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Open Access

Lacticaseibacillus rhamnosus Fmb14 ameliorates hyperuricemia-induced hepatocyte pyroptosis via NLRP3 inflammasome cascade inhibition

Hongyuan Zhaoa, Xiaoyu Chena, Li Zhangb, Fanqiang Menga, Libang Zhoua, Zhaoxin Lua( ), Yingjian Luc,( )
College of Food Science & Technology, Nanjing Agricultural University, Nanjing 210095, China
Institute of Vegetable, Gansu Academy of Agricultural Sciences, Lanzhou 730070, China
College of Food Science & Engineering, Nanjing University of Finance and Economics, Nanjing 210023, China

Peer review under responsibility of Tsinghua University Press.

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Highlights

• L. rhamnosus Fmb14 decreased the ROS and MMP dysbiosis induced by uric acid in HepG2 cells.

• L. rhamnosus Fmb14 prevented uric acid-induced pyroptosis through NLRP3 inflammasome inhibition and IL-1β reduction in HepG2 cells.

• L. rhamnosus Fmb14 attenuated liver injury in purine-induced hyperuricaemic mice by decreasing pyroptosis, especially by reducing the effector GSDMD.

• L. rhamnosus Fmb14 reduced the tumour process of the liver in hyperuricaemia.

Graphical Abstract

Abstract

Hyperuricemia is a high-risk factor for the development of gout and renal fibrosis, but the adverse effects of hyperuricemia on the liver have been seriously neglected. This research investigated the ameliorating effect of Lacticaseibacillus rhamnosus Fmb14 on hyperuricemia induced liver dysfunction both in vitro and in vivo. Cell free extracts of high dose L. rhamnosus Fmb14 treatment reduced the death rate of HepG2 cell lines from 24.1% to 14.9% by inhibiting NLRP3 recruitment, which was mainly activated by reactive oxygen species release and mitochondrial membrane potential disorder. In purine dietary induced hyperuricemia (PDIH) mice model, liver oedema and pyroptosis were ameliorated after L. rhamnosus Fmb14 administration through downregulating the expression levels of NLRP3, caspase-1 and gasdermin-D from 1.61 to 0.86, 3.15 to 1.01 and 5.63 to 2.02, respectively. L. rhamnosus Fmb14 administration restored mitochondrial inner membrane protein (MPV17) and connexin 43 from 2.83 and 0.73 to 0.80 and 0.98 respectively in PDIH mice, indicating that dysbiosis of mitochondrial membrane potential was restored in liver. Intriguingly, PDIH pyroptosis stimulates the process of apoptosis, which leads to severe leakage of hepatocytes, and both of pyroptosis and apoptosis were decreased after L. rhamnosus Fmb14 treatment. Therefore, L. rhamnosus Fmb14 is a promising biological resource to maintain homeostasis of the liver in hyperuricemia and the prevention of subsequent complications.

Keywords

PyroptosisHyperuricemiaNLRP3 pathwayLacticaseibacillus rhamnosus Fmb14

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Food Science and Human Wellness
Volume 13 Issue 4,
July 2024
Pages 2174-2186
DOI: 10.26599/FSHW.2022.9250181
Cite this article:
Zhao H, Chen X, Zhang L, et al. Lacticaseibacillus rhamnosus Fmb14 ameliorates hyperuricemia-induced hepatocyte pyroptosis via NLRP3 inflammasome cascade inhibition. Food Science and Human Wellness, 2024, 13(4): 2174-2186. https://doi.org/10.26599/FSHW.2022.9250181

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Received: 01 December 2022
Revised: 19 December 2022
Accepted: 12 January 2023
Published: 20 May 2024
© 2024 Beijing Academy of Food Sciences. Publishing services by Tsinghua University Press.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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