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Ma G, Gao X, Chen Y, Li H, Cui Y, Guo P, Zhao T, Di F. Chemical migration, digestive behaviors and effect on gut microbiota of PLA and PBAT oligomers. JOURNAL OF HAZARDOUS MATERIALS 2025; 491:137988. [PMID: 40121999 DOI: 10.1016/j.jhazmat.2025.137988] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 03/13/2025] [Accepted: 03/16/2025] [Indexed: 03/25/2025]
Abstract
As biodegradable food contact materials (FCMs), polylactic acid (PLA) and poly(butylene adipate-co-terephthalate) (PBAT) may release oligomers into food and raise potential health concerns. This study investigated the migration characteristics and digestive behaviors of oligomers by combining migration experiments, an in vitro digestion model, and high-resolution mass spectrometry. Moreover, the effects of the migrants from both materials on gut microbiota were evaluated following in vitro colonic fermentation for 48 h. The results indicated that 51 PLA oligomers and 45 PBAT oligomers were released into food simulants, with the migration increasing with ethanol concentration. Cyclic oligomers exhibited higher migration than linear oligomers. During digestion, PLA oligomers were almost completely degraded, whereas PBAT oligomers increased, additionally, cyclic oligomers were more susceptible to degradation. Migrants from both materials exhibited cytotoxicity effect on Caco-2 cells, disrupted the gut microbiota homeostasis, affecting multiple metabolic pathways. Especially, the migrants from PBAT inhibited the production of acetic, butyric, and isobutyric acids, while reducing the degradation of propionic acid. Overall, PBAT may pose a greater hazard than PLA. In conclusion, based on a new perspective of "lifecycle", this systematic study will contribute to a deeper understanding of the safety of PLA and PBAT when utilized as FCMs.
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Affiliation(s)
- Guowei Ma
- School of Light Industry Science and Engineering, Beijing Technology and Business University, Beijing 100048, China.
| | - Xiaomeng Gao
- School of Light Industry Science and Engineering, Beijing Technology and Business University, Beijing 100048, China.
| | - Yuting Chen
- School of Light Industry Science and Engineering, Beijing Technology and Business University, Beijing 100048, China.
| | - Hanfei Li
- School of Light Industry Science and Engineering, Beijing Technology and Business University, Beijing 100048, China.
| | - Yiling Cui
- School of Light Industry Science and Engineering, Beijing Technology and Business University, Beijing 100048, China.
| | - Peixue Guo
- School of Light Industry Science and Engineering, Beijing Technology and Business University, Beijing 100048, China.
| | - Tingting Zhao
- State Key Laboratory of Respiratory Health and Multimorbidity, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China.
| | - Feng Di
- School of Light Industry Science and Engineering, Beijing Technology and Business University, Beijing 100048, China.
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Sun J, Song S, Liu J, Chen F, Li X, Wu G. Gut microbiota as a new target for anticancer therapy: from mechanism to means of regulation. NPJ Biofilms Microbiomes 2025; 11:43. [PMID: 40069181 PMCID: PMC11897378 DOI: 10.1038/s41522-025-00678-x] [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: 09/25/2024] [Accepted: 03/04/2025] [Indexed: 03/15/2025] Open
Abstract
In order to decipher the relationship between gut microbiota imbalance and cancer, this paper reviewed the role of intestinal microbiota in anticancer therapy and related mechanisms, discussed the current research status of gut microbiota as a biomarker of cancer, and finally summarized the reasonable means of regulating gut microbiota to assist cancer therapy. Overall, our study reveals that the gut microbiota can serve as a potential target for improving cancer management.
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Affiliation(s)
- Jiaao Sun
- Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Shiyan Song
- Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Jiahua Liu
- Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Feng Chen
- Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
| | - Xiaorui Li
- Department of oncology, Cancer Hospital of Dalian University of Technology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China.
| | - Guangzhen Wu
- Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
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Rodiño-Janeiro BK, Khannous-Lleiffe O, Pigrau M, Willis JR, Salvo-Romero E, Nieto A, Expósito E, Fortea M, Pardo-Camacho C, Albert-Bayo M, González-Castro AM, Guagnozzi D, Martínez C, Lobo B, Vicario M, Santos J, Gabaldón T, Alonso-Cotoner C. Acute stress triggers sex-dependent rapid alterations in the human small intestine microbiota composition. Front Microbiol 2025; 15:1441126. [PMID: 39881982 PMCID: PMC11778178 DOI: 10.3389/fmicb.2024.1441126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Accepted: 12/16/2024] [Indexed: 01/31/2025] Open
Abstract
Background/aims Digestive disorders of gut-brain interaction (DGBI) are very common, predominant in females, and usually associated with intestinal barrier dysfunction, dysbiosis, and stress. We previously found that females have increased susceptibility to intestinal barrier dysfunction in response to acute stress. However, whether this is associated with changes in the small bowel microbiota remains unknown. We have evaluated changes in the small intestinal microbiota in response to acute stress to better understand stress-induced intestinal barrier dysfunction. Methods Jejunal biopsies were obtained at baseline and 90 min after cold pain or sham stress. Autonomic (blood pressure and heart rate), hormonal (plasma cortisol and adrenocorticotropic hormone) and psychological (Subjective Stress Rating Scale) responses to cold pain and sham stress were monitored. Microbial DNA from the biopsies was analyzed using a 16S metabarcoding approach before and after cold pain stress and sham stress. Differences in diversity and relative abundance of microbial taxa were examined. Results Cold pain stress was associated with a significant decrease in alpha diversity (P = 0.015), which was more pronounced in females, along with significant sex differences in the abundance of specific taxa and the overall microbiota composition. Microbiota alterations significantly correlated with changes in psychological responses, hormones, and gene expression in the intestinal mucosal. Cold pain stress was also associated with activation of autonomic, hormonal and psychological response, with no differences between sexes. Conclusions Acute stress elicits rapid alterations in bacterial composition in the jejunum of healthy subjects and these changes are more pronounced in females. Our results may contribute to the understanding of female predominance in DGBI.
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Affiliation(s)
- Bruno K. Rodiño-Janeiro
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Olfat Khannous-Lleiffe
- Barcelona Supercomputing Centre (BSC-CNS), Barcelona, Spain
- Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain
| | - Marc Pigrau
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain
| | - Jesse R. Willis
- Barcelona Supercomputing Centre (BSC-CNS), Barcelona, Spain
- Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain
| | - Eloísa Salvo-Romero
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Laboratory of Translational Mucosal Immunology, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Adoración Nieto
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Elba Expósito
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Laboratory of Translational Mucosal Immunology, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Marina Fortea
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Laboratory of Translational Mucosal Immunology, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Cristina Pardo-Camacho
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Laboratory of Translational Mucosal Immunology, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Mercé Albert-Bayo
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Laboratory of Translational Mucosal Immunology, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Ana María González-Castro
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Laboratory of Translational Mucosal Immunology, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain
| | - Danila Guagnozzi
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Laboratory of Translational Mucosal Immunology, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain
| | - Cristina Martínez
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Renal Physiopathology Group, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Beatriz Lobo
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain
| | - María Vicario
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Laboratory of Translational Mucosal Immunology, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Javier Santos
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain
| | - Toni Gabaldón
- Barcelona Supercomputing Centre (BSC-CNS), Barcelona, Spain
- Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain
- Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain
- Centro de Investigación Biomédica En Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Carmen Alonso-Cotoner
- Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain
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Zhu M, Yang L, Kong S, Bai Y, Zhao B. Lacticaseibacillus rhamnosus LRa05 alleviates cyclophosphamide-induced immunosuppression and intestinal microbiota disorder in mice. J Food Sci 2024; 89:10003-10017. [PMID: 39592250 DOI: 10.1111/1750-3841.17538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Revised: 10/12/2024] [Accepted: 10/26/2024] [Indexed: 11/28/2024]
Abstract
Probiotics play a crucial role in regulating the gut microbiota and enhancing immune response. Oral administration of probiotics modulates intestinal microbiota composition and immune homeostasis. In this study, we investigated the immunoregulatory effect of Lacticaseibacillus rhamnosus LRa05 on cyclophosphamide (CTX)-induced immunosuppressive mice. The results showed that oral administration of LRa05 reduced weight loss, restored immune organ indices, and maintained the structural integrity of the intestinal tissue in CTX-treated mice. Moreover, oral administration of LRa05 exhibited immune-modulating properties by promoting the secretion of cytokines (tumor necrosis factor-α, interleukin-1β, interleukin-10, and secretory immunoglobulin A) in serum. Moreover, the analysis of 16S rRNA amplicon sequencing revealed that LRa05 increased gut microbiota diversity and regulated its composition. In detail, LRa05 intervention restored the Firmicutes/Bacteroidota ratio and significantly increased the relative abundance of Lachnospiraceae_NK4A136_group, Oscillibacter, Alloprevotella, Parasutterella, and Roseburia in immunocompromised mice. Conversely, the abundances of Helicobacter, Bacteroides, and unclassified_Desulfovibrionaceae were significantly decreased after administration of LRa05. Based on these findings, orally administered LRa05 could effectively maintain intestinal microbiota homeostasis and regulate immunity, suggesting the potential of L. rhamnosus LRa05 as a candidate probiotic strain in the application of dietary supplement. PRACTICAL APPLICATION: Supplement with L. rhamnosus LRa05 can improve immunity, regulate gut microbiota and promote body health.
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Affiliation(s)
- Mingming Zhu
- Wuhan Wecare Probiotic Research Institute, Wuhan, China
| | - Lvzhu Yang
- Wuhan Wecare Probiotic Research Institute, Wuhan, China
| | - Sufen Kong
- Wuhan Wecare Probiotic Research Institute, Wuhan, China
| | - Yuyuan Bai
- National Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, China
| | - Bin Zhao
- Wuhan Wecare Probiotic Research Institute, Wuhan, China
- National Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, China
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Sun Y, Li Z, Yan M, Zhao H, He Z, Zhu M. Responses of Intestinal Antioxidant Capacity, Morphology, Barrier Function, Immunity, and Microbial Diversity to Chlorogenic Acid in Late-Peak Laying Hens. Animals (Basel) 2024; 14:2957. [PMID: 39457887 PMCID: PMC11503754 DOI: 10.3390/ani14202957] [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: 08/11/2024] [Revised: 09/28/2024] [Accepted: 10/07/2024] [Indexed: 10/28/2024] Open
Abstract
This study examined the influence of chlorogenic acid (CGA) on gut antioxidant status, morphology, barrier function, immunity, and cecal microbiota in late-peak laying hens. A total of 240 Hy-Line Brown hens, aged 43 weeks, were randomly assigned to four groups, the basal diet +0, 400, 600, and 800 mg/kg CGA, for 12 weeks. The results revealed that CGA significantly reduced ileal H2O2 and malondialdehyde levels; increased duodenal height, ileal villus height, and villus height-to-crypt depth ratio; while decreasing jejunal crypt depth. The 600 and 800 mg/kg CGA significantly upregulated the duodenal, jejunal, and ileal ZO-1 and occludin gene expression; increased IgG levels in serum and ileum; and upregulated ileal IgA gene expression. The 600 mg/kg CGA significantly upregulated CD3D and CD4 gene expression, while downregulating IL-1β gene expression in duodenum, jejunum, and ileum. Moreover, CGA changed the gut microbiota structure. The SCFA-producing bacteria unclassified_f__Peptostreptococcaceae, unclassified_f_Oscillospiraceae, Pseudoflavonifractor, Lachnospiraceae_FCS020_group, Oscillospira, Elusimicrobium, Eubacterium_ventriosum_group, Intestinimonas, and norank_f_Coriobacteriales_Incertae_Sedis were significantly enriched in the 400, 600, and/or 800 mg/kg CGA groups. The bacteria Lactobacillus, Bacillus, and Akkermansia were significantly enriched in the 600 mg/kg CGA group. Conclusively, dietary CGA (600-800 mg/kg) improved intestinal antioxidant status, morphology, barrier and immune function, and beneficial microbiota growth in late-peak laying hens.
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Affiliation(s)
- Yue Sun
- Jiangsu Key Laboratory of Sericultural Biology and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, China; (Y.S.); (Z.L.); (M.Y.); (H.Z.)
- Key Laboratory of Silkworm and Mulberry Genetic Improvement, Ministry of Agriculture and Rural Affairs, The Sericultural Research Institute, Chinese Academy of Agricultural Sciences, Zhenjiang 212100, China
| | - Zhuang Li
- Jiangsu Key Laboratory of Sericultural Biology and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, China; (Y.S.); (Z.L.); (M.Y.); (H.Z.)
- Key Laboratory of Silkworm and Mulberry Genetic Improvement, Ministry of Agriculture and Rural Affairs, The Sericultural Research Institute, Chinese Academy of Agricultural Sciences, Zhenjiang 212100, China
| | - Ming Yan
- Jiangsu Key Laboratory of Sericultural Biology and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, China; (Y.S.); (Z.L.); (M.Y.); (H.Z.)
- Key Laboratory of Silkworm and Mulberry Genetic Improvement, Ministry of Agriculture and Rural Affairs, The Sericultural Research Institute, Chinese Academy of Agricultural Sciences, Zhenjiang 212100, China
| | - Haitong Zhao
- Jiangsu Key Laboratory of Sericultural Biology and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, China; (Y.S.); (Z.L.); (M.Y.); (H.Z.)
- Key Laboratory of Silkworm and Mulberry Genetic Improvement, Ministry of Agriculture and Rural Affairs, The Sericultural Research Institute, Chinese Academy of Agricultural Sciences, Zhenjiang 212100, China
| | - Zhengxing He
- Dantu Borough Animal Disease Prevention and Control Center, Zhenjiang 212100, China;
| | - Mingkun Zhu
- Jiangsu Key Laboratory of Sericultural Biology and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, China; (Y.S.); (Z.L.); (M.Y.); (H.Z.)
- Key Laboratory of Silkworm and Mulberry Genetic Improvement, Ministry of Agriculture and Rural Affairs, The Sericultural Research Institute, Chinese Academy of Agricultural Sciences, Zhenjiang 212100, China
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Zhang Y, Zhang H. Current understanding and new insights in the treatment of IgA nephropathy. Nephrology (Carlton) 2024; 29 Suppl 2:75-79. [PMID: 38958055 DOI: 10.1111/nep.14340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2023] [Accepted: 06/24/2024] [Indexed: 07/04/2024]
Abstract
IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, and almost all patients are at risk of progression to end-stage kidney disease within their lifetime. The mechanisms responsible for the presentation and development of IgAN are required for the development of highly targeted therapies for this disease. In this review, we first demonstrate the current treatment strategy of IgAN recommended by the 2021 KDIGO guideline. Then, we update the new insights into disease pathogenesis based on the well acknowledged 'multiple-hit hypothesis' and provide the potential therapeutic targets involved in the upstream production of pathogenic IgA1 and the downstream complement activation. Finally, the recent large randomized controlled trials focusing on these novel targets have been summarized, among which Nefecon and Sparsentan have received approval and Telitacicept have been used off-label for IgAN. In the future, emerging treatment approaches for IgAN is likely to evolve, which will signify a shift in the management of the IgAN from traditional immunosuppressive approaches to an era of targeted treatment based on the understanding of the pathogenic mechanisms.
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Affiliation(s)
- Yuemiao Zhang
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China
- Institute of Nephrology, Peking University, Beijing, China
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Peking University, Ministry of Education, Beijing, China
- Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China
| | - Hong Zhang
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China
- Institute of Nephrology, Peking University, Beijing, China
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Peking University, Ministry of Education, Beijing, China
- Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China
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Jung HS, Park YJ, Gu BH, Han G, Ji W, Hwang SM, Kim M. Coumarin derivatives ameliorate the intestinal inflammation and pathogenic gut microbiome changes in the model of infectious colitis through antibacterial activity. Front Cell Infect Microbiol 2024; 14:1362773. [PMID: 39081865 PMCID: PMC11287663 DOI: 10.3389/fcimb.2024.1362773] [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: 12/29/2023] [Accepted: 06/24/2024] [Indexed: 08/02/2024] Open
Abstract
Coumarin, a phenolic compound, is a secondary metabolite produced by plants such as Tanga and Lime. Coumarin derivatives were prepared via Pechmann condensation. In this study, we performed in vitro and in vivo experiments to determine the antimicrobial and gut immune-regulatory functions of coumarin derivatives. For the in vitro antimicrobial activity assay, coumarin derivatives C1 and C2 were selected based on their pathogen-killing activity against various pathogenic microbes. We further demonstrated that the selected coumarin derivatives disrupted bacterial cell membranes. Next, we examined the regulatory function of the coumarin derivatives in gut inflammation using an infectious colitis model. In an in vivo infectious colitis model, administration of selected C1 coumarin derivatives reduced pathogen loads, the number of inflammatory immune cells (Th1 cells and Th17 cells), and inflammatory cytokine levels (IL-6 and IL-1b) in the intestinal tissue after pathogen infection. In addition, we found that the administration of C1 coumarin derivatives minimized abnormal gut microbiome shift-driven pathogen infection. Potential pathogenic gut microbes, such as Enterobacteriaceae and Staphylococcaceae, were increased by pathogen infection. However, this pathogenic microbial expansion was minimized and beneficial bacteria, such as Ligilactobacillus and Limosilactobacillus, increased with C1 coumarin derivative treatment. Functional gene enrichment assessment revealed that the relative abundance of genes associated with lipid and nucleotide metabolism was reduced by pathogen infection; however, this phenomenon was not observed in C1 coumarin derivative-treated animals. Collectively, our data suggest that C1 coumarin derivative is effective antibacterial agents that minimize pathogen-induced gut inflammation and abnormal gut microbiome modulation through their antibacterial activity.
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Affiliation(s)
- Hui-su Jung
- Laboratory of Animal Immunology, Department of Animal Science, College of Natural Resource & Life Science, Pusan National University, Miryang, Republic of Korea
| | - Yei Ju Park
- R & D Center, EyeGene, Goyang, Republic of Korea
| | - Bon-Hee Gu
- Life and Industry Convergence Research Institute, Pusan National University, Miryang, Republic of Korea
| | - Goeun Han
- Laboratory of Animal Immunology, Department of Animal Science, College of Natural Resource & Life Science, Pusan National University, Miryang, Republic of Korea
- Future Earth Research Institute, PNU JYS Science Academy, Pusan National University, Busan, Republic of Korea
| | - Woonhak Ji
- Laboratory of Animal Immunology, Department of Animal Science, College of Natural Resource & Life Science, Pusan National University, Miryang, Republic of Korea
| | - Su mi Hwang
- Department of Biomedical Laboratory Science, College of Health and Medical Science, Sangji University, Wonju, Republic of Korea
| | - Myunghoo Kim
- Laboratory of Animal Immunology, Department of Animal Science, College of Natural Resource & Life Science, Pusan National University, Miryang, Republic of Korea
- Future Earth Research Institute, PNU JYS Science Academy, Pusan National University, Busan, Republic of Korea
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Cho YS, Han K, Xu J, Moon JJ. Novel strategies for modulating the gut microbiome for cancer therapy. Adv Drug Deliv Rev 2024; 210:115332. [PMID: 38759702 PMCID: PMC11268941 DOI: 10.1016/j.addr.2024.115332] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 05/08/2024] [Accepted: 05/13/2024] [Indexed: 05/19/2024]
Abstract
Recent advancements in genomics, transcriptomics, and metabolomics have significantly advanced our understanding of the human gut microbiome and its impact on the efficacy and toxicity of anti-cancer therapeutics, including chemotherapy, immunotherapy, and radiotherapy. In particular, prebiotics, probiotics, and postbiotics are recognized for their unique properties in modulating the gut microbiota, maintaining the intestinal barrier, and regulating immune cells, thus emerging as new cancer treatment modalities. However, clinical translation of microbiome-based therapy is still in its early stages, facing challenges to overcome physicochemical and biological barriers of the gastrointestinal tract, enhance target-specific delivery, and improve drug bioavailability. This review aims to highlight the impact of prebiotics, probiotics, and postbiotics on the gut microbiome and their efficacy as cancer treatment modalities. Additionally, we summarize recent innovative engineering strategies designed to overcome challenges associated with oral administration of anti-cancer treatments. Moreover, we will explore the potential benefits of engineered gut microbiome-modulating approaches in ameliorating the side effects of immunotherapy and chemotherapy.
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Affiliation(s)
- Young Seok Cho
- Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA
| | - Kai Han
- State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 21009, China; Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China
| | - Jin Xu
- Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA
| | - James J Moon
- Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
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9
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Kan L, Zheng Z, Fu W, Ma Y, Wang W, Qian H, Xu L. Recent progress on engineered micro/nanomaterials mediated modulation of gut microbiota for treating inflammatory bowel disease. J Control Release 2024; 370:43-65. [PMID: 38608876 DOI: 10.1016/j.jconrel.2024.04.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Revised: 03/15/2024] [Accepted: 04/05/2024] [Indexed: 04/14/2024]
Abstract
Inflammatory bowel disease (IBD) is a type of chronic recurrent inflammation disease that mainly includes Crohn's disease and ulcerative colitis. Currently, the treatments for IBD remain highly challenging, with clinical treatment drugs showing limited efficacy and adverse side effects. Thus, developing drug candidates with comprehensive therapeutic effects, high efficiency, and low toxicity is urgently needed. Recently, micro/nanomaterials have attracted considerable interest because of their bioavailability, multitarget and efficient effects on IBD. In addition, gut modulation plays a substantial role in restoring intestinal homeostasis. Therefore, efficient microbiota-based strategies modulating gut microenvironment have great potential in remarkably treating IBD. With the development of micro- and nanomaterials for the treatment of IBD and more in-depth studies of their therapeutic mechanisms, it has been found that these treatments also have a tendency to positively regulate the intestinal flora, resulting in an increase in the beneficial flora and a decrease in the level of pathogenic bacteria, thus regulating the composition of the intestinal flora to a normal state. In this review, we first present the interactions among the immune system, intestinal barrier, and gut microbiome. In addition, recent advances in administration routes and methods that positively arouse the regulation of intestinal flora for IBD using probiotics, prebiotics, and redox-active micro/nanomaterials have been reviewed. Finally, the key challenges and critical perspectives of gut microbiota-based micro/nanomaterial treatment are also discussed.
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Affiliation(s)
- Lingling Kan
- School of Biomedical Engineering, Anhui Provincial Institute of Translational Medicine, Anhui Medical University, Hefei, Anhui 230032, PR China; Anhui Engineering Research Center for Medical Micro-Nano Devices, Hefei, Anhui 230012, PR China
| | - Ziwen Zheng
- School of Biomedical Engineering, Anhui Provincial Institute of Translational Medicine, Anhui Medical University, Hefei, Anhui 230032, PR China; Anhui Engineering Research Center for Medical Micro-Nano Devices, Hefei, Anhui 230012, PR China
| | - Wanyue Fu
- School of Biomedical Engineering, Anhui Provincial Institute of Translational Medicine, Anhui Medical University, Hefei, Anhui 230032, PR China; Anhui Engineering Research Center for Medical Micro-Nano Devices, Hefei, Anhui 230012, PR China
| | - Yan Ma
- School of Biomedical Engineering, Anhui Provincial Institute of Translational Medicine, Anhui Medical University, Hefei, Anhui 230032, PR China; Anhui Engineering Research Center for Medical Micro-Nano Devices, Hefei, Anhui 230012, PR China
| | - Wanni Wang
- School of Biomedical Engineering, Anhui Provincial Institute of Translational Medicine, Anhui Medical University, Hefei, Anhui 230032, PR China; Anhui Engineering Research Center for Medical Micro-Nano Devices, Hefei, Anhui 230012, PR China.
| | - Haisheng Qian
- School of Biomedical Engineering, Anhui Provincial Institute of Translational Medicine, Anhui Medical University, Hefei, Anhui 230032, PR China; Anhui Engineering Research Center for Medical Micro-Nano Devices, Hefei, Anhui 230012, PR China.
| | - Lingling Xu
- School of Biomedical Engineering, Anhui Provincial Institute of Translational Medicine, Anhui Medical University, Hefei, Anhui 230032, PR China; Anhui Engineering Research Center for Medical Micro-Nano Devices, Hefei, Anhui 230012, PR China.
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10
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Mei EH, Yao C, Chen YN, Nan SX, Qi SC. Multifunctional role of oral bacteria in the progression of non-alcoholic fatty liver disease. World J Hepatol 2024; 16:688-702. [PMID: 38818294 PMCID: PMC11135273 DOI: 10.4254/wjh.v16.i5.688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Revised: 02/26/2024] [Accepted: 04/07/2024] [Indexed: 05/22/2024] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver disorders of varying severity, ultimately leading to fibrosis. This spectrum primarily consists of NAFL and non-alcoholic steatohepatitis. The pathogenesis of NAFLD is closely associated with disturbances in the gut microbiota and impairment of the intestinal barrier. Non-gut commensal flora, particularly bacteria, play a pivotal role in the progression of NAFLD. Notably, Porphyromonas gingivalis, a principal bacterium involved in periodontitis, is known to facilitate lipid accumulation, augment immune responses, and induce insulin resistance, thereby exacerbating fibrosis in cases of periodontitis-associated NAFLD. The influence of oral microbiota on NAFLD via the "oral-gut-liver" axis is gaining recognition, offering a novel perspective for NAFLD management through microbial imbalance correction. This review endeavors to encapsulate the intricate roles of oral bacteria in NAFLD and explore underlying mechanisms, emphasizing microbial control strategies as a viable therapeutic avenue for NAFLD.
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Affiliation(s)
- En-Hua Mei
- Shanghai Medical College, Fudan University, Shanghai 200000, China
- Department of Prothodontics, Shanghai Stomatological Hospital, Fudan University, Shanghai 200000, China
- Shanghai Key Laboratory of Craniomaxiofacial Development and Diseases, Fudan University, Shanghai 200000, China
| | - Chao Yao
- Department of Prothodontics, Shanghai Stomatological Hospital, Fudan University, Shanghai 200000, China
- Shanghai Key Laboratory of Craniomaxiofacial Development and Diseases, Fudan University, Shanghai 200000, China
| | - Yi-Nan Chen
- Shanghai Medical College, Fudan University, Shanghai 200000, China
| | - Shun-Xue Nan
- Shanghai Medical College, Fudan University, Shanghai 200000, China
| | - Sheng-Cai Qi
- Department of Prothodontics, Shanghai Stomatological Hospital, Fudan University, Shanghai 200000, China
- Shanghai Key Laboratory of Craniomaxiofacial Development and Diseases, Fudan University, Shanghai 200000, China.
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11
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Chen T, Aly RSS, Shen Y, Tang S, Zhao Y, Zhao J, Chen X. The silent threat: Nanopolystyrene and chrysene pollutants disrupt the intestinal mucosal barrier, new insights from juvenile Siniperca chuatsi. THE SCIENCE OF THE TOTAL ENVIRONMENT 2024; 926:172001. [PMID: 38552987 DOI: 10.1016/j.scitotenv.2024.172001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Revised: 03/21/2024] [Accepted: 03/24/2024] [Indexed: 04/05/2024]
Abstract
The intestinal mucosal barrier-comprising microbial, mechanical, chemical, and immunological barriers-is critical to protection against pathogens and maintenance of host health; however, it remains unclear whether it is affected by environmental contaminants. Therefore, the present study assessed whether exposure to ambient concentrations of nanopolystyrene (NP) and chrysene (CHR)-two ubiquitous environmental pollutants in the aquatic environment-affect the intestinal mucosal barrier in juvenile Siniperca chuatsi. After exposure for 21 days, S. chuatsi exhibited intestinal oxidative stress and imbalance of intestinal microbial homeostasis. NP and/or CHR exposure also disrupted the intestinal mechanical barrier, as evidenced by the altered intestinal epithelial cell morphology, disrupted structure of intercellular tight junctions, and decreased expression of tight junction proteins. Damage to the intestinal chemical barrier manifested as thinning of the mucus layer owing to the loss and damage of goblet cells. Furthermore, the intestinal immunological barrier was impaired as indicated by the loss of intestinal intraepithelial lymphocytes and increase in pro-inflammatory cytokines, chemokines, and immunoglobulins. These findings collectively suggest that the intestinal mucosal barrier was damaged. This study is, to the best of our knowledge, the first to report that exposure to NP and/or CHR at environmentally relevant concentrations disrupts the intestinal mucosal barrier in organisms and highlight the significance of nanoplastic/CHR pollution for intestinal health.
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Affiliation(s)
- Tiantian Chen
- Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai 201306, China
| | - Rahma Sakina Said Aly
- Centre for Research on Environmental Ecology and Fish Nutrition of the Ministry of Agriculture, Shanghai Ocean University, Shanghai 201306, China
| | - Yawei Shen
- College of Fisheries, Henan Normal University, Xinxiang 453007, Henan, China
| | - Shoujie Tang
- Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai 201306, China
| | - Yan Zhao
- Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai 201306, China
| | - Jinliang Zhao
- Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai 201306, China
| | - Xiaowu Chen
- Centre for Research on Environmental Ecology and Fish Nutrition of the Ministry of Agriculture, Shanghai Ocean University, Shanghai 201306, China.
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12
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Wu D, Liang S, Du X, Xiao J, Feng H, Ren Z, Yang X, Yang X. Effects of fecal microbiota transplantation and fecal virome transplantation on LPS-induced intestinal injury in broilers. Poult Sci 2024; 103:103316. [PMID: 38128454 PMCID: PMC10776634 DOI: 10.1016/j.psj.2023.103316] [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: 09/26/2023] [Revised: 11/12/2023] [Accepted: 11/18/2023] [Indexed: 12/23/2023] Open
Abstract
The interesting roles and efficiencies of fecal microbiota transplantation (FMT) have attracted considerable attention and have been gradually evidenced in specific animal models. While the growing evidence that bacteriophages play roles in FMT efficacy has attracted considerable interest. In this study, we aimed to explore the effects of FMT and fecal virome transplantation (FVT) in improving inflammatory damage and ileal microbiota disorder in broilers. A total of 224 Arbor Acres broilers were selected at 1-day-old and randomly divided into the following 4 groups, with 56 broilers in each group: the CON group (the negative control group, sterile physiological saline injection + sterile phosphate-buffered saline (PBS) solution gavage), LPS group (the positive control group, lipopolysaccharide (LPS) injection + sterile PBS solution gavage), LPS + FMT group (LPS injection + FMT solution gavage), LPS + FVT group (LPS injection + FVT solution gavage). The results showed that: LPS injection significantly upregulated the mRNA expression levels of IFN-γ (P < 0.05) and IL-8 (P < 0.001) in ileal mucosa of broilers at 11th day of age (D11), while LPS + FMT and LPS + FVT did not; LPS injection significantly upregulated the mRNA expression of ZO-1 in ileal mucosa at D11 (P < 0.01), while LPS + FMT and LPS + FVT did not; at D11, compare to CON group, LPS injection and LPS + FMT significantly increased the relative abundance of virulence factor Rab2 interacting conserved protein A-related genes in broiler ileum contents (P < 0.05), while LPS + FVT had no significant difference with CON group (P > 0.05); at D11, LPS injection significantly downregulated the biosynthesis of antibiotics pathway (P < 0.05) in the ileal contents, while LPS + FVT did not. In conclusion, both FMT and FVT could promote the recovery of inflammation caused by LPS. Furthermore, FVT had shown less disadvantage stimulation on the broilers and could reduce the risk of transmission of pathogenic genes, compared to FMT.
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Affiliation(s)
- Dengyu Wu
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, PR China; Key Laboratory of Livestock Biology, Northwest A&F University, Yangling, Shaanxi 712100, PR China
| | - Saisai Liang
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, PR China; Key Laboratory of Livestock Biology, Northwest A&F University, Yangling, Shaanxi 712100, PR China
| | - Xiaoqian Du
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, PR China; Key Laboratory of Livestock Biology, Northwest A&F University, Yangling, Shaanxi 712100, PR China
| | - Jinhao Xiao
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, PR China; Key Laboratory of Livestock Biology, Northwest A&F University, Yangling, Shaanxi 712100, PR China
| | - Hongyu Feng
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, PR China; Key Laboratory of Livestock Biology, Northwest A&F University, Yangling, Shaanxi 712100, PR China
| | - Zhouzheng Ren
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, PR China; Key Laboratory of Livestock Biology, Northwest A&F University, Yangling, Shaanxi 712100, PR China
| | - Xiaojun Yang
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, PR China; Key Laboratory of Livestock Biology, Northwest A&F University, Yangling, Shaanxi 712100, PR China
| | - Xin Yang
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, PR China; Key Laboratory of Livestock Biology, Northwest A&F University, Yangling, Shaanxi 712100, PR China.
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13
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Zhou Y, Liu X, Gao W, Luo X, Lv J, Wang Y, Liu D. The role of intestinal flora on tumor immunotherapy: recent progress and treatment implications. Heliyon 2024; 10:e23919. [PMID: 38223735 PMCID: PMC10784319 DOI: 10.1016/j.heliyon.2023.e23919] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Revised: 12/08/2023] [Accepted: 12/15/2023] [Indexed: 01/16/2024] Open
Abstract
Immunotherapy, specifically immune checkpoint inhibitors, has emerged as a promising approach for treating malignant tumors. The gut, housing approximately 70 % of the body's immune cells, is abundantly populated with gut bacteria that actively interact with the host's immune system. Different bacterial species within the intestinal flora are in a delicate equilibrium and mutually regulate each other. However, when this balance is disrupted, pathogenic microorganisms can dominate, adversely affecting the host's metabolism and immunity, ultimately promoting the development of disease. Emerging researches highlight the potential of interventions such as fecal microflora transplantation (FMT) to improve antitumor immune response and reduce the toxicity of immunotherapy. These remarkable findings suggest the major role of intestinal flora in the development of cancer immunotherapy and led us to the hypothesis that intestinal flora transplantation may be a new breakthrough in modifying immunotherapy side effects.
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Affiliation(s)
- Yimin Zhou
- School of Basic Medical Sciences, Shandong University, Jinan 250011, China
| | - Xiangdong Liu
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China
| | - Wei Gao
- School of Basic Medical Sciences, Shandong University, Jinan 250011, China
| | - Xin Luo
- School of Basic Medical Sciences, Shandong University, Jinan 250011, China
| | - Junying Lv
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China
| | - Yunshan Wang
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China
| | - Duanrui Liu
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China
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14
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Devan J, Nosi V, Spagnuolo J, Chancellor A, Beshirova A, Loureiro JP, Vacchini A, Hendrik Niess J, Calogero R, Mori L, De Libero G, Hruz P. Surface protein and functional analyses identify CD4+CD39+ TCR αβ+ and activated TCR Vδ1+ cells with distinct pro-inflammatory functions in Crohn's disease lesions. Clin Exp Immunol 2024; 215:79-93. [PMID: 37586415 PMCID: PMC10776239 DOI: 10.1093/cei/uxad098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 07/06/2023] [Accepted: 08/14/2023] [Indexed: 08/18/2023] Open
Abstract
Crohn's disease (CD) is a chronic immune-mediated disorder of the gastrointestinal tract. Extensive screening studies have revealed the accumulation of immune cell subsets with unique plasticity and immunoregulatory properties in patients with CD. We performed phenotypic and functional studies on inflamed and non-inflamed bioptic tissue to investigate the presence of distinct T cells in the intestinal mucosa of CD patients. We analysed hundreds of surface molecules expressed on cells isolated from the intestinal tissue of CD patients using anti-CD45 mAbs-based barcoding. A gene ontology enrichment analysis showed that proteins that regulate the activation of T cells were the most enriched group. We, therefore, designed T-cell focused multicolour flow-cytometry panels and performed clustering analysis which revealed an accumulation of activated TEM CD4+CD39+ T cells producing IL-17 and IL-21 and increased frequency of terminally differentiated TCR Vδ1+ cells producing TNF-α and IFN-γ in inflamed tissue of CD patients. The different functional capacities of CD4+ and TCR Vδ1+ cells in CD lesions indicate their non-overlapping contribution to inflammation. The abnormally high number of terminally differentiated TCR Vδ1+ cells suggests that they are continuously activated in inflamed tissue, making them a potential target for novel therapies.
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Affiliation(s)
- Jan Devan
- Experimental Immunology, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Vladimir Nosi
- Experimental Immunology, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
- Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy
| | - Julian Spagnuolo
- Experimental Immunology, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Andrew Chancellor
- Experimental Immunology, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Aisha Beshirova
- Experimental Immunology, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Jose Pedro Loureiro
- Experimental Immunology, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Alessandro Vacchini
- Experimental Immunology, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Jan Hendrik Niess
- Gastroenterology, Department of Biomedicine, University of Basel, Clarunis, Basel, Switzerland
- Department of Clinical Research, University of Basel, Basel, Switzerland
- University Center for Gastrointestinal and Liver Diseases, Basel, Switzerland
| | - Raffaele Calogero
- Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy
| | - Lucia Mori
- Experimental Immunology, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Gennaro De Libero
- Experimental Immunology, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Petr Hruz
- Experimental Immunology, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
- University Center for Gastrointestinal and Liver Diseases, Basel, Switzerland
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15
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Sender R, Weiss Y, Navon Y, Milo I, Azulay N, Keren L, Fuchs S, Ben-Zvi D, Noor E, Milo R. The total mass, number, and distribution of immune cells in the human body. Proc Natl Acad Sci U S A 2023; 120:e2308511120. [PMID: 37871201 PMCID: PMC10623016 DOI: 10.1073/pnas.2308511120] [Citation(s) in RCA: 98] [Impact Index Per Article: 49.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2023] [Accepted: 09/11/2023] [Indexed: 10/25/2023] Open
Abstract
The immune system is a complex network of cells with critical functions in health and disease. However, a comprehensive census of the cells comprising the immune system is lacking. Here, we estimated the abundance of the primary immune cell types throughout all tissues in the human body. We conducted a literature survey and integrated data from multiplexed imaging and methylome-based deconvolution. We also considered cellular mass to determine the distribution of immune cells in terms of both number and total mass. Our results indicate that the immune system of a reference 73 kg man consists of 1.8 × 1012 cells (95% CI 1.5-2.3 × 1012), weighing 1.2 kg (95% CI 0.8-1.9). Lymphocytes constitute 40% of the total number of immune cells and 15% of the mass and are mainly located in the lymph nodes and spleen. Neutrophils account for similar proportions of both the number and total mass of immune cells, with most neutrophils residing in the bone marrow. Macrophages, present in most tissues, account for 10% of immune cells but contribute nearly 50% of the total cellular mass due to their large size. The quantification of immune cells within the human body presented here can serve to understand the immune function better and facilitate quantitative modeling of this vital system.
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Affiliation(s)
- Ron Sender
- Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 76100, Israel
| | - Yarden Weiss
- Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel
| | - Yoav Navon
- Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 76100, Israel
| | - Idan Milo
- Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel
| | - Nofar Azulay
- Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel
| | - Leeat Keren
- Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel
| | - Shai Fuchs
- Pediatric Endocrine and Diabetes Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan 52621, Israel
| | - Danny Ben-Zvi
- Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel
| | - Elad Noor
- Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 76100, Israel
| | - Ron Milo
- Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 76100, Israel
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16
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Sun L, Zhang B. The digestive system and autoimmunity. BMC Immunol 2023; 24:36. [PMID: 37794375 PMCID: PMC10552442 DOI: 10.1186/s12865-023-00561-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Accepted: 08/07/2023] [Indexed: 10/06/2023] Open
Abstract
Digestive autoimmune conditions are a growing challenge to global health. Risk factors associated with autoimmune digestive diseases are complex, including genetic variation, immunological dysfunction, and various environmental factors. To improve our understanding of the mechanisms behind digestive autoimmune conditions, including factors causing gastrointestinal manifestations and pathogenesis, BMC Immunology has launched a new Collection "The digestive system and autoimmunity".
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Affiliation(s)
- Lina Sun
- Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, 710061, Xi'an, Shaanxi, China
- Institute of Infection and Immunity, Xi'an Jiaotong University Health Science Center, Translational Medicine Institute, 710061, Xi'an, Shaanxi, China
- Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, 710061, Xi'an, Shaanxi, China
- Xi'an Key Laboratory of Immune Related Diseases, 710061, Xi'an, Shannxi, China
| | - Baojun Zhang
- Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, 710061, Xi'an, Shaanxi, China.
- Institute of Infection and Immunity, Xi'an Jiaotong University Health Science Center, Translational Medicine Institute, 710061, Xi'an, Shaanxi, China.
- Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, 710061, Xi'an, Shaanxi, China.
- Xi'an Key Laboratory of Immune Related Diseases, 710061, Xi'an, Shannxi, China.
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17
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Han H, Xing L, Chen BT, Liu Y, Zhou TJ, Wang Y, Zhang LF, Li L, Cho CS, Jiang HL. Progress on the pathological tissue microenvironment barrier-modulated nanomedicine. Adv Drug Deliv Rev 2023; 200:115051. [PMID: 37549848 DOI: 10.1016/j.addr.2023.115051] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2023] [Revised: 07/21/2023] [Accepted: 08/04/2023] [Indexed: 08/09/2023]
Abstract
Imbalance in the tissue microenvironment is the main obstacle to drug delivery and distribution in the human body. Before penetrating the pathological tissue microenvironment to the target site, therapeutic agents are usually accompanied by three consumption steps: the first step is tissue physical barriers for prevention of their penetration, the second step is inactivation of them by biological molecules, and the third step is a cytoprotective mechanism for preventing them from functioning on specific subcellular organelles. However, recent studies in drug-hindering mainly focus on normal physiological rather than pathological microenvironment, and the repair of damaged physiological barriers is also rarely discussed. Actually, both the modulation of pathological barriers and the repair of damaged physiological barriers are essential in the disease treatment and the homeostasis maintenance. In this review, we present an overview describing the latest advances in the generality of these pathological barriers and barrier-modulated nanomedicine. Overall, this review holds considerable significance for guiding the design of nanomedicine to increase drug efficacy in the future.
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Affiliation(s)
- Han Han
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China
| | - Lei Xing
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China; College of Pharmacy, Yanbian University, Yanji 133002, China
| | - Bi-Te Chen
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China
| | - Yang Liu
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China
| | - Tian-Jiao Zhou
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China
| | - Yi Wang
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China
| | - Ling-Feng Zhang
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China
| | - Ling Li
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China.
| | - Chong-Su Cho
- Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, 08826, Korea.
| | - Hu-Lin Jiang
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China; College of Pharmacy, Yanbian University, Yanji 133002, China.
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18
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Alashkar Alhamwe B, López JF, Zhernov Y, von Strandmann EP, Karaulov A, Kolahian S, Geßner R, Renz H. Impact of local human microbiota on the allergic diseases: Organ-organ interaction. Pediatr Allergy Immunol 2023; 34:e13976. [PMID: 37366206 DOI: 10.1111/pai.13976] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Revised: 05/22/2023] [Accepted: 06/02/2023] [Indexed: 06/28/2023]
Abstract
The homogeneous impact of local dysbiosis on the development of allergic diseases in the same organ has been thoroughly studied. However, much less is known about the heterogeneous influence of dysbiosis within one organ on allergic diseases in other organs. A comprehensive analysis of the current scientific literature revealed that most of the relevant publications focus on only three organs: gut, airways, and skin. Moreover, the interactions appear to be mainly unidirectional, that is, dysbiotic conditions of the gut being associated with allergic diseases of the airways and the skin. Similar to homogeneous interactions, early life appears to be not only a crucial period for the formation of the microbiota in one organ but also for the later development of allergic diseases in other organs. In particular, we were able to identify a number of specific bacterial and fungal species/genera in the intestine that were repeatedly associated in the literature with either increased or decreased allergic diseases of the skin, like atopic dermatitis, or the airways, like allergic rhinitis and asthma. The reported studies indicate that in addition to the composition of the microbiome, also the relative abundance of certain microbial species and the overall diversity are associated with allergic diseases of the corresponding organs. As anticipated for human association studies, the underlying mechanisms of the organ-organ crosstalk could not be clearly resolved yet. Thus, further work, in particular experimental animal studies are required to elucidate the mechanisms linking dysbiotic conditions of one organ to allergic diseases in other organs.
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Affiliation(s)
- Bilal Alashkar Alhamwe
- Institute of Laboratory Medicine, Member of the German Center for Lung Research (DZL), and the Universities of Giessen and Marburg Lung Center (UGMLC), Philipps University Marburg, Marburg, Germany
- Institute of Tumor Immunology, Clinic for Hematology, Oncology and Immunology, Center for Tumor Biology and Immunology, Philipps University Marburg, Marburg, Germany
- College of Pharmacy, International University for Science and Technology (IUST), Daraa, Syria
| | - Juan-Felipe López
- Institute for Immunological Research, University of Cartagena, Cartagena, Colombia
| | - Yury Zhernov
- Department of General Hygiene, F. Erismann Institute of Public Health, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
- Department of Chemistry, Lomonosov Moscow State University, Moscow, Russia
| | - Elke Pogge von Strandmann
- Institute of Tumor Immunology, Clinic for Hematology, Oncology and Immunology, Center for Tumor Biology and Immunology, Philipps University Marburg, Marburg, Germany
| | - Alexander Karaulov
- Laboratory of Immunopathology, Department of Clinical Immunology and Allergy, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Saeed Kolahian
- Institute of Laboratory Medicine, Member of the German Center for Lung Research (DZL), and the Universities of Giessen and Marburg Lung Center (UGMLC), Philipps University Marburg, Marburg, Germany
| | - Reinhard Geßner
- Institute of Laboratory Medicine, Member of the German Center for Lung Research (DZL), and the Universities of Giessen and Marburg Lung Center (UGMLC), Philipps University Marburg, Marburg, Germany
| | - Harald Renz
- Institute of Laboratory Medicine, Member of the German Center for Lung Research (DZL), and the Universities of Giessen and Marburg Lung Center (UGMLC), Philipps University Marburg, Marburg, Germany
- Laboratory of Immunopathology, Department of Clinical Immunology and Allergy, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
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Di Filippo P, Venanzi A, Ciarelli F, Panetti B, Di Pillo S, Chiarelli F, Attanasi M. Drug-Induced Enterocolitis Syndrome in Children. Int J Mol Sci 2023; 24:ijms24097880. [PMID: 37175584 PMCID: PMC10178722 DOI: 10.3390/ijms24097880] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 04/16/2023] [Accepted: 04/24/2023] [Indexed: 05/15/2023] Open
Abstract
Drug-Induced Enterocolitis Syndrome (DIES) is a drug-induced hypersensitivity reaction non-IgE mediated involving the gastrointestinal system that occurs 2 to 4 h after drug administration. Antibiotics, specifically amoxicillin or amoxicillin/clavulanate, represent the most frequent drugs involved. Symptoms include nausea, vomiting, abdominal pain, diarrhea, pallor, lethargy, and dehydration, which can be severe and result in hypovolemic shock. The main laboratory finding is neutrophilic leukocytosis. To the best of our knowledge, 12 cases of DIES (9 children-onset and 3 adult-onset cases) were described in the literature. DIES is a rare clinically well-described allergic disease; however, the pathogenetic mechanism is still unclear. It requires to be recognized early and correctly treated by physicians.
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Affiliation(s)
- Paola Di Filippo
- Department of Pediatrics, University of Chieti, 66100 Chieti, Italy
| | | | | | - Beatrice Panetti
- Department of Pediatrics, University of Chieti, 66100 Chieti, Italy
| | - Sabrina Di Pillo
- Department of Pediatrics, University of Chieti, 66100 Chieti, Italy
| | | | - Marina Attanasi
- Department of Pediatrics, University of Chieti, 66100 Chieti, Italy
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20
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Pan Z, Huang J, Hu T, Zhang Y, Zhang L, Zhang J, Cui D, Li L, Wang J, Wu Q. Protective Effects of Selenium Nanoparticles against Bisphenol A-Induced Toxicity in Porcine Intestinal Epithelial Cells. Int J Mol Sci 2023; 24:ijms24087242. [PMID: 37108405 PMCID: PMC10139072 DOI: 10.3390/ijms24087242] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 04/05/2023] [Accepted: 04/09/2023] [Indexed: 04/29/2023] Open
Abstract
Bisphenol A (BPA) is widely used to harden plastics and polycarbonates and causes serious toxic effects in multiple organs, including the intestines. Selenium, as an essential nutrient element for humans and animals, exhibits a predominant effect in various physiological processes. Selenium nanoparticles have attracted more and more attention due to their outstanding biological activity and biosafety. We prepared chitosan-coated selenium nanoparticles (SeNPs) and further compared the protective effects, and investigated the underlying mechanism of SeNPs and inorganic selenium (Na2SeO3) on BPA-induced toxicity in porcine intestinal epithelial cells (IPEC-J2). The particle size, zeta potential, and microstructure of SeNPs were detected by using a nano-selenium particle size meter and a transmission electron microscope. IPEC-J2 cells were exposed to BPA alone or simultaneously exposed to BPA and SeNPs or Na2SeO3. The CCK8 assay was performed to screen the optimal concentration of BPA exposure and the optimal concentration of SeNPs and Na2SeO3 treatment. The apoptosis rate was detected by flow cytometry. Real-time PCR and Western blot methods were used to analyze the mRNA and protein expression of factors related to tight junctions, apoptosis, inflammatory responses and endoplasmic reticulum stress. Increased death and morphological damage were observed after BPA exposure, and these increases were attenuated by SeNPs and Na2SeO3 treatment. BPA exposure disturbed the tight junction function involved with decreased expression of tight junction protein Zonula occludens 1 (ZO-1), occludin, and claudin-1 proteins. Proinflammatory response mediated by the transcription factor nuclear factor-k-gene binding (NF-κB), such as elevated levels of interleukin-1β(IL-1β), interleukin-6 (IL-6), interferon-γ (IFN-γ), interleukin-17 (IL-17), and tumor necrosis factor-α (TNF-α) expression was induced at 6 and 24 h after BPA exposure. BPA exposure also disturbed the oxidant/antioxidant status and led to oxidative stress. IPEC-J2 cell apoptosis was induced by BPA exposure, as indicated by increased BCL-2-associated X protein (Bax), caspase 3, caspase 8, and caspase 9 expression and decreased B-cell lymphoma-2 (Bcl-2) and Bcl-xl expression. BPA exposure activated the endoplasmic reticulum stress (ERS) mediated by the receptor protein kinase receptor-like endoplasmic reticulum kinase (PERK), Inositol requiring enzyme 1 (IRE1α), and activating transcription factor 6 (ATF6). We found that treatment with SeNPs and Na2SeO3 can alleviate the intestinal damage caused by BPA. SeNPs were superior to Na2SeO3 and counteracted BPA-induced tight junction function injury, proinflammatory response, oxidative stress, apoptosis, and ERS stress. Our findings suggest that SeNPs protect intestinal epithelial cells from BPA-induced damage, partly through inhibiting ER stress activation and subsequently attenuating proinflammatory responses and oxidative stress and suppressing apoptosis, thus enhancing the intestinal epithelial barrier function. Our data indicate that selenium nanoparticles may represent an effective and reliable tool for preventing BPA toxicity in animals and humans.
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Affiliation(s)
- Zaozao Pan
- Animal Science and Technology College, Beijing University of Agriculture, Beijing 100096, China
| | - Jiaqiang Huang
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China
| | - Ting Hu
- Animal Science and Technology College, Beijing University of Agriculture, Beijing 100096, China
| | - Yonghong Zhang
- Animal Science and Technology College, Beijing University of Agriculture, Beijing 100096, China
| | - Lingyu Zhang
- Animal Science and Technology College, Beijing University of Agriculture, Beijing 100096, China
| | - Jiaxi Zhang
- Animal Science and Technology College, Beijing University of Agriculture, Beijing 100096, China
| | - Defeng Cui
- Animal Science and Technology College, Beijing University of Agriculture, Beijing 100096, China
| | - Lu Li
- Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100097, China
| | - Jing Wang
- Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100097, China
| | - Qiong Wu
- Animal Science and Technology College, Beijing University of Agriculture, Beijing 100096, China
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21
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Chen X, de Vos P. Structure-function relationship and impact on the gut-immune barrier function of non-digestible carbohydrates and human milk oligosaccharides applicable for infant formula. Crit Rev Food Sci Nutr 2023; 64:8325-8345. [PMID: 37035930 DOI: 10.1080/10408398.2023.2199072] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/11/2023]
Abstract
Human milk oligosaccharides (hMOs) in mothers' milk play a crucial role in guiding the colonization of microbiota and gut-immune barrier development in infants. Non-digestible carbohydrates (NDCs) such as synthetic single hMOs, galacto-oligosaccharides (GOS), inulin-type fructans and pectin oligomers have been added to infant formula to substitute some hMOs' functions. HMOs and NDCs can modulate the gut-immune barrier, which is a multiple-layered functional unit consisting of microbiota, a mucus layer, gut epithelium, and the immune system. There is increasing evidence that the structures of the complex polysaccharides may influence their efficacy in modulating the gut-immune barrier. This review focuses on the role of different structures of individual hMOs and commonly applied NDCs in infant formulas in (i) direct regulation of the gut-immune barrier in a microbiota-independent manner and in (ii) modulation of microbiota composition and microbial metabolites of these polysaccharides in a microbiota-dependent manner. Both have been shown to be essential for guiding the development of an adequate immune barrier, but the effects are very dependent on the structural features of hMO or NDC. This knowledge might lead to tailored infant formulas for specific target groups.
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Affiliation(s)
- Xiaochen Chen
- Immunoendocrinology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Paul de Vos
- Immunoendocrinology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
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Chen J, Xia Y, Hu Y, Zhao X, You J, Zou T. A blend of formic acid, benzoic acid, and tributyrin alleviates ETEC K88-induced intestinal barrier dysfunction by regulating intestinal inflammation and gut microbiota in a murine model. Int Immunopharmacol 2023; 114:109538. [PMID: 36502593 DOI: 10.1016/j.intimp.2022.109538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 11/22/2022] [Accepted: 11/29/2022] [Indexed: 12/13/2022]
Abstract
This study aimed to investigate the effects of an organic acid (OA) blend on intestinal barrier function, intestinal inflammation, and gut microbiota in mice challenged with enterotoxigenic Escherichia coli K88 (ETEC K88). Ninety female Kunming mice (7 weeks old) were randomly allotted to five treatments with six replicates per treatment and three mice per replicate. The five treatments were composed of the non-ETEC K88 challenge group and ETEC K88 challenge + OA blend groups (0, 0.6 %, 1.2 %, and 2.4 % OA blend). The OA blend consisted of 47.5 % formic acid, 47.5 % benzoic acid, and 5 % tributyrin. The feeding trial lasted for 15 days, and mice were intraperitoneally injected with PBS or ETEC K88 solution on day 15. At 24 h post-challenge, one mouse per replicate was selected for sample collection. The results showed that a dosage of 0.6 % OA blend alleviated the ETEC K88-induced intestinal barrier dysfunction, as indicated by the elevated villus height and the ratio of villus height to crypt depth of jejunum, and the reduced serum diamine oxidase (DAO) and D-lactate levels, as well as the up-regulated mRNA levels of ZO-1, Claudin-1, and Occludin in jejunum mucosa of mice. Furthermore, dietary addition with 0.6 % OA blend decreased ETEC K88-induced inflammation response, as suggested by the decreased TNF-α and IL-6 levels, and the increased IgA level in the serum, as well as the down-regulated mRNA level of TNF-α, IL-6, IL-1β, TLR-4, MyD88, and MCP-1 in jejunum mucosa of mice. Regarding gut microbiota, the beta-diversity analysis revealed a remarkable clustering between the 0.6 % OA blend group and the ETEC K88 challenge group. Supplementation of 0.6 % OA blend decreased the relative abundance of Firmicutes, and increased the relative abundance of Bacteroidota, Desulfobacterota, and Verrucomicrobiota of colonic digesta in mice. Also, the butyric acid content in the colonic digesta of mice was increased by dietary 0.6 % OA blend supplementation. Collectively, a dosage of 0.6 % OA blend could alleviate the ETEC K88-induced intestinal barrier dysfunction by regulating intestinal inflammation and gut microbiota of mice.
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Affiliation(s)
- Jun Chen
- Jiangxi Province Key Laboratory of Animal Nutrition, Jiangxi Agricultural University, Nanchang 330045, China; Jiangxi Province Key Innovation Center of Integration in Production and Education for High-quality and Safe Livestock and Poultry, Jiangxi Agricultural University, Nanchang 330045, China
| | - Yingying Xia
- Jiangxi Province Key Laboratory of Animal Nutrition, Jiangxi Agricultural University, Nanchang 330045, China; Jiangxi Province Key Innovation Center of Integration in Production and Education for High-quality and Safe Livestock and Poultry, Jiangxi Agricultural University, Nanchang 330045, China
| | - Youjun Hu
- Guangdong Nuacid Biotech Co., Ltd, Qingyuan 511500, China
| | - Xiaolan Zhao
- Guangdong Nuacid Biotech Co., Ltd, Qingyuan 511500, China
| | - Jinming You
- Jiangxi Province Key Laboratory of Animal Nutrition, Jiangxi Agricultural University, Nanchang 330045, China; Jiangxi Province Key Innovation Center of Integration in Production and Education for High-quality and Safe Livestock and Poultry, Jiangxi Agricultural University, Nanchang 330045, China
| | - Tiande Zou
- Jiangxi Province Key Laboratory of Animal Nutrition, Jiangxi Agricultural University, Nanchang 330045, China; Jiangxi Province Key Innovation Center of Integration in Production and Education for High-quality and Safe Livestock and Poultry, Jiangxi Agricultural University, Nanchang 330045, China.
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23
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Chen YQ, Liu JL. Advances in research of microbiome regulation as a therapy for liver failure. Shijie Huaren Xiaohua Zazhi 2022; 30:971-977. [DOI: 10.11569/wcjd.v30.i22.971] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
Abstract
The intestinal flora of the human body is complex and diverse, and the structure and composition of the intestinal micro-ecosystem formed by the intestinal flora are complicated. Studies have shown that the imbalance of the intestinal micro-ecosystem is closely related to the occurrence and development of liver failure, and the degree of intestinal microecological imbalance is significantly correlated with the severity of liver failure. Therefore, the role of intestinal microbiome regulation in the treatment of liver failure and the improvement of prognosis has increasingly attracting the attention of scholars. However, due to the complexity of the composition and structure of the intestinal flora and its mechanism of action involved in the development of liver failure, the application of intestinal microbiome regulation in the clinic is limited to a certain extent. In this paper, we review the research progress of microbiome regulation as a therapy for liver failure.
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Affiliation(s)
- Yue-Qiao Chen
- Department of Hepatology, The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine, Nanning 530200, Guangxi Zhuang Autonomous Region, China
| | - Jia-Ling Liu
- Department of Hepatology, The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine, Nanning 530200, Guangxi Zhuang Autonomous Region, China
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24
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Russell MW, Mestecky J. Mucosal immunity: The missing link in comprehending SARS-CoV-2 infection and transmission. Front Immunol 2022; 13:957107. [PMID: 36059541 PMCID: PMC9428579 DOI: 10.3389/fimmu.2022.957107] [Citation(s) in RCA: 60] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Accepted: 07/27/2022] [Indexed: 12/21/2022] Open
Abstract
SARS-CoV-2 is primarily an airborne infection of the upper respiratory tract, which on reaching the lungs causes the severe acute respiratory disease, COVID-19. Its first contact with the immune system, likely through the nasal passages and Waldeyer's ring of tonsils and adenoids, induces mucosal immune responses revealed by the production of secretory IgA (SIgA) antibodies in saliva, nasal fluid, tears, and other secretions within 4 days of infection. Evidence is accumulating that these responses might limit the virus to the upper respiratory tract resulting in asymptomatic infection or only mild disease. The injectable systemic vaccines that have been successfully developed to prevent serious disease and its consequences do not induce antibodies in mucosal secretions of naïve subjects, but they may recall SIgA antibody responses in secretions of previously infected subjects, thereby helping to explain enhanced resistance to repeated (breakthrough) infection. While many intranasally administered COVID vaccines have been found to induce potentially protective immune responses in experimental animals such as mice, few have demonstrated similar success in humans. Intranasal vaccines should have advantage over injectable vaccines in inducing SIgA antibodies in upper respiratory and oral secretions that would not only prevent initial acquisition of the virus, but also suppress community spread via aerosols and droplets generated from these secretions.
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Affiliation(s)
- Michael W. Russell
- Department of Microbiology and Immunology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, United States
| | - Jiri Mestecky
- Department of Microbiology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
- Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czechia
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25
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Tang S, Xie J, Fang W, Wen X, Yin C, Meng Q, Zhong R, Chen L, Zhang H. Chronic heat stress induces the disorder of gut transport and immune function associated with endoplasmic reticulum stress in growing pigs. ANIMAL NUTRITION 2022; 11:228-241. [PMID: 36263409 PMCID: PMC9556788 DOI: 10.1016/j.aninu.2022.08.008] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Revised: 08/06/2022] [Accepted: 08/11/2022] [Indexed: 02/07/2023]
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Silent Reactivation of Varicella Zoster Virus in Pregnancy: Implications for Maintenance of Immunity to Varicella. Viruses 2022; 14:v14071438. [PMID: 35891418 PMCID: PMC9318610 DOI: 10.3390/v14071438] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 06/01/2022] [Accepted: 06/22/2022] [Indexed: 02/01/2023] Open
Abstract
We encountered two cases of varicella occurring in newborn infants. Because the time between birth and the onset of the illness was much shorter than the varicella incubation period, the cases suggested that the infection was maternally acquired, despite the fact that neither mother experienced clinical zoster. Thus, we tested the hypothesis that VZV frequently reactivates asymptomatically in late pregnancy. The appearance of DNA-encoding VZV genes in saliva was used as an indicator of reactivation. Saliva was collected from 5 women in the first and 14 women in the third trimesters of pregnancy and analyzed at two different sites, at one using nested PCR and at the other using quantitative PCR (qPCR). No VZV DNA was detected at either site in the saliva of women during the first trimester; however, VZV DNA was detected in the majority of samples of saliva (11/12 examined by nested PCR; 7/10 examined by qPCR) during the third trimester. These observations suggest that VZV reactivation occurs commonly during the third trimester of pregnancy. It is possible that this phenomenon, which remains in most patients below the clinical threshold, provides an endogenous boost to immunity and, thus, is beneficial.
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Jia Z, Pan X, Zhi W, Chen H, Bai B, Ma C, Ma D. Probiotics Surface-Delivering Fiber2 Protein of Fowl Adenovirus 4 Stimulate Protective Immunity Against Hepatitis-Hydropericardium Syndrome in Chickens. Front Immunol 2022; 13:919100. [PMID: 35837390 PMCID: PMC9273852 DOI: 10.3389/fimmu.2022.919100] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 05/27/2022] [Indexed: 12/19/2022] Open
Abstract
Background and ObjectivesHepatitis-hydropericardium syndrome (HHS) caused by Fowl adenoviruses serotype 4 (FAdV-4) leads to severe economic losses to the poultry industry. Although various vaccines are available, vaccines that effectively stimulate intestinal mucosal immunity are still deficient. In the present study, novel probiotics that surface-deliver Fiber2 protein, the major virulence determiner and efficient immunogen for FAdV-4, were explored to prevent this fecal–oral-transmitted virus, and the induced protective immunity was evaluated after oral immunization.MethodsThe probiotic Enterococcus faecalis strain MDXEF-1 and Lactococcus lactis NZ9000 were used as host strains to deliver surface-anchoring Fiber2 protein of FAdV-4. Then the constructed live recombinant bacteria were orally vaccinated thrice with chickens at intervals of 2 weeks. Following each immunization, immunoglobulin G (IgG) in sera, secretory immunoglobulin A (sIgA) in jejunum lavage, immune-related cytokines, and T-cell proliferation were detected. Following challenge with the highly virulent FAdV-4, the protective effects of the probiotics surface-delivering Fiber2 protein were evaluated by verifying inflammatory factors, viral load, liver function, and survival rate.ResultsThe results demonstrated that probiotics surface-delivering Fiber2 protein stimulated humoral and intestinal mucosal immune responses in chickens, shown by high levels of sIgA and IgG antibodies, substantial rise in mRNA levels of cytokines, increased proliferative ability of T cells in peripheral blood, improved liver function, and reduced viral load in liver. Accordingly, adequate protection against homologous challenges and a significant increase in the overall survival rate were observed. Notably, chickens orally immunized with E. faecalis/DCpep-Fiber2-CWA were completely protected from the FAdV-4 challenge, which is better than L. lactis/DCpep-Fiber2-CWA.ConclusionThe recombinant probiotics surface-expressing Fiber2 protein could evoke remarkable humoral and cellular immune responses, relieve injury, and functionally damage target organs. The current study indicates a promising method used for preventing FAdV-4 infection in chickens.
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Affiliation(s)
- Zhipeng Jia
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, China
| | - Xinghui Pan
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, China
| | - Wenjing Zhi
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, China
| | - Hang Chen
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, China
| | - Bingrong Bai
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, China
| | - Chunli Ma
- College of Food Science, Northeast Agricultural University, Harbin, China
- *Correspondence: Chunli Ma, ; Dexing Ma,
| | - Dexing Ma
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, China
- Heilongjiang Key Laboratory for Experimental Animals and Comparative Medicine, Northeast Agricultural University, Harbin, China
- *Correspondence: Chunli Ma, ; Dexing Ma,
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28
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Aldossary AM, Ekweremadu CS, Offe IM, Alfassam HA, Han S, Onyali VC, Ozoude CH, Ayeni EA, Nwagwu CS, Halwani AA, Almozain NH, Tawfik EA. A guide to oral vaccination: Highlighting electrospraying as a promising manufacturing technique toward a successful oral vaccine development. Saudi Pharm J 2022; 30:655-668. [PMID: 35812139 PMCID: PMC9257926 DOI: 10.1016/j.jsps.2022.03.010] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Accepted: 03/10/2022] [Indexed: 11/26/2022] Open
Abstract
Most vaccines approved by regulatory bodies are administered via intramuscular or subcutaneous injections and have shortcomings, such as the risk of needle-associated blood infections, pain and swelling at the injection site. Orally administered vaccines are of interest, as they elicit both systemic and mucosal immunities, in which mucosal immunity would neutralize the mucosa invading pathogen before the onset of an infection. Hence, oral vaccination can eliminate the injection associated adverse effects and enhance the person's compliance. Conventional approaches to manufacturing oral vaccines, such as coacervation, spray drying, and membrane emulsification, tend to alter the structural proteins in vaccines that result from high temperature, organic and toxic solvents during production. Electrohydrodynamic processes, specifically electrospraying, could solve these challenges, as it also modulates antigen release and has a high loading efficiency. This review will highlight the mucosal immunity and biological basis of the gastrointestinal immune system, different oral vaccine delivery approaches, and the application of electrospraying in vaccines development.
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Key Words
- APCs, Antigen-presenting cells
- BALT, Bronchus-associated lymphoid tissue
- DCs, Dendritic cells
- Electrospraying
- FAE, Follicle-associated epithelium
- GALT, Gut-associated lymphoid tissue
- GIT, Gastro-intestinal tract
- HIV, Human immune virus
- IL, Interleukin
- Ig, Immunoglobulin
- Infectious diseases
- MALT, Mucosa-associated lymphoid tissue
- MLN, Mesenteric lymph nodes
- MNPs, Micro/Nanoparticles
- Mucosal immunity
- Mucosal pathogen
- NALT, Nasopharynx-associated lymphoid tissue
- Oral vaccines
- PLGA, Polylactide-co-glycolide acid
- PP, Peyer’s patches
- Secretory, (SIgA1 and SIgA2)
- TGF-β, Transforming growth factor-β
- TLRs, Toll-like receptors
- WHO, World Health Organization
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Affiliation(s)
- Ahmad M. Aldossary
- National Center of Biotechnology, Life Science and Environment Research Institute, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi Arabia
| | - Chinedu S.M. Ekweremadu
- Department of Pharmaceutics and Pharmaceutical Technology, Enugu State University of Science and Technology, Agbani, Enugu State, Nigeria
| | - Ifunanya M. Offe
- Department of Biological Sciences, Faculty of Natural Sciences and Environmental Studies, Godfrey Okoye University, Enugu, Nigeria
| | - Haya A. Alfassam
- KACST-BWH Centre of Excellence for Biomedicine, Joint Centers of Excellence Program, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi Arabia
| | - Sooyeon Han
- UCL Medical School, University College London, London, United Kingdom
| | - Vivian C. Onyali
- Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, United State
| | - Chukwuebuka H. Ozoude
- Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, University of Lagos, College of Medicine Campus, Surulere, Lagos, Nigeria
| | - Emmanuel A. Ayeni
- The Research Unit, New Being Foundation, Abuja, Nigeria
- Department of Pharmacognosy and Drug Development, Faculty of Pharmaceutical Sciences, Ahmadu Bello University, Zaria, Nigeria
| | - Chinekwu S. Nwagwu
- Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Nigeria Nsukka, Nigeria
| | - Abdulrahman A. Halwani
- Pharmaceutics Department, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
- Regenerative Medicine Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Nada H. Almozain
- Pharmaceutical Services Department, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Essam A. Tawfik
- National Center of Biotechnology, Life Science and Environment Research Institute, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi Arabia
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29
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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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30
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Bergmeier LA, Dutzan N, Smith PC, Kraan H. Editorial: Immunology of the Oral Mucosa. Front Immunol 2022; 13:877209. [PMID: 35401502 PMCID: PMC8992007 DOI: 10.3389/fimmu.2022.877209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Accepted: 03/04/2022] [Indexed: 12/03/2022] Open
Affiliation(s)
- Lesley Ann Bergmeier
- Centre for Immunobiology and Regenerative Medicine, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
| | - Nicolas Dutzan
- Department of Conservative Dentistry, Faculty of Dentistry, University of Chile, Santiago, Chile
| | - Patricio C Smith
- School of Dentistry, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Heleen Kraan
- Institute for Translational Vaccinology, Intravacc, Bilthoven, Netherlands
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31
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Presence of Natural Killer B Cells in Simian Immunodeficiency Virus-Infected Colon That Have Properties and Functions Similar to Those of Natural Killer Cells and B Cells but Are a Distinct Cell Population. J Virol 2022; 96:e0023522. [PMID: 35311549 PMCID: PMC9006943 DOI: 10.1128/jvi.00235-22] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
There is low-level but significant mucosal inflammation in the gastrointestinal tract secondary to human immunodeficiency virus (HIV) infection that has long-term consequences for the infected host. This inflammation most likely originates from the immune response that appears as a consequence of HIV. Here, we show in an animal model of HIV that the chronically SIV-infected gut contains cytotoxic natural killer B cells that produce inflammatory cytokines and proliferate during infection.
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32
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He L, Wang C, Simujide H, Aricha H, Zhang J, Liu B, Zhang C, Cui Y, Aorigele C. Effect of Early Pathogenic Escherichia coli Infection on the Intestinal Barrier and Immune Function in Newborn Calves. Front Cell Infect Microbiol 2022; 12:818276. [PMID: 35265533 PMCID: PMC8900010 DOI: 10.3389/fcimb.2022.818276] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Accepted: 02/04/2022] [Indexed: 11/30/2022] Open
Abstract
We studied the effect of early pathogenic Escherichia coli infection on newborn calves’ intestinal barrier and immune function. A total of 64 newborn Holstein male calves (40–43 kg) were divided into two groups: normal (NG) and test (TG), each with 32 heads. At the beginning of the experiment, the TG calves were orally administered pathogenic E. coli O1 (2.5 × 1011 CFU/mL, 100 mL) to establish a calf diarrhea model. In contrast, the NG calves were given the same amount of normal saline. During the 30 d trial period, the feeding and management of the two groups remained constant. Enzyme-linked immunosorbent assay, quantification PCR, and high-throughput 16S rRNA sequencing technology were used to detect indicators related to the intestinal barrier and immune function in the calf serum and tissues. Pathogenic E. coli O1 had a significant effect on calf diarrhea in the TG; it increased the bovine diamine oxidase (P < 0.05) and endotoxin levels in the serum and decreased (P < 0.05) the intestinal trefoil factor (P < 0.05), Occludin, Claudin-1, and Zonula Occludens 1 (ZO-1) levels in the colon tissue, as well as downregulated the mRNA expression of Occludin, Claudin-1,and ZO-1 in the colon mucosa, leading to increased intestinal permeability and impaired intestinal barrier function. Additionally, pathogenic E. coli had a significant impact on the diversity of colonic microbial flora, increasing the relative abundance of Proteobacteria at the phylum level and decreasing the levels of Firmicutes and Bacteroides. At the genus level, the relative abundance of Escherichia and Shigella in the TG increased significantly (P < 0.05), whereas that of Bacteroides, Butyricicoccus, Rikenellaceae_RC9_gut_group, Blautia, and Lactobacillus was significantly decreased (P < 0.05). In addition, the level of IL-6 in the serum of the TG calves was significantly increased (P < 0.05), whereas the IL-4 and IL-10 levels were significantly decreased (P < 0.05), compared to those in the NG calves. Thus, pathogenic E. coli induced diarrhea early in life disrupts intestinal barrier and impairs immune function in calves.
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Affiliation(s)
- Lina He
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot, China
| | - Chunjie Wang
- College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot, China
| | - Huasai Simujide
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot, China
| | - Han Aricha
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot, China
| | - Jian Zhang
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot, China
| | - Bo Liu
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot, China
| | - Chen Zhang
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot, China
| | - Yinxue Cui
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot, China
| | - Chen Aorigele
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot, China
- *Correspondence: Chen Aorigele,
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Nagasawa Y, Misaki T, Ito S, Naka S, Wato K, Nomura R, Matsumoto-Nakano M, Nakano K. Title IgA Nephropathy and Oral Bacterial Species Related to Dental Caries and Periodontitis. Int J Mol Sci 2022; 23:725. [PMID: 35054910 PMCID: PMC8775524 DOI: 10.3390/ijms23020725] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 01/04/2022] [Accepted: 01/07/2022] [Indexed: 12/23/2022] Open
Abstract
A relationship between IgA nephropathy (IgAN) and bacterial infection has been suspected. As IgAN is a chronic disease, bacteria that could cause chronic infection in oral areas might be pathogenetic bacteria candidates. Oral bacterial species related to dental caries and periodontitis should be candidates because these bacteria are well known to be pathogenic in chronic dental disease. Recently, several reports have indicated that collagen-binding protein (cnm)-(+) Streptococcs mutans is relate to the incidence of IgAN and the progression of IgAN. Among periodontal bacteria, Treponema denticola, Porphyromonas gingivalis and Campylobacte rectus were found to be related to the incidence of IgAN. These bacteria can cause IgAN-like histological findings in animal models. While the connection between oral bacterial infection, such as infection with S. mutans and periodontal bacteria, and the incidence of IgAN remains unclear, these bacterial infections might cause aberrantly glycosylated IgA1 in nasopharynx-associated lymphoid tissue, which has been reported to cause IgA deposition in mesangial areas in glomeruli, probably through the alteration of microRNAs related to the expression of glycosylation enzymes. The roles of other factors related to the incidence and progression of IgA, such as genes and cigarette smoking, can also be explained from the perspective of the relationship between these factors and oral bacteria. This review summarizes the relationship between IgAN and oral bacteria, such as cnm-(+) S. mutans and periodontal bacteria.
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Affiliation(s)
- Yasuyuki Nagasawa
- Department of General Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, Hyogo, Japan
| | - Taro Misaki
- Division of Nephrology, Seirei Hamamatsu General Hospital, Hamamatsu 430-8558, Shizuoka, Japan;
- Department of Nursing, Faculty of Nursing, Seirei Christopher University, Hamamatsu 433-8558, Shizuoka, Japan
| | - Seigo Ito
- Department of Internal Medicine, Japan Self-Defense Gifu Hospital, Kakamigahara 502-0817, Gifu, Japan;
| | - Shuhei Naka
- Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8525, Okayama, Japan; (S.N.); (M.M.-N.)
| | - Kaoruko Wato
- Department of Pediatric Dentistry, Division of Oral Infection and Disease Control, Osaka University Graduate School of Dentistry, Suita 565-0871, Osaka, Japan; (K.W.); (R.N.); (K.N.)
| | - Ryota Nomura
- Department of Pediatric Dentistry, Division of Oral Infection and Disease Control, Osaka University Graduate School of Dentistry, Suita 565-0871, Osaka, Japan; (K.W.); (R.N.); (K.N.)
| | - Michiyo Matsumoto-Nakano
- Department of Pediatric Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8525, Okayama, Japan; (S.N.); (M.M.-N.)
| | - Kazuhiko Nakano
- Department of Pediatric Dentistry, Division of Oral Infection and Disease Control, Osaka University Graduate School of Dentistry, Suita 565-0871, Osaka, Japan; (K.W.); (R.N.); (K.N.)
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34
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Lee Y, Kamada N, Moon JJ. Oral nanomedicine for modulating immunity, intestinal barrier functions, and gut microbiome. Adv Drug Deliv Rev 2021; 179:114021. [PMID: 34710529 PMCID: PMC8665886 DOI: 10.1016/j.addr.2021.114021] [Citation(s) in RCA: 81] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Revised: 10/17/2021] [Accepted: 10/20/2021] [Indexed: 12/12/2022]
Abstract
The gastrointestinal tract (GIT) affects not only local diseases in the GIT but also various systemic diseases. Factors that can affect the health and disease of both GIT and the human body include 1) the mucosal immune system composed of the gut-associated lymphoid tissues and the lamina propria, 2) the intestinal barrier composed of mucus and intestinal epithelium, and 3) the gut microbiota. Selective delivery of drugs, including antigens, immune-modulators, intestinal barrier enhancers, and gut-microbiome manipulators, has shown promising results for oral vaccines, immune tolerance, treatment of inflammatory bowel diseases, and other systemic diseases, including cancer. However, physicochemical and biological barriers of the GIT present significant challenges for successful translation. With the advances of novel nanomaterials, oral nanomedicine has emerged as an attractive option to not only overcome these barriers but also to selectively deliver drugs to the target sites in GIT. In this review, we discuss the GIT factors and physicochemical and biological barriers in the GIT. Furthermore, we present the recent progress of oral nanomedicine for oral vaccines, immune tolerance, and anti-inflammation therapies. We also discuss recent advances in oral nanomedicine designed to fortify the intestinal barrier functions and modulate the gut microbiota and microbial metabolites. Finally, we opine about the future directions of oral nano-immunotherapy.
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Affiliation(s)
- Yonghyun Lee
- Department of Pharmacy, College of Pharmacy, Ewha Womans University, Seoul 03760, South Korea; Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, South Korea.
| | - Nobuhiko Kamada
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan, 1150 W. Medical Center Drive, Ann Arbor, MI 48109, USA
| | - James J Moon
- Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109 USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109 USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109 USA.
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35
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Morawska I, Kurkowska S, Bębnowska D, Hrynkiewicz R, Becht R, Michalski A, Piwowarska-Bilska H, Birkenfeld B, Załuska-Ogryzek K, Grywalska E, Roliński J, Niedźwiedzka-Rystwej P. The Epidemiology and Clinical Presentations of Atopic Diseases in Selective IgA Deficiency. J Clin Med 2021; 10:3809. [PMID: 34501259 PMCID: PMC8432128 DOI: 10.3390/jcm10173809] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Revised: 08/22/2021] [Accepted: 08/23/2021] [Indexed: 12/12/2022] Open
Abstract
Selective IgA deficiency (sIgAD) is the most common primary immunodeficiency disease (PID), with an estimated occurrence from about 1:3000 to even 1:150, depending on population. sIgAD is diagnosed in adults and children after the 4th year of age, with immunoglobulin A level below 0.07 g/L and normal levels of IgM and IgG. Usually, the disease remains undiagnosed throughout the patient's life, due to its frequent asymptomatic course. If symptomatic, sIgAD is connected to more frequent viral and bacterial infections of upper respiratory, urinary, and gastrointestinal tracts, as well as autoimmune and allergic diseases. Interestingly, it may also be associated with other PIDs, such as IgG subclasses deficiency or specific antibodies deficiency. Rarely sIgAD can evolve to common variable immunodeficiency disease (CVID). It should also be remembered that IgA deficiency may occur in the course of other conditions or result from their treatment. It is hypothesized that allergic diseases (e.g., eczema, rhinitis, asthma) are more common in patients diagnosed with this particular PID. Selective IgA deficiency, although usually mildly symptomatic, can be difficult for clinicians. The aim of the study is to summarize the connection between selective IgA deficiency and atopic diseases.
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Affiliation(s)
- Izabela Morawska
- Department of Clinical Immunology and Immunotherapy, Medical University of Lublin, Chodźki 4a St., 20-093 Lublin, Poland; (I.M.); (A.M.); (E.G.); (J.R.)
| | - Sara Kurkowska
- Department of Nuclear Medicine, Pomeranian Medical University, Unii Lubelskiej 1 St., 71-252 Szczecin, Poland; (S.K.); (H.P.-B.); (B.B.)
| | - Dominika Bębnowska
- Institute of Biology, University of Szczecin, Felczaka 3c St., 71-412 Szczecin, Poland; (D.B.); (R.H.)
| | - Rafał Hrynkiewicz
- Institute of Biology, University of Szczecin, Felczaka 3c St., 71-412 Szczecin, Poland; (D.B.); (R.H.)
| | - Rafał Becht
- Clinical Department of Oncology, Chemotherapy and Cancer Immunotherapy, Pomeranian Medical University of Szczecin, Unii Lubelskiej 1, 71-252 Szczecin, Poland;
| | - Adam Michalski
- Department of Clinical Immunology and Immunotherapy, Medical University of Lublin, Chodźki 4a St., 20-093 Lublin, Poland; (I.M.); (A.M.); (E.G.); (J.R.)
| | - Hanna Piwowarska-Bilska
- Department of Nuclear Medicine, Pomeranian Medical University, Unii Lubelskiej 1 St., 71-252 Szczecin, Poland; (S.K.); (H.P.-B.); (B.B.)
| | - Bożena Birkenfeld
- Department of Nuclear Medicine, Pomeranian Medical University, Unii Lubelskiej 1 St., 71-252 Szczecin, Poland; (S.K.); (H.P.-B.); (B.B.)
| | - Katarzyna Załuska-Ogryzek
- Department of Pathophysiology, Medical University of Lublin, Jaczewskiego 8b St., 20-090 Lublin, Poland;
| | - Ewelina Grywalska
- Department of Clinical Immunology and Immunotherapy, Medical University of Lublin, Chodźki 4a St., 20-093 Lublin, Poland; (I.M.); (A.M.); (E.G.); (J.R.)
| | - Jacek Roliński
- Department of Clinical Immunology and Immunotherapy, Medical University of Lublin, Chodźki 4a St., 20-093 Lublin, Poland; (I.M.); (A.M.); (E.G.); (J.R.)
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36
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Brea D, Poon C, Benakis C, Lubitz G, Murphy M, Iadecola C, Anrather J. Stroke affects intestinal immune cell trafficking to the central nervous system. Brain Behav Immun 2021; 96:295-302. [PMID: 33989742 PMCID: PMC8672365 DOI: 10.1016/j.bbi.2021.05.008] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Revised: 05/04/2021] [Accepted: 05/09/2021] [Indexed: 12/12/2022] Open
Abstract
Stroke is an acute neurological disease with a strong inflammatory component that can be regulated by the intestinal microbiota and intestinal immune cells. Although stroke has been shown to alter immune cell populations in the gut, the dynamics of cell trafficking have not been elucidated. To study the trafficking of gut-derived immune cells after stroke, we used mice expressing the photoconvertible protein Kikume Green-Red, which turns form green to red when exposed to violet light. Mice underwent laparotomy and the small intestine was exposed to violet laser light. Immune cells were isolated from the small intestine immediately after photoconversion and 2 days later. Percentage of immune cells (CD45+KikR+) that expressed the red variant of the protein (KikR) was higher immediately after photoconversion than 2 days later, indicating cell egress from the small intestine. To investigate whether intestinal immune cells traffic to the periphery and/or the central nervous system (CNS) after stroke, we analyzed KikR+ immune cells (2 days after photoconversion) in peripheral lymphoid organs, meninges and brain, 3 and 14 days after transient occlusion of the middle cerebral artery (tMCAo) or sham-surgery. Although migration was observed in naïve and sham animals, stroke induced a higher mobilization of gut KikR+ immune cells, especially at 3 days after stroke, to all the organs analyzed. Notably, we detected a significant migration of CD45hi immune cells from the gut to the brain and meninges at 3 days after stroke. Comparison of cell trafficking between organs revealed a significant preference of intestinal CD11c+ cells to migrate from the small intestine to brain and meninges after stroke. We conclude that stroke increases immune cell trafficking from the small intestine to peripheral lymphoid organs and the CNS where they might contribute to post-stroke inflammation.
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Affiliation(s)
- David Brea
- Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, NY, United States.
| | | | | | | | | | | | - Josef Anrather
- Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, NY, United States.
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37
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Bemark M, Angeletti D. Know your enemy or find your friend?-Induction of IgA at mucosal surfaces. Immunol Rev 2021; 303:83-102. [PMID: 34331314 PMCID: PMC7612940 DOI: 10.1111/imr.13014] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Accepted: 06/28/2021] [Indexed: 12/15/2022]
Abstract
Most antibodies produced in the body are of the IgA class. The dominant cell population producing them are plasma cells within the lamina propria of the gastrointestinal tract, but many IgA-producing cells are also found in the airways, within mammary tissues, the urogenital tract and inside the bone marrow. Most IgA antibodies are transported into the lumen by epithelial cells as part of the mucosal secretions, but they are also present in serum and other body fluids. A large part of the commensal microbiota in the gut is covered with IgA antibodies, and it has been demonstrated that this plays a role in maintaining a healthy balance between the host and the bacteria. However, IgA antibodies also play important roles in neutralizing pathogens in the gastrointestinal tract and the upper airways. The distinction between the two roles of IgA - protective and balance-maintaining - not only has implications on function but also on how the production is regulated. Here, we discuss these issues with a special focus on gut and airways.
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Affiliation(s)
- Mats Bemark
- Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Department of Clinical Immunology and Transfusion Medicine, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Davide Angeletti
- Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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38
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Suárez LJ, Arboleda S, Angelov N, Arce RM. Oral Versus Gastrointestinal Mucosal Immune Niches in Homeostasis and Allostasis. Front Immunol 2021; 12:705206. [PMID: 34290715 PMCID: PMC8287884 DOI: 10.3389/fimmu.2021.705206] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Accepted: 06/22/2021] [Indexed: 12/15/2022] Open
Abstract
Different body systems (epidermis, respiratory tract, cornea, oral cavity, and gastrointestinal tract) are in continuous direct contact with innocuous and/or potentially harmful external agents, exhibiting dynamic and highly selective interaction throughout the epithelia, which function as both a physical and chemical protective barrier. Resident immune cells in the epithelia are constantly challenged and must distinguish among antigens that must be either tolerated or those to which a response must be mounted for. When such a decision begins to take place in lymphoid foci and/or mucosa-associated lymphoid tissues, the epithelia network of immune surveillance actively dominates both oral and gastrointestinal compartments, which are thought to operate in the same immune continuum. However, anatomical variations clearly differentiate immune processes in both the mouth and gastrointestinal tract that demonstrate a wide array of independent immune responses. From single vs. multiple epithelia cell layers, widespread cell-to-cell junction types, microbial-associated recognition receptors, dendritic cell function as well as related signaling, the objective of this review is to specifically contrast the current knowledge of oral versus gut immune niches in the context of epithelia/lymphoid foci/MALT local immunity and systemic output. Related differences in 1) anatomy 2) cell-to-cell communication 3) antigen capture/processing/presentation 4) signaling in regulatory vs. proinflammatory responses and 5) systemic output consequences and its relations to disease pathogenesis are discussed.
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Affiliation(s)
- Lina J Suárez
- Departamento de Ciencias Básicas y Medicina Oral, Universidad Nacional de Colombia, Bogotá, Colombia
| | - Silie Arboleda
- Department of Periodontics and Dental Hygiene, School of Dentistry, University of Texas Health Science Center at Houston, Houston, TX, United States
| | - Nikola Angelov
- Department of Periodontics and Dental Hygiene, School of Dentistry, University of Texas Health Science Center at Houston, Houston, TX, United States
| | - Roger M Arce
- Department of Periodontics and Dental Hygiene, School of Dentistry, University of Texas Health Science Center at Houston, Houston, TX, United States
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39
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Keller HR, Ligons DL, Li C, Hwang S, Luckey MA, Prakhar P, Liman N, Crossman A, Lazarevic V, Park YK, Park JH. The molecular basis and cellular effects of distinct CD103 expression on CD4 and CD8 T cells. Cell Mol Life Sci 2021; 78:5789-5805. [PMID: 34129058 DOI: 10.1007/s00018-021-03877-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Revised: 05/24/2021] [Accepted: 06/08/2021] [Indexed: 10/21/2022]
Abstract
Integrin CD103 mediates the adhesion and tissue retention of T cells by binding to E-cadherin which is abundant on epithelial cells. Notably, CD103 is highly expressed on CD8 T cells but conspicuously absent on most CD4 T cells. The mechanism controlling such lineage-specific expression of CD103 remains unclear. Using a series of genetically engineered mouse models, here, we demonstrate that the regulatory mechanism of CD103 expression is distinct between CD4 and CD8 T cells, and that the transcription factor Runx3 plays an important but not an essential role in this process. We further found that the availability of integrin β7 which heterodimerizes with CD103 was necessary but also constrained the surface expression of CD103. Notably, the forced surface expression of CD103 did not significantly alter the thymic development of conventional T cells but severely impaired the generation of MHC-II-restricted TCR transgenic T cells, revealing previously unappreciated aspects of CD103 in the selection and maturation of CD4 T cells. Unlike its effect on CD4 T cell development, however, CD103 overexpression did not significantly affect CD4 T cells in peripheral tissues. Moreover, the frequency and number of CD4 T cells in the small intestine epithelium did not increase even though E-cadherin is highly expressed in this tissue. Collectively, these results suggest that most mature CD4 T cells are refractory to the effects of CD103 expression, and that they presumably utilize CD103-independent pathways to control their tissue retention and residency.
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Affiliation(s)
- Hilary R Keller
- Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, 20892, USA.,Department of Surgery, Guthrie Robert Packer Hospital, Sayre, PA, 18840, USA
| | - Davinna L Ligons
- Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, 20892, USA
| | - Can Li
- Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, 20892, USA
| | - SuJin Hwang
- Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, 20892, USA
| | - Megan A Luckey
- Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, 20892, USA
| | - Praveen Prakhar
- Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, 20892, USA
| | - Nurcin Liman
- Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, 20892, USA
| | - Assiatu Crossman
- Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, 20892, USA
| | - Vanja Lazarevic
- Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, 20892, USA
| | - Yoo Kyoung Park
- Department of Medical Nutrition-AgeTech-Service Convergence Major, Graduate School of East-West Medical Science, Kyung Hee University, Yongin-si, Gyeonggi-do, 17104, South Korea.
| | - Jung-Hyun Park
- Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, 20892, USA.
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40
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Xu Y, Zhu J, Feng B, Lin F, Zhou J, Liu J, Shi X, Lu X, Pan Q, Yu J, Zhang Y, Li L, Cao H. Immunosuppressive effect of mesenchymal stem cells on lung and gut CD8 + T cells in lipopolysaccharide-induced acute lung injury in mice. Cell Prolif 2021; 54:e13028. [PMID: 33738881 PMCID: PMC8088466 DOI: 10.1111/cpr.13028] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 03/03/2021] [Accepted: 03/04/2021] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVES Acute lung injury (ALI) not only affects pulmonary function but also leads to intestinal dysfunction, which in turn contributes to ALI. Mesenchymal stem cell (MSC) transplantation can be a potential strategy in the treatment of ALI. However, the mechanisms of synergistic regulatory effects by MSCs on the lung and intestine in ALI need more in-depth study. MATERIALS AND METHODS We evaluated the therapeutic effects of MSCs on the murine model of lipopolysaccharide (LPS)-induced ALI through survival rate, histopathology and bronchoalveolar lavage fluid. Metagenomic sequencing was performed to assess the gut microbiota. The levels of pulmonary and intestinal inflammation and immune response were assessed by analysing cytokine expression and flow cytometry. RESULTS Mesenchymal stem cells significantly improved the survival rate of mice with ALI, alleviated histopathological lung damage, improved intestinal barrier integrity, and reduced the levels of inflammatory cytokines in the lung and gut. Furthermore, MSCs inhibited the inflammatory response by decreasing the infiltration of CD8+ T cells in both small-intestinal lymphocytes and Peyer's patches. The gut bacterial community diversity was significantly altered by MSC transplantation. Furthermore, depletion of intestinal bacterial communities with antibiotics resulted in more severe lung and gut damages and mortality, while MSCs significantly alleviated lung injury due to their immunosuppressive effect. CONCLUSIONS The present research indicates that MSCs attenuate lung and gut injury partly via regulation of the immune response in the lungs and intestines and gut microbiota, providing new insights into the mechanisms underlying the therapeutic effects of MSC treatment for LPS-induced ALI.
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Affiliation(s)
- Yanping Xu
- State Key Laboratory for the Diagnosis and Treatment of Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou CityChina
- National Clinical Research Center for Infectious DiseasesHangzhou CityChina
| | - Jiaqi Zhu
- State Key Laboratory for the Diagnosis and Treatment of Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou CityChina
- National Clinical Research Center for Infectious DiseasesHangzhou CityChina
| | - Bing Feng
- State Key Laboratory for the Diagnosis and Treatment of Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou CityChina
- National Clinical Research Center for Infectious DiseasesHangzhou CityChina
| | - Feiyan Lin
- State Key Laboratory for the Diagnosis and Treatment of Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou CityChina
- National Clinical Research Center for Infectious DiseasesHangzhou CityChina
| | - Jiahang Zhou
- State Key Laboratory for the Diagnosis and Treatment of Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou CityChina
- National Clinical Research Center for Infectious DiseasesHangzhou CityChina
| | - Jingqi Liu
- State Key Laboratory for the Diagnosis and Treatment of Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou CityChina
- National Clinical Research Center for Infectious DiseasesHangzhou CityChina
| | - Xiaowei Shi
- State Key Laboratory for the Diagnosis and Treatment of Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou CityChina
| | - Xuan Lu
- State Key Laboratory for the Diagnosis and Treatment of Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou CityChina
- National Clinical Research Center for Infectious DiseasesHangzhou CityChina
| | - Qiaoling Pan
- State Key Laboratory for the Diagnosis and Treatment of Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou CityChina
- National Clinical Research Center for Infectious DiseasesHangzhou CityChina
| | - Jiong Yu
- State Key Laboratory for the Diagnosis and Treatment of Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou CityChina
- National Clinical Research Center for Infectious DiseasesHangzhou CityChina
| | - Ying Zhang
- State Key Laboratory for the Diagnosis and Treatment of Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou CityChina
- National Clinical Research Center for Infectious DiseasesHangzhou CityChina
| | - Lanjuan Li
- State Key Laboratory for the Diagnosis and Treatment of Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou CityChina
- National Clinical Research Center for Infectious DiseasesHangzhou CityChina
| | - Hongcui Cao
- State Key Laboratory for the Diagnosis and Treatment of Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou CityChina
- National Clinical Research Center for Infectious DiseasesHangzhou CityChina
- Zhejiang Provincial Key Laboratory for Diagnosis and Treatment of Aging and Physic‐chemical Injury DiseasesHangzhou CityChina
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Zheng R, Wang P, Cao B, Wu M, Li X, Wang H, Chai L. Intestinal response characteristic and potential microbial dysbiosis in digestive tract of Bufo gargarizans after exposure to cadmium and lead, alone or combined. CHEMOSPHERE 2021; 271:129511. [PMID: 33445016 DOI: 10.1016/j.chemosphere.2020.129511] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Revised: 12/29/2020] [Accepted: 12/29/2020] [Indexed: 06/12/2023]
Abstract
The gastrointestinal tract is the largest immune organ in the body and meanwhile, accommodates a large number of microorganisms. Heavy metals could disturb the intestinal homeostasis and change the gut microbial composition. However, the information regarding the links between dysbiosis of gut microbiota and imbalance of host intestinal homeostasis induced by the mixture of heavy metals is insufficient. The present study investigates the effects of Cd/Pb, both single and combination exposure, on the growth performance, intestinal histology, digestive enzymes activity, oxidative stress and immune parameters, and intestinal microbiota in Bufo gargarizans tadpoles. Our results revealed that co-exposure of Cd-Pb induced more severe impacts not only on the host, but the intestinal microbiota. On the one hand, co-exposure of Cd-Pb significantly induced growth retardation, intestinal histological injury, decreased activities of digestive enzymes. On the other hand, Cd and Pb exposure, especially in mixed form, changed the diversity and richness, structure of microbiota. Also, the intestinal microbial composition was altered by Cd/Pb exposure (alone and combination) both at the different levels. Proteobacteria, act as front-line responder, was significantly increased in tadpoles under the exposure of metals. Finally, the functional prediction revealed that the disorders of metabolism and immune responses of intestinal microbiota was increased in tadpoles exposed to Cd/Pb (especially the mixture of Cd and Pb). Our research complements the understanding of links between changes in host fitness loss and intestinal microbiota and will add a new dimension of knowledge to the ecological risks of mixed heavy metals in amphibian.
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Affiliation(s)
- Rui Zheng
- College of Life Science, Shaanxi Normal University, Xi'an, 710119, China
| | - Pengju Wang
- Henan Key Laboratory of Immunology and Targeted Therapy, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan, 453003, China
| | - Baoping Cao
- Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Minyao Wu
- College of Life Science, Shaanxi Normal University, Xi'an, 710119, China
| | - Xinyi Li
- College of Life Science, Shaanxi Normal University, Xi'an, 710119, China
| | - Hongyuan Wang
- College of Life Science, Shaanxi Normal University, Xi'an, 710119, China.
| | - Lihong Chai
- School of Environmental Science and Engineering, Chang'an University, Xi'an, 710054, People's Republic of China; Key Laboratory of Subsurface Hydrology and Ecological Effect in Arid Region of Ministry of Education, Xi'an, 710062, People's Republic of China.
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42
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Zhou R, He D, Xie J, Zhou Q, Zeng H, Li H, Huang L. The Synergistic Effects of Polysaccharides and Ginsenosides From American Ginseng ( Panax quinquefolius L.) Ameliorating Cyclophosphamide-Induced Intestinal Immune Disorders and Gut Barrier Dysfunctions Based on Microbiome-Metabolomics Analysis. Front Immunol 2021; 12:665901. [PMID: 33968068 PMCID: PMC8100215 DOI: 10.3389/fimmu.2021.665901] [Citation(s) in RCA: 79] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Accepted: 03/29/2021] [Indexed: 12/15/2022] Open
Abstract
Cyclophosphamide (CTX), used in cancer chemotherapy, a high dose of which would cause immunosuppressive effect and intestinal mucosa damage. American ginseng (Panax quinquefolius L.) has a long history of functional food use for immunological disorder, colitis, cancer, and so on. This study aimed to illustrate the underlying mechanism of American ginseng’s immunomodulatory effect in CTX-induced mice. In this study, all groups of American ginseng (American ginseng polysaccharide [AGP], American ginseng ginsenoside [AGG], co-treated with American ginseng polysaccharide and ginsenoside [AGP_AGG]) have relieve the immune disorder by reversing the lymphocyte subsets ratio in spleen and peripheral blood, as well as stimulating CD4+T cells and IgA-secreting cells in small intestine. These three treatment groups, especially AGP_AGG co-treated group recovered the intestine morphology that up-regulated villus height (VH)/crypt depth (CD) ratio, areas of mucins expression, quantity of goblet cells, and expression of tight junction proteins (ZO-1, occludin). Importantly, the microbiome-metabolomics analysis was applied in this study to illustrate the possible immuno-modulating mechanism. The synergistic effect of polysaccharides and ginsenosides (AGP_AGG group) restored the gut microbiota composition and increased various beneficial mucosa-associated bacterial taxa Clostridiales, Bifidobacterium, and Lachnospiraceae, while decreased harmful bacteria Escherichia-Shigella and Peptococcaceae. Also, AGP_AGG group altered various fecal metabolites such as uric acid, xanthurenic acid, acylcarnitine, 9,10-DHOME, 13-HDoHE, LysoPE15:0, LysoPC 16:0, LysoPI 18:0, and so on, that associated with immunometabolism or protective effect of gut barrier. These results suggest AG, particularly co-treated of polysaccharide and ginsenoside may be used as immunostimulants targeting microbiome-metabolomics axis to prevent CTX-induced side effects in cancer patients.
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Affiliation(s)
- Rongrong Zhou
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China.,National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
| | - Dan He
- Hunan Academy of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
| | - Jing Xie
- Hunan Academy of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
| | - Qingyijun Zhou
- Hunan Academy of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
| | - Hongliang Zeng
- Hunan Academy of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
| | - Hongmei Li
- Insitute of Chinese Materia, China Academy of Chinese Medical Sciences, Beijing, China
| | - Luqi Huang
- National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
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Gusmao-Silva G, Aguiar SLF, Miranda MCG, Guimarães MA, Alves JL, Vieira AT, Cara DC, Miyoshi A, Azevedo VA, Oliveira RP, Faria AMC. Hsp65-Producing Lactococcocus lactis Prevents Antigen-Induced Arthritis in Mice. Front Immunol 2020; 11:562905. [PMID: 33072101 PMCID: PMC7538670 DOI: 10.3389/fimmu.2020.562905] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Accepted: 08/18/2020] [Indexed: 01/22/2023] Open
Abstract
Oral tolerance is the physiological process that enables the immune system to differentiate between harmless dietary and microbiota antigens from pathogen derived antigens. It develops at the mucosal surfaces and can result in local and systemic regulatory and anti-inflammatory effects. Translation of these benefits to the clinical practice faces limitations involving specificity and doses of antigen as well as regimens of feeding. To circumvent these problems, we developed a recombinant Hsp65 delivered by the acid lactic bacteria Lactococcus lactis NCDO 2118 directy in the intestinal mucosa. Hsp65 is a ubiquitous protein overexpressed in inflamed tissues and capable of inducing immunoregulatory mechanisms. L. lactis has probiotic properties and is commonly and safely used in dairy products. In this study, we showed that continuous delivery of HSP65 in the gut mucosa by L. lactis is a potent tolerogenic stimulus inducing regulatory CD4+LAP+ T cells that prevented collagen-induced and methylated bovine serum albumin-induced arthritis in mice. Clinical and histological signs of arthritis were inhibited as well as levels of inflammatory cytokines such as IL-17 and IFN-γ, serum titers of anti-collagen antibodies and rheumatoid factor. Oral administration of L. lactis induced alterations in microbiota composition toward an increased abundance of anaerobic bacteria such as Bifidobacterium and Lactobacillus. Tolerance to HSP65 and arthritis prevention induced by the recombinant L. lactis was associated with increase in IL-10 production by B cells and it was dependent on LAP+ T cells, IL-10 and TLR2 signaling. Therefore, HSP65-producing treatment induced effective tolerance and prevented arthritis development suggesting it can be used as a therapeutic tool for autoimmune diseases.
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Affiliation(s)
- Guilherme Gusmao-Silva
- Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Sarah Leão Fiorini Aguiar
- Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | | | - Mauro Andrade Guimarães
- Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Juliana Lima Alves
- Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Angélica Thomaz Vieira
- Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Denise Carmona Cara
- Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Anderson Miyoshi
- Departamento de Genética, Evolução e Ecologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Vasco Ariston Azevedo
- Departamento de Genética, Evolução e Ecologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | | | - Ana Maria Caetano Faria
- Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.,Instituto de Investigação em Imunologia, São Paulo, Brazil
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Kavanagh K, Hsu FC, Davis AT, Kritchevsky SB, Rejeski WJ, Kim S. Biomarkers of leaky gut are related to inflammation and reduced physical function in older adults with cardiometabolic disease and mobility limitations. GeroScience 2019; 41:923-933. [PMID: 31654268 DOI: 10.1007/s11357-019-00112-z] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Accepted: 10/09/2019] [Indexed: 12/14/2022] Open
Abstract
Intestinal barrier dysfunction is hypothesized to be a contributing determinant of two prominent characteristics of aging: inflammation and decline in physical function. A relationship between microbial translocation (MT), or their biomarkers (lipopolysaccharide binding protein-1 [LBP-1], soluble cluster of differentiation [sCD]-14), and physical function has been reported in healthy older adults, rats, and invertebrates. However, it is not known whether the existence of comorbidities, or clinical interventions intended to reduce comorbidities through weight loss or exercise, alters this connection. We measured inflammation, MT, and physical function in 288 overweight/obese older patients with cardiometabolic disease and self-reported mobility limitations who were enrolled in a weight loss and lifestyle intervention study. At baseline, inflammatory cytokines and LBP-1 were positively correlated after adjustment for age, gender, and body mass index. A higher LBP-1 was significantly associated with poorer physical functional after covariate adjustment. Further, even when IL-6 levels were included in the models, 400-m walk time (p = 0.003), short physical performance battery (p = 0.07), and IL-8 (p < 0.001) remained positively associated with LBP-1. Lifestyle interventions improved body mass and some functional measures; however, MT and inflammation were unchanged. MT is reliably related to inflammation, and to poorer physical function in older adults with comorbid conditions. Intestinal barrier function did not appear to improve as a result of intervention assignment, suggesting alternative strategies are needed to target this pro-inflammatory pathway in aging.
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Affiliation(s)
- Kylie Kavanagh
- Department of Pathology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157-1009, USA. .,School of Medicine, University of Tasmania, TAS, Hobart, Australia.
| | - Fang-Chi Hsu
- Division of Public Health Sciences, Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Ashley T Davis
- Department of Pathology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157-1009, USA
| | - Stephen B Kritchevsky
- Sticht Center on Healthy Aging and Alzheimer's Prevention, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - W Jack Rejeski
- Department of Health and Exercise Science, Wake Forest University, Winston-Salem, NC, USA
| | - Sunghye Kim
- Department of Internal Medicine, Section of Rheumatology, Wake Forest School of Medicine, Winston-Salem, NC, USA
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45
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McManus D, Novaira HJ, Hamers AAJ, Pillai AB. Isolation of Lamina Propria Mononuclear Cells from Murine Colon Using Collagenase E. J Vis Exp 2019. [PMID: 31609324 DOI: 10.3791/59821] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
The intestine is the home to the largest number of immune cells in the body. The small and large intestinal immune systems police exposure to exogenous antigens and modulate responses to potent microbially derived immune stimuli. For this reason, the intestine is a major target site of immune dysregulation and inflammation in many diseases including but, not limited to inflammatory bowel diseases such as Crohn's disease and ulcerative colitis, graft-versus-host disease (GVHD) after bone marrow transplantation (BMT), and many allergic and infectious conditions. Murine models of gastrointestinal inflammation and colitis are heavily used to study GI complications and to pre-clinically optimize strategies for prevention and treatment. Data gleaned from these models via isolation and phenotypic analysis of immune cells from the intestine is critical to further immune understanding that can be applied to ameliorate gastrointestinal and systemic inflammatory disorders. This report describes a highly effective protocol for the isolation of mononuclear cells (MNC) from the colon using a mixed silica-based density gradient interface. This method reproducibly isolates a significant number of viable leukocytes while minimizing contaminating debris, allowing subsequent immune phenotyping by flow cytometry or other methods.
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Affiliation(s)
- Duneia McManus
- Department of Pediatrics, Division of Hematology / Oncology and Bone Marrow Transplantation, University of Miami Miller School of Medicine; Batchelor Children's Research Institute, University of Miami Miller School of Medicine; Department of Microbiology & Immunology, University of Miami Miller School of Medicine; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine
| | - Horacio J Novaira
- Department of Pediatrics, Division of Hematology / Oncology and Bone Marrow Transplantation, University of Miami Miller School of Medicine; Batchelor Children's Research Institute, University of Miami Miller School of Medicine; Department of Microbiology & Immunology, University of Miami Miller School of Medicine; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine
| | - Anouk A J Hamers
- Department of Pediatrics, Division of Hematology / Oncology and Bone Marrow Transplantation, University of Miami Miller School of Medicine; Batchelor Children's Research Institute, University of Miami Miller School of Medicine; Department of Microbiology & Immunology, University of Miami Miller School of Medicine; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine
| | - Asha B Pillai
- Department of Pediatrics, Division of Hematology / Oncology and Bone Marrow Transplantation, University of Miami Miller School of Medicine; Batchelor Children's Research Institute, University of Miami Miller School of Medicine; Department of Microbiology & Immunology, University of Miami Miller School of Medicine; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine; Holtz Children's Hospital, University of Miami Miller School of Medicine;
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Yang J, Qian K, Wang C, Wu Y. Roles of Probiotic Lactobacilli Inclusion in Helping Piglets Establish Healthy Intestinal Inter-environment for Pathogen Defense. Probiotics Antimicrob Proteins 2019; 10:243-250. [PMID: 28361445 DOI: 10.1007/s12602-017-9273-y] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The gastrointestinal tract of pigs is densely populated with microorganisms that closely interact with the host and with ingested feed. Gut microbiota benefits the host by providing nutrients from dietary substrates and modulating the development and function of the digestive and immune systems. An optimized gastrointestinal microbiome is crucial for pigs' health, and establishment of the microbiome in piglets is especially important for growth and disease resistance. However, the microbiome in the gastrointestinal tract of piglets is immature and easily influenced by the environment. Supplementing the microbiome of piglets with probiotic bacteria such as Lactobacillus could help create an optimized microbiome by improving the abundance and number of lactobacilli and other indigenous probiotic bacteria. Dominant indigenous probiotic bacteria could improve piglets' growth and immunity through certain cascade signal transduction pathways. The piglet body provides a permissive habitat and nutrients for bacterial colonization and growth. In return, probiotic bacteria produce prebiotics such as short-chain fatty acids and bacteriocins that benefit piglets by enhancing their growth and reducing their risk of enteric infection by pathogens. A comprehensive understanding of the interactions between piglets and members of their gut microbiota will help develop new dietary interventions that can enhance piglets' growth, protect piglets from enteric diseases caused by pathogenic bacteria, and maximize host feed utilization.
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Affiliation(s)
- Jiajun Yang
- The Institute of Animal Husbandry and Veterinary Medicine, Anhui Academy of Agricultural Sciences, No. 40 Nongke South Road, Hefei, 230031, Anhui province, People's Republic of China
| | - Kun Qian
- The Institute of Animal Husbandry and Veterinary Medicine, Anhui Academy of Agricultural Sciences, No. 40 Nongke South Road, Hefei, 230031, Anhui province, People's Republic of China.
| | - Chonglong Wang
- The Institute of Animal Husbandry and Veterinary Medicine, Anhui Academy of Agricultural Sciences, No. 40 Nongke South Road, Hefei, 230031, Anhui province, People's Republic of China
| | - Yijing Wu
- The Institute of Animal Husbandry and Veterinary Medicine, Anhui Academy of Agricultural Sciences, No. 40 Nongke South Road, Hefei, 230031, Anhui province, People's Republic of China
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Li B, Schroyen M, Leblois J, Wavreille J, Soyeurt H, Bindelle J, Everaert N. Effects of inulin supplementation to piglets in the suckling period on growth performance, postileal microbial and immunological traits in the suckling period and three weeks after weaning. Arch Anim Nutr 2018; 72:425-442. [PMID: 30160174 DOI: 10.1080/1745039x.2018.1508975] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The aim of this study was to investigate the effect of inulin (IN) supplementation to suckling piglets at and 3 weeks post-weaning. A total of 72 newborn piglets were used. Twenty-four piglets per group received different amounts of IN during the suckling period: (a) CON: no IN; (b) IN-0.5: 0.5 g IN/d on the 1st week, 1 g IN/d on the 2nd week, 1.5 g IN/d on the 3rd week and 2 g IN/d on the 4th week, or (c) IN-0.75: 0.75 g IN/d on the 1st week, 1.5 g IN/d on the 2nd week, 2.25 g IN/d on the 3rd week and 3 g IN/d on the 4th week. Starting at 28 d of age, piglets were weaned and received a post-weaning diet without inulin during the following 3 weeks. At both 28 d and 49 d of age, piglets were euthanised for sampling. Piglets of group IN-0.5 had the highest body weight starting from the 3rd week (p < 0.05), concomitant with the highest villus height and the ratio of villus height/crypt depth in the jejunum and ileum on both sampling days (p < 0.05). At 28 d of age, an increased concentration of propionate, iso-butyrate or total short chain fatty acids was observed between treatment IN-0.5 and the other groups in the caecum or colon (p < 0.05). Moreover, the relative abundance of Escherichia coli (p = 0.05) and Enterobacteriaceae (p = 0.01) in colonic digesta were reduced in IN-0.5-treated piglets, and in both IN-supplemented groups, colonic interleukin-8, tumor necrosis factor-α and toll-like receptor-4 mRNA abundance were decreased compared to the CON group (p < 0.05). However, at 49 d of age, most of these differences disappeared. In conclusion, treatment IN-0.5 improved during the suckling period of piglets development of intestine, but these beneficial effects were not lasting after weaning, when IN supplementation was terminated. Treatment IN-0.75, however, did not display a prebiotic effect.
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Affiliation(s)
- Bing Li
- a Precision livestock and nutrition unit, Gembloux Agro-Bio Tech, Teaching and Research Centre , University of Liège , Gembloux , Belgium
| | - Martine Schroyen
- a Precision livestock and nutrition unit, Gembloux Agro-Bio Tech, Teaching and Research Centre , University of Liège , Gembloux , Belgium
| | - Julie Leblois
- a Precision livestock and nutrition unit, Gembloux Agro-Bio Tech, Teaching and Research Centre , University of Liège , Gembloux , Belgium.,b Research Foundation for Industry and Agriculture , Fonds De La Recherche Scientifique - FNRS , Brussels , Belgium
| | - José Wavreille
- c Department of Production and Sectors , Walloon Agricultural Research Centre , Gembloux , Belgium
| | - Hélène Soyeurt
- d Laboratory of statistics, informatics and modelling applied to bioengineering, agrobiochem department, Gembloux Agro-Bio Tech, Teaching and Research Centre , University of Liège , Gembloux , Belgium
| | - Jérôme Bindelle
- a Precision livestock and nutrition unit, Gembloux Agro-Bio Tech, Teaching and Research Centre , University of Liège , Gembloux , Belgium
| | - Nadia Everaert
- a Precision livestock and nutrition unit, Gembloux Agro-Bio Tech, Teaching and Research Centre , University of Liège , Gembloux , Belgium
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Sun Y, Qian J, Xu X, Tang Y, Xu W, Yang W, Jiang Y, Yang G, Ding Z, Cong Y, Wang C. Dendritic cell-targeted recombinantLactobacilli induce DC activation and elicit specific immune responses against G57 genotype of avian H9N2 influenza virus infection. Vet Microbiol 2018; 223:9-20. [PMID: 30173758 DOI: 10.1016/j.vetmic.2018.07.009] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2018] [Revised: 07/11/2018] [Accepted: 07/15/2018] [Indexed: 12/21/2022]
Abstract
H9N2 avian influenza viruses are of significance in poultry and public health for the past two decades. Vaccination plays an important role in preventing the infection in domestic poultry. Current H9N2 vaccines have not yet offered ideal protection and eliminated shedding of G57 genotype viruses responsible for H9N2 outbreaks during 2010-2013. Targeted vaccination is a promising strategy to improve vaccine effectiveness. Such a vaccine strategy can be achieved if it is targeted to dendritic cells (DCs) that directly elicit mucosal and adaptive immune responses against microbe challenge. For this purpose, we develop a DC-targeted mucosal vaccine for the oral delivery of the HA protein fused to a DCpep by using Lactobacillus plantarum as an antigen delivery system against G57 virus infection. It showed that Lactobacillus plantarum expressing HA-DCpep confers efficient protection against G57 H9N2 infection, due to have the potential to activate DCs by the TLR-induced NF-κB pathway, to promote DC migration by the CCR7-CCL19/CCL21 axis, thereby enhancing the presentation of immunogen to T and B lymphocytes, resulting in skewing T cells polarization towards Th1, Th2 and Treg cells and evoking more efficient mucosal and adaptive immunity responses. The presented oral mucosal vaccine strategy illustrates the feasibility and efficacy of antigen targeting to DCs through genetic fusion of vaccines to DC-targeting peptides and aids in the design and selection of indications that could be used with this oral vaccine platform against influenza.
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Affiliation(s)
- Yixue Sun
- Engineering Research Center of Jilin Province for Animals Probiotics, College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
| | - Jing Qian
- Laboratory of Infectious Diseases, College of Veterinary Medicine, Jilin University, Changchun, China; Key Laboratory of Zoonosis Research, Ministry of Education, Jilin University, Changchun, China
| | - Xiaohong Xu
- Laboratory of Infectious Diseases, College of Veterinary Medicine, Jilin University, Changchun, China; Key Laboratory of Zoonosis Research, Ministry of Education, Jilin University, Changchun, China
| | - Yubo Tang
- Laboratory of Infectious Diseases, College of Veterinary Medicine, Jilin University, Changchun, China; Key Laboratory of Zoonosis Research, Ministry of Education, Jilin University, Changchun, China
| | - Wenzhang Xu
- Laboratory of Infectious Diseases, College of Veterinary Medicine, Jilin University, Changchun, China; Key Laboratory of Zoonosis Research, Ministry of Education, Jilin University, Changchun, China
| | - Wentao Yang
- Engineering Research Center of Jilin Province for Animals Probiotics, College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
| | - Yanlong Jiang
- Engineering Research Center of Jilin Province for Animals Probiotics, College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
| | - Guilian Yang
- Engineering Research Center of Jilin Province for Animals Probiotics, College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
| | - Zhuang Ding
- Laboratory of Infectious Diseases, College of Veterinary Medicine, Jilin University, Changchun, China; Key Laboratory of Zoonosis Research, Ministry of Education, Jilin University, Changchun, China.
| | - Yanlong Cong
- Laboratory of Infectious Diseases, College of Veterinary Medicine, Jilin University, Changchun, China; Key Laboratory of Zoonosis Research, Ministry of Education, Jilin University, Changchun, China.
| | - Chunfeng Wang
- Engineering Research Center of Jilin Province for Animals Probiotics, College of Animal Science and Technology, Jilin Agricultural University, Changchun, China.
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High-fat diet induces systemic B-cell repertoire changes associated with insulin resistance. Mucosal Immunol 2017; 10:1468-1479. [PMID: 28422186 DOI: 10.1038/mi.2017.25] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2016] [Accepted: 02/22/2017] [Indexed: 02/04/2023]
Abstract
The development of obesity-associated insulin resistance is associated with B-lymphocyte accumulation in visceral adipose tissue (VAT) and is prevented by B-cell ablation. To characterize potentially pathogenic B-cell repertoires in this disorder, we performed high-throughput immunoglobulin (Ig) sequencing from multiple tissues of mice fed high-fat diet (HFD) and regular diet (RD). HFD significantly changed the biochemical properties of Ig heavy-chain complementarity-determining region-3 (CDRH3) sequences, selecting for IgA antibodies with shorter and more hydrophobic CDRH3 in multiple tissues. A set of convergent antibodies of highly similar sequences found in the VAT of HFD mice but not RD mice showed significant somatic mutation, suggesting a response shared between mice to a common antigen or antigens. These findings indicate that a simple high-fat dietary intervention has a major impact on mouse B-cell repertoires, particularly in adipose tissues.
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Takiishi T, Fenero CIM, Câmara NOS. Intestinal barrier and gut microbiota: Shaping our immune responses throughout life. Tissue Barriers 2017; 5:e1373208. [PMID: 28956703 DOI: 10.1080/21688370.2017.1373208] [Citation(s) in RCA: 593] [Impact Index Per Article: 74.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
The gastrointestinal (GI) tract is considered the largest immunological organ in the body having a central role in regulating immune homeostasis. Contrary to earlier belief, the intestinal epithelial barrier is not a static physical barrier but rather strongly interacts with the gut microbiome and cells of the immune system. This intense communication between epithelial cells, immune cells and microbiome will shape specific immune responses to antigens, balancing tolerance and effector immune functions. Recent studies indicate that composition of the gut microbiome affects immune system development and modulates immune mediators, which in turn affect the intestinal barrier. Moreover, dysbiosis may favor intestinal barrier disruption and could be related to increased susceptibility to certain diseases. This review will be focused on the development of the intestinal barrier and its function in host immune defense and how gut microbiome composition throughout life can affect this role.
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Affiliation(s)
- Tatiana Takiishi
- a Department of Immunology, Institute of Biomedical Sciences , University of São Paulo (USP), São Paulo - SP , Brazil
| | - Camila Ideli Morales Fenero
- a Department of Immunology, Institute of Biomedical Sciences , University of São Paulo (USP), São Paulo - SP , Brazil
| | - Niels Olsen Saraiva Câmara
- a Department of Immunology, Institute of Biomedical Sciences , University of São Paulo (USP), São Paulo - SP , Brazil
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