|
1
|
Lokesh MN, Kumar R, Jacob N, Sachdeva N, Rawat A, Yadav J, Dayal D. Supplementation of High-Strength Oral Probiotics Improves Immune Regulation and Preserves Beta Cells among Children with New-Onset Type 1 Diabetes Mellitus: A Randomised, Double-Blind Placebo Control Trial. Indian J Pediatr 2025; 92:277-283. [PMID: 38557820 DOI: 10.1007/s12098-024-05074-5] [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: 09/30/2023] [Accepted: 01/24/2024] [Indexed: 04/04/2024]
Abstract
OBJECTIVES To investigate the mechanism of glycemic control in children with type 1 diabetes (T1D) following high-strength probiotics supplementation by assessing immune-regulatory markers. METHODS In this single-centre randomised double-blinded placebo-controlled study, children with new-onset T1D on regular insulin therapy were randomised into probiotic or placebo groups with 30 children each. The probiotics group received oral powder of Vivomixx®, and the placebo group received corn starch for six months. The primary outcome parameters included induced T regulatory cells (i-Tregs) percentage, insulin autoantibodies (IAA), insulinoma associated 2 autoantibodies (IA2), glutamic acid decarboxylase autoantibodies (GAD 65) and plasma interleukin-10 (IL-10) levels. The secondary outcome variables were changes in plasma C-peptide levels and glycemic control parameters. RESULTS Twenty-three children in the placebo group and 27 in the probiotic group completed the study. There was a significant increase in the percentage of iTregs (3.40 in the probiotic vs. 2.46 in the placebo group; p = 0.034). Median glycated hemoglobin (HbA1c) levels significantly decreased from 68 mmol/mol (8.35%) in the placebo group to 60 mmol/mol (7.55%) in the probiotic group (p = 0.017). Median C-peptide levels were significantly higher in probiotics (0.72 ng/ml) vs. placebo group (0.11 ng/ml) (p = 0.036). The plasma IL-10 levels significantly increased in the probiotic group after six months of treatment (p = 0.002). CONCLUSIONS The high-strength probiotics improved the immunoregulatory milieu, thereby preserving the beta-cell function and better glycemic control.
Collapse
Affiliation(s)
- M N Lokesh
- Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India
| | - Rakesh Kumar
- Endocrinology and Diabetes Unit, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research (PGIMER), Sector 12, Chandigarh, 160012, India.
| | - Neenu Jacob
- Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India
| | - Naresh Sachdeva
- Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India
| | - Amit Rawat
- Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India
| | - Jaivinder Yadav
- Endocrinology and Diabetes Unit, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research (PGIMER), Sector 12, Chandigarh, 160012, India
| | - Devi Dayal
- Endocrinology and Diabetes Unit, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research (PGIMER), Sector 12, Chandigarh, 160012, India
| |
Collapse
|
|
2
|
Wang CY, Wang JY, Chou YY, Lin CC, Lin YT, Wu CS, Lin JS, Chu CL. The fungal protein Lingzhi-8 ameliorates psoriasis-like dermatitis in mice through gut CD103 + tolerogenic dendritic cells, retinaldehyde dehydrogenase 2, and Dectin-1. Biomed Pharmacother 2025; 184:117910. [PMID: 39954596 DOI: 10.1016/j.biopha.2025.117910] [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: 06/21/2024] [Revised: 01/26/2025] [Accepted: 02/05/2025] [Indexed: 02/17/2025] Open
Abstract
The gut CD103+ tolerogenic dendritic cells play a key role in maintaining immune balance by inducing oral tolerance, which has been implied in reducing autoimmunity. We recently reported that the oral administration of a fungal protein Lingzhi-8 (LZ-8) prevented autoimmune colitis in mice via maintaining barrier integrity. Here, we examined the functional effect of LZ-8 on gut CD103+ DCs and on autoimmune psoriasis in a mouse model. After orally administered LZ-8 to mice, the numbers of CD103+ DCs and their retinaldehyde dehydrogenase 2 (RALDH2) activities were increased in the mesenteric lymph nodes (mLNs), which were associated with increased regulatory T cell (Treg) in the spleen and LNs. This suggests that LZ-8 induces oral tolerance by enhancing the RALDH2 activity of CD103+ DCs. In addition, the imiquimod (IMQ)-induced psoriasis-like dermatitis was attenuated in mice after LZ-8 pretreatment. In the mechanistic study, we generated gut CD103+ DC-like cells from bone marrow (BM) of wild-type mouse and cultured them in the presence of retinoic acid (RA) in vitro. We found that LZ-8 directly enhanced the RALDH2 activity of these RA-primed CD103+ DCs, which was dependent on Dectin-1 and Syk signaling pathways but not TLR4. Together, our study demonstrated that LZ-8 facilitated gut tolerogenic CD103+ DC-mediated immunosuppression by enhancing RALDH2 activity, increasing Treg cell population, and signaling through Dectin-1 and Syk. Our findings provide a novel strategy for treating psoriasis and potentially other autoimmune diseases.
Collapse
Affiliation(s)
- Chen-Yu Wang
- Graduate Institute of Immunology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jen-Yu Wang
- Graduate Institute of Immunology, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Dermatology, MacKay Memorial Hospital, Taipei, Taiwan; Mackay Junior College of Medicine, Nursing, and Management, New Taipei City, Taiwan; Department of Medicine, Mackay Medical College, New Taipei City, Taiwan
| | - Yi-Yi Chou
- Graduate Institute of Immunology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chi-Chien Lin
- Institute of Biomedical Sciences, National Chung-Hsing University, Taichung, Taiwan
| | - Yu-Tsun Lin
- Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan
| | - Chi-Sheng Wu
- Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan; Department of Otolaryngology-Head & Neck Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
| | - Jr-Shiuan Lin
- Graduate Institute of Immunology, National Taiwan University College of Medicine, Taipei, Taiwan.
| | - Ching-Liang Chu
- Graduate Institute of Immunology, National Taiwan University College of Medicine, Taipei, Taiwan.
| |
Collapse
|
|
3
|
Li J, Xie Z, Yang L, Guo K, Zhou Z. The impact of gut microbiome on immune and metabolic homeostasis in type 1 diabetes: Clinical insights for prevention and treatment strategies. J Autoimmun 2025; 151:103371. [PMID: 39883994 DOI: 10.1016/j.jaut.2025.103371] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Revised: 01/17/2025] [Accepted: 01/21/2025] [Indexed: 02/01/2025]
Abstract
Type 1 diabetes (T1D) is a complex disease triggered by a combination of genetic and environmental factors, where abnormal autoimmune responses lead to progressive damage of the pancreatic β cells and severe glucose metabolism disorder. Recent studies have increasingly highlighted the close link between gut microbiota dysbiosis and the development of T1D. This review delves into existing population studies to explore the intricate interactions between the gut microbiota and the immune and metabolic homeostasis in T1D. It summarizes how changes in the structure and function of the gut microbiota are closely associated with the onset and progression of T1D across its natural course and clinical stages. More importantly, based on evidence accumulated from clinical observations and trials, we pioneer the discussion on gut microbiota-based T1D prevention and treatment strategies, this not only enriches our understanding of the complex pathological mechanisms of T1D but also provides potential directions for developing novel prevention and treatment strategies.
Collapse
Affiliation(s)
- Jiaqi Li
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Zhiguo Xie
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Lin Yang
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.
| | - Keyu Guo
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.
| | - 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 Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| |
Collapse
|
|
4
|
Nikola L, Iva L. Gut microbiota as a modulator of type 1 diabetes: A molecular perspective. Life Sci 2024; 359:123187. [PMID: 39488260 DOI: 10.1016/j.lfs.2024.123187] [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: 05/22/2024] [Revised: 10/04/2024] [Accepted: 10/24/2024] [Indexed: 11/04/2024]
Abstract
Type 1 diabetes (T1D) is defined as an autoimmune metabolic disorder, characterized by destruction of pancreatic β-cells and high blood sugar levels. If left untreated, T1D results in severe health complications, including cardiovascular and kidney disease, as well as nerve damage, with ultimately grave consequences. Besides the role of genetic and certain environmental factors in T1D development, in the last decade, one new player emerged to affect T1D pathology as well, and that is a gut microbiota. Dysbiosis of gut bacteria can contribute to T1D by gut barrier disruption and the activation of autoimmune response, leading to the destruction of insulin producing cells, causing the development and aggravation of T1D symptoms. The relationship between gut microbiota and diabetes is complex and varies between individuals and additional research is needed to fully understand the effects of gut microbiome alternations in T1D pathogenesis. Therefore, the goal of this review is to understand the current knowledge in underlying molecular mechanism of gut microbiota effects, which leads to the new approaches for further studies in the prevention and treatment of T1D.
Collapse
Affiliation(s)
- Lukic Nikola
- Laboratory for Molecular Biology and Endocrinology, Institute of Nuclear Sciences "Vinca", National Institute of the Republic of Serbia, University of Belgrade, Serbia
| | - Lukic Iva
- Laboratory for Molecular Biology and Endocrinology, Institute of Nuclear Sciences "Vinca", National Institute of the Republic of Serbia, University of Belgrade, Serbia.
| |
Collapse
|
|
5
|
Prapa I, Yanni AE, Kompoura V, Mitropoulou G, Panas P, Kostomitsopoulos N, Kourkoutas Y. Functional Modulation of Gut Microbiota and Blood Parameters in Diabetic Rats Following Dietary Intervention with Free or Immobilized Pediococcus acidilactici SK Cells on Pistachio Nuts. Nutrients 2024; 16:4221. [PMID: 39683613 DOI: 10.3390/nu16234221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Revised: 12/01/2024] [Accepted: 12/02/2024] [Indexed: 12/18/2024] Open
Abstract
BACKGROUND/OBJECTIVES The gut microbiota is linked to the pathogenesis of type 1 diabetes mellitus (T1DM), while supplementation with probiotics may result in positive alterations in the composition of the gut microbiome. This research aimed to map the changes in the gut microbiome and blood markers of streptozotocin-induced diabetic rats after a dietary intervention with free or immobilized cells of the presumptive probiotic Pediococcus acidilactici SK on pistachio nuts. METHODS Twenty-four male Wistar rats were studied and divided into four groups (healthy or diabetic) which received the free or the immobilized P. acidilactici SK cells on pistachio nuts for 4 weeks. Blood, fecal, and intestinal tissue samples were examined. RESULTS The diabetic rats exhibited an elevated concentration of HDL-c, while the inflammatory IL-1β levels were significantly lower in the diabetic animals that received the immobilized cells compared to the group that received the free cells. The dietary intervention with immobilized cells led to decreased counts of fecal staphylococci and enterococci in the diabetic animals, while the diet with both free and immobilized P. acidilactici SK cells rendered levels of these populations in normal values in the feces and intestinal tissue of the diabetic animals. Noticeably, the Lactobacillus and Bifidobacterium genera were elevated after the supplementation with immobilized P. acidilactici SK cells on pistachio nuts. CONCLUSIONS Dietary supplementation with P. acidilactici SK cells (in free or in immobilized form) beneficially affected the gut microbiota/microbiome of streptozotocin-induced diabetic rats, leading to the alleviation of dysbiosis and inflammation and control over their lipid levels.
Collapse
Affiliation(s)
- Ioanna Prapa
- Laboratory of Applied Microbiology and Biotechnology, Department of Molecular Biology and Genetics, Democritus University of Thrace, 68100 Alexandroupolis, Greece
| | - Amalia E Yanni
- Laboratory of Chemistry, Biochemistry, Physical Chemistry of Foods, Department of Nutrition and Dietetics, Harokopio University of Athens, 17671 Athens, Greece
| | - Vasiliki Kompoura
- Laboratory of Applied Microbiology and Biotechnology, Department of Molecular Biology and Genetics, Democritus University of Thrace, 68100 Alexandroupolis, Greece
| | - Gregoria Mitropoulou
- Laboratory of Applied Microbiology and Biotechnology, Department of Molecular Biology and Genetics, Democritus University of Thrace, 68100 Alexandroupolis, Greece
| | | | - Nikolaos Kostomitsopoulos
- Laboratory Animal Facility, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece
| | - Yiannis Kourkoutas
- Laboratory of Applied Microbiology and Biotechnology, Department of Molecular Biology and Genetics, Democritus University of Thrace, 68100 Alexandroupolis, Greece
| |
Collapse
|
|
6
|
Prapa I, Kompoura V, Pavlatou C, Nelios G, Mitropoulou G, Kostomitsopoulos N, Plessas S, Bezirtzoglou E, Karathanos VT, Yanni AE, Kourkoutas Y. Effects of Free or Immobilized Pediococcus acidilactici ORE5 on Corinthian Currants on Gut Microbiome of Streptozotocin-Induced Diabetic Rats. Microorganisms 2024; 12:2004. [PMID: 39458313 PMCID: PMC11509866 DOI: 10.3390/microorganisms12102004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 09/29/2024] [Accepted: 09/29/2024] [Indexed: 10/28/2024] Open
Abstract
The present study aimed to investigate the effect of a dietary intervention including free or immobilized cells of the presumptive probiotic Pediococcus acidilactici ORE5 on Corinthian currants, a food with beneficial impact in the condition of Type-1 Diabetes Mellitus (T1DM), on the microbiome composition of STZ-induced diabetic rats. Twenty four male Wistar rats were divided into four groups (n = 6 per group): healthy animals, which received the free (H_FP) or the immobilized Pediococcus acidilactici ORE5 cells (H_IPC), and diabetic animals, which received the free (D_FP) or the immobilized Pediococcus acidilactici ORE5 cells(D_IPC) for 4 weeks (109 cfu/day, in all groups). At the end of the dietary intervention, the D_IPC group exerted a lower concentration of the inflammatory cytokine IL-1 beta compared to D_FP. Consumption of immobilized P. acidilactici ORE5 cells on Corinthian currants by diabetic animals led to increased loads of fecal lactobacilli and lower Enterobacteriaceae, coliforms, and Escherichia coli levels, while Actinobacteria phylum, Akkermansia, and Bifidobacterium genera abundances were increased, and fecal lactic acid was elevated. Overall, the results of the present research demonstrated that functional ingredients could ameliorate gut dysbiosis present in T1DM and could be used to design dietary patterns aiming at T1DM management. However, well-designed clinical trials are necessary, in order to confirm the beneficial effects in humans.
Collapse
Affiliation(s)
- Ioanna Prapa
- Laboratory of Applied Microbiology and Biotechnology, Department of Molecular Biology and Genetics, Democritus University of Thrace, Dragana, 68100 Alexandroupolis, Greece; (I.P.); (V.K.); (C.P.); (G.N.); (G.M.)
| | - Vasiliki Kompoura
- Laboratory of Applied Microbiology and Biotechnology, Department of Molecular Biology and Genetics, Democritus University of Thrace, Dragana, 68100 Alexandroupolis, Greece; (I.P.); (V.K.); (C.P.); (G.N.); (G.M.)
| | - Chrysoula Pavlatou
- Laboratory of Applied Microbiology and Biotechnology, Department of Molecular Biology and Genetics, Democritus University of Thrace, Dragana, 68100 Alexandroupolis, Greece; (I.P.); (V.K.); (C.P.); (G.N.); (G.M.)
| | - Grigorios Nelios
- Laboratory of Applied Microbiology and Biotechnology, Department of Molecular Biology and Genetics, Democritus University of Thrace, Dragana, 68100 Alexandroupolis, Greece; (I.P.); (V.K.); (C.P.); (G.N.); (G.M.)
| | - Gregoria Mitropoulou
- Laboratory of Applied Microbiology and Biotechnology, Department of Molecular Biology and Genetics, Democritus University of Thrace, Dragana, 68100 Alexandroupolis, Greece; (I.P.); (V.K.); (C.P.); (G.N.); (G.M.)
| | - Nikolaos Kostomitsopoulos
- Laboratory Animal Facility, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece;
| | - Stavros Plessas
- Laboratory of Microbiology, Biotechnology and Hygiene, Faculty of Agricultural Development, Democritus University of Thrace, 68200 Orestiada, Greece;
| | - Eugenia Bezirtzoglou
- Laboratory of Hygiene and Environmental Protection, Department of Medicine, Democritus University of Thrace, Dragana, 68100 Alexandroupolis, Greece;
| | - Vaios T. Karathanos
- Laboratory of Chemistry, Biochemistry, Physical Chemistry of Foods, Department of Nutrition and Dietetics, Harokopio University of Athens, 17671 Athens, Greece;
- Agricultural Cooperatives’ Union of Aeghion, Corinthou 201, 25100 Aeghion, Greece
| | - Amalia E. Yanni
- Laboratory of Chemistry, Biochemistry, Physical Chemistry of Foods, Department of Nutrition and Dietetics, Harokopio University of Athens, 17671 Athens, Greece;
| | - Yiannis Kourkoutas
- Laboratory of Applied Microbiology and Biotechnology, Department of Molecular Biology and Genetics, Democritus University of Thrace, Dragana, 68100 Alexandroupolis, Greece; (I.P.); (V.K.); (C.P.); (G.N.); (G.M.)
| |
Collapse
|
|
7
|
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.
Collapse
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.)
| |
Collapse
|
|
8
|
Zeng L, Yang K, He Q, Zhu X, Long Z, Wu Y, Chen J, Li Y, Zeng J, Cui G, Xiang W, Hao W, Sun L. Efficacy and safety of gut microbiota-based therapies in autoimmune and rheumatic diseases: a systematic review and meta-analysis of 80 randomized controlled trials. BMC Med 2024; 22:110. [PMID: 38475833 PMCID: PMC10935932 DOI: 10.1186/s12916-024-03303-4] [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: 06/27/2023] [Accepted: 02/13/2024] [Indexed: 03/14/2024] Open
Abstract
BACKGROUND Previous randomized controlled trials (RCTs) suggested that gut microbiota-based therapies may be effective in treating autoimmune diseases, but a systematic summary is lacking. METHODS Pubmed, EMbase, Sinomed, and other databases were searched for RCTs related to the treatment of autoimmune diseases with probiotics from inception to June 2022. RevMan 5.4 software was used for meta-analysis after 2 investigators independently screened literature, extracted data, and assessed the risk of bias of included studies. RESULTS A total of 80 RCTs and 14 types of autoimmune disease [celiac sprue, SLE, and lupus nephritis (LN), RA, juvenile idiopathic arthritis (JIA), spondyloarthritis, psoriasis, fibromyalgia syndrome, MS, systemic sclerosis, type 1 diabetes mellitus (T1DM), oral lichen planus (OLP), Crohn's disease, ulcerative colitis] were included. The results showed that gut microbiota-based therapies may improve the symptoms and/or inflammatory factor of celiac sprue, SLE and LN, JIA, psoriasis, PSS, MS, systemic sclerosis, Crohn's disease, and ulcerative colitis. However, gut microbiota-based therapies may not improve the symptoms and/or inflammatory factor of spondyloarthritis and RA. Gut microbiota-based therapies may relieve the pain of fibromyalgia syndrome, but the effect on fibromyalgia impact questionnaire score is not significant. Gut microbiota-based therapies may improve HbA1c in T1DM, but its effect on total insulin requirement does not seem to be significant. These RCTs showed that probiotics did not increase the incidence of adverse events. CONCLUSIONS Gut microbiota-based therapies may improve several autoimmune diseases (celiac sprue, SLE and LN, JIA, psoriasis, fibromyalgia syndrome, PSS, MS, T1DM, Crohn's disease, and ulcerative colitis).
Collapse
Affiliation(s)
- Liuting Zeng
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Graduate School of Peking Union Medical College, Nanjing, China.
| | - Kailin Yang
- Hunan University of Chinese Medicine, Changsha, China
| | - Qi He
- People's Hospital of Ningxiang City, Ningxiang, China
| | | | - Zhiyong Long
- Department of Rehabilitation Medicine, Guangzhou Panyu Central Hospital, Guangzhou, China
| | - Yang Wu
- Department of Rheumatology, National Clinical Research Center for Dermatologic and Immunologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | | | - Yuwei Li
- Hunan University of Science and Technology, Xiangtan, China
| | - Jinsong Zeng
- Department of Rheumatology, National Clinical Research Center for Dermatologic and Immunologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Ge Cui
- Department of Epidemiology and Statistics, School of Public Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Wang Xiang
- Department of Rheumatology, The First People's Hospital Changde City, Changde, China
| | - Wensa Hao
- Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lingyun Sun
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Graduate School of Peking Union Medical College, Nanjing, China.
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
| |
Collapse
|
|
9
|
Zheng SJ, Luo Y, Wang JB, Chen XM, Xu Y, Xiao JH. Regulated intestinal microbiota and gut immunity to ameliorate type 1 diabetes mellitus: A novel mechanism for stem cell-based therapy. Biomed Pharmacother 2024; 170:116033. [PMID: 38128181 DOI: 10.1016/j.biopha.2023.116033] [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: 10/01/2023] [Revised: 12/10/2023] [Accepted: 12/14/2023] [Indexed: 12/23/2023] Open
Abstract
Although stem cell transplantation is an effective strategy in the treatment of type 1 diabetes mellitus (T1DM), the mechanisms underlying its therapeutic effects remain unclear. We hypothesized that stem cells target gut microbiota and intestinal mucosal immunity to promote therapeutic effects against T1DM. We investigated the effects of human amniotic mesenchymal stem cells (hAMSCs) on intestinal microbiota and mucosal immunity in streptozotocin-induced T1DM mice. hAMSCs promoted significant reductions in blood glucose levels and increased the number of insulin-secreting cells in the T1DM model. Compared with T1DM model mice, 16S rRNA sequencing revealed significant differences in the composition, diversity, and abundance of microbiota in the ileum of hAMSC-treated mice. Bifidobacterium, Prevotella, and Alcaligenes species were among the 15 most abundant differential bacterial species. LC-MS revealed significant changes in ileal metabolites, and among the top 100 differential metabolites identified, we found that a significant increase in taurine was closely associated with hAMSC therapy. Additionally, we detected significant differences between the two groups with respect to the frequency and phenotype of CD4+ T cell subsets in mesenteric lymph nodes, and hAMSCs promoted significant increases in Th2 and Treg cell frequencies and reduced the frequencies of Th1 and Th17 cells. Moreover, correlation analysis revealed pairwise correlations between differential microflora and differential metabolites and immune signatures. hAMSCs thus have positive effects on the microbiota and their metabolites in the ileum and intestinal mucosal immunity in T1DM. Our findings indicate that gut microbiota and intestinal mucosal immunity may play vital roles in the hAMSC-based treatment of T1DM.
Collapse
Affiliation(s)
- Shu-Juan Zheng
- Institute of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China
| | - Yi Luo
- Institute of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China; Guizhou Provincial Key Laboratory of Medicinal Biotechnology & Research Center for Translational Medicine in Colleges and Universities, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China
| | - Jian-Bin Wang
- Institute of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China; Guizhou Provincial Key Laboratory of Medicinal Biotechnology & Research Center for Translational Medicine in Colleges and Universities, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China
| | - Xue-Mei Chen
- Institute of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China; Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China.
| | - Yan Xu
- Institute of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China; Guizhou Provincial Key Laboratory of Medicinal Biotechnology & Research Center for Translational Medicine in Colleges and Universities, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China
| | - Jian-Hui Xiao
- Institute of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China; Guizhou Provincial Key Laboratory of Medicinal Biotechnology & Research Center for Translational Medicine in Colleges and Universities, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China; Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China.
| |
Collapse
|
|
10
|
Luo M, Sun M, Wang T, Zhang S, Song X, Liu X, Wei J, Chen Q, Zhong T, Qin J. Gut microbiota and type 1 diabetes: a two-sample bidirectional Mendelian randomization study. Front Cell Infect Microbiol 2023; 13:1163898. [PMID: 37313342 PMCID: PMC10258312 DOI: 10.3389/fcimb.2023.1163898] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Accepted: 05/12/2023] [Indexed: 06/15/2023] Open
Abstract
Objective The real causal relationship between human gut microbiota and T1D remains unclear and difficult to establish. Herein, we adopted a two-sample bidirectional mendelian randomization (MR) study to evaluate the causality between gut microbiota and T1D. Methods We leveraged publicly available genome-wide association study (GWAS) summary data to perform MR analysis. The gut microbiota-related GWAS data from 18,340 individuals from the international consortium MiBioGen were used. The summary statistic data for T1D (n = 264,137) were obtained from the latest release from the FinnGen consortium as the outcome of interest. The selection of instrumental variables conformed strictly to a series of preset inclusion and exclusion criteria. MR-Egger, weighted median, inverse variance weighted (IVW), and weighted mode methods were used to assess the causal association. The Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis were conducted to identify heterogeneity and pleiotropy. Results At the phylum level, only Bacteroidetes was indicated to have causality on T1D (OR = 1.24, 95% CI = 1.01-1.53, P = 0.044) in the IVW analysis. When it comes to their subcategories, Bacteroidia class (OR = 1.28, 95% CI = 1.06-1.53, P = 0.009, P FDR = 0.085), Bacteroidales order (OR = 1.28, 95% CI = 1.06-1.53, P = 0.009, P FDR = 0.085), and Eubacterium eligens group genus (OR = 0.64, 95% CI = 0.50-0.81, P = 2.84×10-4, P FDR = 0.031) were observed to have a causal relationship with T1D in the IVW analysis. No heterogeneity and pleiotropy were detected. Conclusions The present study reports that Bacteroidetes phylum, Bacteroidia class, and Bacteroidales order causally increase T1D risk, whereas Eubacterium eligens group genus, which belongs to the Firmicutes phylum, causally decreases T1D risk. Nevertheless, future studies are warranted to dissect the underlying mechanisms of specific bacterial taxa's role in the pathophysiology of T1D.
Collapse
Affiliation(s)
- Manjun Luo
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China
| | - Mengting Sun
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China
| | - Tingting Wang
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China
| | - Senmao Zhang
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China
| | - Xinli Song
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China
| | - Xiaoying Liu
- Changsha Medical University Public Health Institute, Changsha, China
- The Hospital of Trade-Business in Hunan Province, Changsha, China
| | - Jianhui Wei
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China
| | - Qian Chen
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China
| | - Taowei Zhong
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China
| | - Jiabi Qin
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China
- Hunan Provincial Key Laboratory of Clinical Epidemiology, Changsha, China
| |
Collapse
|
|
11
|
Devi MB, Sarma HK, Mukherjee AK, Khan MR. Mechanistic Insights into Immune-Microbiota Interactions and Preventive Role of Probiotics Against Autoimmune Diabetes Mellitus. Probiotics Antimicrob Proteins 2023:10.1007/s12602-023-10087-1. [PMID: 37171690 DOI: 10.1007/s12602-023-10087-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/04/2023] [Indexed: 05/13/2023]
Abstract
Recent studies on genetically susceptible individuals and animal models revealed the potential role of the intestinal microbiota in the pathogenesis of type 1 diabetes (T1D) through complex interactions with the immune system. T1D incidence has been increasing exponentially with modern lifestyle altering normal microbiota composition, causing dysbiosis characterized by an imbalance in the gut microbial community. Dysbiosis has been suggested to be a potential contributing factor in T1D. Moreover, several studies have shown the potential role of probiotics in regulating T1D through various mechanisms. Current T1D therapies target curative measures; however, preventive therapeutics are yet to be proven. This review highlights immune microbiota interaction and the immense role of probiotics and postbiotics as important immunological interventions for reducing the risk of T1D.
Collapse
Affiliation(s)
- M Bidyarani Devi
- Molecular Biology and Microbial Biotechnology Laboratory, Life Sciences Division, Institute of Advanced Study in Science and Technology (IASST), Guwahati, Assam, India
- Department of Biotechnology, Gauhati University, Guwahati, Assam, India
| | | | - Ashis K Mukherjee
- Molecular Biology and Microbial Biotechnology Laboratory, Life Sciences Division, Institute of Advanced Study in Science and Technology (IASST), Guwahati, Assam, India
| | - Mojibur R Khan
- Molecular Biology and Microbial Biotechnology Laboratory, Life Sciences Division, Institute of Advanced Study in Science and Technology (IASST), Guwahati, Assam, India.
| |
Collapse
|
|
12
|
Markelova M, Senina A, Khusnutdinova D, Siniagina M, Kupriyanova E, Shakirova G, Odintsova A, Abdulkhakov R, Kolesnikova I, Shagaleeva O, Lyamina S, Abdulkhakov S, Zakharzhevskaya N, Grigoryeva T. Association between Taxonomic Composition of Gut Microbiota and Host Single Nucleotide Polymorphisms in Crohn's Disease Patients from Russia. Int J Mol Sci 2023; 24:ijms24097998. [PMID: 37175705 PMCID: PMC10178390 DOI: 10.3390/ijms24097998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Revised: 04/25/2023] [Accepted: 04/26/2023] [Indexed: 05/15/2023] Open
Abstract
Crohn's disease (CD) is a chronic relapsing inflammatory bowel disease of unknown etiology. Genetic predisposition and dysbiotic gut microbiota are important factors in the pathogenesis of CD. In this study, we analyzed the taxonomic composition of the gut microbiota and genotypes of 24 single nucleotide polymorphisms (SNP) associated with the risk of CD. The studied cohorts included 96 CD patients and 24 healthy volunteers from Russia. Statistically significant differences were found in the allele frequencies for 8 SNPs and taxonomic composition of the gut microbiota in CD patients compared with controls. In addition, two types of gut microbiota communities were identified in CD patients. The main distinguishing driver of bacterial families for the first community type are Bacteroidaceae and unclassified members of the Clostridiales order, and the second type is characterized by increased abundance of Streptococcaceae and Enterobacteriaceae. Differences in the allele frequencies of the rs9858542 (BSN), rs3816769 (STAT3), and rs1793004 (NELL1) were also found between groups of CD patients with different types of microbiota communities. These findings confirm the complex multifactorial nature of CD.
Collapse
Affiliation(s)
- Maria Markelova
- Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 420008 Kazan, Russia
| | - Anastasia Senina
- Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 420008 Kazan, Russia
| | - Dilyara Khusnutdinova
- Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 420008 Kazan, Russia
| | - Maria Siniagina
- Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 420008 Kazan, Russia
| | - Elena Kupriyanova
- Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 420008 Kazan, Russia
| | | | | | - Rustam Abdulkhakov
- Hospital Therapy Department, Kazan State Medical University, 420012 Kazan, Russia
| | - Irina Kolesnikova
- Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, 119435 Moscow, Russia
| | - Olga Shagaleeva
- Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, 119435 Moscow, Russia
| | - Svetlana Lyamina
- Molecular Pathology of Digestion Laboratory, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, 127473 Moscow, Russia
| | - Sayar Abdulkhakov
- Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 420008 Kazan, Russia
| | - Natalia Zakharzhevskaya
- Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, 119435 Moscow, Russia
| | - Tatiana Grigoryeva
- Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 420008 Kazan, Russia
| |
Collapse
|
|
13
|
Synbiotic Intervention Ameliorates Oxidative Stress and Gut Permeability in an In Vitro and In Vivo Model of Ethanol-Induced Intestinal Dysbiosis. Biomedicines 2022; 10:biomedicines10123285. [PMID: 36552041 PMCID: PMC9816946 DOI: 10.3390/biomedicines10123285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 12/13/2022] [Indexed: 12/24/2022] Open
Abstract
Alcoholic liver disease (ALD) alters gut microbiota and tight junctions, causing bacterial components to enter the portal vein and induce oxidative stress-induced inflammation in the liver. Only corticosteroids and liver transplants are treatment options for severe alcoholic hepatitis. ALD's pathophysiology is unknown. However, acetaldehyde's toxic effects cause oxidative stress and intestinal permeability. This study investigates the influence of a synbiotic (a combination of aged garlic extract (AGE) and Lactobacillus rhamnosus MTCC1423) on colonic oxidative stress and inflammation in ALD male Wistar rats and Caco2 cells. MDA measurement by HPLC in CaCo2 cells, blood serum, and colon tissue demonstrated that synbiotic treatment in the ALD model reduces oxidative stress. Further, fecal high-throughput 16S rRNA gene sequencing revealed the microbiome's shift towards Firmicutes in the synbiotic group compared to ethanol. In addition, DCFDA labeling and H/E staining demonstrate that the synbiotic is beneficial in inhibiting the development of ALD. In the colon, the synbiotic reduces the activation of CYP2E1 and the inflammatory markers TNF-a and IL-6 while elevating the mRNA expression of ZO-1, occludin, and IL-10. Synbiotics colonize Lactobacillus to restore barrier function and microbiota and reduce colon oxidative stress. Thus, a synbiotic combination can be used in ALD treatment.
Collapse
|
|
14
|
Jing Z, Li Y, Ma Y, Zhang X, Liang X, Zhang X. Leverage biomaterials to modulate immunity for type 1 diabetes. Front Immunol 2022; 13:997287. [PMID: 36405706 PMCID: PMC9667795 DOI: 10.3389/fimmu.2022.997287] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Accepted: 09/20/2022] [Indexed: 09/08/2024] Open
Abstract
The pathogeny of type 1 diabetes (T1D) is mainly provoked by the β-cell loss due to the autoimmune attack. Critically, autoreactive T cells firsthand attack β-cell in islet, that results in the deficiency of insulin in bloodstream and ultimately leads to hyperglycemia. Hence, modulating immunity to conserve residual β-cell is a desirable way to treat new-onset T1D. However, systemic immunosuppression makes patients at risk of organ damage, infection, even cancers. Biomaterials can be leveraged to achieve targeted immunomodulation, which can reduce the toxic side effects of immunosuppressants. In this review, we discuss the recent advances in harness of biomaterials to immunomodulate immunity for T1D. We investigate nanotechnology in targeting delivery of immunosuppressant, biological macromolecule for β-cell specific autoreactive T cell regulation. We also explore the biomaterials for developing vaccines and facilitate immunosuppressive cells to restore immune tolerance in pancreas.
Collapse
Affiliation(s)
- Zhangyan Jing
- Department of Pharmacology, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, Guangdong, China
| | - Yuan Li
- Department of Pharmacology, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, Guangdong, China
| | - Yumeng Ma
- Department of Pharmacology, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, Guangdong, China
| | - Xiaozhou Zhang
- Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Key Laboratory of Stem Cell and Regenerative Tissue Engineering, School of Basic Medical Sciences, Guangdong Medical University, Dongguan, China
| | - Xin Liang
- Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Key Laboratory of Stem Cell and Regenerative Tissue Engineering, School of Basic Medical Sciences, Guangdong Medical University, Dongguan, China
| | - Xudong Zhang
- Department of Pharmacology, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, Guangdong, China
| |
Collapse
|
|
15
|
Zeng L, Deng Y, Yang K, Chen J, He Q, Chen H. Safety and efficacy of fecal microbiota transplantation for autoimmune diseases and autoinflammatory diseases: A systematic review and meta-analysis. Front Immunol 2022; 13:944387. [PMID: 36248877 PMCID: PMC9562921 DOI: 10.3389/fimmu.2022.944387] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2022] [Accepted: 08/29/2022] [Indexed: 11/13/2022] Open
Abstract
Objective To evaluate the safety and efficacy of fecal microbiota transplantation for autoimmune diseases and autoinflammatory diseases. Methods Relevant literature was retrieved from the PubMed database, Embase database, Cochrane Library database, etc. The search period is from the establishment of the database to January 2022. The outcomes include clinical symptoms, improvement in biochemistry, improvement in intestinal microbiota, improvement in the immune system, and adverse events. Literature screening and data extraction were independently carried out by two researchers according to the inclusion and exclusion criteria, and RevMan 5.3 software was used for statistics and analysis. Results Overall, a total of 14 randomized controlled trials (RCTs) involving six types of autoimmune diseases were included. The results showed the following. 1) Type 1 diabetes mellitus (T1DM): compared with the autologous fecal microbiota transplantation (FMT) group (control group), the fasting plasma C peptide in the allogenic FMT group at 12 months was lower. 2) Systemic sclerosis: at week 4, compared with one of two placebo controls, three patients in the experimental group reported a major improvement in fecal incontinence. 3) Ulcerative colitis, pediatric ulcerative colitis, and Crohn's disease: FMT may increase clinical remission, clinical response, and endoscopic remission for patients with ulcerative colitis and increase clinical remission for patients with Crohn's disease. 4) Psoriatic arthritis: there was no difference in the ratio of ACR20 between the two groups. Conclusion Based on current evidence, the application of FMT in the treatment of autoimmune diseases is effective and relatively safe, and it is expected to be used as a method to induce remission of active autoimmune diseases. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021235055, identifier CRD42021235055.
Collapse
Affiliation(s)
- Liuting Zeng
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Ying Deng
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Kailin Yang
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, China
| | - Junpeng Chen
- School of Mechanical Engineering, Hunan University of Science and Technology, Xiangtan, China
| | - Qi He
- People's Hospital of Ningxiang City, Ningxiang City, China
| | - Hua Chen
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| |
Collapse
|
|
16
|
Nguyen TD, Watanabe A, Burleigh S, Ghaffarzadegan T, Kanklai J, Prykhodko O, Hållenius FF, Nyman M. Monobutyrin and monovalerin improve gut-blood-brain biomarkers and alter gut microbiota composition in high-fat fed apolipoprotein-E-knockout rats. Sci Rep 2022; 12:15454. [PMID: 36104381 PMCID: PMC9475028 DOI: 10.1038/s41598-022-19502-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 08/30/2022] [Indexed: 11/09/2022] Open
Abstract
Monobutyrin (MB) and monovalerin (MV), glycerol esters of short-chain fatty acids (SCFAs), have been shown to positively influence lipid profile and biomarkers in the gut and brain. This study examined whether MB and MV in high-fat diets, affected microbiota composition and gut-blood-brain markers in apolipoprotein E deficient (ApoE-/-) rats, a model for studies of lipid-associated disorders, and neurodegenerative processes in Alzheimer's disease (AD). ApoE-/- rats fed MB and MV increased Tenericutes and the brain neurotransmitter γ-aminobutyric acid (GABA), while the blood stress hormone corticosterone decreased compared to control rats. Only rats that received MB showed a significant increase in cholic acid and Adlercreutzia in the caecum. In rats fed MV, the decrease of Proteobacteria was associated with decreased corticosterone levels. Conclusively, dietary supplementation of SCFA glycerol esters can modulate gut-blood-brain markers and alter gut microbiota composition in ApoE-/- rats, suggesting that SCFAs also could counteract lipid disorders-related diseases.
Collapse
Affiliation(s)
- Thao Duy Nguyen
- Department of Food Technology, Engineering and Nutrition, Lund University, Lund, Sweden.
| | - Ayako Watanabe
- Laboratory of Nutritional Biochemistry, Department of Applied Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Aichi, Japan
- Department of Gastroenterology and Hepatology, Fujita Health University, Aichi, Japan
| | - Stephen Burleigh
- Department of Food Technology, Engineering and Nutrition, Lund University, Lund, Sweden
| | - Tannaz Ghaffarzadegan
- Department of Food Technology, Engineering and Nutrition, Lund University, Lund, Sweden
- MTM Research Centre, School of Science and Technology, Örebro University, Örebro, Sweden
| | - Jirapat Kanklai
- Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai, 50200, Thailand
| | - Olena Prykhodko
- Department of Food Technology, Engineering and Nutrition, Lund University, Lund, Sweden
| | - Frida Fåk Hållenius
- Department of Food Technology, Engineering and Nutrition, Lund University, Lund, Sweden
| | - Margareta Nyman
- Department of Food Technology, Engineering and Nutrition, Lund University, Lund, Sweden
| |
Collapse
|
|
17
|
Majumdar S, Lin Y, Bettini ML. Host-microbiota interactions shaping T-cell response and tolerance in type 1 diabetes. Front Immunol 2022; 13:974178. [PMID: 36059452 PMCID: PMC9434376 DOI: 10.3389/fimmu.2022.974178] [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] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Accepted: 07/25/2022] [Indexed: 11/29/2022] Open
Abstract
Type-1 Diabetes (T1D) is a complex polygenic autoimmune disorder involving T-cell driven beta-cell destruction leading to hyperglycemia. There is no cure for T1D and patients rely on exogenous insulin administration for disease management. T1D is associated with specific disease susceptible alleles. However, the predisposition to disease development is not solely predicted by them. This is best exemplified by the observation that a monozygotic twin has just a 35% chance of developing T1D after their twin's diagnosis. This makes a strong case for environmental triggers playing an important role in T1D incidence. Multiple studies indicate that commensal gut microbiota and environmental factors that alter their composition might exacerbate or protect against T1D onset. In this review, we discuss recent literature highlighting microbial species associated with T1D. We explore mechanistic studies which propose how some of these microbial species can modulate adaptive immune responses in T1D, with an emphasis on T-cell responses. We cover topics ranging from gut-thymus and gut-pancreas communication, microbial regulation of peripheral tolerance, to molecular mimicry of islet antigens by microbial peptides. In light of the accumulating evidence on commensal influences in neonatal thymocyte development, we also speculate on the link between molecular mimicry and thymic selection in the context of T1D pathogenesis. Finally, we explore how these observations could inform future therapeutic approaches in this disease.
Collapse
Affiliation(s)
- Shubhabrata Majumdar
- Immunology Graduate Program, Baylor College of Medicine, Houston, TX, United States
- Department of Pathology, University of Utah, Salt Lake City, UT, United States
| | - Yong Lin
- Immunology Graduate Program, Baylor College of Medicine, Houston, TX, United States
- Department of Pathology, University of Utah, Salt Lake City, UT, United States
| | - Matthew L. Bettini
- Department of Pathology, University of Utah, Salt Lake City, UT, United States
| |
Collapse
|
|
18
|
Ismail HM, Evans-Molina C. Does the Gut Microbiome Play a Role in Obesity in Type 1 Diabetes? Unanswered Questions and Review of the Literature. Front Cell Infect Microbiol 2022; 12:892291. [PMID: 35873174 PMCID: PMC9304930 DOI: 10.3389/fcimb.2022.892291] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Accepted: 06/16/2022] [Indexed: 11/18/2022] Open
Abstract
Evidence suggests that type 1 diabetes (T1D) risk and progression are associated with gut bacterial imbalances. Children with either T1D or islet antibody positivity exhibit gut dysbiosis (microbial imbalance) characterized by lower gram-positive to gram-negative gut bacterial ratios compared to healthy individuals, leading to a pro-inflammatory milieu. In addition, specific gut microbiome changes, including increased virulence factors, elevated phage, prophage, and motility genes, and higher amplitude stress responses, have been identified in individuals who have or are progressing towards T1D. Additionally, gut microbiome differences are associated with and thought to contribute to obesity, a comorbidity that is increasingly prevalent among persons with T1D. Obesity in T1D is problematic because individuals with obesity progress faster to T1D, have reduced insulin sensitivity compared to their lean counterparts, and have higher risk of complications. Animal and human studies suggest higher relative abundance of bacterial taxa associated with changes in bile acid and short chain fatty acid biosynthesis in obesity. However, it is unknown to what extent the gut microbiome plays a role in obesity in T1D and these worse outcomes. In this review, we aim to evaluate potential gut microbiome changes and associations in individuals with T1D who are obese, highlighting the specific gut microbiome changes associated with obesity and with T1D development. We will identify commonalities and differences in microbiome changes and examine potential microbiota-host interactions and the metabolic pathways involved. Finally, we will explore interventions that may be of benefit to this population, in order to modify disease and improve outcomes.
Collapse
Affiliation(s)
- Heba M. Ismail
- Department of Pediatrics and the Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, United States
- *Correspondence: Heba M. Ismail, ; Carmella Evans-Molina,
| | - Carmella Evans-Molina
- Department of Pediatrics and the Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, United States
- Center for Diabetes and Metabolic Diseases, Indiana University School of Medicine, Indianapolis, IN, United States
- Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, United States
- Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, United States
- Richard L. Roudebush Veterans Affairs (VA) Medical Center, Indiana University School of Informatics and Computing, Indianapolis, IN, United States
- *Correspondence: Heba M. Ismail, ; Carmella Evans-Molina,
| |
Collapse
|
|
19
|
Zanetta P, Ormelli M, Amoruso A, Pane M, Azzimonti B, Squarzanti DF. Probiotics as Potential Biological Immunomodulators in the Management of Oral Lichen Planus: What's New? Int J Mol Sci 2022; 23:ijms23073489. [PMID: 35408849 PMCID: PMC8998608 DOI: 10.3390/ijms23073489] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 03/17/2022] [Accepted: 03/21/2022] [Indexed: 02/04/2023] Open
Abstract
Oral lichen planus (OLP) is a T cell-mediated chronic inflammatory disorder with multifactorial aetiology and malignant transformation potential. Despite the treatments so far identified, new tailored and safe specific measures are needed. Recently, human microbiota imbalance has been linked to several immune-mediated diseases, opening new therapeutic perspectives for probiotics; besides their ability to directly interact with the host microbiota, they also display a strain-specific immune-modulatory effect. Thus, this non-systematic review aims to elucidate the molecular pathways underlying probiotic activity, mainly those of Lactobacilli and Bifidobacteria and their metabolites in OLP pathogenesis and malignant transformation, focusing on the most recent in vitro and in vivo research evidence. Findings related to their activity in other immune-mediated diseases are here included, suggesting a probiotic translational use in OLP. Probiotics show immune-modulatory and microbiota-balancing activities; they protect the host from pathogens, hamper an excessive effector T cell response, reduce nuclear factor-kappa B (NF-kB) signalling and basal keratinocytes abnormal apoptosis, shifting the mucosal response towards the production of anti-inflammatory cytokines, thus preventing uncontrolled damage. Therefore, probiotics could be a highly encouraging prevention and immunotherapeutic approach for a safer and more sustainable OLP management.
Collapse
Affiliation(s)
- Paola Zanetta
- Laboratory of Applied Microbiology, Department of Health Sciences (DiSS), Center for Translational Research on Allergic and Autoimmune Diseases (CAAD), School of Medicine, Università del Piemonte Orientale (UPO), Corso Trieste 15/A, 28100 Novara, Italy; (P.Z.); (M.O.)
| | - Margherita Ormelli
- Laboratory of Applied Microbiology, Department of Health Sciences (DiSS), Center for Translational Research on Allergic and Autoimmune Diseases (CAAD), School of Medicine, Università del Piemonte Orientale (UPO), Corso Trieste 15/A, 28100 Novara, Italy; (P.Z.); (M.O.)
| | - Angela Amoruso
- Probiotical Research Srl, Via Mattei 3, 28100 Novara, Italy; (A.A.); (M.P.)
| | - Marco Pane
- Probiotical Research Srl, Via Mattei 3, 28100 Novara, Italy; (A.A.); (M.P.)
| | - Barbara Azzimonti
- Laboratory of Applied Microbiology, Department of Health Sciences (DiSS), Center for Translational Research on Allergic and Autoimmune Diseases (CAAD), School of Medicine, Università del Piemonte Orientale (UPO), Corso Trieste 15/A, 28100 Novara, Italy; (P.Z.); (M.O.)
- Correspondence: (B.A.); (D.F.S.); Tel.: +39-0321-660-870 (B.A.)
| | - Diletta Francesca Squarzanti
- Laboratory of Applied Microbiology, Department of Health Sciences (DiSS), Center for Translational Research on Allergic and Autoimmune Diseases (CAAD), School of Medicine, Università del Piemonte Orientale (UPO), Corso Trieste 15/A, 28100 Novara, Italy; (P.Z.); (M.O.)
- Correspondence: (B.A.); (D.F.S.); Tel.: +39-0321-660-870 (B.A.)
| |
Collapse
|
|
20
|
Zhao Y, Li M, Wang Y, Geng R, Fang J, Liu Q, Kang SG, Zeng WC, Huang K, Tong T. Understanding the mechanism underlying the anti-diabetic effect of dietary component: a focus on gut microbiota. Crit Rev Food Sci Nutr 2022; 63:7378-7398. [PMID: 35243943 DOI: 10.1080/10408398.2022.2045895] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Diabetes has become one of the biggest non-communicable diseases and threatens human health worldwide. The management of diabetes is a complex and multifaceted process including drug therapy and lifestyle interventions. Dietary components are essential for both diabetes management and health and survival of trillions of the gut microbiota (GM). Herein, we will discuss the relationship between diets and GM, the mechanism linking diabetes and gut dysbiosis, and the effects of dietary components (nutrients, phytochemicals, probiotics, food additives, etc.) on diabetes from the perspective of modulating GM. The GM of diabetic patients differs from that of health individuals and GM disorder contributes to the onset and maintenance of diabetes. Studies in humans and animal models consolidate that dietary component is a key regulator of diabetes and increasing evidence suggests that the alteration of GM plays a salient role in dietary interventions for diabetes. Given that diabetes is a major public health issue, especially that diabetes is linked with a high risk of mortality from COVID-19, this review provides compelling evidence for that targeting GM by dietary components is a promising strategy, and offers new insights into potential preventive or therapeutic approaches (dietary and pharmacological intervention) for the clinical management of diabetes.
Collapse
Affiliation(s)
- Yuhan Zhao
- Key Laboratory of Precision Nutrition and Food Quality, Key Laboratory of Functional Dairy, Ministry of Education; College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
| | - Mengjie Li
- Key Laboratory of Precision Nutrition and Food Quality, Key Laboratory of Functional Dairy, Ministry of Education; College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
| | - Yanan Wang
- Key Laboratory of Precision Nutrition and Food Quality, Key Laboratory of Functional Dairy, Ministry of Education; College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
| | - Ruixuan Geng
- Key Laboratory of Precision Nutrition and Food Quality, Key Laboratory of Functional Dairy, Ministry of Education; College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
| | - Jingjing Fang
- Key Laboratory of Precision Nutrition and Food Quality, Key Laboratory of Functional Dairy, Ministry of Education; College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
| | - Qing Liu
- Jilin Green Food Engineering Research Institute, Changchun, China
| | - Seong-Gook Kang
- Department of Food Engineering, Mokpo National University, Chungkyemyon, Muangun, Jeonnam, Korea
| | - Wei Cai Zeng
- Antioxidant Polyphenols Team, Department of Food Engineering, Sichuan University, Chengdu, China
| | - Kunlun Huang
- Key Laboratory of Precision Nutrition and Food Quality, Key Laboratory of Functional Dairy, Ministry of Education; College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
- Ministry of Agriculture, Key Laboratory of Safety Assessment of Genetically Modified Organism (Food Safety), Beijing, China
- Beijing Laboratory for Food Quality and Safety, Beijing, China
| | - Tao Tong
- Key Laboratory of Precision Nutrition and Food Quality, Key Laboratory of Functional Dairy, Ministry of Education; College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
- Ministry of Agriculture, Key Laboratory of Safety Assessment of Genetically Modified Organism (Food Safety), Beijing, China
- Beijing Laboratory for Food Quality and Safety, Beijing, China
| |
Collapse
|
|
21
|
Evidence and possible mechanisms of probiotics in the management of type 1 diabetes mellitus. J Diabetes Metab Disord 2022; 21:1081-1094. [PMID: 35673472 PMCID: PMC9167374 DOI: 10.1007/s40200-022-01006-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Accepted: 02/12/2022] [Indexed: 10/19/2022]
Abstract
Abstract Type 1 diabetes mellitus (T1DM) is one of the most common chronic immune-mediated diseases. The prevalence is worldwide especially among children and young adults. The destruction of the pancreatic β-cells due to some abnormalities in the immune system characterizes T1DM. Considering the high burden of the disease and its impact on human health, researchers have made great efforts during the last decades; investigating the disease pathogenesis and discovering new strategies for its management. Fortunately, probiotics have been found as potential remedies for T1DM. This review aims to explore the potentialities of probiotics in managing T1DM and its complications. Based on the outcomes of human and animal studies carried out from 2016 to 2021, the review hopes to assess the effectiveness of probiotics in the prevention and treatment of T1DM and its complications. We first tried to explain the disease's pathogenesis, and highlighted the possible mechanisms involved in these potentialities of probiotics. We concluded that, probiotics can be used as possible therapeutic tools for the management of T1DM. Possible mechanisms of action of probiotics include; the modulation of the gut microbiota, the regulation of inflammation-related cytokines, the production of short chain fatty acids (SCFAs), and the regulation of GLP-1. However, we recommend further studies especially human trials should be carried out to investigate these potentialities of probiotics. Highlights • T1DM is highly prevalent worldwide, causing high morbidity and mortality especially among children and young adults• Gut microbiota plays a significant role in the pathogenesis of T1DM via an interconnection with the immune system• Probiotics can be used as possible therapeutic tools for the management of T1DM• Possible mechanisms of action of probiotics include the modulation of the gut microbiota, the regulation of inflammation-related cytokines, the production of SCFAs, and the regulation of GLP-1.
Collapse
|
|
22
|
Zhang T, Gao G, Sakandar HA, Kwok LY, Sun Z. Gut Dysbiosis in Pancreatic Diseases: A Causative Factor and a Novel Therapeutic Target. Front Nutr 2022; 9:814269. [PMID: 35242797 PMCID: PMC8885515 DOI: 10.3389/fnut.2022.814269] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Accepted: 01/21/2022] [Indexed: 12/12/2022] Open
Abstract
Pancreatic-related disorders such as pancreatitis, pancreatic cancer, and type 1 diabetes mellitus (T1DM) impose a substantial challenge to human health and wellbeing. Even though our understanding of the initiation and progression of pancreatic diseases has broadened over time, no effective therapeutics is yet available for these disorders. Mounting evidence suggests that gut dysbiosis is closely related to human health and disease, and pancreatic diseases are no exception. Now much effort is under way to explore the correlation and eventually potential causation between the gut microbiome and the course of pancreatic diseases, as well as to develop novel preventive and/or therapeutic strategies of targeted microbiome modulation by probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT) for these multifactorial disorders. Attempts to dissect the intestinal microbial landscape and its metabolic profile might enable deep insight into a holistic picture of these complex conditions. This article aims to review the subtle yet intimate nexus loop between the gut microbiome and pancreatic diseases, with a particular focus on current evidence supporting the feasibility of preventing and controlling pancreatic diseases via microbiome-based therapeutics and therapies.
Collapse
Affiliation(s)
- Tao Zhang
- Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, China
- Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, China
- Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, China
| | - Guangqi Gao
- Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, China
- Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, China
- Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, China
| | - Hafiz Arbab Sakandar
- Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, China
- Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, China
- Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, China
| | - Lai-Yu Kwok
- Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, China
- Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, China
- Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, China
| | - Zhihong Sun
- Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, China
- Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, China
- Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, China
- *Correspondence: Zhihong Sun
| |
Collapse
|
|
23
|
Rawat P, Dhingra M, Kosta K, Das A. Microflora impacts immune system and its antitumor function. MICROBIAL CROSSTALK WITH IMMUNE SYSTEM 2022:177-205. [DOI: 10.1016/b978-0-323-96128-8.00007-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
|
24
|
Zheng SJ, Luo Y, Xiao JH. The Impact of Intestinal Microorganisms and Their Metabolites on Type 1 Diabetes Mellitus. Diabetes Metab Syndr Obes 2022; 15:1123-1139. [PMID: 35431564 PMCID: PMC9012311 DOI: 10.2147/dmso.s355749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Accepted: 03/24/2022] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Type 1 diabetes mellitus (T1DM) is an autoimmune disease with a complex etiology comprising numerous genetic and environmental factors; however, many of the mechanisms underlying disease development remain unclear. Nevertheless, a critical role has recently been assigned to intestinal microorganisms in T1DM disease pathogenesis. In particular, a decrease in intestinal microbial diversity, increase in intestinal permeability, and the translocation of intestinal bacteria to the pancreas have been reported in patients and animal models with T1DM. Moreover, intestinal microbial metabolites differ between healthy individuals and patients with T1DM. Specifically, short-chain fatty acid (SCFA) production, which contributes to intestinal barrier integrity and immune response regulation, is significantly reduced in patients with T1DM. Considering this correlation between intestinal microorganisms and T1DM, many studies have investigated the potential of intestinal microbiota in preventive and therapeutic strategies for T1DM. OBJECTIVE The aim of this review is to provide further support for the notion that intestinal microbiota contributes to the regulation of T1DM occurrence and development. In particular, this article reviews the involvement of the intestinal microbiota and the associated metabolites in T1DM pathogenesis, as well as recent studies on the involvement of the intestinal microbiota in T1DM prevention and treatment. CONCLUSION Intestinal microbes and their metabolites contribute to T1DM occurrence and development and may become a potential target for novel therapeutics.
Collapse
Affiliation(s)
- Shu-Juan Zheng
- Zunyi Municipal Key Laboratory of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, People’s Republic of China
| | - Yi Luo
- Zunyi Municipal Key Laboratory of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, People’s Republic of China
- Guizhou Provincial Research Center for Translational Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, People’s Republic of China
| | - Jian-Hui Xiao
- Zunyi Municipal Key Laboratory of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, People’s Republic of China
- Guizhou Provincial Research Center for Translational Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, People’s Republic of China
- Correspondence: Jian-Hui Xiao, Guizhou Provincial Research Center for Translational Medicine, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, HuiChuan District, Zunyi, 563003, People’s Republic of China, Email
| |
Collapse
|
|
25
|
Piccioni A, Cicchinelli S, Valletta F, De Luca G, Longhitano Y, Candelli M, Ojetti V, Sardeo F, Navarra S, Covino M, Franceschi F. Gut Microbiota and Autoimmune Diseases: A Charming Real World Together with Probiotics. Curr Med Chem 2022; 29:3147-3159. [PMID: 34551690 DOI: 10.2174/0929867328666210922161913] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 07/28/2021] [Accepted: 08/18/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND The role of gut microbiota in human disease is fascinating for hundreds of researchers worldwide. Many works have highlighted that gut microbiota modulates the immune system and that its disruption can trigger autoimmune and inflammatory immune-mediated diseases. Probiotics are able to positively modify microbiota composition. OBJECTIVE The aim of this review is to report the most important findings regarding the effects of probiotics administration in the most common autoimmune disease and inflammatory immune-mediated diseases. METHODS Literature research was performed in PubMed, Google Scholar, and Medline, as well as in specific journal websites using the keywords: "autoimmunity", "microbiota", and "probiotics". The article selection has been made independently by three authors, and controversies have been solved by a fourth researcher. Only English-language articles were included and preference was given to clinical trials, meta-analysis, and case series. After the review process, 68 articles have been considered. RESULTS Relying on this evidence, many studies have investigated the potential of probiotics in restoring gut eubiosis, thus affecting pathogenesis, clinical manifestations, and course of these pathologies. Even in the light of few and sometimes contradictory studies, physicians should start to consider these preliminary findings when approaching patients suffering from autoimmune disease. After an accurate case-by-case evaluation of potential candidates, probiotics might be introduced besides the standard therapeutic plan as supportive measures.
Collapse
Affiliation(s)
- Andrea Piccioni
- Emergency Department, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Sara Cicchinelli
- Emergency Department, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Federico Valletta
- Emergency Department, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Giulio De Luca
- Emergency Department, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Yaroslava Longhitano
- Department of Internal Medicine, University of Genoa - Dietetics and Clinical Nutrition Unit, IRCCS Polyclinic Hospital San Martino, 16132 Genoa, Italy
| | - Marcello Candelli
- Emergency Department, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Veronica Ojetti
- Emergency Department, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Francesco Sardeo
- Emergency Department, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Simone Navarra
- Emergency Department, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Marcello Covino
- Emergency Department, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Francesco Franceschi
- Emergency Department, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| |
Collapse
|
|
26
|
Wang S, Tan Q, Hou Y, Dou H. Emerging Roles of Myeloid-Derived Suppressor Cells in Diabetes. Front Pharmacol 2021; 12:798320. [PMID: 34975496 PMCID: PMC8716856 DOI: 10.3389/fphar.2021.798320] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Accepted: 12/01/2021] [Indexed: 12/12/2022] Open
Abstract
Diabetes is a syndrome characterized by hyperglycemia with or without insulin resistance. Its etiology is attributed to the combined action of genes, environment and immune cells. Myeloid-derived suppressor cell (MDSC) is a heterogeneous population of immature cells with immunosuppressive ability. In recent years, different studies have debated the quantity, activity changes and roles of MDSC in the diabetic microenvironment. However, the emerging roles of MDSC have not been fully documented with regard to their interactions with diabetes. Here, the manifestations of MDSC and their subsets are reviewed with regard to the incidence of diabetes and diabetic complications. The possible drugs targeting MDSC are discussed with regard to their potential of treating diabetes. We believe that understanding MDSC will offer opportunities to explain pathological characteristics of different diabetes. MDSC also will be used for personalized immunotherapy of diabetes.
Collapse
Affiliation(s)
- Shiqi Wang
- The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China
- Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, China
- Department of Burns and Plastic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Qian Tan
- Department of Burns and Plastic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Yayi Hou
- The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China
- Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, China
| | - Huan Dou
- The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China
- Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, China
| |
Collapse
|
|
27
|
Wee HN, Liu JJ, Ching J, Kovalik JP, Lim SC. The Kynurenine Pathway in Acute Kidney Injury and Chronic Kidney Disease. Am J Nephrol 2021; 52:771-787. [PMID: 34753140 PMCID: PMC8743908 DOI: 10.1159/000519811] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Accepted: 09/15/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND The kynurenine pathway (KP) is the major catabolic pathway for tryptophan degradation. The KP plays an important role as the sole de novo nicotinamide adenine dinucleotide (NAD+) biosynthetic pathway in normal human physiology and functions as a counter-regulatory mechanism to mitigate immune responses during inflammation. Although the KP has been implicated in a variety of disorders including Huntington's disease, seizures, cardiovascular disease, and osteoporosis, its role in renal diseases is seldom discussed. SUMMARY This review summarizes the roles of the KP and its metabolites in acute kidney injury (AKI) and chronic kidney disease (CKD) based on current literature evidence. Metabolomics studies demonstrated that the KP metabolites were significantly altered in patients and animal models with AKI or CKD. The diagnostic and prognostic values of the KP metabolites in AKI and CKD were highlighted in cross-sectional and longitudinal human observational studies. The biological impact of the KP on the pathophysiology of AKI and CKD has been studied in experimental models of different etiologies. In particular, the activation of the KP was found to confer protection in animal models of glomerulonephritis, and its immunomodulatory mechanism may involve the regulation of T cell subsets such as Th17 and regulatory T cells. Manipulation of the KP to increase NAD+ production or diversion toward specific KP metabolites was also found to be beneficial in animal models of AKI. Key Messages: KP metabolites are reported to be dysregulated in human observational and animal experimental studies of AKI and CKD. In AKI, the magnitude and direction of changes in the KP depend on the etiology of the damage. In CKD, KP metabolites are altered with the onset and progression of CKD all the way to advanced stages of the disease, including uremia and its related vascular complications. The activation of the KP and diversion to specific sub-branches are currently being explored as therapeutic strategies in these diseases, especially with regards to the immunomodulatory effects of certain KP metabolites. Further elucidation of the KP may hold promise for the development of biomarkers and targeted therapies for these kidney diseases.
Collapse
Affiliation(s)
| | - Jian-Jun Liu
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Singapore
| | - Jianhong Ching
- Duke-NUS Medical School, Singapore, Singapore
- KK Research Centre, KK Women's and Children's Hospital, Singapore, Singapore
| | | | - Su Chi Lim
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Singapore
- Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
- Diabetes Centre, Admiralty Medical Centre, Singapore, Singapore
| |
Collapse
|
|
28
|
Prophylactic Treatment of Probiotic and Metformin Mitigates Ethanol-Induced Intestinal Barrier Injury: In Vitro, In Vivo, and In Silico Approaches. Mediators Inflamm 2021; 2021:5245197. [PMID: 34616233 PMCID: PMC8490080 DOI: 10.1155/2021/5245197] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Accepted: 08/09/2021] [Indexed: 02/07/2023] Open
Abstract
Ethanol depletes intestinal integrity and promotes gut dysbiosis. Studies have suggested the individual role of probiotics and metformin Met in protecting intestinal barrier function from injuries induced by ethanol. The objective of the current study is to investigate the potential mechanism by which coadministration of probiotic Visbiome® (V) and Met blocks the ethanol-induced intestinal barrier dysfunction/gut leakiness utilizing Caco-2 monolayers, a rat model with chronic ethanol injury, and in silico docking interaction models. In Caco-2 monolayers, exposure to ethanol significantly disrupted tight junction (TJ) localization, elevated monolayer permeability, and oxidative stress compared with controls. However, cotreatment with probiotic V and Met largely ameliorated the ethanol-induced mucosal barrier dysfunction, TJ disruption, and gut oxidative stress compared with ethanol-exposed monolayers and individual treatment of either agent. Rats fed with ethanol-containing Lieber-DeCarli liquid diet showed decreased expression of TJ proteins, and increased intestinal barrier injury resulting in pro-inflammatory response and oxidative stress in the colon. We found that co-administration of probiotic V and Met improved the expression of intestinal TJ proteins (ZO-1 and occludin) and upregulated the anti-inflammatory response, leading to reduced ER stress. Moreover, co-administration of probiotic V and Met inhibited the CYP2E1 and NOX gene expression, and increase the translocation of Nrf-2 as well as anti-oxidative genes (SOD, catalase, Gpx, and HO-1), leading to reduced colonic ROS content and malondialdehyde levels. The combined treatment of probiotic V and Met also improved their binding affinities towards HO-1, Nrf-2, SLC5A8, and GPR109A, which could be attributed to their synergistic effect. Our findings based on in-vitro, in-vivo, and in-silico analyses suggest that the combination of probiotic V and Met potentially acts in synergism, attributable to their property of inhibition of inflammation and oxidative stress against ethanol-induced intestinal barrier injury.
Collapse
|
|
29
|
Benjak Horvat I, Gobin I, Kresović A, Hauser G. How can probiotic improve irritable bowel syndrome symptoms? World J Gastrointest Surg 2021; 13:923-940. [PMID: 34621470 PMCID: PMC8462084 DOI: 10.4240/wjgs.v13.i9.923] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Revised: 03/22/2021] [Accepted: 08/06/2021] [Indexed: 02/06/2023] Open
Abstract
The onset and manifestations of irritable bowel syndrome (IBS) is associated with several factors, and the pathophysiology involves various central and peripheral mechanisms. Most studies indicate that the management of gut microbiota could significantly affect the improvement of subjective disorders in patients with IBS. Numerous clinical trials have assessed the efficacy of probiotics for IBS with controversial conclusions. Several clinical trials have suggested that probiotics can improve global IBS symptoms, while others only improve individual IBS symptoms, such as bloating scores and abdominal pain scores. Only a few clinical trials have found no apparent effect of probiotics on IBS symptoms. Generally, probiotics appear to be safe for patients with IBS. However, the question of which probiotics should be used for certain IBS subtypes remains unresolved. In everyday practice, the dose of the recommended probiotic remains questionable, as well as how long the probiotic should be used in therapy. The use of probiotics in the M subtype and non-classified IBS is particularly problematic, in which combination therapy should be recommended due to the change in symptoms. Therefore, new approaches are needed in the design of clinical studies that should address certain subtypes of IBS.
Collapse
Affiliation(s)
- Indira Benjak Horvat
- Department of Gastroenterology, Varaždin General Hospital, Varažin 42000, Croatia
| | - Ivana Gobin
- Department of Microbiology and Parasitology, Faculty of Medicine, University of Rijeka, Rijeka 51000, Croatia
| | - Andrea Kresović
- Department of Gastroenterology, Clinical Hospital Center Rijeka, Rijeka 51000, Croatia
| | - Goran Hauser
- Department of Gastroenterology, Faculty of Medicine, Clinical Hospital Center Rijeka, University of Rijeka, Rijeka 51000, Croatia
| |
Collapse
|
|
30
|
Krupa A, Kowalska I. The Kynurenine Pathway-New Linkage between Innate and Adaptive Immunity in Autoimmune Endocrinopathies. Int J Mol Sci 2021; 22:9879. [PMID: 34576041 PMCID: PMC8469440 DOI: 10.3390/ijms22189879] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 09/09/2021] [Accepted: 09/10/2021] [Indexed: 12/18/2022] Open
Abstract
The kynurenine pathway (KP) is highly regulated in the immune system, where it promotes immunosuppression in response to infection or inflammation. Indoleamine 2,3-dioxygenase 1 (IDO1), the main enzyme of KP, has a broad spectrum of activity on immune cells regulation, controlling the balance between stimulation and suppression of the immune system at sites of local inflammation, relevant to a wide range of autoimmune and inflammatory diseases. Various autoimmune diseases, among them endocrinopathies, have been identified to date, but despite significant progress in their diagnosis and treatment, they are still associated with significant complications, morbidity, and mortality. The precise cellular and molecular mechanisms leading to the onset and development of autoimmune disease remain poorly clarified so far. In breaking of tolerance, the cells of the innate immunity provide a decisive microenvironment that regulates immune cells' differentiation, leading to activation of adaptive immunity. The current review provided a comprehensive presentation of the known role of IDO1 and KP activation in the regulation of the innate and adaptive arms of the immune system. Significant attention has been paid to the immunoregulatory role of IDO1 in the most prevalent, organ-specific autoimmune endocrinopathies-type 1 diabetes mellitus (T1DM) and autoimmune thyroiditis.
Collapse
Affiliation(s)
- Anna Krupa
- Department of Internal Medicine and Metabolic Diseases, Medical University of Bialystok, M. Sklodowskiej-Curie 24A, 15-276 Bialystok, Poland
| | - Irina Kowalska
- Department of Internal Medicine and Metabolic Diseases, Medical University of Bialystok, M. Sklodowskiej-Curie 24A, 15-276 Bialystok, Poland
| |
Collapse
|
|
31
|
Zhang Z, Xue C, Ju M, Guo J, Wang M, Yi S, Yi X. Maternal Gut Dysbiosis Alters Offspring Microbiota and Social Interactions. Microorganisms 2021; 9:microorganisms9081742. [PMID: 34442821 PMCID: PMC8401725 DOI: 10.3390/microorganisms9081742] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 08/08/2021] [Indexed: 12/22/2022] Open
Abstract
Increasing application of antibiotics changes the gut microbiota composition, leading to dysbiosis of the gut microbiota. Although growing evidence suggests the potential role of gut dysbiosis as the cause of neurodevelopmental disorders and behavioral defects, a broad gap of knowledge remains to be narrowed to better understand the exact mechanisms by which maternal gut dysbiosis alters microbiota development and social interactions of offspring. Here, we showed that maternal gut dysbiosis during gestation is a critical determinant of gut microbiota and social interactions off mouse offspring. Gut microbiota of 2-week-old offspring showed significant changes in response to maternal antibiotic treatment. We even detected distinct effects of maternal oral antibiotics on gut microbiota of 14-week-old offspring. Compared to controls, offspring born to antibiotics-treated mothers displayed reduction in sociability and preference for social novelty, suggesting that the altered offspring social behavior was closely linked to dysbiosis of maternal gut microbiota. Our study opens the possibility to better understand the mechanism of how maternal gut microbiota vertically impairs social interactions of offspring in animal models, providing support to the maternal gut microbiota as a potential mediator between offspring microbiota and behaviors.
Collapse
Affiliation(s)
- Zihan Zhang
- College of Life Sciences, Qufu Normal University, Qufu 273165, China; (Z.Z.); (C.X.); (M.J.); (J.G.); (M.W.)
| | - Chao Xue
- College of Life Sciences, Qufu Normal University, Qufu 273165, China; (Z.Z.); (C.X.); (M.J.); (J.G.); (M.W.)
| | - Mengyao Ju
- College of Life Sciences, Qufu Normal University, Qufu 273165, China; (Z.Z.); (C.X.); (M.J.); (J.G.); (M.W.)
| | - Jiawei Guo
- College of Life Sciences, Qufu Normal University, Qufu 273165, China; (Z.Z.); (C.X.); (M.J.); (J.G.); (M.W.)
| | - Minghui Wang
- College of Life Sciences, Qufu Normal University, Qufu 273165, China; (Z.Z.); (C.X.); (M.J.); (J.G.); (M.W.)
| | - Sijie Yi
- College of Life and Environmental Sciences, University of Exeter, Exeter EX4 4QD, UK
- Correspondence: (S.Y.); (X.Y.)
| | - Xianfeng Yi
- College of Life Sciences, Qufu Normal University, Qufu 273165, China; (Z.Z.); (C.X.); (M.J.); (J.G.); (M.W.)
- Correspondence: (S.Y.); (X.Y.)
| |
Collapse
|
|
32
|
Song X, Wang W, Ding S, Liu X, Wang Y, Ma H. Puerarin ameliorates depression-like behaviors of with chronic unpredictable mild stress mice by remodeling their gut microbiota. J Affect Disord 2021; 290:353-363. [PMID: 34049088 DOI: 10.1016/j.jad.2021.04.037] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Revised: 04/19/2021] [Accepted: 04/21/2021] [Indexed: 12/28/2022]
Abstract
BACKGROUND Puerarin is an isoflavone derivative isolated from the traditional Chinese medicine Pueraria Lobelia, which has proven to relieve depression-like behavior. However, its underlying antidepressant mechanisms have been poorly characterized. Herein, we explored whether Puerarin's antidepressant effect is associated with changes in the gut microbiota (GM). METHODS The model of depression in mice featuring chronic unpredictable mild stress (CUMS) was eastablished, and its antidepressant effect was estimated by sugar water preference and forced swimming test. Genomic DNA extracted from fecal samples was employed to sequence the 16S rRNA gene for gut microbiota identification. RESULTS Puerarin (100 mg/kg) treatment was found to alleviate the CUMS-induced depression-like behaviors. Furthermore, chronic stress led to pathological microbial flora, which was principally marked by the increased abundance of pathogenic bacteria (Proteobacteria, Flexispira, Desulfovibrio) and the decreased abundance of beneficial bacteria (Firmicutes, Bacillales, Lactobacillus). Intriguingly, puerarin treatment reversed these changes. LIMITATIONS The specific role and anti-depression mechanism of characteristic gut microflora were not confirmed. CONCLUSION Puerarin can remedy stress-induced disruptions of normal gut microflora. It is suggested that the antidepressant mechanism of puerarin may closely interact with restoring beneficial microflora.
Collapse
Affiliation(s)
- Xujiao Song
- School of Chemical and Biological Engineering, Yichun University, Yichun 336000, China
| | - Weihao Wang
- School of Chemical and Biological Engineering, Yichun University, Yichun 336000, China
| | - Shanshan Ding
- School of Chemical and Biological Engineering, Yichun University, Yichun 336000, China
| | - Xingyue Liu
- School of Chemical and Biological Engineering, Yichun University, Yichun 336000, China
| | - Yan Wang
- School of Chemical and Biological Engineering, Yichun University, Yichun 336000, China
| | - Hao Ma
- School of Aesthetic Medicine, Yichun University, Yichun 336000, China.
| |
Collapse
|
|
33
|
Stojanović I, Saksida T, Miljković Đ, Pejnović N. Modulation of Intestinal ILC3 for the Treatment of Type 1 Diabetes. Front Immunol 2021; 12:653560. [PMID: 34149694 PMCID: PMC8209467 DOI: 10.3389/fimmu.2021.653560] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Accepted: 05/18/2021] [Indexed: 11/22/2022] Open
Abstract
Gut-associated lymphoid tissue (GALT) is crucial for the maintenance of the intestinal homeostasis, but it is also the potential site of the activation of autoreactive cells and initiation/propagation of autoimmune diseases in the gut and in the distant organs. Type 3 innate lymphoid cells (ILC3) residing in the GALT integrate signals from food ingredients and gut microbiota metabolites in order to control local immunoreactivity. Notably, ILC3 secrete IL-17 and GM-CSF that activate immune cells in combating potentially pathogenic microorganisms. ILC3 also produce IL-22 that potentiates the strength and integrity of epithelial tight junctions, production of mucus and antimicrobial peptides thus enabling the proper function of the intestinal barrier. The newly discovered function of small intestine ILC3 is the secretion of IL-2 and the promotion of regulatory T cell (Treg) generation and function. Since the intestinal barrier dysfunction, together with the reduction in small intestine ILC3 and Treg numbers are associated with the pathogenesis of type 1 diabetes (T1D), the focus of this article is intestinal ILC3 modulation for the therapy of T1D. Of particular interest is free fatty acids receptor 2 (FFAR2), predominantly expressed on intestinal ILC3, that can be stimulated by available selective synthetic agonists. Thus, we propose that FFAR2-based interventions by boosting ILC3 beneficial functions may attenuate autoimmune response against pancreatic β cells during T1D. Also, it is our opinion that treatments based on ILC3 stimulation by functional foods can be used as prophylaxis in individuals that are genetically predisposed to develop T1D.
Collapse
Affiliation(s)
- Ivana Stojanović
- Department of Immunology, Institute for Biological Research "Siniša Stanković" - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Tamara Saksida
- Department of Immunology, Institute for Biological Research "Siniša Stanković" - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Đorđe Miljković
- Department of Immunology, Institute for Biological Research "Siniša Stanković" - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Nada Pejnović
- Department of Immunology, Institute for Biological Research "Siniša Stanković" - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
| |
Collapse
|
|
34
|
Changes in leptin, serotonin, and cortisol after eight weeks of aerobic exercise with probiotic intake in a cuprizone-induced demyelination mouse model of multiple sclerosis. Cytokine 2021; 144:155590. [PMID: 34049259 DOI: 10.1016/j.cyto.2021.155590] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Revised: 04/23/2021] [Accepted: 05/18/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND Multiple sclerosis (MS) is the most common non-traumatic neurological cause of disability in young adults. Physical activity, particularly exercise training, is an evidence-based approach to managing symptoms, restoring function, and improving overall wellness in people with MS. As well, the use of probiotics can be effective in reducing the damage from inflammation in MS patients. OBJECTIVE The study aimed to address changes in leptin, serotonin, and cortisol following eight weeks of aerobic exercise along with probiotic intake in a cuprizone-induced demyelination mouse model of MS. METHODS Mice were exposed to cuprizone for 12 weeks. After 5 weeks, beam and performance tests were performed on them. The mice (n = 5 per group) were randomly divided into five groups: control (C), MS, MS with exercise (MS + Exe), MS with probiotic (MS + Prob), and MS with probiotic and exercise (MS + Prob + Exe). Exercise groups performed aerobic exercises 5 days a week, 10 min in the first week, 20 min in the second week, and 30 min daily in the third week until the eighth week. In the probiotic groups, the mice received probiotic by gavage. They were sacrificed after 3 months. Biochemical and molecular biology analyses were performed. RESULTS The results showed that leptin gene expression values in the MS + Prob + Exe, MS + Prob, and MS + Exe groups showed a decrease compared to the MS group, but the reduction was not significant (p > 0.05). Also, the leptin Elisa test in these intervention groups showed a significant decrease (P < 0.05). The serotonin gene expression values in the MS + Prob + Exe, MS + Prob, and MS + Exe groups were increased compared to the MS group, but the increase was not significant (p > 0.05). Furthermore, the serotonin Elisa test in these intervention groups showed a significant increase (P < 0.05). The cortisol Elisa test values in the MS + Exe and MS + Prob groups exhibited a decrease compared to the MS group, but the reduction was not significant (p > 0.05). CONCLUSION Overall, these results suggest that lifestyle interventions can be effective in improving pathological factors in patients with MS.
Collapse
|
|
35
|
Maintaining Digestive Health in Diabetes: The Role of the Gut Microbiome and the Challenge of Functional Foods. Microorganisms 2021; 9:microorganisms9030516. [PMID: 33802371 PMCID: PMC8001283 DOI: 10.3390/microorganisms9030516] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Revised: 02/22/2021] [Accepted: 02/26/2021] [Indexed: 12/15/2022] Open
Abstract
Over the last decades, the incidence of diabetes has increased in developed countries and beyond the genetic impact, environmental factors, which can trigger the activation of the gut immune system, seem to affect the induction of the disease process. Since the composition of the gut microbiome might disturb the normal interaction with the immune system and contribute to altered immune responses, the restoration of normal microbiota composition constitutes a new target for the prevention and treatment of diabetes. Thus, the interaction of gut microbiome and diabetes, focusing on mechanisms connecting gut microbiota with the occurrence of the disorder, is discussed in the present review. Finally, the challenge of functional food diet on maintaining intestinal health and microbial flora diversity and functionality, as a potential tool for the onset inhibition and management of the disease, is highlighted by reporting key animal studies and clinical trials. Early onset of the disease in the oral cavity is an important factor for the incorporation of a functional food diet in daily routine.
Collapse
|
|
36
|
Abstract
Gut dysbiosis in diabetes mellitus is associated with decreased short-chain fatty acids and epithelial barrier disruption. Microbial-derived toxins move across the "leaky gut" and incur systemic inflammation and insulin resistance. In children, gut dysbiosis has been associated with risk of developing type 1 diabetes mellitus. In animal models, the obesity phenotype is transferable via microbiota transplantation. Plant-based low protein diets and certain anti-diabetic drugs have been associated with positive microbiome effects. Clinical trials with prebiotics and probiotics have yielded mixed results. Further investigations are needed to evaluate the gut microbiome as a potential therapeutic target for diabetes prevention and management.
Collapse
Affiliation(s)
- Wei Ling Lau
- Division of Nephrology, University of California, Irvine School of Medicine, Orange, CA.
| | - Tiffany Tran
- Division of Nephrology, University of California, Irvine School of Medicine, Orange, CA
| | - Connie M Rhee
- Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology, University of California, Irvine School of Medicine, Orange, CA
| | - Kamyar Kalantar-Zadeh
- Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology, University of California, Irvine School of Medicine, Orange, CA
| | - Nosratola D Vaziri
- Division of Nephrology, University of California, Irvine School of Medicine, Orange, CA
| |
Collapse
|
|
37
|
Purton T, Staskova L, Lane MM, Dawson SL, West M, Firth J, Clarke G, Cryan JF, Berk M, O'Neil A, Dean O, Hadi A, Honan C, Marx W. Prebiotic and probiotic supplementation and the tryptophan-kynurenine pathway: A systematic review and meta analysis. Neurosci Biobehav Rev 2021; 123:1-13. [PMID: 33482244 DOI: 10.1016/j.neubiorev.2020.12.026] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Revised: 12/18/2020] [Accepted: 12/19/2020] [Indexed: 12/20/2022]
Abstract
This systematic review aimed to synthesise the results from studies investigating the effects of prebiotics and probiotics on kynurenine pathway metabolism. Thirteen studies were identified for inclusion, comprising 12 probiotic and two prebiotic arms. Participants included healthy individuals and individuals with various clinical conditions. Twelve metabolites were examined across the studies, using a range of biological samples. Across all interventions, 11 reported an effect on ≤ metabolite. Although limited by clinical and methodological heterogeneity, pooled analysis (n = 253) found probiotics to significantly affect serum kynurenine (g = 0.315, CI = 0.070 to 0.560, p = 0.012, 4 studies, I2 = 0%) and the kynurenine:tryptophan ratio (g = 0.442, CI = 0.074 to 0.810, p = 0.018, 4 studies, I2 = 42 %). Risk of bias across the studies was generally low. The results provide preliminary evidence that probiotics can modulate kynurenine pathway metabolism, with less evidence available regarding prebiotics. Future studies which further consider methodological confounds and sample characteristics are required, to establish intervention efficacy. PROSPERO registration #CRD42019154677.
Collapse
Affiliation(s)
- Terry Purton
- School of Psychological Sciences, College of Health and Medicine, University of Tasmania, Locked Bag 1342, Launceston, Tasmania, 7250, Australia.
| | - Lada Staskova
- Murdoch Children's Research Institute, Royal Children's Hospital, Environmental & Genetic Epidemiology Research, Parkville, Australia; RMIT University, School of Science, Melbourne, Australia; Florey Institute for Neuroscience and Mental Health, Parkville, Australia
| | - Melissa M Lane
- Deakin University, IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia
| | - Samantha L Dawson
- Murdoch Children's Research Institute, Royal Children's Hospital, Environmental & Genetic Epidemiology Research, Parkville, Australia; Deakin University, IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia
| | - Madeline West
- Deakin University, IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia
| | - Joseph Firth
- Division of Psychology and Mental Health, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK; NICM Health Research Institute, Western Sydney University, Westmead, Australia
| | - Gerard Clarke
- Department of Psychiatry and Neurobehavioural Science, and APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - John F Cryan
- Department of Anatomy and Neuroscience, and APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Michael Berk
- Deakin University, IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia; Orygen, The National Centre of Excellence in Youth Mental Health, Centre for Youth Mental Health, and the Department of Psychiatry, The University of Melbourne, Melbourne, Australia; Florey Institute for Neuroscience and Mental Health, Parkville, Australia
| | - Adrienne O'Neil
- Deakin University, IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia
| | - Olivia Dean
- Deakin University, IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia; Florey Institute for Neuroscience and Mental Health, Parkville, Australia
| | - Amir Hadi
- Halal Research Center of IRI, FDA, Tehran, Iran
| | - Cynthia Honan
- School of Psychological Sciences, College of Health and Medicine, University of Tasmania, Locked Bag 1342, Launceston, Tasmania, 7250, Australia
| | - Wolfgang Marx
- Deakin University, IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia
| |
Collapse
|
|
38
|
Verduci E, Mameli C, Amatruda M, Petitti A, Vizzuso S, El Assadi F, Zuccotti G, Alabduljabbar S, Terranegra A. Early Nutrition and Risk of Type 1 Diabetes: The Role of Gut Microbiota. Front Nutr 2021; 7:612377. [PMID: 33425976 PMCID: PMC7785819 DOI: 10.3389/fnut.2020.612377] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Accepted: 11/30/2020] [Indexed: 12/12/2022] Open
Abstract
Type 1 diabetes (T1D) appears most frequently in childhood, with an alarming increasing incidence in the last decades. Although the genetic predisposition is a major risk factor, it cannot solely explain the complex etiology of T1D which is still not fully understood. In this paper, we reviewed the most recent findings on the role of early nutrition and the involvement of the gut microbiota in the etiopathogenesis of T1D. The main conclusions that are withdrawn from the current literature regarding alleviating the risk of developing T1D through nutrition are the encouragement of long-term breast-feeding for at least the first 6 months of life and the avoidance of early complementary foods and gluten introduction (before 4 months of age) as well as cow milk introduction before 12 months of life. These detrimental feeding habits create a gut microbiota dysbiotic state that can contribute to the onset of T1D in infancy. Finally, we discussed the possibility to introduce probiotics, prebiotics and post-biotics in the prevention of T1D.
Collapse
Affiliation(s)
- Elvira Verduci
- Department of Pediatrics, Vittore Buzzi Children's Hospital, University of Milan, Milan, Italy.,Department of Health Sciences, University of Milan, Milan, Italy
| | - Chiara Mameli
- Department of Pediatrics, Vittore Buzzi Children's Hospital, University of Milan, Milan, Italy
| | - Matilde Amatruda
- Department of Health Sciences, University of Milan, Milan, Italy
| | - Agnese Petitti
- Department of Pediatrics, Vittore Buzzi Children's Hospital, University of Milan, Milan, Italy
| | - Sara Vizzuso
- Department of Health Sciences, University of Milan, Milan, Italy
| | - Farah El Assadi
- College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar
| | - Gianvincenzo Zuccotti
- Department of Pediatrics, Vittore Buzzi Children's Hospital, University of Milan, Milan, Italy
| | | | | |
Collapse
|
|
39
|
Pearson JA, McKinney EF, Walker LSK. 100 years post-insulin: immunotherapy as the next frontier in type 1 diabetes. IMMUNOTHERAPY ADVANCES 2021; 1:ltab024. [PMID: 35156097 PMCID: PMC8826223 DOI: 10.1093/immadv/ltab024] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 11/15/2021] [Accepted: 11/20/2021] [Indexed: 02/03/2023] Open
Abstract
Type 1 diabetes (T1D) is an autoimmune disease characterised by T cell-mediated destruction of the insulin-producing β cells in the pancreas. Similar to other autoimmune diseases, the incidence of T1D is increasing globally. The discovery of insulin 100 years ago dramatically changed the outlook for people with T1D, preventing this from being a fatal condition. As we celebrate the centenary of this milestone, therapeutic options for T1D are once more at a turning point. Years of effort directed at developing immunotherapies are finally starting to pay off, with signs of progress in new onset and even preventative settings. Here, we review a selection of immunotherapies that have shown promise in preserving β cell function and highlight future considerations for immunotherapy in the T1D setting.
Collapse
Affiliation(s)
- James A Pearson
- Diabetes Research Group, Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, Wales, UK
| | - Eoin F McKinney
- Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge, England, UK
- Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, England, UK
- Cambridge Centre for Artificial Intelligence in Medicine, University of Cambridge, Cambridge, England, UK
| | - Lucy S K Walker
- Division of Infection and Immunity, Institute or Immunity and Transplantation, University College London, Royal Free Campus, London, UK
| |
Collapse
|
|
40
|
Marx W, Lane M, Hockey M, Aslam H, Berk M, Walder K, Borsini A, Firth J, Pariante CM, Berding K, Cryan JF, Clarke G, Craig JM, Su KP, Mischoulon D, Gomez-Pinilla F, Foster JA, Cani PD, Thuret S, Staudacher HM, Sánchez-Villegas A, Arshad H, Akbaraly T, O'Neil A, Segasby T, Jacka FN. Diet and depression: exploring the biological mechanisms of action. Mol Psychiatry 2021; 26:134-150. [PMID: 33144709 DOI: 10.1038/s41380-020-00925-x] [Citation(s) in RCA: 313] [Impact Index Per Article: 78.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 10/01/2020] [Accepted: 10/09/2020] [Indexed: 02/08/2023]
Abstract
The field of nutritional psychiatry has generated observational and efficacy data supporting a role for healthy dietary patterns in depression onset and symptom management. To guide future clinical trials and targeted dietary therapies, this review provides an overview of what is currently known regarding underlying mechanisms of action by which diet may influence mental and brain health. The mechanisms of action associating diet with health outcomes are complex, multifaceted, interacting, and not restricted to any one biological pathway. Numerous pathways were identified through which diet could plausibly affect mental health. These include modulation of pathways involved in inflammation, oxidative stress, epigenetics, mitochondrial dysfunction, the gut microbiota, tryptophan-kynurenine metabolism, the HPA axis, neurogenesis and BDNF, epigenetics, and obesity. However, the nascent nature of the nutritional psychiatry field to date means that the existing literature identified in this review is largely comprised of preclinical animal studies. To fully identify and elucidate complex mechanisms of action, intervention studies that assess markers related to these pathways within clinically diagnosed human populations are needed.
Collapse
Affiliation(s)
- Wolfgang Marx
- Deakin University, IMPACT (the Institute for Mental and Physical Health and Clinical Translation), Food & Mood Centre, Geelong, VIC, Australia.
| | - Melissa Lane
- Deakin University, IMPACT (the Institute for Mental and Physical Health and Clinical Translation), Food & Mood Centre, Geelong, VIC, Australia
| | - Meghan Hockey
- Deakin University, IMPACT (the Institute for Mental and Physical Health and Clinical Translation), Food & Mood Centre, Geelong, VIC, Australia
| | - Hajara Aslam
- Deakin University, IMPACT (the Institute for Mental and Physical Health and Clinical Translation), Food & Mood Centre, Geelong, VIC, Australia
| | - Michael Berk
- Deakin University, IMPACT (the Institute for Mental and Physical Health and Clinical Translation), Food & Mood Centre, Geelong, VIC, Australia
- Orygen, The National Centre of Excellence in Youth Mental Health, Centre for Youth Mental Health, Florey Institute for Neuroscience and Mental Health, Melbourne, VIC, Australia
- Department of Psychiatry, The University of Melbourne, Melbourne, VIC, Australia
| | - Ken Walder
- Deakin University, IMPACT (the Institute for Mental and Physical Health and Clinical Translation), Metabolic Research Unit, Geelong, VIC, Australia
| | - Alessandra Borsini
- Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Joseph Firth
- Division of Psychology and Mental Health, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
- NICM Health Research Institute, Western Sydney University, Westmead, NSW, Australia
| | - Carmine M Pariante
- Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Kirsten Berding
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - John F Cryan
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
| | - Gerard Clarke
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland
- INFANT Research Centre, University College Cork, Cork, Ireland
| | - Jeffrey M Craig
- Deakin University, IMPACT (the Institute for Mental and Physical Health and Clinical Translation), Geelong, VIC, Australia
| | - Kuan-Pin Su
- Departments of Psychiatry and Mind-Body Interface Laboratory (MBI-Lab), China Medical University Hospital, Taichung, Taiwan
- An-Nan Hospital, China Medical University, Tainan, Taiwan
- College of Medicine, China Medical University, Taichung, Taiwan
| | - David Mischoulon
- Department of Psychiatry, Depression Clinical and Research Program, Massachusetts General Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Fernando Gomez-Pinilla
- Departments of Neurosurgery and Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA, USA
| | - Jane A Foster
- Department of Psychiatry & Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada
| | - Patrice D Cani
- UCLouvain, Université catholique de Louvain, WELBIO-Walloon Excellence in Life Sciences and BIOtechnology, Louvain Drug Research Institute, Metabolism and Nutrition Research Group, Brussels, Belgium
| | - Sandrine Thuret
- Basic and Clinical Neuroscience Department, Institute of Psychiatry Psychology and Neuroscience, King's College London, London, UK
| | - Heidi M Staudacher
- Deakin University, IMPACT (the Institute for Mental and Physical Health and Clinical Translation), Food & Mood Centre, Geelong, VIC, Australia
| | - Almudena Sánchez-Villegas
- Nutrition Research Group, Research Institute of Biomedical and Health Sciences, University of Las Palmas de Gran Canaria, Gran Canaria, Spain
- Biomedical Research Center Network on Obesity and Nutrition (CIBERobn) Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Madrid, Spain
| | - Husnain Arshad
- Université Paris-Saclay, UVSQ, Inserm, CESP, "DevPsy", 94807, Villejuif, France
| | - Tasnime Akbaraly
- Université Paris-Saclay, UVSQ, Inserm, CESP, "DevPsy", 94807, Villejuif, France
- Department of Epidemiology and Public Health, University College London, London, UK
| | - Adrienne O'Neil
- Deakin University, IMPACT (the Institute for Mental and Physical Health and Clinical Translation), Food & Mood Centre, Geelong, VIC, Australia
| | - Toby Segasby
- Basic and Clinical Neuroscience Department, Institute of Psychiatry Psychology and Neuroscience, King's College London, London, UK
| | - Felice N Jacka
- Deakin University, IMPACT (the Institute for Mental and Physical Health and Clinical Translation), Food & Mood Centre, Geelong, VIC, Australia
- Centre for Adolescent Health, Murdoch Children's Research Institute, Melbourne, VIC, Australia
- Black Dog Institute, Randwick, NSW, Australia
- James Cook University, Townsville, QLD, Australia
| |
Collapse
|
|
41
|
Elhag DA, Kumar M, Al Khodor S. Exploring the Triple Interaction between the Host Genome, the Epigenome, and the Gut Microbiome in Type 1 Diabetes. Int J Mol Sci 2020; 22:ijms22010125. [PMID: 33374418 PMCID: PMC7795494 DOI: 10.3390/ijms22010125] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Revised: 12/13/2020] [Accepted: 12/15/2020] [Indexed: 12/11/2022] Open
Abstract
Type 1 diabetes (T1D) is an auto-immune disorder characterized by a complex interaction between the host immune system and various environmental factors in genetically susceptible individuals. Genome-wide association studies (GWAS) identified different T1D risk and protection alleles, however, little is known about the environmental factors that can be linked to these alleles. Recent evidence indicated that, among those environmental factors, dysbiosis (imbalance) in the gut microbiota may play a role in the pathogenesis of T1D, affecting the integrity of the gut and leading to systemic inflammation and auto-destruction of the pancreatic β cells. Several studies have identified changes in the gut microbiome composition in humans and animal models comparing T1D subjects with controls. Those changes were characterized by a higher abundance of Bacteroides and a lower abundance of the butyrate-producing bacteria such as Clostridium clusters IV and XIVa. The mechanisms by which the dysbiotic bacteria and/or their metabolites interact with the genome and/or the epigenome of the host leading to destructive autoimmunity is still not clear. As T1D is a multifactorial disease, understanding the interaction between different environmental factors such as the gut microbiome, the genetic and the epigenetic determinants that are linked with the early appearance of autoantibodies can expand our knowledge about the disease pathogenesis. This review aims to provide insights into the interaction between the gut microbiome, susceptibility genes, epigenetic factors, and the immune system in the pathogenesis of T1D.
Collapse
|
|
42
|
Kessell AK, McCullough HC, Auchtung JM, Bernstein HC, Song HS. Predictive interactome modeling for precision microbiome engineering. Curr Opin Chem Eng 2020. [DOI: 10.1016/j.coche.2020.08.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2023]
|
|
43
|
Alvarenga L, Cardozo LF, Borges NA, Lindholm B, Stenvinkel P, Shiels PG, Fouque D, Mafra D. Can nutritional interventions modulate the activation of the NLRP3 inflammasome in chronic kidney disease? Food Res Int 2020; 136:109306. [DOI: 10.1016/j.foodres.2020.109306] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Revised: 04/28/2020] [Accepted: 05/07/2020] [Indexed: 02/06/2023]
|
|
44
|
Mondanelli G, Orecchini E, Volpi C, Panfili E, Belladonna ML, Pallotta MT, Moretti S, Galarini R, Esposito S, Orabona C. Effect of Probiotic Administration on Serum Tryptophan Metabolites in Pediatric Type 1 Diabetes Patients. Int J Tryptophan Res 2020; 13:1178646920956646. [PMID: 33061415 PMCID: PMC7534075 DOI: 10.1177/1178646920956646] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Accepted: 08/11/2020] [Indexed: 01/11/2023] Open
Abstract
Type 1 diabetes (T1D) is characterized by anomalous functioning of the immuno regulatory, tryptophan-catabolic enzyme indoleamine 2,3 dioxygenase 1 (IDO1). In T1D, the levels of kynurenine-the first byproduct of tryptophan degradation via IDO1-are significantly lower than in nondiabetic controls, such that defective immune regulation by IDO1 has been recognized as potentially contributing to autoimmunity in T1D. Because tryptophan catabolism-and the production of immune regulatory catabolites-also occurs via the gut microbiota, we measured serum levels of tryptophan, and metabolites thereof, in pediatric, diabetic patients after a 3-month oral course of Lactobacillus rhamnosus GG. Daily administration of the probiotic significantly affected circulating levels of tryptophan as well as the qualitative pattern of metabolite formation in the diabetic patients, while it decreased inflammatory cytokine production by the patients. This study suggests for the first time that a probiotic treatment may affect systemic tryptophan metabolism and restrain proinflammatory profile in pediatric T1D.
Collapse
Affiliation(s)
- Giada Mondanelli
- Department of Experimental Medicine, University of Perugia, Perugia, Italy
| | - Elena Orecchini
- Department of Experimental Medicine, University of Perugia, Perugia, Italy
| | - Claudia Volpi
- Department of Experimental Medicine, University of Perugia, Perugia, Italy
| | - Eleonora Panfili
- Department of Experimental Medicine, University of Perugia, Perugia, Italy
| | | | | | - Simone Moretti
- Istituto Zooprofilattico Sperimentale dell'Umbria e delle Marche "Togo Rosati," Perugia, Italy
| | - Roberta Galarini
- Istituto Zooprofilattico Sperimentale dell'Umbria e delle Marche "Togo Rosati," Perugia, Italy
| | - Susanna Esposito
- Pietro Barilla Children's Hospital, Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Ciriana Orabona
- Department of Experimental Medicine, University of Perugia, Perugia, Italy
| |
Collapse
|
|
45
|
Al Theyab A, Almutairi T, Al-Suwaidi AM, Bendriss G, McVeigh C, Chaari A. Epigenetic Effects of Gut Metabolites: Exploring the Path of Dietary Prevention of Type 1 Diabetes. Front Nutr 2020; 7:563605. [PMID: 33072796 PMCID: PMC7541812 DOI: 10.3389/fnut.2020.563605] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Accepted: 08/26/2020] [Indexed: 12/12/2022] Open
Abstract
Type 1 diabetes (T1D) has increased over the past half century and has now become the second most frequent autoimmune disease in childhood and one of major public health concern worldwide. Evidence suggests that modern lifestyles and rapid environmental changes are driving factors that underlie this increase. The integration of these two factors brings about changes in food intake. This, in turn, alters epigenetic regulations of the genome and intestinal microbiota composition, which may ultimately play a role in pathogenesis of T1D. Recent evidence shows that dysbiosis of the gut microbiota is closely associated with T1D and that a dietary intervention can influence epigenetic changes associated with this disease and may modify gene expression patterns through epigenetic mechanisms. In this review focus on how a diet can shape the gut microbiome, its effect on the epigenome in T1D, and the future of T1D management by microbiome therapy.
Collapse
Affiliation(s)
| | | | | | | | | | - Ali Chaari
- Premedical Division, Weill Cornell Medicine Qatar, Doha, Qatar
| |
Collapse
|
|
46
|
Effects of Lactobacillus casei Strain T2 (IBRC-M10783) on the Modulation of Th17/Treg and Evaluation of miR-155, miR-25, and IDO-1 Expression in a Cuprizone-Induced C57BL/6 Mouse Model of Demyelination. Inflammation 2020; 44:334-343. [PMID: 32914363 DOI: 10.1007/s10753-020-01339-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Revised: 08/19/2020] [Accepted: 09/03/2020] [Indexed: 12/15/2022]
Abstract
Multiple sclerosis (MS) is a complex inflammatory disease in which demyelination occurs in the central nervous system affecting approximately 2.5 million people worldwide. Recent reports have shown that the gut microbiome plays a crucial role in the functioning of the immune system in inflammatory diseases such as MS. In this study, the cuprizone-induced demyelination mouse model was used to investigate the effect of Lactobacillus casei strain T2 (IBRC-M10783) on the alleviation of these mice. Female C57BL/6 mice (8-10 weeks old) were divided into 6 groups: group 1, normal control; group 2, cuprizone control (oral administration of cuprizone 0.2% w/w for 4 weeks); group 3, probiotic control (oral administration of 1 × 109 CFU/ml probiotic for 4 weeks); group 4, treatment 1 (probiotic for 4 weeks then cuprizone for 4 weeks); group 5, treatment 2 (cuprizone for 4 weeks then probiotic for 4 weeks); and group 6, treatment 3 (cuprizone for 4 weeks then probiotic for 4 weeks with vitamin D3 at a dose of 20 IU/day). Then, TGF-β and IL-17 were measured by ELISA, and the expression of miR-155, miR-25, and IDO-1 was evaluated by real-time PCR. Among the measured microRNAs, the results showed that there was a significant decrease in miR-155 expression between the treatment 1 group and the cuprizone group. In the case of IL-17, the results also showed a significant reduction between the three treatment groups and the cuprizone group. These observations suggest that L. casei can reduce proinflammatory cytokines and reduce demyelinating symptoms in the mouse model.
Collapse
|
|
47
|
Ilchmann-Diounou H, Menard S. Psychological Stress, Intestinal Barrier Dysfunctions, and Autoimmune Disorders: An Overview. Front Immunol 2020; 11:1823. [PMID: 32983091 PMCID: PMC7477358 DOI: 10.3389/fimmu.2020.01823] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Accepted: 07/07/2020] [Indexed: 12/12/2022] Open
Abstract
Autoimmune disorders (ADs) are multifactorial diseases involving, genetic, epigenetic, and environmental factors characterized by an inappropriate immune response toward self-antigens. In the past decades, there has been a continuous rise in the incidence of ADs, which cannot be explained by genetic factors alone. Influence of psychological stress on the development or the course of autoimmune disorders has been discussed for a long time. Indeed, based on epidemiological studies, stress has been suggested to precede AD occurrence and to exacerbate symptoms. Furthermore, compiling data showed that most of ADs are associated with gastrointestinal symptoms, that is, microbiota dysbiosis, intestinal hyperpermeability, and intestinal inflammation. Interestingly, social stress (acute or chronic, in adult or in neonate) is a well-described intestinal disrupting factor. Taken together, those observations question a potential role of stress-induced defect of the intestinal barrier in the onset and/or the course of ADs. In this review, we aim to present evidences supporting the hypothesis for a role of stress-induced intestinal barrier disruption in the onset and/or the course of ADs. We will mainly focus on autoimmune type 1 diabetes, multiple sclerosis and systemic lupus erythematosus, ADs for which we could find sufficient circumstantial data to support this hypothesis. We excluded gastrointestinal (GI) ADs like coeliac disease to privilege ADs not focused on intestinal disorders to avoid confounding factors. Indeed, GIADs are characterized by antibodies directed against intestinal barrier actors.
Collapse
MESH Headings
- Animals
- Autoimmune Diseases/epidemiology
- Autoimmune Diseases/immunology
- Autoimmune Diseases/metabolism
- Autoimmune Diseases/microbiology
- Autoimmunity
- Diabetes Mellitus, Type 1/epidemiology
- Diabetes Mellitus, Type 1/immunology
- Diabetes Mellitus, Type 1/metabolism
- Diabetes Mellitus, Type 1/microbiology
- Dysbiosis
- Gastrointestinal Microbiome
- Host-Pathogen Interactions
- Humans
- Intestinal Mucosa/immunology
- Intestinal Mucosa/metabolism
- Intestinal Mucosa/microbiology
- Lupus Erythematosus, Systemic/epidemiology
- Lupus Erythematosus, Systemic/immunology
- Lupus Erythematosus, Systemic/metabolism
- Lupus Erythematosus, Systemic/microbiology
- Multiple Sclerosis/epidemiology
- Multiple Sclerosis/immunology
- Multiple Sclerosis/metabolism
- Multiple Sclerosis/microbiology
- Permeability
- Risk Factors
- Stress, Psychological/epidemiology
- Stress, Psychological/immunology
- Stress, Psychological/metabolism
- Stress, Psychological/microbiology
Collapse
Affiliation(s)
| | - Sandrine Menard
- Neuro-Gastroenterology and Nutrition Team, Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRAE, ENVT, INP-Purpan, UPS, Toulouse, France
| |
Collapse
|
|
48
|
Lau WL, Chang Y, Vaziri ND. The consequences of altered microbiota in immune-related chronic kidney disease. Nephrol Dial Transplant 2020; 36:1791-1798. [PMID: 32437554 DOI: 10.1093/ndt/gfaa087] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Indexed: 12/24/2022] Open
Abstract
The normal gut microbiome modulates host enterocyte metabolism and shapes local and systemic immunity. Accumulation of urea and other waste products in chronic kidney disease induces gut dysbiosis and intestinal wall inflammation (leaky gut). There are decreased numbers of bacteria that generate short-chain fatty acids, which are an important nutrient source for host enterocytes and also contribute to regulation of the host immune system. Anaerobic proteolytic bacteria that express urease, uricase and indole and p-cresol enzymes, such as Enterobacteria and Enterococci, are increased. Microbial-derived uremic toxins such as indoxyl sulfate and trimethylamine N-oxide contribute to the pathophysiology of immune-related kidney diseases such as diabetic nephropathy, lupus nephritis and immunoglobulin A (IgA) nephropathy. Animal and clinical studies suggest potential benefits of dietary and probiotic interventions in slowing the progression of immune-related kidney diseases.
Collapse
Affiliation(s)
- Wei Ling Lau
- Division of Nephrology and Hypertension, University of California Irvine, Orange, CA, USA
| | - Yongen Chang
- Division of Nephrology and Hypertension, University of California Irvine, Orange, CA, USA
| | - Nosratola D Vaziri
- Division of Nephrology and Hypertension, University of California Irvine, Orange, CA, USA
| |
Collapse
|
|
49
|
Microbiota derived factors as drivers of type 1 diabetes. PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE 2020; 171:215-235. [PMID: 32475523 DOI: 10.1016/bs.pmbts.2020.04.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Type 1 diabetes (T1D) is an autoimmune disease caused by complex interactions between host genetics and environmental factors, culminating in the T-cell mediated destruction of the insulin producing cells in the pancreas. The rapid increase in disease frequency over the past 50 years or more has been too rapid to attribute to genetics. Dysbiosis of the gut microbiota is currently being widely investigated as a major contributor to environmental change driving increased T1D onset. In this chapter, we discuss the major changes in gut microbiota composition and function linked to T1D risk as well as the potential origin of these changes including infant diet, antibiotic use and host genetics. We examine the interaction between inflammation and gut barrier function and the dysbiotic gut microbiota that have been linked to T1D.
Collapse
|
|
50
|
Cheng FS, Pan D, Chang B, Jiang M, Sang LX. Probiotic mixture VSL#3: An overview of basic and clinical studies in chronic diseases. World J Clin Cases 2020; 8:1361-1384. [PMID: 32368530 PMCID: PMC7190945 DOI: 10.12998/wjcc.v8.i8.1361] [Citation(s) in RCA: 74] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 03/27/2020] [Accepted: 04/08/2020] [Indexed: 02/05/2023] Open
Abstract
Probiotics are known as “live microorganisms” and have been proven to have a health effect on hosts at the proper dose. Recently, a kind of probiotic mixture including eight live bacterial strains, VSL#3, has attracted considerable attention for its combined effect. VSL#3 is the only probiotic considered as a kind of medical food; it mainly participates in the regulation of the intestinal barrier function, including improving tight junction protein function, balancing intestinal microbial composition, regulating immune-related cytokine expression and so on. The objective of this review is to discuss the treatment action and mechanism for the administration of VSL#3 in chronic diseases of animals and humans (including children). We found that VSL#3 has a therapeutic or preventive effect in various systemic diseases per a large number of studies, including digestive systemic diseases (gastrointestinal diseases and hepatic diseases), obesity and diabetes, allergic diseases, nervous systemic diseases, atherosclerosis, bone diseases, and female reproductive systemic diseases.
Collapse
Affiliation(s)
- Fang-Shu Cheng
- Department of Dermatology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
- Class 85 of 101k, China Medical University, Shenyang 110004, Liaoning Province, China
| | - Dan Pan
- Department of Geriatrics, the First Affiliated Hospital, China Medical University, Shenyang 110001, Liaoning Province, China
| | - Bing Chang
- Department of Gastroenterology, the First Affiliated Hospital, China Medical University, Shenyang 110001, Liaoning Province, China
| | - Min Jiang
- Department of Gastroenterology, the First Affiliated Hospital, China Medical University, Shenyang 110001, Liaoning Province, China
| | - Li-Xuan Sang
- Department of Geriatrics, the First Affiliated Hospital, China Medical University, Shenyang 110001, Liaoning Province, China
| |
Collapse
|