Gut microbiome and metabolic activity in type 1 diabetes: An analysis based on the presence of GADA

被引：11

作者：

Luo, Sihui ^{[1
]}

Yue, Tong ^{[1
]}

Liu, Ziyu ^{[2
]}

Yang, Daizhi ^{[2
]}

Xu, Mengyun ^{[1
]}

Ding, Yu ^{[1
]}

Jiang, Weiwei ^{[2
]}

Xu, Wen ^{[2
]}

Yan, Jinhua ^{[2
]}

Weng, Jianping ^{[1
]}

Zheng, Xueying ^{[1
]}

机构：

[1] Univ Sci & Technol China, Affiliated Hosp 1, USTC, Div Life Sci & Med,Dept Endocrinol, Hefei, Peoples R China

[2] Sun Yat sen Univ, Affiliated Hosp 3, Dept Endocrinol & Metab, Guangzhou, Peoples R China

来源：

FRONTIERS IN ENDOCRINOLOGY | 2022年 / 13卷

基金：

中国国家自然科学基金;

关键词：

T1D (type 1 diabetes); GADA; gut microbiome; serum metabolites; tryptophan metabolism; ONSET; PROGRESSION;

D O I：

10.3389/fendo.2022.938358

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

ObjectiveType 1 diabetes (T1D) progression is affected by circulating glutamic acid decarboxylase antibody (GADA) that persist for many years. This study aimed at investigating whether and how the gut microbiome and its correlated metabolites change in T1D with the presence of GADA. MethodsWe used a radiobinding assay to measure GADA titers and identify the 49 T1D patients with GADA+ and 52 T1D patients with GADA-. The fresh feces and serum were analyzed using 16S rRNA gene sequencing and GC/MS. Then gut microbiome and serum metabolites were compared between the GADA+ patients and the GADA- patients. The association between gut microbial community and metabolites was assessed using the Spearman's rank correlation. ResultsThe gut microbiome in diversity, composition, and function differed between these two groups. The abundance of genus Alistipes, Ruminococcus significantly increased in patients with GADA+ compared to that observed in the samples of GADA-. There were 54 significantly altered serum metabolites associated with tryptophan metabolism, phenylalanine, and tyrosine biosynthesis in individuals with GADA+ compared with those of GADA-For the serum metabolites, compared with those of GADA-, there were 54 significantly different metabolites with tryptophan metabolism, phenylalanine, and tyrosine and tryptophan biosynthesis decreased in individuals with GADA+. The abundance of Alistipes was positively correlated with altered metabolites involved in tryptophan metabolism. ConclusionWe demonstrate that T1D patients with GADA+ are characterised by aberrant profiles of gut microbiota and serum metabolites. The abundance of Alistipes disturbances may participate in the development of T1D patients with GADA by modulating the host's tryptophan metabolism. These findings extend our insights into the association between the gut microbiota and tryptophan metabolism and GADA and might be targeted for preventing the development of T1D.

引用

页数：10

共 42 条

[1] Introducing the Endotype Concept to Address the Challenge of Disease Heterogeneity in Type 1 Diabetes [J].

Battaglia, Manuela ;

Ahmed, Simi ;

Anderson, Mark S. ;

Atkinson, Mark A. ;

Becker, Dorothy ;

Bingley, Polly J. ;

Bosi, Emanuele ;

Brusko, Todd M. ;

DiMeglio, Linda A. ;

Evans-Molina, Carmella ;

Gitelman, Stephen E. ;

Greenbaum, Carla J. ;

Gottlieb, Peter A. ;

Herold, Kevan C. ;

Hessner, Martin J. ;

Knip, Mikael ;

Jacobsen, Laura ;

Krischer, Jeffrey P. ;

Long, S. Alice ;

Lundgren, Markus ;

McKinney, Eoin F. ;

Morgan, Noel G. ;

Oram, Richard A. ;

Pastinen, Tomi ;

Peters, Michael C. ;

Petrelli, Alessandra ;

Qian, Xiaoning ;

Redondo, Maria J. ;

Roep, Bart O. ;

Schatz, Desmond ;

Skibinski, David ;

Peakman, Mark .

DIABETES CARE, 2020, 43 (01) :5-12

[2] Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2 [J].

Bolyen, Evan ;

Rideout, Jai Ram ;

Dillon, Matthew R. ;

Bokulich, NicholasA. ;

Abnet, Christian C. ;

Al-Ghalith, Gabriel A. ;

Alexander, Harriet ;

Alm, Eric J. ;

Arumugam, Manimozhiyan ;

Asnicar, Francesco ;

Bai, Yang ;

Bisanz, Jordan E. ;

Bittinger, Kyle ;

Brejnrod, Asker ;

Brislawn, Colin J. ;

Brown, C. Titus ;

Callahan, Benjamin J. ;

Caraballo-Rodriguez, Andres Mauricio ;

Chase, John ;

Cope, Emily K. ;

Da Silva, Ricardo ;

Diener, Christian ;

Dorrestein, Pieter C. ;

Douglas, Gavin M. ;

Durall, Daniel M. ;

Duvallet, Claire ;

Edwardson, Christian F. ;

Ernst, Madeleine ;

Estaki, Mehrbod ;

Fouquier, Jennifer ;

Gauglitz, Julia M. ;

Gibbons, Sean M. ;

Gibson, Deanna L. ;

Gonzalez, Antonio ;

Gorlick, Kestrel ;

Guo, Jiarong ;

Hillmann, Benjamin ;

Holmes, Susan ;

Holste, Hannes ;

Huttenhower, Curtis ;

Huttley, Gavin A. ;

Janssen, Stefan ;

Jarmusch, Alan K. ;

Jiang, Lingjing ;

Kaehler, Benjamin D. ;

Bin Kang, Kyo ;

Keefe, Christopher R. ;

Keim, Paul ;

Kelley, Scott T. ;

Knights, Dan .

NATURE BIOTECHNOLOGY, 2019, 37 (08) :852-857

[3] Increased intestinal permeability precedes clinical onset of type 1 diabetes [J].

Bosi, E. ;

Molteni, L. ;

Radaelli, M. G. ;

Folini, L. ;

Fermo, I. ;

Bazzigaluppi, E. ;

Piemonti, L. ;

Pastore, M. R. ;

Paroni, R. .

DIABETOLOGIA, 2006, 49 (12) :2824-2827

[4]

Callahan BJ, 2016, NAT METHODS, V13, P581, DOI [10.1038/NMETH.3869, 10.1038/nmeth.3869]

[5] Residual β-cell function after 10 years of autoimmune type 1 diabetes: prevalence, possible determinants, and implications for metabolism [J].

Cheng, Jin ;

Yin, Min ;

Tang, Xiaohan ;

Yan, Xiang ;

Xie, Yuting ;

He, Binbin ;

Li, Xia ;

Zhou, Zhiguang .

ANNALS OF TRANSLATIONAL MEDICINE, 2021, 9 (08)

[6] Intestinal microbiota-derived tryptophan metabolites are predictive of Ah receptor activity [J].

Dong, Fangcong ;

Hao, Fuhua ;

Murray, Iain A. ;

Smith, Philip B. ;

Koo, Imhoi ;

Tindall, Alyssa M. ;

Kris-Etherton, Penny M. ;

Gowda, Krishne ;

Amin, Shantu G. ;

Patterson, Andrew D. ;

Perdew, Gary H. .

GUT MICROBES, 2020, 12 (01) :1-24

[7]

Douglas GM, 2018, METHODS MOL BIOL, V1849, P169, DOI 10.1007/978-1-4939-8728-3_11

[8] Associated autoimmunity in Type 1 Diabetes and latent autoimmune diabetes of adults: The role of glutamic-acid decarboxylase autoantibodies [J].

Gougourelas, Dimitrios ;

Tsentidis, Charalampos ;

Koufadaki, Athina Maria ;

Koutsovasilis, Anastasios ;

Gougourela, Eupraxia ;

Karanasios, Spyridon ;

Sotiropoulos, Alexios ;

Bousboulas, Stavros ;

Karavanaki, Kyriaki Athina .

DIABETES RESEARCH AND CLINICAL PRACTICE, 2021, 175

[9] Clostridium species as probiotics: potentials and challenges [J].

Guo, Pingting ;

Zhang, Ke ;

Ma, Xi ;

He, Pingli .

JOURNAL OF ANIMAL SCIENCE AND BIOTECHNOLOGY, 2020, 11 (01)

[10] Serum analysis of tryptophan catabolism pathway: Correlation with Crohn's disease activity [J].

Gupta, Nitin K. ;

Thaker, Ameet I. ;

Kanuri, Navya ;

Riehl, Terrence E. ;

Rowley, Christopher W. ;

Stenson, William F. ;

Ciorba, Matthew A. .

INFLAMMATORY BOWEL DISEASES, 2012, 18 (07) :1214-1220

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