Beneficial Effects of Micronutrient Supplementation in Restoring the Altered Microbiota and Gut-Retina Axis in Patients with Neovascular Age-Related Macular Degeneration-A Randomized Clinical Trial

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Reviewed Marked as Reviewed by KateRasheed on 2025-6-16
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Baldi S, Pagliai G, Di Gloria L, Pallecchi M, Barca F, Pieri B, Bartolucci G, Ramazzotti M, Amedei A, Palendri G, Sofi F
Journal
Nutrients
Year
2024
Keywords:
gut microbiota, gut–retina axis, lutein, nAMD, saffron, short-chain fatty acids, zeaxanthin
Background/Objectives: Age-related macular degeneration (AMD) is a leading cause of visual impairment in the elderly and is characterized by a multifactorial etiology. Emerging evidence points to the potential involvement of the gut-retina axis in AMD pathogenesis, prompting exploration into novel therapeutic strategies. This study aims to investigate the effects of some micronutrients (such as lutein and zeaxanthin) and saffron (as a supplement)-known for their anti-inflammatory properties-on ophthalmological and microbial parameters in neovascular AMD (nAMD) patients. Methods: Thirty naive nAMD patients were randomized to receive daily micronutrient supplementation alongside anti-VEGF (vascular endothelial growth factor) therapy, or anti-VEGF treatment alone, over a 6-month period, with comparisons made to a healthy control (HC) group (N = 15). Ophthalmological assessments, biochemical measurements, and stool samples were obtained before and after treatment. Gut microbiota (GM) characterization was performed using 16S rRNA sequencing, while short-chain fatty acids (SCFAs), medium-chain fatty acids (MCFAs), and long-chain fatty acids (LCFAs) were analyzed with a gas chromatography-mass spectrometry protocol. Results: Compared to HC, nAMD patients exhibited reduced GM alpha diversity, altered taxonomic composition, and decreased total SCFA levels, in addition to elevated levels of proinflammatory octanoic and nonanoic acids. Micronutrient supplementation was associated with improved visual acuity relative to the group treated with anti-VEGF alone, along with a decrease in the total amount of MCFAs, which are metabolites known to have adverse ocular effects. Conclusions: In conclusion, despite certain limitations-such as the limited sample size and the low taxonomic resolution of 16S rRNA sequencing-this study highlights compositional and functional imbalances in the GM of nAMD patients and demonstrates that micronutrient supplementation may help restore the gut-retina axis. These findings suggest the therapeutic potential of micronutrients in enhancing ocular outcomes for nAMD patients, underscoring the complex interaction between GM and ocular health.

Experiment 1


Reviewed Marked as Reviewed by KateRasheed on 2025-6-16

Curated date: 2025/06/11

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Subjects

Location of subjects
Italy
Host species Species from which microbiome was sampled. Contact us to have more species added.
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Age-related macular degeneration AAMD - Age related macular degeneration,AGE RELAT MACULOPATHIES,AGE RELAT MACULOPATHY,Age Related Macular Degeneration,age related macular degeneration,Age related macular degeneration (disorder) [Ambiguous],Age Related Maculopathies,age related Maculopathies,Age related maculopathy,age related maculopathy,age-related macular degeneration,Age-related macular degeneration (disorder),Age-Related Macular Degenerations,Age-Related Maculopathies,Age-Related Maculopathy,AMD,AMD - Age-related macular degeneration,Amended,ARMD,ARMD - Age-related macular degeneration,Degeneration, Age-Related Macular,Degeneration, Macular,Degenerations, Age-Related Macular,Degenerations, Macular,Dystrophies, Macular,Dystrophy, Macular,Macular Degeneration,Macular degeneration (disorder),Macular degeneration (senile) of retina, unspecified,MACULAR DEGENERATION NOS,Macular Degeneration, Age-Related,macular degeneration, age-related,Macular Degenerations,Macular Degenerations, Age-Related,Macular Dystrophies,Macular Dystrophy,MACULOPATHIES AGE RELAT,Maculopathies, Age Related,Maculopathies, Age-Related,MACULOPATHY AGE RELAT,Maculopathy, Age Related,Maculopathy, Age-Related,Senile macular degeneration,Senile macular degeneration of retina,Senile macular retinal degeneration,SMD - Senile macular degeneration,Unspecified senile macular degeneration,Age-related macular degeneration
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
nAMD (neovascular Age-related macular degeneration) patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Elderly patients with nAMD (neovascular Age-related macular degeneration)
Group 0 sample size Number of subjects in the control (unexposed) group
15
Group 1 sample size Number of subjects in the case (exposed) group
30
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
2 months

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V3-V4
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
raw counts
Statistical test
DESeq2
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes

Alpha Diversity

Pielou Quantifies how equal the community is numerically
decreased
Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Richness Number of species
decreased

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-6-16

Curated date: 2025/06/11

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Figure 3 and Table S2

Description: Significant differentially abundant taxa in stool samples of nAMD patients compared to HC

Abundance in Group 1: increased abundance in nAMD (neovascular Age-related macular degeneration) patients

NCBI Quality ControlLinks
Anaerobutyricum hallii
Escherichia/Shigella sp.
Lactobacillales
Streptococcaceae
Streptococcus
Turicibacter
Peptostreptococcales-TissierellalesPeptostreptococcales-Tissierellales

Revision editor(s): Anne-mariesharp

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-6-16

Curated date: 2025/06/11

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Figure 3 and Table S2

Description: Significant differentially abundant taxa in stool samples of nAMD patients compared to HC

Abundance in Group 1: decreased abundance in nAMD (neovascular Age-related macular degeneration) patients

NCBI Quality ControlLinks
Bacteroidales
Bacteroides
Bacteroidota
Burkholderiales
Eubacterium coprostanoligenes
Faecalibacterium
Lachnospira
Lachnospira eligens
Lachnospiraceae
Lachnospiraceae bacterium NK4A136
Methanobrevibacter
Parabacteroides
Phascolarctobacterium
Prevotellaceae
Sutterella
Sutterellaceae
[Eubacterium] siraeum
Rikenellaceae_RC9_gut_groupRikenellaceae_RC9_gut_group
UCG-002UCG-002

Revision editor(s): Anne-mariesharp