Pyroglutamyl leucine, a peptide in fermented foods, attenuates dysbiosis by increasing host antimicrobial peptide

Shirako, Saki; Kojima, Yumi; Tomari, Naohiro; Nakamura, Yasushi; Matsumura, Yukihiko; Ikeda, Kaori; Inagaki, Nobuya; Satô, Kenji

doi:10.1038/s41538-019-0050-z

Cited by 33 publications

(27 citation statements)

References 26 publications

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“…Therefore, gut microbiota can modulate obesity. We have earlier demonstrated that the administration of 1 mg/kg body weight of pyroGlu-Leu attenuates high fat (60%) diet-induced dysbiosis in rats by increasing host antimicrobial peptide (Shirako et al, 2019). These facts suggest that administration of short-chain hydrophobic pyroglutamyl peptides present in miso could represent a potential dietary approach to curb obesity via the modulation of gut microbiota.…”

Section: Discussionmentioning

confidence: 96%

“…A high fat diet has been shown to increase the abundance of Firmicutes and decrease the abundance of Bacteroidetes in gut microbiota in animal models (Zhang et al, 2012;Shirako et al, 2019). Firmicutes is known to increase host energy intake by converting indigestible substances in the gut to substances accessible to the host digestive system (Bä ckhed et al, 2005;Turnbaugh et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, administration of pyroGlu-Leu and pyroGlu-Asn-Ile at low doses (0.1-1 mg/kg body weight) attenuates dextran sulfate sodium (DSS)-induced colitis and colitis-induced dysbiosis (disturbance of microbiota) in mice (Wada et al, 2013;Kiyono et al, 2016). Administration of pyroGlu-Leu also attenuates high fat diet-induced dysbiosis by increasing host antimicrobial peptide (Shirako et al, 2019), and has been shown to exert antidepressant-like effects (Yamamoto et al, 2015). Moreover, pyroglutamyl peptides exhibit anti-inflammatory activity against LPS-stimulated macrophages (Hirai et al, 2014) and IL-1β stimulated hepatocytes (Oishi et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

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Identification of short-chain pyroglutamyl peptides in Japanese salted fermented soy paste (miso) and their anti-obesity effect

Shirako¹,

Kojima²,

Hasegawa³

et al. 2020

Journal of Food Bioactives

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Miso, a paste of salted fermented soybean, is a seasoning used extensively in traditional Japanese cuisine. Herein, pyroglutamyl peptides present in miso were identified by a liquid chromatography-tandem mass spectrometry (LC-MS/MS), detecting precursor ions, which generated immonium ion of pyroglutamyl residue. By using this method, 13 pyroglutamyl peptides were identified in four types of miso. Administration of the water extract prepared from 0.6 g soybean miso/kg body weight/day significantly suppressed high fat diet-induced weight gain. A similar effect was exerted by the hydrophobic pyroglutamyl peptide fraction, including pyroglutamyl proline (pEP), pEV, pEI, and pEL. Administration of a mixture of synthetic pEP, pEV, pEI, and pEL in a ratio to that in miso or pEL alone also suppressed the weight gain in a dose dependent manner. These results suggest that the short-chain hydrophobic pyroglutamyl peptides present in miso are effective in suppressing high fat diet-induced obesity.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Identification of short-chain pyroglutamyl peptides in Japanese salted fermented soy paste (miso) and their anti-obesity effect

Shirako¹,

Kojima²,

Hasegawa³

et al. 2020

Journal of Food Bioactives

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“…Kiyono et al identified 19 pyroglutamyl peptides in sake, and pyroGlu-Gln and pyroGlu-Leu were the major components [ 55 ]. PyroGlu-Leu has been reported to possess anti-microbial [ 56 ] and anti-inflammatory [ 57 ] activities. Tatsukami et al identified four peptides, [Leu/Ile]-[Leu/Ile]-[Leu/Ile], Phe-Pro-[Leu/Ile], [Leu/Ile]-[Leu/Ile]-[Leu/Ile]-Pro, and [Leu/Ile]-[Leu/Ile]-[Leu/Ile]-[Leu/Ile]-Pro, and predicted two compounds, the steroidal agent androsterone, identified as C 19 H 28 O, and angeloyloxylupanine or acetoxymatrine, identified as C 17 H 26 N 2 O 3 , in the fermentative process of “yamahai-ginjo-shikomi” sake [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

A novel aqueous extract from rice fermented with Aspergillus oryzae and Saccharomyces cerevisiae possesses an anti-influenza A virus activity

Shoji

Sugimoto

Matsuno³

et al. 2021

PLoS ONE

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Human influenza virus infections occur annually worldwide and are associated with high morbidity and mortality. Hence, development of novel anti-influenza drugs is urgently required. Rice Power® extract developed by the Yushin Brewer Co. Ltd. is a novel aqueous extract of rice obtained via saccharization and fermentation with various microorganisms, such as Aspergillus oryzae, yeast [such as Saccharomyces cerevisiae], and lactic acid bacteria, possessing various biological and pharmacological properties. In our previous experimental screening with thirty types of Rice Power® extracts, we observed that the 30th Rice Power® (Y30) extract promoted the survival of influenza A virus-infected Madin-Darby canine kidney (MDCK) cells. Therefore, to identify compounds for the development of novel anti-influenza drugs, we aimed to investigate whether the Y30 extract exhibits anti-influenza A virus activity. In the present study, we demonstrated that the Y30 extract strongly promoted the survival of influenza A H1N1 Puerto Rico 8/34 (A/PR/8/34), California 7/09, or H3N2 Aichi 2/68 (A/Aichi/2/68) viruses-infected MDCK cells and inhibited A/PR/8/34 or A/Aichi/2/68 viruses infection and growth in the co-treatment and pre-infection experiments. The pre-treatment of Y30 extract on MDCK cells did not induce anti-influenza activity in the cell. The Y30 extract did not significantly affect influenza A virus hemagglutination, and neuraminidase and RNA-dependent RNA polymerase activities. Interestingly, the electron microscopy experiment revealed that the Y30 extract disrupts the integrity of influenza A virus particles by permeabilizing the viral membrane envelope, suggesting that Y30 extract has a direct virucidal effect against influenza A virus. Furthermore, we observed that compared to the ethyl acetate (EtOAc) extract, the water extract of Y30 extract considerably promoted the survival of cells infected with A/PR/8/34 virus. These results indicated that more anti-influenza components were present in the water extract of Y30 extract than in the EtOAc extract. Our results highlight the potential of a rice extract fermented with A. oryzae and S. cerevisiae as an anti-influenza medicine and a drug source for the development of anti-influenza compounds.

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“…Soybeans are rich in soybean-specific proteins (glycinin and conglycinin), vitamin E, isoflavones (daidzein, daidzin, genistein, and glycitein), lipids rich in polyunsaturated fatty acids, lecithin, and saponin [ 17 , 44 , 45 ]. Miso also contains pyroglutamyl leucine [ 46 ], which is spontaneously generated from peptides with a glutaminyl residue at the amino terminal, during storage and processing [ 47 ]. Pyroglutamyl leucine was found to improve gut dysbiosis and colitis in mice [ 46 , 48 , 49 ] and, in fact, suppresses the excess proliferation of phylum Firmicutes , which is associated with obesity [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Habitual Miso (Fermented Soybean Paste) Consumption Is Associated with a Low Prevalence of Sarcopenia in Patients with Type 2 Diabetes: A Cross-Sectional Study

et al. 2020

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Insulin resistance is a risk of sarcopenia, and the presence of sarcopenia is high in patients with type 2 diabetes (T2DM). It has been reported that habitual miso soup consumption was associated with lower insulin resistance. However, the association between habitual miso consumption and the presence of sarcopenia in patients with T2DM, especially sex difference, was unclear. In this cross-sectional study, 192 men and 159 women with T2DM were included. Habitual miso consumption was defined as consuming miso soup regularly. Having both low skeletal muscle mass index (<28.64% for men, <24.12% for women) and low adjusted hand grip strength (<51.26% for men, <35.38% for women) was defined as sarcopenia. The proportions of sarcopenia were 8.7% in men and 22.6% in women. The proportions of habitual miso consumption were 88.0% in men and 83.6% in women. Among women, the presence of sarcopenia was lower in the group with habitual miso consumption (18.8% versus 42.3%, p = 0.018); however, there was no association between habitual miso consumption and the presence of sarcopenia in men. Habitual miso consumption was negatively associated with the presence of sarcopenia in women (adjusted odds ratio (OR), 0.20 (95% confidence interval (CI): 0.06–0.62), p = 0.005) but not in men. This study indicated that habitual miso consumption was associated with the presence of sarcopenia in women but not in men.

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Pyroglutamyl leucine, a peptide in fermented foods, attenuates dysbiosis by increasing host antimicrobial peptide

Cited by 33 publications

References 26 publications

Identification of short-chain pyroglutamyl peptides in Japanese salted fermented soy paste (miso) and their anti-obesity effect

Identification of short-chain pyroglutamyl peptides in Japanese salted fermented soy paste (miso) and their anti-obesity effect

A novel aqueous extract from rice fermented with Aspergillus oryzae and Saccharomyces cerevisiae possesses an anti-influenza A virus activity

Habitual Miso (Fermented Soybean Paste) Consumption Is Associated with a Low Prevalence of Sarcopenia in Patients with Type 2 Diabetes: A Cross-Sectional Study

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