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. 2017 Mar 22;12(3):e0174099.
doi: 10.1371/journal.pone.0174099. eCollection 2017.

Dysbiosis and compositional alterations with aging in the gut microbiota of patients with heart failure

Takehiro Kamo  1 , Hiroshi Akazawa  1 , Wataru Suda  2   3 , Akiko Saga-Kamo  1 , Yu Shimizu  1 , Hiroki Yagi  1 , Qing Liu  1 , Seitaro Nomura  1 , Atsuhiko T Naito  1 , Norifumi Takeda  1 , Mutsuo Harada  1 , Haruhiro Toko  1 , Hidetoshi Kumagai  1   4 , Yuichi Ikeda  1 , Eiki Takimoto  1 , Jun-Ichi Suzuki  4 , Kenya Honda  3   5 , Hidetoshi Morita  6 , Masahira Hattori  2   7 , Issei Komuro  1
Affiliations

Dysbiosis and compositional alterations with aging in the gut microbiota of patients with heart failure

Takehiro Kamo et al. PLoS One. .

Abstract

Emerging evidence has suggested a potential impact of gut microbiota on the pathophysiology of heart failure (HF). However, it is still unknown whether HF is associated with dysbiosis in gut microbiota. We investigated the composition of gut microbiota in patients with HF to elucidate whether gut microbial dysbiosis is associated with HF. We performed 16S ribosomal RNA gene sequencing of fecal samples obtained from 12 HF patients and 12 age-matched healthy control (HC) subjects, and analyzed the differences in gut microbiota. We further compared the composition of gut microbiota of 12 HF patients younger than 60 years of age with that of 10 HF patients 60 years of age or older. The composition of gut microbial communities of HF patients was distinct from that of HC subjects in both unweighted and weighted UniFrac analyses. Eubacterium rectale and Dorea longicatena were less abundant in the gut microbiota of HF patients than in that of HC subjects. Compared to younger HF patients, older HF patients had diminished proportions of Bacteroidetes and larger quantities of Proteobacteria. The genus Faecalibacterium was depleted, while Lactobacillus was enriched in the gut microbiota of older HF patients. These results suggest that patients with HF harbor significantly altered gut microbiota, which varies further according to age. New concept of heart-gut axis has a great potential for breakthroughs in the development of novel diagnostic and therapeutic approach for HF.

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Conflict of interest statement

Competing Interests: The study was supported in part by Takeda Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Shionogi & Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Bristol-Myers Squibb K.K., MSD K.K., Sanofi K.K., and Sumitomo Dainippon Pharma Co., Ltd. There are no patents, products in development, or marketed products to declare.

Figures

Fig 1
Fig 1. Richness, diversity, and UniFrac distances of gut microbiota in heart failure patients and healthy control subjects.
Chao1-estimated operational taxonomic unit (OTU) number (A) and Shannon index (B) of gut microbiota samples obtained from younger heart failure (HF-Y) patients and healthy control (HC) subjects. Unweighted UniFrac analysis (C, D) and weighted UniFrac analysis (E, F) of gut microbiota samples obtained from HF-Y patients and HC subjects. Principal Coordinate Analysis (PCoA) of UniFrac distances between gut microbial communities of the individuals (C, E), and UniFrac distances between gut microbial communities of the individuals within each group and between the two groups (D, F). Data are presented as mean ± SEM. NS, not significant. * p < 0.05, ** p < 0.00001.
Fig 2
Fig 2. Abundances of taxa in gut microbiota of heart failure patients and healthy control subjects.
Relative abundances of taxa in gut microbiota samples obtained from younger heart failure (HF-Y) patients and healthy control (HC) subjects. (A) Phylum level. (B) Genus level. (C) Species level. Data are presented as mean ± SEM. Horizontal bars indicate means. * p < 0.05. NS, not significant.
Fig 3
Fig 3. Richness, diversity, and UniFrac distances of gut microbiota in younger and older patients with heart failure.
Chao1-estimated operational taxonomic unit (OTU) number (A) and Shannon index (B) of gut microbiota samples obtained from younger and older patients with heart failure (HF-Y and HF-O, respectively). Unweighted UniFrac analysis (C, D) and weighted UniFrac analysis (E, F) of gut microbiota samples obtained from HF-Y and HF-O. Principal Coordinate Analysis (PCoA) of UniFrac distances between gut microbial communities of the individuals (C, E), and UniFrac distances between gut microbial communities of the individuals within each group and between the two groups (D, F). Data are presented as mean ± SEM. NS, not significant. ** p < 0.01.
Fig 4
Fig 4. Abundances of taxa in gut microbiota of younger and older patients with heart failure.
Relative abundances of taxa in gut microbiota samples obtained from younger and older patients with heart failure (HF-Y and HF-O, respectively). (A) Phylum level. (B) Genus level. (C) Species level. Data are presented as mean ± SEM. Horizontal bars indicate means. * p < 0.05, ** p < 0.01. NS, not significant.
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Grants and funding

This work was supported in part by grants from Japan Society for the Promotion of Science (KAKENHI 26670395, https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-26670395/) to H.A., and Core Research for Evolutionary Medical Science and Technology (CREST) from Japan Agency for Medical Research and Development (AMED) (M1501, http://www.amed.go.jp/program/list/01/07/023_02.html) to K.H., H.M. H.A. has received research funding from Takeda Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Shionogi & Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Bristol-Myers Squibb K.K., MSD K.K., Sanofi K.K., and Sumitomo Dainippon Pharma Co., Ltd. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials.