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Yuan R, Wang T, Zhang L, Jeevithan L, Wang C, Li X, Wu W. Immunomodulatory Effects of L-Arginine-Modified Silkworm Pupae Protein Enteral Nutrition on Murine Intestinal Morphology and Immunity. Int J Mol Sci 2025; 26:3209. [PMID: 40244038 PMCID: PMC11989753 DOI: 10.3390/ijms26073209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2025] [Revised: 03/20/2025] [Accepted: 03/28/2025] [Indexed: 04/18/2025] Open
Abstract
L-arginine, a semi-essential amino acid, is well-documented for its role in nitric oxide (NO) synthesis, its anti-inflammatory properties, and its modulation of immune responses. Studies suggest it may improve gut barrier function and reduce inflammation in conditions such as colitis or sepsis. However, its specific efficacy in diabetic enteropathy (a complication of diabetes involving intestinal dysfunction, inflammation, and neuropathy) is less studied. To verify whether L-arginine and silkworm pupae components have a role in the treatment of diabetic enteropathy via the regulation of other cytokines and suppression of CD4+ T lymphocyte proliferation, a special medical-purpose formula containing both of these components was tested. For the first time, we have integrated L-arginine and silkworm pupae protein into enteral nutrition formulations for testing its anti-inflammatory potential. We have found that these formulations can improve the characteristics of diabetic intestinal inflammation through nutrient-modulating effects and nutritional efficacy. In addition, L-arginine (L-arginine, L-arg) enhances the immunomodulatory effects of special medical purpose formulas for diabetes mellitus. We utilized an oxidative stress model of small intestinal epithelial cells induced by high glucose and an inflammation model of the small intestine triggered by lipopolysaccharide in mice. The aim was to further investigate the protective effects of L-arginine and enteral nutritional preparations derived from silkworm pupae protein components on the intestinal tract. This research seeks to establish a theoretical foundation for understanding how L-arginine and these nutritional preparations regulate intestinal inflammation in vivo.
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Affiliation(s)
- Rui Yuan
- Department of Marine Bio-Pharmacology, College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China; (R.Y.); (L.Z.); (L.J.)
| | - Tianming Wang
- Department of Marine Bio-Pharmacology, College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China; (R.Y.); (L.Z.); (L.J.)
| | - Linling Zhang
- Department of Marine Bio-Pharmacology, College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China; (R.Y.); (L.Z.); (L.J.)
| | - Lakshmi Jeevithan
- Department of Marine Bio-Pharmacology, College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China; (R.Y.); (L.Z.); (L.J.)
- Department of Biomaterials Engineering, Faculty of Health Sciences, UCAM-Universidad Catolica San-Antonio de Murcia, 30107 Murcia, Spain
| | - Chunxiao Wang
- Department of Marine Bio-Pharmacology, College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China; (R.Y.); (L.Z.); (L.J.)
| | - Xiaohui Li
- Department of Marine Bio-Pharmacology, College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China; (R.Y.); (L.Z.); (L.J.)
| | - Wenhui Wu
- Department of Marine Bio-Pharmacology, College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China; (R.Y.); (L.Z.); (L.J.)
- National R&D Branch Center for Freshwater Aquatic Products Processing Technology, Shanghai 201306, China
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Özgüç Çömlek F, Körez MK. Can consumption of traditional fermented foods protect against Hashimoto's thyroiditis? NUTR HOSP 2025. [PMID: 40195756 DOI: 10.20960/nh.05508] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/09/2025] Open
Abstract
BACKGROUND this study examined fermented food consumption habits and the relationship between other factors and Hashimoto's thyroiditis. METHODS the study included 90 children and their mothers, 45 of whom had HT and 45 of whom did not. Participants answered a survey questioning about their fermented food consumption habits and the status of various environmental factors. RESULTS mothers who consumed homemade pickles during pregnancy (OR: 0.341, [95 % CI: 0.117 to 0.990]) homemade yogurt (OR: 0.091, [95 % CI: 0.011 to 0.752]), tarhana (OR: 0.325 [95 % CI: 0.136 to 0.778)]) and olive oil (OR: 0.163 [95 % CI: 0.033 to 0.792]) were found to have a statistically significant lower risk of developing Hashimoto's disease in their children. The risk of HT in children who consumed homemade yogurt (OR: 0.091 [95 % CI: 0.011 to 0.752]), cheese (OR: 0.242 [95 % CI: 0.100 to 0.590]), and olive oil (OR: 0.042 [95 % CI: 0.002 to 0.750]) was found to be significantly lower than in children who did not consume it. CONCLUSIONS fermented food consumption habits can be protective against autoimmune diseases such as HT by affecting the immune system through the intestinal microbiota.
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Affiliation(s)
- Fatma Özgüç Çömlek
- Department of Pediatric Endocrinology. Faculty of Medicine. Selçuk University
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Liu R, Zhang J, Chen S, Xiao Y, Hu J, Zhou Z, Xie L. Intestinal mucosal immunity and type 1 diabetes: Non-negligible communication between gut and pancreas. Diabetes Obes Metab 2025; 27:1045-1064. [PMID: 39618164 PMCID: PMC11802406 DOI: 10.1111/dom.16101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2024] [Revised: 11/16/2024] [Accepted: 11/18/2024] [Indexed: 02/08/2025]
Abstract
Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by T cell-mediated pancreatic β cell loss, resulting in lifelong absolute insulin deficiency and hyperglycaemia. Environmental factors are recognized as a key contributor to the development of T1D, with the gut serving as a primary interface for environmental stimuli. Recent studies have revealed that the alterations in the intestinal microenvironment profoundly affect host immune responses, contributing to the aetiology and pathogenesis of T1D. However, the dominant intestinal immune cells and the underlying mechanisms remain incompletely elucidated. In this review, we provide an overview of the possible mechanisms of the intestinal mucosal system that underpin the pathogenesis of T1D, shedding light on the roles of both non-classical and classical immune cells in T1D. Our goal is to gain insights into how modulating these immune components may hold potential implications for T1D prevention and provide novel perspectives for immune-mediated therapy.
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Affiliation(s)
- Ruonan Liu
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and EndocrinologyThe Second Xiangya Hospital of Central South UniversityChangshaChina
| | - Jing Zhang
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and EndocrinologyThe Second Xiangya Hospital of Central South UniversityChangshaChina
| | - Si Chen
- State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life ScienceHunan Normal UniversityChangshaChina
| | - Yang Xiao
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and EndocrinologyThe Second Xiangya Hospital of Central South UniversityChangshaChina
| | - Jingyi Hu
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and EndocrinologyThe Second Xiangya Hospital of Central South UniversityChangshaChina
| | - Zhiguang Zhou
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and EndocrinologyThe Second Xiangya Hospital of Central South UniversityChangshaChina
| | - Lingxiang Xie
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and EndocrinologyThe Second Xiangya Hospital of Central South UniversityChangshaChina
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Liu Y, Xu Z, Zhang D, Zhang Y, Li W, Liu W, Li X. Effect of fucoidan supplementation on glycolipid metabolism, systemic inflammation and gut microbiota in prediabetes: A randomized controlled trial. Int J Biol Macromol 2025; 287:138415. [PMID: 39645105 DOI: 10.1016/j.ijbiomac.2024.138415] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 11/18/2024] [Accepted: 12/03/2024] [Indexed: 12/09/2024]
Abstract
Prediabetes is characterized as a transitional phase between normal blood glucose and diabetes, and the potential role of fucoidan in the progression of diabetes is still debated. The randomized, double-blind, placebo-controlled trial was designed to assess the effect of fucoidan supplementation on glycolipid metabolism, systemic inflammation and gut microbiota in individuals with prediabetes. A total of 70 Chinese participants with prediabetes were randomized to either fucoidan or placebo group, receiving daily doses of 1000 mg fucoidan or placebo capsules for 12 weeks. Glycolipid metabolism and systemic inflammation levels were assessed using standard laboratory techniques, while gut microbiota was analyzed by 16S rRNA sequencing. Following the 12-week intervention period, subjects consuming fucoidan exhibited a lower increase in GSP and a notable reduction in TNF-α, IL-6 and LPS compared to those receiving placebo (P < 0.05). Furthermore, fucoidan supplementation led to an increased abundance of Megamonas and Blautia while decreasing Klebsiella (P < 0.05). These findings suggested that the daily administration of 1000 mg fucoidan may partially modulate glucose metabolism and improve systemic inflammation, potentially linked to its modulation of gut microbiota in Chinese individuals with prediabetes. Thus, fucoidan could be considered as a potential dietary supplement for diabetes prevention.
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Affiliation(s)
- Yaping Liu
- College of Food and Bioengineering, Zhengzhou University of Light Industry, 136 Science Road, Zhengzhou 450001, Henan, China
| | - Ze Xu
- Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, 100 Science Road, Zhengzhou, 450001, Henan, China
| | - Dongdong Zhang
- Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, 100 Science Road, Zhengzhou, 450001, Henan, China
| | - Yujing Zhang
- Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, 100 Science Road, Zhengzhou, 450001, Henan, China
| | - Wenjie Li
- Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, 100 Science Road, Zhengzhou, 450001, Henan, China
| | - Wenyi Liu
- President's Office, The Third Affiliated Hospital of Zhengzhou University, 7 Kangfuqian Street, Zhengzhou 450015, Henan, China
| | - Xing Li
- Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, 100 Science Road, Zhengzhou, 450001, Henan, China; Department of Hematology, The First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Zhengzhou 450099, Henan, China.
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Bhutta NK, Xu X, Jian C, Wang Y, Liu Y, Sun J, Han B, Wu S, Javeed A. Gut microbiota mediated T cells regulation and autoimmune diseases. Front Microbiol 2024; 15:1477187. [PMID: 39749132 PMCID: PMC11694513 DOI: 10.3389/fmicb.2024.1477187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Accepted: 11/29/2024] [Indexed: 01/04/2025] Open
Abstract
Gut microbiota regulates the immune system, the development and progression of autoimmune diseases (AIDs) and overall health. Recent studies have played a crucial part in understanding the specific role of different gut bacterial strains and their metabolites in different AIDs. Microbial signatures in AIDs are revealed by advanced sequencing and metabolomics studies. Microbes such as Faecalibacterium prausnitzii, Akkermansia muciniphila, Anaerostipes caccae, Bacteroides sp., Roseburia sp., Blautia sp., Blautia faecis, Clostridium lavalense, Christensenellaceae sp., Coprococcus sp., Firmicutes sp., Ruminococcaceae sp., Lachnospiraceae sp., Megamonas sp., Monoglobus sp., Streptococcus pneumoniae and Bifidobacterium sp. help maintain immune homeostasis; whereas, Prevotella copri, Ruminococcus gnavus, Lactobacillus salivarius, Enterococcus gallinarum, Elizabeth menigoseptica, Collinsella sp., Escherichia sp., Fusobacterium sp., Enterobacter ludwigii, Enterobacteriaceae sp., Proteobacteria, Porphyromonas gingivalis, Porphyromonas nigrescens, Dorea sp., and Clostridium sp. cause immuno-pathogenesis. A complex web of interactions is revealed by understanding the influence of gut microbiota on immune cells and various T cell subsets such as CD4+ T cells, CD8+ T cells, natural killer T cells, γδ T cells, etc. Certain AIDs, including rheumatoid arthritis, diabetes mellitus, atopic asthma, inflammatory bowel disease and non-alcoholic fatty liver disease exhibit a state of dysbiosis, characterized by alterations in microbial diversity and relative abundance of specific taxa. This review summarizes recent developments in understanding the role of certain microbiota composition in specific AIDs, and the factors affecting specific regulatory T cells through certain microbial metabolites and also focuses the potential application and therapeutic significance of gut microbiota-based interventions as novel adjunctive therapies for AIDs. Further research to determine the precise association of each gut bacterial strain in specific diseases is required.
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Affiliation(s)
- Nabeel Khalid Bhutta
- Laboratory of Anti-allergic Functional Molecules, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China
| | - Xiujin Xu
- Laboratory of Anti-allergic Functional Molecules, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China
| | - Cuiqin Jian
- Laboratory of Anti-allergic Functional Molecules, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China
| | - Yifan Wang
- Laboratory of Anti-allergic Functional Molecules, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China
| | - Yi Liu
- Hangzhou Zheda Dixun Biological Gene Engineering Co., Ltd., Hangzhou, China
| | - Jinlyu Sun
- Beijing Key Laboratory of Precision Medicine for Diagnosis and Treatment of Allergic Diseases, Department of Allergy, National Clinical Research Center for Dermatologic and Immunologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Bingnan Han
- Laboratory of Anti-allergic Functional Molecules, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China
| | - Shandong Wu
- Hangzhou Zheda Dixun Biological Gene Engineering Co., Ltd., Hangzhou, China
| | - Ansar Javeed
- Laboratory of Anti-allergic Functional Molecules, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China
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Fernandez Trigo N, Kalbermatter C, Yilmaz B, Ganal-Vonarburg SC. The protective effect of the intestinal microbiota in type-1 diabetes in NOD mice is limited to a time window in early life. Front Endocrinol (Lausanne) 2024; 15:1425235. [PMID: 39391872 PMCID: PMC11464356 DOI: 10.3389/fendo.2024.1425235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Accepted: 09/05/2024] [Indexed: 10/12/2024] Open
Abstract
Introduction The incidence of type-1 diabetes is on the rise, particularly in developed nations, and predominantly affects the youth. While genetic predisposition plays a substantial role, environmental factors, including alterations in the gut microbiota, are increasingly recognized as significant contributors to the disease. Methods In this study, we utilized germ-free non-obese diabetic mice to explore the effects of microbiota colonization during early life on type-1 diabetes susceptibility. Results Our findings reveal that microbiota introduction at birth, rather than at weaning, significantly reduces the risk of type-1 diabetes, indicating a crucial window for microbiota-mediated modulation of immune responses. This protective effect was independent of alterations in intestinal barrier function but correlated with testosterone levels in male mice. Additionally, early life colonization modulated T cell subset frequencies, particularly T helper cells and regulatory T cells, in the intestine, potentially shaping type-1 diabetes predisposition. Discussion Our findings underscore the pivotal role of early-life microbial interactions in immune regulation and the development of autoimmune diseases.
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Affiliation(s)
- Nerea Fernandez Trigo
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, Bern, Switzerland
- Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland
| | - Cristina Kalbermatter
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, Bern, Switzerland
- Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland
| | - Bahtiyar Yilmaz
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, Bern, Switzerland
- Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland
| | - Stephanie C. Ganal-Vonarburg
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, Bern, Switzerland
- Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland
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Berryman MA, Ilonen J, Triplett EW, Ludvigsson J. Functional metagenomic analysis reveals potential inflammatory triggers associated with genetic risk for autoimmune disease. J Autoimmun 2024; 148:103290. [PMID: 39033688 DOI: 10.1016/j.jaut.2024.103290] [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: 10/24/2023] [Revised: 04/28/2024] [Accepted: 07/14/2024] [Indexed: 07/23/2024]
Abstract
To assess functional differences between the microbiomes of individuals with autoimmune risk-associated human leukocyte antigen (HLA) genetics and autoimmune protection-associated HLA, we performed a metagenomic analysis of stool samples from 72 infants in the All Babies in Southeast Sweden general-population cohort and assessed haplotype-peptide binding affinities. Infants with risk-associated HLA DR3-DQ2.5 and DR4-DQ8 had a higher abundance of known pathogen-associated molecular patterns and virulence related genes than infants with protection-associated HLA DR15-DQ6.2. However, there was limited overlap in the type of inflammatory trigger between risk groups. Supported by a high Firmicutes/Bacteroides ratio and differentially abundant flagellated species, genes related to the synthesis of flagella were prominent in those with HLA DR3-DQ2.5. However, this haplotype had a significantly lower likelihood of binding affinity to flagellin peptides. O-antigen biosynthesis genes were significantly correlated with the risk genotypes and absent from protective genotype association, supported by the differential abundance of gram-negative bacteria seen in the risk-associated groups. Genes related to vitamin B biosynthesis stood out in higher abundance in infants with HLA DR3-DQ2.5/DR4-DQ8 heterozygosity compared to those with autoimmune-protective genetics. Prevotella species and genus were significantly abundant in all infant groups with high risk for autoimmune disease. The potential inflammatory triggers associated with genetic risk for autoimmunity have significant implications. These results suggest that certain HLA haplotypes may be creating the opportunity for dysbiosis and subsequent inflammation early in life by clearing beneficial microbes or not clearing proinflammatory microbes. This HLA gatekeeping may prevent genetically at-risk individuals from benefiting from probiotic therapies by restricting the colonization of those beneficial bacteria.
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Affiliation(s)
- Meghan A Berryman
- Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL, USA
| | - Jorma Ilonen
- Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland
| | - Eric W Triplett
- Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL, USA.
| | - Johnny Ludvigsson
- Crown Princess Victoria's Children's Hospital and Division of Pediatrics, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
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Yuan X, Yang X, Xu Z, Li J, Sun C, Chen R, Wei H, Chen L, Du H, Li G, Yang Y, Chen X, Cui L, Fu J, Wu J, Chen Z, Fang X, Su Z, Zhang M, Wu J, Chen X, Zhou J, Luo Y, Zhang L, Wang R, Luo F. The profile of blood microbiome in new-onset type 1 diabetes children. iScience 2024; 27:110252. [PMID: 39027370 PMCID: PMC11255850 DOI: 10.1016/j.isci.2024.110252] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 02/09/2024] [Accepted: 06/10/2024] [Indexed: 07/20/2024] Open
Abstract
Blood microbiome signatures in patients with type 1 diabetes (T1D) remain unclear. We profile blood microbiome using 16S rRNA gene sequencing in 77 controls and 64 children with new-onset T1D, and compared it with the gut and oral microbiomes. The blood microbiome of patients with T1D is characterized by increased diversity and perturbed microbial features, with a significant increase in potentially pathogenic bacteria compared with controls. Thirty-six representative genera of blood microbiome were identified by random forest analysis, providing strong discriminatory power for T1D with an AUC of 0.82. PICRUSt analysis suggested that bacteria capable of inducing inflammation were more likely to enter the bloodstream in T1D. The overlap of the gut and oral microbiome with the blood microbiome implied potential translocation of bacteria from the gut and oral cavity to the bloodstream. Our study raised the necessity of further mechanistic investigations into the roles of blood microbiome in T1D.
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Affiliation(s)
- Xiaoxiao Yuan
- Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children’s Hospital of Fudan University, Shanghai 201102, China
| | - Xin Yang
- Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai 200120, China
- Department of Food Science and Technology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China
- Section of Endocrinology, Internal Medicine, School of Medicine, Yale University, New Haven, CT 06511, United States
| | - Zhenran Xu
- Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children’s Hospital of Fudan University, Shanghai 201102, China
| | - Jie Li
- Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai 200120, China
- Teaching and Research Division, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong 999077, China
| | - ChengJun Sun
- Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children’s Hospital of Fudan University, Shanghai 201102, China
| | - Ruimin Chen
- Fuzhou Children’s Hospital of Fujian Medical University, Fuzhou 350000, China
| | - Haiyan Wei
- Department of Endocrinology and Inherited Metabolic, Children’s Hospital Affiliated to Zhengzhou University, Zhengzhou 450000, China
| | - Linqi Chen
- Children’s Hospital of Soochow University, Suzhou 215000, China
| | - Hongwei Du
- The First Hospital of Jilin University, Jilin 130000, China
| | - Guimei Li
- Department of Pediatric Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China
| | - Yu Yang
- The Affiliated Children’s Hospital of Nanchang University, Nanchang 330006, China
| | - Xiaojuan Chen
- Department of Endocrinology, Genetics and Metabolism, The Children’s Hospital of Shanxi Province, Taiyuan 030013, China
| | - Lanwei Cui
- The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China
| | - Junfen Fu
- Department of Endocrinology, Children’s Hospital, Zhejiang University School of Medicine, Hangzhou 310005, China
| | - Jin Wu
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China
| | - Zhihong Chen
- Department of Neuroendocrinology Pediatrics, Affiliated Hospital of Qingdao University, Qingdao 266003, China
| | - Xin Fang
- Fujian Medical University Union Hospital, Fuzhou 350001, China
| | - Zhe Su
- Shenzhen Children’s Hospital, Shenzhen 518038, China
| | - Miaoying Zhang
- Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children’s Hospital of Fudan University, Shanghai 201102, China
| | - Jing Wu
- Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children’s Hospital of Fudan University, Shanghai 201102, China
| | - Xin Chen
- Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai 200120, China
| | - Jiawei Zhou
- Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai 200120, China
| | - Yue Luo
- Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China
| | - Lei Zhang
- Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai 200120, China
| | - Ruirui Wang
- Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai 200120, China
| | - Feihong Luo
- Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children’s Hospital of Fudan University, Shanghai 201102, China
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Mihailović M, Soković Bajić S, Arambašić Jovanović J, Brdarić E, Dinić S, Grdović N, Uskoković A, Rajić J, Đorđević M, Tolinački M, Golić N, Živković M, Vidaković M. Beneficial Effects of Probiotic Lactobacillus paraplantarum BGCG11 on Pancreatic and Duodenum Function in Diabetic Rats. Int J Mol Sci 2024; 25:7697. [PMID: 39062940 PMCID: PMC11277547 DOI: 10.3390/ijms25147697] [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: 06/04/2024] [Revised: 07/09/2024] [Accepted: 07/11/2024] [Indexed: 07/28/2024] Open
Abstract
Diabetes mellitus, as a chronic metabolic disorder, significantly impacts the pancreas and among other organs, affects duodenal function. Emerging evidence suggests that probiotics can exert beneficial effects on gut health and metabolism. In our previous research, we evaluated the probiotic Lactobacillus paraplantarum BGCG11 primarily for its protective properties against diabetic rats' damaged liver and kidneys. In this work, we further examined the effects of probiotic strain BGCG11 on the function of the duodenum and pancreas in diabetic rats. We explored the potential mechanisms underlying the probiotic's effects, focusing on general indicators of diabetes, the architecture and morphology of pancreatic islets, duodenal integrity (measuring the transfer of fluid and serum zonulin level), and the modulation of gut microbiota composition. Our findings reveal the protective and regulatory roles of L. paraplantarum BGCG11 in mitigating diabetes-induced pancreatic and duodenal dysfunction regardless of its application time (pre- or post-treatment), highlighting its therapeutic potential in managing diabetes-related gastrointestinal complications.
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Affiliation(s)
- Mirjana Mihailović
- Institute for Biological Research “Siniša Stanković”, University of Belgrade, Bulevar Despota Stefana 142, 10060 Belgrade, Serbia; (M.M.); (J.A.J.); (S.D.); (N.G.); (A.U.); (J.R.); (M.Đ.)
| | - Svetlana Soković Bajić
- Institute of Molecular Genetics and Genetics Engineering, University of Belgrade, Vojvode Stepe 444a, P.O. Box 23, 11010 Belgrade, Serbia (E.B.); (M.T.); (N.G.)
| | - Jelena Arambašić Jovanović
- Institute for Biological Research “Siniša Stanković”, University of Belgrade, Bulevar Despota Stefana 142, 10060 Belgrade, Serbia; (M.M.); (J.A.J.); (S.D.); (N.G.); (A.U.); (J.R.); (M.Đ.)
| | - Emilija Brdarić
- Institute of Molecular Genetics and Genetics Engineering, University of Belgrade, Vojvode Stepe 444a, P.O. Box 23, 11010 Belgrade, Serbia (E.B.); (M.T.); (N.G.)
| | - Svetlana Dinić
- Institute for Biological Research “Siniša Stanković”, University of Belgrade, Bulevar Despota Stefana 142, 10060 Belgrade, Serbia; (M.M.); (J.A.J.); (S.D.); (N.G.); (A.U.); (J.R.); (M.Đ.)
| | - Nevena Grdović
- Institute for Biological Research “Siniša Stanković”, University of Belgrade, Bulevar Despota Stefana 142, 10060 Belgrade, Serbia; (M.M.); (J.A.J.); (S.D.); (N.G.); (A.U.); (J.R.); (M.Đ.)
| | - Aleksandra Uskoković
- Institute for Biological Research “Siniša Stanković”, University of Belgrade, Bulevar Despota Stefana 142, 10060 Belgrade, Serbia; (M.M.); (J.A.J.); (S.D.); (N.G.); (A.U.); (J.R.); (M.Đ.)
| | - Jovana Rajić
- Institute for Biological Research “Siniša Stanković”, University of Belgrade, Bulevar Despota Stefana 142, 10060 Belgrade, Serbia; (M.M.); (J.A.J.); (S.D.); (N.G.); (A.U.); (J.R.); (M.Đ.)
| | - Marija Đorđević
- Institute for Biological Research “Siniša Stanković”, University of Belgrade, Bulevar Despota Stefana 142, 10060 Belgrade, Serbia; (M.M.); (J.A.J.); (S.D.); (N.G.); (A.U.); (J.R.); (M.Đ.)
| | - Maja Tolinački
- Institute of Molecular Genetics and Genetics Engineering, University of Belgrade, Vojvode Stepe 444a, P.O. Box 23, 11010 Belgrade, Serbia (E.B.); (M.T.); (N.G.)
| | - Nataša Golić
- Institute of Molecular Genetics and Genetics Engineering, University of Belgrade, Vojvode Stepe 444a, P.O. Box 23, 11010 Belgrade, Serbia (E.B.); (M.T.); (N.G.)
| | - Milica Živković
- Institute of Molecular Genetics and Genetics Engineering, University of Belgrade, Vojvode Stepe 444a, P.O. Box 23, 11010 Belgrade, Serbia (E.B.); (M.T.); (N.G.)
| | - Melita Vidaković
- Institute for Biological Research “Siniša Stanković”, University of Belgrade, Bulevar Despota Stefana 142, 10060 Belgrade, Serbia; (M.M.); (J.A.J.); (S.D.); (N.G.); (A.U.); (J.R.); (M.Đ.)
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Zhang Y, Huang A, Li J, Munthali W, Cao S, Putri UMP, Yang L. The Effect of Microbiome-Modulating Agents (MMAs) on Type 1 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients 2024; 16:1675. [PMID: 38892608 PMCID: PMC11174426 DOI: 10.3390/nu16111675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 05/24/2024] [Accepted: 05/27/2024] [Indexed: 06/21/2024] Open
Abstract
Gut microbiome-modulating agents (MMAs), including probiotics, prebiotics, postbiotics, and synbiotics, are shown to ameliorate type 1 diabetes (T1D) by restoring the microbiome from dysbiosis. The objective of this systematic review and meta-analysis was to assess the impact of MMAs on hemoglobin A1c (HbA1c) and biomarkers associated with (T1D). A comprehensive search was conducted in PubMed, Web of Science, Embase, Cochrane Library, National Knowledge Infrastructure, WeiPu, and WanFang Data up to 30 November 2023. Ten randomized controlled trials (n = 630) were included, with study quality evaluated using the Cochrane risk-of-bias tool. Random-effect models with standardized mean differences (SMDs) were utilized. MMA supplementation was associated with improvements in HbA1c (SMD = -0.52, 95% CI [-0.83, -0.20]), daily insulin usage (SMD = -0.41, 95% confidence interval (CI) [-0.76, -0.07]), and fasting C-peptide (SMD = 0.99, 95% CI [0.17, 1.81]) but had no effects on FBG, CRP, TNF-α, IL-10, LDL, HDL, and the Shannon index. Subgroup analysis of HbA1c indicated that a long-term intervention (>3 months) might exert a more substantial effect. These findings suggest an association between MMAs and glycemic control in T1D. Further large-scale clinical trials are necessary to confirm these findings with investigations on inflammation and gut microbiota composition while adjusting confounding factors such as diet, physical activity, and the dose and form of MMA intervention.
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Affiliation(s)
- Ying Zhang
- Xiangya School of Public Health, Central South University, Changsha 410128, China; (Y.Z.)
| | - Aiying Huang
- Department of Chemistry, University of Washington, Seattle, WA 98195, USA
| | - Jun Li
- School of Psychology, South China Normal University, Guangzhou 510631, China
| | - William Munthali
- Xiangya School of Public Health, Central South University, Changsha 410128, China; (Y.Z.)
| | - Saiying Cao
- Xiangya School of Public Health, Central South University, Changsha 410128, China; (Y.Z.)
| | | | - Lina Yang
- Xiangya School of Public Health, Central South University, Changsha 410128, China; (Y.Z.)
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11
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Sun Y, Wang Y, Lin Z, Zhang F, Zhang Y, Ren T, Wang L, Qiao Q, Shen M, Wang J, Song Y, Sun Y, Lin P. Irisin delays the onset of type 1 diabetes in NOD mice by enhancing intestinal barrier. Int J Biol Macromol 2024; 265:130857. [PMID: 38493812 DOI: 10.1016/j.ijbiomac.2024.130857] [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: 01/16/2024] [Revised: 03/11/2024] [Accepted: 03/12/2024] [Indexed: 03/19/2024]
Abstract
Type 1 diabetes (T1D), a complex autoimmune disease, is intricately linked to the gut's epithelial barrier function. Emerging evidence emphasizes the role of irisin, an exercise-related hormone, in preserving intestinal integrity. This study investigates whether irisin could delay T1D onset by enhancing the colon intestinal barrier. Impaired colon intestinal barriers were observed in newly diagnosed T1D patients and non-obese diabetic (NOD) mice, worsening with age and accompanied by islet inflammation. Using an LPS-induced colonic inflammation model, a dose-dependent impact of LPS on colon cells irisin expression, secretion, and barrier function was revealed. Exogenous irisin demonstrated remarkable effects, mitigating islet insulitis, enhancing energy expenditure, and alleviating autoimmune symptoms by reducing colon intestinal permeability. Single-cell RNA sequencing (scRNA-seq) highlighted irisin's positive impact on colon epithelial cell clusters, effectively restoring the intestinal barrier. Irisin also selectively modulated bacterial composition, averting potential bacterial translocation. Mechanistically, irisin enhanced colon intestinal barrier tight junction proteins through the AMPK/PI3K/AKT pathway, with FAM120A playing a crucial role. Irisin upregulated MUC3 expression, a protector against damage and inflammation. Harnessing irisin's exercise-mimicking properties suggests therapeutic potential in clinical settings for preventing T1D progression, offering valuable insights into fortifying the colon's intestinal barrier and managing autoimmune conditions associated with T1DM.
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Affiliation(s)
- Yujing Sun
- Department of Endocrine and Metabolic Diseases, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China; Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine and Health, Jinan, Shandong 250012, China; Jinan Clinical Research Center for Endocrine and Metabolic Disease, Jinan, Shandong 250012, China
| | - Yilin Wang
- Department of Orthopedics and Traumatology, Peking University People's Hospital, Beijing, China
| | - Ziang Lin
- Qilu Hospital of Shandong University, Jinan, 250012, Shandong Province, China
| | - Fuhua Zhang
- Department of Endocrine and Metabolic Diseases, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Yan Zhang
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Tongxin Ren
- Department of Endocrine and Metabolic Diseases, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Lina Wang
- Department of Endocrine and Metabolic Diseases, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Qincheng Qiao
- Department of Endocrine and Metabolic Diseases, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Mengyang Shen
- Department of Endocrine and Metabolic Diseases, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China; Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine and Health, Jinan, Shandong 250012, China; Jinan Clinical Research Center for Endocrine and Metabolic Disease, Jinan, Shandong 250012, China
| | - Juncheng Wang
- Advanced Medical Research Institute, Meili Lake Translational Research Park, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China
| | - Youchen Song
- Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
| | - Yu Sun
- Department of Endocrine and Metabolic Diseases, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China; Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine and Health, Jinan, Shandong 250012, China; Jinan Clinical Research Center for Endocrine and Metabolic Disease, Jinan, Shandong 250012, China.
| | - Peng Lin
- Department of Endocrine and Metabolic Diseases, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China; Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine and Health, Jinan, Shandong 250012, China; Jinan Clinical Research Center for Endocrine and Metabolic Disease, Jinan, Shandong 250012, China.
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12
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Ping Y, Liu J, Wang L, Qiu H, Zhang Y. Research progress on the mechanism of TCM regulating intestinal microbiota in the treatment of DM mellitus. Front Endocrinol (Lausanne) 2024; 15:1308016. [PMID: 38601207 PMCID: PMC11004430 DOI: 10.3389/fendo.2024.1308016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Accepted: 03/12/2024] [Indexed: 04/12/2024] Open
Abstract
In recent years, with the improvement of people's living standards, the incidence of DM has increased year by year in China. DM is a common metabolic syndrome characterized by hyperglycemia caused by genetic, environmental and other factors. At the same time, long-term suffering from DM will also have an impact on the heart, blood vessels, eyes, kidneys and nerves, and associated serious diseases. The human body has a large and complex gut microbiota, which has a significant impact on the body's metabolism. Research shows that the occurrence and development of DM and its complications are closely related to intestinal microbiota. At present, western medicine generally treats DM with drugs. The hypoglycemic effect is fast and strong, but it can have a series of side effects on the human body. Compared with western medicine, Chinese medicine has its unique views and methods in treating DM. TCM can improve symptoms and treat complications by improving the imbalance of microbiota in patients with DM. Its characteristics of health, safety, and reliability are widely accepted by the general public. This article reviews the relationship between intestinal microbiota and DM, as well as the mechanism of TCM intervention in DM by regulating intestinal microbiota.
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Affiliation(s)
- Yang Ping
- College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang, China
- Heilongjiang Pharmaceutical Research Institute, Jiamusi, Heilongjiang, China
| | - Jianing Liu
- College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang, China
| | - Lihong Wang
- College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang, China
| | - Hongbin Qiu
- College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang, China
| | - Yu Zhang
- College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang, China
- Heilongjiang Pharmaceutical Research Institute, Jiamusi, Heilongjiang, China
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13
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Peng J, Lu C, Luo Y, Su X, Li S, Ho CT. Hypoglycemic effects and associated mechanisms of resveratrol and related stilbenes in diet. Food Funct 2024; 15:2381-2405. [PMID: 38376230 DOI: 10.1039/d3fo04761j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2024]
Abstract
Hyperglycemia has become a global health problem due to changes in diet and lifestyle. Most importantly, persistent hyperglycemia can eventually develop into type II diabetes. While the usage of current drugs is limited by their side effects, stilbenes derived from fruits and herbal/dietary plants are considered as important phytochemicals with potential hypoglycemic properties. Herein, the most common stilbenoids in consumed foods, i.e. resveratrol, pterostilbene, piceatannol, oxyresveratrol, and 2,3,5,4'-tetrahydroxystilbene-2-O-β-glucopyranoside (THSG), are reviewed in this paper. These stilbenes are found to regulate glucose homeostasis via (a) modulation of feeding behaviour and nutrition absorption; (b) restoration of insulin signalling by enhancing insulin production/insulin sensitivity; (c) improvement of gut permeability, gut microbial profile and resulting metabolomes; and (d) amelioration of circadian rhythm disruption. In this review, we have summarized the underlying mechanisms for the hypoglycemic effects of the five most common dietary stilbenoids listed above, providing a comprehensive framework for future study and applications.
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Affiliation(s)
- Jie Peng
- Department of Food Science, Rutgers University, New Brunswick 08901, USA
| | - Chenyang Lu
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products and School of Marine Science, Ningbo University, Ningbo 315211, China.
| | - Yue Luo
- Department of Food Science, Rutgers University, New Brunswick 08901, USA
| | - Xiurong Su
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products and School of Marine Science, Ningbo University, Ningbo 315211, China.
| | - Shiming Li
- Department of Food Science, Rutgers University, New Brunswick 08901, USA
- College of Life Sciences, Huanggang Normal University, Hubei 438000, China
| | - Chi-Tang Ho
- Department of Food Science, Rutgers University, New Brunswick 08901, USA
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14
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Gajecka M, Gutaj P, Jaskiewicz K, Rydzanicz M, Szczapa T, Kaminska D, Kosewski G, Przyslawski J, Ploski R, Wender-Ozegowska E. Effects of maternal type 1 diabetes and confounding factors on neonatal microbiomes. Diabetologia 2024; 67:312-326. [PMID: 38030736 PMCID: PMC10789840 DOI: 10.1007/s00125-023-06047-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 10/02/2023] [Indexed: 12/01/2023]
Abstract
AIMS/HYPOTHESIS Body niche-specific microbiota in maternal-neonatal dyads from gravidae with type 1 diabetes have not been quantitatively and functionally examined. Similarly, the impact of pregnancy-specific factors, such as the presence of comorbidities known to occur more frequently among gravidae with type 1 diabetes, including Caesarean delivery, as well as antibiotic prophylaxis, level of glycaemic control during each trimester of pregnancy and insulin administration, has not been adequately considered. The aims of this study were to characterise the maternal and neonatal microbiomes, assess aspects of microbiota transfer from the maternal microbiomes to the neonatal microbiome and explore the impact of type 1 diabetes and confounding factors on the microbiomes. METHODS In this observational case-control study, we characterised microbiome community composition and function using 16S rRNA amplicon sequencing in a total of 514 vaginal, rectal and ear-skin swabs and stool samples derived from 92 maternal-neonatal dyads (including 50 gravidae with type 1 diabetes) and in-depth clinical metadata from throughout pregnancy and delivery. RESULTS Type 1 diabetes-specific microbiota were identified among gravidae with type 1 diabetes and their neonates. Neonatal microbiome profiles of ear-skin swabs and stool samples were established, indicating the taxa more prevalent among neonates born to mothers with type 1 diabetes compared with neonates born to control mothers. Without taking into account the type 1 diabetes status of mothers, both delivery mode and intrapartum antibiotic prophylaxis were found to have an influence on neonatal microbiota composition (both p=0.001). In the logistic regression analysis involving all confounding variables, neonatal ear-skin microbiome variation was explained by maternal type 1 diabetes status (p=0.020) and small for gestational age birthweight (p=0.050). Moreover, in women with type 1 diabetes, a relationship was found between HbA1c levels >55 mmol/mol (>7.2%) measured in the first trimester of pregnancy and neonatal ear-skin microbiota composition (p=0.008). In the PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) assessment, pathways concerning carbohydrate biosynthesis were predicted as key elements of the microbial functional profiles dysregulated in type 1 diabetes. Additionally, in SourceTracker analysis, we found that, on average, 81.0% of neonatal microbiota was attributed to maternal sources. An increase in the contribution of maternal rectum microbiota and decrease in the contribution of maternal cervix microbiota were found in ear-skin samples of vaginally delivered neonates of mothers with type 1 diabetes compared with neonates born to control mothers (83.2% vs 59.5% and 0.7% vs 5.2%, respectively). CONCLUSIONS/INTERPRETATION These findings indicate that, in addition to maternal type 1 diabetes, glycaemic dysregulation before/in the first trimester of pregnancy, mode of delivery and intrapartum antibiotic prophylaxis may contribute to the inoculation and formation of the neonatal microbiomes. DATA AVAILABILITY The BioProject (PRJNA961636) and associated SRA metadata are available at http://www.ncbi.nlm.nih.gov/bioproject/961636 . Processed data on probiotic supplementation and the PICRUSt analysis are available in the Mendeley Data Repository ( https://doi.org/10.17632/g68rwnnrfk.1 ).
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Affiliation(s)
- Marzena Gajecka
- Chair and Department of Genetics and Pharmaceutical Microbiology, Poznan University of Medical Sciences, Poznan, Poland.
- Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
| | - Pawel Gutaj
- Department of Reproduction, Poznan University of Medical Sciences, Poznan, Poland
| | | | | | - Tomasz Szczapa
- Department of Neonatology, Poznan University of Medical Sciences, Poznan, Poland
| | - Dorota Kaminska
- Chair and Department of Genetics and Pharmaceutical Microbiology, Poznan University of Medical Sciences, Poznan, Poland
| | - Grzegorz Kosewski
- Chair and Department of Bromatology, Poznan University of Medical Sciences, Poznan, Poland
| | - Juliusz Przyslawski
- Chair and Department of Bromatology, Poznan University of Medical Sciences, Poznan, Poland
| | - Rafal Ploski
- Department of Medical Genetics, Medical University of Warsaw, Warsaw, Poland
| | - Ewa Wender-Ozegowska
- Department of Reproduction, Poznan University of Medical Sciences, Poznan, Poland
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15
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Jeong H, Park YS, Yoon SS. A2 milk consumption and its health benefits: an update. Food Sci Biotechnol 2024; 33:491-503. [PMID: 38274187 PMCID: PMC10806982 DOI: 10.1007/s10068-023-01428-5] [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: 07/05/2023] [Revised: 08/26/2023] [Accepted: 08/30/2023] [Indexed: 01/27/2024] Open
Abstract
Milk is a widely consumed nutrient-rich food containing protein variants such as casein A2 and A1. A1 differs from A2 in an amino acid at position 67 (Pro67 to His67). The breakdown of β-casein yields β-casomorphins (BCM), among which BCM-7 is extensively studied for its effects on the human body. Animal studies have shown that A1 β-casein milk increases digestive transit time and enhances myeloperoxidase activity. Individuals with lactose intolerance prefer A2 milk to conventional A1 milk, as BCM-7 in A1 milk can lead to inflammation and discomfort in sensitive individuals. A2 milk, which contains A2 β-casein, is believed to be more easily digestible than A1 β-casein. Its popularity has grown owing to reports linking A1 casein to diseases such as type 1 diabetes, heart disease, and autism. A2 milk has gained popularity as an alternative to A1 milk, primarily because of its potential benefits for individuals with certain diseases. This review aims to provide an updated understanding of A2 milk consumption and its health benefits. This review aims to provide an updated understanding of A2 milk consumption and its health benefits.
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Affiliation(s)
- Huijin Jeong
- Department of Food Science and Biotechnology, Gachon University, Seongnam, 13120 Republic of Korea
| | - Young-Seo Park
- Department of Food Science and Biotechnology, Gachon University, Seongnam, 13120 Republic of Korea
| | - Sung-Sik Yoon
- Division of Biological Science and Technology, Yonsei University, Wonju, 26493 Republic of Korea
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16
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DaFonte TM, Valitutti F, Kenyon V, Locascio JJ, Montuori M, Francavilla R, Passaro T, Crocco M, Norsa L, Piemontese P, Baldassarre M, Fasano A, Leonard MM. Zonulin as a Biomarker for the Development of Celiac Disease. Pediatrics 2024; 153:e2023063050. [PMID: 38062791 PMCID: PMC10754681 DOI: 10.1542/peds.2023-063050] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/17/2023] [Indexed: 12/31/2023] Open
Abstract
OBJECTIVES Increased intestinal permeability seems to be a key factor in the pathogenesis of autoimmune diseases, including celiac disease (CeD). However, it is unknown whether increased permeability precedes CeD onset. This study's objective was to determine whether intestinal permeability is altered before celiac disease autoimmunity (CDA) in at-risk children. We also examined whether environmental factors impacted zonulin, a widely used marker of gut permeability. METHODS We evaluated 102 children in the CDGEMM study from 2014-2022. We included 51 CDA cases and matched controls, who were enrolled for 12 months or more and consumed gluten. We measured serum zonulin from age 12 months to time of CDA onset, and the corresponding time point in controls, and examined clinical factors of interest. We ran a mixed-effects longitudinal model with dependent variable zonulin. RESULTS Children who developed CDA had a significant increase in zonulin in the 18.3 months (range 6-78) preceding CDA compared to those without CDA (slope differential = β = 0.1277, 95% CI: 0.001, 0.255). Among metadata considered, zonulin trajectory was only influenced by increasing number of antibiotic courses, which increased the slope of trajectory of zonulin over time in CDA subjects (P = .04). CONCLUSIONS Zonulin levels significantly rise in the months that precede CDA diagnosis. Exposure to a greater number of antibiotic courses was associated with an increase in zonulin levels in CDA subjects. This suggests zonulin may be used as a biomarker for preclinical CeD screening in at-risk children, and multiple antibiotic courses may increase their risk of CDA by increasing zonulin levels.
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Affiliation(s)
- Tracey M. DaFonte
- Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, MassGeneral Hospital for Children, Harvard Medical School, Boston, Massachusetts
- Mucosal Immunology and Biology Research Center
- Center for Celiac Research and Treatment
| | | | - Victoria Kenyon
- Mucosal Immunology and Biology Research Center
- Center for Celiac Research and Treatment
| | - Joseph J. Locascio
- Departments of Biostatistics, Harvard Catalyst Biostatistical Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA
- Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Monica Montuori
- Pediatric Gastroenterology Unit, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
| | - Ruggiero Francavilla
- Pediatric Unit “Bruno Trambusti,” Osp Pediatrico Giovanni XXIII, University of Bari, Bari, Italy
| | - Tiziana Passaro
- Celiac Disease Referral Center, “San Giovanni di Dio e Ruggi d’Aragona” University Hospital, Pole of Cava de' Tirreni, Salerno, Italy
| | - Marco Crocco
- Pediatrics, IRCCS Ospedale Giannina Gaslini, Genova, Italy
| | - Lorenzo Norsa
- Pediatric Hepatology, Gastroenterology, and Transplant Unit, Ospedale Papa Giovanni XXIII, Bergamo, Italy
| | - Pasqua Piemontese
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
| | | | - Alessio Fasano
- Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, MassGeneral Hospital for Children, Harvard Medical School, Boston, Massachusetts
- Mucosal Immunology and Biology Research Center
- Center for Celiac Research and Treatment
- European Biomedical Research Institute of Salerno (EBRIS), Salerno, Italy
| | - Maureen M. Leonard
- Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, MassGeneral Hospital for Children, Harvard Medical School, Boston, Massachusetts
- Mucosal Immunology and Biology Research Center
- Center for Celiac Research and Treatment
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17
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Guo J, Zhou B, Niu Y, Liu L, Yang L. Engineered probiotics introduced to improve intestinal microecology for the treatment of chronic diseases: present state and perspectives. J Diabetes Metab Disord 2023; 22:1029-1038. [PMID: 37975092 PMCID: PMC10638336 DOI: 10.1007/s40200-023-01279-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Accepted: 08/05/2023] [Indexed: 11/19/2023]
Abstract
Purpose Correcting intestinal microecological imbalance has become one of the core strategies to treat chronic diseases. Some traditional microecology-based therapies targeting intestine, such as prebiotic therapy, probiotic therapy and fecal microbiota transplantation therapy, have been used in the prevention and treatment of clinical chronic diseases, which still facing low safety and poor controllability problems. The development of synthetic biology technology has promoted the development of intestinal microecology-based therapeutics for chronic diseases, which exhibiting higher robustness and controllability, and become an important part of the next generation of microecological therapy. The purpose of this review is to summarize the application of synthetic biology in intestinal microecology-based therapeutics for chronic diseases. Methods The available literatures were searched to find out experimental studies and relevant review articles on the application of synthetic biology in intestinal microecology-based therapeutics for chronic diseases from year 1990 to 2023. Results Evidence proposed that synthetic biology has been applied in the intestinal microecology-based therapeutics for chronic diseases, covering metabolic diseases (e.g. diabetes, obesity, nonalcoholic fatty liver disease and phenylketonuria), digestive diseases (e.g. inflammatory bowel disease and colorectal cancer), and neurodegenerative diseases (e.g. Alzheimer's disease and Parkinson's disease). Conclusion This review summarizes the application of synthetic biology in intestinal microecology-based therapeutics for major chronic diseases and discusses the opportunities and challenges in the above process, providing clinical possibilities of synthetic biology technology applied in microecological therapies.
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Affiliation(s)
- Jianquan Guo
- Key Laboratory of Coal Environmental Pathogenicity and Prevention, (Shanxi Medical University), Ministry of Education, Taiyuan, PR China
- School of Public Health, Shanxi Medical University, Taiyuan, 030001 Shanxi PR China
| | - Bangyuan Zhou
- School of Public Health, Shanxi Medical University, Taiyuan, 030001 Shanxi PR China
| | - Yali Niu
- School of Public Health, Shanxi Medical University, Taiyuan, 030001 Shanxi PR China
| | - Liangpo Liu
- School of Public Health, Shanxi Medical University, Taiyuan, 030001 Shanxi PR China
| | - Liyang Yang
- School of Basic Medical Sciences, Shanxi University of Chinese Medicine, 030619 Jinzhong, PR China
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18
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Xin Y, Huang C, Zheng M, Zhou W, Zhang B, Zhao M, Lu Q. Fecal microbiota transplantation in the treatment of systemic lupus erythematosus: What we learnt from the explorative clinical trial. J Autoimmun 2023; 141:103058. [PMID: 37179170 DOI: 10.1016/j.jaut.2023.103058] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 04/26/2023] [Accepted: 05/03/2023] [Indexed: 05/15/2023]
Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease with the characterized presence of autoantibodies and resulting in multiple organ damage, which is incurable and can be lethal. The current treatments are limited and less progress has been made in drug discovery for the last few decades. Researches imply that gut dysbiosis exists in both patients and murine models with SLE, taking part in the pathogenesis of SLE through multiple mechanisms such as microbiota translocation and molecular mimicry. Intestinal interventions on the gut microbiome by fecal transplantations to reconstitute the gut-immunity homeostasis serve as a novel therapeutic option for SLE patients. Fecal microbiota transplantation (FMT), which is usually used in intestinal diseases, has been firstly demonstrated to be safe and efficient in recovering gut microbiota structure of SLE patients and reducing lupus activity in our recent clinical trial, which is the first trial testing FMT therapy in SLE treatment. In this paper, we reviewed the results of the single-arm clinical trial and made recommendations on FMT practice in SLE treatment including therapeutic indications, screening items and dosage regimen, trying to provide references for future study and clinical practice. We also came up with the unanswered questions that need to be solved by the ongoing randomized controlled trial as well as the future expectations for the intestinal intervention strategies of SLE patients.
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Affiliation(s)
- Yue Xin
- Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China; Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, China
| | - Cancan Huang
- Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Meiling Zheng
- Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Wenhui Zhou
- Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Bo Zhang
- Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China; Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, China
| | - Ming Zhao
- Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China; Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, China; Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, Second Xiangya Hospital, Central South University, Changsha, 410011, China.
| | - Qianjin Lu
- Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China; Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, China; Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, Second Xiangya Hospital, Central South University, Changsha, 410011, China.
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19
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Ma MH, Gao LL, Chen CB, Gu FL, Wu SQ, Li F, Han BX. Dendrobium huoshanense Polysaccharide Improves High-Fat Diet Induced Liver Injury by Regulating the Gut-Liver Axis. Chem Biodivers 2023; 20:e202300980. [PMID: 37831331 DOI: 10.1002/cbdv.202300980] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 10/04/2023] [Accepted: 10/11/2023] [Indexed: 10/14/2023]
Abstract
Dendrobium huoshanense is an important Traditional Chinese medicine that thickens the stomach and intestines. Its active ingredient Dendrobium huoshanense polysaccharide (DHP), was revealed to relieve the symptoms of liver injury. However, its mechanism of action remains poorly understood. This study aimed to investigate the mechanism of DHP in protecting the liver. The effects of DHP on lipid levels, liver function, and intestinal barrier function were investigated in mice with high-fat diet-induced liver damage. Changes in the gut flora and their metabolites were analyzed using 16S rRNA sequencing and metabolomics. The results showed that DHP reduced lipid levels, liver injury, and intestinal permeability. DHP altered the intestinal flora structure and increased the relative abundance of Bifidobacterium animalis and Clostridium disporicum. Furthermore, fecal metabolomics revealed that DHP altered fecal metabolites and significantly increased levels of gut-derived metabolites, spermidine, and indole, which have been reported to inhibit liver injury and improve lipid metabolism and the intestinal barrier. Correlation analysis showed that spermidine and indole levels were significantly negatively correlated with liver injury-related parameters and positively correlated with the intestinal species B. animalis enriched by DHP. Overall, this study confirmed that DHP prevented liver injury by regulating intestinal microbiota dysbiosis and fecal metabolites.
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Affiliation(s)
- Meng-Hua Ma
- Traditional Chinese Medicine Institute of Anhui Dabie Mountain, West Anhui University, Lu'an City, 237012, China
- College of Biology and Pharmaceutical Engineering, West Anhui University, Lu'an City, 237012, China
- Anhui Engineering Research Center for Eco-agriculture of Traditional Chinese Medicine, Lu'an City, 237012, China
| | - Lei-Lei Gao
- Traditional Chinese Medicine Institute of Anhui Dabie Mountain, West Anhui University, Lu'an City, 237012, China
- College of Biology and Pharmaceutical Engineering, West Anhui University, Lu'an City, 237012, China
| | - Chuang-Bo Chen
- College of Biology and Pharmaceutical Engineering, West Anhui University, Lu'an City, 237012, China
| | - Fang-Li Gu
- Traditional Chinese Medicine Institute of Anhui Dabie Mountain, West Anhui University, Lu'an City, 237012, China
| | - Si-Qi Wu
- College of Biology and Pharmaceutical Engineering, West Anhui University, Lu'an City, 237012, China
| | - Fang Li
- College of Biology and Pharmaceutical Engineering, West Anhui University, Lu'an City, 237012, China
| | - Bang-Xing Han
- Traditional Chinese Medicine Institute of Anhui Dabie Mountain, West Anhui University, Lu'an City, 237012, China
- College of Biology and Pharmaceutical Engineering, West Anhui University, Lu'an City, 237012, China
- Anhui Engineering Research Center for Eco-agriculture of Traditional Chinese Medicine, Lu'an City, 237012, China
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20
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Veneti S, Grammatikopoulou MG, Kintiraki E, Mintziori G, Goulis DG. Ketone Bodies in Diabetes Mellitus: Friend or Foe? Nutrients 2023; 15:4383. [PMID: 37892458 PMCID: PMC10609881 DOI: 10.3390/nu15204383] [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: 09/18/2023] [Revised: 10/12/2023] [Accepted: 10/14/2023] [Indexed: 10/29/2023] Open
Abstract
In glucose-deprived conditions, ketone bodies are produced by the liver mitochondria, through the catabolism of fatty acids, and are used peripherally, as an alternative energy source. Ketones are produced in the body under normal conditions, including during pregnancy and the neonatal period, when following a ketogenic diet (KD), fasting, or exercising. Additionally, ketone synthesis is also augmented under pathological conditions, including cases of diabetic ketoacidosis (DKA), alcoholism, and several metabolic disorders. Nonetheless, diet is the main regulator of total body ketone concentrations. The KDs are mimicking the fasting state, altering the default metabolism towards the use of ketones as the primary fuel source. Recently, KD has gained recognition as a medical nutrition therapy for a plethora of metabolic conditions, including obesity and diabetes mellitus (DM). The present review aims to discuss the role of ketones, KDs, ketonemia, and ketonuria in DM, presenting all the available new evidence in a comprehensive manner.
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Affiliation(s)
- Stavroula Veneti
- Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece; (S.V.); (E.K.)
| | - Maria G. Grammatikopoulou
- Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece; (S.V.); (E.K.)
- Unit of Immunonutrition and Clinical Nutrition, Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, GR-41110 Larissa, Greece
| | - Evangelia Kintiraki
- Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece; (S.V.); (E.K.)
| | - Gesthimani Mintziori
- Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece; (S.V.); (E.K.)
| | - Dimitrios G. Goulis
- Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece; (S.V.); (E.K.)
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21
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Berryman MA, Ilonen J, Triplett EW, Ludvigsson J. Important denominator between autoimmune comorbidities: a review of class II HLA, autoimmune disease, and the gut. Front Immunol 2023; 14:1270488. [PMID: 37828987 PMCID: PMC10566625 DOI: 10.3389/fimmu.2023.1270488] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Accepted: 09/11/2023] [Indexed: 10/14/2023] Open
Abstract
Human leukocyte antigen (HLA) genes are associated with more diseases than any other region of the genome. Highly polymorphic HLA genes produce variable haplotypes that are specifically correlated with pathogenically different autoimmunities. Despite differing etiologies, however, many autoimmune disorders share the same risk-associated HLA haplotypes often resulting in comorbidity. This shared risk remains an unanswered question in the field. Yet, several groups have revealed links between gut microbial community composition and autoimmune diseases. Autoimmunity is frequently associated with dysbiosis, resulting in loss of barrier function and permeability of tight junctions, which increases HLA class II expression levels and thus further influences the composition of the gut microbiome. However, autoimmune-risk-associated HLA haplotypes are connected to gut dysbiosis long before autoimmunity even begins. This review evaluates current research on the HLA-microbiome-autoimmunity triplex and proposes that pre-autoimmune bacterial dysbiosis in the gut is an important determinant between autoimmune comorbidities with systemic inflammation as a common denominator.
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Affiliation(s)
- Meghan A. Berryman
- Triplett Laboratory, Institute of Food and Agricultural Sciences, Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, United States
| | - Jorma Ilonen
- Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland
| | - Eric W. Triplett
- Triplett Laboratory, Institute of Food and Agricultural Sciences, Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, United States
| | - Johnny Ludvigsson
- Crown Princess Victoria’s Children’s Hospital and Division of Pediatrics, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
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22
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Kwain S, Dominy BN, Whitehead KJ, Miller BA, Whitehead DC. Exploring the interactive mechanism of acarbose with the amylase SusG in the starch utilization system of the human gut symbiont Bacteroides thetaiotaomicron through molecular modeling. Chem Biol Drug Des 2023; 102:486-499. [PMID: 37062591 DOI: 10.1111/cbdd.14251] [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: 01/24/2023] [Revised: 03/15/2023] [Accepted: 04/04/2023] [Indexed: 04/18/2023]
Abstract
The α-amylase, SusG, is a principal component of the Bacteroides thetaiotaomicron (Bt) starch utilization system (Sus) used to metabolize complex starch molecules in the human gastrointestinal (GI) tract. We previously reported the non-microbicidal growth inhibition of Bt by the acarbose-mediated arrest of the Sus as a potential therapeutic strategy. Herein, we report a computational approach using density functional theory (DFT), molecular docking, and molecular dynamics (MD) simulation to explore the interactive mechanism between acarbose and SusG at the atomic level in an effort to understand how acarbose shuts down the Bt Sus. The docking analysis reveals that acarbose binds orthosterically to SusG with a binding affinity of -8.3 kcal/mol. The MD simulation provides evidence of conformational variability of acarbose at the active site of SusG and also suggests that acarbose interacts with the main catalytic residues via a general acid-base double-displacement catalytic mechanism. These results suggest that small molecule competitive inhibition against the SusG protein could impact the entire Bt Sus and eliminate or reduce the system's ability to metabolize starch. This computational strategy could serve as a potential avenue for structure-based drug design to discover other small molecules capable of inhibiting the Sus of Bt with high potency, thus providing a holistic approach for selective modulation of the GI microbiota.
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Affiliation(s)
- Samuel Kwain
- Department of Chemistry, Clemson University, Clemson, South Carolina, USA
| | - Brian N Dominy
- Department of Chemistry, Clemson University, Clemson, South Carolina, USA
| | - Kristi J Whitehead
- Department of Biological Sciences, Clemson University, Clemson, South Carolina, USA
| | - Brock A Miller
- Department of Chemistry, Clemson University, Clemson, South Carolina, USA
| | - Daniel C Whitehead
- Department of Chemistry, Clemson University, Clemson, South Carolina, USA
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23
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Wei L, Ji L, Miao Y, Han X, Li Y, Wang Z, Fu J, Guo L, Su Y, Zhang Y. Constipation in DM are associated with both poor glycemic control and diabetic complications: Current status and future directions. Biomed Pharmacother 2023; 165:115202. [PMID: 37506579 DOI: 10.1016/j.biopha.2023.115202] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Revised: 07/15/2023] [Accepted: 07/18/2023] [Indexed: 07/30/2023] Open
Abstract
Constipation is a major complications of diabetes mellitus. With the accelerating prevalence of diabetes worldwide and an aging population, there is considerable research interest regarding the altered function and structure of the gastrointestinal tract in diabetic patients. Despite current advances in hyperglycemic treatment strategies, the specific pathogenesis of diabetic constipation remains unknown. Patients with constipation, may be reluctant to eat regularly, which may worsen glycemic control and thus worsen symptoms associated with underlying diabetic bowel disease. This paper presents a review of the complex relationship between diabetes and constipation, exploring the morphological alterations and biomechanical remodeling associated with intestinal motility dysfunction, as well as alterations in intestinal neurons, cellular signaling pathways, and oxidative stress. Further studies focusing on new targets that may play a role in the pathogenesis of diabetic constipation may, provide new ideas for the development of novel therapies to treat or even prevent diabetic constipation.
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Affiliation(s)
- Luge Wei
- Tianjin University of Traditional Chinese Medicine, China.
| | - Lanqi Ji
- Tianjin University of Traditional Chinese Medicine, China
| | - Yulu Miao
- Tianjin University of Traditional Chinese Medicine, China
| | - Xu Han
- Tianjin University of Traditional Chinese Medicine, China
| | - Ying Li
- Tianjin University of Traditional Chinese Medicine, China
| | - Zhe Wang
- Tianjin University of Traditional Chinese Medicine, China
| | - Jiafeng Fu
- Tianjin University of Traditional Chinese Medicine, China
| | - Liuli Guo
- Tianjin University of Traditional Chinese Medicine, China
| | - Yuanyuan Su
- Tianjin University of Traditional Chinese Medicine, China
| | - Yanjun Zhang
- Tianjin University of Traditional Chinese Medicine, China; First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, China
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24
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Koivusaari K, Niinistö S, Nevalainen J, Honkanen J, Ruohtula T, Koreasalo M, Ahonen S, Åkerlund M, Tapanainen H, Siljander H, Miettinen ME, Alatossava T, Ilonen J, Vaarala O, Knip M, Virtanen SM. Infant Feeding, Gut Permeability, and Gut Inflammation Markers. J Pediatr Gastroenterol Nutr 2023; 76:822-829. [PMID: 36913717 DOI: 10.1097/mpg.0000000000003756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/15/2023]
Abstract
OBJECTIVES Increased gut permeability and gut inflammation have been linked to the development of type 1 diabetes. Little is known on whether and how intake of different foods is linked to these mechanisms in infancy. We investigated whether the amount of breast milk and intake of other foods are associated with gut inflammation marker concentrations and permeability. METHODS Seventy-three infants were followed from birth to 12 months of age. Their diet was assessed with structured questionnaires and 3-day weighed food records at the age of 3, 6, 9, and 12 months. Gut permeability was assessed with the lactulose/mannitol test and fecal calprotectin and human β-defensin-2 (HBD-2) concentrations were analyzed from stool samples at the age of 3, 6, 9, and 12 months. The associations between foods and gut inflammation marker concentrations and permeability were analyzed using generalized estimating equations. RESULTS Gut permeability and gut inflammation marker concentrations decreased during the first year of life. Intake of hydrolyzed infant formula ( P = 0.003) and intake of fruits and juices ( P = 0.001) were associated with lower intestinal permeability. Intake of fruits and juices ( P < 0.001), vegetables ( P < 0.001), and oats ( P = 0.003) were associated with lower concentrations of HBD-2. Higher intake of breast milk was associated with higher fecal calprotectin concentrations ( P < 0.001), while intake of fruits and juices ( P < 0.001), vegetables ( P < 0.001), and potatoes ( P = 0.007) were associated with lower calprotectin concentrations. CONCLUSIONS Higher intake of breast milk may contribute to higher calprotectin concentration, whereas several complementary foods may decrease gut permeability and concentrations of calprotectin and HBD-2 in infant gut.
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Affiliation(s)
- Katariina Koivusaari
- From the Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland
- the Department of Food and Nutrition, University of Helsinki, Helsinki, Finland
| | - Sari Niinistö
- From the Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Jaakko Nevalainen
- the Faculty of Social Sciences, Unit of Health Sciences, Tampere University, Tampere, Finland
| | - Jarno Honkanen
- the Research Program for Translational Immunology, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Terhi Ruohtula
- the Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Mirva Koreasalo
- From the Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Suvi Ahonen
- From the Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Mari Åkerlund
- From the Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Heli Tapanainen
- From the Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Heli Siljander
- From the Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Maija E Miettinen
- From the Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Tapani Alatossava
- the Department of Food and Nutrition, University of Helsinki, Helsinki, Finland
| | - Jorma Ilonen
- the Immunogenetics Laboratory, University of Turku, Turku, Finland
| | - Outi Vaarala
- the Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Mikael Knip
- From the Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Suvi M Virtanen
- From the Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland
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25
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Tan X, Wang Y, Gong T. The interplay between oral microbiota, gut microbiota and systematic diseases. J Oral Microbiol 2023; 15:2213112. [PMID: 37200866 PMCID: PMC10187086 DOI: 10.1080/20002297.2023.2213112] [Citation(s) in RCA: 43] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 05/02/2023] [Accepted: 05/08/2023] [Indexed: 05/20/2023] Open
Abstract
Over the past two decades, the importance of microbiota in health and disease has become evident. The human gut microbiota and oral microbiota are the largest and second-largest microbiome in the human body, respectively, and they are physically connected as the oral cavity is the beginning of the digestive system. Emerging and exciting evidence has shown complex and important connections between gut microbiota and oral microbiota. The interplay of the two microbiomes may contribute to the pathological processes of many diseases, including diabetes, rheumatoid arthritis, nonalcoholic fatty liver disease, inflammatory bowel disease, pancreatic cancer, colorectal cancer, and so on. In this review, we discuss possible routes and factors of oral microbiota to affect gut microbiota, and the contribution of this interplay between oral and gut microbiota to systemic diseases. Although most studies are association studies, recently, there have been increasing mechanistic investigations. This review aims to enhance the interest in the connection between oral and gut microbiota, and shows the tangible impact of this connection on human health.
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Affiliation(s)
- Xiujun Tan
- Stomatological Hospital of Chongqing Medical University, Chongqing, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China
| | - Yizhong Wang
- Department of Research & Development, Zhejiang Charioteer Pharmaceutical CO. LTD, Taizhou, China
| | - Ting Gong
- Stomatological Hospital of Chongqing Medical University, Chongqing, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China
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26
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Lo Conte M, Cosorich I, Ferrarese R, Antonini Cencicchio M, Nobili A, Palmieri V, Massimino L, Lamparelli LA, Liang W, Riba M, Devecchi E, Bolla AM, Pedone E, Scavini M, Bosi E, Fasano A, Ungaro F, Diana J, Mancini N, Falcone M. Alterations of the intestinal mucus layer correlate with dysbiosis and immune dysregulation in human Type 1 Diabetes. EBioMedicine 2023; 91:104567. [PMID: 37062177 PMCID: PMC10139895 DOI: 10.1016/j.ebiom.2023.104567] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 03/09/2023] [Accepted: 03/30/2023] [Indexed: 04/18/2023] Open
Abstract
BACKGROUND In preclinical models of Type 1 Diabetes (T1D) the integrity of the gut barrier (GB) is instrumental to avoid dysregulated crosstalk between the commensal microbiota and immune cells and to prevent autoimmunity. The GB is composed of the intestinal epithelial barrier (IEB) and of the mucus layer containing mucins and antimicrobial peptides (AMPs) that are crucial to maintain immune tolerance. In preclinical models of T1D the alterations of the GB primarily affect the mucus layer. In human T1D increased gut permeability and IEB damage have been demonstrated but the integrity of the mucus layer was never assessed. METHODS We evaluated GB integrity by measuring serological markers of IEB damage (serological levels of zonulin) and bacterial translocation such as lipopolysaccharide binding protein (LBP) and myeloid differentiation protein 2 (MD2), and mRNA expression of tight junction proteins, mucins and AMPs in intestinal tissue of T1D patients and healthy controls (HC). Simultaneously, we performed immunological profiling on intestinal tissue and 16S rRNA analysis on the mucus-associated gut microbiota (MAGM). FINDINGS Our data show a GB damage with mucus layer alterations and reduced mRNA expression of several mucins (MUC2, MUC12, MUC13, MUC15, MUC20, MUC21) and AMPs (HD4 and HD5) in T1D patients. Mucus layer alterations correlated with reduced relative abundance of short chain fatty acids (SCFA)-producing bacteria such as Bifidobacterium dentium, Clostridium butyricum and Roseburia intestinalis that regulate mucin expression and intestinal immune homeostasis. In T1D patients we also found intestinal immune dysregulation with higher percentages of effector T cells such as T helper (Th) 1, Th17 and TNF-α+ T cells. INTERPRETATION Our data show that mucus layer alterations are present in T1D subjects and associated with dysbiosis and immune dysregulation. FUNDING Research Grants from the Juvenile Diabetes Foundation (Grant 1-INO-2018-640-A-N to MF and 2-SRA-2019-680-S-B to JD) and from the Italian Ministry of Health (Grant RF19-12370721 to MF).
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Affiliation(s)
- Marta Lo Conte
- Autoimmune Pathogenesis Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Ilaria Cosorich
- Autoimmune Pathogenesis Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Roberto Ferrarese
- Virology and Microbiology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Martina Antonini Cencicchio
- Autoimmune Pathogenesis Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Angelica Nobili
- Autoimmune Pathogenesis Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Vittoria Palmieri
- Autoimmune Pathogenesis Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Luca Massimino
- Experimental Gastroenterology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | | | | | - Michela Riba
- Center for OMICS Sciences, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Elisabetta Devecchi
- Clinical Nutrition Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Andrea Mario Bolla
- Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Erika Pedone
- Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Marina Scavini
- Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Emanuele Bosi
- Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy; San Raffaele Vita Salute University, Milan, Italy
| | - Alessio Fasano
- Department of Pediatrics, Harvard Medical School, MA, USA
| | - Federica Ungaro
- Experimental Gastroenterology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | | | - Nicasio Mancini
- Virology and Microbiology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; San Raffaele Vita Salute University, Milan, Italy
| | - Marika Falcone
- Autoimmune Pathogenesis Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.
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27
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Bélteky M, Milletich PL, Ahrens AP, Triplett EW, Ludvigsson J. Infant gut microbiome composition correlated with type 1 diabetes acquisition in the general population: the ABIS study. Diabetologia 2023; 66:1116-1128. [PMID: 36964264 DOI: 10.1007/s00125-023-05895-7] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Accepted: 01/17/2023] [Indexed: 03/26/2023]
Abstract
AIMS/HYPOTHESIS While autoantibodies are traditional markers for type 1 diabetes development, we identified gut microbial biomarkers in 1-year-old infants associated with future type 1 diabetes up to 20 years before diagnosis. METHODS Infants enrolled in the longitudinal general population cohort All Babies In Southeast Sweden (ABIS) provided a stool sample at a mean age of 12.5 months. Samples (future type 1 diabetes, n=16; healthy controls, n=268) were subjected to 16S ribosomal RNA (rRNA) sequencing and quantitative PCR. Microbial differences at the taxonomic and core microbiome levels were assessed. PICRUSt was used to predict functional content from the 16S rRNA amplicons. Sixteen infants, with a future diagnosis of type 1 diabetes at a mean age of 13.3±5.4 years, and one hundred iterations of 32 matched control infants, who remained healthy up to 20 years of age, were analysed. RESULTS Parasutterella and Eubacterium were more abundant in healthy control infants, while Porphyromonas was differentially more abundant in infants with future type 1 diabetes diagnosis. Ruminococcus was a strong determinant in differentiating both control infants and those with future type 1 diabetes using random forest analysis and had differing trends of abundance when comparing control infants and those with future type 1 diabetes. Flavonifractor and UBA1819 were the strongest factors for differentiating control infants, showing higher abundance in control infants compared with those with future type 1 diabetes. Alternatively, Alistipes (more abundant in control infants) and Fusicatenibacter (mixed abundance patterns when comparing case and control infants) were the strongest factors for differentiating future type 1 diabetes. Predicted gene content regarding butyrate production and pyruvate fermentation was differentially observed to be higher in healthy control infants. CONCLUSIONS/INTERPRETATION This investigation suggests that microbial biomarkers for type 1 diabetes may be present as early as 1 year of age, as reflected in the taxonomic and functional differences of the microbial communities. The possibility of preventing disease onset by altering or promoting a 'healthy' gut microbiome is appealing. DATA AVAILABILITY The forward and reverse 16S raw sequencing data generated in this study are available through the NCBI Sequence Read Archive under BioProject PRJNA875929. Associated sample metadata used for statistical comparison are available in the source data file. R codes used for statistical comparisons and figure generation are available at: https://github.com/PMilletich/T1D_Pipeline .
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Affiliation(s)
- Malin Bélteky
- Crown Princess Victoria's Children's Hospital, Region Östergötland, Linköping, Sweden
| | - Patricia L Milletich
- Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, USA
| | - Angelica P Ahrens
- Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, USA
| | - Eric W Triplett
- Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, USA.
| | - Johnny Ludvigsson
- Crown Princess Victoria's Children's Hospital, Region Östergötland, Linköping, Sweden
- Division of Pediatrics, Linköping University, Linköping, Sweden
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Strachan E, Clemente-Casares X, Tsai S. Maternal provisions in type 1 diabetes: Evidence for both protective & pathogenic potential. Front Immunol 2023; 14:1146082. [PMID: 37033940 PMCID: PMC10073710 DOI: 10.3389/fimmu.2023.1146082] [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: 01/16/2023] [Accepted: 03/08/2023] [Indexed: 04/11/2023] Open
Abstract
Maternal influences on the immune health and development of an infant begin in utero and continue well into the postnatal period, shaping and educating the child's maturing immune system. Two maternal provisions include early microbial colonizers to initiate microbiota establishment and the transfer of antibodies from mother to baby. Maternal antibodies are a result of a lifetime of antigenic experience, reflecting the infection history, health and environmental exposure of the mother. These same factors are strong influencers of the microbiota, inexorably linking the two. Together, these provisions help to educate the developing neonatal immune system and shape lymphocyte repertoires, establishing a role for external environmental influences even before birth. In the context of autoimmunity, the transfer of maternal autoantibodies has the potential to be harmful for the child, sometimes targeting tissues and cells with devastating consequences. Curiously, this does not seem to apply to maternal autoantibody transfer in type 1 diabetes (T1D). Moreover, despite the rising prevalence of the disease, little research has been conducted on the effects of maternal dysbiosis or antibody transfer from an affected mother to her offspring and thus their relevance to disease development in the offspring remains unclear. This review seeks to provide a thorough evaluation of the role of maternal microorganisms and antibodies within the context of T1D, exploring both their pathogenic and protective potential. Although a definitive understanding of their significance in infant T1D development remains elusive at present, we endeavor to present what has been learned with the goal of spurring further interest in this important and intriguing question.
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Affiliation(s)
| | | | - Sue Tsai
- Department of Medical Microbiology & Immunology, University of Alberta, Edmonton, AB, Canada
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Jian H, Liu Y, Wang X, Dong X, Zou X. Akkermansia muciniphila as a Next-Generation Probiotic in Modulating Human Metabolic Homeostasis and Disease Progression: A Role Mediated by Gut-Liver-Brain Axes? Int J Mol Sci 2023; 24:ijms24043900. [PMID: 36835309 PMCID: PMC9959343 DOI: 10.3390/ijms24043900] [Citation(s) in RCA: 64] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Revised: 02/09/2023] [Accepted: 02/12/2023] [Indexed: 02/17/2023] Open
Abstract
Appreciation of the importance of Akkermansia muciniphila is growing, and it is becoming increasingly relevant to identify preventive and/or therapeutic solutions targeting gut-liver-brain axes for multiple diseases via Akkermansia muciniphila. In recent years, Akkermansia muciniphila and its components such as outer membrane proteins and extracellular vesicles have been known to ameliorate host metabolic health and intestinal homeostasis. However, the impacts of Akkermansia muciniphila on host health and disease are complex, as both potentially beneficial and adverse effects are mediated by Akkermansia muciniphila and its derivatives, and in some cases, these effects are dependent upon the host physiology microenvironment and the forms, genotypes, and strain sources of Akkermansia muciniphila. Therefore, this review aims to summarize the current knowledge of how Akkermansia muciniphila interacts with the host and influences host metabolic homeostasis and disease progression. Details of Akkermansia muciniphila will be discussed including its biological and genetic characteristics; biological functions including anti-obesity, anti-diabetes, anti-metabolic-syndrome, anti-inflammation, anti-aging, anti-neurodegenerative disease, and anti-cancer therapy functions; and strategies to elevate its abundance. Key events will be referred to in some specific disease states, and this knowledge should facilitate the identification of Akkermansia muciniphila-based probiotic therapy targeting multiple diseases via gut-liver-brain axes.
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Igudesman D, Crandell J, Corbin KD, Zaharieva DP, Addala A, Thomas JM, Bulik CM, Pence BW, Pratley RE, Kosorok MR, Maahs DM, Carroll IM, Mayer-Davis EJ. Associations of disordered eating with the intestinal microbiota and short-chain fatty acids among young adults with type 1 diabetes. Nutr Metab Cardiovasc Dis 2023; 33:388-398. [PMID: 36586772 PMCID: PMC9925402 DOI: 10.1016/j.numecd.2022.11.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 11/05/2022] [Accepted: 11/10/2022] [Indexed: 11/18/2022]
Abstract
BACKGROUND AND AIMS Disordered eating (DE) in type 1 diabetes (T1D) includes insulin restriction for weight loss with serious complications. Gut microbiota-derived short chain fatty acids (SCFA) may benefit host metabolism but are reduced in T1D. We evaluated the hypothesis that DE and insulin restriction were associated with reduced SCFA-producing gut microbes, SCFA, and intestinal microbial diversity in adults with T1D. METHODS AND RESULTS We collected stool samples at four timepoints in a hypothesis-generating gut microbiome pilot study ancillary to a weight management pilot in young adults with T1D. 16S ribosomal RNA gene sequencing measured the normalized abundance of SCFA-producing intestinal microbes. Gas-chromatography mass-spectrometry measured SCFA (total, acetate, butyrate, and propionate). The Diabetes Eating Problem Survey-Revised (DEPS-R) assessed DE and insulin restriction. Covariate-adjusted and Bonferroni-corrected generalized estimating equations modeled the associations. COVID-19 interrupted data collection, so models were repeated restricted to pre-COVID-19 data. Data were available for 45 participants at 109 visits, which included 42 participants at 65 visits pre-COVID-19. Participants reported restricting insulin "At least sometimes" at 53.3% of visits. Pre-COVID-19, each 5-point DEPS-R increase was associated with a -0.34 (95% CI -0.56, -0.13, p = 0.07) lower normalized abundance of genus Anaerostipes; and the normalized abundance of Lachnospira genus was -0.94 (95% CI -1.5, -0.42), p = 0.02 lower when insulin restriction was reported "At least sometimes" compared to "Rarely or Never". CONCLUSION DE and insulin restriction were associated with a reduced abundance of SCFA-producing gut microbes pre-COVID-19. Additional studies are needed to confirm these associations to inform microbiota-based therapies in T1D.
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Affiliation(s)
- Daria Igudesman
- Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, 27599, USA; AdventHealth Translational Research Institute, Orlando, 32804, USA.
| | - Jamie Crandell
- Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, 27599, USA
| | - Karen D Corbin
- AdventHealth Translational Research Institute, Orlando, 32804, USA
| | - Dessi P Zaharieva
- Department of Pediatrics, Division of Endocrinology, Stanford University, Stanford, 94304, USA
| | - Ananta Addala
- Department of Pediatrics, Division of Endocrinology, Stanford University, Stanford, 94304, USA
| | - Joan M Thomas
- Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, 27599, USA
| | - Cynthia M Bulik
- Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, 27599, USA; Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, USA; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Brian W Pence
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, 27599, USA
| | | | - Michael R Kosorok
- Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, 27599, USA
| | - David M Maahs
- Department of Pediatrics, Division of Endocrinology, Stanford University, Stanford, 94304, USA
| | - Ian M Carroll
- Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, 27599, USA
| | - Elizabeth J Mayer-Davis
- Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, 27599, USA; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, 27599, USA
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Lo Conte M, Antonini Cencicchio M, Ulaszewska M, Nobili A, Cosorich I, Ferrarese R, Massimino L, Andolfo A, Ungaro F, Mancini N, Falcone M. A diet enriched in omega-3 PUFA and inulin prevents type 1 diabetes by restoring gut barrier integrity and immune homeostasis in NOD mice. Front Immunol 2023; 13:1089987. [PMID: 36713378 PMCID: PMC9880528 DOI: 10.3389/fimmu.2022.1089987] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Accepted: 12/23/2022] [Indexed: 01/15/2023] Open
Abstract
Introduction The integrity of the gut barrier (GB) is fundamental to regulate the crosstalk between the microbiota and the immune system and to prevent inflammation and autoimmunity at the intestinal level but also in organs distal from the gut such as the pancreatic islets. In support to this idea, we recently demonstrated that breakage of GB integrity leads to activation of islet-reactive T cells and triggers autoimmune Type 1 Diabetes (T1D). In T1D patients as in the NOD mice, the spontaneous model of autoimmune diabetes, there are alterations of the GB that specifically affect structure and composition of the mucus layer; however, it is yet to be determined whether a causal link between breakage of the GB integrity and occurrence of autoimmune T1D exists. Methods Here we restored GB integrity in the NOD mice through administration of an anti-inflammatory diet (AID- enriched in soluble fiber inulin and omega 3-PUFA) and tested the effect on T1D pathogenesis. Results We found that the AID prevented T1D in NOD mice by restoring GB integrity with increased mucus layer thickness and higher mRNA transcripts of structural (Muc2) and immunoregulatory mucins (Muc1 and Muc3) as well as of tight junction proteins (claudin1). Restoration of GB integrity was linked to reduction of intestinal inflammation (i.e., reduced expression of IL-1β, IL-23 and IL-17 transcripts) and expansion of regulatory T cells (FoxP3+ Treg cells and IL-10+ Tr1 cells) at the expenses of effector Th1/Th17 cells in the intestine, pancreatic lymph nodes (PLN) and intra-islet lymphocytes (IIL) of AID-fed NOD mice. Importantly, the restoration of GB integrity and immune homeostasis were associated with enhanced concentrations of anti-inflammatory metabolites of the ω3/ω6 polyunsaturated fatty acids (PUFA) and arachidonic pathways and modifications of the microbiome profile with increased relative abundance of mucus-modulating bacterial species such as Akkermansia muciniphila and Akkermansia glycaniphila. Discussion Our data provide evidence that the restoration of GB integrity and intestinal immune homeostasis through administration of a tolerogenic AID that changed the gut microbial and metabolic profiles prevents autoimmune T1D in preclinical models.
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Affiliation(s)
- Marta Lo Conte
- Autoimmune Pathogenesis Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy,Università Vita-Salute San Raffaele, Milan, Italy
| | - Martina Antonini Cencicchio
- Autoimmune Pathogenesis Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy,Università Vita-Salute San Raffaele, Milan, Italy
| | - Marynka Ulaszewska
- Proteomics and Metabolomics Facility (ProMeFa), IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Angelica Nobili
- Autoimmune Pathogenesis Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Ilaria Cosorich
- Autoimmune Pathogenesis Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Roberto Ferrarese
- Laboratory of Medical Microbiology and Virology, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Luca Massimino
- Experimental Gastroenterology Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Annapaola Andolfo
- Proteomics and Metabolomics Facility (ProMeFa), IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Federica Ungaro
- Experimental Gastroenterology Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Nicasio Mancini
- Laboratory of Medical Microbiology and Virology, IRCCS San Raffaele Scientific Institute, Milan, Italy,Laboratory of Medical Microbiology and Virology, Università “Vita-Salute” San Raffaele, Milan, Italy
| | - Marika Falcone
- Autoimmune Pathogenesis Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy,*Correspondence: Marika Falcone,
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Harsini S, Rezaei N. Autoimmune diseases. Clin Immunol 2023. [DOI: 10.1016/b978-0-12-818006-8.00001-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
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Koloski NA, Jones M, Walker MM, Horowitz M, Holtmann G, Talley NJ. Diabetes mellitus is an independent risk factor for a greater frequency of early satiation and diarrhea at one and three years: Two prospective longitudinal population-based studies. Neurogastroenterol Motil 2023; 35:e14471. [PMID: 36210758 PMCID: PMC10078260 DOI: 10.1111/nmo.14471] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Revised: 08/07/2022] [Accepted: 08/23/2022] [Indexed: 12/31/2022]
Abstract
BACKGROUND Psychological and lifestyle factors have been associated with gastrointestinal (GI) symptoms in individuals with diabetes mellitus, but it remains unclear whether they explain the relationship over time. We aimed to determine in two independent population-based studies whether diabetes is an independent risk factor for GI symptoms at a 1- and 3-year follow-up, adjusting for these factors. METHODS In study 1, 1900 individuals completed a baseline and 1-year follow-up survey, while in study 2, 1322 individuals completed a baseline and 3-year follow-up survey. Both studies asked about self-reported diagnoses of diabetes and GI symptoms over the previous 3 months. Psychological, lifestyle factors (body mass index [BMI], smoking) and age and sex were assessed. KEY RESULTS The baseline prevalence of diabetes was 7.8% in Survey 1 and 8.9% in Survey 2. In a multivariate model that included age, sex, BMI, anxiety, depression and smoking status at follow-up, reporting diabetes at baseline was an independent predictor of at least weekly early satiation (OR 1.58, 95% CI 1.05, 2.39, p = 0.03; OR = 1.67, 95% CI 1.14, 2.45, p = 0.009), fecal urgency (OR 1.44,95% CI 1.06, 1.95, p = 0.02; OR = 2.17, 95% CI 1.47, 3.22, p = 0.0001), > 3 bowel motions a day (OR 1.50, 95% CI 1.08, 2.07, p = 0.02; OR = 1.67, 95% CI 1.11, 2.51, p = 0.01), and loose stools (OR 1.40, 95% CI 1.04, 1.90, p = 0.03; OR = 1.68, 95% CI 1.13, 2.51, p = 0.01) at the 1- and 3-year follow-ups, respectively. CONCLUSIONS & INFERENCES Diabetes is an independent risk factor for a greater frequency of early satiation and diarrhea, adjusting for lifestyle and psychological factors.
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Affiliation(s)
- Natasha A. Koloski
- School of Medicine and Public HealthUniversity of NewcastleCallaghanNew South WalesAustralia
- Department of Gastroenterology & HepatologyPrincess Alexandra HospitalBrisbaneAustralia
- Faculty of MedicineUniversity of QueenslandBrisbaneAustralia
| | - Michael Jones
- School of Psychological SciencesMacquarie UniversityRydeNew South WalesAustralia
| | - Marjorie M. Walker
- School of Medicine and Public HealthUniversity of NewcastleCallaghanNew South WalesAustralia
| | - Michael Horowitz
- Endocrine and Metabolic UnitUniversity of AdelaideAdelaideSouth AustraliaAustralia
| | - Gerald Holtmann
- Department of Gastroenterology & HepatologyPrincess Alexandra HospitalBrisbaneAustralia
- Faculty of MedicineUniversity of QueenslandBrisbaneAustralia
| | - Nicholas J. Talley
- School of Medicine and Public HealthUniversity of NewcastleCallaghanNew South WalesAustralia
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Del Chierico F, Rapini N, Deodati A, Matteoli MC, Cianfarani S, Putignani L. Pathophysiology of Type 1 Diabetes and Gut Microbiota Role. Int J Mol Sci 2022; 23:ijms232314650. [PMID: 36498975 PMCID: PMC9737253 DOI: 10.3390/ijms232314650] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 11/09/2022] [Accepted: 11/22/2022] [Indexed: 11/25/2022] Open
Abstract
Type 1 diabetes (T1D) is a multifactorial autoimmune disease driven by T-cells against the insulin-producing islet β-cells, resulting in a marked loss of β-cell mass and function. Although a genetic predisposal increases susceptibility, the role of epigenetic and environmental factors seems to be much more significant. A dysbiotic gut microbial profile has been associated with T1D patients. Moreover, new evidence propose that perturbation in gut microbiota may influence the T1D onset and progression. One of the prominent features in clinically silent phase before the onset of T1D is the presence of a microbiota characterized by low numbers of commensals butyrate producers, thus negatively influencing the gut permeability. The loss of gut permeability leads to the translocation of microbes and microbial metabolites and could lead to the activation of immune cells. Moreover, microbiota-based therapies to slow down disease progression or reverse T1D have shown promising results. Starting from this evidence, the correction of dysbiosis in early life of genetically susceptible individuals could help in promoting immune tolerance and thus in reducing the autoantibodies production. This review summarizes the associations between gut microbiota and T1D for future therapeutic perspectives and other exciting areas of research.
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Affiliation(s)
- Federica Del Chierico
- Multimodal Laboratory Medicine Research Area, Unit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy
| | - Novella Rapini
- Diabetes & Growth Disorders Unit, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy
| | - Annalisa Deodati
- Diabetes & Growth Disorders Unit, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy
| | - Maria Cristina Matteoli
- Diabetes & Growth Disorders Unit, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy
| | - Stefano Cianfarani
- Diabetes & Growth Disorders Unit, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy
- Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy
- Department of Women’s and Children Health, Karolisnska Institute and University Hospital, 17177 Stockholm, Sweden
| | - Lorenza Putignani
- Department of Diagnostic and Laboratory Medicine, Unit of Microbiology and Diagnostic Immunology, Unit of Microbiomics and Multimodal Laboratory Medicine Research Area, Unit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy
- Correspondence: ; Tel.: +39-0668592980
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Maternal energy-adjusted fatty acid intake during pregnancy and the development of cows' milk allergy in the offspring. Br J Nutr 2022; 128:1607-1614. [PMID: 34763730 DOI: 10.1017/s0007114521004475] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Cows' milk allergy (CMA) is one of the earliest manifestations of allergic diseases. Early dietary factors, like maternal diet during pregnancy, may play a role in the development of allergic diseases in the offspring. We aimed to investigate the association between maternal intake of fatty acids during pregnancy and the risk of CMA in the offspring. Our study was conducted in a population-based cohort, the Finnish Type 1 Diabetes Prediction and Prevention study. We collected the maternal dietary data by a validated FFQ. We obtained the information on CMA in the study participants (n 448) from registers and from the parents. Dietary data and information on CMA were available for 4921 children. We used logistic regression in the analyses, and fatty acid intakes were energy adjusted. The maternal intake of SFA, MUFA, PUFA, n-3 PUFA, n-6 PUFA, trans fatty acids, ratio of n-3 PUFA to n-6 PUFA or ratio of linoleic acid to α-linolenic acid was not associated with the risk of CMA in the offspring when adjusted for perinatal factors, background factors, parental history of asthma or allergic rhinitis and infant animal contacts. The intake of α-linolenic acid was associated with a decreased risk (OR 0·72; 95 % CI 0·56, 0·93) of CMA in the offspring of mothers without a history of allergic rhinitis or asthma. In conclusion, the maternal intake of fatty acids during pregnancy is not associated with the risk of CMA in the offspring.
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Helminen O, Pokka T, Aspholm S, Ilonen J, Simell O, Knip M, Veijola R. Early glucose metabolism in children at risk for type 1 diabetes based on islet autoantibodies compared to low-risk control groups. Front Endocrinol (Lausanne) 2022; 13:972714. [PMID: 36171903 PMCID: PMC9511031 DOI: 10.3389/fendo.2022.972714] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2022] [Accepted: 08/19/2022] [Indexed: 11/16/2022] Open
Abstract
Background Anatomic variation or early differences in glucose metabolism have been linked to the development of type 1 diabetes. We aimed to describe early glucose metabolism based on HbA1c, oral glucose tolerance test (OGTT), and random plasma glucose years before the presentation of type 1 diabetes in five risk groups based on autoantibody combinations. For the first time, we were able to include for comparison children with very low risk of progression to type 1 diabetes. Methods The Finnish Diabetes Prediction and Prevention birth cohort study screened newborn infants for HLA susceptibility to type 1 diabetes since 1994. Those carrying a risk genotype were prospectively followed up with islet autoantibody testing. Glucose parameters were obtained starting from the time of seroconversion. By 31 August 2014, 1162 children had developed at least one islet autoantibody and were included in the current study. Type 1 diabetes was diagnosed in 335 children (progressors). In the non-progressor groups, 207 developed multiple (≥2) biochemical islet autoantibodies, 229 a single biochemical autoantibody, 370 ICA only, and 64 transient autoantibodies. Children were divided into five risk groups. Glucose metabolism was evaluated. Results We observed lower HbA1c values in early follow-up 4.5 to 6.0 years before diagnosis in the progressors when compared to the same time in children with a single biochemical autoantibody or low-risk (ICA only and transient) participants, who did not progress to clinical type 1 diabetes. However, no such differences were observed in OGTTs or random plasma glucose. The variation was minimal in glucose values in the low-risk groups. Conclusion We report the possibility of early alteration in glucose metabolism in future progressors. This could suggest early defects in multiple glucose-regulating hormones.
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Affiliation(s)
- Olli Helminen
- Department of Pediatrics, PEDEGO Research Group, Medical Research Center, Oulu University, Hospital and University of Oulu, Oulu, Finland
- Surgery Research Unit, Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland
| | - Tytti Pokka
- Department of Pediatrics, PEDEGO Research Group, Medical Research Center, Oulu University, Hospital and University of Oulu, Oulu, Finland
| | - Susanna Aspholm
- Tampere Centre for Child Health Research, Tampere University Hospital, Tampere, Finland
| | - Jorma Ilonen
- Immunogenetics Laboratory, University of Turku, Turku, Finland
- Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland
| | - Olli Simell
- Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland
| | - Mikael Knip
- Tampere Centre for Child Health Research, Tampere University Hospital, Tampere, Finland
- Pediatric Research Center, New Children’s Hospital, Helsinki University Hospital, Helsinki, Finland
- Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Riitta Veijola
- Department of Pediatrics, PEDEGO Research Group, Medical Research Center, Oulu University, Hospital and University of Oulu, Oulu, Finland
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Cai H, Cao X, Qin D, Liu Y, Liu Y, Hua J, Peng S. Gut microbiota supports male reproduction via nutrition, immunity, and signaling. Front Microbiol 2022; 13:977574. [PMID: 36060736 PMCID: PMC9434149 DOI: 10.3389/fmicb.2022.977574] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Accepted: 08/02/2022] [Indexed: 12/12/2022] Open
Abstract
Gut microbiota (GM) is a major component of the gastrointestinal tract. Growing evidence suggests that it has various effects on many distal organs including the male reproductive system in mammals. GM and testis form the gut-testis axis involving the production of key molecules through microbial metabolism or de novo synthesis. These molecules have nutrition, immunity, and hormone-related functions and promote the male reproductive system via the circulatory system. GM helps maintain the integral structure of testes and regulates testicular immunity to protect the spermatogenic environment. Factors damaging GM negatively impact male reproductive function, however, the related mechanism is unknown. Also, the correlation between GM and testis remains to be yet investigated. This review discusses the complex influence of GM on the male reproductive system highlighting the impact on male fertility.
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Affiliation(s)
- Hui Cai
- Shaanxi Centre of Stem Cells Engineering and Technology, College of Veterinary Medicine, Northwest A&F University, Shaanxi, China
| | - Xuanhong Cao
- Shaanxi Centre of Stem Cells Engineering and Technology, College of Veterinary Medicine, Northwest A&F University, Shaanxi, China
| | - Dezhe Qin
- State Key Laboratory for Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
| | - Yundie Liu
- Shaanxi Centre of Stem Cells Engineering and Technology, College of Veterinary Medicine, Northwest A&F University, Shaanxi, China
| | - Yang Liu
- Shaanxi Centre of Stem Cells Engineering and Technology, College of Veterinary Medicine, Northwest A&F University, Shaanxi, China
| | - Jinlian Hua
- Shaanxi Centre of Stem Cells Engineering and Technology, College of Veterinary Medicine, Northwest A&F University, Shaanxi, China
| | - Sha Peng
- Shaanxi Centre of Stem Cells Engineering and Technology, College of Veterinary Medicine, Northwest A&F University, Shaanxi, China
- *Correspondence: Sha Peng,
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Xie X, Zhang M, Sun L, Wang T, Zhu Z, Shu R, Wu F, Li Z. Crocin-I Protects Against High-Fat Diet-Induced Obesity via Modulation of Gut Microbiota and Intestinal Inflammation in Mice. Front Pharmacol 2022; 13:894089. [PMID: 36034852 PMCID: PMC9403484 DOI: 10.3389/fphar.2022.894089] [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: 03/28/2022] [Accepted: 06/06/2022] [Indexed: 12/05/2022] Open
Abstract
Crocin-I can regulate physiological changes in the human body by altering inflammation and microbial composition. Gut microbiota are also involved in modulating the pathophysiology of obesity. However, crocin-I's effect on obesity and the mechanism underlying its effects on gut microbiota and inflammation remain poorly understood. Here, high-fat diet (HFD) -induced obese mice were administrated crocin-I (20 mg/kg/day) for 10 weeks using an oral gavage (HFD-C20 group). HFD-C20, HFD, and Normal chow (NC) groups were compared. The fat content, colon tissue inflammatory cytokine levels, gut microbiota, and short-chain fatty acids (SCFAs) levels were measured. We show that crocin-I reduced body weight and liver weight and improved glucose resistance in HFD-induced mice, and reduced the lipid accumulation in the liver. Strikingly, crocin-I alleviated intestinal microbial disorders and decreased the F/B ratio and the abundance of Proteobacteria in HFD-induced obese mice. Crocin-I also rescued the decrease in the levels of SCFAs and repaired altered intestinal barrier functioning and intestinal inflammation in HFD-induced obese mice. These findings indicate that crocin-I may inhibit obesity by modulating the composition of gut microbiota and intestinal inflammation.
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Affiliation(s)
- Xiaoxian Xie
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, China
| | - Mengya Zhang
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, China
| | - Lei Sun
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, China
| | - Ting Wang
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, China
| | - Zhengyan Zhu
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, China
| | - Ruonan Shu
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, China
| | - Fengchun Wu
- Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China
- Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, China
| | - Zezhi Li
- Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China
- Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, China
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Mazenc A, Mervant L, Maslo C, Lencina C, Bézirard V, Levêque M, Ahn I, Alquier-Bacquié V, Naud N, Héliès-Toussaint C, Debrauwer L, Chevolleau S, Guéraud F, Pierre FHF, Théodorou V, Olier M. Maternal heme-enriched diet promotes a gut pro-oxidative status associated with microbiota alteration, gut leakiness and glucose intolerance in mice offspring. Redox Biol 2022; 53:102333. [PMID: 35588638 PMCID: PMC9119830 DOI: 10.1016/j.redox.2022.102333] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Revised: 05/06/2022] [Accepted: 05/06/2022] [Indexed: 12/17/2022] Open
Abstract
Maternal environment, including nutrition and microbiota, plays a critical role in determining offspring's risk of chronic diseases such as diabetes later in life. Heme iron requirement is amplified during pregnancy and lactation, while excessive dietary heme iron intake, compared to non-heme iron, has shown to trigger acute oxidative stress in the gut resulting from reactive aldehyde formation in conjunction with microbiota reshape. Given the immaturity of the antioxidant defense system in early life, we investigated the extent to which a maternal diet enriched with heme iron may have a lasting impact on gut homeostasis and glucose metabolism in 60-day-old C3H/HeN mice offspring. As hypothesized, the form of iron added to the maternal diet differentially governed the offspring's microbiota establishment despite identical fecal iron status in the offspring. Importantly, despite female offspring was unaffected, oxidative stress markers were however higher in the gut of male offspring from heme enriched-fed mothers, and were accompanied by increases in fecal lipocalin-2, intestinal para-cellular permeability and TNF-α expression. In addition, male mice displayed blood glucose intolerance resulting from impaired insulin secretion following oral glucose challenge. Using an integrated approach including an aldehydomic analysis, this male-specific phenotype was further characterized and revealed close covariations between unidentified putative reactive aldehydes and bacterial communities belonging to Bacteroidales and Lachnospirales orders. Our work highlights how the form of dietary iron in the maternal diet can dictate the oxidative status in gut offspring in a sex-dependent manner, and how a gut microbiota-driven oxidative challenge in early life can be associated with gut barrier defects and glucose metabolism disorders that may be predictive of diabetes development.
Maternal heminic vs. non-heminic iron intake differentially and persistently imprints the offspring's fecal microbiota. Males from heme-fed dams exhibit increased gut lumen reactive aldehydes in absence of direct dietary exposure to heme iron. Some of the increased reactive aldehydes closely covariated with Orders belonging to Bacteroidales and Lachnospirales. Maternal exposure to dietary heme iron impairs gut barrier and glucose tolerance in male offspring.
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Affiliation(s)
- Anaïs Mazenc
- Toxalim (Research Centre in Food Toxicology), INRAE, Université de Toulouse, ENVT, INP-Purpan, UPS, Toulouse, France
| | - Loïc Mervant
- Toxalim (Research Centre in Food Toxicology), INRAE, Université de Toulouse, ENVT, INP-Purpan, UPS, Toulouse, France; Metatoul-AXIOM Plaform, National Infrastructure for Metabolomics and Fluxomics, MetaboHUB, Toulouse, France
| | - Claire Maslo
- Toxalim (Research Centre in Food Toxicology), INRAE, Université de Toulouse, ENVT, INP-Purpan, UPS, Toulouse, France
| | - Corinne Lencina
- Toxalim (Research Centre in Food Toxicology), INRAE, Université de Toulouse, ENVT, INP-Purpan, UPS, Toulouse, France
| | - Valérie Bézirard
- Toxalim (Research Centre in Food Toxicology), INRAE, Université de Toulouse, ENVT, INP-Purpan, UPS, Toulouse, France
| | - Mathilde Levêque
- Toxalim (Research Centre in Food Toxicology), INRAE, Université de Toulouse, ENVT, INP-Purpan, UPS, Toulouse, France
| | - Ingrid Ahn
- Toxalim (Research Centre in Food Toxicology), INRAE, Université de Toulouse, ENVT, INP-Purpan, UPS, Toulouse, France
| | - Valérie Alquier-Bacquié
- Toxalim (Research Centre in Food Toxicology), INRAE, Université de Toulouse, ENVT, INP-Purpan, UPS, Toulouse, France
| | - Nathalie Naud
- Toxalim (Research Centre in Food Toxicology), INRAE, Université de Toulouse, ENVT, INP-Purpan, UPS, Toulouse, France
| | - Cécile Héliès-Toussaint
- Toxalim (Research Centre in Food Toxicology), INRAE, Université de Toulouse, ENVT, INP-Purpan, UPS, Toulouse, France
| | - Laurent Debrauwer
- Toxalim (Research Centre in Food Toxicology), INRAE, Université de Toulouse, ENVT, INP-Purpan, UPS, Toulouse, France; Metatoul-AXIOM Plaform, National Infrastructure for Metabolomics and Fluxomics, MetaboHUB, Toulouse, France
| | - Sylvie Chevolleau
- Toxalim (Research Centre in Food Toxicology), INRAE, Université de Toulouse, ENVT, INP-Purpan, UPS, Toulouse, France; Metatoul-AXIOM Plaform, National Infrastructure for Metabolomics and Fluxomics, MetaboHUB, Toulouse, France
| | - Françoise Guéraud
- Toxalim (Research Centre in Food Toxicology), INRAE, Université de Toulouse, ENVT, INP-Purpan, UPS, Toulouse, France
| | - Fabrice H F Pierre
- Toxalim (Research Centre in Food Toxicology), INRAE, Université de Toulouse, ENVT, INP-Purpan, UPS, Toulouse, France
| | - Vassilia Théodorou
- Toxalim (Research Centre in Food Toxicology), INRAE, Université de Toulouse, ENVT, INP-Purpan, UPS, Toulouse, France
| | - Maïwenn Olier
- Toxalim (Research Centre in Food Toxicology), INRAE, Université de Toulouse, ENVT, INP-Purpan, UPS, Toulouse, France.
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Shen X, Wei H, Li J, Wei W, Zhang B, Lu C, Yan C, Li S, Bao L, Zhang J, Zhang C, Li Y. Ectopic Colonization and Immune Landscapes of Periodontitis Microbiota in Germ-Free Mice With Streptozotocin-Induced Type 1 Diabetes Mellitus. Front Microbiol 2022; 13:889415. [PMID: 35756043 PMCID: PMC9226645 DOI: 10.3389/fmicb.2022.889415] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Accepted: 05/10/2022] [Indexed: 02/05/2023] Open
Abstract
A two-way relationship between diabetes and periodontitis has been discussed recently. Periodontitis microbiota might affect the immune homeostasis of diabetes, but the molecular mechanism of their interactions is still not clear. The aims of this study were to clarify the possible immune regulatory effects of periodontitis microbiota on diabetes and the correlation between immunomodulation and ectopic colonization. A model of germ-free mice with streptozotocin-induced type 1 diabetes mellitus (T1D), which was orally inoculated with mixed saliva samples for 2 weeks, was used in this study. Those mice were randomly divided into two groups, namely, SP (where the T1D mice were orally inoculated with mixed saliva samples from periodontitis patients) and SH (where the T1D mice were orally inoculated with mixed saliva samples from healthy subjects). Ectopic colonization of saliva microbiota was assessed using culture-dependent method and Sanger sequencing, and the composition of gut microbiota was analyzed using 16S rRNA gene sequencing. Changes in 15 types of immune cells and six cytokines either from the small intestine or spleen were detected by multicolor flow cytometry. The correlation between gut microbiota and immune cells was evaluated by redundancy analysis. Although periodontitis microbiota minorly colonized the lungs, spleens, and blood system, they predominantly colonized the gut, which was mainly invaded by Klebsiella. SH and SP differed in beta diversity of the gut bacterial community. Compared to SH, microbial alteration in small intestine occurred with an increase of Lacticaseibacillus, Bacillus, Agathobacter, Bacteroides, and a decrease of Raoultella in SP. More types of immune cells were disordered in the spleen than in the small intestine by periodontitis microbiota, mainly with a dramatical increase in the proportion of macrophages, plasmacytoid dendritic cells (pDCs), monocytes, group 3 innate lymphoid cells, CD4-CD8- T cells and Th17 cells, as well as a decline of αβT cells in SP. Cytokines of IFNγ, IL17, and IL22 produced by CD4 + T cells as well as IL22 produced by ILCs of small intestine rose in numbers, and the intestinal and splenic pDCs were positively regulated by gut bacterial community in SP. In conclusion, periodontitis microbiota invasion leads to ectopic colonization of the extra-oral sites and immune cells infiltration, which might cause local or systemic inflammation. Those cells are considered to act as a “bridge” between T1D and periodontitis.
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Affiliation(s)
- Xin Shen
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Hong Wei
- Central Laboratory, Clinical Medicine Scientific and Technical Innovation Park, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China
| | - Jian Li
- Institute of Immunology, PLA, Army Medical University, Chongqing, China
| | - Wei Wei
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Bo Zhang
- Department of Stomatology, Minda Hospital of Hubei Minzu University, Enshi, China
| | - Changqing Lu
- Department of Anatomy, West China School of Basic Medical and Forensic Medicine, Sichuan University, Chengdu, China
| | - Caixia Yan
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Shuzhen Li
- CAS Key Laboratory of Environmental Biotechnology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China
| | - Lirong Bao
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Jinmei Zhang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Cheng Zhang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Yan Li
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
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Gut microbiome profiles and associated metabolic pathways in patients of adult-onset immunodeficiency with anti-interferon-gamma autoantibodies. Sci Rep 2022; 12:9126. [PMID: 35650243 PMCID: PMC9159984 DOI: 10.1038/s41598-022-13289-9] [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: 12/27/2021] [Accepted: 05/05/2022] [Indexed: 11/08/2022] Open
Abstract
Autoantibodies against interferon-gamma (AutoAbs-IFN-γ) can cause the immunodeficiency condition following various opportunistic infections. Gut microbiota can affect the human immune system in many ways. Many studies have shown that gut dysbiosis was associated with some immune diseases, such as autoimmune diseases and human immunodeficiency virus (HIV) infection, while its relationship at anti-IFN-γ AAbs remains unknown. We aimed to identify the anti-IFN-γ AAbs specific microbiome and the possible association with immunodeficiency. We profiled fecal microbiome for two cohorts of forty subjects, including seven patients with anti-IFN-γ AAbs and 33 individuals with competent immune. The study shows that patients with anti-IFN-γ AAbs have characterized the gut microbiome and have lower alpha diversity indexes than healthy controls (HC). There are significant differences in the microbiome structure at both the family and genera level between the two cohorts. The anti-IFN-γ AAbs cohort featured some microbiome such as Clostridium, including the possible opportunistic pathogen and fewer genera including Bacteroides, Ruminococcus, and Faecalibacterium, some of them with possible immune-related genera. The PICRUSt2 pathway demonstrated the decreased abundance of some immune-related pathways and one potential pathway related to the immune alternations in the anti- IFN-γ AAbs cohort. This was the first study to examine the gut microbiome characteristics in patients with anti-IFN-γ AAbs. It could be involved in the pathogenesis of anti-IFN-γ AAbs and contribute to the derived immune condition in this disease. This could lead to new strategies for treating and preventing patients suffering from this disease.
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Vijay A, Valdes AM. Role of the gut microbiome in chronic diseases: a narrative review. Eur J Clin Nutr 2022; 76:489-501. [PMID: 34584224 PMCID: PMC8477631 DOI: 10.1038/s41430-021-00991-6] [Citation(s) in RCA: 220] [Impact Index Per Article: 73.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 06/29/2021] [Accepted: 07/27/2021] [Indexed: 02/07/2023]
Affiliation(s)
- Amrita Vijay
- Division of Rheumatology, Orthopaedics and Dermatology, School of Medicine, The University of Nottingham, Nottingham, UK.
| | - Ana M Valdes
- Division of Rheumatology, Orthopaedics and Dermatology, School of Medicine, The University of Nottingham, Nottingham, UK
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
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Linh H, Iwata Y, Senda Y, Sakai-Takemori Y, Nakade Y, Oshima M, Yoneda-Nakagawa S, Ogura H, Sato K, Minami T, Kitajima S, Toyama T, Yamamura Y, Miyakawa T, Hara A, Shimizu M, Furuichi K, Sakai N, Yamada H, Asanuma K, Matsushima K, Wada T. Intestinal Bacterial Translocation Contributes to Diabetic Kidney Disease. J Am Soc Nephrol 2022; 33:1105-1119. [PMID: 35264456 PMCID: PMC9161796 DOI: 10.1681/asn.2021060843] [Citation(s) in RCA: 53] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 02/22/2022] [Indexed: 11/03/2022] Open
Abstract
Background In recent years, many studies have focused on the intestinal environment to elucidate pathogenesis of various diseases, including kidney diseases. Impairment of the intestinal barrier function, the "leaky gut," reportedly contributes to pathological processes in some disorders. Mitochondrial antiviral signaling protein (MAVS), a component of innate immunity, maintains intestinal integrity. The effects of disrupted intestinal homeostasis associated with MAVS signaling in diabetic kidney disease remains unclear. Methods To evaluate the contribution of intestinal barrier impairment to kidney injury under diabetic conditions, we induced diabetic kidney disease in wild-type and MAVS knockout mice through unilateral nephrectomy and streptozotocin treatment. We then assessed effects on the kidney, intestinal injuries, and bacterial translocation. Results MAVS knockout diabetic mice showed more severe glomerular and tubular injuries compared with wild-type diabetic mice. Owing to impaired intestinal integrity, the presence of intestine-derived Klebsiella oxytoca and elevated IL-17 were detected in the circulation and kidneys of diabetic mice, especially in diabetic MAVS knockout mice. Stimulation of tubular epithelial cells with K. oxytoca activated MAVS pathways and the phosphorylation of Stat3 and ERK1/2, leading to the production of kidney injury molecule-1 (KIM-1). Nevertheless, MAVS inhibition induced inflammation in the intestinal epithelial cells and KIM-1 production in tubular epithelial cells under K. oxytoca supernatant or IL-17 stimulation. Treatment with neutralizing anti-IL-17 antibody treatment had renoprotective effects. In contrast, lipopolysaccharide administration accelerated kidney injury in the murine diabetic kidney disease model. Conclusions Impaired MAVS signaling both in the kidney and intestine contributes to the disrupted homeostasis, leading to diabetic kidney disease progression. Controlling intestinal homeostasis may offer a novel therapeutic approach for this condition.
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Affiliation(s)
- Hoang Linh
- H Linh, Department of Nephrology and Laboratory Medicine, Kanazawa University, Kanazawa, Japan
| | - Yasunori Iwata
- Y Iwata, Department of Nephrology and Laboratory Medicine, Kanazawa University, Kanazawa, Japan
| | - Yasuko Senda
- Y Senda, Division of Infection Control, Kanazawa University Hospital, Kanazawa, Japan
| | - Yukiko Sakai-Takemori
- Y Sakai-Takemori, Division of Infection Control, Kanazawa University Hospital, Kanazawa, Japan
| | - Yusuke Nakade
- Y Nakade, Division of Infection Control, Kanazawa University Hospital, Kanazawa, Japan
| | - Megumi Oshima
- M Oshima, Department of Nephrology and Laboratory Medicine, Kanazawa University, Kanazawa, Japan
| | - Shiori Yoneda-Nakagawa
- S Yoneda-Nakagawa, Department of Nephrology and Laboratory Medicine, Kanazawa University, Kanazawa, Japan
| | - Hisayuki Ogura
- H Ogura, Department of Nephrology and Laboratory Medicine, Kanazawa University, Kanazawa, Japan
| | - Koichi Sato
- K Sato, Department of Nephrology and Laboratory Medicine, Kanazawa University, Kanazawa, Japan
| | - Taichiro Minami
- T Minami, Department of Nephrology and Laboratory Medicine, Kanazawa University, Kanazawa, Japan
| | - Shinji Kitajima
- S Kitajima, Department of Nephrology and Laboratory Medicine, Kanazawa University, Kanazawa, Japan
| | - Tadashi Toyama
- T Toyama, Department of Nephrology and Laboratory Medicine, Kanazawa University, Kanazawa, Japan
| | - Yuta Yamamura
- Y Yamamura, Department of Nephrology and Laboratory Medicine, Kanazawa University, Kanazawa, Japan
| | - Taro Miyakawa
- T Miyakawa, Department of Nephrology and Laboratory Medicine, Kanazawa University, Kanazawa, Japan
| | - Akinori Hara
- A Hara, Department of Nephrology and Laboratory Medicine, Kanazawa University, Kanazawa, Japan
| | - Miho Shimizu
- M Shimizu, Department of Nephrology and Laboratory Medicine, Kanazawa University, Kanazawa, Japan
| | - Kengo Furuichi
- K Furuichi, Division of Nephrology, Kanazawa Medical University School of Medicine Graduate School of Medicine, Kahoku-gun, Japan
| | - Norihiko Sakai
- N Sakai, Department of Nephrology and Laboratory Medicine, Kanazawa University, Kanazawa, Japan
| | - Hiroyuki Yamada
- H Yamada, Department of Nephrology, Chiba University Graduate School of Medicine School of Medicine, Chiba, Japan
| | - Katsuhiko Asanuma
- K Asanuma, Department of Nephrology, Chiba University Graduate School of Medicine School of Medicine, Chiba, Japan
| | - Kouji Matsushima
- K Matsushima, Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute of Biomedical Sciences, Tokyo University of Science, Shinjuku-ku, Japan
| | - Takashi Wada
- T Wada, Nephrology and Laboratory Medicine, Kanazawa University, Kanazawa, Japan
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Cabrera SM, Coren AT, Pant T, Ciecko AE, Jia S, Roethle MF, Simpson PM, Atkinson SN, Salzman NH, Chen YG, Hessner MJ. Probiotic normalization of systemic inflammation in siblings of type 1 diabetes patients: an open-label pilot study. Sci Rep 2022; 12:3306. [PMID: 35228584 PMCID: PMC8885673 DOI: 10.1038/s41598-022-07203-6] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 02/10/2022] [Indexed: 12/14/2022] Open
Abstract
The incidence of type 1 diabetes (T1D) has increased, coinciding with lifestyle changes that have likely altered the gut microbiota. Dysbiosis, gut barrier dysfunction, and elevated systemic inflammation consistent with microbial antigen exposure, have been associated with T1D susceptibility and progression. A 6-week, single-arm, open-label pilot trial was conducted to investigate whether daily multi-strain probiotic supplementation could reduce this familial inflammation in 25 unaffected siblings of T1D patients. Probiotic supplementation was well-tolerated as reflected by high participant adherence and no adverse events. Community alpha and beta diversity were not altered between the pre- and post-supplement stool samplings. However, LEfSe analyses identified post-supplement enrichment of the family Lachnospiraceae, producers of the anti-inflammatory short chain fatty acid butyrate. Systemic inflammation was measured by plasma-induced transcription and quantified with a gene ontology-based composite inflammatory index (I.I.com). Post-supplement I.I.com was significantly reduced and pathway analysis predicted inhibition of numerous inflammatory mediators and activation of IL10RA. Subjects with the greatest post-supplement reduction in I.I.com exhibited significantly lower CD4+ CD45RO+ (memory):CD4+ CD45RA+ (naïve) T-cell ratios after supplementation. Post-supplement IL-12p40, IL-13, IL-15, IL-18, CCL2, and CCL24 plasma levels were significantly reduced, while post-supplement butyrate levels trended 1.4-fold higher. Probiotic supplementation may modify T1D susceptibility and progression and warrants further study.
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Affiliation(s)
- Susanne M Cabrera
- The Max McGee Research Center for Juvenile Diabetes, Children's Research Institute of Children's Wisconsin, Milwaukee, WI, USA
- Division of Endocrinology, Department of Pediatrics, Section of Endocrinology, The Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA
| | - Alison T Coren
- The Max McGee Research Center for Juvenile Diabetes, Children's Research Institute of Children's Wisconsin, Milwaukee, WI, USA
- Division of Endocrinology, Department of Pediatrics, Section of Endocrinology, The Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA
| | - Tarun Pant
- The Max McGee Research Center for Juvenile Diabetes, Children's Research Institute of Children's Wisconsin, Milwaukee, WI, USA
- Division of Endocrinology, Department of Pediatrics, Section of Endocrinology, The Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA
| | - Ashley E Ciecko
- The Max McGee Research Center for Juvenile Diabetes, Children's Research Institute of Children's Wisconsin, Milwaukee, WI, USA
- Division of Endocrinology, Department of Pediatrics, Section of Endocrinology, The Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA
| | - Shuang Jia
- The Max McGee Research Center for Juvenile Diabetes, Children's Research Institute of Children's Wisconsin, Milwaukee, WI, USA
- Division of Endocrinology, Department of Pediatrics, Section of Endocrinology, The Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA
| | - Mark F Roethle
- The Max McGee Research Center for Juvenile Diabetes, Children's Research Institute of Children's Wisconsin, Milwaukee, WI, USA
- Division of Endocrinology, Department of Pediatrics, Section of Endocrinology, The Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA
| | - Pippa M Simpson
- Division of Quantitative Health Sciences, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, 53226, USA
| | - Samantha N Atkinson
- Center for Microbiome Research, Medical College of Wisconsin, Milwaukee, WI, 53226, USA
- Department of Microbiology & Immunology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA
| | - Nita H Salzman
- Center for Microbiome Research, Medical College of Wisconsin, Milwaukee, WI, 53226, USA
- Department of Microbiology & Immunology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA
- Division of Gastroenterology, Department of Pediatrics, The Medical College of Wisconsin, Milwaukee, WI, USA
| | - Yi-Guang Chen
- The Max McGee Research Center for Juvenile Diabetes, Children's Research Institute of Children's Wisconsin, Milwaukee, WI, USA
- Division of Endocrinology, Department of Pediatrics, Section of Endocrinology, The Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA
| | - Martin J Hessner
- The Max McGee Research Center for Juvenile Diabetes, Children's Research Institute of Children's Wisconsin, Milwaukee, WI, USA.
- Division of Endocrinology, Department of Pediatrics, Section of Endocrinology, The Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA.
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Rossella C, Laura F, Grazia MM, Raffaele B, Antonio T, Maria P, Francesco DV, Giovanni G. The crosstalk between gut microbiota, intestinal immunological niche and visceral adipose tissue as a new model for the pathogenesis of metabolic and inflammatory diseases: the paradigm of type 2 diabetes mellitus. Curr Med Chem 2022; 29:3189-3201. [PMID: 34986766 DOI: 10.2174/0929867329666220105121124] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2021] [Revised: 11/12/2021] [Accepted: 11/21/2021] [Indexed: 11/22/2022]
Abstract
Gut microbiota (GM) comprises more than one thousand microorganisms between bacterial species, viruses, fungi, and protozoa, and represents the main actor of a wide net of molecular interactions, involving, among others, the endocrine system, immune responses, and metabolism. GM influences many endocrine functions such as adrenal steroidogenesis, thyroid function, sexual hormones, IGF-1 pathway and peptides produced in gastrointestinal system. It is fundamental in glycaemic control and obesity, while also exerting an important function in modulating the immune system and associated inflammatory disease. The result of this crosstalk in gut mucosa is the formation of the intestinal immunological niche. Visceral adipose tissue (VAT) produces about 600 different peptides, it is involved in lipid and glucose metabolism and in some immune reactions through several adipokines. GM and VAT interact in a bidirectional fashion: while gut dysbiosis can modify VAT adipokines and hormone secretion, VAT hyperplasia modifies GM composition. Acquired or genetic factors leading to gut dysbiosis or increasing VAT (i.e., Western diet) induce a proinflammatory condition, which plays a pivotal role in the development of dysmetabolic and immunologic conditions, such as diabetes mellitus. Diabetes is clearly associated with specific patterns of GM alterations, with an abundance or reduction of GM species involved in controlling mucosal barrier status, glycaemic levels and exerting a pro- or anti-inflammatory activity. All these factors could explain the higher incidence of several inflammatory conditions in Western countries; furthermore, besides the specific alterations observed in diabetes, this paradigm could represent a common pathway acting in many metabolic conditions and could pave the way to a new, interesting therapeutic approach.
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Affiliation(s)
- Cianci Rossella
- Dipartimento di Medicina e Chirurgia Traslazionale Università Cattolica del Sacro Cuore Fondazione Policlinico Universitario A. Gemelli, IRCCS Largo A. Gemelli, 8 00168 Rome, Italy
| | - Franza Laura
- Emergency Medicine, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
| | - Massaro Maria Grazia
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
| | - Borriello Raffaele
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
| | - Tota Antonio
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
| | - Pallozzi Maria
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
| | - De Vito Francesco
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
| | - Gambassi Giovanni
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
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Sargin P, Roethle MF, Jia S, Pant T, Ciecko AE, Atkinson SN, Salzman NH, Teng RJ, Chen YG, Cabrera SM, Hessner MJ. Lactiplantibacillus plantarum 299v supplementation modulates β-cell ER stress and antioxidative defense pathways and prevents type 1 diabetes in gluten-free BioBreeding rats. Gut Microbes 2022; 14:2136467. [PMID: 36261888 PMCID: PMC9586621 DOI: 10.1080/19490976.2022.2136467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 09/23/2022] [Accepted: 10/03/2022] [Indexed: 02/04/2023] Open
Abstract
The increasing incidence of Type 1 diabetes has coincided with the emergence of the low-fiber, high-gluten Western diet and other environmental factors linked to dysbiosis. Since Lactiplantibacillus plantarum 299 v (Lp299v) supplementation improves gut barrier function and reduces systemic inflammation, we studied its effects in spontaneously diabetic DRlyp/lyp rats provided a normal cereal diet (ND) or a gluten-free hydrolyzed casein diet (HCD). All rats provided ND developed diabetes (62.5±7.7 days); combining ND with Lp299v did not improve survival. Diabetes was delayed by HCD (72.2±9.4 days, p = .01) and further delayed by HCD+Lp299v (84.9±14.3 days, p < .001). HCD+Lp299v pups exhibited increased plasma propionate and butyrate levels, which correlated with enriched fecal Bifidobacteriaceae and Clostridiales taxa. Islet transcriptomic and histologic analyses at 40-days of age revealed that rats fed HCD expressed an autophagy profile, while those provided HCD+Lp299v expressed ER-associated protein degradation (ERAD) and antioxidative defense pathways, including Nrf2. Exposing insulinoma cells to propionate and butyrate promoted the antioxidative defense response but did not recapitulate the HCD+Lp299v islet ERAD transcriptomic profile. Here, both diet and microbiota influenced diabetes susceptibility. Moreover, Lp299v supplement modulated antioxidative defense and ER stress responses in β-cells, potentially offering a new therapeutic direction to thwart diabetes progression and preserve insulin secretion.
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Affiliation(s)
- Pinar Sargin
- The Max McGee Research Center for Juvenile Diabetes, Children’s Research Institute of Children’s Hospital of Wisconsin, Milwaukee, WI, USA
- Department of Pediatrics, Division of Endocrinology, the Medical College of Wisconsin, Milwaukee, WI, USA
| | - Mark F. Roethle
- The Max McGee Research Center for Juvenile Diabetes, Children’s Research Institute of Children’s Hospital of Wisconsin, Milwaukee, WI, USA
- Department of Pediatrics, Division of Endocrinology, the Medical College of Wisconsin, Milwaukee, WI, USA
| | - Shuang Jia
- The Max McGee Research Center for Juvenile Diabetes, Children’s Research Institute of Children’s Hospital of Wisconsin, Milwaukee, WI, USA
- Department of Pediatrics, Division of Endocrinology, the Medical College of Wisconsin, Milwaukee, WI, USA
| | - Tarun Pant
- The Max McGee Research Center for Juvenile Diabetes, Children’s Research Institute of Children’s Hospital of Wisconsin, Milwaukee, WI, USA
- Department of Pediatrics, Division of Endocrinology, the Medical College of Wisconsin, Milwaukee, WI, USA
| | - Ashley E. Ciecko
- The Max McGee Research Center for Juvenile Diabetes, Children’s Research Institute of Children’s Hospital of Wisconsin, Milwaukee, WI, USA
- Department of Pediatrics, Division of Endocrinology, the Medical College of Wisconsin, Milwaukee, WI, USA
| | - Samantha N. Atkinson
- Center for Microbiome Research, Medical College of Wisconsin, Milwaukee, WI, USA
- Department of Microbiology & Immunology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Nita H. Salzman
- Center for Microbiome Research, Medical College of Wisconsin, Milwaukee, WI, USA
- Department of Microbiology & Immunology, Medical College of Wisconsin, Milwaukee, WI, USA
- Department of Pediatrics, Division of Gastroenterology, the Medical College of Wisconsin, Milwaukee, WI, USA
| | - Ru-Jeng Teng
- Department of Pediatrics, Division of Neonatology, the Medical College of Wisconsin, Milwaukee, WI, USA
| | - Yi-Guang Chen
- The Max McGee Research Center for Juvenile Diabetes, Children’s Research Institute of Children’s Hospital of Wisconsin, Milwaukee, WI, USA
- Department of Pediatrics, Division of Endocrinology, the Medical College of Wisconsin, Milwaukee, WI, USA
| | - Susanne M. Cabrera
- The Max McGee Research Center for Juvenile Diabetes, Children’s Research Institute of Children’s Hospital of Wisconsin, Milwaukee, WI, USA
- Department of Pediatrics, Division of Endocrinology, the Medical College of Wisconsin, Milwaukee, WI, USA
| | - Martin J. Hessner
- The Max McGee Research Center for Juvenile Diabetes, Children’s Research Institute of Children’s Hospital of Wisconsin, Milwaukee, WI, USA
- Department of Pediatrics, Division of Endocrinology, the Medical College of Wisconsin, Milwaukee, WI, USA
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Clos-Garcia M, Ahluwalia TS, Winther SA, Henriksen P, Ali M, Fan Y, Stankevic E, Lyu L, Vogt JK, Hansen T, Legido-Quigley C, Rossing P, Pedersen O. Multiomics signatures of type 1 diabetes with and without albuminuria. Front Endocrinol (Lausanne) 2022; 13:1015557. [PMID: 36531462 PMCID: PMC9755599 DOI: 10.3389/fendo.2022.1015557] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Accepted: 11/11/2022] [Indexed: 12/05/2022] Open
Abstract
AIMS/HYPOTHESIS To identify novel pathophysiological signatures of longstanding type 1 diabetes (T1D) with and without albuminuria we investigated the gut microbiome and blood metabolome in individuals with T1D and healthy controls (HC). We also mapped the functional underpinnings of the microbiome in relation to its metabolic role. METHODS One hundred and sixty-one individuals with T1D and 50 HC were recruited at the Steno Diabetes Center Copenhagen, Denmark. T1D cases were stratified based on levels of albuminuria into normoalbuminuria, moderate and severely increased albuminuria. Shotgun sequencing of bacterial and viral microbiome in stool samples and circulating metabolites and lipids profiling using mass spectroscopy in plasma of all participants were performed. Functional mapping of microbiome into Gut Metabolic Modules (GMMs) was done using EggNog and KEGG databases. Multiomics integration was performed using MOFA tool. RESULTS Measures of the gut bacterial beta diversity differed significantly between T1D and HC, either with moderately or severely increased albuminuria. Taxonomic analyses of the bacterial microbiota identified 51 species that differed in absolute abundance between T1D and HC (17 higher, 34 lower). Stratified on levels of albuminuria, 10 species were differentially abundant for the moderately increased albuminuria group, 63 for the severely increased albuminuria group while 25 were common and differentially abundant both for moderately and severely increased albuminuria groups, when compared to HC. Functional characterization of the bacteriome identified 23 differentially enriched GMMs between T1D and HC, mostly involved in sugar and amino acid metabolism. No differences in relation to albuminuria stratification was observed. Twenty-five phages were differentially abundant between T1D and HC groups. Six of these varied with albuminuria status. Plasma metabolomics indicated differences in the steroidogenesis and sugar metabolism and circulating sphingolipids in T1D individuals. We identified association between sphingolipid levels and Bacteroides sp. abundances. MOFA revealed reduced interactions between gut microbiome and plasma metabolome profiles albeit polar metabolite, lipids and bacteriome compositions contributed to the variance in albuminuria levels among T1D individuals. CONCLUSIONS Individuals with T1D and progressive kidney disease stratified on levels of albuminuria show distinct signatures in their gut microbiome and blood metabolome.
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Affiliation(s)
- Marc Clos-Garcia
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- LEITAT Technological Center, Terrassa, Spain
| | - Tarunveer S. Ahluwalia
- Complications Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
- The Bioinformatics Center, Department of Biology, University of Copenhagen, Copenhagen, Denmark
| | - Signe A. Winther
- Complications Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
| | - Peter Henriksen
- Complications Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
| | - Mina Ali
- Complications Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
| | - Yong Fan
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Evelina Stankevic
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Liwei Lyu
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Josef K. Vogt
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Clinical Microbiomics, Copenhagen, Denmark
| | - Torben Hansen
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | | | - Peter Rossing
- Complications Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Oluf Pedersen
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Center for Clinical Metabolic Research, Gentofte University Hospital, Copenhagen, Denmark
- *Correspondence: Oluf Pedersen,
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Hu J, Zhang R, Zou H, Xie L, Zhou Z, Xiao Y. Latent Autoimmune Diabetes in Adults (LADA): From Immunopathogenesis to Immunotherapy. Front Endocrinol (Lausanne) 2022; 13:917169. [PMID: 35937817 PMCID: PMC9350734 DOI: 10.3389/fendo.2022.917169] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2022] [Accepted: 05/26/2022] [Indexed: 11/26/2022] Open
Abstract
Latent autoimmune diabetes in adults (LADA) is a type of diabetes characterized by slow autoimmune damage of pancreatic β cells without insulin treatment in the early clinical stage. There are differences between LADA and classical type 1 diabetes (T1D) and type 2 diabetes (T2D) in genetic background, autoimmune response, rate of islet function decline, clinical metabolic characteristics, and so on. The disease progression and drug response of patients with LADA are closely related to the level of islet autoimmunity, thus exploring the pathogenesis of LADA is of great significance for its prevention and treatment. Previous studies reported that adaptive immunity and innate immunity play a critical role in the etiology of LADA. Recent studies have shown that the intestinal microbiota which impacts host immunity hugely, participates in the pathogenesis of LADA. In addition, the progression of autoimmune pancreatic β cell destruction in LADA is slower than in classical T1D, providing a wider window of opportunities for intervention. Therefore, therapies including antidiabetic drugs with immune-regulation effects and immunomodulators could contribute to promising interventions for LADA. We also shed light on potential interventions targeting the gut microbiota and gut-associated immunity, which may be envisaged to halt or delay the process of autoimmunity in LADA.
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Liu J, Zhang Y, Tian Y, Huang W, Tong N, Fu X. Integrative biology of extracellular vesicles in diabetes mellitus and diabetic complications. Theranostics 2022; 12:1342-1372. [PMID: 35154494 PMCID: PMC8771544 DOI: 10.7150/thno.65778] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Accepted: 12/11/2021] [Indexed: 11/14/2022] Open
Abstract
Diabetes mellitus (DM) is a chronic systemic disease with increasing prevalence globally. An important aspect of diabetic pathogenesis is cellular crosstalk and information exchange between multiple metabolic organs and tissues. In the past decade, increasing evidence suggested that extracellular vesicles (EVs), a class of cell-derived membrane vesicles that transmit information and perform inter-cellular and inter-organ communication, are involved in the pathological changes of insulin resistance (IR), inflammation, and endothelial injury, and implicated in the development of DM and its complications. The biogenesis and cargo sorting machinery dysregulation of EVs may mediate their pathogenic roles under diabetic conditions. Moreover, the biogenesis of EVs, their ubiquitous production by different cells, their function as mediators of inter-organ communication, and their biological features in body fluids have generated great promise as biomarkers and clinical treatments. In this review, we summarize the components of EV generation and sorting machinery and highlight their role in the pathogenesis of DM and associated complications. Furthermore, we discuss the emerging clinical implications of EVs as potential biomarkers and therapeutic strategies for DM and diabetic complications. A better understanding of EVs will deepen our knowledge of the pathophysiology of DM and its complications and offer attractive approaches to improve the prevention, diagnosis, treatment, and prognosis of these disorders.
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Affiliation(s)
- Jing Liu
- Division of Endocrinology and Metabolism, National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy and Cancer Center, West China Medical School, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Yanyan Zhang
- Division of Endocrinology and Metabolism, National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy and Cancer Center, West China Medical School, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
- Department of Geriatric Medicine, Lanzhou University Secondary Hospital, Lanzhou, Gansu, China
| | - Yan Tian
- Division of Endocrinology and Metabolism, National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy and Cancer Center, West China Medical School, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Wei Huang
- Department and Laboratory of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu, China
| | - Nanwei Tong
- Division of Endocrinology and Metabolism, Center for Diabetes and Metabolism Research, Laboratory of Diabetes and Islet Transplantation Research, West China Medical School, West China Hospital, Sichuan University, Chengdu, China
| | - Xianghui Fu
- Division of Endocrinology and Metabolism, National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy and Cancer Center, West China Medical School, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
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Danenberg AH. The etiology of gut dysbiosis and its role in chronic disease. MICROBIOME, IMMUNITY, DIGESTIVE HEALTH AND NUTRITION 2022:71-91. [DOI: 10.1016/b978-0-12-822238-6.00020-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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