Gallstones: Bad Company for the Steatotic Liver

Alvaro, Domenico

doi:10.1053/j.gastro.2017.03.020

Cited by 4 publications

(4 citation statements)

References 19 publications

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“…1M ). These data suggested that the oral administration of L. reuteri and L. plantarum could ameliorate the histological damage in the gallbladder and liver and improve the hepatic steatosis and liver lipid metabolism, which is associated with reduction of CGS formation ( 28 , 29 ).…”

Section: Resultsmentioning

confidence: 88%

FXR Signaling-Mediated Bile Acid Metabolism Is Critical for Alleviation of Cholesterol Gallstones by Lactobacillus Strains

Huang

Dong

et al. 2022

Microbiol Spectr

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Section: Resultsmentioning

confidence: 88%

FXR Signaling-Mediated Bile Acid Metabolism Is Critical for Alleviation of Cholesterol Gallstones by Lactobacillus Strains

Huang

Dong

et al. 2022

Microbiol Spectr

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“…1H). These data suggested that the oral administration of LR and LP can ameliorate hepatic steatosis, which is associated with cholesterol gallstones [24]. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were similarly reduced in the LR and LP treated groups (Fig.…”

Section: Lr and Lp Treatments Reduced Ld-induced Gallstones And Metabmentioning

confidence: 72%

Alleviation of Cholesterol Gallstones by Lactobacillus Targeting the Gut Microbiota Depends on Global Farnesoid X Receptor-Mediated Bile Acid Metabolism

Wan¹,

Zhuang³

et al. 2020

Preprint

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Background Cholesterol gallstone (CGS) disease is characterized by an imbalance in bile acid (BA) metabolism and is closely associated with gut microbiota disorders. However, the role and mechanism by which probiotics targeting the gut microbiota attenuate CGS are still unknown. In this study, Lactobacillus reuteri CGMCC 17942 (LR) and L. plantarum CGMCC 14407 (LP) were individually administered to lithogenic diet (LD)-fed mice at a dosage of 109 CFU/day for 8 weeks. Results Both Lactobacillus strains significantly reduced LD-induced gallstones, hepatic steatosis, and hyperlipidemia. These strains modulated serum BA profiles, with significantly decreased conjugated primary BA taurine-β-muricholic acid (T-β-MCA), an FXR antagonist. At the molecular level, LR and LP increased Farnesoid X Receptor (FXR) expression in the liver but not in the ileum, increased the levels of ileum and liver fibroblast growth factor 15 (FGF15) and liver FGFR4, small heterodimer partner (SHP), and subsequently reduced cholesterol 7α-hydroxylase (CYP7A1) and cytochrome P450 family 7 subfamily B polypeptide 1 (CYP7B1) to inhibit BA synthesis in the liver. At the same time, the two strains enhanced BA transport by increasing the levels of multidrug-resistance-associated protein homologs (MRP) 3/4, multidrug-resistance-associated protein homologs (MRP) 3/4, hepatic multidrug resistance protein (MDR2) and bile salt export pump (BSEP) mRNA in the liver. In addition, both LR and LP reduced LD-associated gut microbiota dysbiosis. LR increased the relative abundance of Muribaculaceae, while LP increased that of Akkermansia. The changed gut microbiota was significantly negatively correlated with the grade and incidence of gallstones, hyperlipidemia, the level of T-β-MCA in serum, or the gene expression levels of Fxr in liver. Furthermore, the protective effects of the two strains were abolished by a global but not intestinal-specific FXR antagonist. Conclusions Taken together, our results suggested that Lactobacillus might relieve gallstones through FXR-dependent regulation of BA synthesis and transport.

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“…Previously, abdominal visceral fat accumulation[ 5 - 7 ] and excessive heme iron consumption[ 8 ] were found to be related to a higher risk of gallstone disease. Liver fat accumulation associated with increased body cholesterol synthesis and hypersecretion of biliary cholesterol may also be related to cholelithiasis development[ 7 ], and nonalcoholic fatty liver disease (NAFLD) is an independent risk factor for cholelithiasis development[ 9 - 11 ] as well as gallstone-related diseases with an odds ratio (OR) of 3.6[ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Liver fat accumulation measured by high-speed T2-corrected multi-echo magnetic resonance spectroscopy can predict risk of cholelithiasis

Chen¹,

Zeng²,

Shi³

et al. 2020

WJG

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BACKGROUND Liver fat accumulation is associated with increased cholesterol synthesis and hypersecretion of biliary cholesterol, which may be related to the development of cholelithiasis. AIM To investigate whether liver fat accumulation measured by high-speed T2-corrected multi-echo magnetic resonance spectroscopy (MRS) is a risk factor for cholelithiasis. METHODS Forty patients with cholelithiasis and thirty-one healthy controls were retrospectively enrolled. The participants underwent high-speed T2-corrected multi-echo single-voxel MRS of the liver at a 3T MR scanner. The proton density fat fraction (PDFF) and R2 value were calculated. Serum parameters and waist circumference (WC) were recorded. Spearman’s correlation analysis was used to analyze the relationship between PDFF, R2, and WC values. Multivariate logistic regression analysis was carried out to determine the significant predictors of the risk of cholelithiasis. Receiver operating characteristic curve (ROC) analysis was used to evaluate the discriminative performance of significant predictors. RESULTS Patients with cholelithiasis had higher PDFF, R2, and WC values compared with healthy controls (5.8% ± 4.2% vs 3.3% ± 2.4%, P = 0.001; 50.4 ± 24.8/s vs 38.3 ± 8.8/s, P = 0.034; 85.3 ± 9.0 cm vs 81.0 ± 6.9 cm, P = 0.030; respectively). Liver iron concentration extrapolated from R2 values was significantly higher in the cholelithiasis group (2.21 ± 2.17 mg/g dry tissue vs 1.22 ± 0.49 mg/g dry tissue, P = 0.034) than in the healthy group. PDFF was positively correlated with WC ( r = 0.502, P < 0.001) and R2 ( r = 0.425, P < 0.001). Multivariate logistic regression analysis showed that only PDFF was an independent risk factor for cholelithiasis (odds ratio = 1.79, 95%CI: 1.22-2.62, P = 0.003). ROC analysis showed that the area under the curve of PDFF was 0.723 for discriminating cholelithiasis from healthy controls, with a sensitivity of 55.0% and specificity of 83.9% when the cut-off value of PDFF was 4.4%. CONCLUSION PDFF derived from high speed T2-corrected multi-echo MRS can predict the risk of cholelithiasis.

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Gallstones: Bad Company for the Steatotic Liver

Abstract: is an Advisory board member for Gilead Sciences, Abbvie, Bristol-Myers Squibb (BMS), and Merck; a speaker for Gilead Sciences, Abbvie, Merck, BMS, Roche Diagnostics; and receives research/grant support (to institution) from Gilead, Abbvie. J. Howell discloses no conflicts.

Cited by 4 publications

References 19 publications

FXR Signaling-Mediated Bile Acid Metabolism Is Critical for Alleviation of Cholesterol Gallstones by Lactobacillus Strains

FXR Signaling-Mediated Bile Acid Metabolism Is Critical for Alleviation of Cholesterol Gallstones by Lactobacillus Strains

Alleviation of Cholesterol Gallstones by Lactobacillus Targeting the Gut Microbiota Depends on Global Farnesoid X Receptor-Mediated Bile Acid Metabolism

Liver fat accumulation measured by high-speed T2-corrected multi-echo magnetic resonance spectroscopy can predict risk of cholelithiasis

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