Abstract

The pathogenesis of type 2 diabetes mellitus (T2DM) is commonly associated with altered gut bacteria. However, whether the microbial dysbiosis that exists in human diabetic patients with or without retinopathy is different remains largely unknown. Here, we collected clinical information and fecal samples from 75 participants, including 25 diabetic patients without retinopathy (DM), 25 diabetic patients with retinopathy (DR), and 25 healthy controls (HC). The gut microbial composition in the three groups was analyzed using 16S ribosomal RNA (rRNA) gene sequencing. Microbial structure and composition differed in the three groups. The α and β diversities in both the DM and DR groups were reduced compared with those in the HC group. Blautia was the most abundant genus, especially in the DM group. In addition, increased levels of Bifidobacterium and Lactobacillus and decreased levels of Escherichia-Shigella, Faecalibacterium, Eubacterium_hallii_group and Clostridium genera were observed in the DM and DR groups compared with the HC group. Furthermore, a biomarker set of 25 bacterial families, which could distinguish patients in the DR group from those in the DM and HC groups was identified, with the area under the curve values ranging from 0.69 to 0.85. Of note, Pasteurellaceae, which was increased in DM and decreased in DR compared with HC, generated a high AUC (0.74) as an individual predictive biomarker. Moreover, 14 family biomarkers were associated with fasting blood glucose levels or diabetes, with most of them being negatively correlated. In summary, our study establishes compositional alterations of gut microbiota in DM and DR, suggesting the potential use of gut microbiota as a non-invasive biomarker for clinical and differential diagnosis, as well as identifying potential therapeutic targets of diabetic retinopathy.

Highlights

  • Countless gut microbiota colonizes the human intestine

  • Depending on the absence or presence of diabetic retinopathy, diabetic patients were divided into the diabetes mellitus without retinopathy group (DM, n = 25) or the diabetes mellitus with retinopathy group (DR, n = 25)

  • Comparisons of age and body mass index (BMI) in the three groups did not show statistically significant differences (p > 0.05), while fasting blood glucose (FBG) and duration showed significant differences (p < 0.001); additional detailed characteristics of the study subjects are included in the Supporting Information (Supplementary Table S1)

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Summary

Introduction

The number of bacteria in the adult gut increases to 1014, weighing approximately 1.13 kg, which is 10 times more than the total number of human cells (1013) (Shivaji, 2017). These microorganisms constitute a complex symbiotic ecosystem and are believed to interact with the host environment, influencing important physiological. Disorder in gut bacterial composition and function has been associated with many human systemic diseases, including diabetes mellitus (Qin et al, 2012), obesity (Haro et al, 2016), depression (Zheng et al, 2020), Alzheimer’s disease (Wang et al, 2019), and cardiovascular disease (Battson et al, 2018). Several underlying mechanisms have been demonstrated in mouse studies, including host signaling through lipopolysaccharides (LPS) derived from cell walls of gram-negative bacteria, short-chain fatty acids (SCFAs) produced by bacterial fermentation of dietary fiber, and bacterial regulation of bile acids (Allin et al, 2015)

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