The human microbiome encodes resistance to the antidiabetic drug acarbose

Balaich, Jared N.; Estrella, Michael; Wu, Guojun; Jeffrey, Philip D.; Biswas, Abhishek; Zhao, Liping; Korennykh, Alexei; Donia, Mohamed S.

doi:10.1038/s41586-021-04091-0

Cited by 61 publications

(38 citation statements)

References 61 publications

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“…Nine HO1518 by our group, can be grouped into two types, namely acarviostatin I03-type (1-6) and acarviostatin II03-type (7)(8)(9), based on the number of pseudo-trisaccharide units. Since the amine residues of aminooligosaccharides are readily protonated [25], the positive-ion mode HRMS/MS analysis of nine references was performed.…”

Section: Resultsmentioning

confidence: 99%

“…Acarbose, a typical anti-diabetes drug functioning as an α -glucosidases inhibitor, potently inhibits the α -glucosidases in vivo to retard carbohydrate digestion and avoid blood glucose elevation [ 6 , 7 ]. However, the specific kinase Mak1 derived from the human microbiome selectively phosphorylates acarbose at the C6-OH of C 7 N cyclohexitol ring in acarbose, leading to its inactivation [ 8 ]. Therefore, an urgent demand for the discovery of new α -glucosidase inhibitors with high efficacy has declared a public-health imperative for the treatment of T2DM.…”

Section: Introductionmentioning

confidence: 99%

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Rapid Mining of Novel α-Glucosidase and Lipase Inhibitors from Streptomyces sp. HO1518 Using UPLC-QTOF-MS/MS

Liu

Feng

et al. 2022

Marine Drugs

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A rapid and sensitive method using ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) was applied for the analysis of the metabolic profile of acarviostatin-containing aminooligosaccharides derived from Streptomyces sp. HO1518. A total of ninety-eight aminooligosaccharides, including eighty potential new compounds, were detected mainly based on the characteristic fragment ions originating from quinovosidic bond cleavages in their molecules. Following an LC-MS-guided separation technique, seven new aminooligosaccharides (10–16) along with four known related compounds (17–20) were obtained directly from the crude extract of strain HO1518. Compounds 10–13 represent the first examples of aminooligosaccharides with a rare acarviostatin II02-type structure. In addition, all isolates displayed considerable inhibitory effects on three digestive enzymes, which revealed that the number of the pseudo-trisaccharide core(s), the feasible length of the oligosaccharides, and acyl side chain exerted a crucial influence on their bioactivities. These results demonstrated that the UPLC-QTOF-MS/MS-based metabolomics approach could be applied for the rapid identification of aminooligosaccharides and other similar structures in complex samples. Furthermore, this study highlights the potential of acylated aminooligosaccharides with conspicuous α-glucosidase and lipase inhibition for the future development of multi-target anti-diabetic drugs.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Rapid Mining of Novel α-Glucosidase and Lipase Inhibitors from Streptomyces sp. HO1518 Using UPLC-QTOF-MS/MS

Liu

Feng

et al. 2022

Marine Drugs

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“…Indeed, it has been indicated that the bacterial members in the gut might modulate the availability and efficacy of therapeutic drugs ( Klünemann et al, 2021 ). Most recently, investigators have confirmed that the gut microbiome–encoded enzymes to selectively inactivate acarbose, a clinically used antidiabetic drug ( Balaich et al, 2021 ). Therefore, the intestinal bacteria and metabolites might also affect the pharmacodynamics of the ACEI/ARB drugs, leading to a discrepancy in the treatment outcome of the well-control and poor-control groups.…”

Section: Discussionmentioning

confidence: 99%

Antihypertensive Therapy by ACEI/ARB Is Associated With Intestinal Flora Alterations and Metabolomic Profiles in Hypertensive Patients

Dong

Wang

Jiao

et al. 2022

Front. Cell Dev. Biol.

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Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ACEI/ARB) are the first-line drugs for the treatment of essential hypertension (HTN), one of the most important risk factors for cardiovascular and cerebrovascular diseases. Intestinal flora and microbial metabolites have been demonstrated to play important roles in blood pressure (BP) regulation and HTN development. However, it remains elusive that intestinal bacteria and metabolites are associated with the protective effects of ACEI/ARB anti-hypertensive drugs against HTN. In this study, we evaluated the effect of ACEI/ARB on gut microbiome and metabolites in patients suffering from HTN. We performed 16S rRNA sequencing and fecal metabolomic analysis of 36 HTN patients placed on ACEI/ARB therapy and 19 newly diagnosed HTN patients with no history of anti-hypertensive treatment. Patients under medication treatment were further classified into well-controlled (n = 24) and poor-controlled (n = 12) groups according to their BP levels. The ACEI/ARB improved the intestinal microbiome of the HTN patients by reducing potentially pathogenic bacteria such as Enterobacter and Klebsiella and increasing beneficial bacteria such as Odoribacter. Moreover, ACEI/ARB therapy was correlated with significant metabolomic changes in the HTN patients, including progressively enhanced inositol from poor-controlled to well-controlled groups. The profiles of gut bacteria were linked to the production of metabolites, and inositol was negatively correlated with Klebsiella, Enterobacter, and Proteobacteria. Our study suggests that ACEI/ARB modulates gut microbial composition and functions and alters microbial metabolites in HTN patients.

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“…Currently, increasing evidence demonstrates that the gut microbiota can contribute to T2DM, and microbiota composition is altered in diabetic patients ( Adeshirlarijaney and Gewirtz, 2020 ; Fan and Pedersen, 2021 ). In addition, the human microbiome contributes to the drug resistance of antidiabetic drug, acarbose ( Balaich et al, 2021 ). Thus, targeting of gut microbiota is a defensive strategy against T2DM.…”

Section: Hfd/streptozotocin-induced Type 2 Diabetes Mellitusmentioning

confidence: 99%

Targeting Gut Microbiota With Natural Polysaccharides: Effective Interventions Against High-Fat Diet-Induced Metabolic Diseases

et al. 2022

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Unhealthy diet, in particular high-fat diet (HFD) intake, can cause the development of several metabolic disorders, including obesity, hyperlipidemia, type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and metabolic syndrome (MetS). These popular metabolic diseases reduce the quality of life, and induce premature death worldwide. Evidence is accumulating that the gut microbiota is inextricably associated with HFD-induced metabolic disorders, and dietary intervention of gut microbiota is an effective therapeutic strategy for these metabolic dysfunctions. Polysaccharides are polymeric carbohydrate macromolecules and sources of fermentable dietary fiber that exhibit biological activities in the prevention and treatment of HFD-induced metabolic diseases. Of note, natural polysaccharides are among the most potent modulators of the gut microbiota composition. However, the prebiotics-like effects of polysaccharides in treating HFD-induced metabolic diseases remain elusive. In this review, we introduce the critical role of gut microbiota human health and HFD-induced metabolic disorders. Importantly, we review current knowledge about the role of natural polysaccharides in improving HFD-induced metabolic diseases by regulating gut microbiota.

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The human microbiome encodes resistance to the antidiabetic drug acarbose

Cited by 61 publications

References 61 publications

Rapid Mining of Novel α-Glucosidase and Lipase Inhibitors from Streptomyces sp. HO1518 Using UPLC-QTOF-MS/MS

Rapid Mining of Novel α-Glucosidase and Lipase Inhibitors from Streptomyces sp. HO1518 Using UPLC-QTOF-MS/MS

Antihypertensive Therapy by ACEI/ARB Is Associated With Intestinal Flora Alterations and Metabolomic Profiles in Hypertensive Patients

Targeting Gut Microbiota With Natural Polysaccharides: Effective Interventions Against High-Fat Diet-Induced Metabolic Diseases

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