Gut microbiome changes in people with diabetic retinopathy in India. DRMS-India report # 1: operational protocol and trends from first 100 participants.

Abstract

Background: Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus (DM), and the leading cause of vision impairment and blindness. India is among the top three countries in DM prevalence, and both DM and DR are projected to rise sharply in the future. There is no accepted strategy for the prevention of DR other than DM control. Recent studies suggest that DM is associated with alterations in a core group of gut microbiota, and progression to DR may be influenced by changes within this core group, highlighting a potential link between DR and gut microbiome. We studied these changes in a protocol-driven large case-control study, the Diabetic Retinopathy Microbiome Study-India (DRMS-India: CTRI/2024/02/062511), analysed the results of the first 100 individuals, and evaluated variations in gut microbiome in DR.

Methods: The DRMS is designed to recruit 462 people aged ≥ 30 years into three cohorts: healthy controls (HCs), DM, and DR, at 17 independent sites in India. Shotgun metagenomic sequencing of first-pass morning fecal samples is performed at a centralized laboratory and correlated with disease status, lifestyle, dietary, and systemic factors.

Results: The first 100 participants included 26 HC, 33 DM, and 41 DR. The trends showed the DR group had 1, 6, and 10 unique core phyla, genera, and species, respectively. Alpha diversity was highest in the DR group; Beta diversity plots showed separate clusters of HCs and DR, with DM overlapping both. Firmicutes (highest in DR), Proteobacteria (highest in DM), Bacteroidetes, and Actinobacteria (highest in HC) were common phyla. Segatella was the most common genus, and Segatella copri was the most common species across all groups to date. Most microbial gene families were annotated to Molecular Functions (MF), and the pathways attributed to carbohydrate, amino acid, lipid, and nucleotide metabolism, indicating distinct functional adaptations in their gut microbiome.

Conclusion: Trends from the first 100 individuals indicate that the gut microbiome of Indians with DR exhibits discriminatory features in microbial diversity and abundance, as well as in gene families and pathways that impact host gut metabolism. Data trends from DRMS-India indicate a region-specific non-invasive biomarker that may guide preventive therapy for DR.