Butyrate, a bacterial metabolite, induces apoptosis and autophagic cell death in gingival epithelial cells

Tsuda, Hiromasa; Ochiai, Kuniyasu; Suzuki, Naoto; Otsuka, Kichibee

doi:10.1111/j.1600-0765.2010.01277.x

Cited by 79 publications

(95 citation statements)

References 32 publications

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“…Short-chain fatty acids can disrupt host defense systems by different mechanisms, such as induction of apoptosis in immune cells (Stehle et al, 2001;Abe, 2012) and gingival epithelial cells (Tsuda et al, 2010) and alteration of cell function and gene expression in human gingival fibroblasts (Chang et al, 2013). Previous studies have demonstrated higher concentrations of short-chain fatty acids in the gingival crevicular fluid of periodontitis patients (Lu et al, 2008;Qiqiang et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Phylogenetic and functional gene structure shifts of the oral microbiomes in periodontitis patients

et al. 2014

The ISME Journal

155

126

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Determining the composition and function of subgingival dental plaque is crucial to understanding human periodontal health and disease, but it is challenging because of the complexity of the interactions between human microbiomes and human body. Here, we examined the phylogenetic and functional gene differences between periodontal and healthy individuals using MiSeq sequencing of 16S rRNA gene amplicons and a specific functional gene array (a combination of GeoChip 4.0 for biogeochemical processes and HuMiChip 1.0 for human microbiomes). Our analyses indicated that the phylogenetic and functional gene structure of the oral microbiomes were distinctly different between periodontal and healthy groups. Also, 16S rRNA gene sequencing analysis indicated that 39 genera were significantly different between healthy and periodontitis groups, and Fusobacterium, Porphyromonas, Treponema, Filifactor, Eubacterium, Tannerella, Hallella, Parvimonas, Peptostreptococcus and Catonella showed higher relative abundances in the periodontitis group. In addition, functional gene array data showed that a lower gene number but higher signal intensity of major genes existed in periodontitis, and a variety of genes involved in virulence factors, amino acid metabolism and glycosaminoglycan and pyrimidine degradation were enriched in periodontitis, suggesting their potential importance in periodontal pathogenesis. However, the genes involved in amino acid synthesis and pyrimidine synthesis exhibited a significantly lower relative abundance compared with healthy group. Overall, this study provides new insights into our understanding of phylogenetic and functional gene structure of subgingival microbial communities of periodontal patients and their importance in pathogenesis of periodontitis.

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Section: Discussionmentioning

confidence: 99%

Phylogenetic and functional gene structure shifts of the oral microbiomes in periodontitis patients

et al. 2014

The ISME Journal

155

126

View full text Add to dashboard Cite

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“…We have shown that butyrate concentrations of 0.5 mM or higher induce death of epithelial cells (70). Although some dead cells exhibit features of apoptosis, such as phosphatidylserine redistribution, increased caspase-3 activity, and decreased anti-apoptotic bcl-2 expression, only a small number were rescued by treatment with zVAD-fmk, a pan-caspase inhibitor (70). We also observed induction of a couple of autophagic features by butyrate, such as autophagic flux and increased-LC3 lipidation (70).…”

Section: Possible Relationship Of Cell Death To Periodontal Diseasementioning

confidence: 91%

“…Although some dead cells exhibit features of apoptosis, such as phosphatidylserine redistribution, increased caspase-3 activity, and decreased anti-apoptotic bcl-2 expression, only a small number were rescued by treatment with zVAD-fmk, a pan-caspase inhibitor (70). We also observed induction of a couple of autophagic features by butyrate, such as autophagic flux and increased-LC3 lipidation (70). Furthermore, cell death was reduced by the autophagy inhibitor 3-methyladenine, which suggests that butyrate induced autophagic cell death of gingival epithelial cells (70).…”

Section: Possible Relationship Of Cell Death To Periodontal Diseasementioning

confidence: 99%

Programmed cell death and its possible relationship with periodontal disease

et al. 2012

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Cell death occurs in physiological conditions and as a result of injury or disease. Programmed cell death has an important role in the development and homeostasis of human tissue. Aberrant regulation of this process is thought to cause numerous diseases, including developmental disorders, neurodegenerative disease, and cancer. Apoptosis is the main type of programmed cell death and is well understood. However, recent intensive studies have revealed other types of programmed cell death. Here, we include an overview of three types of programmed cell death: apoptosis, necroptosis, and autophagic cell death. We also provide information on damage-associated molecular patterns (DAMPs), which have proinflammatory effects and are reportedly associated with cell death. Finally, we discuss the link between programmed cell death and periodontal disease and propose a hypothetical role for programmed cell death and DAMPs-which are released from cytoplasm of necrotic cells-in periodontal disease initiation. (J Oral Sci 54, 137-149, 2012)

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“…In addition to energy production, amino acid metabolism is important for understanding bacterial virulence, because the end products of short-chain fatty acids, e.g. butyrate, exhibit cytotoxicity against periodontal epithelial cells (14). In fact, the concentration of butyrate is increased in subgingival fluid in periodontal patients (15), and these compounds are proposed to be involved in the initiation and progression of these diseases (16).…”

mentioning

confidence: 99%

Identification and Characterization of Prokaryotic Dipeptidyl-peptidase 5 from Porphyromonas gingivalis

Ohara‐Nemoto

Rouf

Naito

et al. 2014

Journal of Biological Chemistry

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Background: Dipeptidyl-peptidases (DPPs) are key factors for amino acid metabolism and bacterial growth of asaccharolytic Porphyromonas gingivalis. Results: DPP5, which is specific for Ala and hydrophobic residues, is expressed in the periplasmic space of P. gingivalis. Conclusion: DPP5 was discovered in prokaryotes for the first time. Significance: The discovery of DPP5 expands understanding of amino acid and energy metabolism in prokaryotes.

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Butyrate, a bacterial metabolite, induces apoptosis and autophagic cell death in gingival epithelial cells

Abstract: These data suggest that butyrate induces apoptosis and autophagic cell death.

Cited by 79 publications

References 32 publications

Phylogenetic and functional gene structure shifts of the oral microbiomes in periodontitis patients

Phylogenetic and functional gene structure shifts of the oral microbiomes in periodontitis patients

Programmed cell death and its possible relationship with periodontal disease

Identification and Characterization of Prokaryotic Dipeptidyl-peptidase 5 from Porphyromonas gingivalis

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