Apostichopus japonicus Oligopeptide Induced Heterogeneity in the Gastrointestinal Tract Microbiota and Alleviated Hyperuricemia in a Microbiota‐Dependent Manner

Abstract

Scope: This study aims to investigate the protective effect of Apostichopus japonicus oligopeptide (AJOP) on hyperuricemia, demonstrate the modulation of the gastrointestinal tract (GIT) microbiota, and clarify the underlying microbiota-dependent mechanism. Methods and Results: Hyperuricemic mice treated with AJOP and subjected to corresponding fecal microbiota transplantation (FMT) are used to observe the beneficial effects of AJOP and microbiota. Gene transcriptions are measured using quantitative real-time PCR. The GIT (stomach, colon, cecum, and feces) microbiota is analyzed by 16S rDNA sequencing and the short-chain fatty acids are detected using GC-MS. Dietary administration of AJOP significantly alleviates hyperuricemia, regulates uric acid metabolism, inhibites the activation of the NLRP3 inflammasome and NF-B-related signaling pathway, and restores m6A methylation levels. In addition, substantial heterogeneity is observed in GIT microbiota. Furthermore, FMT effectively alleviates hyperuricemia in mice by selectively regulating the corresponding pathways associated with AJOP treatment, indicating that the mechanism underlying the protective effects of AJOP is partly microbiota-dependent. Conclusion: This study demonstrates that AJOP exerts a protective effect on hyperuricemic mice by regulating uric acid metabolism, resulting in substantial heterogeneity among the GIT microbiota, thus mediating the beneficial effects in a microbiota-dependent manner.

Sacha Inchi Oil Press-Cake Protein Hydrolysates Exhibit Anti-Hyperuricemic Activity via Attenuating Renal Damage and Regulating Gut Microbiota

“…Gut microbiota, as an important component of the intestine, plays an active role in UA excretion [ 9 , 47 ]. In accordance, previous studies indicated that the anti-hyperuricemic effects of some oligopeptides were mediated by the gut microbiota, such as tuna meat oligopeptides [ 40 ], Val-Val-Tyr-Pro peptide [ 48 ], and Apostichopus japonicus oligopeptide [ 49 ]. As reported, the diversity of intestinal flora in the hyperuricemia group is generally lower than that in the normal group [ 50 ].…”

Gut microbiota remodeling: A promising therapeutic strategy to confront hyperuricemia and gout

“…Both peptides, as potential microbiota modulators, reduced gut microbiota richness and diversity, altering the composition at the phylum and genus levels ( Fan et al., 2022 ). Apostichopus japonicus oligopeptide (AJOP) can significantly alleviate HUA, regulate UA metabolism, inhibit the activation of NLRP3 inflammasome and NF-kB-related signaling pathways, and restore the m6A methylation levels ( Lu et al., 2021 ). Furthermore, fecal microbiota transplantation (FMT) effectively alleviated HUA in mice by selectively modulating the corresponding pathways associated with AJOP treatment ( Lu et al., 2021 ), suggesting that the underlying mechanism of AJOP’s protective effect is partially dependent on the microbiota.…”

“…Apostichopus japonicus oligopeptide (AJOP) can significantly alleviate HUA, regulate UA metabolism, inhibit the activation of NLRP3 inflammasome and NF-kB-related signaling pathways, and restore the m6A methylation levels ( Lu et al., 2021 ). Furthermore, fecal microbiota transplantation (FMT) effectively alleviated HUA in mice by selectively modulating the corresponding pathways associated with AJOP treatment ( Lu et al., 2021 ), suggesting that the underlying mechanism of AJOP’s protective effect is partially dependent on the microbiota. In a mouse model of diet-induced HUA, both EH-JAP and EH-LEU inhibited UA biosynthesis and promoted UA excretion ( Wan et al., 2020 ), thereby alleviating the hyperuricemic phenotype.…”

“…Washing microbiota transplantation reduces the serum UA levels in gout patients, is associated with a reduction in the frequency and duration of acute gout flares, reduces the diamine oxidase and endotoxin levels, and helps improve their damaged gut barrier function ( Xie et al., 2021 ). The antihyperuricemic effects of TMOP and AJOP can be transmitted by transplanting fecal microbiota from TMOP/AJOP-treated mice ( Han et al., 2020 ; Lu et al., 2021 ). Anserine treatment reversed gut dysbiosis, repaired the intestinal epithelial barrier, and increased SCFA production, and an anti-HUA effect was demonstrated by the transplantation of fecal microbiota from anserine-treated mice ( Han et al., 2021 ).…”

Novel anti-hyperuricemic hexapeptides derived fromApostichopus japonicushydrolysate and their modulation effects on the gut microbiota and host microRNA profile

“…6 As previously reported, Apostichopus japonicus oligopeptide (AJOP), prepared with an edible protein, is a safer alternative that exerts anti-HUA effects by rebalancing uric acid metabolism and inhibiting the NLRP3 inflammasome and NF-κB signaling pathway activation. 3,7 The various components and their multiple targets not only contribute to the comprehensive anti-HUA effects of AJOP but also hinder the further development of AJOP due to the unclear understanding of key peptides with anti-HUA effects. The purify-and-identify method has been widely used to screen peptides with distinct functions and structures via iterative rounds, but this method is one-sided, labor intensive and time-consuming.…”