Bile Acids, Gut Microbiome and the Road to Fatty Liver Disease

Hylemon, Phillip B.; L, Su; Zheng, Po-Cheng; Bajaj, Jasmohan S.; Zhou, Huiping

doi:10.1002/cphy.c210024

Cited by 13 publications

(15 citation statements)

References 93 publications

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“…Sevelamer is a non-absorbable polymer that not only binds bile acids in the intestine to form non-absorbable complexes and reduces bile acid uptake by intestinal epithelial cells but also modulates the gut microbiome and bile acid metabolism [60] . The role of bile acids and gut microbiome in NAFLD has also been reviewed recently [22] …”

Section: Bile Acids and Sphingolipids In Nafldmentioning

confidence: 99%

“…In the past 2 decades, numerous studies have shown that bile acid-mediated activation of the nuclear receptor, farnesoid X receptor (FXR), and G protein-coupled receptors (GPCRs), Takeda G-protein- coupled receptor 5 (TGR5) and sphingosine-1 phosphate receptor 2 (S1PR2), play important roles in the progression of NAFLD and other metabolic diseases via modulating hepatic lipid metabolism, immune responses, and the gut microbiome. [22,23,33] Sphingolipid metabolism and signaling pathways Sphingolipids are essential structural components of all eukaryotic membranes. The synthetic pathways of sphingolipids have been well characterized.…”

Section: Pathology Of Nafldmentioning

confidence: 99%

“…In the past decade, numerous studies have shown that sphingolipid metabolism dysregulation is closely associated with multiple metabolic disorders, including NAFLD [17–20] . Furthermore, the role of bile acid-mediated signaling pathways in NAFLD has recently been extensively discussed [22,23] . In this review, we will highlight the recent advances in the sphingolipid field and discuss connections between bile acids and sphingolipid signaling with a focus on NAFLD.…”

Section: Introductionmentioning

confidence: 99%

“…[17][18][19][20] Furthermore, the role of bile acid-mediated signaling pathways in NAFLD has recently been extensively discussed. [22,23] In this review, we will highlight the recent advances in the sphingolipid field and discuss connections between bile acids and sphingolipid signaling with a focus on NAFLD.…”

Section: Introductionmentioning

confidence: 99%

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Bile acids and sphingolipids in non-alcoholic fatty liver disease

Jackson

Way

Zhou

2022

Chinese Medical Journal

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Non-alcoholic fatty liver disease (NAFLD) is one of the fastest-growing diseases, and its global prevalence is estimated to increase >50% by 2030. NAFLD is comorbid with metabolic syndrome, obesity, type 2 diabetes, and insulin resistance. Despite extensive research efforts, there are no pharmacologic or biological therapeutics for the treatment of NAFLD. Bile acids and sphingolipids are well-characterized signaling molecules. Over the last few decades, researchers have uncovered potential mechanisms by which bile acids and sphingolipids regulate hepatic lipid metabolism. Dysregulation of bile acid and sphingolipid metabolism has been linked to steatosis, inflammation, and fibrosis in patients with NAFLD. This clinical observation has been recapitulated in animal models, which are well-accepted by experts in the hepatology field. Recent transcriptomic and lipidomic studies also show that sphingolipids are important players in the pathogenesis of NAFLD. Moreover, the identification of bile acids as activators of sphingolipid-mediated signaling pathways established a novel theory for bile acid and sphingolipid biology. In this review, we summarize the recent advances in the understanding of bile acid and sphingolipid-mediated signaling pathways as potential contributors to NAFLD. A better understanding of the pathologic effects mediated by bile acids and sphingolipids will facilitate the development of new diagnostic and therapeutic strategies for NAFLD.

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Section: Bile Acids and Sphingolipids In Nafldmentioning

confidence: 99%

Section: Pathology Of Nafldmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bile acids and sphingolipids in non-alcoholic fatty liver disease

Jackson

Way

Zhou

2022

Chinese Medical Journal

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“…Changes in the systemic bile acid profile and quantities are linked to many different health outcomes like the early microbiome development [ 13 ], NAFLD [ 14 ], liver cancer [ 15 ], and the change of the intestinal topology after bariatric surgery [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Ring Trial on Quantitative Assessment of Bile Acids Reveals a Method- and Analyte-Specific Accuracy and Reproducibility

Haange

Till²,

Bergh

et al. 2022

Metabolites

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(1) Background: Bile acids are a key mediator of the molecular microbiome-host interaction, and various mass spectrometry-based assays have been developed in the recent decade to quantify a wide range of bile acids. We compare existing methodologies to harmonize them. (2) Methods: Methodology for absolute quantification of bile acids from six laboratories in Europe were compared for the quantification of the primary bile acids cholic acid (CA) and chenodeoxycholic acid (CDCA) and conjugated products glycocholic acid (GCA) and taurocholic acid (TCA). For the bacterially modified secondary bile acids, the quantification of deoxycholic acid (DCA) and lithocholic acid (LCA) was compared. For the murine bile acids, we used the primary muricholic acids (α-MCA and, β-MCA) and the intestinally produced secondary bile acid muricholic (ω-MCA). The standards were spiked into methanol:water (1:1) mix as well as in human and murine serum at either low concentration range (150–3000 nM) or high concentration range (1500–40,000 nM). (3) Results: The precision was better for higher concentrations. Measurements for the hydrophobic unconjugated bile acids LCA and ω-MCA were the most challenging. (4) Conclusions: The quality assessments were generally very similar, and the comprehensive analyses demonstrated that data from chosen locations can be used for comparisons between studies.

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Gut‐liver axis: Potential mechanisms of action of food‐derived extracellular vesicles

Zhang,

Wang,

Tan

et al. 2024

J of Extracellular Vesicle

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Food‐derived extracellular vesicles (FEVs) are nanoscale membrane vesicles obtained from dietary materials such as breast milk, plants and probiotics. Distinct from other EVs, FEVs can survive the harsh degrading conditions in the gastrointestinal tract and reach the intestines. This unique feature allows FEVs to be promising prebiotics in health and oral nanomedicine for gut disorders, such as inflammatory bowel disease. Interestingly, therapeutic effects of FEVs have recently also been observed in non‐gastrointestinal diseases. However, the mechanisms remain unclear or even mysterious. It is speculated that orally administered FEVs could enter the bloodstream, reach remote organs, and thus exert therapeutic effects therein. However, emerging evidence suggests that the amount of FEVs reaching organs beyond the gastrointestinal tract is marginal and may be insufficient to account for the significant therapeutic effects achieved regarding diseases involving remote organs such as the liver. Thus, we herein propose that FEVs primarily act locally in the intestine by modulating intestinal microenvironments such as barrier integrity and microbiota, thereby eliciting therapeutic impact remotely on the liver in non‐gastrointestinal diseases via the gut‐liver axis. Likewise, drugs delivered to the gastrointestinal system through FEVs may act via the gut‐liver axis. As the liver is the main metabolic hub, the intestinal microenvironment may be implicated in other metabolic diseases. In fact, many patients with non‐alcoholic fatty liver disease, obesity, diabetes and cardiovascular disease suffer from a leaky gut and dysbiosis. In this review, we provide an overview of the recent progress in FEVs and discuss their biomedical applications as therapeutic agents and drug delivery systems, highlighting the pivotal role of the gut‐liver axis in the mechanisms of action of FEVs for the treatment of gut disorders and metabolic diseases.

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Bile Acids, Gut Microbiome and the Road to Fatty Liver Disease

Cited by 13 publications

References 93 publications

Bile acids and sphingolipids in non-alcoholic fatty liver disease

Bile acids and sphingolipids in non-alcoholic fatty liver disease

Ring Trial on Quantitative Assessment of Bile Acids Reveals a Method- and Analyte-Specific Accuracy and Reproducibility

Gut‐liver axis: Potential mechanisms of action of food‐derived extracellular vesicles

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