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 TrialOriginal paper
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease, four years before the first published case study.
Read MoreWhat was studied?
This randomized trial asked whether a micronutrient supplement could restore gut microbiota changes linked to neovascular age-related macular degeneration (nAMD) through a gut-retina axis. Researchers compared stool microbiota and fatty acids in nAMD patients versus healthy people. They then tested a daily supplement of lutein, zeaxanthin, vitamin C, vitamin E, zinc, and saffron added to standard anti-VEGF injections over six months. Gut microbiota was profiled by 16S rRNA sequencing. Short-, medium-, and long-chain fatty acids in stool were measured by gas chromatography-mass spectrometry.
Who was studied?
The study enrolled 30 treatment-naive nAMD patients (19 women, 11 men, mean age 77.8 years) and 15 healthy controls (mean age 75.2 years) in Florence, Italy. All nAMD patients received intravitreal anti-VEGF (aflibercept). Half of the patients (15) also took the daily micronutrient supplement, while 15 received anti-VEGF alone as the comparator group. Assessments and stool samples were collected at baseline and after six months for the supplemented group.
What were the most important findings?
Compared with healthy controls, nAMD patients had significantly lower gut microbial alpha diversity (Shannon p=0.001) and distinct composition (PERMANOVA p below 0.0001). They showed reduced Bacteroidota, Faecalibacterium, and other short-chain fatty acid producers. nAMD patients had lower total short-chain fatty acids (p=1x10 to the minus 5) but higher proinflammatory octanoic (p=0.034) and nonanoic (p=0.043) acids. The supplement improved best-corrected visual acuity (0.52 to 0.30 logMAR, p=0.012), with no change in controls. It also cut total medium-chain fatty acids (p=0.008).
What are the greatest implications of this study?
The findings support a gut-retina axis in nAMD, linking gut microbiota imbalance and altered fatty acids to retinal disease. A lutein, zeaxanthin, and saffron supplement may aid ocular outcomes alongside anti-VEGF therapy. The visual acuity gain and lower proinflammatory medium-chain fatty acids suggest a plausible microbiota-related mechanism. Because the sample was small and 16S sequencing has limited resolution, these associations need larger confirmatory trials before clinical use.