Significant Alterations in Intestinal Microbiota Observed in Patients with AMD

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Age-related macular degeneration (AMD) pathophysiology may be linked to changes in gut-related metabolic pathways, with new research suggesting patients with AMD have different gut microbiota compared with healthy controls.¹

Patients with AMD were found to have significantly lower proportions of Firmicutes and markedly increased proportions of Proteobacteria and Bacteroidota at the phylum level, while the genus level revealed a notably increased abundance of Escherichia-Shigella and decreased abundance of Blautia and Anaerostipes, compared with those in the control group.

“These findings clarify the mechanism underlying AMD from the perspective of intestinal microbial dysbiosis,” wrote the investigative team. “In addition, the findings provide a foundation prospect for improving the balance of the intestinal microenvironment to treat AMD."

The team, led by Yuanyuan Zhang, Department of Ophthalmology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, noted that the intestinal microbiota might be involved in the pathogenesis of ocular diseases and could provide new avenues for exploring the etiology and therapeutic modalities for AMD. Their current investigation aimed to elucidate the mechanisms underlying AMD pathogenesis by employing 16S rRNA gene sequencing to describe the intestinal microbiota of patients with AMD. Zhang’s team searched for potential microbial biomarkers for the development of AMD and innovative treatment methods for AMD.

The inclusion criteria for the study were defined as an age ≥50 years old, residence in Shanghai, and having advanced AMD clinical features after receiving an ophthalmic examination. The age and sex of the healthy controls were matched with the patients with AMD; no abnormality was found in the fundus. DNA extraction and PCR amplification of the samples were additionally performed to identify intestinal microbial alterations. The team used BugBase for phenotypic prediction and PICRUSt2 for KEGG Orthology (KO) as well as metabolic feature prediction.

A total of 30 patients with AMD and 17 healthy controls were recruited to participate in the study. Each group showed no significant differences in gender and age, and the clinical characteristics of body mass index (BMI), hypertension, hyperglycemia, drinking, and smoking history were also comparable. In order to investigate the gut microbiota signature, investigators assessed the relative abundance of bacteria at the phylum and genus levels.

Overall, a total of 16 phyla and 276 genera were identified, and 12 of the 16 phyla were shared between the AMD and healthy groups. Investigators noted Deinococcota and WPS-2 were unique to the AMD group, and Acidobacteriota and Planctomycetota were specific to the control group. They found a total of 196 genera in the two groups, but 65 genera were specific to the AMD group and 15 genera were only present in the control group.

At the phylum level, data showed Firmicutes, Actinobacteria, Proteobacteria, and Bacteroidota were the predominant phyla in both AMD and control groups. Both groups had Blautia in the highest proportion at the genus level, but the abundance was lower in the AMD group. Overall, the intestinal bacterial compositions in the AMD group were altered at different taxonomic levels when compared to those in the control group.

Zhang and colleagues indicated the intestinal bacterial compositions in the AMD group were altered at different taxonomic levels when compared to those in the control group. Phenotypic prediction revealed obvious differences in 4 phenotypes between the 2 groups, according to Zhang and colleagues.

The analysis found the relative abundance of microorganisms with Stress-Tolerant, Gram-Negative, and Potentially-Pathogenic phenotypes significantly higher in the AMD group, while the Gram-Positive phenotype had a lower abundance in the AMD group than in the control group. The PICRUSt2 analysis further revealed KOs and pathways associated with altered intestinal microbiota, showing the abundance of the top 8 KOs were higher in the AMD group than in the control group.

The investigative team noted the research limitations included its small sample size, requiring expanded, multicenter studies to expand the sample size. Additionally, since the research predicted metabolic functions of gut microbiota in patients AMD and healthy controls, there is a need for further analysis of bacterial metabolites to examine their potential underlying mechanisms.

“Whether to change the abundances of these bacteria in the guts of patients with AMD or to use the metabolites produced by these bacteria to treat AMD remains to be further explored,” investigators wrote.

References

1. Zhang Y, Wang T, Wan Z, et al. Alterations of the intestinal microbiota in age-related macular degeneration. Front Microbiol. 2023;14:1069325. Published 2023 Apr 5. doi:10.3389/fmicb.2023.1069325