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Modulation of Gut Microbiota by Low Methoxyl Pectin Attenuates Type 1 Diabetes in Non-obese Diabetic Mice.
Front Immunol. 2019; 10:1733.FI

Abstract

Intestinal homeostasis underpins the development of type 1 diabetes (T1D), and dietary manipulations to enhance intestinal homeostasis have been proposed to prevent T1D. The current study aimed to investigate the efficacy of supplementing a novel specific low-methoxyl pectin (LMP) dietary fiber in preventing T1D development. Female NOD mice were weaned onto control or 5% (wt/wt) LMP supplemented diets for up to 40 weeks of age, overt diabetes incidence and blood glucose were monitored. Then broad-spectrum antibiotics (ABX) treatment per os for 7 days followed by gut microbiota transfer was performed to demonstrate gut microbiota-dependent effects. Next-generation sequencing was used for analyzing the composition of microbiota in caecum. Concentration of short chain fatty acids were determined by GC-MS. The barrier reinforcing tight junction proteins zonula occludens-2 (ZO-2), claudin-1 and NOD like receptor protein 3 (NLRP3) inflammasome activation were determined by Western blot. The proportion of CD25+Foxp3+CD4+ regulatory T cell (Foxp3+ Treg) in the pancreas, pancreatic and mesenteric lymph nodes was analyzed by flow cytometry. We found that LMP supplementation ameliorated T1D development in non-obese diabetic (NOD) mice, as evidenced by decreasing diabetes incidence and fasting glucose levels in LMP fed NOD mice. Further microbiota analysis revealed that LMP supplementation prevented T1D-associated caecal dysbiosis and selectively enriched caecal bacterial species to produce more SCFAs. The LMP-mediated microbial balance further enhanced caecal barrier function and shaped gut-pancreatic immune environment, as characterized by higher expression of tight junction proteins claudin-1, ZO-2 in caecum, increased Foxp3+ Treg population and decreased NLRP3 inflammasome activation in both caecum and pancreas. The microbiota-dependent beneficial effect of LMP on T1D was further proven by the fact that aberration of caecal microbiota by ABX treatment worsened T1D autoimmunity and could be restored with transfer of feces of LMP-fed NOD mice. These data demonstrate that this novel LMP limits T1D development by inducing caecal homeostasis to shape pancreatic immune environment. This finding opens a realistic option for gut microbiota manipulation and prevention of T1D in humans.

Authors+Show Affiliations

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China. School of Food Science and Technology, Jiangnan University, Wuxi, China.School of Medicine, Jiangnan University, Wuxi, China.State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China. School of Food Science and Technology, Jiangnan University, Wuxi, China.State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China. School of Food Science and Technology, Jiangnan University, Wuxi, China.State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China. School of Food Science and Technology, Jiangnan University, Wuxi, China.State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China. School of Food Science and Technology, Jiangnan University, Wuxi, China.State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China. School of Food Science and Technology, Jiangnan University, Wuxi, China.State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China. School of Food Science and Technology, Jiangnan University, Wuxi, China.State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China. School of Food Science and Technology, Jiangnan University, Wuxi, China.State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China. School of Food Science and Technology, Jiangnan University, Wuxi, China.Department of Surgery, University of California, Irvine, Orange, CA, United States.Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital, Huddinge, Sweden.Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China. School of Food Science and Technology, Jiangnan University, Wuxi, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31417546

Citation

Wu, Chengfei, et al. "Modulation of Gut Microbiota By Low Methoxyl Pectin Attenuates Type 1 Diabetes in Non-obese Diabetic Mice." Frontiers in Immunology, vol. 10, 2019, p. 1733.
Wu C, Pan LL, Niu W, et al. Modulation of Gut Microbiota by Low Methoxyl Pectin Attenuates Type 1 Diabetes in Non-obese Diabetic Mice. Front Immunol. 2019;10:1733.
Wu, C., Pan, L. L., Niu, W., Fang, X., Liang, W., Li, J., Li, H., Pan, X., Chen, W., Zhang, H., Lakey, J. R. T., Agerberth, B., de Vos, P., & Sun, J. (2019). Modulation of Gut Microbiota by Low Methoxyl Pectin Attenuates Type 1 Diabetes in Non-obese Diabetic Mice. Frontiers in Immunology, 10, 1733. https://doi.org/10.3389/fimmu.2019.01733
Wu C, et al. Modulation of Gut Microbiota By Low Methoxyl Pectin Attenuates Type 1 Diabetes in Non-obese Diabetic Mice. Front Immunol. 2019;10:1733. PubMed PMID: 31417546.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modulation of Gut Microbiota by Low Methoxyl Pectin Attenuates Type 1 Diabetes in Non-obese Diabetic Mice. AU - Wu,Chengfei, AU - Pan,Li-Long, AU - Niu,Wenying, AU - Fang,Xin, AU - Liang,Wenjie, AU - Li,Jiahong, AU - Li,Hongli, AU - Pan,Xiaohua, AU - Chen,Wei, AU - Zhang,Hao, AU - Lakey,Jonathan R T, AU - Agerberth,Birgitta, AU - de Vos,Paul, AU - Sun,Jia, Y1 - 2019/07/30/ PY - 2019/04/16/received PY - 2019/07/09/accepted PY - 2019/8/17/entrez PY - 2019/8/17/pubmed PY - 2020/10/8/medline KW - autoimmune diabetes KW - gut microbiota KW - immunomodulation KW - intestinal homeostasis KW - low-methoxyl pectin SP - 1733 EP - 1733 JF - Frontiers in immunology JO - Front Immunol VL - 10 N2 - Intestinal homeostasis underpins the development of type 1 diabetes (T1D), and dietary manipulations to enhance intestinal homeostasis have been proposed to prevent T1D. The current study aimed to investigate the efficacy of supplementing a novel specific low-methoxyl pectin (LMP) dietary fiber in preventing T1D development. Female NOD mice were weaned onto control or 5% (wt/wt) LMP supplemented diets for up to 40 weeks of age, overt diabetes incidence and blood glucose were monitored. Then broad-spectrum antibiotics (ABX) treatment per os for 7 days followed by gut microbiota transfer was performed to demonstrate gut microbiota-dependent effects. Next-generation sequencing was used for analyzing the composition of microbiota in caecum. Concentration of short chain fatty acids were determined by GC-MS. The barrier reinforcing tight junction proteins zonula occludens-2 (ZO-2), claudin-1 and NOD like receptor protein 3 (NLRP3) inflammasome activation were determined by Western blot. The proportion of CD25+Foxp3+CD4+ regulatory T cell (Foxp3+ Treg) in the pancreas, pancreatic and mesenteric lymph nodes was analyzed by flow cytometry. We found that LMP supplementation ameliorated T1D development in non-obese diabetic (NOD) mice, as evidenced by decreasing diabetes incidence and fasting glucose levels in LMP fed NOD mice. Further microbiota analysis revealed that LMP supplementation prevented T1D-associated caecal dysbiosis and selectively enriched caecal bacterial species to produce more SCFAs. The LMP-mediated microbial balance further enhanced caecal barrier function and shaped gut-pancreatic immune environment, as characterized by higher expression of tight junction proteins claudin-1, ZO-2 in caecum, increased Foxp3+ Treg population and decreased NLRP3 inflammasome activation in both caecum and pancreas. The microbiota-dependent beneficial effect of LMP on T1D was further proven by the fact that aberration of caecal microbiota by ABX treatment worsened T1D autoimmunity and could be restored with transfer of feces of LMP-fed NOD mice. These data demonstrate that this novel LMP limits T1D development by inducing caecal homeostasis to shape pancreatic immune environment. This finding opens a realistic option for gut microbiota manipulation and prevention of T1D in humans. SN - 1664-3224 UR - https://www.unboundmedicine.com/medline/citation/31417546/Modulation_of_Gut_Microbiota_by_Low_Methoxyl_Pectin_Attenuates_Type_1_Diabetes_in_Non_obese_Diabetic_Mice_ L2 - https://doi.org/10.3389/fimmu.2019.01733 DB - PRIME DP - Unbound Medicine ER -