<i>Akkermansia muciniphila</i> attenuates LPS-induced acute kidney injury by inhibiting TLR4/NF-κB pathway

Shi, Jun Yi; Wang, Feng; Tang, Lei; Li, Zhiqiang; Yu, Manshu; Bai, Yu; Weng, Zebin; Sheng, Maoyin; He, Weiming; Chen, Yugen

doi:10.1093/femsle/fnac103

Cited by 7 publications

(5 citation statements)

References 27 publications

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“…Of note, the statistically significant difference in Verrucomicrobia was also observed at the species level, for Akkermansia muciniphila (A. muciniphila; p value = 0.005). A recent report observed that pretreatment with A.muciniphila protected against lipopolysaccharide-induced acute kidney in mice (22), implying that this strain is physiologically important.…”

Section: Discussionmentioning

confidence: 94%

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Commensal Microbiota Regulate Renal Gene Expression

Moore

Pluznick

2022

Preprint

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The gut microbiome impacts host gene expression not only in the colon, but also at distal sites including liver, white adipose tissue, and spleen. The gut microbiome also influences the kidney and is associated with renal diseases and pathologies; however, a role for the gut microbiome to modulate renal gene expression has not been examined. To determine if microbes modulate renal gene expression, we used whole-organ RNA sequencing (RNA-Seq) to compare gene expression in C57Bl/6 mice that are germ-free (lacking gut microbiota) versus conventionalized (with gut microbiota). 16S sequencing showed that males and females were similarly conventionalized, although Verrucomicrobia was higher in male mice. We find that renal gene expression is differentially regulated in the presence versus absence of microbiota, and that these changes are largely sex-specific. Although microbes also influence gene expression in the liver and large intestine, most differentially expressed genes (DEGs) in the kidney are not similarly regulated in the liver or large intestine. This demonstrates that the influence of the gut microbiota on gene expression is tissue specific. However, a minority of genes (n=4 in males, n=6 in females) were similarly regulated in all three tissues examined, including genes associated with circadian rhythm (Per1 in males and Per2 in females) and metal binding (Mt1 and Mt2 in both males and females). Finally, using a previously published single cell RNA-Seq (scRNA-Seq) dataset, we assigned a subset of DEGs to specific kidney cell types, revealing clustering of DEGs by cell type and/or sex.

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Section: Discussionmentioning

confidence: 94%

“…A recent report observed that pre-treatment with A . muciniphila protected against lipopolysaccharide-induced acute kidney in mice (22), implying that this strain is physiologically important.…”

Section: Discussionmentioning

confidence: 99%

Commensal Microbiota Regulate Renal Gene Expression

Moore

Pluznick

2022

Preprint

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“…Since the kidneys are the primary excretory organs for metabolites and toxins, the renal tubular epithelium is susceptible to various damages. LPS is a significant contributor to AKI. − Furthermore, renal tubular epithelial cells are more easily exposed to a high concentration of the LPS microenvironment from the intestinal entrance, which significantly impacts the morphology and function of the renal tubular epithelial cells. , After 24 h and 48h incubation, cell viability cocultured with LPS (10 μg/mL) was reduced to 87.5 ± 5.7 and 79.8 ± 1.4% compared to the control group ( p < 0.05). The 20 μM PJ16 noticeably prevented LPS-induced cell injury with the cell survival rate of 100 ± 1.5 and 95.9 ± 5.5% ( p < 0.05) (Figure A).…”

Section: Resultsmentioning

confidence: 99%

“…Studies have shown that “metabolic endotoxemia” encourages the onset of obesity and metabolic disorders, which is also the primary cause of AKI . Through the TLR4 signaling pathway, lipopolysaccharide (LPS) contributes to the onset and progression of kidney disease. − Therefore, in vitro models of LPS-stimulating macrophages and renal tubular epithelial cells were constructed to detect how PJ16 modulates macrophage function and protects LPS-injured renal tubular epithelial cells. Consistent with the results in vitro, we established a unilateral ureteral obstruction (UUO) mouse model to verify the effect of PJ16 in vivo.…”

Section: Introductionmentioning

confidence: 99%

Pyxinol Fatty Acid Ester Derivatives J16 against AKI by Selectively Promoting M1 Transition to M2c Macrophages

Wang,

Li,

Chen

et al. 2024

J. Agric. Food Chem.

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Acute kidney injury (AKI) is a common, multicause clinical condition that, if ignored, often progresses to chronic kidney disease (CKD) and end-stage kidney disease, with a mortality rate of 40−50%. However, there is a lack of universal treatment for AKI. Inflammation is the basic pathological change of early kidney injury, and inflammation can exacerbate AKI. Macrophages are the primary immune cells involved in the inflammatory microenvironment of kidney disease. Therefore, regulating the function of macrophages is a crucial breakthrough for the AKI intervention. Our team chemically modified pyxinol, an ocotillol-type ginsenoside, to prepare PJ16 with higher solubility and bioavailability. In vitro, using a model of macrophages stimulated by LPS, it was found that PJ16 could regulate macrophage function, including inhibiting the secretion of inflammatory factors, promoting phagocytosis, inhibiting M1 macrophages, and promoting M1 transition to the M2c macrophage. Further investigation revealed that PJ16 may shield renal tubular epithelial cells (HK-2) damaged by LPS in vitro. Based on this, PJ16 was validated in the animal model of unilateral ureteral obstruction, which showed that it improves renal function and inhibits renal tissue fibrosis by decreasing inflammatory responses, reducing macrophage inflammatory infiltration, and preferentially upregulating M2c macrophages. In conclusion, our study is the first to show that PJ16 resists AKI and fibrosis by mechanistically regulating macrophage function by modulating the phenotypic transition from M1 to M2 macrophages, mainly M2c macrophages.

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“…Akkermansia protects the intestinal mucus layer and maintains intestinal homeostasis, reducing the entry of LPS into the bloodstream ( 89 ). Vesicles secreted by Akkermansia are also able to reduce the expression of TLR4, thereby regulating the NF-κB pathway ( 90 ). Therefore, insufficient Akkermansia genera might disrupt the balance of Th17/Treg through activating TLR4 signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Altered intestinal microbiota enhances adenoid hypertrophy by disrupting the immune balance

Liu,

Jiang,

Liu

et al. 2023

Front. Immunol.

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IntroductionAdenoid hypertrophy (AH) is a common upper respiratory disorder in children. Disturbances of gut microbiota have been implicated in AH. However, the interplay of alteration of gut microbiome and enlarged adenoids remains elusive.Methods119 AH children and 100 healthy controls were recruited, and microbiome profiling of fecal samples in participants was performed using 16S rRNA gene sequencing. Fecal microbiome transplantation (FMT) was conducted to verify the effects of gut microbiota on immune response in mice.ResultsIn AH individuals, only a slight decrease of diversity in bacterial community was found, while significant changes of microbial composition were observed between these two groups. Compared with HCs, decreased abundances of Akkermansia, Oscillospiraceae and Eubacterium coprostanoligenes genera and increased abundances of Bacteroides, Faecalibacterium, Ruminococcus gnavus genera were revealed in AH patients. The abundance of Bacteroides remained stable with age in AH children. Notably, a microbial marker panel of 8 OTUs were identified, which discriminated AH from HC individuals with an area under the curve (AUC) of 0.9851 in the discovery set, and verified in the geographically different validation set, achieving an AUC of 0.9782. Furthermore, transfer of mice with fecal microbiota from AH patients dramatically reduced the proportion of Treg subsets within peripheral blood and nasal-associated lymphoid tissue (NALT) and promoted the expansion of Th2 cells in NALT.ConclusionThese findings highlight the effect of the altered gut microbiota in the AH pathogenesis.

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Akkermansia muciniphila attenuates LPS-induced acute kidney injury by inhibiting TLR4/NF-κB pathway

Cited by 7 publications

References 27 publications

Commensal Microbiota Regulate Renal Gene Expression

Commensal Microbiota Regulate Renal Gene Expression

Pyxinol Fatty Acid Ester Derivatives J16 against AKI by Selectively Promoting M1 Transition to M2c Macrophages

Altered intestinal microbiota enhances adenoid hypertrophy by disrupting the immune balance

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