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拟杆菌属缓解胰岛素抵抗通过激活肠道 GPR109a。

Parabacteroides distasonis ameliorates insulin resistance via activation of intestinal GPR109a.

机构信息

State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, China.

China-Canada Joint Lab of Food Science and Technology, Nanchang University, Nanchang, China.

出版信息

Nat Commun. 2023 Nov 25;14(1):7740. doi: 10.1038/s41467-023-43622-3.

DOI:10.1038/s41467-023-43622-3
PMID:38007572
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10676405/
Abstract

Gut microbiota plays a key role in insulin resistance (IR). Here we perform a case-control study of Chinese adults (ChiCTR2200065715) and identify that Parabacteroides distasonis is inversely correlated with IR. Treatment with P. distasonis improves IR, strengthens intestinal integrity, and reduces systemic inflammation in mice. We further demonstrate that P. distasonis-derived nicotinic acid (NA) is a vital bioactive molecule that fortifies intestinal barrier function via activating intestinal G-protein-coupled receptor 109a (GPR109a), leading to ameliorating IR. We also conduct a bioactive dietary fiber screening to induce P. distasonis growth. Dendrobium officinale polysaccharide (DOP) shows favorable growth-promoting effects on P. distasonis and protects against IR in mice simultaneously. Finally, the reduced P. distasonis and NA levels were also validated in another human type 2 diabetes mellitus cohort. These findings reveal the unique mechanisms of P. distasonis on IR and provide viable strategies for the treatment and prevention of IR by bioactive dietary fiber.

摘要

肠道微生物群在胰岛素抵抗（IR）中起着关键作用。在这里，我们对中国成年人进行了病例对照研究（ChiCTR2200065715），并发现副拟杆菌（Parabacteroides distasonis）与 IR 呈负相关。用 P. distasonis 治疗可改善 IR，增强肠道完整性，并减少小鼠的全身炎症。我们进一步证明，P. distasonis 衍生的烟酸（NA）是一种重要的生物活性分子，通过激活肠道 G 蛋白偶联受体 109a（GPR109a）增强肠道屏障功能，从而改善 IR。我们还进行了生物活性膳食纤维筛选以诱导 P. distasonis 生长。铁皮石斛多糖（Dendrobium officinale polysaccharide，DOP）对 P. distasonis 具有良好的促生长作用，同时可保护小鼠免受 IR 的影响。最后，在另一个人类 2 型糖尿病队列中也验证了 P. distasonis 和 NA 水平降低。这些发现揭示了 P. distasonis 对 IR 的独特作用机制，并为通过生物活性膳食纤维治疗和预防 IR 提供了可行的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a9f/10676405/56cf9f5483d2/41467_2023_43622_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a9f/10676405/451a1f8587f3/41467_2023_43622_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a9f/10676405/f45902e1dd7a/41467_2023_43622_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a9f/10676405/07ee151ad40a/41467_2023_43622_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a9f/10676405/318cff82b4bd/41467_2023_43622_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a9f/10676405/3890030c32fc/41467_2023_43622_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a9f/10676405/65bbe36f62a6/41467_2023_43622_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a9f/10676405/56cf9f5483d2/41467_2023_43622_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a9f/10676405/451a1f8587f3/41467_2023_43622_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a9f/10676405/f45902e1dd7a/41467_2023_43622_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a9f/10676405/07ee151ad40a/41467_2023_43622_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a9f/10676405/318cff82b4bd/41467_2023_43622_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a9f/10676405/3890030c32fc/41467_2023_43622_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a9f/10676405/65bbe36f62a6/41467_2023_43622_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a9f/10676405/56cf9f5483d2/41467_2023_43622_Fig7_HTML.jpg

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本文引用的文献

[1]
The gut microbiota in obesity and weight management: microbes as friends or foe?

Nat Rev Endocrinol. 2023-5

[2]
Gut commensal alleviates inflammatory arthritis.

Gut. 2023-9

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NAD precursors cycle between host tissues and the gut microbiome.

Cell Metab. 2022-12-6

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Yeast β-Glucan Improves Insulin Sensitivity and Hepatic Lipid Metabolism in Mice Humanized with Obese Type 2 Diabetic Gut Microbiota.

Mol Nutr Food Res. 2022-11

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Front Endocrinol (Lausanne). 2022

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Oral administration of Blautia wexlerae ameliorates obesity and type 2 diabetes via metabolic remodeling of the gut microbiota.

Nat Commun. 2022-8-18

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Fecal microbial transplantation and fiber supplementation in patients with severe obesity and metabolic syndrome: a randomized double-blind, placebo-controlled phase 2 trial.

Nat Med. 2021-7

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