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. 2020 Dec 1;15(12):e0243077.
doi: 10.1371/journal.pone.0243077. eCollection 2020.

Gut mycobiomes are altered in people with type 2 Diabetes Mellitus and Diabetic Retinopathy

Rajagopalaboopathi Jayasudha  1 , Taraprasad Das  2 , Sama Kalyana Chakravarthy  1 , Gumpili Sai Prashanthi  1 , Archana Bhargava  3 , Mudit Tyagi  2 , Padmaja Kumari Rani  2 , Rajeev Reddy Pappuru  2 , Sisinthy Shivaji  1
Affiliations

Gut mycobiomes are altered in people with type 2 Diabetes Mellitus and Diabetic Retinopathy

Rajagopalaboopathi Jayasudha et al. PLoS One. .

Abstract

Studies have documented dysbiosis in the gut mycobiome in people with Type 2 diabetes mellitus (T2DM). However, it is not known whether dysbiosis in the gut mycobiome of T2DM patients would be reflected in people with diabetic retinopathy (DR) and if so, is the observed mycobiome dysbiosis similar in people with T2DM and DR. Gut mycobiomes were generated from healthy controls (HC), people with T2DM and people with DR through Illumina sequencing of ITS2 region. Data were analysed using QIIME and R software. Dysbiotic changes were observed in people with T2DM and DR compared to HC at the phyla and genera level. Mycobiomes of HC, T2DM and DR could be discriminated by heat map analysis, Beta diversity analysis and LEfSE analysis. Spearman correlation of fungal genera indicated more negative correlation in HC compared to T2DM and DR mycobiomes. This study demonstrates dysbiosis in the gut mycobiomes in people with T2DM and DR compared to HC. These differences were significant both at the phyla and genera level between people with T2DM and DR as well. Such studies on mycobiomes may provide new insights and directions to identification of specific fungi associated with T2DM and DR and help developing novel therapies for Diabetes Mellitus and DR.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Fungal diversity in the gut mycobiomes of healthy controls (HC, n = 30), Type 2 Diabetes Mellitus (T2DM, n = 21) and Diabetic Retinopathy (DR, n = 24) individuals.
(A) Of the four Alpha diversity indices, Shannon and Simpson indices were statistically significant between HC and T2DM (indicated by ★) and the observed number of OTUs and Chao1 index were statistically significant between HC and DR (indicated by ★★) and T2DM and DR (indicated by #) (P = < 0.05). (B) Abundance and (C) mean abundance (%) of different fungal phyla.
Fig 2
Fig 2. Diversity of different fungal genera in the gut mycobiomes of healthy controls (HC, n = 30), Type 2 Diabetes Mellitus (T2DM, n = 21) and Diabetic Retinopathy (DR, n = 24) patients.
(A) Abundance and (B) mean abundance (%) of different fungal genera. Genera with < 1% mean abundance were categorized as ‘‘less abundant genera”. (C) Fungal genera exhibiting significant (Wilcoxon test, BH corrected p < 0.05) differential abundance in the gut mycobiomes HC, T2DM and DR patients. Median abundances (horizontal line) and inter-quartile ranges are indicated in the plots. Statistically significantly abundant genera between HC and T2DM are indicated by ★, between HC and DR are indicated by ★★ and between T2DM and DR are indicated by #.
Fig 3
Fig 3. Gut fungal mycobiomes differ significantly across healthy controls (HC, n = 30), Type 2 Diabetes Mellitus (T2DM, n = 21) and Diabetic Retinopathy (DR, n = 24) patients.
(A) Two dimensional heat map showing rank normalized abundances (scaled between 0 and 1) of 29 differentially abundant fungal genera determined by Wilcoxon test. Discriminating genera have been arranged along the two dimensions (axes) based on hierarchical clustering. (B) Beta diversity analysis using NMDS plots based on Bray-Curtis dissimilarity of discriminating genera in the gut microbiomes of HC and T2DM, (C) HC and DR and (D) T2DM and DR. The fecal mycobiomes appeared to vary significantly (PERMANOVA, P = 0.001).
Fig 4
Fig 4. Spearman correlation.
Correlation analysis of fungal genera having a median abundance of > 0.5% in the gut mycobiomes of (A) healthy controls (HC, n = 30), (B) Type 2 Diabetes Mellitus (T2DM, n = 21) and (C) Diabetic Retinopathy (DR, n = 24) patients.
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