Ampicillin exacerbates acetaminophen‐induced acute liver injury by inducing intestinal microbiota imbalance and butyrate reduction

Li, Zhanming; Kong, Chao‐Yue; Mao, Yuqin; Huang, Jiating; Chen, Huiling; Han, Bing; Wang, Li‐Shun

doi:10.1111/liv.15512

Cited by 9 publications

(9 citation statements)

References 45 publications

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“…Ampicillin disrupts intestinal microecology, significantly decreases Lactobacillus abundance, and aggravates hepatic injury in APAP-induced acute liver failure. 32 Clinical case reports described that A. muciniphila abundance was reduced in patients with alcoholic fatty liver. 33 Similarly, this study determined that the intestinal A. muciniphila abundance was markedly decreased after being intraperitoneally injected with a high dose of APAP.…”

Section: Discussionmentioning

confidence: 99%

“…However, the precise role of gut microbiota in APAP‐induced DILI remains unclear. Ampicillin disrupts intestinal microecology, significantly decreases Lactobacillus abundance, and aggravates hepatic injury in APAP‐induced acute liver failure 32 . Clinical case reports described that A. muciniphila abundance was reduced in patients with alcoholic fatty liver 33 .…”

Section: Discussionmentioning

confidence: 99%

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Wolfberry, Yam, and Chrysanthemum polysaccharides increased intestinal Akkermansia muciniphila abundance and hepatic YAP1 expression to alleviate DILI

Lu,

Gong,

Gao

et al. 2023

The FASEB Journal

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Drug‐induced liver injury (DILI) is frequently induced by high dose of acetaminophen (APAP) and is concomitant with disturbances of gut flora. Akkermansia muciniphila is beneficial for the repair of liver injury. Lycium barbarum polysaccharide, yam polysaccharide, and chrysanthemum polysaccharide all have anti‐inflammatory and antioxidation effects. The objective of this study is to investigate the potential of lycium barbarum polysaccharide, yam polysaccharide, and chrysanthemum polysaccharide (LYC) in improving DILI by increasing the abundance of A. muciniphila. Initially, screening for the optimal concentrations of wolfberry, yam, and chrysanthemum (WYC) or LYC to promote A. muciniphila proliferation in vitro and validated in antibiotic (ATB)‐treated KM mice. Subsequently, APAP‐induced DILI model in BALB/c mice were constructed to examine the treatment effects of LYC. Our findings indicate that the optimal concentration ratio of WYC was 2:3:2, and LYC was 1:1:1. WYC increased A. muciniphila proliferation in vitro and in ATB‐treated mice under this ratio. Meanwhile, LYC increased A. muciniphila abundance in vitro and the combination LYC with A. muciniphila promoted the proliferation of A. muciniphila in ATB‐treated mice. The overdose of APAP resulted in the impairment of the intestinal barrier function and subsequent leakage of lipopolysaccharide (LPS). Moreover, LYC increased A. muciniphila abundance, reduced intestinal inflammation and permeability, and upregulated the expression of the tight junction protein zonula occludens protein 1 (ZO‐1) and occludin contents in the gut. Lastly, LYC inhibited LPS leakage and upregulated hepatic YAP1 expression, ultimately leading to the repair of DILI.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Wolfberry, Yam, and Chrysanthemum polysaccharides increased intestinal Akkermansia muciniphila abundance and hepatic YAP1 expression to alleviate DILI

Lu,

Gong,

Gao

et al. 2023

The FASEB Journal

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“…At the genus level, the abundances of Bacteroides, Blautia, Colidextribacter, Enterococcus, Erysipelatoclostridium, Eubacterium_brachy_group, Eubacterium_fissicatena_group, Eubacterium_nodatum_group, Family_XIII_AD3011_group, Gordonibacter, Mucispirillum, no-rank_f_Eubacterium_coprostanoligenes_group, norank_f_norank_o_Clostridia_UCG-014, and Oscillibacter were increased, and the abundances of Bifidobacterium, Candidatus_Saccharimonas, Dubosiella, Lactobacillus, Odoribacter, and Prevotellaceae_UCG-001 were decreased by APAP treatment. Additionally, ampicillin aggravated APAP-induced liver injury by reducing the diversity and altering the composition of the gut microbiota [30]. It has also been found that other drugs, such as methotrexate (anti-cancer drug), tacrine (anti-Alzheimer's disease drug), and triclosan (antimicrobial ingredient) could change the gut microbiota composition of mice or rats, and the alterations in gut microbiota are closely correlated with the liver injury induced by these drugs [31][32][33].…”

Section: Gut Microbiotamentioning

confidence: 99%

Gut–Liver Axis as a Therapeutic Target for Drug-Induced Liver Injury

Tao,

Fan,

Wei

2024

CIMB

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Drug-induced liver injury (DILI) is a liver disease that remains difficult to predict and diagnose, and the underlying mechanisms are yet to be fully clarified. The gut–liver axis refers to the reciprocal interactions between the gut and the liver, and its homeostasis plays a prominent role in maintaining liver health. It has been recently reported that patients and animals with DILI have a disrupted gut–liver axis, involving altered gut microbiota composition, increased intestinal permeability and lipopolysaccharide translocation, decreased short-chain fatty acids production, and impaired bile acid metabolism homeostasis. The present review will summarize the evidence from both clinical and preclinical studies about the role of the gut–liver axis in the pathogenesis of DILI. Moreover, we will focus attention on the potential therapeutic strategies for DILI based on improving gut–liver axis function, including herbs and phytochemicals, probiotics, fecal microbial transplantation, postbiotics, bile acids, and Farnesoid X receptor agonists.

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“…Recent studies have shown a link between SCFAs and AILI [ 84 ]. Akkermansia muciniphila alleviates APAP-induced liver injury by enhancing the production of SCFAs [ 84 , 99 ]. Furthermore, ampicillin exacerbates APAP-induced liver injury by reducing butyrate levels, which can be reversed by supplementation with Lactobacilli [ 99 ].…”

Section: Effects Of Gut Microbiota On Dilimentioning

confidence: 99%

“…Akkermansia muciniphila alleviates APAP-induced liver injury by enhancing the production of SCFAs [ 84 , 99 ]. Furthermore, ampicillin exacerbates APAP-induced liver injury by reducing butyrate levels, which can be reversed by supplementation with Lactobacilli [ 99 ]. Butyrate is a nutrient for intestinal cells that promotes cell regeneration, maintains intestinal barrier function, and possesses anti-inflammatory properties [ 100 ].…”

Section: Effects Of Gut Microbiota On Dilimentioning

confidence: 99%

Role of Gut Microecology in the Pathogenesis of Drug-Induced Liver Injury and Emerging Therapeutic Strategies

Huang,

Zhang,

et al. 2024

Molecules

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Drug-induced liver injury (DILI) is a common clinical pharmacogenic disease. In the United States and Europe, DILI is the most common cause of acute liver failure. Drugs can cause hepatic damage either directly through inherent hepatotoxic properties or indirectly by inducing oxidative stress, immune responses, and inflammatory processes. These pathways can culminate in hepatocyte necrosis. The role of the gut microecology in human health and diseases is well recognized. Recent studies have revealed that the imbalance in the gut microecology is closely related to the occurrence and development of DILI. The gut microecology plays an important role in liver injury caused by different drugs. Recent research has revealed significant changes in the composition, relative abundance, and distribution of gut microbiota in both patients and animal models with DILI. Imbalance in the gut microecology causes intestinal barrier destruction and microorganism translocation; the alteration in microbial metabolites may initiate or aggravate DILI, and regulation and control of intestinal microbiota can effectively mitigate drug-induced liver injury. In this paper, we provide an overview on the present knowledge of the mechanisms by which DILI occurs, the common drugs that cause DILI, the gut microbiota and gut barrier composition, and the effects of the gut microbiota and gut barrier on DILI, emphasizing the contribution of the gut microecology to DILI.

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Ampicillin exacerbates acetaminophen‐induced acute liver injury by inducing intestinal microbiota imbalance and butyrate reduction

Cited by 9 publications

References 45 publications

Wolfberry, Yam, and Chrysanthemum polysaccharides increased intestinal Akkermansia muciniphila abundance and hepatic YAP1 expression to alleviate DILI

Wolfberry, Yam, and Chrysanthemum polysaccharides increased intestinal Akkermansia muciniphila abundance and hepatic YAP1 expression to alleviate DILI

Gut–Liver Axis as a Therapeutic Target for Drug-Induced Liver Injury

Role of Gut Microecology in the Pathogenesis of Drug-Induced Liver Injury and Emerging Therapeutic Strategies

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