Is bariatric surgery resolving NAFLD via microbiota-mediated bile acid ratio reversal? A comprehensive review

Talavera-Urquijo, Eider; Beisani, Marc; Alverdy, John C.

doi:10.1016/j.soard.2020.03.013

Cited by 26 publications

(31 citation statements)

References 96 publications

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“…This anatomical change may have more conjugated bile acids to be actively reabsorbed in terminal ileum while parallelly allow more PBA to enter into colon to be transformed to SBA by the gut microbiota. Studies have showed that in MAFLD patients, the PBA/SBA ratio in plasma were significantly higher when comparing with healthy subjects and correlates to the severity of MAFLD (51,52). Interestingly, current data also showed the bariatric surgery consistently decrease the PBA/SBA ratio which might be related to the metabolic benefits of MAFLD by bariatric surgery (51).…”

Section: Bariatric Surgery Bile Acids and Mafldsupporting

confidence: 47%

“…Given that the mechanisms of bile acids in regulating glucose and lipid metabolism have been established, the alteration in bile acids composition after bariatric surgery is considered an explanation to its metabolic effects (25,51). Briefly, the primary bile acids (PBA) are synthesized and conjugated in the liver, excreted to the intestine, deconjugated and/or transformed to secondary bile acids (SBA) by the gut microbiota, and recycled through reabsorption in the terminal ileum (51). The RYGB has foods bypass the gastroduodenal portion, reducing consumption of bile acids, and creates a shortcut for bile acids to reach the lower intestine (19).…”

Section: Bariatric Surgery Bile Acids and Mafldmentioning

confidence: 99%

“…Studies have showed that in MAFLD patients, the PBA/SBA ratio in plasma were significantly higher when comparing with healthy subjects and correlates to the severity of MAFLD (51,52). Interestingly, current data also showed the bariatric surgery consistently decrease the PBA/SBA ratio which might be related to the metabolic benefits of MAFLD by bariatric surgery (51). However, it should be noted the bile acids have numerous chemical structures which exhibits quite different affinity to FXR and TGR5 and represent divergent downstream bioactivities, making interpretations of the altered bile acids composition more complicated (25).…”

Section: Bariatric Surgery Bile Acids and Mafldmentioning

confidence: 99%

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Mining Gut Microbiota From Bariatric Surgery for MAFLD

Chen

Lee

et al. 2021

Front. Endocrinol.

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The progression of metabolic dysfunction associated fatty liver disease (MAFLD) leads to steatohepatitis, liver fibrosis and hepatocellular carcinoma. Thus far, there have been no FDA-approved medications for MAFLD. Bariatric surgery (BS) has been found to improve insulin resistance, steatohepatitis and liver fibrosis but is not recommended for treating MAFLD due to its invasiveness. Recent studies suggest the improved glucose metabolism after BS is a result of, at least partly, alterations to the gut microbiota and its associated metabolites, including short chain fatty acids and bile acids. It makes sense the improved steatohepatitis and fibrosis after BS are also induced by the gut microbiota that involves in host metabolic modulation, for example, through altering bile acids composition. Given that the gut–liver axis is a path that may harbor unexplored mechanisms behind MAFLD, we review current literatures about disentangling the metabolic benefits of MAFLD after BS, with a focus on gut microbiota. Some useful research tools including the rodent BS model, the multiomics approach, and the human microbiota associated (HMA) mice are presented and discussed. We believe, by taking advantage of these modern translational tools, researchers will uncover microbiota related pathways to serve as potential therapeutic targets for treating MAFLD.

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Section: Bariatric Surgery Bile Acids and Mafldsupporting

confidence: 47%

Section: Bariatric Surgery Bile Acids and Mafldmentioning

confidence: 99%

Section: Bariatric Surgery Bile Acids and Mafldmentioning

confidence: 99%

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Mining Gut Microbiota From Bariatric Surgery for MAFLD

Chen

Lee

et al. 2021

Front. Endocrinol.

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“…44 Furthermore, BAs may also alter the gut microbiome by inhibiting bacterial development and altering the microbiome composition, by acting as a detergent according to the hydroxyl groups and amino acid portion, exerting this deleterious effect on the Bacteroidetes phyla especially. 17,44 BAs represent a crucial partaker in liver-microbiota communication, and their composition and concentration seem to have a positive correlation with metabolism and hepatic fibrosis. 45,46 The composition of BAs is important in many metabolic diseases, it has been described that patients with T2DM present a change from PBA to SBA with an increase in deoxycholic acid levels.…”

Section: Ba Compositionmentioning

confidence: 99%

Gut Microbiota in Metabolic-associated Fatty Liver Disease and in Other Chronic Metabolic Diseases

Hernández-Ceballos¹,

Córdova-Gallardo²,

Méndez-Sánchez³

2021

Journal of Clinical and Translational Hepatology

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The gut microbiome plays a key role in the health-disease balance in the human body. Although its composition is unique for each person and tends to remain stable throughout lifetime, it has been shown that certain bacterial patterns may be determining factors in the onset of certain chronic metabolic diseases, such as type 2 diabetes mellitus (T2DM), obesity, metabolic-associated fatty liver disease (MAFLD), and metabolic syndrome. The gut-liver axis embodies the close relationship between the gut and the liver; disturbance of the normal gut microbiota, also known as dysbiosis, may lead to a cascade of mechanisms that modify the epithelial properties and facilitate bacterial translocation. Regulation of gut microbiota is fundamental to maintaining gut integrity, as well as the bile acids composition. In the present review, we summarize the current knowledge regarding the microbiota, bile acids composition and their association with MAFLD, obesity, T2DM and metabolic syndrome.

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“…Significant weight loss through lifestyle modification (Vilar-Gomez et al, 2015) or bariatric surgery (Talavera-Urquijo et al, 2020) have been shown to be helpful in resolution of NASH.…”

Section: Introductionmentioning

confidence: 99%

iPSC-derived hepatocytes generated from NASH donors provide a valuable platform for disease modeling and drug discovery

Gurevich¹,

Burton²,

Munn³

et al. 2020

Biology Open

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Non-alcoholic fatty liver disease (NAFLD) affects 30 to 40% of adults and 10% of children in the US. About 20% of people with NAFLD develop non-alcoholic steatohepatitis (NASH), which may lead to cirrhosis and liver cancer, and is projected to be a leading cause of liver transplantation in the near future. Human induced pluripotent stem cells (iPSC) from NASH patients are useful for generating a large number of hepatocytes for NASH modeling applications and identification of potential drug targets. We developed a novel defined in vitro differentiation process to generate cryopreservable hepatocytes using an iPSC panel of NASH donors and apparently healthy normal (AHN) controls. iPSC-derived hepatocytes displayed stage specific phenotypic markers, hepatocyte morphology, with bile canaliculi. Importantly, both fresh and cryopreserved Definitive Endoderm and Hepatoblasts successfully differentiated to pure and functional hepatocytes with increased CYP3A4 activity in response to rifampicin and lipid accumulation upon fatty acid (FA) treatment. End stage hepatocytes integrated into three dimensional liver organoids and demonstrated increased levels of albumin secretion compared to aggregates consisting of hepatocytes alone. End stage hepatocytes derived from NASH donors demonstrated spontaneous lipidosis without fatty acid supplementation, recapitulating a feature of NASH hepatocytes in vivo. Cryopreserved hepatocytes generated by this protocol across multiple donors will provide a critical cell source to facilitate the fundamental understanding of NAFLD/NASH biology and potential high throughput screening applications for preclinical evaluation of therapeutic targets.

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Is bariatric surgery resolving NAFLD via microbiota-mediated bile acid ratio reversal? A comprehensive review

Cited by 26 publications

References 96 publications

Mining Gut Microbiota From Bariatric Surgery for MAFLD

Mining Gut Microbiota From Bariatric Surgery for MAFLD

Gut Microbiota in Metabolic-associated Fatty Liver Disease and in Other Chronic Metabolic Diseases

iPSC-derived hepatocytes generated from NASH donors provide a valuable platform for disease modeling and drug discovery

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