Gut Microbiota Composition and Fecal Metabolic Profiling in Patients With Diabetic Retinopathy.

Zixi Zhou,Jiaxin Pu,Hao Yao,Jingying Peng,Zheng Zheng,Xu Chen,Qingwei Chen,Xiaojing Xiong

doi:10.3389/fcell.2021.732204

Abstract

Recent evidence suggests there is a link between metabolic diseases and gut microbiota. To investigate the gut microbiota composition and fecal metabolic phenotype in diabetic retinopathy (DR) patients. DNA was extracted from 50 fecal samples (21 individuals with type 2 diabetes mellitus-associated retinopathy (DR), 14 with type 2 diabetes mellitus but without retinopathy (DM) and 15 sex- and age-matched healthy controls) and then sequenced by high-throughput 16S rDNA analysis. Liquid chromatography mass spectrometry (LC-MS)-based metabolomics was simultaneously performed on the samples. A significant difference in the gut microbiota composition was observed between the DR and healthy groups and between the DR and DM groups. At the genus level, Faecalibacterium, Roseburia, Lachnospira and Romboutsia were enriched in DR patients compared to healthy individuals, while Akkermansia was depleted. Compared to those in the DM patient group, five genera, including Prevotella, were enriched, and Bacillus, Veillonella, and Pantoea were depleted in DR patients. Fecal metabolites in DR patients significantly differed from those in the healthy population and DM patients. The levels of carnosine, succinate, nicotinic acid and niacinamide were significantly lower in DR patients than in healthy controls. Compared to those in DM patients, nine metabolites were enriched, and six were depleted in DR patients. KEGG annotation revealed 17 pathways with differentially abundant metabolites between DR patients and healthy controls, and only two pathways with differentially abundant metabolites were identified between DR and DM patients, namely, the arginine-proline and α-linolenic acid metabolic pathways. In a correlation analysis, armillaramide was found to be negatively associated with Prevotella and Subdoligranulum and positively associated with Bacillus. Traumatic acid was negatively correlated with Bacillus. Our study identified differential gut microbiota compositions and characteristic fecal metabolic phenotypes in DR patients compared with those in the healthy population and DM patients. Additionally, the gut microbiota composition and fecal metabolic phenotype were relevant. We speculated that the gut microbiota in DR patients may cause alterations in fecal metabolites, which may contribute to disease progression, providing a new direction for understanding DR.

Highlights

Diabetic retinopathy (DR) is one of the most common complications of diabetes mellitus and leads to vision-threatening damage to the retina, eventually leading to blindness
A total of 2,638,100 effective tags were obtained from the fecal samples of 21 patients with diabetic retinopathy (DR), patients with DM and healthy controls, with a mean of 52,762 per sample
The sequences were clustered into operational taxonomic units (OTUs) with 97% identity, yielding a total of 2,226 OTUs, and the OTU sequences were annotated with the Silva 132 database for species annotation

Summary

Introduction

Diabetic retinopathy (DR) is one of the most common complications of diabetes mellitus and leads to vision-threatening damage to the retina, eventually leading to blindness. If urgent action was not taken, the number with vision-threatening diabetic retinopathy (VTDR) would increase from 37.3 to 56.3 million (Zheng et al, 2012). NLR family pyrin domain containing 3 (NLRP3) inflammasome disorder might cause diabetic retinal damage and destruction via the proinflammatory cytokines IL-1β and IL-18 (Raman and Matsubara, 2020). P2 × 7R, a member of the P2XR family of ATP-gated plasma membrane receptors, has been verified to regulate inflammatory and immune responses. The above mentioned studies suggested that an abnormal immune response and the release of inflammatory factors may play an important role in DR progression. The human gut microbiota and its effects on the metabolic phenotypes have been shown to play a critical role in the maintenance of immune homeostasis (Scher et al, 2015) and anti-inflammation (Al Bander et al, 2020)

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