Metagenomic Sequencing Analysis Identifies Cross-Cohort Gut Microbial Signatures Associated With Age-Related Macular Degeneration

Abstract

Purpose Alterations in the gut microbiota have been associated with age-related macular degeneration (AMD). However, the dysbiosis shared by different ethnicity and geographic groups, which may associate with the disease pathogenesis, remain underexplored. Here, we characterized dysbiosis of the gut microbiota in patients with AMD from Chinese and Swiss cohorts and identified cross-cohort signatures associated with AMD. Methods Shotgun metagenomic sequencing was performed on fecal samples from 30 patients with AMD and 30 healthy subjects. Published datasets with 138 samples from Swiss patients with AMD and healthy subjects were re-analyzed. Comprehensive taxonomic profiling was conducted by matching to the RefSeq genome database, metagenome-assembled genome (MAG) database, and Gut Virome Database (GVD). Functional profiling was performed by reconstruction of the MetaCyc pathways. Results The α-diversity of the gut microbiota was decreased in patients with AMD according to taxonomic profiles generated using MAG but not RefSeq database as reference. The Firmicutes/Bacteroidetes ratio was also decreased in patients with AMD. Among AMD-associated bacteria shared between Chinese and Swiss cohorts, Ruminococcus callidus , Lactobacillus gasseri , and Prevotellaceae (f) uSGB 2135 were enriched in patients with AMD, whereas Bacteroidaceae (f) uSGB 1825 was depleted in patients with AMD and was negatively associated with hemorrhage size. Bacteroidaceae was one of the major hosts of phages associated with AMD. Three degradation pathways were reduced in AMD. Conclusions These results demonstrated that dysbiosis of the gut microbiota was associated with AMD. We identified cross-cohort gut microbial signatures involving bacteria, viruses, and metabolic pathways, which potentially serve as promising targets for the prevention or treatment of AMD.

Targeting the Gut–Eye Axis: An Emerging Strategy to Face Ocular Diseases

“…For example, while Burri et al reported an increase in Negativicutes and a decrease in Oscillibacter in 57 AMD patients as compared to 58 healthy controls, Zhang et al showed that AMD subjects are enriched in the pro-inflammatory Escherichia-Shigella and depleted in the SCFA-producing Blautia and Anaerostipes [63,64]. Moreover, Xue et al identified Ruminococcus callidus and Lactobacillus gasseri (both belonging to the Firmicutes phylum) as the most significantly associated with AMD after combining data from two population cohorts (Chinese and Swiss) [65], while Zinkernagel et al showed an increase in Oscillibacter, Anaerotruncus, Eubacterium ventriosum, and Ruminococcus torques in AMD patients versus control subjects that, instead, presented a higher content of Bacteroides eggerthii [49]. Still, a reduced Firmicutes/Bacteroides ratio seems to characterize AMD across the different studies [63,65].…”

“…Moreover, Xue et al identified Ruminococcus callidus and Lactobacillus gasseri (both belonging to the Firmicutes phylum) as the most significantly associated with AMD after combining data from two population cohorts (Chinese and Swiss) [65], while Zinkernagel et al showed an increase in Oscillibacter, Anaerotruncus, Eubacterium ventriosum, and Ruminococcus torques in AMD patients versus control subjects that, instead, presented a higher content of Bacteroides eggerthii [49]. Still, a reduced Firmicutes/Bacteroides ratio seems to characterize AMD across the different studies [63,65]. Metabolically, glutamate degradation, arginine synthesis, and L-alanine fermentation are upregulated in the intestinal microbes from AMD patients [49].…”

Comprehensive analysis of the oral microbiota and metabolome change in patients of burning mouth syndrome with psychiatric symptoms

“…Given these constraints, we recommend that future research incorporate more comprehensive approaches alongside the 16S V3-V4 sequencing, such as shotgun metagenomic sequencing. Using a more expansive method will allow for a deeper exploration of the microbiome at the species level and enhance understanding of microbial functionalities [ 49 ]. In addition the administration of antibiotics exerts a significant and lasting impact on the microbiome, with notable alterations in its composition and potentially its operations.…”

Role of traditional Chinese medicine in age-related macular degeneration: exploring the gut microbiota’s influence

“…A positive correlation was observed between the relative abundance of Clostridials and Firmicutes unknown species-level genome bins and lesion size, central pit thickness, hemorrhage size, and angiographic leakage. In contrast, a negative correlation was observed between lesion and hemorrhage size and the relative abundance of Bacteroidales ( Xue et al, 2023 ).…”

“…The occurrence and progression of AMD are linked to abnormal alterations in the GM composition. Although the relationship is unclear, GM dysregulation may play a role in AMD progression by enhancing the signaling pathway to activate the complement system abnormally ( Xue et al, 2023 ). When the complement system is over-activated or dysregulated, the out-of-control complement system becomes a key link in triggering infection and inflammation.…”