A New Perspective for Microbial Therapy to Prevent and Treat Gut Dysbiosis. Biomedicines 2022; 10:biomedicines10102392. [PMID: 36289654 PMCID: PMC9599024 DOI: 10.3390/biomedicines10102392] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 09/20/2022] [Accepted: 09/22/2022] [Indexed: 12/03/2022] Open
Abstract
Postbiotics are non-viable probiotic preparations that confer a health benefit on the host. In the last years, scientific literature has proved that postbiotics have health-promoting features and technological advantages compared to probiotics, augmenting their full potential application in the food and pharmaceutical industries. The current work comprehensively summarizes the benefits and potential applications of postbiotics and essential mineral-enriched biomass and proposes a new strategy for microbial therapy—mineral-enriched postbiotics. We hypothesize and critically review the relationship between micronutrients (calcium, magnesium, iron, zinc, selenium) and postbiotics with gut microbiota, which has been barely explored yet, and how the new approach could be involved in the gut microbiome modulation to prevent and treat gut dysbiosis. Additionally, the bioactive molecules and minerals from postbiotics could influence the host mineral status, directly or through gut microbiota, which increases the mineral bioavailability. The review increases our understanding of the health improvements of mineral-enriched postbiotics, including antioxidant functions, highlighting their perspective on microbial therapy to prevent and threaten gut-related diseases.
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Kaur H, Ali SA, Yan F. Interactions between the gut microbiota-derived functional factors and intestinal epithelial cells - implication in the microbiota-host mutualism. Front Immunol 2022; 13:1006081. [PMID: 36159834 PMCID: PMC9492984 DOI: 10.3389/fimmu.2022.1006081] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Accepted: 08/23/2022] [Indexed: 12/13/2022] Open
Abstract
Mutual interactions between the gut microbiota and the host play essential roles in maintaining human health and providing a nutrient-rich environment for the gut microbial community. Intestinal epithelial cells (IECs) provide the frontline responses to the gut microbiota for maintaining intestinal homeostasis. Emerging evidence points to commensal bacterium-derived components as functional factors for the action of commensal bacteria, including protecting intestinal integrity and mitigating susceptibility of intestinal inflammation. Furthermore, IECs have been found to communicate with the gut commensal bacteria to shape the composition and function of the microbial community. This review will discuss the current understanding of the beneficial effects of functional factors secreted by commensal bacteria on IECs, with focus on soluble proteins, metabolites, and surface layer components, and highlight the impact of IECs on the commensal microbial profile. This knowledge provides a proof-of-concept model for understanding of mechanisms underlying the microbiota-host mutualism.
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Affiliation(s)
- Harpreet Kaur
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Syed Azmal Ali
- German Cancer Research Center, Division of Proteomics of Stem Cell and Cancer, Heidelberg, Germany
| | - Fang Yan
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, United States,Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, United States,*Correspondence: Fang Yan,
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Holmes ZC, Villa MM, Durand HK, Jiang S, Dallow EP, Petrone BL, Silverman JD, Lin PH, David LA. Microbiota responses to different prebiotics are conserved within individuals and associated with habitual fiber intake. MICROBIOME 2022; 10:114. [PMID: 35902900 PMCID: PMC9336045 DOI: 10.1186/s40168-022-01307-x] [Citation(s) in RCA: 70] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Accepted: 06/15/2022] [Indexed: 05/12/2023]
Abstract
BACKGROUND Short-chain fatty acids (SCFAs) derived from gut bacteria are associated with protective roles in diseases ranging from obesity to colorectal cancers. Intake of microbially accessible dietary fibers (prebiotics) lead to varying effects on SCFA production in human studies, and gut microbial responses to nutritional interventions vary by individual. It is therefore possible that prebiotic therapies will require customizing to individuals. RESULTS Here, we explored prebiotic personalization by conducting a three-way crossover study of three prebiotic treatments in healthy adults. We found that within individuals, metabolic responses were correlated across the three prebiotics. Individual identity, rather than prebiotic choice, was also the major determinant of SCFA response. Across individuals, prebiotic response was inversely related to basal fecal SCFA concentration, which, in turn, was associated with habitual fiber intake. Experimental measures of gut microbial SCFA production for each participant also negatively correlated with fiber consumption, supporting a model in which individuals' gut microbiota are limited in their overall capacity to produce fecal SCFAs from fiber. CONCLUSIONS Our findings support developing personalized prebiotic regimens that focus on selecting individuals who stand to benefit, and that such individuals are likely to be deficient in fiber intake. Video Abstract.
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Affiliation(s)
- Zachary C. Holmes
- Department of Molecular Genetics and Microbiology, Duke University, 3 Genome Court, Durham, NC 27705 USA
| | - Max M. Villa
- Department of Molecular Genetics and Microbiology, Duke University, 3 Genome Court, Durham, NC 27705 USA
- Center for Genomic and Computational Biology, Duke University, 3 Genome Court, Durham, NC 27705 USA
| | - Heather K. Durand
- Department of Molecular Genetics and Microbiology, Duke University, 3 Genome Court, Durham, NC 27705 USA
- Center for Genomic and Computational Biology, Duke University, 3 Genome Court, Durham, NC 27705 USA
| | - Sharon Jiang
- Department of Molecular Genetics and Microbiology, Duke University, 3 Genome Court, Durham, NC 27705 USA
- Center for Genomic and Computational Biology, Duke University, 3 Genome Court, Durham, NC 27705 USA
| | - Eric P. Dallow
- Department of Molecular Genetics and Microbiology, Duke University, 3 Genome Court, Durham, NC 27705 USA
- Center for Genomic and Computational Biology, Duke University, 3 Genome Court, Durham, NC 27705 USA
| | - Brianna L. Petrone
- Department of Molecular Genetics and Microbiology, Duke University, 3 Genome Court, Durham, NC 27705 USA
- Medical Scientist Training Program, Duke University, 3 Genome Court, Durham, NC 27705 USA
| | - Justin D. Silverman
- College of Information Science and Technology, Penn State University, Westgate Bldg, University Park, PA 16802 USA
- Department of Medicine, Penn State University, Hershey, Westgate Bldg, University Park, PA 16802 USA
- Institute for Computational and Data Science, Penn State University, Westgate Bldg, University Park, PA 16802 USA
| | - Pao-Hwa Lin
- Duke Molecular Physiology Institute, Duke University, Stedman Nutrition Ctr, 3475 Erwin Rd, Durham, NC 27705 USA
- Department of Medicine, Duke University Medical Center, Stedman Nutrition Ctr, 3475 Erwin Rd, Durham, NC 27705 USA
| | - Lawrence A. David
- Department of Molecular Genetics and Microbiology, Duke University, 3 Genome Court, Durham, NC 27705 USA
- Center for Genomic and Computational Biology, Duke University, 3 Genome Court, Durham, NC 27705 USA
- Program in Computational Biology and Bioinformatics, Duke University, 3 Genome Court, Durham, NC 27705 USA
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Guo L, Wang YY, Wang JH, Zhao HP, Yu Y, Wang GD, Dai K, Yan YZ, Yang YJ, Lv J. Associations of gut microbiota with dyslipidemia based on sex differences in subjects from Northwestern China. World J Gastroenterol 2022; 28:3455-3475. [PMID: 36158270 PMCID: PMC9346449 DOI: 10.3748/wjg.v28.i27.3455] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Revised: 05/17/2022] [Accepted: 06/20/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The gut microbiota (GM) has been proven to play a role in the regulation of host lipid metabolism, which provides a new theory about the pathogenesis of dyslipidemia. However, the associations of GM with dyslipidemia based on sex differences remain unclear and warrant elucidation. AIM To investigate the associations of GM features with serum lipid profiles based on sex differences in a Chinese population. METHODS This study ultimately recruited 142 participants (73 females and 69 males) at Honghui Hospital, Xi'an Jiaotong University. The anthropometric and blood metabolic parameters of all participants were measured. According to their serum lipid levels, female and male participants were classified into a high triglyceride (H_TG) group, a high total cholesterol (H_CHO) group, a low high-density lipoprotein cholesterol (L_HDL-C) group, and a control (CON) group with normal serum lipid levels. Fresh fecal samples were collected for 16S rRNA gene sequencing. UPARSE software, QIIME software, the RDP classifier and the FAPROTAX database were used for sequencing analyses. RESULTS The GM composition at the phylum level included Firmicutes and Bacteroidetes as the core GM. Different GM features were identified between females and males, and the associations between GM and serum lipid profiles were different in females and males. The GM features in different dyslipidemia subgroups changed in both female patients and male patients. Proteobacteria, Lactobacillaceae, Lactobacillus and Lactobacillus_salivarius were enriched in H_CHO females compared with CON females, while Coriobacteriia were enriched in L_HDL-C females. In the comparison among the three dyslipidemia subgroups in females, Lactobacillus_salivarius were enriched in H_CHO females, and Prevotellaceae were enriched in L_HDL-C females. Compared with CON or H_TG males, Prevotellaceae, unidentified_Ruminococcaceae, Roseburia and Roseburia_inulinivorans were decreased in L_HDL-C males (P value < 0.05), and linear discriminant analysis effect size analysis indicated an enrichment of the above GM taxa in H_TG males compared with other male subgroups. Additionally, Roseburia_inulinivorans abundance was positively correlated with serum TG and total cholesterol levels, and Roseburia were positively correlated with serum TG level. Furthermore, Proteobacteria (0.724, 95%CI: 0.567-0.849), Lactobacillaceae (0.703, 95%CI: 0.544-0.832), Lactobacillus (0.705, 95%CI: 0.547-0.834) and Lactobacillus_salivarius (0.706, 95%CI: 0.548-0.835) could distinguish H_CHO females from CON females, while Coriobacteriia (0.710, 95%CI: 0.547-0.841), Coriobacteriales (0.710, 95%CI: 0.547-0.841), Prevotellaceae (0.697, 95%CI: 0.534-0.830), Roseburia (0.697, 95%CI: 0.534-0.830) and Roseburia_inulinivorans (0.684, 95%CI: 0.520-0.820) could discriminate H_TG males from CON males. Based on the predictions of GM metabolic capabilities with the FAPROTAX database, a total of 51 functional assignments were obtained in females, while 38 were obtained in males. This functional prediction suggested that cellulolysis increased in L_HDL-C females compared with CON females, but decreased in L_HDL-C males compared with CON males. CONCLUSION This study indicates associations of GM with serum lipid profiles, supporting the notion that GM dysbiosis may participate in the pathogenesis of dyslipidemia, and sex differences should be considered.
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Affiliation(s)
- Lei Guo
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi Province, China
| | - Yang-Yang Wang
- School of Electronics and Information, Northwestern Polytechnical University, Xi'an 710129, Shaanxi Province, China
| | - Ji-Han Wang
- Institute of Medical Research, Northwestern Polytechnical University, Xi'an 710072, Shaanxi Province, China
| | - He-Ping Zhao
- Department of Clinical Laboratory, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi Province, China
| | - Yan Yu
- Department of Clinical Laboratory, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi Province, China
| | - Guo-Dong Wang
- Department of Quality Control, Xi’an Mental Health Center, Xi'an 710100, Shaanxi Province, China
| | - Kun Dai
- Department of Clinical Laboratory, Yanliang Railway Hospital of Xi’an, Xi'an 710089, Shaanxi Province, China
| | - Yu-Zhu Yan
- Department of Clinical Laboratory, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi Province, China
| | - Yan-Jie Yang
- Department of Cardiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China
| | - Jing Lv
- Department of Clinical Laboratory, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, Shaanxi Province, China
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Jourova L, Satka S, Frybortova V, Zapletalova I, Anzenbacher P, Anzenbacherova E, Hermanova PP, Drabonova B, Srutkova D, Kozakova H, Hudcovic T. Butyrate Treatment of DSS-Induced Ulcerative Colitis Affects the Hepatic Drug Metabolism in Mice. Front Pharmacol 2022; 13:936013. [PMID: 35928257 PMCID: PMC9343805 DOI: 10.3389/fphar.2022.936013] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Accepted: 06/15/2022] [Indexed: 12/18/2022] Open
Abstract
The development of inflammatory bowel disease (IBD) is associated with alterations in the gut microbiota. There is currently no universal treatment for this disease, thus emphasizing the importance of developing innovative therapeutic approaches. Gut microbiome-derived metabolite butyrate with its well-known anti-inflammatory effect in the gut is a promising candidate. Due to increased intestinal permeability during IBD, butyrate may also reach the liver and influence liver physiology, including hepatic drug metabolism. To get an insight into this reason, the aim of this study was set to clarify not only the protective effects of the sodium butyrate (SB) administration on colonic inflammation but also the effects of SB on hepatic drug metabolism in experimental colitis induced by dextran sodium sulfate (DSS) in mice. It has been shown here that the butyrate pre-treatment can alleviate gut inflammation and reduce the leakiness of colonic epithelium by restoration of the assembly of tight-junction protein Zonula occludens-1 (ZO-1) in mice with DSS-induced colitis. In this article, butyrate along with inflammation has also been shown to affect the expression and enzyme activity of selected cytochromes P450 (CYPs) in the liver of mice. In this respect, CYP3A enzymes may be very sensitive to gut microbiome-targeted interventions, as significant changes in CYP3A expression and activity in response to DSS-induced colitis and/or butyrate treatment have also been observed. With regard to medications used in IBD and microbiota-targeted therapeutic approaches, it is important to deepen our knowledge of the effect of gut inflammation, and therapeutic interventions were followed concerning the ability of the organism to metabolize drugs. This gut–liver axis, mediated through inflammation as well as microbiome-derived metabolites, may affect the response to IBD therapy.
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Affiliation(s)
- Lenka Jourova
- Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czechia
- *Correspondence: Lenka Jourova,
| | - Stefan Satka
- Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czechia
| | - Veronika Frybortova
- Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czechia
| | - Iveta Zapletalova
- Department of Pharmacology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czechia
| | - Pavel Anzenbacher
- Department of Pharmacology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czechia
| | - Eva Anzenbacherova
- Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czechia
| | - Petra Petr Hermanova
- Laboratory of Gnotobiology, Institute of Microbiology of the Czech Academy of Sciences, Novy Hradek, Czechia
| | - Barbora Drabonova
- Laboratory of Gnotobiology, Institute of Microbiology of the Czech Academy of Sciences, Novy Hradek, Czechia
| | - Dagmar Srutkova
- Laboratory of Gnotobiology, Institute of Microbiology of the Czech Academy of Sciences, Novy Hradek, Czechia
| | - Hana Kozakova
- Laboratory of Gnotobiology, Institute of Microbiology of the Czech Academy of Sciences, Novy Hradek, Czechia
| | - Tomas Hudcovic
- Laboratory of Gnotobiology, Institute of Microbiology of the Czech Academy of Sciences, Novy Hradek, Czechia
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Jung TH, Han KS, Park JH, Hwang HJ. Butyrate modulates mucin secretion and bacterial adherence in LoVo cells via MAPK signaling. PLoS One 2022; 17:e0269872. [PMID: 35834581 PMCID: PMC9282476 DOI: 10.1371/journal.pone.0269872] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Accepted: 05/29/2022] [Indexed: 11/25/2022] Open
Abstract
Short-chain fatty acids contribute to normal bowel function and prevent bacterial infections. In particular, butyrate is a promising candidate that plays an important role in regulating the functional integrity of the gastrointestinal tract by stimulating mucin secretion. We investigated whether butyrate treatment modulates mucin secretion and bacterial adherence in LoVo cells. In addition, the possible signaling pathways were also examined in connection with the upregulation of mucin secretion. The results showed that butyrate induced mucin secretion in LoVo cells, resulting in the inhibition of Escherichia coli adhesion by increasing the adherence of Lactobacillus acidophilus and Bifidobacterium longum. The gene expression analysis suggests that mitogen-activated protein kinase (MAPK) signaling pathways including Cdc42-PAK pathway appears to be involved in stimulating mucin secretion. More importantly, butyrate induced the increased actin expression and polymerization in LoVo cells, which could be attributable to the Cdc42-PAK signaling pathway, implicated in actin cytoskeleton and mucin secretion. Our results provide a molecular basis in modulating bacterial adherence and the MAPK signaling pathway for the improved homeostasis of colonic epithelial cells.
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Affiliation(s)
- Tae-Hwan Jung
- Department of Food and Nutrition, Sahmyook University, Seoul, Korea
| | - Kyoung-Sik Han
- Department of Food and Nutrition, Sahmyook University, Seoul, Korea
| | - Jeong-Hyeon Park
- Department of Biological Sciences, Xi’an Jiaotong-Liverpool University, Suzhou, China
| | - Hyo-Jeong Hwang
- Department of Food and Nutrition, Sahmyook University, Seoul, Korea
- * E-mail:
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Zhang Z, Yang P, Zhao J. Ferulic acid mediates prebiotic responses of cereal-derived arabinoxylans on host health. ANIMAL NUTRITION 2022; 9:31-38. [PMID: 35949987 PMCID: PMC9344318 DOI: 10.1016/j.aninu.2021.08.004] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Revised: 08/05/2021] [Accepted: 08/30/2021] [Indexed: 10/25/2022]
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Cao Q, Mertens RT, Sivanathan KN, Cai X, Xiao P. Macrophage orchestration of epithelial and stromal cell homeostasis in the intestine. J Leukoc Biol 2022; 112:313-331. [PMID: 35593111 PMCID: PMC9543232 DOI: 10.1002/jlb.3ru0322-176r] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 04/29/2022] [Accepted: 05/02/2022] [Indexed: 11/06/2022] Open
Abstract
The intestinal tract is a complex ecosystem where numerous cell types of epithelial, immune, neuronal, and endothelial origin coexist in an intertwined, highly organized manner. The functional equilibrium of the intestine relies heavily on the proper crosstalk and cooperation among each cell population. Furthermore, macrophages are versatile, innate immune cells that participate widely in the modulation of inflammation and tissue remodeling. Emerging evidence suggest that macrophages are central in orchestrating tissue homeostasis. Herein, we describe how macrophages interact with epithelial cells, neurons, and other types of mesenchymal cells under the context of intestinal inflammation, followed by the therapeutic implications of cellular crosstalk pertaining to the treatment of inflammatory bowel disease.
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Affiliation(s)
- Qian Cao
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Inflammatory Bowel Disease Center, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Randall Tyler Mertens
- Department of Immunology, Harvard Medical School, Boston, Massachusetts, USA.,Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Kisha Nandini Sivanathan
- Department of Immunology, Harvard Medical School, Boston, Massachusetts, USA.,Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Xuechun Cai
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Inflammatory Bowel Disease Center, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Peng Xiao
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Inflammatory Bowel Disease Center, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Department of Immunology, Harvard Medical School, Boston, Massachusetts, USA.,Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts, USA.,The Key Laboratory for Immunity and Inflammatory Diseases of Zhejiang Province, Hangzhou, China.,Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China
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Abstract
The utilization of dietary cellulose by resident bacteria in the large intestine of mammals, both herbivores and omnivores (including humans), has been a subject of interest since the nineteenth century. Cellulolytic bacteria are key participants in this breakdown process of cellulose, which is otherwise indigestible by the host. They critically contribute to host nutrition and health through the production of short-chain fatty acids, in addition to maintaining the balance of intestinal microbiota. Despite this key role, cellulolytic bacteria have not been well studied. In this review, we first retrace the history of the discovery of cellulolytic bacteria in the large intestine. We then focus on the current knowledge of cellulolytic bacteria isolated from the large intestine of various animal species and humans and discuss the methods used for isolating these bacteria. Moreover, we summarize the enzymes and the mechanisms involved in cellulose degradation. Finally, we present the contribution of these bacteria to the host.
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Affiliation(s)
- Alicia Froidurot
- Université Bourgogne Franche–Comté, Institut Agro Dijon, PAM UMR A 02.102, Dijon, France,CONTACT Alicia Froidurot Université Bourgogne Franche–Comté, Institut Agro Dijon, PAM UMR A 02.102Dijon, France
| | - Véronique Julliand
- Université Bourgogne Franche–Comté, Institut Agro Dijon, PAM UMR A 02.102, Dijon, France
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Choi H, Lee D, Mook-Jung I. Gut Microbiota as a Hidden Player in the Pathogenesis of Alzheimer's Disease. J Alzheimers Dis 2022; 86:1501-1526. [PMID: 35213369 DOI: 10.3233/jad-215235] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Alzheimer's disease (AD), the most common neurodegenerative disorder, is accompanied by cognitive impairment and shows representative pathological features, including senile plaques and neurofibrillary tangles in the brain. Recent evidence suggests that several systemic changes outside the brain are associated with AD and may contribute to its pathogenesis. Among the factors that induce systemic changes in AD, the gut microbiota is increasingly drawing attention. Modulation of gut microbiome, along with continuous attempts to remove pathogenic proteins directly from the brain, is a viable strategy to cure AD. Seeking a holistic understanding of the pathways throughout the body that can affect the pathogenesis, rather than regarding AD solely as a brain disease, may be key to successful therapy. In this review, we focus on the role of the gut microbiota in causing systemic manifestations of AD. The review integrates recently emerging concepts and provides potential mechanisms about the involvement of the gut-brain axis in AD, ranging from gut permeability and inflammation to bacterial translocation and cross-seeding.
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Affiliation(s)
- Hyunjung Choi
- Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, Republic of Korea.,SNU Dementia Research Center, College of Medicine, Seoul National University, Seoul, Republic of Korea
| | - Dongjoon Lee
- Department of Biochemistry and Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Republic of Korea.,SNU Dementia Research Center, College of Medicine, Seoul National University, Seoul, Republic of Korea
| | - Inhee Mook-Jung
- Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, Republic of Korea.,Department of Biochemistry and Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Republic of Korea.,SNU Dementia Research Center, College of Medicine, Seoul National University, Seoul, Republic of Korea
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Bergstrom K, Xia L. The barrier and beyond: Roles of intestinal mucus and mucin-type O-glycosylation in resistance and tolerance defense strategies guiding host-microbe symbiosis. Gut Microbes 2022; 14:2052699. [PMID: 35380912 PMCID: PMC8986245 DOI: 10.1080/19490976.2022.2052699] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Over the past two decades, our appreciation of the gut mucus has moved from a static lubricant to a dynamic and essential component of the gut ecosystem that not only mediates the interface between host tissues and vast microbiota, but regulates how this ecosystem functions to promote mutualistic symbioses and protect from microbe-driven diseases. By delving into the complex chemistry and biology of the mucus, combined with innovative in vivo and ex vivo approaches, recent studies have revealed novel insights into the formation and function of the mucus system, the O-glycans that make up this system, and how they mediate two major host-defense strategies - resistance and tolerance - to reduce damage caused by indigenous microbes and opportunistic pathogens. This current review summarizes these findings by highlighting the emerging roles of mucus and mucin-type O-glycans in influencing host and microbial physiology with an emphasis on host defense strategies against bacteria in the gastrointestinal tract.
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Affiliation(s)
- Kirk Bergstrom
- Department of Biology, University of British Columbia, Okanagan Campus, 3333 University Way, Kelowna, British ColumbiaV1V 1V7, Canada,Kirk Bergstrom Department of Biology, University of British Columbia, 3333 University Way, Kelowna, B.C. Canada
| | - Lijun Xia
- Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, OK, Oklahoma73104, USA,Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, OK, Oklahoma73104, USA,CONTACT Lijun Xia Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, OK, Oklahoma73104, USA
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Chemically Protected Sodium Butyrate Improves Growth Performance and Early Development and Function of Small Intestine in Broilers as One Effective Substitute for Antibiotics. Antibiotics (Basel) 2022; 11:antibiotics11020132. [PMID: 35203735 PMCID: PMC8868412 DOI: 10.3390/antibiotics11020132] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 01/07/2022] [Accepted: 01/12/2022] [Indexed: 01/14/2023] Open
Abstract
The purpose of this study was to investigate the effects of chemically protected sodium butyrate (CSB) on growth performance and the early development and function of small intestine in broilers as one potential substitute for antibiotics. A total of 192 one-day-old Arbor Acres male broilers were randomly assigned into three dietary treatment groups (eight replicates per treatment): the control (CON) diet; ANT diet, CON diet supplemented with the antibiotics (enramycin, 8 mg/kg and aureomycin, 100 mg/kg); CSB diet, CON diet supplemented with 1000 mg/kg CSB, respectively. The results showed that dietary CSB and antibiotics addition significantly improved the growth performance of broilers by increasing the body weight gain (BWG) and feed conversion ratio (FCR) during different stages (p < 0.05). On day 21, the supplement of CSB in diet improved the structure of small intestine (duodenum, jejunum, and ileum) in broilers by increasing the ratio of villus height to crypt depth (VH/CD) (p < 0.05) and enhanced the butyric acid (BA) (p < 0.05) and total short chain fatty acids (SCFA) concentrations of small intestine (jejunum and ileum) compared with the CON and ANT diets. Besides that, the superoxide dismutase (SOD), total antioxidant capacity (TAC) and TAC to malondialdehyde (TAC/MDA) ratio of the ileal and jejunal mucosa were significantly higher (p < 0.05) in the CSB and ANT than in the CON. In addition, the supplement of CSB in diet markedly significantly enhanced α-amylase, lipase, and trypsin activities of the ileum (p < 0.05) as compared to the ANT diet. 16S rRNA gene sequencing indicated that CSB markedly increased the microbiota diversity of ileum in broilers at 21 days of age as compared to CON and ANT (p < 0.05). Furthermore, we found that Firmicutes was the predominant phyla and Lactobacillus was the major genus in the ileum of broilers. Compared with the ANT diet, the supplement of CSB in diet increased the relative abundance of some genera microbiota (e.g., Candidatus_Arthromitus, Romboutsia) by decreasing the relative abundance of Lactobacillus. Moreover, Akkermansia in the CSB was the highest in comparison to that in the CON and ANT. In addition, Kitasatospora that belongs to the phylum Actinobacteriota was only found in ileum of broilers fed the ANT diet. In summary, the supplement of 1000 mg/kg CSB in the diet improved the growth performance by promoting early development and function of the small intestine, which is associated with the regulation of intestinal flora and reestablishment of micro-ecological balance in broilers. Thus, CSB has great potential value as one of effective substitutes for in-feed antibiotics in the broiler industry.
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Elzinga J, van der Lugt B, Belzer C, Steegenga WT. Characterization of increased mucus production of HT29-MTX-E12 cells grown under Semi-Wet interface with Mechanical Stimulation. PLoS One 2021; 16:e0261191. [PMID: 34928974 PMCID: PMC8687553 DOI: 10.1371/journal.pone.0261191] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Accepted: 11/24/2021] [Indexed: 12/29/2022] Open
Abstract
The intestinal mucus layer plays a crucial role in human health. To study intestinal mucus function and structure in vitro, the mucus-producing intestinal cell line HT29-MTX-E12 has been commonly used. However, this cell line produces only low amounts of the intestine-specific MUC2. It has been shown previously that HT29-MTX-E12 cells cultured under Semi-Wet interface with Mechanical Stimulation (SWMS) produced higher amounts of MUC2, concomitant with a thicker mucus layer, compared to cells cultured conventionally. However, it remains unknown which underlying pathways are involved. Therefore, we aimed to further explore the cellular processes underlying the increased MUC2 production by HT29-MTX-E12 cells grown under SWMS conditions. Cells grown on Transwell membranes for 14 days under static and SWMS conditions (after cell seeding and attachment) were subjected to transcriptome analysis to investigate underlying molecular pathways at gene expression level. Caco-2 and LS174T cell lines were included as references. We characterized how SWMS conditions affected HT29-MTX-E12 cells in terms of epithelial barrier integrity, by measuring transepithelial electrical resistance, and cell metabolism, by monitoring pH and lactate production per molecule glucose of the conditioned medium. We confirmed higher MUC2 production under SWMS conditions at gene and protein level and demonstrated that this culturing method primarily stimulated cell growth. In addition, we also found evidence for a more aerobic cell metabolism under SWMS, as shown previously for similar models. In summary, we suggest different mechanisms by which MUC2 production is enhanced under SWMS and propose potential applications of this model in future studies.
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Affiliation(s)
- Janneke Elzinga
- Laboratory of Microbiology, Wageningen University and Research, Wageningen, The Netherlands
| | - Benthe van der Lugt
- Division of Human Nutrition and Health, Wageningen University and Research, Wageningen, The Netherlands
| | - Clara Belzer
- Laboratory of Microbiology, Wageningen University and Research, Wageningen, The Netherlands
| | - Wilma T Steegenga
- Division of Human Nutrition and Health, Wageningen University and Research, Wageningen, The Netherlands
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Gut Microbial Metabolite-Mediated Regulation of the Intestinal Barrier in the Pathogenesis of Inflammatory Bowel Disease. Nutrients 2021; 13:nu13124259. [PMID: 34959809 PMCID: PMC8704337 DOI: 10.3390/nu13124259] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Revised: 11/20/2021] [Accepted: 11/25/2021] [Indexed: 12/14/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disease. The disease has a multifactorial aetiology, involving genetic, microbial as well as environmental factors. The disease pathogenesis operates at the host-microbe interface in the gut. The intestinal epithelium plays a central role in IBD disease pathogenesis. Apart from being a physical barrier, the epithelium acts as a node that integrates environmental, dietary, and microbial cues to calibrate host immune response and maintain homeostasis in the gut. IBD patients display microbial dysbiosis in the gut, combined with an increased barrier permeability that contributes to disease pathogenesis. Metabolites produced by microbes in the gut are dynamic indicators of diet, host, and microbial interplay in the gut. Microbial metabolites are actively absorbed or diffused across the intestinal lining to affect the host response in the intestine as well as at systemic sites via the engagement of cognate receptors. In this review, we summarize insights from metabolomics studies, uncovering the dynamic changes in gut metabolite profiles in IBD and their importance as potential diagnostic and prognostic biomarkers of disease. We focus on gut microbial metabolites as key regulators of the intestinal barrier and their role in the pathogenesis of IBD.
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42
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Zhang Y, Wang L, Ocansey DKW, Wang B, Wang L, Xu Z. Mucin-Type O-Glycans: Barrier, Microbiota, and Immune Anchors in Inflammatory Bowel Disease. J Inflamm Res 2021; 14:5939-5953. [PMID: 34803391 PMCID: PMC8598207 DOI: 10.2147/jir.s327609] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Accepted: 09/19/2021] [Indexed: 12/21/2022] Open
Abstract
Inflammatory bowel disease (IBD), which affects about 7 million people globally, is a chronic inflammatory condition of the gastrointestinal tract caused by gut microbiota alterations, immune dysregulation, and genetic and environmental factors. The association of microbial and immune molecules with mucin-type O-glycans has been increasingly noticed by researchers. Mucin is the main component of mucus, which forms a protective barrier between the microbiota and immune cells in the colon. Mucin-type O-glycans alter the diversity of gastrointestinal microorganisms, which in turn increases the level of O-glycosylation of host intestinal proteins via the utilization of glycans. Additionally, alterations in mucin-type O-glycans not only increase the activity and stability of immune cells but are also involved in the maintenance of intestinal mucosal immune tolerance. Although there is accumulating evidence indicating that mucin-type O-glycans play an important role in IBD, there is limited literature that integrates available data to present a complete picture of exactly how O-glycans affect IBD. This review emphasizes the roles of the mucin-type O-glycans in IBD. This seeks to provide a better understanding and encourages future studies on IBD glycosylation and the design of novel glycan-inspired therapies for IBD.
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Affiliation(s)
- Yaqin Zhang
- Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, 212013, People's Republic of China
| | - Lan Wang
- Danyang Blood Station, Zhenjiang, Jiangsu, 212300, People's Republic of China
| | - Dickson Kofi Wiredu Ocansey
- Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, 212013, People's Republic of China.,Directorate of University Health Services, University of Cape Coast, PMB, Cape Coast, Ghana
| | - Bo Wang
- Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, 212013, People's Republic of China
| | - Li Wang
- Huai'an Maternity and Children Hospital, Huaian, Jiangsu, 223002, People's Republic of China
| | - Zhiwei Xu
- Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, 212013, People's Republic of China
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43
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Li Y, Cao H, Wang X, Guo L, Ding X, Zhao W, Zhang F. Diet-mediated metaorganismal relay biotransformation: health effects and pathways. Crit Rev Food Sci Nutr 2021:1-19. [PMID: 34802351 DOI: 10.1080/10408398.2021.2004993] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
In recent years, the concept of metaorganism expands our insight into how diet-microbe-host interactions contribute to human health and diseases. We realized that many biological metabolic processes in the host can be summarized into metaorganismal relay pathways, in which metabolites such as trimethylamine-N‑oxide, short-chain fatty acids and bile acids act as double-edged swords (beneficial or harmful effects) in the initiation and progression of diseases. Pleiotropic effects of metabolites are derived from several influencing factors including dose level, targeted organ of effect, action duration and species of these metabolites. Based on the pleiotropic effects of metabolites, personalized therapeutic approaches including microecological agents, enzymatic regulators and changes in dietary habits to govern related metabolite production may provide a new insight in promoting human health. In this review, we summarize our current knowledge of metaorganismal relay pathways and elaborate on the pleiotropic effects of metabolites in these pathways, with special emphasis on related therapeutic nutritional interventions.
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Affiliation(s)
- Yanmin Li
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Hong Cao
- Department of Nutrition, Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Xiaoqian Wang
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Lichun Guo
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Xiaoying Ding
- Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wei Zhao
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Feng Zhang
- Department of Nutrition, Affiliated Hospital of Jiangnan University, Wuxi, China
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44
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Debnath N, Kumar R, Kumar A, Mehta PK, Yadav AK. Gut-microbiota derived bioactive metabolites and their functions in host physiology. Biotechnol Genet Eng Rev 2021; 37:105-153. [PMID: 34678130 DOI: 10.1080/02648725.2021.1989847] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Every individual harbours a complex, diverse and mutualistic microbial flora in their intestine and over the time it became an integral part of the body, affecting a plethora of activities of the host. Interaction between host and gut-microbiota affects several aspects of host physiology. Gut-microbiota affects host metabolism by fermenting unabsorbed/undigested carbohydrates in the large intestine. Not only the metabolic functions, any disturbances in the composition of the gut-microbiota during first 2-3 years of life may impact on the brain development and later affects cognition and behaviour. Thus, gut-dysbiosis causes certain serious pathological conditions in the host including metabolic disorders, inflammatory bowel disease and mood alterations, etc. Microbial-metabolites in recent times have emerged as key mediators and are responsible for microbiota induced beneficial effects on host. This review provides an overview of the mechanism of microbial-metabolite production, their respective physiological functions and the impact of gut-microbiome in health and diseases. Metabolites from dietary fibres, aromatic amino acids such as tryptophan, primary bile acids and others are the potential substances and link microbiota to host physiology. Many of these metabolites act as signalling molecules to a number of cells types and also help in the secretion of hormones. Moreover, interaction of microbiota derived metabolites with their host, immunity boosting mechanisms, protection against pathogens and modulation of metabolism is also highlighted here. Understanding all these functional attributes of metabolites produced from gut-microbiota may lead to the opening of a new avenue for preventing and developing potent therapies against several diseases.
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Affiliation(s)
- Nabendu Debnath
- Centre for Molecular Biology, Central University of Jammu, Samba, Jammu & Kashmir, India
| | | | - Ashwani Kumar
- Department of Nutrition Biology, Central University of Haryana, Mahendergarh, Jant-Pali, India
| | - Praveen Kumar Mehta
- Centre for Molecular Biology, Central University of Jammu, Samba, Jammu & Kashmir, India
| | - Ashok Kumar Yadav
- Centre for Molecular Biology, Central University of Jammu, Samba, Jammu & Kashmir, India
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45
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Gregory AL, Pensinger DA, Hryckowian AJ. A short chain fatty acid-centric view of Clostridioides difficile pathogenesis. PLoS Pathog 2021; 17:e1009959. [PMID: 34673840 PMCID: PMC8530303 DOI: 10.1371/journal.ppat.1009959] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
Clostridioides difficile is an opportunistic diarrheal pathogen responsible for significant morbidity and mortality worldwide. A disrupted (dysbiotic) gut microbiome, commonly engendered by antibiotic treatment, is the primary risk factor for C. difficile infection, highlighting that C. difficile–microbiome interactions are critical for determining the fitness of this pathogen. Here, we review short chain fatty acids (SCFAs): a major class of metabolites present in the gut, their production by the gut microbiome, and their impacts on the biology of the host and of C. difficile. We use these observations to illustrate a conceptual model whereby C. difficile senses and responds to SCFAs as a marker of a healthy gut and tunes its virulence accordingly in order to maintain dysbiosis. Future work to learn the molecular mechanisms and genetic circuitry underlying the relationships between C. difficile and SCFAs will help to identify precision approaches, distinct from antibiotics and fecal transplant, for mitigating disease caused by C. difficile and will inform similar investigations into other gastrointestinal pathogens.
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Affiliation(s)
- Anna L. Gregory
- Department of Medicine, University of Wisconsin School of Medicine & Public Health, Madison, Wisconsin, United States of America
- Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine & Public Health, Madison, Wisconsin, United States of America
- Microbiology Doctoral Training Program, University of Wisconsin-Madison, Madison, Wisconsin, United States of America
| | - Daniel A. Pensinger
- Department of Medicine, University of Wisconsin School of Medicine & Public Health, Madison, Wisconsin, United States of America
- Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine & Public Health, Madison, Wisconsin, United States of America
| | - Andrew J. Hryckowian
- Department of Medicine, University of Wisconsin School of Medicine & Public Health, Madison, Wisconsin, United States of America
- Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine & Public Health, Madison, Wisconsin, United States of America
- * E-mail:
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46
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Low DY, Pluschke AM, Flanagan B, Sonni F, Grant LJ, Williams BA, Gidley MJ. Isolated pectin (apple) and fruit pulp (mango) impact gastric emptying, passage rate and short chain fatty acid (SCFA) production differently along the pig gastrointestinal tract. Food Hydrocoll 2021. [DOI: 10.1016/j.foodhyd.2021.106723] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
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47
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Yang P, Zhao J. Variations on gut health and energy metabolism in pigs and humans by intake of different dietary fibers. Food Sci Nutr 2021; 9:4639-4654. [PMID: 34401110 PMCID: PMC8358348 DOI: 10.1002/fsn3.2421] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Revised: 06/03/2021] [Accepted: 06/04/2021] [Indexed: 12/15/2022] Open
Abstract
Many studies have reported that dietary fibers play a crucial role in promoting intestinal health of the host, since it strengthens functions of epithelial barrier and meanwhile maintains intestinal homeostasis of the host by modulating gut microbiota and short-chain fatty acid (SCFA) production. Pig is a good animal model to study effects of dietary fiber on gut health and microbial community. This review has summarized the relevant knowledge available based on roles of various dietary fibers in gut health and energy metabolism of pigs and humans. Evidences summarized in our review indicated that modulating intestinal microbial composition and SCFA production by consuming specific dietary fibers properly could be conducive to health improvement and disease prevention of the host. However, types of dietary fiber from edible foods exert divergent impacts on gut health, energy metabolism, microbial composition, and SCFA production. Therefore, more attention should be focused on different responses of various dietary fibers intake on host metabolism and health.
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Affiliation(s)
- Pan Yang
- State Key Laboratory of Animal NutritionCollege of Animal Science and TechnologyChina Agricultural UniversityBeijingChina
| | - Jinbiao Zhao
- State Key Laboratory of Animal NutritionCollege of Animal Science and TechnologyChina Agricultural UniversityBeijingChina
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48
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de Souza CB, Saad SMI, Venema K. Lean and obese microbiota: differences in in vitro fermentation of food-by-products. Benef Microbes 2021; 12:91-105. [PMID: 34323161 DOI: 10.3920/bm2020.0151] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
The aim of the study was to investigate the potential prebiotic effects of food-by-products (cassava bagasse (n=3), orange bagasse (n=2) and passion fruit peel (n=3)) using an in vitro model simulating the proximal colon, and to assess possible differences in fermentation when using faecal microbiota from lean or obese people. Fermentation of the by-products was compared to a control medium and the prebiotic inulin. The effects of the by-products on the dynamics of the gut microbiota differed according to the type of microbiota, as well as the type of by-product used. Principal Coordinate Analysis of the microbiota showed evidence of a clear separate clustering of lean and obese microbiota before the addition of substrates, which disappeared after fermentation, and instead, distinct clusters due to primary carbohydrate composition of the by-products (starch, fructan and pectin) were present. This is evidence that the substrates drove the obese microbiota to a healthier profile, more similar to that of the lean microbiota. Cassava bagasses enriched the beneficial genus Bifidobacterium in the obese microbiota. The production of total SCFA by cassava bagasses by the obese microbiota was higher than for control medium and inulin. Orange bagasses stimulated the growth of the butyrate-producing genus Coprococcus. Passion fruit peels were poorly fermented and generated negligible amounts of intermediate metabolites, indicating slow fermentation. Nevertheless, passion fruit peel fermentation resulted in a microbiota with the highest diversity and evenness, a positive trait regarding host health. In conclusion, the use of food-by-products could be an important step to tackle obesity and decrease the waste of valuable food material and consequently environmental pollution. They are an inexpensive and non-invasive way to be used as a dietary intervention to improve health, as they were shown here to drive the composition of the obese microbiota to a healthier profile.
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Affiliation(s)
- C Bussolo de Souza
- Maastricht University - campus Venlo, Centre for Healthy Eating & Food Innovation, Villafloraweg 1, 5928 SZ Venlo, the Netherlands
| | - S M I Saad
- University of São Paulo, School of Pharmaceutical Sciences, Dept. Biochemical and Pharmaceutical Technology, Av. Professor Lineu Prestes 580, 05508-000 São Paulo, Brazil
| | - K Venema
- Maastricht University - campus Venlo, Centre for Healthy Eating & Food Innovation, Villafloraweg 1, 5928 SZ Venlo, the Netherlands.,Beneficial Microbes Consultancy, Johan Karschstraat 3, 6709 TN Wageningen, the Netherlands
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49
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Hernández-González T, González-Barrio R, Escobar C, Madrid JA, Periago MJ, Collado MC, Scheer FAJL, Garaulet M. Timing of chocolate intake affects hunger, substrate oxidation, and microbiota: A randomized controlled trial. FASEB J 2021; 35:e21649. [PMID: 34164846 DOI: 10.1096/fj.202002770rr] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 04/20/2021] [Accepted: 04/21/2021] [Indexed: 11/11/2022]
Abstract
Eating chocolate in the morning or in the evening/at night, may differentially affect energy balance and impact body weight due to changes in energy intake, substrate oxidation, microbiota (composition/function), and circadian-related variables. In a randomized controlled trial, postmenopausal females (n = 19) had 100 g of chocolate in the morning (MC), in the evening/at night (EC), or no chocolate (N) for 2 weeks and ate any other food ad libitum. Our results show that 14 days of chocolate intake did not increase body weight. Chocolate consumption decreased hunger and desire for sweets (P < .005), and reduced ad libitum energy intake by ~300 kcal/day during MC and ~150 kcal/day during EC (P = .01), but did not fully compensate for the extra energy contribution of chocolate (542 kcal/day). EC increased physical activity by +6.9%, heat dissipation after meals +1.3%, and carbohydrate oxidation by +35.3% (P < .05). MC reduced fasting glucose (4.4%) and waist circumference (-1.7%) and increased lipid oxidation (+25.6%). Principal component analyses showed that both timings of chocolate intake resulted in differential microbiota profiles and function (P < .05). Heat map of wrist temperature and sleep records showed that EC induced more regular timing of sleep episodes with lower variability of sleep onset among days than MC (60 min vs 78 min; P = .028). In conclusion, having chocolate in the morning or in the evening/night results in differential effects on hunger and appetite, substrate oxidation, fasting glucose, microbiota (composition and function), and sleep and temperature rhythms. Results highlight that the "when" we eat is a relevant factor to consider in energy balance and metabolism.
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Affiliation(s)
- Teresa Hernández-González
- Department of Physiology, Regional Campus of International Excellence, University of Murcia, Murcia, Spain.,Biomedical Research Institute of Murcia, IMIB-Arrixaca-UMU, University Clinical Hospital, Murcia, Spain
| | - Rocío González-Barrio
- Biomedical Research Institute of Murcia, IMIB-Arrixaca-UMU, University Clinical Hospital, Murcia, Spain.,Department of Food Technology, Food Science and Nutrition, Faculty of Veterinary Sciences, Regional Campus of Internacional Excellence, University of Murcia, Murcia, Spain
| | - Carolina Escobar
- Department of Anatomy, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico
| | - Juan Antonio Madrid
- Department of Physiology, Regional Campus of International Excellence, University of Murcia, Murcia, Spain.,Biomedical Research Institute of Murcia, IMIB-Arrixaca-UMU, University Clinical Hospital, Murcia, Spain
| | - Maria Jesús Periago
- Biomedical Research Institute of Murcia, IMIB-Arrixaca-UMU, University Clinical Hospital, Murcia, Spain.,Department of Food Technology, Food Science and Nutrition, Faculty of Veterinary Sciences, Regional Campus of Internacional Excellence, University of Murcia, Murcia, Spain
| | - Maria Carmen Collado
- Institute of Agrochemistry and Food Technology-National Research Council (IATA-CSIC), Paterna, Spain
| | - Frank A J L Scheer
- Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, and Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA
| | - Marta Garaulet
- Department of Physiology, Regional Campus of International Excellence, University of Murcia, Murcia, Spain.,Biomedical Research Institute of Murcia, IMIB-Arrixaca-UMU, University Clinical Hospital, Murcia, Spain.,Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, and Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA
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50
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Yang S, Yu M. Role of Goblet Cells in Intestinal Barrier and Mucosal Immunity. J Inflamm Res 2021; 14:3171-3183. [PMID: 34285541 PMCID: PMC8286120 DOI: 10.2147/jir.s318327] [Citation(s) in RCA: 165] [Impact Index Per Article: 41.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Accepted: 06/29/2021] [Indexed: 12/17/2022] Open
Abstract
Goblet cells and the mucus they secrete serve as an important barrier, preventing pathogens from invading the mucosa to cause intestinal inflammation. The perspective regarding goblet cells and mucus has changed, with current evidence suggesting that they are not passive but play a positive role in maintaining intestinal tract immunity and mucosal homeostasis. Goblet cells could obtain luminal antigens, presenting them to the underlying antigen-presenting cells (APCs) that induces adaptive immune responses. Various immunomodulatory factors can promote the differentiation and maturation of goblet cells, and the secretion of mucin. The abnormal proliferation and differentiation of goblet cells, as well as the deficiency synthesis and secretion of mucins, result in intestinal mucosal barrier dysfunction. This review provides an extensive outline of the signaling pathways that regulate goblet cell proliferation and differentiation and control mucins synthesis and secretion to elucidate how altering these pathways affects goblet functionality. Furthermore, the interaction between mucins and goblet cells in intestinal mucosal immunology is described. Therefore, the contribution of goblet cells and mucus in promoting gut defense and homeostasis is illustrated, while clarifying the regulatory mechanisms involved may allow the development of new therapeutic strategies for intestinal disorders.
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Affiliation(s)
- Songwei Yang
- Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), Chongqing University Cancer Hospital, Chongqing, 400030, People's Republic of China
| | - Min Yu
- Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, People's Republic of China
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