Home > Archive>Volume 17, Issue 5, 2024 >883-895. DOI:10.18240/ijo.2024.05.13
HTML XML Export Cite reminder
Gut microbiota induced abnormal amino acids and their correlation with diabetic retinopathy
Author:
Corresponding Author:

Jian-Su Chen and Shi-Bo Tang. Ai’er Building, No.188, Section 1, Furong South Road, Tianxin District, Changsha 410000, Hunan Province, China. chenjiansu2000@163.com; tangshibo@vip.163.com

  • Article
    • | |
  • Metrics
    • |
  • Reference [74]
    • |
  • Related
    • |
  • Cited by
    • | |
  • Comments
    Abstract:

    AIM: To explore the correlation of gut microbiota and the metabolites with the progression of diabetic retinopathy (DR) and provide a novel strategy to elucidate the pathological mechanism of DR. METHODS: The fecal samples from 32 type 2 diabetes patients with proliferative retinopathy (PDR), 23 with non-proliferative retinopathy (NPDR), 27 without retinopathy (DM), and 29 from the sex-, age- and BMI- matched healthy controls (29 HC) were analyzed by 16S rDNA gene sequencing. Sixty fecal samples from PDR, DM, and HC groups were assayed by untargeted metabolomics. Fecal metabolites were measured using liquid chromatography-mass spectrometry (LC-MS) analysis. Associations between gut microbiota and fecal metabolites were analyzed. RESULTS: A cluster of 2 microbiome and 12 metabolites accompanied with the severity of DR, and the close correlation of the disease progression with PDR-related microbiome and metabolites were found. To be specific, the structure of gut microbiota differed in four groups. Diversity and richness of gut microbiota were significantly lower in PDR and NPDR groups, than those in DM and HC groups. A cluster of microbiome enriched in PDR group, including Pseudomonas, Ruminococcaceae-UCG-002, Ruminococcaceae-UCG-005, Christensenellaceae-R-7, was observed. Functional analysis showed that the glucose and nicotinate degradations were significantly higher in PDR group than those in HC group. Arginine, serine, ornithine, and arachidonic acid were significantly enriched in PDR group, while proline was enriched in HC group. Functional analysis illustrated that arginine biosynthesis, lysine degradation, histidine catabolism, central carbon catabolism in cancer, D-arginine and D-ornithine catabolism were elevated in PDR group. Correlation analysis revealed that Ruminococcaceae-UCG-002 and Christensenellaceae-R-7 were positively associated with L-arginine, ornithine levels in fecal samples. CONCLUSION: This study elaborates the different microbiota structure in the gut from four groups. The relative abundance of Ruminococcaceae-UCG-002 and Parabacteroides are associated with the severity of DR. Amino acid and fatty acid catabolism is especially disordered in PDR group. This may help provide a novel diagnostic parameter for DR, especially PDR.

    Reference
    1 Hou XH, Wang LM, Zhu DL, et al, China National Diabetic Chronic Complications Study Group. Prevalence of diabetic retinopathy and vision-threatening diabetic retinopathy in adults with diabetes in China. Nat Commun 2023;14(1):4296.
    2 Zhang P, Xue WW, Huang XB, Xu Y, Lu LN, Zheng KR, Zou HD. Prevalence and risk factors of diabetic retinopathy in patients with type 2 diabetes in Shanghai. Int J Ophthalmol 2021;14(7):1066-1072.
    3 Rinninella E, Mele MC, Merendino N, et al. The role of diet, micronutrients and the gut microbiota in age-related macular degeneration: new perspectives from the Gut⁻Retina axis. Nutrients 2018;10(11):1677.
    4 Chaiwiang N, Poyomtip T. Microbial dysbiosis and microbiota-gut-retina axis: the lesson from brain neurodegenerative diseases to primary open-angle glaucoma pathogenesis of autoimmunity. Acta Microbiol Immunol Hung 2019;66(4):541-558.
    5 Verma A, Xu K, Du T, et al. Expression of human ACE2 in lactobacillus and beneficial effects in diabetic retinopathy in mice. Mol Ther Methods Clin Dev 2019;14:161-170.
    6 Rowan S, Taylor A. The role of microbiota in retinal disease. Adv Exp Med Biol 2018;1074:429-435.
    7 Rowan S, Jiang SH, Korem T, et al. Involvement of a gut-retina axis in protection against dietary glycemia-induced age-related macular degeneration. Proc Natl Acad Sci U S A 2017;114(22): E4472-E4481.
    8 Parkman HP, Wilson LA, Farrugia G, et al, Gastroparesis Clinical Research Consortium (GpCRC) NIDDK. Delayed gastric emptying associates with diabetic complications in diabetic patients with symptoms of gastroparesis. Am J Gastroenterol 2019;114(11): 1778-1794.
    9 Singh P, Adderley N, Subramanian A, et al. The impact of bariatric surgery on incident microvascular complications in patients with type 2 diabetes: a matched controlled population-based retrospective cohort study. Diabetes Care 2021;44(1):116-124.
    10 Koutoukidis DA, Jebb SA, Zimmerman M, et al. The association of weight loss with changes in the gut microbiota diversity, composition, and intestinal permeability: a systematic review and meta-analysis. Gut Microbes 2022;14(1):2020068.
    11 Scheithauer TPM, Davids M, Winkelmeijer M, et al. Compensatory intestinal antibody response against pro-inflammatory microbiota after bariatric surgery. Gut Microbes 2022;14(1):2031696.
    12 Huang YH, Wang ZJ, Ma HJ, Ji SL, Chen ZP, Cui ZK, Chen JS, Tang SB. Dysbiosis and implication of the gut microbiota in diabetic retinopathy. Front Cell Infect Microbiol 2021;11:646348.
    13 Sun LL, Xie C, Wang G, et al. Gut microbiota and intestinal FXR mediate the clinical benefits of metformin. Nat Med 2018;24(12): 1919-1929.
    14 Das T, Jayasudha R, Chakravarthy S, et al. Alterations in the gut bacterial microbiome in people with type 2 diabetes mellitus and diabetic retinopathy. Sci Rep 2021;11(1):2738.
    15 Kang QZ, Yang CX. Oxidative stress and diabetic retinopathy: molecular mechanisms, pathogenetic role and therapeutic implications. Redox Biol 2020;37:101799.
    16 Spencer BG, Estevez JJ, Liu E, Craig JE, Finnie JW. Pericytes, inflammation, and diabetic retinopathy. Inflammopharmacology 2020;28(3):697-709.
    17 Järgen P, Dietrich A, Herling AW, Hammes HP, Wohlfart P. The role of insulin resistance in experimental diabetic retinopathy-Genetic and molecular aspects. PLoS One 2017;12(6):e0178658.
    18 Wang ZY, Tang JY, Jin EZ, et al. Serum untargeted metabolomics reveal potential biomarkers of progression of diabetic retinopathy in asians. Front Mol Biosci 2022;9:871291.
    19 Midena E, Frizziero L, Midena G, Pilotto E. Intraocular fluid biomarkers (liquid biopsy) in human diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol 2021;259(12):3549-3560.
    20 Wang HY, Li S, Wang C, Wang YH, Fang JW, Liu K. Plasma and vitreous metabolomics profiling of proliferative diabetic retinopathy. Invest Ophthalmol Vis Sci 2022;63(2):17.
    21 Floyd JL, Grant MB. The gut-eye axis: lessons learned from murine models. Ophthalmol Ther 2020;9(3):499-513.
    22 Ye PP, Zhang XY, Xu YF, Xu J, Song XX, Yao K. Alterations of the gut microbiome and metabolome in patients with proliferative diabetic retinopathy. Front Microbiol 2021;12:667632.
    23 Caporaso JG, Kuczynski J, Stombaugh J, et al. QIIME allows analysis of high-throughput community sequencing data. Nat Methods 2010;7(5):335-336.
    24 Zelena E, Dunn WB, Broadhurst D, et al. Development of a robust and repeatable UPLC-MS method for the long-term metabolomic study of human serum. Anal Chem 2009;81(4):1357-1364.
    25 Want EJ, Masson P, Michopoulos F, et al. Global metabolic profiling of animal and human tissues via UPLC-MS. Nat Protoc 2013;8:17-32.
    26 Zhou ZX, Zheng Z, Xiong XJ, et al. Gut microbiota composition and fecal metabolic profiling in patients with diabetic retinopathy. Front Cell Dev Biol 2021;9:732204.
    27 Krych Ł, Nielsen DS, Hansen AK, Hansen CHF. Gut microbial markers are associated with diabetes onset, regulatory imbalance, and IFN-γ level in NOD mice. Gut Microbes 2015;6(2):101-109.
    28 Yang R, Jia Q, Mehmood S, Ma SF, Liu XF. Genistein ameliorates inflammation and insulin resistance through mediation of gut microbiota composition in type 2 diabetic mice. Eur J Nutr 2021;60(4):2155-2168.
    29 Alvarez-Silva C, Kashani A, Hansen TH, et al. Trans-ethnic gut microbiota signatures of type 2 diabetes in Denmark and India. Genome Med 2021;13(1):37.
    30 Chen ZL, Radjabzadeh D, Chen LM, et al. Association of insulin resistance and type 2 diabetes with gut microbial diversity: a microbiome-wide analysis from population studies. JAMA Netw Open 2021;4(7):e2118811.
    31 Rose SMSF, Contrepois K, Moneghetti KJ, et al. A longitudinal big data approach for precision health. Nat Med 2019;25(5):792-804.
    32 Vojinovic D, Radjabzadeh D, Kurilshikov A, et al. Relationship between gut microbiota and circulating metabolites in population-based cohorts. Nat Commun 2019;10(1):5813.
    33 Dedrick S, Sundaresh B, Huang Q, et al. The role of gut microbiota and environmental factors in type 1 diabetes pathogenesis. Front Endocrinol 2020;11:78.
    34 Yang KL, Niu JK, Zuo T, et al. Alterations in the gut virome in obesity and type 2 diabetes mellitus. Gastroenterology 2021;161(4):1257-1269.e13.
    35 Penney NC, Yeung DKT, Garcia-Perez I, et al. Multi-omic phenotyping reveals host-microbe responses to bariatric surgery, glycaemic control and obesity. Commun Med 2022;2:127.
    36 Zheng SJ, Wang YN, Fang JJ, et al. Oleuropein ameliorates advanced stage of type 2 diabetes in db/db mice by regulating gut microbiota. Nutrients 2021;13(7):2131.
    37 Girdhar K, Huang Q, Chow IT, et al. A gut microbial peptide and molecular mimicry in the pathogenesis of type 1 diabetes. Proc Natl Acad Sci U S A 2022;119(31):e2120028119.
    38 Anhê FF, Zlitni S, Zhang SY, et al. Human gut microbiota after bariatric surgery alters intestinal morphology and glucose absorption in mice independently of obesity. Gut 2023;72(3):460-471.
    39 Larsen N, Vogensen FK, van den Berg et al. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS One 2010;5(2):e9085.
    40 Karlsson FH, Tremaroli V, Nookaew I, et al. Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature 2013;498(7452):99-103.
    41 Wang YY, Ye XL, Ding DF, Lu YB. Characteristics of the intestinal flora in patients with peripheral neuropathy associated with type 2 diabetes. J Int Med Res 2020;48(9):300060520936806.
    42 Beli E, Yan YQ, Moldovan ancet Diabetes Endocrinol 2017;5(12):965-974.
    75 Zong G, Liu G, Willett WC, Wanders AJ, Alssema M, Zock PL, Hu FB, Sun Q. Associations between linoleic acid intake and incident type 2 diabetes among U.S. men and women. Diabetes Care 2019;42(8):1406-1413.
    76 Das UN. Arachidonic acid and lipoxin A4 as possible endogenous anti-diabetic molecules. Prostaglandins Leukot Essent Fatty Acids 2013;88(3):201-210.
    77 Kalofoutis A, Lekakis J. Changes of platelet phospholipids in diabetes mellitus. Diabetologia 1981;21(6):540-543.
    78 Colwell JA, Winocour PD, Halushka PV. Do platelets have anything to do with diabetic microvascular disease? Diabetes 1983;32(Suppl 2): 14-19.
    79 Katayama S, Inaba M, Maruno Y, Omoto A, Kawazu S, Ishii J, Sawada M. Increased renal TXA2 synthesis in diabetes mellitus: simultaneous determination of urinary TXB2 and 2, 3-dinor-TXB2. Prostaglandins Leukot Essent Fatty Acids 1990;39(1):47-51.
    80 Phillips BE, Garciafigueroa Y, Engman C, et al. Arrest in the progression of type 1 diabetes at the mid-stage of insulitic autoimmunity using an autoantigen-decorated all- trans retinoic acid and transforming growth factor beta-1 single microparticle formulation. Front Immunol 2021;12:586220.
    81 Sato Y, Atarashi K, Plichta DR, et al. Novel bile acid biosynthetic pathways are enriched in the microbiome of centenarians. Nature 2021;599(7885):458-464.
    82 Perino A, Schoonjans K. Metabolic Messengers: bile acids. Nat Metab 2022;4(4):416-423.
    83 Liu BW, Zhuang ST, Tian RZ, Liu Y, Wang YQ, Lei XG, Wang C. Chemoproteomic profiling reveals the mechanism of bile acid tolerance in bacteria. ACS Chem Biol 2022;17(9):2461-2470.rwez I, Ozair M. Culture-based screening of aerobic microbiome in diabetic foot subjects and developing non-healing ulcers. Front Microbiol 2016;7:1792.
    52 iMSMS Consortium Electronic address: sergio baranzini@ucsf edu, Consortium I. Gut microbiome of multiple sclerosis patients and paired household healthy controls reveal associations with disease risk and course. Cell 2022;185(19):3467-3486.e16.
    53 Xuan QH, Ouyang Y, Wang YF, et al. Multiplatform metabolomics reveals novel serum metabolite biomarkers in diabetic retinopathy subjects. Adv Sci 2020;7(22):2001714.
    54 Chen Y, Wang N, Dong XL, Zhu JF, Chen Y, Jiang QW, Fu CW. Associations between serum amino acids and incident type 2 diabetes in Chinese rural adults. Nutr Metab Cardiovasc Dis 2021;31(8): 2416-2425.
    55 Hu ZH, Zhang CL, Sifuentes-Dominguez L, et al. Small proline-rich protein 2A is a gut bactericidal protein deployed during helminth infection. Science 2021;374(6568):eabe6723.
    56 Koutroubakis IE, Petinaki E, Dimoulios P, et al. Serum laminin and collagen IV in inflammatory bowel disease. J Clin Pathol 2003;56(11):817-820.
    57 Yam M, Engel AL, Wang YK, et al. Proline mediates metabolic communication between retinal pigment epithelial cells and the retina. J Biol Chem 2019;294(26):10278-10289.
    58 Ueda M, Masu Y, Ando A, Maeda H, Del Monte MA, Uyama M, Ito S. Prevention of ornithine cytotoxicity by proline in human retinal pigment epithelial cells. Invest Ophthalmol Vis Sci 1998;39(5):820-827.
    59 Yoo JS, Sakamoto T, Spee C, Kimura H, Harris MS, Hinton DR, Kay EP, Ryan SJ. Cis-Hydroxyproline inhibits proliferation, collagen synthesis, attachment, and migration of cultured bovine retinal pigment epithelial cells. Invest Ophthalmol Vis Sci 1997;38(2):520-528.
    60 Vangipurapu J, Fernandes Silva L, Kuulasmaa T, Smith U, Laakso M. Microbiota-related metabolites and the risk of type 2 diabetes. Diabetes Care 2020;43(6):1319-1325.
    61 Guasch-Ferré M, Hruby A, Toledo E, et al. Metabolomics in prediabetes and diabetes: a systematic review and meta-analysis. Diabetes Care 2016;39(5):833-846.
    62 Kim EK, Lee KA, Hyeon DY, Kyung M, Jun KY, Seo SH, Hwang D, Kwon Y, Lee WJ. Bacterial nucleoside catabolism controls quorum sensing and commensal-to-pathogen transition in the drosophila gut. Cell Host Microbe 2020;27(3):345-357.e6.
    63 Chen TL, Ni Y, Ma XJ, et al. Branched-chain and aromatic amino acid profiles and diabetes risk in Chinese populations. Sci Rep 2016;6:20594.
    64 Chai JC, Chen GC, Yu B, et al. Serum metabolomics of incident diabetes and glycemic changes in a population with high diabetes burden: the hispanic community health study/study of latinos. Diabetes 2022;71(6):1338-1349.
    65 Wang TJ, Larson MG, Vasan RS, et al. Metabolite profiles and the risk of developing diabetes. Nat Med 2011;17(4):448-453.
    66 Paris LP, Johnson CH, Aguilar E, et al. Global metabolomics reveals metabolic dysregulation in ischemic retinopathy. Metabolomics 2016;12:15.
    67 Abhary S, Kasmeridis N, Burdon KP, Kuot A, Whiting MJ, Yew WP, Petrovsky N, Craig JE. Diabetic retinopathy is associated with elevated serum asymmetric and symmetric dimethylarginines. Diabetes Care 2009;32(11):2084-2086.
    68 Sumarriva K, Uppal K, Ma CY, et al. Arginine and carnitine metabolites are altered in diabetic retinopathy. Invest Ophthalmol Vis Sci 2019;60(8):3119-3126.
    69 Cao YF, Li J, Zhang ZP, et al. Plasma levels of amino acids related to urea cycle and risk of type 2 diabetes mellitus in Chinese adults. Front Endocrinol 2019;10:50.
    70 Caldwell RW, Rodriguez PC, Toque HA, Narayanan SP, Caldwell RB. Arginase: a multifaceted enzyme important in health and disease. Physiol Rev 2018;98(2):641-665.
    71 Atawia RT, Bunch KL, Fouda AY, et al. Role of arginase 2 in murine retinopathy associated with western diet-induced obesity. J Clin Med 2020;9(2):317.
    72 Peters KS, Rivera E, Warden C, et al. Plasma arginine and citrulline are elevated in diabetic retinopathy. Am J Ophthalmol 2022;235:154-162.
    73 Ley SH, Hamdy O, Mohan V, Hu FB. Prevention and management of type 2 diabetes: dietary components and nutritional strategies. Lancet 2014;383(9933):1999-2007.
    74 Wu JHY, Marklund M, Imamura F, et al, Cohorts for Heart and Aging Research in Genomic Epidemiology Fatty Acids and Outcomes Research Consortium. Omega-6 fatty acid biomarkers and incident type 2 diabetes: pooled analysis of individual-level data for 39 740 adults from 20 prospective cohort studies. L
    Related
    Cited by
Get Citation

Sheng-Qun Jiang, Su-Na Ye, Yin-Hua Huang,/et al.Gut microbiota induced abnormal amino acids and their correlation with diabetic retinopathy. Int J Ophthalmol, 2024,17(5):883-895

Copy
Share
Article Metrics
  • Abstract:103
  • PDF: 877
  • HTML: 0
  • Cited by: 0
Publication History
  • Received:June 05,2023
  • Revised:February 20,2024
  • Online: April 24,2024
You are the  Visitors
Governing Body：Department of Health, Provincial Government of Shaanxi, China
Organizer：Xi'an Medical Association of China
Address：Room 11707-08, Building 2, Unit 1, Wanda Plaza, No.8 Yanta North Road, Xi'an 710054, Shaanxi Province, China
Fax：(8629)82245172 Phone：(+8629)82245172/82210956
Email：ijopress@163.com
International Journal of Ophthalmology ® 2025 All Rights Reserved   The terms of CC BY-NC-ND 4.0 are applicable to all open access content.