Alterations of the intestinal microbiota in age-related macular degeneration

Purpose Age-related macular degeneration (AMD) is the leading cause of vision loss in those over the age of 50. Recently, intestinal microbiota has been reported to be involved in the pathogenesis of ocular diseases. The purpose of this study was to discover more about the involvement of the intestinal microbiota in AMD patients. Methods Fecal samples from 30 patients with AMD (AMD group) and 17 age- and sex-matched healthy controls (control group) without any fundus disease were collected. DNA extraction, PCR amplification, and 16S rRNA gene sequencing of the samples were performed to identify intestinal microbial alterations. Further, we used BugBase for phenotypic prediction and PICRUSt2 for KEGG Orthology (KO) as well as metabolic feature prediction. Results The intestinal microbiota was found to be significantly altered in the AMD group. The AMD group had a significantly lower level of Firmicutes and relatively higher levels of Proteobacteria and Bacteroidota compared to those in the control group. At the genus level, the AMD patient group showed a considerably higher proportion of Escherichia-Shigella and lower proportions of Blautia and Anaerostipes compared with those in the control group. Phenotypic prediction revealed obvious differences in the four phenotypes between the two groups. PICRUSt2 analysis revealed KOs and pathways associated with altered intestinal microbiota. The abundance of the top eight KOs in the AMD group was higher than that in the control group. These KOs were mainly involved in lipopolysaccharide biosynthesis. Conclusion The findings of this study indicated that AMD patients had different gut microbiota compared with healthy controls, and that AMD pathophysiology might be linked to changes in gut-related metabolic pathways. Therefore, intestinal microbiota might serve as non-invasive indicators for AMD clinical diagnosis and possibly also as AMD treatment targets.

[1]  Dongya Zhang,et al.  Microbiota in health and diseases , 2022, Signal Transduction and Targeted Therapy.

[2]  R. Nouchi,et al.  Gut microbiota in patients with Alzheimer’s disease spectrum: a systematic review and meta-analysis , 2022, Aging.

[3]  A. Minnella,et al.  Gut Microbiome in Retina Health: The Crucial Role of the Gut-Retina Axis , 2022, Frontiers in Microbiology.

[4]  Y. Ran,et al.  Multiomics Study Reveals Enterococcus and Subdoligranulum Are Beneficial to Necrotizing Enterocolitis , 2021, Frontiers in Microbiology.

[5]  Wei Chen,et al.  Lactobacillus plantarum CCFM1143 Alleviates Chronic Diarrhea via Inflammation Regulation and Gut Microbiota Modulation: A Double-Blind, Randomized, Placebo-Controlled Study , 2021, Frontiers in Immunology.

[6]  Wei Chen,et al.  Blautia—a new functional genus with potential probiotic properties? , 2021, Gut microbes.

[7]  H. Völzke,et al.  Long-term instability of the intestinal microbiome is associated with metabolic liver disease, low microbiota diversity, diabetes mellitus and impaired exocrine pancreatic function , 2020, Gut.

[8]  E. Prifti,et al.  From correlation to causality: the case of Subdoligranulum , 2020, Gut microbes.

[9]  S. Wolf,et al.  Associations of the intestinal microbiome with the complement system in neovascular age-related macular degeneration , 2020, npj Genomic Medicine.

[10]  K. Verbeke,et al.  Short chain fatty acids in human gut and metabolic health. , 2020, Beneficial microbes.

[11]  J. Gilbert,et al.  The early gut microbiome could protect against severe retinopathy of prematurity. , 2020, Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus.

[12]  M. Grant,et al.  The Gut–Eye Axis: Lessons Learned from Murine Models , 2020, Ophthalmology and Therapy.

[13]  C. Zuo,et al.  Gut microbiota compositional profile and serum metabolic phenotype in patients with primary open-angle glaucoma. , 2020, Experimental eye research.

[14]  S. Imoto,et al.  Blautia genus associated with visceral fat accumulation in adults 20–76 years of age , 2019, npj Biofilms and Microbiomes.

[15]  F. Reis,et al.  Diabetic gut microbiota dysbiosis as an inflammaging and immunosenescence condition that fosters progression of retinopathy and nephropathy. , 2019, Biochimica et biophysica acta. Molecular basis of disease.

[16]  M. Surette,et al.  Gut Microbiota in Patients With Irritable Bowel Syndrome-A Systematic Review. , 2019, Gastroenterology.

[17]  Jaehyeon Lee,et al.  Kluyvera ascorbata as a Pathogen in Adults and Children: Clinical Features and Antibiotic Susceptibilities in a Single Center Study. , 2019, Japanese journal of infectious diseases.

[18]  Ronald N. Jones,et al.  The Microbiology of Bloodstream Infection: 20-Year Trends from the SENTRY Antimicrobial Surveillance Program , 2019, Antimicrobial Agents and Chemotherapy.

[19]  Phoebe Lin.  Importance of the intestinal microbiota in ocular inflammatory diseases: A review , 2019, Clinical & experimental ophthalmology.

[20]  K. Liedl,et al.  Toward novel inhibitors against KdsB: a highly specific and selective broad-spectrum bacterial enzyme , 2019, Journal of biomolecular structure & dynamics.

[21]  P. Mitchell,et al.  Age-related macular degeneration , 2018, The Lancet.

[22]  U. Schmidt-Erfurth,et al.  Comparison of SD-Optical Coherence Tomography Angiography and Indocyanine Green Angiography in Type 1 and 2 Neovascular Age-related Macular Degeneration. , 2018, Investigative ophthalmology & visual science.

[23]  U. Ijaz,et al.  Fecal Enterobacteriales enrichment is associated with increased in vivo intestinal permeability in humans , 2018, Physiological reports.

[24]  P. Bork,et al.  Nutritional preferences of human gut bacteria reveal their metabolic idiosyncrasies , 2018, Nature Microbiology.

[25]  I. Kimura,et al.  Gut Microbiota Dysbiosis Drives and Implies Novel Therapeutic Strategies for Diabetes Mellitus and Related Metabolic Diseases , 2017, Front. Immunol..

[26]  Daniel J. Burnside,et al.  Global landscape of cell envelope protein complexes in Escherichia coli , 2017, Nature Biotechnology.

[27]  M. Yassour,et al.  A novel Ruminococcus gnavus clade enriched in inflammatory bowel disease patients , 2017, Genome Medicine.

[28]  Mei Chen,et al.  Diabetic retinopathy and dysregulated innate immunity , 2017, Vision Research.

[29]  F. Marotta,et al.  Gut microbiota: A player in aging and a target for anti-aging intervention , 2017, Ageing Research Reviews.

[30]  A. Leichtle,et al.  Association of the Intestinal Microbiome with the Development of Neovascular Age-Related Macular Degeneration , 2017, Scientific Reports.

[31]  N. Ajami,et al.  Gut microbiota as a source of a surrogate antigen that triggers autoimmunity in an immune privileged site , 2017, Gut microbes.

[32]  S. Lynch,et al.  The Human Intestinal Microbiome in Health and Disease. , 2016, The New England journal of medicine.

[33]  F. Sennlaub,et al.  Gut microbiota influences pathological angiogenesis in obesity‐driven choroidal neovascularization , 2016, EMBO molecular medicine.

[34]  G. Blandino,et al.  Impact of gut microbiota on diabetes mellitus. , 2016, Diabetes & metabolism.

[35]  F. Bäckhed,et al.  The gut microbiota and metabolic disease: current understanding and future perspectives , 2016, Journal of internal medicine.

[36]  Colin J. Brislawn,et al.  Gut Microbial Alterations Associated With Protection From Autoimmune Uveitis , 2016, Investigative ophthalmology & visual science.

[37]  R. Burcelin.  Gut microbiota and immune crosstalk in metabolic disease , 2016, Molecular metabolism.

[38]  Lawrence A. David,et al.  The severity of nonalcoholic fatty liver disease is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota , 2016, Hepatology.

[39]  I. Martínez,et al.  Disparate Metabolic Responses in Mice Fed a High-Fat Diet Supplemented with Maize-Derived Non-Digestible Feruloylated Oligo- and Polysaccharides Are Linked to Changes in the Gut Microbiota , 2016, PloS one.

[40]  K. Honda,et al.  Microbiota-Dependent Activation of an Autoreactive T Cell Receptor Provokes Autoimmunity in an Immunologically Privileged Site. , 2015, Immunity.

[41]  R. Talukdar,et al.  Role of the normal gut microbiota. , 2015, World journal of gastroenterology.

[42]  G. Rogler,et al.  Extraintestinal Manifestations of Inflammatory Bowel Disease , 2015, Inflammatory bowel diseases.

[43]  S. Andrews,et al.  A Complete Pathway Model for Lipid A Biosynthesis in Escherichia coli , 2015, PloS one.

[44]  T. Nielsen,et al.  Mechanisms in endocrinology: Gut microbiota in patients with type 2 diabetes mellitus. , 2015, European journal of endocrinology.

[45]  S. Dowd,et al.  Modulation of the faecal microbiome of healthy adult dogs by inclusion of potato fibre in the diet. , 2015, The British journal of nutrition.

[46]  Robert G. Beiko,et al.  STAMP: statistical analysis of taxonomic and functional profiles , 2014, Bioinform..

[47]  L. Hyman,et al.  Oral Microbiome Link to Neurodegeneration in Glaucoma , 2014, PloS one.

[48]  C. Dozois,et al.  Iron, copper, zinc, and manganese transport and regulation in pathogenic Enterobacteria: correlations between strains, site of infection and the relative importance of the different metal transport systems for virulence , 2013, Front. Cell. Infect. Microbiol..

[49]  Trevor Lithgow,et al.  Structural insight into the biogenesis of β-barrel membrane proteins , 2013, Nature.

[50]  Fredrik H. Karlsson,et al.  Gut metagenome in European women with normal, impaired and diabetic glucose control , 2013, Nature.

[51]  Qiang Feng,et al.  A metagenome-wide association study of gut microbiota in type 2 diabetes , 2012, Nature.

[52]  Sanjoy Ghosh,et al.  Colonic microbiota alters host susceptibility to infectious colitis by modulating inflammation, redox status, and ion transporter gene expression. , 2011, American journal of physiology. Gastrointestinal and liver physiology.

[53]  J. Baardsnes,et al.  Characterization of interactions between LPS transport proteins of the Lpt system. , 2011, Biochemical and biophysical research communications.

[54]  R. Casson,et al.  Microglial activation in the visual pathway in experimental glaucoma: spatiotemporal characterization and correlation with axonal injury. , 2010, Investigative ophthalmology & visual science.

[55]  D. Baker,et al.  Inflammation in neurodegenerative diseases , 2010, Immunology.

[56]  Harry J Flint,et al.  The role of pH in determining the species composition of the human colonic microbiota. , 2009, Environmental microbiology.

[57]  H. Inoko,et al.  Association of Toll-like receptor 4 gene polymorphisms with normal tension glaucoma. , 2008, Investigative ophthalmology & visual science.

[58]  S. Rowan,et al.  The Role of Microbiota in Retinal Disease. , 2018, Advances in experimental medicine and biology.

[59]  M. Kawahara,et al.  Analysis of endoscopic brush samples identified mucosa-associated dysbiosis in inflammatory bowel disease , 2017, Journal of Gastroenterology.

[60]  K. Zimmermann,et al.  A vegan or vegetarian diet substantially alters the human colonic faecal microbiota , 2012, European Journal of Clinical Nutrition.

[61]  N. Seeram,et al.  Of the major phenolic acids formed during human microbial fermentation of tea, citrus, and soy flavonoid supplements, only 3,4-dihydroxyphenylacetic acid has antiproliferative activity. , 2006, The Journal of nutrition.